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the presently preferred embodiments and methodology described herein are applicable to coronary angioplasty procedures and are specifically described in the context of dilation balloon catheters . it should be understood , however , that the embodiments and methodology of the present invention may be adapted for use with other types of intravascular therapeutic devices , such as atherectomy catheters , as well as diagnostic catheters , such as ultrasonic catheters . referring to fig1 a first embodiment of a single - operator exchange type intravascular apparatus is indicated generally at 10 . the intravascular apparatus 10 includes a balloon dilation catheter 12 having an elongated shaft 14 . a proximal portion 16 of the shaft 14 is adapted to extend outside the body of a patient during use , and a distal portion 18 of the shaft 14 is positionable intravascularly during use by manipulation of the proximal portion 16 . a dilation balloon 20 is located at and connected to the distal portion 18 of the catheter shaft 14 . the balloon 20 can be formed from a polyolefin copolymer or other polymer material . for example , in one embodiment , the balloon 20 is formed of a polyolefin copolymer ( such as that sold by dupont under the tradename surlyn as resin no . 8527 ) using secondary treatment with 5 to 50 mega - rad electron beam irradiation to enhance strength in the region of the balloon 20 . preferably , the balloon 20 has a proximal neck portion 22 defining a proximal opening 24 , and a distal neck portion 26 defining a distal opening 28 . the proximal neck portion 22 preferably has an outer diameter of about 0 . 040 inches and an inner diameter of about 0 . 034 inches . the distal neck portion 26 preferably has an outer diameter of about 0 . 030 inches and an inner diameter of about 0 . 025 inches . the distal portion 18 of the shaft 14 extends into the proximal opening 24 in the balloon 20 and is preferably connected to the proximal neck portion 22 . the shaft 14 includes an inflation lumen 30 extending therethrough and has a proximal opening 32 and a distal opening 34 . a manifold 36 is connected to the proximal portion 16 of the shaft 14 and the dilation balloon 20 is in fluid flow communication with the inflation lumen 30 . inflation fluid is conveyed via the lumen 30 from the manifold 36 to inflate the balloon 20 and therefore dilate a vessel in a conventional manner known in the art . in a preferred embodiment , the shaft 14 has a length of approximately 135 cm . the proximal portion 16 of the shaft 14 is preferably made of stainless steel hypodermic tubing and the distal portion 18 is made of a relatively flexible polymeric material such as a polyolefin copolymer or polyethylene . this type of shaft is disclosed in u . s . patent application ser . no . 07 / 833 , 099 , filed feb . 10 , 1992 , the disclosure of which is specifically incorporated herein by reference . in order to minimize the profile of the distal portion 18 of shaft 14 , the shape of the shaft 14 and lumen 30 converges from a circular cross - section at the proximal portion 16 thereof ( fig3 ) to a kidney - shaped cross section at the distal portion thereof ( fig4 - 6 ). an upper wall 38 and a lower wall 40 of the shaft 14 converge distally of the distal opening 34 in the lumen 30 and extend across the balloon 20 to a position adjacent the distal neck portion 26 of the balloon 20 . preferably , a stiffening wire 42 extends distally from a distal end of the steel tubing and is attached to a distal end of the balloon 20 as disclosed in the &# 39 ; 113 patent to provide additional support for the manipulation of the catheter 12 . alternatively , the stiffening wire 42 can be attached to an underside of the upper wall 38 of the shaft and extend to approximately the center of the balloon 20 as shown in fig1 and 2 . to facilitate the operation and exchange of the components of the intravascular apparatus 10 , an elongated guide lumen 44 is adapted to extend through the proximal and distal openings 24 and 28 of the balloon 20 for slidable movement relative to the balloon 20 during use . the guide lumen 44 also has an inner chamber 50 extending therethrough from a proximal end 52 to a distal end 53 thereof for slidably receiving a conventional guide wire 54 . the guide lumen 44 has a sufficient length , preferably about 135 cm , so that a proximal portion 46 of the guide lumen 44 can extend outside the body of a patient during use while a distal portion 48 extends distally of the balloon 20 . preferably , the guide lumen 44 is approximately the same length as a conventional catheter . the guide lumen 44 may also be provided in different sizes to accommodate different size devices . for example , the guide lumen 44 can be provided with an inner diameter of 0 . 017 inches and an outer diameter of 0 . 020 inches for use with a 0 . 014 inch guide wire . for use with a 0 . 010 inch guide wire , the guide lumen 44 may be provided with an inner diameter of 0 . 013 inches and an outer diameter of 0 . 016 inches . preferably , the guide lumen 44 is made of a polymeric material , such as polyimide , and has a low friction coating , such as teflon ®, on both the inner and outer surfaces thereof . a coating on the inner surface enhances guide wire movement through the chamber 50 , and a coating on the outer surface enhances movement of the guide lumen 44 through a guiding catheter , a vessel , or the balloon 20 . alternatively , the guide lumen 44 can be made of other materials , such as polyurethane , polyester , or other polymers . the guide lumen 44 can also be made of a polyimide - teflon composite material , or reinforced with wire or a braid of metal or plastic or other materials . to provide greater stiffness at the proximal portion 46 of the guide lumen 44 compared to the distal portion 48 , the pitch of a wound reinforcing wire can be varied a desired amount along the length of the guide lumen 44 . the variable pitch wire can provide increased stiffness at the proximal portion 46 of the guide lumen 44 to facilitate manipulation of the entire guide lumen 44 . the variable pitch wire can also provide sufficient flexibility at the distal portion 48 of the guide lumen 44 to allow the guide lumen 44 to easily follow the guide wire 54 through a vessel . also alternatively , the coatings may be made of other materials such as a hydrophilic or silicone coating . in addition to or instead of the low friction coating , a metallic or foil coating may also be incorporated on the inner or outer surface of the guide lumen 44 . the guide wire 54 has a sufficient length , preferably about 160 - 190 cm , so that a proximal portion 56 of the guide wire 54 can extend outside the body of a patient from an opening in the proximal end 52 in the guide lumen 44 while a distal portion 58 extends distally from an opening in the distal end 53 of the guide lumen 44 . the proximal portion 56 of the guide wire 54 can also extend out of an opening in the guide lumen located distally of the proximal end 52 of the guide lumen 44 . in addition , the guide wire 54 can have an outer diameter between 0 . 008 and 0 . 022 inches , although conventional guide wires typically have a diameter of 0 . 010 , 0 . 014 or 0 . 018 inches . in a first embodiment , a proximal seal member 62 is sealingly connected to the proximal neck portion 22 of the balloon 20 and a distal seal member 64 is sealingly connected to the distal neck portion 26 of the balloon 20 . the proximal and distal seal members 62 and 64 have passageways 66 and 68 therethrough for slidably receiving the guide lumen 44 . the seal members 62 and 64 are preferably configured as collars and are made of a polymeric material , such as polyimide , polyurethane , polyester or the like . an upper portion of the proximal seal member 62 is attached to the curved bottom wall 40 of the catheter shaft 14 , and a lower portion is attached to the proximal neck portion 22 of the balloon 20 . the entire periphery of the distal seal member 64 is attached to the distal neck portion 26 , and a distal end 70 of the shaft 14 is attached to a top portion of the distal seal member 64 proximally of the neck portion 26 . in use , the distal portion 48 of the guide lumen 44 is adapted to extend distally from an end 71 of the distal seal member 64 while the proximal portion 46 is outside the body of a patient . preferably , the outer diameter of the guide lumen 44 is only slightly smaller than the inner diameters of the proximal and distal seal members 62 and 64 to create a tolerance fit which allows slidable movement of the guide lumen 44 through the seal member passageways 66 and 68 . when the balloon 20 is inflated with fluid , the tolerance fit between the guide lumen 44 and the proximal and distal seal members 62 and 64 inhibits inflation fluid from exiting the balloon 20 . in addition , the distal seal member 64 preferably extends proximally into the balloon 20 and has an expandable , tubular valve member 72 made of an elastomeric material such as tecothane or the like . as shown in dashed lines in fig2 the valve member 72 expands radially inward against the guide lumen 44 when the balloon 20 is inflated to further seal any space between the guide lumen 44 and the distal seal member 64 . a valve member of similar construction can also be incorporated into the proximal seal member 62 if desired . in accordance with the present invention , a longitudinally extendable guide lumen 44 is provided in the distal seal member 64 . positioned within the longitudinally extendable guide lumen 44 is preferably a therapeutic and / or diagnostic device 54 , such as an ivus device . during an angioplasty procedure , the balloon 20 is positioned adjacent an occluded site and inflated to dilate the occluding matter . thereafter , the intravascular apparatus 10 may be withdrawn relative to the vessel while the guide lumen 44 and the ivus device 54 may remain substantially at the revascularized portion of the vessel . thus , the dilatation balloon 20 may be effectively moved proximally away from the ivus device 54 and the guide lumen 44 , while the ivus device 54 and the guide lumen 44 remain substantially adjacent the revascularized portion of the vessel . the ivus device 54 may then be used to provide an image of the revascularized portion of the vessel . it is noted that the extendable guide lumen 44 may provide protection to the ivus device 54 while the intravascular apparatus 10 is withdrawn proximally therefrom . in addition , and because the extendable guide lumen 44 remains substantially across the occluded site or lesion , the intravascular apparatus 10 may easily be repositioned across the site by simply advancing the intravascular apparatus 10 over the extendable guide lumen 44 . this configuration provides an efficient means for dilating a vessel with a dilation balloon , and imaging the vessel between selected dilatations . fig9 - 19 illustrate alternative embodiments of the present invention . since these embodiments are similar to the previously described embodiment , similar parts appearing in fig9 - 19 are represented by the same , corresponding reference numeral , except for the corresponding letter in the numerals of the latter . in the embodiment shown in fig9 - 11 , a pair of split o - ring type seals are provided to prevent inflation fluid from exiting the balloon 20a . an upper portion of a proximal split o - ring 80 is attached to the curved bottom wall 40a of the catheter shaft 14a , and a lower portion is attached to the proximal neck portion 22a of the balloon 20a . the entire periphery of a distal o - ring 82 can be attached to the distal seal member 64a as shown in fig9 or bonded directly to the distal neck portion 26a of the balloon 20 . the split o - rings 80 and 82 are preferably made of a relatively soft durometer urethane material or the like and can be pre - formed or molded into the balloon 20a . in a molding operation , a polyurethane adhesive or the like can be injected into a shaped mold temporarily positioned in the neck portion of the balloon 20a . although the contact surfaces of the o - rings 80 and 82 are shown as rounded surfaces , the o - rings can be formed in any desired shape to facilitate slidable movement of the guide lumen 44a while providing an effective seal when the balloon 20a is inflated . the shape and material of the o - ring allows greater deformation as a result of pressure from the inflation fluid , which may provide a more effective seal . moreover , the &# 34 ; single point &# 34 ; contact of the proximal and distal o - rings 80 and 82 with the guide lumen 44a may facilitate advancement and withdrawal of the catheter 12a over the guide lumen 44a because the decreased contact area tends to reduce frictional forces acting on the guide lumen 44a . in the embodiment shown in fig1 - 13 , the guide lumen 44b is configured with an enclosed , deformable bladder - type sheath 84 surrounding a portion thereof . the sheath 84 has a constant volume of fluid therein ( not shown ) and is approximately the same length as the distance between the proximal and distal seal members 62b and 64b of the balloon 20b . prior to inflation of the balloon 20b , the guide lumen 44b is advanced or withdrawn until proximal and distal end portions 86 and 88 of the sheath 84 are substantially aligned with the proximal and distal seal members 62b and 64b ( fig1 ). when the balloon 20b is inflated with fluid , the fluid in the sheath 84 is displaced outwardly toward the end portions 86 and 88 ( fig1 ). as a result , the volume of space occupied by the end portions 86 and 88 increases such that the end portions bear against the seal members 62b and 64b to create an effective seal which prevents the inflation fluid from exiting the balloon 20b . alternatively , the sheath 84b can be provided in the form of spaced apart proximal and distal sheaths 90 and 92 surrounding the guide lumen 44c as shown in fig1 and 15 . the distance between the sheaths 90 and 92 is approximately the same as the distance between the seal members 62c and 64c . the sheaths 90 and 92 are aligned with the corresponding seal members 62c and 64c prior to inflation of the balloon 20c ( fig1 ), and the inflation fluid displaces the fluid in the sheaths 90 and 92 outwardly to create a seal between the sheaths 90 and 92 and the corresponding seal members 62c and 64c . in either of the embodiments shown in fig1 - 15 , the seal members can be eliminated and the sheaths can be configured to bear directly against the corresponding neck portions of the balloon when displaced by the inflation fluid . alternatively , a bladder - type valve member which surrounds the guide lumen 44 and expands when filled with fluid can provide an active seal . valve members of this type are disclosed in u . s . pat . no . 5 , 085 , 636 , issued feb . 4 , 1992 , the disclosure of which is specifically incorporated herein by reference . such a seal could be activated by the inflation fluid which fills the balloon 20 or by a separate flow of fluid through a micro - tube connected to the bladder . in any of the embodiments described herein , the proximal and distal seal members can be configured to slidably receive and provide an effective seal around a guide wire without the use of a guide lumen ( see , e . g ., fig9 a ). one advantage of this configuration may be the reduced profile of the balloon 20 resulting from the elimination of an inner tube inside the balloon 20 . such a configuration may also facilitate the flow of a radiopaque dye solution which is typically introduced into the vessel after an angioplasty procedure to determine whether an acceptable blood flow has been established through the vessel . when a 0 . 014 inch guide wire is used , the proximal neck portion 22 preferably has an outer diameter of about 0 . 036 inches and an inner diameter of about 0 . 030 inches . the distal neck portion 26 preferably has an outer diameter of about 0 . 025 inches and an inner diameter of about 0 . 020 inches . thus , the distal and proximal seals inhibit fluid from exiting the balloon 20 without separating the movable guide wire from the inflation fluid in the balloon . fig1 - 19 illustrate yet another embodiment of the present invention . in this embodiment , the shaft 14d has a relatively large diameter body portion 100 and a smaller diameter distal end portion 102 which extends through the proximal and distal openings 24d and 28d in the balloon 20d . preferably , the juncture of the body portion 100 and the distal end portion 102 is defined by a tapered shoulder 103 adjacent the balloon 20d . the distal end portion 102 of shaft 14d is sealingly attached to the proximal and distal neck portions 22d and 26d of the balloon 20d . the balloon 20d is inflated by conveying fluid via the inflation lumen 30d of the shaft 14d through a plurality of openings 104 formed in the distal end portion 102 of the shaft . instead of slidably attaching the guide lumen 44d to the balloon 20d and positioning the entire guide lumen 44d outside the shaft 14d , a portion of the guide lumen 44d is movably positioned within a distal portion of the inflation lumen 30d of shaft 14d . because the guide lumen 44d is positioned within the reduced diameter shaft lumen 30d rather than outside the shaft 14d , the profile of catheter 12d is minimized to allow insertion into relatively small vessels . the constant outer diameter of the distal end portion 102 of the shaft 14d also may provide a better joint between the balloon 20d and the shaft 14d . an opening 106 is provided in the body portion 100 of the shaft 14d , preferably about 10 - 30 cm proximally from the balloon 20d , for receiving the guide lumen 44d . the guide lumen 44d is guided by an inner core 108 which extends distally a relatively short distance , preferably about 5 - 15 mm , into the inflation lumen 30d from the opening 106 . an end portion 110 of the core 108 is flared to direct the guide lumen 44d into the core 108 when the guide lumen 44d is inserted in a proximal direction through the distal end portion 102 of the shaft 14d . to prevent fluid from exiting through the core 108 and out the opening 106 , a seal member 110 is sealingly connected to the core 108 . the seal member 110 is preferably a split o - ring type seal which is described in more detail above . a split o - ring type seal member 112 can also be provided in the distal neck portion 26d for sealingly engaging the guide lumen 44d . alternatively , the opening 106 and core 108 of the shaft 14d , along with the seal members 110 and 112 , can be configured to slidably receive a guide wire or other intravascular device without the use of the guide lumen 44d . the elimination of the guide lumen would allow the shaft to be configured with a smaller outer diameter , thus reducing the profile of the catheter . in operation of the intravascular apparatus 10 , intravascular access is initially made in a conventional manner . if the procedure is a percutaneous translumenal angioplasty ( pcta ) procedure , access is made via the femoral artery . a conventional introducer and guiding catheter ( not shown ) can be employed in a manner that is well known in the art . when used with the described embodiments of the present invention , a guiding catheter should have a lumen of sufficient size to accommodate the catheter 12 , guide lumen 44 and guide wire 54 . to initially position the intravascular apparatus 10 in a patient &# 39 ; s vessel , the guide wire 54 is preferably inserted into the guide lumen 44 while the entire guide lumen is outside the body such that the distal tip portion 58 of the guide wire 54 extends beyond the guide lumen 44 . the combination of the guide wire 54 and guide lumen 44 is then advanced to a desired location in a vessel , and the catheter 12 is advanced over the guide lumen 44 . the guide wire 54 can be inserted into the vessel prior to advancement of the guide lumen 44 over the guide wire , or the guide lumen 44 can be inserted into the vessel prior to advancement of the guide wire 54 through the guide lumen 44 . if the catheter 12 is configured to receive the guide wire 54 without the guide lumen 44 , the guide wire 54 can be advanced to a desired location in a vessel in a &# 34 ; bare wire &# 34 ; technique and the catheter 12 can be passed over the guide wire 54 . preferably , the combination guide wire 54 and guide lumen 44 are advanced until the distal portions 48 and 58 thereof reach a distal end of the guiding catheter . the guide wire 54 may be further advanced in the vessel alone , or the guide lumen 44 may be advanced along with the guide wire 54 . thus , the distal portion 48 of the guide lumen 44 can provide additional support for the distal portion 58 of the guide wire 54 when desired . for example , when the guide wire 54 is initially advanced alone , it may become difficult at some point to further advance the guide wire because it does not have sufficient stiffness for effective manipulation . the guide lumen 44 can then be advanced to support the guide wire 54 and assist its advancement in the vessel . thus , using the guide lumen 44 may avoid having to exchange the guide wire 54 for another guide wire having a larger diameter . if an exchange is required because the size or configuration of the guide wire 54 is inappropriate for further advancement in the vessel , the guide lumen 44 is advanced until the distal end 53 reaches a distal end 60 of the guide wire 54 . the guide wire 54 is withdrawn from the guide lumen 44 , and a desired bend can be formed in the distal portion 58 of the guide wire 54 or another guide wire can be obtained . the newly configured guide wire is then advanced through the guide lumen 44 to the previously attained position . the guide lumen 44 can also be used to straighten a bend in the distal portion 58 of the guide wire 54 while inside a vessel . as noted above , the distal portion 58 of the guide wire 54 is often bent a desired amount prior to insertion into the body of a patient to allow manipulation of the guide wire 54 through various vessels . the distal portion 58 of the guide wire 54 may also bend as a result of advancement of the guide wire 54 when movement of the distal tip is impeded in the vessel . if the bend is inappropriate for further advancement of the guide wire 54 to the desired location in the vessel or for advancement into a different vessel , the guide lumen 44 can be advanced over the guide wire 54 to straighten the distal portion 58 a desired amount . in addition , the guide lumen 44 can be advanced over the guide wire 54 after the guide wire is advanced past a stenosis in the vessel to pre - dilate the stenosis before insertion of the balloon 20 . the guide wire 54 can also be moved within the guide lumen 44 when the balloon 20 is inflated inside a vessel . as best shown in fig1 a substantial portion of the guide lumen 44 and guide wire 54 is positioned outside the catheter shaft 14 to allow a single - operator exchange of the catheter 12 for a second catheter . when a different size or configuration catheter is required , the catheter 12 is withdrawn so that the balloon 20 passes over the guide lumen 44 while an operator maintains a hold on the proximal portion 46 of the guide lumen 44 and the proximal portion 56 of the guide wire 54 . the balloon of a second catheter can then be advanced over the guide lumen 44 to position the second catheter in the same location previously attained by the first balloon catheter 12 . this single - operator exchange type configuration allows the operator to maintain a hold on the guide lumen 44 and guide wire 54 without using an extension or a relatively long guide lumen and guide wire . the guide lumen 44 therefore provides for the independent or substantially contemporaneous exchange of the guide wire 54 and the catheter 12 . when an exchange of the guide wire 54 is required , the guide wire 54 is withdrawn through the guide lumen 44 and replaced with a second guide wire . thus , the guide wire 54 can be exchanged before the catheter 12 has been inserted in the vessel , while the catheter 12 remains in the vessel , or after the catheter 12 has been withdrawn . likewise , the catheter 12 can be exchanged while the guide wire 54 remains in the vessel or after the guide wire 54 has been withdrawn . in either procedure , the position of the guide lumen 44 is maintained in the vessel by holding onto the proximal portion 46 of the guide lumen . referring now to fig2 - 21 , an over - the - wire type balloon dilatation catheter is indicated generally at 120 . in accordance with the illustrative embodiment , the balloon catheter 120 includes an inflation tube 122 with an inflation lumen 128 extending therethrough . attached to a distal end portion of the inflation tube 122 is an inflatable balloon 124 . the interior 130 of the inflatable balloon 124 is in fluid communication with the inflation lumen 128 of the inflation tube 122 , via inflation port 126 . the proximal end of the inflation tube is attached to a proximal manifold 134 . the proximal manifold 134 includes a fluid port 136 , which is in fluid communication with the inflation lumen 128 as shown . the inflatable balloon 124 is expanded by applying fluid pressure to the inflation lumen 128 via fluid port 136 . to provide a longitudinally extending guide wire lumen , it is contemplated that an elongated guide member 132 may be provided . the elongated guide member 132 preferably coextends interiorly within at least a portion of the inflation lumen 128 , and is in a slidable relation therewith . because the elongated guide member 132 coextends interiorly within at least a portion of the inflation lumen 128 , a seal 125 is provided . the seal 125 slidably receives the guide member 132 and provides a seal between the inflation lumen 128 and the exterior of the intravascular catheter 120 . in a preferred embodiment , the seal 125 comprises a seal between the inflation tube 122 and the guide member 132 , as shown . the seal 125 may be a friction fit seal , such as an o - ring seal . in this configuration , the guide member 132 may be slidably positioned relative to the dilatation balloon 124 . in addition , an ivus device 152 which is positioned within the guide member 132 , may be slidably positioned relative to the dilatation balloon 124 ( see , fig2 ). it is contemplated that a seal 138 may be provided between the manifold 134 and the guide member 132 . during an angioplasty procedure , the balloon 124 is positioned adjacent an occluded site within a vessel ( not shown ) and inflated to dilate the occluding matter . to view the revascularized portion of the vessel , the ivus device 152 may be advanced down the guide member 132 until the ivus device 152 is adjacent the desired site . thereafter , the balloon dilatation catheter 120 may be withdrawn proximally relative to the guide member 132 , as shown in fig2 . in this configuration , the dilatation balloon 124 is effectively moved proximally away from the ivus device 152 , and the ivus device 152 and the guide member 132 remain adjacent the revascularized portion of the vessel . the ivus device 152 may then be used to provide an image of the occluded vessel . preferably , the ivus device 132 remains within the guide member 132 so that the guide member 132 can provide protection to the ivus device 152 . because the guide member 132 remains across the occluded site or lesion , the balloon catheter 120 can easily be repositioned across the site by simply advancing the balloon catheter 120 over the guide member 132 . this provides an efficient means for imaging a vessel between selected dilatations . in accordance with the above , an illustrative method is contemplated that includes the steps of : providing a catheter 120 that has a movable guide member 132 therein and a balloon 124 located on the distal end thereof , wherein the catheter 120 is positioned within the body such that the balloon 124 is located adjacent a selected portion of the vessel ; providing an elongated device 150 that has an imaging device 152 located near the distal end thereof , wherein the elongated device 150 is positioned within the guide member 132 as shown ; moving the catheter 120 proximally of the selected portion of the vessel while leaving the movable guide member 132 substantially stationary relative to the selected portion of the vessel ; positioning the imaging device 152 adjacent the selected portion of the vessel , if necessary ; and imaging the selected portion of the vessel with the imaging device 152 . in an alternative method , it is recognized that the movable guide member may have a distal portion thereof positioned distal of the balloon by actually sliding the movable guide member in a distal direction while the balloon remains substantially stationary if it is desired to image distal of the balloon . further , it is recognized that a combination of moving the balloon catheter and associated balloon in a proximal direction and moving the movable guide member in a distal direction can also be utilized . in either method or combination , the desired results is achieved in that the movable guide member has a distal portion thereof positioned distal of the balloon of the balloon catheter for use of an imaging device . referring now to fig2 - 23 , a standard over - the - wire type balloon dilatation catheter is indicated generally at 162 . in the illustrative embodiment , the standard balloon catheter 162 is combined with a lumen extension device 160 ( see , fig2 ). the lumen extension device 160 is a separate device that is used in conjunction with catheter 162 . the lumen extension device 160 allows a user to effectively extend the guide wire lumen of a standard catheter 162 by a selected amount . in the illustrative embodiment , the lumen extension device 160 includes an elongated guide member 170 for slidably receiving an elongated device , such as an ivus device ( not shown ). the guide member 170 is adapted to be slidably disposed within the guide wire lumen of the standard catheter 162 . attached to the proximal end of the guide member 170 is a housing 172 . the housing 172 preferably engages the proximal end of the catheter 162 , and has a control mechanism 174 for controlling the relative longitudinal position of the guide member 170 relative to the catheter 162 . preferably , the catheter 162 has a manifold 164 on the proximal end thereof , and the housing 172 is attached to the manifold 164 , as shown in fig2 . the control mechanism 174 of the lumen extension device 160 preferably comprises a block that is slidably disposed in the housing 172 . the block is attached to the proximal end of the guide member 170 . attached to the block is a handle 178 , and the handle 178 extends out of the housing 172 through a slot 179 . by manipulating the handle 178 , the longitudinal position of the guide member 170 relative to the housing 172 may be changed , as shown at 182 . since the housing 172 is preferably mounted to a manifold 164 of catheter 162 , the handle 178 may be used to change the longitudinal position of the guide member 170 relative to the catheter 162 . for example , by moving the handle proximally as shown at 190 , the guide member 170 may be moved proximally relative to the balloon 168 , as shown at 192 . likewise , by moving the handle distally , as shown at 186 , the guide member 170 may be moved distally relative to the balloon 168 , as shown at 188 . preferably , the block 174 has a tapered aperture 176 for guiding an elongated device , such as a ivus device into the guide member 170 . in accordance with this embodiment , a method is contemplated including the steps of : providing a catheter 162 that has a guide wire lumen extending longitudinally therethrough , and a balloon 168 located on the distal end thereof , the catheter 162 being inserted into the body such that the balloon 168 is positioned adjacent a selected portion of a vessel ( not shown ); providing a lumen extension device 160 comprising a elongated tube 170 , wherein the lumen extension device 160 is slidably positioned within the guide wire lumen of the catheter 162 ; providing an elongated device ( not shown ) that has an imaging device located near the distal end thereof , said elongated device being positioned within the elongated tube 170 of the lumen extension device 160 ; moving the catheter 162 proximally of the selected portion of the vessel while leaving the lumen extension device 162 substantially stationary relative to the selected portion of the vessel ; positioning the elongated device ( not shown ) adjacent the selected portion of the vessel , if necessary ; and imaging the selected portion of the vessel with the imaging device . as with the other disclosed embodiments , an alternative method can include extending a distal portion of the elongated tube of the lumen extension device distal of the balloon while maintaining the balloon in a stationary position if it is desired to image distal of the balloon . further , a combination of moving the elongated tube in a distal direction and the balloon in a proximal direction can also be utilized so that the elongated tube distal portion is positioned distal of the balloon . although the present invention has been described with reference to preferred embodiments , those skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention . as such , it is intended that the foregoing detailed description be regarded as illustrative rather than limiting and that it is the following claims , including all equivalents thereof , which are intended to define the scope of the invention . | a method and apparatus for introducing therapeutic and / or diagnostic devices through a balloon dilatation catheter and to an occlusion site , while longitudinally moving the dilatation balloon proximally from the occlusion area . this may enable , for example , an intra - vascular ultra - sonic device to produce non - distorted images of an occluded site between balloon dilatations of an angioplasty procedure . |
the present invention provides mutants of cmvpp65 which exhibit substantially no protein kinase activity but retain the immunological activity of the native sequence whereby they are capable of eliciting an antibody response and / or a ctl response against cmv in a suitable host . these mutants may differ in primary sequence from native cmvpp65 by one or more amino acid residues . one preferred embodiment comprises a mutant form of cmvpp65 that contains a point mutation that preserves native immunologically important epitopes but eliminates protein kinase activity . the invention provides methods to augment the immune response of a host who is naive to cmv or to a patient latently infected with cmv and at risk for reactivation of cmv infection , wherein t cells are removed from a donor individual and treated in vitro with a mutant cmvpp65 dna of the present invention that has been transfected into an hla - matched antigen presenting cell . the resulting cmv - reactive ctl are infused into a recipient to provide protection from cmv disease . the above methods also can be used to confer immunity against a cmv infection in a previously uninfected individual such as , for example , a woman of child - bearing years to prevent maternal - infant or maternal - fetus transmission of cmv . the methods can be used to vaccinate children to reduce the spread of cmv infection in , for example , day care centers . vaccines may take any form known in the art , such as protein vaccines , dna vaccines or recombinant live virus vaccines containing a dna of this invention . adjuvants may form part of vaccine compositions . any adjuvant known in the art which is suitable may be used . examples include freund &# 39 ; s adjuvant , alum or any known adjuvant suitable for use with a protein vaccine . for in vivo use in humans , such adjuvants are not preferred . a dna adjuvant may be used with a protein vaccine in humans , if desired . genetic adjuvants may be used to enhance the effect of dna immunization , for example genes encoding gm - csf or il - 2 . these genes may be inserted into the modified vector to enhance ctl activity . carriers may be used with the vaccine compositions , including any pharmaceutically acceptable carrier known in the art . exemplary carriers may include sterile water , saline solutions , liposomes or solutions containing cyclo - dextrin . liposomes and cyclo - dextrin may be used to enhance uptake of the dna by the antigen presenting cells . any suitable vector may be used in dna vaccine compositions according to the invention . for example , pmg vector ( invitrogen ) has been developed with two different promoters , one of which is the elongation factor 1α / htlv hybrid . this is a strong promoter suitable for use with the dna vaccines of this invention . the selection of hygromycin ( bacteria ) or zeocin ( mammalian ) yields stable transfectants in two weeks . the peptides of the mutant protein of the present invention may be administered to previously infected or uninfected patients , or in vitro to t cells , in the form of a protein vaccine or a polynucleotide ( dna - based ) vaccine , or as a component of a recombinant viral vaccine . suitable gene transfer vectors , such as a plasmid or an engineered viral vector that contains dna encoding the cmvpp65 protein or a fragment thereof under the control of appropriate expression regulatory sequences may be administered to the patient or to t cells in culture for later administration to the patient . therefore , the present invention provides a vaccinia , canarypox or other eukaryotic virus vector containing a dna sequence encoding the immunologically active protein . the vector infects an antigen presenting cell which in turn presents antigen that will be recognized by ctl of patients having a latent ( inactive ) cmv infection . a dna vaccine permits direct and efficient expression of the protein of interest ( pp65mii ), that can be transfected easily in vitro or in vivo into an antigen presenting cell and trigger a cytotoxic t cell response . to accomplish this , a plasmid which has a promoter with high expression levels ( e . g ., the cmv ie promoter as used in pcdnaintpp65mii ) is used . preferably , the promoter also has an intron ( e . g ., intron a of the cmv ie gene as used in pcdnaintpp65mii ) which stabilizes the expression of the dna due to the presence of transcriptional enhancers . finally , the preferred dna vaccines have a polyadenylation termination sequence ( e . g ., bovine growth hormone poly a sequence as used in pcdnaintpp65mii ). the vaccine sequence exemplified below ( pcdnaintpp65mii ) was derived from pcdna3 . 1 + ( invitrogen ), but for a safer vaccine , the ampicillin gene is preferably removed because it confers resistance to penicillin and is replaced with the kanamycin gene . in addition , the viral sv40 ori and pa preferably are removed to improve safety by diminishing the likelihood of integration into the host genome . in regard to recombinant virus vectors , it is possible to use recombinant viruses that encode the cmv pp65mii gene to enhance the immunological response . poxvirus recombinants such as recombinant vaccinia , modified vaccinia virus ankara ( mva ), and canarypox may be used for this type of recombinant viral vaccine production . attenuated recombinant virus vaccine strains can be produced with multiple virus epitopes and with soluble cytokine factors that further augment the immune response . in vivo immunization of cmv seronegative subjects may be done with a dnaintpp65mii priming followed by a recombinant virus ( e . g ., vaccinia - pp65mii or mvapp65mii ) boost to elicit specific ctl proliferation . the in vitro expansion of specific ctl may be done with matched - hla stably transfected with pcdnaintpp65mii cell lines such as ebv - transformed b cells , such as lcl , and stimulators such as anti - cd3 antibody . the invention also relates to diagnostic reagents for detection of the presence of active versus quiescent cmv infections . a human cell line , a293 , stably transfected with pcdnaintpp65mii has been established and expresses the pp65mii protein . these cells can be used in a diagnostic assay to detect the presence of antibody to cmv in plasma and thus determine the cmv serology status by immunofluorescence or any suitable method . the specific ctl response can be assayed ex vivo using a cytokine - based assay , such as an ifn - γ elispot assay or facs intracellular ifn - γ assay , whereby the t cells are stimulated in vitro for a period of time , with matched - hla transfected / not transfected pp65mii lcl and the number of cytokine positive cells are determined . the ifn - γ positive cd8 + cells are ctl that have been stimulated by the expression of the mutant peptide expressed in the lcl ; the ifn - γ positive cd4 + cells are the t helper cd4 cells that have been stimulated to induce a th1 pathway and generate more ctl . because the native pk activity of cmvpp65 may be harmful if expressed in healthy cells , vaccine methods using cmvpp65 which lacks this potentially harmful activity were created . to reduce or eliminate the pk activity of cmvpp65 , expression plasmids were constructed in the pqe9 vector using site - specific mutations within the cmvpp65 protein , including mutations within the putative pk domains ii and viii at amino - acid locations 436 and 465 . in addition , a complete carboxy - terminal truncation was created in pqe9 pp65 mtth that represented a deletion of all the putative pk domains of cmvpp65 ( aa398 - 552 ). a plasmid containing cmvpp150 served as an additional negative control to check for background pk activity of the expression system . see fig1 and example 1 . the plasmids containing mutated cmvpp65 were compared to plasmid pqe9 pp65n , containing the native cmvpp65 , for kinase activity and protein expression . the bacterial expression system used here allowed pk activity to be tested without possible contamination of mammalian cellular kinases . other suitable plasmids are well known in the art . other suitable plasmids are continuously being developed as better expression vectors for in gene therapy or vaccine research . the mutant pp65 gene may be inserted in any of these vectors as seems fit . therefore , any suitable plasmid is contemplated for use with this invention . the choice of cmvpp65 sequences to mutagenize was based on available sequences that conformed to the conserved catalytic subdomains of known threonine / serine pks ( hanks 1991 ) and yet did not overlap with known cmvpp65 - specific ctl epitopes . cmvpp65 contains the conserved pk subdomains i , ii , vib , viii , and xi . ctl epitopes overlap in domains i and in various parts of the cmvpp65 carboxy terminal sequence ( 50 ). therefore , only domains ii and viii were selected for modification . subdomain ii contains lysine 436 that corresponds to the invariant lysine present in several pks that is known to interact with atp analogs that inhibit pk ( 27 ). in addition , mutating the lysine in domain ii suppresses the pk activity of other typical protein kinases , such as the insulin receptor , the egf receptor , and viral proteins , such as p130 gag - fps of the fujinami sarcoma virus and p37 mos the transforming gene product of moloney murine leukemia virus ( 5 , 23 , 24 , 49 ). subdomain viii , although out of sequence order compared to vi b , contains the triplet ala - pro - glu that lies near the pk catalytic site and that has been linked to a nearby autophosphorylation site ( 22 ). therefore , lysine 436 and glutamic acid 465 were selected for mutagenesis . the expression products of the plasmids containing the mutated sequences were first tested for protein kinase activity by dot blot using the exogenous substrate , casein . as shown in fig2 ( upper row ), the ( native protein ) cmvpp65n possesses intrinsic protein kinase activity , resulting in phosphorylation of the exogenous substrate casein . the mutant cmvpp65mii , containing the k436n mutation , showed no detectable kinase activity . the mutant cmvpp65 mviii showed approximately the same ability to phosphorylate casein as the native sequence , although there was a slight reduction in detectable phosphorylation . the combined mutant cmvpp65mii / viii , with both k436n and e465k mutations demonstrated phosphorylation levels similar to the single mutant cmvpp65mii . the negative controls , cmvpp65 mtth and cmvpp150 , showed the level of background casein phosphorylation in the assay . the cmvp65mii mutant remained recognizable by a specific monoclonal antibody , as shown in western blot experiments . see fig3 . in addition , the cmvpp65mii protein localized to the nucleus of infected cells , as indicated by monoclonal antibody staining ( data not shown ), suggesting that the mutation did not significantly affected the normal trafficking of this protein . however , because the humoral immune response to cmvpp65 is not considered the most important element in the immune response to infection to viruses , it was more important to determine the effect of this mutation on ctl recognition and activation ( cellular immunity ). therefore , cells infected with vaccinia - cmvpp65mii were tested for recognition as targets by a ctl clone derived from natural human infection . cells expressing native sequence ( cmvpp65n ), the mutated sequence ( cmvpp65mii ), wild type vaccinia virus ( no sequence ) or an hla - mismatched control cells expressing the mutated sequence were all tested by chromium release assay for lysis by a human cd8 + ctl clone specific for a cmvpp65 hla a2 epitope . this cd8 + ctl clone , 3 . 3f4 described in ( 10 ) the disclosures of which are hereby incorporated by reference , was obtained from a healthy cmv - seropositive human volunteer who had mounted a successful immune response to cmv , and is specifically reactive to hla autologous targets expressing native cmvpp65 . cytolytic function against cells expressing the mutant was similar to that directed toward the native cmvpp65 . the mutant cmvpp56 proteins therefore are demonstrated to retain the immunological characteristics shown to be important in immune function in the human response to cmv infection , particularly cell - mediated immunity . the in vitro chromium release assays discussed above are well - recognized in the art to successfully correspond to in vivo function of the same cells . therefore , hla specific recognition of cells expressing the native protein by the human t lymphocyte clone 3 . 3f4 clearly demonstrates an equivalent cell - mediated immune response which is predictive of in vivo recognition , activation and cytolysis . further , data show ctl activation by cmvpp65 in a well - accepted animal model used for prediction of human vaccine responses . the hla - a2 . 1 transgenic mouse model is accepted for use where no animal model is available to study the immunologic responses to a particular human virus . see vitiello et al ., j . exp . med . 173 : 1007 , 1991 . the cytotoxic response in hla - a2 . 1 transgenic mice is shown to recognize the same epitopes as the ones presented in human cells in hcv ( wentworth et al ., int . immunol ., 1996 ), influenza ( man et al ., int . immunol ., 1995 ) or hiv ( ishioka et al ., j . immunol ., 1999 ). the data therefore clearly demonstrate the feasibility of this approach for modifying the immune systems of human patients to protect both healthy and immunocompromised persons from cmv disease . the following examples are provided as illustrations of methods of the invention and are not intended to be limiting in any way . the cmvpp65 gene , cloned into the bamhi and ecori restriction sites of pbluescript ii ks dna ( 35 ) was used to create the constructs . cmv nucleotide coordinates were used as published ( 4 ). mutations of the cmvpp65 dna were made using a quikchange ™ site - directed mutagenesis kit ( stratagene , san diego , calif .) using the following pairs of mutagenic primers developed using the published pk domain characteristics ( 22 , 28 ). 5 ′ gcgggccgc aac cgcaaatcagcatcc 3 ′ and 5 ′ ggatgctgatttgcg gtt gcggcccgc 3 ′ ( nt : 1270 - 1296 ; seq . id nos : 2 and 3 ) were used to mutate the indicated lysine into asparagine in the putative pk domain ii ( mii ) of cmvpp65 ( the k436n mutation ). 5 ′ gagtccaccgtcgcgccc aaa gaggacaccgacgag 3 ′ and 5 ′ ctcgtcggtgtcctc ttt gggggcgacggtggactc 3 ′ ( nt : 1345 - 1377 ; seq id nos : 4 and 5 ) were used to mutate the indicated glutamic acid into lysine in the putative pk domain viii ( mviii ) ( the e465k mutation ). the codon for the presumed functional amino acid k436 or e465 of cmvpp65 is shown underlined . another mutant plasmid which contains both mii and mviii ( pp65mii / viii ) was also generated . the mutations were confirmed by dna sequencing . a negative control lacking the putative cmvpp65 phosphokinase domain was created in pbluescript ii ks ( pp65 mtth ) by digesting the cmvpp65 gene with tth111i and nsii ( new england biolabs , beverly , mass .) to delete the nucleotides which encode cmvpp65 ( amino acids 398 - 552 ). overhanging sequences were removed with mung bean nuclease ( new england biolabs , beverly , mass .) and the ends re - ligated using t4 dna ligase ( life technologies , inc ., gaithersburg , md .). to express the proteins in a bacterial system , the cmvpp65 dna was removed from pbluescript using sal i - bam hi digestion and inserted downstream from the cmv promoter in the pqe9 vector ( qiagen , valencia , calif .). the pqe9 cmvpp65 expression plasmid was used to transform e . coli strain m15 , which contains the repressor prep4 plasmid , and the proteins were expressed following the manufacturer &# 39 ; s protocol ( qiagen , valencia , calif .). the mtth modification of cmvpp65 was created to establish a kinase - deficient cmvpp65 control by inserting the tth111i and nsii truncations into the pqe9 plasmid . as shown in fig1 , the plasmid containing the native cmvpp65 was designated pqe9 pp65n , the k436n subdomain ii mutant was pqe9 pp65mii , the e465k subdomain viii mutant was pqe9 pp65 mviii , the combined k436n / e465k mutant was pqe9 pp65mii / viii , and the truncation control was pqe9 pp65 mtth . pqe9 pp150 was used as a negative plasmid control . the cmvpp65 mutant sequences were subcloned into transfer vector psc11 and then transfected using lipofectamine ( life technologies , inc ., gaithersburg , md .) into cv - 1 cells that had been simultaneously infected with wild - type wr strain vaccinia virus using the method of elroy - stein and moss ( 12 ). recombinant virus was cloned and correct insertion was confirmed by pcr and dna sequencing . the efficiency of protein expression in the constructs was verified by western blot . the proteins were purified from cells transfected with the indicated pqe9 vector , separated using 12 . 5 % sds - page , transferred to a nitrocellulose membrane and probed with mab 28 - 103 specific for the detection of the pp65 protein ( see britt et al ., j . clin . microbiol . 28 : 1229 - 1235 , 1990 ), followed by abc peroxidase staining using a vectastain abc kit ( vector laboratories , inc ., burlingame , calif .). all the proteins of the constructs bearing the intact carboxy - terminus of cmvpp65 were detected by the mab , including the mutant cmvpp65 . the level of expression was qualitatively similar in all constructs , suggesting that the mutations did not alter protein expression . in addition , mutation did not appear to significantly affect the immune recognition of the proteins . the cmvpp65 native and mutant proteins were expressed in the pqe9 bacterial system according to a qiagen ™ protocol . cell pellets were extracted and subjected to immunoprecipitation as described by michelson et al . ( 32 ) with modifications . briefly , the bacterial pellets were frozen and thawed three times and incubated in lysis buffer ( 20 mm tris / hcl ph 8 . 0 , 300 mm nacl , 10 % glycerol , 2 mm edta , 0 . 0 . 5 % nonidet p - 40 ) in the presence of protease inhibitor ( 5 μg / ml aprotinin and 5 μg / ml leupeptin ) for 20 minutes at 4 ° c . the cell lysates were incubated with mouse igg to remove non - specific proteins , sonicated and then clarified by centrifugation at 15 , 000 × g for 5 minutes at 4 ° c . the cmvpp65 protein was immunoprecipitated with mab28 - 103 , specific for cmvpp65 . protein extract ( 200 μg ) was mixed with 10 μl mab28 - 103 unpurified ascites in 500 μl buffer a ( 10 mm tris - hcl , ph 7 . 4 , 150 mm nacl , 2 mm edta , 1 % np - 40 , with 5 μg / ml aprotinin and 5 μg / ml leupeptin ( 32 )) and incubated at 4 ° c . for 90 minutes with agitation . when relevant , 100 pg mrc - 5 cell lysate in 1 % sds was added to the mixture to check whether cellular kinases co - immunoprecipitated with the cvmpp65 protein . the immune complex was captured with 100 μl 50 % protein a - sepharose 4 fast flow beads ( amersham pharmacia biotech , piscataway , n . j .) co - incubated with the extract at 4 ° c . for 45 minutes and then washed three times by centrifugation with buffer a . the immunoprecipitated native and mutant cmvpp65 proteins , still bound to the sepharose beads , were tested for protein kinase ( pk ) activity . pqe9 ppls0 was also processed in the same way , as a negative control . casein kinase ii ( promega , madison , wis .) enzyme was used as a positive control . dot blot pk assays were performed according to the methods of glover and allis ( 20 ). briefly , 100 μl samples to be assayed were immobilized on a nitrocellulose membrane ( hybond ecl , amersham pharmacia biotech , piscataway , n . j .) by vacuum filtration using a commercial dot blot manifold ( minifold , schleicher & amp ; schuell , inc .). dephosphorylated bovine casein ( sigma chemical co , st louis , mich .) ( 100 μl 1 mg / ml ) was added to each well as substrate , followed by incubation at room temperature for 30 minutes with 100 μl reaction mix ( 25 mm tris ph 8 . 5 , 100 mm nacl , 10 mm mgcl 2 , 1 mm dithiothreitol , 0 . 1 μm [ γ - 32 p ] atp ). at the end of the incubation , free radioactive atp was removed by washing the membrane 10 times in pbs at 37 ° c . followed by incubation at 37 ° c . in a shaking bath containing 100 ml stripping solution ( 4 m guanidine hydrochloride , 1 % sds , 0 . 1 % tween - 20 , 0 . 5 % β - mercaptoethanol ) for 30 minutes , with a final wash in distilled water . incorporation of [ 32 p ]- atp into protein was visualized by autoradiography . see fig2 . mutant cmvpp65mii showed no kinase activity . to quantitate the amount of phosphokinase activity , serial dilutions of casein kinase ii ( promega , madison , wis .) were assayed , and a standard curve was established using a phosphorimager 445 si ( molecular dynamics , sunnyvale , calif .). the data were plotted and fitted to a linear curve from which cmvpp65 - pk units were derived . one unit was defined as the amount of kinase needed to transfer 1 picomole of phosphate per minute at 37 ° c . using casein as substrate . any values below 1 . 0 were considered negative . because native cmvpp65 undergoes autophosphorylation ( 3 ), the signals detected by pk assay using cmvpp65 are actually the combined results of both casein and cmvpp65 phosphorylation . to separate the two activities , a protein kinase assay was performed in solution according to the method described by roby et al . ( 41 ) and then analyzed by sds - page . immunoprecipitated recombinant proteins , including cmvpp65n , cmvpp65mii , cmvpp65 mviii , cmvpp65mii / viii , cmvpp65tth and cmvpp150 , were used in protein kinase reactions in solution and then separated by 12 . 5 % sds - page . typically , 50 μl sample and 50 μl casein substrate ( 1 mg / ml ) were added to 100 μl of a twofold - concentrated reaction mix as described above . the reaction was incubated at 37 ° c . for 30 minutes and terminated by adding 20 μl 100 μm edta , and then heated in boiling water for 3 minutes , releasing the cmvpp65 protein from the sepharose beads , and sedimented at 15 , 000 × g for 1 minute . the phosphorylated proteins were precipitated with 10 % trichloroacetic acid , washed in acetone , and resuspended in loading buffer to be analyzed by 12 . 5 % sds - page . phosphorylation of the separated proteins on the gel was visualized by autoradiography using x - omat ™ ar5 film ( kodak , rochester , n . y .). since the immunoprecipitation step may copurify other kinases from human - derived cells as well as the specific cmvpp65 protein ( 16 ), the bacterial lysate was mixed with 100 μg of mrc - 5 cell lysate . the results are shown in fig2 ( lower row ). no increase in phosphate signal was detected in any of the samples , including the negative controls . the cmvpp65mii remained negative , suggesting that it did not bind cellular kinases . to quantify the phosphokinase activities among the various mutants , with or without the addition of human - derived cell lysate , serial dilutions of casein kinase ii were used to standardize the activity as units per assay ( standardization data not shown ). the ckii positive control had 10 u pk activity , the cmvpp65n had 10 . 3 u , cmvpp65 mviii had 7 . 8 u , and cmvpp65mii , cmvpp65mii / viii , cmvpp65 mtth and cmvpp150 had no activity . when the mrc - 5 cell lysate was added to the reaction , cmvpp65n and cmvpp65 mviii had an activity equivalent to 10 . 4 u and 7 . 0 u respectively , whereas the other reactions remained negative . these results show that no detectable cellular kinases were coimmunoprecipitated from the system containing human - derived cell lysates using the mab 28 - 103 to precipitate the cmvpp65 specific kinase . the efficiency of the protein expression in the constructs was verified by western blot as shown in fig3 . proteins expressed from the constructs bearing the intact carboxy - terminus of cmvpp65 are shown in this western blot . the cmvpp65 mutations are detected by mab 28 - 103 . the level of expression appears to be similar in all constructs , suggesting that the mutations did not alter protein expression . to perform the blot , a 1 ml culture of bacterial cells containing the expressed proteins in pqe9 were lysed in 100 μl lysis buffer , sonicated on ice three times for 30 seconds and sedimented at 15 , 000 × g for 5 minutes . the protein concentration of the supernatants was measured and 100 μg protein was subjected to 12 . 5 % sds - page , transferred to a nitrocellulose membrane and incubated with mab 28 - 103 followed by staining with peroxidase . see fig3 . as shown in fig4 , cmvpp65 and casein were phosphorylated by cmvpp65n and cmvpp65 mviii . cmvpp65mii , containing the substitution at k436n , showed not only complete loss of phosphorylation of casein but also absence of autophosphorylation . the same absence of autophosphorylation was observed with cmvpp65mii / viii , as well as the negative controls cmvpp65 mtth and cmvpp150 . to further characterize which residues were phosphorylated , an sds - page membrane blot containing the phosphorylated products was incubated with specific monoclonal antibodies directed to the phosphorylated residues of serine and threonine . the pk assay was performed according to the same methods of the dot blot assay described above , except that unlabeled atp ( 30 mm ) was used in the sample reaction . phosphorylation was detected by incubating the membrane with specific anti - phosphoserine or anti - phosphothreonine antibodies ( 2 μg / ml ), ( sigma chemical co ., st . louis , mo .) and revealed by immunoperoxidase staining using a vectastain abc kit ( vector laboratories , inc ., burlingame , calif .) ( 40 ). the results ( fig5 ) showed that autophosphorylation ( without casein as substrate ) and casein phosphorylation were revealed using anti - phosphothreonine antibody only with the cmvpp65n and cmvpp65 mviii reactions , but not with cmvpp65mii and cmvpp65m ii / viii or with the negative control cmvpp65 mtth and cmvpp150 . no serine phosphorylation was detected in any of the immunoprecipitated cmvpp65 protein ( data not shown ). see fig5 . to investigate whether the mutation of the pk domains in cmvpp65 interferes with epitope presentation on a target cell surface for recognition by ctl , chromium release assays were performed . a human cd8 + ctl clone 3 . 3f4 , with specificity for cmvpp65 hla a2 epitope ( 10 ) was used as the effector in a chromium release assay using hla - type ( lcl - a2 ) matched or mismatched ( lcl - all ) ebv - transformed b lymphocyte targets . all target cells were infected with vac - pp65n , vac - pp65mii or wild - type vaccinia virus ( vac - wt ) overnight at moi = 5 , then incubated for four hours with 200 μci 51 cr ( icn pharmaceuticals inc ., costa mesa , calif .). the mhc - mismatched control lcl - all also was infected with vac - pp65mii . the cells were assayed using the methods of mclaughlin - taylor et al . ( 30 ). spontaneous release ( without effector ) and maximum release ( lysed in 2 % sds ) of radioactivity were determined for each target . specific cytotoxicity was expressed as ( effector cpm − spontaneous release cpm )/( maximum release cpm − spontaneous release cpm )× 100 . as shown in fig6 , clone 3 . 3f4 recognized cells presenting the cmvpp65 mli epitope as efficiently as cells expressing the cmvpp65n ( native ) epitope . there was no significant difference in cytolytic effect at any of the various effector - to - target ( e : t ) ratios . this suggests that the point mutation of the invariant lysine k436n , which eliminates pk activity , does not negatively affect the hla - restricted presentation of cmvpp65 ctl epitope . transgenic hla a * 0201 mice were immunized with cmvpp65 dna to test for ctl activity in response to the immunogen . the transgenic mice have been described previously by benmohammed et al ., hum . immunol . 61 : 764 - 778 , 2000 and vitiello et al ., j . exp . med . 173 : 1007 , 1991 . the known cmv epitope , nlvpmvatv ( seq id no : 6 ; peninsula laboratories , inc . san carlos , calif . ; 95 % pure ) was used in a specific chromium release assay to demonstrate the efficacy of the dna vaccine administered to the mice . the mice express human hla antigens , therefore this mouse model permits the study of the immunologic response to human cmv as presented in the context of a normal human hla molecule and to evaluate the protection a vaccine will elicit in humans . the specific epitope of seq id no : 6 is known to elicit human cd8 + t cell activity in hla a * 0201 cmv - seropositve individuals . the cmvpp65 gene was inserted into the pbluescriptii ks + vector and was modified as follows . the cmv intron a of the immediate - early gene ( 823 bp ) was inserted in front of the pp65 gene at the spe1 / bamh1 site using pcr with the following primers : forward : 5 ′- gaattcactagtgtaagtaccgcc - 3 ′. ( seq id no : 7 ) ecor1 spe1 reverse : 5 ′- gactggatccctgcagaaaagaccc - 3 ′. ( seq . id no : 8 ) bamh1 the introna / cmvpp65 gene , still in pbluescript ( see fig7 ), was mutagenized as described in example 1 using the quickchange ™ site - directed mutagenesis kit ( strategene , san diego , calif .). the introna / cmvpp65 mutant ii gene ( pcdnaintpp65mii ), the expression product of which exhibits no phosphokinase activity , was removed from pbluescript with the spe1 and ecor1 site of the pcdna 3 . 1 + vector ( invitrogen , san diego , calif .). the control plasmids , including the introna / cmvpp65 native ( pcdnaintpp65n ) and the intron a alone ( pcdnaint ), were inserted in the pcdna3 . 1 + vector as well . all plasmids &# 39 ; dna were transformed in dh5α competent cells , grown in terrific broth ( gibco - brl life technologies , grand island , n . y .) and isolated using the qiagen maxi kit ( qiagen , valencia , calif .). the introna / cmvpp65n and introna / cmvpp65mii dna were removed from pbluescript , inserted into the psc11 vector at the spei and kpni site , and transfected into cv1 cells as described above in example 1 . the cv1 cells were simultaneously infected with wr strain vaccinia and the recombinant plasmid and were plaque purified three times to ensure clonality and purity . to titer the vaccinia virus in the ovaries , cv1 cells were plated at a density of 1 . 25 × 10 5 cells per well in a 24 well plate . the ovaries were collected , dissected free of fat tissue , weighed and frozen at − 80 ° c . until ready for processing . they were homogenized with a teflon homogenizer on ice , sonicated three times for 30 seconds , resuspended in 100 μl of medium and diluted serially . an aliquot was added to the cv - 1 cells , incubated overnight and stained with crystal violet the next day . transgenic hla - a2 . 1 mice were constructed by microinjection of a chimeric molecule containing the α2 domains of the hla - a * 0201 gene and the α3 domain of murine h - 2 kb into fertilized eggs from c57bl / 6 mice as described previously ( hogan , et al ., 1986 . manipulating the mouse embryo - laboratory manual cold spring harbor laboratory . cold spring harbor , n . y . ; vitiello et al ., j . exp . med . 173 : 1007 , 1991 ). the hla - a * 0201 expression was verified by facs using mab bb7 . 2 , parham et al ., hum . immunol . 3 : 277 - 99 , 1981 ; benmohammed et al ., hum . immunol . 61 : 764 - 779 , 2000 , and by pcr according to a modified protocol described by krausa et al ., tissue antigens 45 : 223 - 231 , 1995 . the transgenic mice were called tga2 / k b for the chimeric mhc molecule . six to eight week old tga2 k b mice were inoculated intra - muscularly every 4 weeks with 50 μg qiagen column purified dna in 50 μl sterile pbs in each thigh . the mice were immunized with pcdnaintpp65n , pcdnaintpp65mii and pcdnaint as control plasmid . the spleens were collected 4 weeks after the last immunization . when applicable , the mice were challenged on day 7 after the last inoculation , ip , with 5 × 10 6 pfu of recombinant vaccinia expressing pp65n and the ovaries were collected 5 days later to titer vaccinia . the spleens were collected as well to check for the presence of specific cmvpp65 ctl . blood samples were collected prior to each injection during the immunization process and the sera isolated and frozen at − 20 ° c . the sera were diluted at 1 / 50 and 1 / 100 and incubated with mrc - 5 cells previously infected with toledo cmv strain for 3 days . the presence of the pp65 protein was revealed with a biotinylated antimouse igg and immunoperoxidase labeling ( vector laboratories , inc ., burlingame , calif .). when the sera were positive for pp65 ab , they were subjected to an elisa for quantitation . three days before the harvest of effector cells from immunized tga2 k b mice , blasts cells were prepared from syngeneic spleen cells ( 1 spleen for 3 immunized mice ) and cultured at a concentration of 1 × 10 6 cells / ml in complete rpmi ( 10 % heat - inactivated fbs , 50 units / ml pen / strep , 10 mm hepes , 2 mm l - glutamine , 5 × 10 − 5 m β - mercaptoethanol ) and stimulated with 25 μg / ml lps ( sigma , st louis , mo .) and 7 μg / ml dextran sulfate ( sigma , st louis , mo .). the cells were subjected to in vitro stimulation ( ivs ) as follows . stimulated blast cells ( targets ), resuspended at a concentration of 25 × 10 6 cells / 0 . 2 ml serum - free rpmi with 100 μm cmvpp65peptide 495 ( seq id no : 6 ) and 3 μg / ml of β2 - microglobulin , were incubated at 37 ° c . for 4 hours with regular mixing to load the targets with peptide . the cells then were irradiated at 3000 rads using a isomedix model 19 gammator ( nuclear canada , parsippany , n . j .) and plated in a 24 well plate ( 1 × 10 6 blasts per well ) in complete rpmi supplemented with 10 % rat t - stim culture supplement ( becton - dickinson , franklin lakes , n . j .). each well also contained 3 × 10 6 immunized spleen cells . a second ivs procedure was done 7 days later using the same protocol . t2 cells ( atcc crl - 1992 ), lcl - a2 cells ( human ebv transformed cell ), el4a2 cells ( mouse h - 2b cell stably transfected with the a2 gene ) presenting the hla - a * 0201 allele and lcl - a3 cells ( control hla cell line ) were used as targets . for chromium release assay ( hla - specific , antigen - specific cytolysis assay ), the target cells were incubated with 200 μci 51 cr with or without peptide ( 100 μm ) and 12 - microglobulin ( 3 μg / ml ) for 1 hour at 37 ° c . they were washed and mixed at a effector : target ( e / t ) ratio of 100 : 1 to 10 : 1 in a 96 - well bottom plate with effector cells ( immunized spleen cells ). the effectors and targets were co - incubated for 4 hours and an aliquot was counted using a topcount tm counter ( packard instrument co , downers grove , ill .). specific ctl clones ( e . g . 19m3 ) were maintained in culture by weekly stimulation with peptide loaded blasts in complete rpmi with 10 % rat stim or 20 units / ml of rhil - 2 . four mice were immunized with pcdnaintpp65n and two mice with pcdnaint ( controls ). one out of four mice generated specific ctl which recognized and lysed peptide pp65495 loaded t2 cells after one in vitro stimulation ( 20 % lysis ), and two after a second in vitro stimulation ( 39 % and 44 % lysis ). the effector cells from mice immunized with control dna did not lyse the target cells , showing that the assay was specific . the other control hla - mismatch lcla3 target cells were not lysed by either responsive ctl cells m2 and m4 . the results show that construct , pcdnaintpp65n , which expresses the native gene of cmvpp65 , elicits ctl activity in the transgenic mouse model . more importantly , the ctl generated specifically recognize the minimal cytotoxic epitope of pp65 for the hla a * 0201 , nlvpmvatv ( seq . id no : 6 ), presented by the human cell line t2 . see fig8 for results . the methods of example 6 were repeated , except that the mice were vaccinated with pcdnapp65mii gene inserted in the same mammalian expression vector as pcdnapp65n . two out of 3 mice responded to pcdnapp65mii dna immunization with almost 90 % specific lysis of the target t2 cell loaded with the epitope of seq id no : 6 . see fig9 . the mutated cmv protein therefore is at least equivalent to the native sequence in its ability to elicit a ctl response . a ctl clone generated from mutant cmvpp65 immunization specifically recognizes only hla compatible targets a ctl clone ( 19m3 ) generated by the mutant pp65 immunization and weekly stimulation with seq id no : 6 loaded blasts was grown in culture and used to lyse the following target cell lines : t2 , lcla2 , el4a2 and lcla3 ( hla mismatch ). only the hla a * 0201 expressing cells were lysed . see fig1 . these results demonstrate that the mutant cmvpp65 protein elicits specific ctl activity and performs the functions necessary for successful vaccination . two ctl clones were not able to lyse hcmv - infected fibroblasts , however fibroblasts infected with the towne strain of cmv at an moi of 5 were lysed at 30 % and peptide loaded t2 cells at 85 % by the ctl clones . see fig1 and table i . the serum from immunized mice were tested for specific antibody response to the pp65 protein by immunohistochemistry on cmv - infected mrc - 5 cells ( infected for 3 days at moi : 02 ). the mice in each immunization group , pp65n or pp65mii , which developed cytolytic activity to the pp65 protein , responded with antibody production . sterile microtiter plates are coated with 100 μl per well rat anti - mouse ifn - γ ( 2 μg / ml ) in 50 mm sterile filtered carbonate buffer , ph 9 . 6 ( 21 μl / 10 . 5 ml ) with overnight incubation . the plates then are washed twice with rpmic and blocked for 1 - 3 hours . the medium is replaced and 2 × or 3 × serial dilutions of effector cells ( from 1 × 10 6 to 1 . 25 × 10 5 in 100 μl ) irradiated feeder / target cells ( 2 . 5 × 10 5 cells plus / minus peptide or transfected with pp65mii in 50 μl or 5 × 10 6 c / ml ). stimulation factors ( cona , peptides , pp65 ) are added , plus rat stim . cell lines such as t2 ( loaded or not loaded with peptides ) also may be used . after 8 - 24 hours incubation , the plate is washed with dih 2 o cycle p03m8 to remove the cells , then with 1 × pbs plus 0 . 05 % tween - 20 ( pbst ) with cycle p03m8 and blotted . biotinylated anti - ifn - γ ( 100 μl / well ; 1 . 25 μg / ml in pbst ; pharmingen , san diego ) was incubated in the wells overnight at 4 ° c . the bound antibody is detected with an alkaline phosphatase streptavidin according to known methods . table i cytolytic response to cmvpp65 dna immunization with a vaccinia challenge ( recvacpp65n ). response after two response after one in vitro vaccinia titer ex vivo response in vitro stimulation stimulations per ovary e / t 10 30 100 10 30 100 10 100 100 ratio dnapp65mii m2 1 . 8 4 9 . 2 7 . 8 15 . 2 45 . 6 nd nd nd 3 . 4 × 10 4 m4 1 . 5 1 . 6 4 . 4 0 . 2 8 . 3 16 . 7 nd nd nd 3 . 9 × 10 4 m4 ( 2 ) 1 . 1 0 . 3 3 . 4 3 . 97 1 . 81 13 . 24 22 51 . 2 81 . 7 5 m3 − 1 . 3 − 3 . 7 − 3 . 4 0 . 2 − 2 . 2 − 1 . 1 nd nd nd 9 . 5 × 10 4 m3 ( 2 ) 1 . 9 0 . 3 0 . 4 − 3 . 9 3 . 31 0 . 12 1 . 3 8 . 9 24 4 × 10 6 ml − 2 . 1 − 1 . 3 2 . 9 − 1 . 8 − 0 . 6 1 . 9 nd nd nd 1 . 25 × 10 5 dnapp65n m3 − 1 . 4 0 . 2 − 2 . 7 2 . 3 2 . 83 18 . 17 8 . 49 12 . 11 28 . 09 2 . 75 × 10 4 ml 3 . 2 0 4 . 3 − 0 . 7 − 1 . 43 − 2 . 2 − 2 . 63 0 . 59 5 . 92 6 × 10 4 m2 − 3 − 1 . 1 1 . 2 − 1 . 6 0 . 47 − 4 . 9 5 . 46 6 . 38 3 . 55 1 . 4 × 10 5 m4 − 2 . 2 − 2 . 4 − 2 . 6 0 . 24 − 3 . 2 − 2 . 6 0 . 59 − 1 . 97 0 . 53 5 pcdnaint c1 − 0 . 6 − 1 1 . 9 − 2 . 7 − 4 . 14 − 2 . 35 − 6 . 12 − 2 . 57 − 1 . 78 2 × 10 4 c2 − 1 . 2 − 0 . 7 − 1 . 7 − 2 . 02 − 0 . 45 − 0 . 33 1 . 64 2 . 96 12 . 11 2 . 3 × 10 4 ( 12 ) elroy - stein et al ., new york , n . y . : greene publishing ; p . 16 - 63 , 1991 . ( 19 ) glover et al ., san diego , calif . : academic press , inc . ; pp . 85 - 90 , 1991 . | this invention relates to mutated cmvpp65 , a viral structural protein which activates cell mediated immunity in humans infected with cmv . the mutations remove undesirable protein kinase activity naturally present in the protein and make it suitable for the production of both dna and protein vaccines . therefore , the invention provides proteins and dnas , as well as vaccines comprising the proteins and dnas , including cellular vaccines and vectors . other embodiments of the invention relate to methods of enhancing immune response and vaccinating against cmv , including gene therapy methods and vectors . |
fig1 shows a first exemplary embodiment of an upright wheeled walker 100 with a frame 102 supported above a surface 104 on four wheel assemblies 106 a - d , which each define one of the ( in this example ) four vertices of a polygonal walker footprint 103 on surface 104 , and with an upper body support assembly 108 . wheel assemblies 106 a - d may be appreciated with reference to the left front wheel assembly 106 b ( see fig1 ), which includes a wheel 110 b and a wheel suspension assembly 112 b that is fixed to frame 102 at a junction 114 b . the polygonal walker footprint may , of course , be defined by three wheels located at three vertices or any larger number as well . during use , a user 300 ( see fig7 b ) stands between the two anterior frame elements 116 a - b within polygonal walker footprint 103 and grasps each of the upper handles 118 a - b with a respective hand 302 a - b ( fig7 b ) while resting a respective forearm 304 a - b ( fig7 b ) in each of the armrest gutters 120 a - b , thereby resting at least some weight on upright wheeled walker 100 and surface 104 . the user may then walk forward in the direction shown by the arrow 122 as upright wheeled walker 100 rolls over surface 104 while supporting at least some weight , thereby assisting the user to walk over surface 104 . fig1 also illustrates an x - folder element 124 and an upper folder element 126 that are useful for collapsing upright wheeled walker 100 for convenient storage and transportation . the elevation adjusters 128 a - b are useful for adjusting the elevation of upper body support assembly 108 above surface 104 for a particular user height and each of the angle adjusters 130 a - b are useful for adjusting the angle of the respective upper handle 118 a - b . the lower handles 132 a - b are useful for several purposes such as providing user support when arising from a seated position ( not shown ), for example . fig1 also shows exemplary dispositions for the various sensor , processor and control elements of walker 100 . for example , several small microwave doppler sensors 134 a - d are shown ( see also fig4 ) attached to a respective wheel suspension assembly exemplified by the microwave doppler sensor 134 b shown attached to wheel suspension assembly 112 b . and the incline sensors 136 a - b are each shown attached to a respective lower frame element 138 a - b to detect longitudinal tilting of lower frame elements 138 a - b . the 3d infrared ( ir ) sensors 140 a - b are each shown attached to a respective posterior frame element 142 a - b to detect mid - level obstacles . a system controller assembly 144 is shown attached to one side of upper folder element 126 in a disposition permitting folding ( not shown ) of the walker without interference . a graphical user interface ( gui ) display 146 is disposed within convenient reach of the user and a loud - speaker ( not shown ) for emitting audio signals to the user may also be provided nearby ( see fig8 a , for example ). a simple optical sensor 148 is shown attached to upper body support assembly 108 in a position that operates as a user sensing means for producing a user detection signal responsive to a user disposed properly within the polygonal walker footprint . finally , fig1 shows an exemplary disposition of a plurality of kinetic motors , exemplified by the kinetic motor 150 a in right armrest gutter 120 a , the kinetic motor 150 b in left armrest gutter 120 b , the kinetic motor 152 a in right upper handle 118 a and the kinetic motor 152 b in left upper handle 118 b ( see also fig5 ). according to this invention the kinetic motors are disposed to provide haptic signaling to the user for a variety of purposes , such as alerting the user to obstacles and terrain hazards , suggesting a steering operation , for example . similarly , the handle touch sensors 154 a - b are each shown disposed on a respective upper handle 118 a - b to produce a user touch signal responsive to touching of the respective upper handle 118 a - b by the user . according to this invention , this user touch signal may be used in a user safety controller ( fig2 ) to operate an automatic electrohydraulic braking system ( fig1 - 14 ), for example . the various signal and power connections among the various sensor , processor and control elements attached to walker 100 are not shown in fig1 but may be appreciated with reference to the following fig2 - 20 . fig2 is a functional block diagram of an exemplary walker control system embodiment 149 illustrating the relationship among several control system elements and signals provided for automatic obstacle avoidance and user safety in an exemplary walker embodiment . the various elements are labeled with the numerals used above with respect to fig1 . additionally , system controller assembly 144 includes a microprocessor 155 , with a random access memory ( ram ) 156 coupled by means of a digital data bus 157 to gui 146 and the other elements substantially as shown . one such element is the electrohydraulic braking system 158 coupled to data bus 157 , which includes a braking controller 159 , a hydraulic system 160 for producing pressure in a hydraulic line 161 , and a plurality of caliper pistons 162 a - b each disposed to impose a braking force on a respective caliper assembly ( see fig1 - 14 ). handle touch sensors 154 a - b are each shown producing a user touch signal that is coupled to microprocessor 155 by means of digital data bus 157 . incline sensors 136 a - b are each shown producing an incline detection signal that is coupled to microprocessor 155 by means of digital data bus 157 . a plurality of kinetic motors exemplified by kinetic motors 150 a - b and 152 a - b are disposed ( fig1 ) to produce a haptic sensation in the user responsive to a user alert signal 141 transferred on digital data bus 157 . microwave doppler sensors 134 a - b and 3d ir sensors 140 a - b each produce a respective obstacle detection signal exemplified by the obstacle detection signal 143 , which is also transferred on digital data bus 157 to microprocessor 155 for use in computing user alert signal 141 . a loudspeaker 163 may be coupled through an audio controller 164 to data bus 157 for creating audio response to a second user alert signal 145 as desired . user alert signals 141 and 145 are produced by microprocessor 155 according to a stored program from ram 153 responsive to the several sensor output signals exemplified by obstacle detection signal 143 ( see also fig2 a - f ). finally , fig2 shows the plurality of kinetic motors exemplified by kinetic motors 150 a - b to each include a respective haptic controller 166 a - b to facilitate coupling to user alert signal 141 presented on data bus 157 . fig3 shows a second exemplary embodiment of an upright wheeled walker 400 with a frame 402 supported above a surface on four wheel assemblies exemplified by wheel assemblies 406 a - b , which each define one of a plurality of vertices of a polygonal walker footprint on a surface ( see the above discussion of fig1 ), and with an upper body support assembly 408 . the four wheel assemblies , exemplified by the visible wheel assemblies 406 a - b in fig3 , may be better appreciated with reference to fig1 detailing right rear wheel assembly 406 a , which includes a wheel 410 a and a wheel suspension assembly 412 a that is fixed to frame 402 at a junction 414 a . the circumferential brake housing 416 a housed and partially conceals a circumferential brake disk 506 and a circumferential braking element 508 that are discussed below in connection with fig1 - 17 . fig4 illustrates the operation of the obstacle avoidance features of upright wheeled walker 100 mentioned above in connection with fig2 and described in more detail hereinbelow . the various elements are labeled with the numerals used above with respect to the discussion of fig1 . exemplary obstacles and hazards such as a curved wall 168 , a curb 170 and a stairway 172 are illustrated to improve appreciation of the function and operation of doppler microwave sensors 134 a - d and 3d infrared ( ir ) sensors 140 a - b . fig5 is an oblique view of the upper body supporting elements of the walker embodiment of fig1 illustrating an exemplary disposition of the plurality of upper handle touch sensors 154 a - b , upper handle kinetic motors 152 a - b and armrest gutter kinetic motors 150 a - b suitable for providing haptic feedback signals to the user grasping upper handles 118 a - b during use . fig6 is an oblique view of the upper body supporting elements of fig5 illustrating exemplary dispositions of gui display 146 , processor 144 and a user sensing camera 174 on upper folder element 126 for producing a user detection signal . fig7 a illustrates a closer view of upper handle kinetic motors 152 a - b and armrest gutter kinetic motor 150 a from fig1 and 5 for providing haptic feedback signals to the user . fig7 b shows how the user 300 may engage these haptic feedback elements with hands 302 a - b and forearms 304 a - b while standing and walking within the polygonal walker footprint ( see also fig1 and 5 ). fig8 a - b show other exemplary embodiments and dispositions of a forward - looking infrared ( ir ) obstacle sensor 176 ( directed along the arrow 122 in fig1 ), a system controller and speaker assembly 178 and a cell phone gui display 180 suitable for use with the walker of this invention . gui display 180 may be embodied with , for example , an ios or android cell phone os and connected to system controller and speaker assembly 178 with , for example , a data cable , a bluetooth link or a wi - fi link ( not shown ). a dedicated software application ( a walker app , for example ) may be adapted to log and track bioinformatics and link to a central server ( not shown ). the relevant bioinformatics database maybe maintained on a remote or local server including hosting and load balancing functionality . biometric data collected from the user may be provided by external or internal user devices and transmitted to , for example , a walker app hosted in the cell phone comprising gui display 180 . fig9 is a block diagram illustrating the operation of a first alternative walker control system embodiment 182 . a plurality of walker sensors each produce a digital sensor output signal , exemplified by the digital sensor output signal 184 a , responsive to a respective sensor input ( not shown ), such as an input to ( see fig1 - 2 ) optical sensor 148 , handle touch sensor 154 a , incline sensor 136 a or doppler microwave sensor 134 a , for example without limitation . these digital sensor output signals are coupled by means of a data bus 186 to the microprocessor 188 in any useful manner known in the art . microprocessor 188 produces a digital control output signal 190 responsive to the digital sensor input signals on data bus 186 according to program instructions ( not shown ) stored in a ram 192 . digital control output signal 190 is transferred by data bus 186 to a kinetic motor driver 194 , which produces a kinetic motor driver signal 196 . kinetic motor driver signal 196 , which may be an analog voltage , for example , is applied to a kinetic motor 198 a to produce a vibration wave responsive to driver signal 196 . as described above , kinetic motor 198 a is disposed in an armrest gutter or an upper handle whereby the vibration wave will be felt by the user in hand or forearm as a haptic feedback signal ( see also fig2 , and 7b ) alerting the user according to the features of the stored program in ram 192 . fig1 illustrates the operation of a simpler walker control system embodiment 200 , showing kinetic motors 198 a - b , microwave doppler sensors 134 a - b , microprocessor 155 , ram 156 , 3d infrared ( ir ) sensor 140 a and a speed - sensitive braking control system the operation of which may be appreciated with reference to the above discussion of fig2 and the discussion below . fig1 illustrates an exemplary sensor embodiment 202 known in the art that is suitable for use with the walker of this invention . fig1 illustrates an exemplary sensor detection circuit embodiment 204 known in the art that is suitable for use with the walker of this invention . fig1 shows the detail of wheel assembly 106 b ( fig1 ) to better illustrate the hydraulic brake disk 206 and the brake caliper housing 208 . fig1 shows the functional operation of electrohydraulic braking system 158 ( fig2 ). system controller assembly 144 ( fig2 ) produces the digital braking control signal 212 on data bus 157 ( fig2 ), which is received by braking controller 159 . braking controller 159 produces a brake release signal 214 and a braking signal 216 responsive to digital braking control signal 212 . signals 214 and 216 may be analog voltages , for example , and each operates a respective hydraulic valve in hydraulic system 160 as follows . braking signal 216 operates the apply valve 218 to increase the hydraulic pressure in the brake line 220 and brake release signal 214 operates the release valve 222 to reduce the pressure in brake line 220 , thereby closing or opening the brake calipers 224 by moving a piston exemplified by piston 158 a ( fig2 ), thereby seizing or releasing hydraulic brake disk 206 in the usual manner . fig1 shows the details of wheel assembly 406 a ( fig3 ) to better illustrate partially - visible circumferential brake disk 506 and circumferential braking element 508 rendered visibly within a partially - transparent rendering of housing 416 a . fig1 is a schematic cross - sectional view of an exemplary embodiment of a circumferential braking system 500 of this invention . circumferential braking element 508 engages with the outer rim 518 of circumferential braking element 508 in the manner shown . increasing the pressure in a hydraulic chamber 510 forces one side of a lever arm 512 down - ward about the fixed axis 514 , the other side of lever arm 512 urges the coupler 516 upward , drawing circumferential braking element 508 upward to tighten the grip about outer rim 518 of circumferential brake disk 508 . this tightening operates to brake wheel 410 a ( fig3 and 15 ) by means of the increased friction between outer rim 518 and circumferential braking element 508 in the usual manner . reducing or releasing the pressure in hydraulic chamber 510 reverses this process and releases the brake at wheel 410 a . user control of circumferential braking system 500 is accomplished by touching and moving the handle 520 about the hinge 522 in a well - known manner to increase the pressure in the hydraulic chamber 524 , which pressure is transferred through the hydraulic line 526 in communication with hydraulic chamber 510 . in this manner , user movement of handle 520 controls the pressure in hydraulic chamber 510 , and the braking of wheel 410 a . fig1 provides a schematic oblique view of circumferential braking system 500 of fig1 to better illustrate the functional relationship among the various elements discussed above in connection with fig1 . any other suitable element for transferring force or power , such as cables or electrical power transfer means , for example without limitation , may also be used instead of the exemplary hydraulic elements ( e . g ., 510 , 524 and 526 ) illustrated in fig1 - 17 , as will be readily appreciated by those skilled in the art . fig1 a - b illustrates an exemplary embodiment of an electromechanical fail - safe braking control 228 . in one manner of operation , the user ( not shown ) grips a handle 118 a ( e . g ., fig7 a - b ) and squeezes the brake handle 532 to force it to turn about the hinge 534 and pull the cable element 536 attached to the underside of a rocker arm 538 . when squeezed by the user , handle 532 draws cable 536 about a pulley 540 to force rocker arm 538 down against a fail - safe switch 542 while rotating about the hinge 544 and compressing the spring element 546 . fail safe switch 542 is useful for signaling a braking system ( for example , electrohydraulic braking system 158 in fig1 ) to apply braking signal 216 when open and brake release signal 214 when closed to control the wheel brakes in an upright wheeled walker , for example . referring to fig1 a , fail - safe switch 542 is shown closed under pressure from rocker arm 538 , which is shown depressed against spring element 546 by the combination of user forearm weight and a user touch ( not shown ) on brake handle 532 . referring to fig1 b , fail - safe switch 542 is shown open as rocker arm 538 is forced upward by spring element 544 because of the release of all user forearm weight and user touch on brake handle 532 . in another manner of operation , if spring 546 is selected to be sufficiently weak , the weight and pressure of a user forearm ( not shown ) on top of rocker arm 538 may alone be useful to urge closure of fail - safe switch 542 with no need for a user grip on handle 532 . either method may serve to control a fail - safe braking system to ensure that upright walker wheel brakes cannot be released without a user grip on brake handle 532 or a user forearm force on rocker arm 538 or some combination thereof . fig1 illustrates an alternative gui touch panel display 226 suitable for use with the walker of this invention . fig2 a - f illustrate several exemplary signal processing specifications suitable for use with system controller 144 ( fig2 ) and each specification may be implemented in the program instructions stored in ram 156 , for example . these signal specification examples are neither exhaustive nor exclusive . fig2 a illustrates an exemplary relationship between the obstacle detection signal 552 from doppler microwave sensor 134 a ( fig1 ) and kinetic motor driver signal 196 to kinetic motors 150 a - b and 152 a - b in the handles and armrest gutters . fig2 b illustrates an exemplary relationship between the user detection signal 556 from optical sensor 148 and digital braking control signal 212 . fig2 c illustrates an exemplary relationship between the incline detection signal 558 from incline sensor 136 a and digital braking control signal 212 . fig2 d illustrates an exemplary relationship between output signal 552 from doppler microwave sensor 134 a ( fig1 ) and user alert signal 145 ( fig2 ) to speaker 163 . fig2 e illustrates an exemplary relationship between a user touch signal 560 from handle touch sensor 154 a and digital braking control signal 212 . fig2 f illustrates an exemplary relationship between the frequency of kinetic motor driver signal 196 and the computed obstacle distance derived from a sensor output signal combination 562 from obstacle sensors such as doppler microwave sensors 134 a or 3d infrared ( ir ) sensors 140 a , for example . clearly , other embodiments and modifications of this invention may occur readily to those of ordinary skill in the art in view of these teachings . therefore , this invention is to be limited only by the following claims , which include all such embodiments and modifications when viewed in conjunction with the above specification and accompanying drawing . | an upright wheeled walker with bilateral stabilizing wheel suspensions , and an automatic braking system integrated with obstacle avoidance systems , terrain sensors and user feedback controls . the walker provides user upper body weight support in a wheeled walker with a user safety system including a plurality of sensor , processor and control elements and an automatic braking system for avoiding unseen obstacles and automatic speed limiting on inclines . |
referring to the drawings in detail , the fishing lure of the present invention is designated by reference numeral 8 and is comprised of three basic parts , namely , a body member 10 , a flap member 12 pivotally mounted on the front portion of the body , and a hook assembly 14 attached to the underside of the rear portion of the body . in the preferred embodiment hook assembly is attached to body 10 by a pair of self - taping screws 15 . body member 10 is of two - piece construction comprising half - sections 16 , 18 as best shown in fig4 . externally the assembled body member 10 is of a substantially circular cross section the diameter of which decreases gradually from the nose portion 20 to the tail portion 22 . in the preferred embodiment , sections 16 , 18 of body 10 are made of abs plastic material . nose portion 20 is in the form of two substantially flat surfaces 24 and 26 which intersect along a substantially straight edge 28 at the front of body 10 . surface 24 is larger relative to surface 26 and extends at an angle of approximately 50 ° with respect to the horizontal axis a of the lure as shown in fig1 . the smaller surface 26 extends at an angle of approximately 35 ° with respect to axis a and the edge 28 between surfaces 24 and 26 lies a short distance below the axis a as also shown in fig1 . the included angle between surfaces 24 and 26 is approximately 85 °. referring to fig3 the body 10 of the lure ( comprising half sections 16 and 18 ) has an internal cavity 28 in which a stabilizer weight member 30 is mounted . weight member 30 is made of lead or other suitable material and is mounted in the central lower portion of the cavity 28 . the function of weight 30 is to provide the required weight for effective casting with a fishing rod and reel and to lower the overall center of gravity of the lure to thereby stabilize its action as it is retrieved through the water by the fisherman . the lure can be made to sink by adding a second weight 32 . in the preferred embodiment weight 32 is in the form of a lead ball loosely captured in a compartment 34 at the rear end of cavity 28 . the lure can be made in the form of a &# 34 ; floating &# 34 ; type lure by simply eliminating both weight members 30 and 32 . flap member 12 is comprised of a relatively large bill portion 36 , a pair of spaced arm portions 38 , 38 extending from the outer edge portions of bill portion 36 and a pair of mounting ears 40 , 40 extending downwardly at right angles from arms 38 . the included angle between the plane of bill portion 36 and the plane of arm portions 38 is approximately 135 °. in the preferred embodiment flap member 12 is made of a stainless steel stamping with bill 36 , arm portions 38 and ears 40 formed integrally with each other . flap member is freely pivotally mounted on the nose portion 20 of body 10 by a pin member 42 . pin 42 in the preferred embodiment is in the form of a stainless steel rivet and it extends through aligned openings in ears 40 and aligned openings in the half sections 16 , 18 of body 10 . bill portion 36 is provided with an opening 42 for connecting the lure to the end of a fishing line . opening 42 is located in the center of bill portion closely adjacent the leading edge 43 thereof . the location of the pivotal connection between flap member 12 and body 10 is important . as shown in fig1 the pivotally connection is located below the horizontal axis a of body 10 and slightly forward of the rear most portion of nose face 24 . the &# 34 ; action &# 34 ; or hydrodynamic movement of the lure in the water when it is pulled through the water by trolling or retrieving with a casting rod and reel can best be explained by reference to fig1 and 6 . assume for purposes of explanation that a &# 34 ; floating &# 34 ; type lure ( no weight members 30 or 32 ) is to be used with a conventional spin casting rod and reel . the lure is casted out by the fisherman and will land on the surface of the water . if the lure is allowed to remain idle in the water it will float . when the lure is retrieved it will initially dive downwardly in the water to a depth of approximately 4 - 5 feet below the surface at which level it will level off for the balance of the retrieve . the depth to which it will dive before leveling off will depend primarily on the speed of the retrieve . as the lure is retrieved through the water at any given level the flap member 12 will pivot with respect to body 10 and at the same time the body 10 will move up and down in what can best be described as a vertical rocking movement . more specifically , the extreme upper pivotal position of flap member 12 is shown in fig5 and the extreme lower pivotal position of flap member 12 is shown in fig6 . the fig1 position of flap member 12 is an intermediate position . it will be noted that the extreme upper pivotal position of flap 12 , as shown in fig5 is limited by the physical contact between the edge 44 of bill portion 36 with the face 24 on body 10 . the extreme lower pivotal position of flap member 12 , as shown in fig5 is determined by the hydrodynamic forces acting on the lure . to summarize , the overall action of the lure is a combination of a rapid pivotal up and down movement of flap member 12 with a simultaneous rapid up and down rocking movement of the body 10 . such rapid combination of pivotal and rocking motions will be &# 34 ; continuous &# 34 ; as the lure is retrieved or trolled through the water . experience has shown that the vibrations produced by the pivotal movement of flapper 12 together with the rocking up and down movement of body 10 combines to produce an effective game fish lure . referring now to the &# 34 ; sinking &# 34 ; version of the lure requiring the provision of the extra weight members 32 and 30 , such sinking type lure when cast out by the fisherman is allowed to sink ( tail first ) to the desired depth . it is then retrieved at such depth . the action of the &# 34 ; sinking &# 34 ; version of the lure as it is retrieved through the water at the desired depth is very similar to that of the &# 34 ; floating &# 34 ; version as described above . the weight 34 loosely captured in compartment will &# 34 ; rattle &# 34 ; therein as the lure is retrieved to thereby send out additional sound waves through the water . | a fishing lure having a body member , a treble hook fastened to the body member , and a flap member pivotally connected to the nose portion of the body member . the nose portion of the body member is comprised of upper and lower substantially flat surfaces which intersect along a substantially horizontal straight line at the front most edge of the nose . the flap member is comprised of a forwardly extending flat bill portion and a pair of flat arm portions extending rearwardly from the side edges of the bill portion . the flat arm portions are pivotally connected to the nose of the body member . |
the system of the present invention can be used to collect the freshly voided urine specimen in familiar surroundings of the feline &# 39 ; s home , without the use of expensive equipment , or can be used in the vetinarians office , in an atmosphere familiar to a cat since it resembles a conventional litter box . in its &# 39 ; simplest form , it includes a nonabsorbent litter contained within a receptacle . for convenience , the litter can be initially contained in a bag which is opened or unfolded to expose the litter and refolded to provide for ease of disposal of the litter after usage of the system in a urine diagnostic procedure . in a further embodiment , a urine collection device can be provided which includes the nonabsorbent litter , a claw proof screen , a spacer and a urine impermeable member , all of which can be placed in a standard cat litter receptacle . in this embodiment , the receptacle does not have to be sterile since it does not come into contact with the urine . in another embodiment , the receptacle and the urine impermeable member are combined as one integrated , disposable unit . the spacer serves the function of keeping the feet of the cat away from the urine after the cat void , in order to avoid contamination of the specimen . since it is desirable that the receptacle be clean , and advantageously sterile a disposable receptacle provides desirable advantages . in a preferred embodiment , a sterile three - layer system is employed . the three layer system includes a claw proof screen , a spacer and a moisture impermeable membrane . the system and a nonabsorbent , chemically inert litter , are placed in a standard litter box . nonabsorbent mineral particles allow for the rapid entrance of the cat urine into the diagnostic pad with minimal absorption . the cat urine is transferred directly from overlying litter particles , through a cat claw resistant screen into a nonabsorbent spacer member of inert , self - supporting material and is collected on the liquid impervious bottom sheet . the liquid impervious bottom sheet can be secured to the litter box by means of the self - contained adhesive strips . immediate testing can be performed or the entire liner can be folded and stored in the refrigerator for later transportation to the veterinarian &# 39 ; s office where more than ten tests can be performed within a few minutes using commercially available dipsticks . people wishing to monitor their cats on a routine basis can be supplied with the instant invention in combination with the appropriate dipsticks . collection of the urine specimen involves lifting the system from the litter box , piercing the center of the liquid impervious sheet and collecting the urine in a specimen cup or delivering the urine directly onto a dipstick . a test device for detecting the presence of constituents in a liquid test sample , and method of preparation are disclosed in u . s . pat . no . 4 , 301 , 115 . the patent discusses the advancement of analytical chemistry and the popularity of the dip sticks . u . s . pat . no . 3 , 438 , 737 discloses a test composition , device and method for detecting protein in fluids comprising a ph chromogenic indicator material exhibiting protein error . the patent discloses the need for rapid , accurate test results . additional methods of improving the accuracy , ease and rapidity of testing results from body fluids are disclosed in u . s . pat . nos . 4 , 147 , 514 , 4 , 038 , 031 , 3 , 814 , 668 , 3 , 585 , 001 and 3 , 986 , 833 . in order to provide a clear understanding of the instant invention , the various aspects of the invention are hereinafter described in detail . the diagnostic pad structure of the instant invention includes a protective screening and a moisture impermeable liner . a protective screening is fully disclosed in u . s . pat . no . 4 , 640 , 225 , issued feb . 3 , 1987 , the disclosure of which is incorporated herein by reference thereto , as though disclosed herein in detail . the screen must be capable of withstanding the clawing action of an animal such as a cat , to protect the bottom layers . the amount of exposure to the cat &# 39 ; s claws is extremely limited in a diagnostic system and therefore the weight of the protective screening is not a critical factor and the weight and strength factors disclosed in the aforenoted patent can be reduced . other inert protective means can be used , preferably flexible , however they must meet the criteria set forth below . the holes in the screen are sized small enough to prevent the animal &# 39 ; s claws from reaching the underlying layers , while numerous and large enough to allow for rapid passage liquids . the screen is sealed to a moisture impermeable material along at least a substantial portion of their peripheral edges . a plastic film , such as polyethylene or polyurethane , or other inexpensive material can be used . the granular material as employed in the instant invention is utilized to satisfy the digging instinct of the animal and should not provide absorptive qualities . consequently , inexpensive nonabsorbent materials such as mineral particles such as small pebbles , rocks , stones gravel , coarse sand and the like , previously unsuitable as a cat litter material because of the lack of absorbency or ability to hold urine that pools in the bottom of the litter box can now be used as a more effective cat litter box filler when used with diagnostic pads . sand is a well known medium for use as cat litter . sand particles , such as used on construction and children &# 39 ; s sandboxes , do not absorb the urine in the manner that clay and other commercial litters absorb and hold large quantities of urine . in the case of sand , the urine appears to be held by surface tension within the densely packed material . consequently , common sand can not be used with the present invention and coarse or large size particles is critical to the proper operation of the invention . in contradistinction to the flow of liquid in sand , the more numerous air spaces between the larger particles in coarse mineral grit gives it an inherent ability to allow urine to rapidly drain into the collection region without impeding the flow or spread of the urine through out the pad . very fine particle such as fine sand or soil , will not act as good cat box filler because the flow of urine into the pad is impeded by the numerous , closely packed particles . unlike the commonly employed systems in which the granular material must be used in sufficient quantity to provide the required absorptive qualities and digging qualities , minimal quantities of the granular material can be used , as described herein , and sorbtion must be avoided . hence , proper sized nonabsorbent mineral particle cat box filler serves the function of ; 2 . allowing cat urine to fall rapidly over the particles into the diagnostic pad ; 3 . preventing scatter out of the litter box less than light weight clays and similar absorbent litters due to the density of the mineral particles ; 4 . litter is sufficiently inert such that it does not impart any contaminants to the urine which can affect the tests found on a commonly used dip stick , and 5 . producing less dust than clay , when washed and not being friable , therefor creating no dust of its own , allowing for cleaner specimens for testing . the use of a surfactant on the screen material can enhance the moisture transfer capability of the screen and is essential in combination with hydrophobic or low hydrophilicity screen materials . the selection of the surfactant must be such that it is chemically inert with respect to the urine and the reagents of the diagnostic tests . the quality of being chemically inert with respect to the diagnostice reagents is true for all elements of the system which come into contact with the urine . the particle size distribution can range from a few millimeters to several centimeters . common fine sand having a particle size at the lower end of sands , that is at the 200 mesh ( 0 . 074 mm .) size , pack so densely as to limit or restrict liquid flow between the particles . at the upper end of the particle size the sand or gravel material can be rejected by the cats . while reference has been made in particular to grit , it should be understood that nonabosorbent materials , in particular other inorganic minerals , in general will provide similar results . particularly suited to the instant invention is a coarse sand referred to as fine gravel commonly found in central new jersey . these gravels and sands were deposited during the formation of the early coastal plain . the grit is mined from beds that can be from glacial , riverbed or ocean basin origin . the sands and gravels consist mostly of quartz or silica . the available particles are found in a wide range of particle sizes and must be sieved to obtain the desired particle size distribution . the nonabsorbent particles must be sufficiently free of friable materials , such as clay , in order to avoid the filling of the interstices . the particles can be as small as one millimeter in diameter and as large as three centimeters . the preferred range , however , is between two millimeters and about one centimeter . it should be understood that the particles typically are not round , but rather , most typically are oval or irregular in shape and the diameter referred to is the average diameter of the particle . the particles are washed to get rid of the small dust particles and then air or oven dried prior to use as a nonabsorbent litter . alternate litter materials include grits formed from crushed stone , limestone and other naturally occurring reactive mineral systems . from an economic stand point , the optimum material is calcium carbonate , in the form of naturally occurring limestone . for aesthetic effect , the particles can be dyed to a particular color . mordant dyes can be used where the particles are silica . the particles can be coated to moderate the hydrophobicity or hydrophilicity of the surface of the particles . the use of waxes , silicons , and the like can be used in this regard . the use of water repellent coatings enables the use of materials whose absorbency would other wise be too high for the instant application . the coating can be of the type disclosed in u . s . pat . no . 3 , 562 , 153 ( tully et al , issued feb . 9 , 1971 ), the disclosure of which is incorporated herein , by reference . although the aforenoted patent relates to an oil absorbent material , the disclosure is generally applicable in regard to the instant invention to the extent that it teaches the means for coating a particle to render the particle water repellent . it should be noted that the disclosure in the patent of relevant particles sizes is totally inapplicable to the present invention and the teaching of the instant disclosure must be followed . as noted in u . s . pat . no . 3 , 562 , 153 the coating material can be an organosilicon compound , such as an organohalosilane , organosilylamines and organodisilazanes . additionally , the coating process and materials can be in accordance with the teachings of u . s . pat . no . 3 , 464 , 920 and 3 , 382 , 170 , the disclosure of which is incorporated herein by reference . the higher the hydrophobicity of the particles , the greater should be the particles size in order to prevent the water from hanging up above the particles . the thinner the layer of particles which is used , the finer the particles can be without the water being prevent from passing through the particles . in order to ensure that cat urine cannot penetrate the micro - cracks and pores on the surface of each granule and possibly cause odor formation , interact with particles or be unavailable for testing , it has now been found that various water repellent and water - proofing agents can be used to prevent this occurrence . also , each grit particle having water - repellent characteristics tends to cause the majority of the urine void to enter the urine collection region rather than cling to each particle or gather in the in spaces in between each particle . a variety of compounds can be used to treat mineral grit particles so as to make them water - repellent or water - proof economically . metallic stearates can be applied conveniently to mineral surfaces in a powder , liquid or suspension form . various stearates such as aluminum , calcium or zinc can be used . the hydrophobic nature of specific metallic stearates enables them to inhibit capillary absorption of water . hydrocarbon solvent solutions of witco aluminum stearates are utilized for water - repellent application to surfaces . to enable good penetration , an aluminum stearate solution should be as fluid as possible and should be applied to dry hardened surfaces . solutions of 2 to 10 % by weight of aluminum stearate non - gel a are used for low viscosity spray - on or brush - on applications . dow corning 772 water repellent is a nonflammable water soluble sodium methyl siliconate solution designed to impart water repeliency to a wide variety of surfaces . supplied at a 30 % solids in water , this water repellent is diluted to a concentration of 3 % before being applied . the siliconate reacts with moisture and carbon dioxide in the air to form an insoluble water - resistant resin within 24 hours . dimethyl emulsions and other types of silicone fluids can be used to effectively seal off micropores and make the granules waterproof . aqueous emulsions and solutions are desirable because they impart no odor to the granules . the process of application can be by tumbling , immersion , spraying or brushing . usually about 80 ml . of silicone liquid is added per 50 pounds of grit , however , this concentration can be altered to thin or thicken the coating . once coated , the grit particles are allowed to dry . the coating process also aids the &# 34 ; dustless &# 34 ; characteristics of the mineral grit as small dust particles are adhered and coated to the larger mineral particles . thus the coating process serves to wash the mineral grit as well as prevent the escape of any remaining particles . ______________________________________sieve size grit characteristics______________________________________pass 3 / 8 but large pebbles : no scatter but notonly 10 - 30 % thru # 4 suitable for use as cat0 - 10 % - # 8 litter . transmission rates acceptable85 - 100 % pass # 4 proper size for cat litter . minimumonly 10 - 40 % pass # 8 scatter or tracking . dustless . transmission rates acceptable085 - 100 % pass # 8 transmission rates still acceptable 10 - 40 % pass # 16 very small particles - still suitable for cat litter but trackless , scatterless properties now lost . 80 - 100 % pass # 8 particles too small to allow50 - 85 % pass # 16 required transmission rates . 25 - 60 % pass # 3010 - 30 % pass # 50 2 - 10 % pass # 100 too much scattering . ______________________________________ although glass beads , teflon coated particles , polypropylene or polyethylene , synthetic and natural resins can serve as the same function as nonabsorbent coarse sand or fine gravel , a large number of cats will reject the use of these products as a cat box filler . moreover , such particles , due to their low density , float on the urine and are difficult to separate from the urine due to wetting of their surfaces by the urine . very large particles such as large pebbles or gravel , rocks , etc ., tend to be undesirably heavy and rejected by cats when used as a cat box filler . digging is difficult with large heavy particles , thus contributing to rejection by cats . coase sand , by way of contrast , mimics the appearance of the commercially available absorbent clay litters and thus provides a familiar appearance to cats . further , it is readily used by the cat for digging and as a waste matter repository and has the advantage of resisting scattering and tracking by the cat . in addition , the nonabsorbent granules are non - friable and dusting is consequently negated . this feature is critical in diagnostic applications because of the need to separate the urine from the cat litter material . 1 - a bottom , impervious sheet 12 made from polyethylene or polypropylene serves to catch and hold the urine which flows down from the upper spacing layer . 2 - the middle layer or spacer 14 is constructed of a nonabsorbent material , such as a high loft , non - woven material , such as spray bonded high loft polyester , or other material that allows urine to pass through to the bottom impervious layer while providing support to the nonabsorbent grit digging medium above . examples of materials which would provide the required characteristics are those such as the spray bonded polyester sold by union wadding inc . ; thermobonded polyester , as sold by the burnett company ; the non - woven fabrics sold by stearns under the trademark fabray as well as any other economical materials that have body , are inert to urine and allow the urine from the above ripproof layer to flow through and collect on the bottom polyethylene sheet . the spacer 14 need only be about 1 / 8 &# 34 ; to 1 / 4 &# 34 ; high and serves to prevent the weight of the cat and the nonabsorbent litter from pressing down and dispersing the urine specimen over a broad area or back up into the nonabsorbent litter . 3 - a liquid transmitting , nonabsorbent , ripproof layer 16 covers and protects the space layer 14 and impervious sheet 12 . the ripproof sheet 16 serves to prevent the cat from tearing into the spacing layer 14 with its claws and , most importantly , from tearing the moisture impermeable bottom sheet 12 . it also serves to keep the nonabsorbent litter 18 from entering into and contaminating the urine specimen contained in the spacer layer 14 . the rip proof layer 16 , as described in u . s . pat . no . 4 , 774 , 907 , can be made of james river &# 39 ; s spunbonded nylon sold under the trademark cerex . the material weight can range from 0 . 5 to 1 . 0 oz . per sq . yard . a nonabsorbent litter 18 layer is placed on the ripproof layer 16 of the diagnostic pad 10 to provide a digging medium for the cat . the nonabsorbent litter 18 can be made of plastic resin beads of any type plastic , glass , etc . the preferred material , however , for economic and functional reasons , is the nonabsorbent mineral grit particles as described in copending u . s . patent application ser . no . 07 / 224 , 944 , filed jul . 27 , 1988 , which case is a continuation of 06 / 885 , 932 , filed jul . 15 , 1986 , the disclosures of which are incorporated by reference , as though set forth herein in detail . about 1 / 4 - inch deep of the nonabsorbent litter 18 sufficient to satisfy the cat &# 39 ; s digging urge . after the cat voids , the ripproof layer 16 and nonabsorbent litter 18 are removed , allowing for the urine be tested directly in the impermeable liner 12 or the entire impermeable liner 12 can be refrigerated and taken to the vet &# 39 ; s office . alternatively , the ripproof layer 16 and the impermeable liner 14 can be bonded along the periphery of the ripproof layer 16 . the urine can be removed from the bonded diagnostic pad 10 by puncturing the impermeable liner 12 and pouring the urine into a container . fig2 illustrates an alternate embodiment wherein the imprevious sheet 12 of fig1 is replaced by a receptacle or litter box 22 . this embodiment provides an diagnostic unit in which the entire unit is disposable . the receptacle 22 can be made of water proofed cardboard , plastic coated cardboard , or a vacuum formed plastic . the spacer 24 is placed in the receptacle 22 at time of manufacture and kept in place by the ripproof layer 16 which can be sealed to the sides of the receptacle 22 . the nonabsorbent litter 28 is placed on prior to use . alternatively , the ripproof layer 26 can be manufactured oversized with adhesive strips along the edges and the unit can be assembled prior to use . in fig3 an additional embodiment of the instant disclosure is disclosed wherein the nonabsorbent litter 34 is packaged in a bag 32 consisting of the same ripproof nonwoven known as james river cerex 0 . 5 to 1 . 0 oz . spunbonded nylon or other similar nonwovens such as dupont &# 39 ; s remay spunbonded polyester ( style 2214 ). in fig3 a drawstring bag 32 is illustrated , however this is done for simplicity as to illustrate all the various ways the bag 32 could be folded , tied and / or secured would be cumulative . the bag 32 is opened or unfolded to expose the litter and refolded after usage for ease of disposal . adhesive strips 36 consisting of hot melt adhesive and a wax paper overlay , as well known in the prior art , line the sides of the bag so that when it is placed in a litter box , the weight of the nonabsorbent litter 34 holds the bottom of the bag in place while the adhesive strips 36 provide for releasable attachment to the sides of the litter box . preferably , a high loft non - woven is used as a spacer between the grit and litter box for better collection of the urine specimen while not affecting the securing design of the mass produced unit . in fig4 a spacer 42 has been included as part of the bag 44 , thus providing an all - in - one unit which can be easily placed in a standard litter box . once a cat voids design , the urine sample will be found at the bottom of the litter box once the bag 32 is lifted out . if sterilization is required , particularly when used for different cats , it can be done via gamma irradiation . an alternate to the above use of a standard litter box is illustrated in fig5 wherein a specifically designed , inexpensive , sterile litter box 50 is provided with the bag 32 . the litter box 50 is designed with chambers 52 along the bottom to catch the urine more effectively and can incorporate a pour spout 54 for easier removal of the urine . the bottom of the litter box 50 can also be manufactured with waffle , randomly depressed , etc ., instead of the channels 52 . any type of depressions in the bottom can be used to collect the urine and the exact configuration would be based on manufacturing preferences . providing pre - sterilized litter and bag along with the sterile litter box would allow for collected urine to be analyzed for pathogenic organisms . the pre - sterilized diagnostic units would also eliminate the need for veterinarians to sterilize the litter boxes after each use . the sterile litter box 50 does not need to have the rigidity of a standard litter box due to its limited use and can be sized to fit inside of a standard litter box , which would provide the rigidity . a mirror image top can be provided to facilitate pouring the urine out of the litter box 50 . the bottom / snap top combinations are well known in the container art and are used extensively for store salad bars , packaging muffins , etc . an alternative to using dip sticks , manufactured by boehringer mannheim and ames division of miles laboratory , under the trademarks chemstrips and miles multistix , respectively , would be the use of biochemically impregnated paper . the impregnated paper can be placed in the bottom of the litter box 50 so that urine filtering down through the nonabsorbent litter and ripproof layer enters the pads . hence the pads can be checked after each void or daily , etc ., to see if the urine is acid , alkaline , contains blood , sugar , etc . the versatility of this design allows for easy individualized diagnosis as the impregnated paper can be provided for a specific individual &# 39 ; s needs . fig6 illustrates an alternate to fig3 and 4 wherein one or two large filter paper pads 62 and 64 would be used in conjunction with , and protected by , the claw resist nonwoven bag 60 . when the claw resistant bag 60 is produced the bottom is provided with an additional layer of fabric 66 , open on one side , which forms a pocket into which the filter paper pads 62 and 64 are placed . when the urine passes through immediate test results would be provided . an example of the system would be filter paper pads impregnated with phenol red at a ph of 6 . 0 in one and guiac solution in the other . when urine passes through the nonabsorbent litter and the porous bag , it enters the absorbent pads . if blood is present in the urine , the pad containing the guiac solution turns blue . the pad containing the phenol red solution will give the ph of the urine . cats with a past history of kidney stones or urinary tract blockage should have an acid urine if they are to avoid continuous problems . the absorbent pad treated with phenol red would display a yellow color for acid urine , yellow - orange for neutral and red to red - purple for alkaline urine . the presence of blood in analkaline urine could indicate crystalline formation within the cat &# 39 ; s urinary tract . a further embodiment is disclosed in fig7 wherein an absorbent layer 74 is placed between the impervious layer 72 and the spacer 76 . the absorbent layer 74 is similar to the biochemically impregnated card as described above , and is overlaid by the optional spacer 76 and the ripproof layer 78 , as describe in fig1 . the absorbent layer 74 is an absorbent non - woven or paper material which has been treated with the proper indicators of blood , ph , etc . as an alternative , the treated absorbent layer 74 can be replaced with a non - treated absorbent white pad for those not wishing to use an occult blood test , simply knowing that they should observe the white pad for blood stains is enough to guarantee that health problems associated with the aforementioned can be immediately recognized and treated . in an alternate embodiment to fig7 only the top three layers would be used and the urine would collect directly into the sterile litter box . the embodiment of fig6 and 7 allow for rapid observation of ph , blood , etc ., while using an existing litter box . it should be understood that the absorbent layer is not equivalent in function or purpose to that of absorbent litter . in the instant embodiment , the absorbent layer serves as a medium for the diagnostic reagents . the absorbent paper pads can be impregnated with other chemicals for detecting glucose , albumen ( protein ) ketones , etc ., and used in the urine collecting litter box in place of the ph or blood detecting pads . optionally , all reagents can be combined within one large absorbent pad for simultaneously running of a plurality of different tests . an alternate means of immediate diagnostic determination can be made by use of the diagnostic pad or diagnostic units described above , wherein after the cat voids biochemical reagents in liquid form would be added directly to the top layer of the liner . the colors would develop and give visible evidence to the ph of the urine , blood , etc . | the invention relates to a diagnostic system for testing animal urine and includes a device for the collection of the urine . the system uses granular particles which are nonabsorbent particles having sufficiently large diameter to provide sufficient interparticle spacing to permit free flow of urine from the particles to the collection region below . the base of the litter box can serve as the urine collector , but preferably , a moisture impermeable liner provides this function . in the use of the instant device for diagnostic purposes , the urine is allowed to pass through the grit , due to its non absorbency , into collection areas . early evidence of many diseases can be detected , as well as the monitoring of ongoing treatment , through urine analysis . the grit can be used in combination with waffle type support inserts , plastic liners or a spacer member . |
the aim of the present invention is to create a device that makes it possible to overcome the drawbacks of the devices based on the described state of the anterior technique . it consists of a resilient endocardial device designed to reduce one or more diameters , as well as the volume of the ventricle , by reducing its mitral annulus and / or equatorial circumference and / or apex . this resilient device has the characteristic of being elastically deformable radially and plastically deformable axially . the construction characteristics of the said device also have the advantages of allowing a multiple and modular distribution of the aid to systolic function , a gradually increasing resilience that is non - linearly related to end - diastolic pressure , from the systolic to the diastolic phase , thus avoiding greater volumetric constriction and the possible consequence of diastolic interference . a further advantage of the device of the present invention is that it can be applied without the need to reduce cardiac mass . its axial plastic deformability allows its adjustment to the endocardial wall remodeling the left ventricle in the original shape by means of the prosthetic device of the invention , it is possible the reconstruction of optimal cardiac chamber geometry obtaining a wall stress that is modularly redistributed on the prosthetic material and the cardiac wall . the device is characterised by elastic properties appropriately designed according to a non - linear law . the said non - linear elasticity allows the device to act as an aid to systolic function during the contraction phase ; as far as diastolic function is concerned , the same non - linear law of elasticity means that the device does not interfere with diastolic function : in fact , although opposing a progressively increasing resistance against dilatation , the said device does not statically constrict the heart by impeding its expansion within physiological limits , as in the case of the devices described in wo9814136 and wo9944534 . it is possible to combine the implantation of this device with other epicardial and intracardiac procedures ( mitral valvuloplasty , mitral valve replacement , aortic valve replacement . cabg , etc ) made necessary by the disease , and it is likewise possible to personalise the ventricular remodeling on the basis of the functional , volumetric and geometric characteristics of the patient &# 39 ; s ventricle by using the device in different ways ( in different numbers and sizes ). the figures make it possible to understand better the inventive aspects of the device . fig1 is a cross - section of a ventricular cavity , with the device located in various positions ; fig9 shows a cross - section of a ventricular cavity with devices connected by axial elastic elements ; fig1 shows a cross - section of a ventricular cavity with devices connected by elastic elements having axial and radial components ; fig1 shows another type of device with a covering fig1 shows another type of device with a covering . fig1 shows a ventricular cavity / left ventricle 1 in which , at the top , the aorta 9 is visible ; the devices of the present invention are inserted on the endocardium 2 of the ventricular cavity 1 , and consist of devices 6 , 7 or 8 , which are substantially elliptical , circular or asymmetrical in shape ( see fig2 - 8 ) and are in any case adjustable to different sections 3 , 4 or 5 of the internal perimeter of the endocardium 2 , in a number depending on the characteristics of the dysfunctioning ventricle . without modifying the functioning underlying the present invention , the devices may have different shapes and different sections . they may likewise be open or closed , as shown respectively from fig2 to fig8 , in order to leave free the normally functioning areas of the ventricle . the different sizes of the said devices depend on the dimensions of the ventricle and also on the different diameters of sections of the same ventricle . in fact , with reference to fig1 , device 6 can be positioned on the diameter relating to the mitral annulus 3 , or device 7 can be positioned on an equatorial diameter 4 , and device 8 can be positioned on the apical diameter 5 . with reference to fig2 , the devices have a solid rectangular section , visible in the centre , and may be an open band , as shown on the left , or a closed ring , as shown on the right . with reference to fig3 , the devices have a solid circular section , visible in the centre , and may be an open band , as shown on the left , or a closed ring , as shown on the right . with reference to fig4 , the devices have a hollow bellows - like circular section , visible in the centre , and may be an open band , as shown on the left , or a closed ring , as shown on the right . with reference to fig5 , the devices are made as open or closed bands in the form of a flat spring , which may be continuous or discontinuous . with reference to fig6 , the devices are made as open or closed bands in the form of a helicoid spring , which may be continuous or discontinuous . as already said , the devices are plastic in the direction of the axis of the ventricle ( see fig7 and 8 ) and elastic in the direction of the ventricular radius : this leads to an active diastolic expansion in which the resilience of the device , under endoventricular - pressure , allows its radial dilatation to a predetermined useful extent and the simultaneous accumulation of elastic energy : at its maximum load , the device returns to its resting dimensions , thus operating an active systolic return as a result of its elastic force . the function of elasticity illustrated by the devices is not linear because , in the diastolic phase , they must oppose little resistance against expansion ; the elasticity of the material must diminish in an inverse relationship with endoventricular pressure in such a way as to ensure that the device opposes greater resistance to dilation as it expand towards its maximum diameter , which coincides with the maximum value of end - diastolic pressure . the device charged with elastic energy will invert its direction of movement from this point of maximum dilatation and begin to contract : being sutured to the endocardial wall of the ventricle or running through the myocardial wall , it will exercise a direct inward force on the wall itself that will aid the contraction of the ventricle ( systolic phase ). in the implementation shown in fig9 , the devices 6 , 7 and 8 are connected by means of elastic elements 10 in order to produce forces of a predetermined intensity along the axis of the ventricle 1 ; the said forces may be symmetrical or asymmetrical . the elastic elements 10 are attached to devices 6 , 7 and 8 or sutured to the walls of the ventricle 1 . with reference to fig1 , the devices 6 , 7 and 8 are connected at various points of their circumference by means of elastic elements 10 , whose radial and axial components are designed to produce forces of a predetermined intensity . in a preferential implementation , with reference to fig1 , 11 , 12 and 13 , they are constructed of biocompatible material covered by a sheath or woven covering of biological or biocompatible material presenting two lips or lateral flaps suitable for suturing ; the material constituting the said woven covering can be , for example , autologous pericardium or heterologous pericardium , or a non - thrombogenic biocompatible material of the types already existing on the market ( teflon , dacron , silicone ). it is also possible to construct the devices of biocompatible material of the invention in such a way that their transversal dimensions vary along the perimeter , narrowing in parts that are suitable for being directly sutured to the endocardium without the need for the sheath . the method of application of the said devices is to suture the lips of the covering sheath using detached stitches , possibly u - shaped , reinforced with pladgets of dacron or another biological material of the type described . using this method , the stitches do not interfere with the elastic and flexible element making up the prosthetic device . the suturing must be complete : that is , two circumferential sutures of detached stitches for each device , unless the stitches have to be transmural . another method of application of the device is that of a mattress suture accomplished with the open ring / band itself running through the thickness of the muscular wall and the junction of the tips at a predetermined measure . the sutures applied for the longitudinal and transversal connection of the prosthetic elements are made with a predetermined elasticity . any component of the device must be characterized by radioopacity by means of intrinsic radioopacity of the material used ( metal spring ) or the addition of radioopaque elements inside the elastic material or the coverage material . ( a ) an increase in the ejection fraction , by which is meant the ratio between the end - diastolic volume and the difference between end - diastolic volume and end - systolic volume , ( b ) the elimination of mitral valve insufficiency by maintaining the physiological elasticity of the native annulus , ( c ) an aid to systolic function using the intrinsic force of the device , ( e ) chronic radiographic control of the device function and its relationship with the cardiac function . it can be directly derived that the present invention is suitable for different shapes and implementations of the device , while remaining within the ambit of the same inventive concept . | an endocardial heart function intervention device that optimizes the cardiac geometry in patients with heart failure . the device comprises one or more elastic elements sutured in place within a heart that will establish radial elasticity in a direction towards the inside of the ventricle and plastic deformation in a direction that is transversal to the ventricle and is configured to be adjusted axially and radially to and along a section of the endocardial wall while in a neutral rest condition and can thereafter expand to receive energy from the endocardial wall during the diastolic phase , to cede energy received to the endocardial wall during a systolic phase . |
a good place to start the detailed description is the preparation of soymilk for making tofu , which when turned into tofu puree by homogenizing dispersion , forms the principal basis of the frozen desserts described herein . it must be remembered , however , that the process for soymilk described here is one benchtop model only . many variants of soymilk processing have been scaled up for commercial production by process and equipment vendors such as prosoya inc . ( ottawa , ontario , canada ), takai tofu & amp ; soymilk equipment co . ( ishikawa - ken , japan ), izumi food machinery co ., ltd . ( hyogo , japan ), and ta ti hsing machinery company ltd . ( taoyuan , taiwan ). here , soymilk with minimal beany flavor , is prepared by the hot - grinding of soaked soybeans : dry soybeans , weighing about 200 g , were washed and soaked in water at 25 ° c . for 6 to 8 hours to about 450 g to 500 g drained weight . then the soaked beans were drained and ground , with 1 . 6 g monoglyceride ( supplied by danisco canada inc ., scarborough , ontario , canada ) added as a defoamer , using a silverson model l4rt laboratory mixer , supplied by silverson machines , inc ., east longmeadow , mass ., and equipped with one - inch disintegrating head , at 5 , 000 rpm for 5 minutes , with about 1 . 5 kg of near - boiling water at 95 to 100 ° c . for lipoxygenase inactivation . the covered hot slurry was kept in a hot water bath for 15 minutes , at 85 to 90 ° c ., for the inactivation of microbes and anti - nutritional factors like trypsin inhibitors . it was then filtered through a cheesecloth bag to remove the insoluble residue , or okara , to obtain the soymilk , which contained about 8 . 6 % soy solids . this soymilk was then ready for making into tofu . it was either cooled to 25 to 30 ° c . for the preparation of unpressed extra soft silken tofu , or kept at 80 to 85 ° c . for the preparation of pressed firm tofu . soymilk must first be turned into tofu , before frozen desserts comprising principally of tofu puree can be prepared , as per the generic steps outlined in paragraph [ 0030 ] earlier on . i must emphasize , however , that while i can illustrate this invention with just one variety of tofu , or two or more varieties of tofu working together , i have chosen to illustrate this invention using two varieties of tofu , namely , unpressed extra soft silken tofu and pressed firm tofu . it must be understood that the implementation of this invention is not limited by the choices of these two tofu varieties , because the generic steps herein described will work well with a single , or three or more varieties of tofu together , only the weight ratio of tofu varieties will differ in each case , as obvious to a person skilled in the art . it must also be remembered that the tofu processes described here are benchtop models only , but they share similar principles and bring about similar qualitative coagulative change of soymilk into tofu , as in scaled - up models . in fact , many variants of tofu processing , some made continuous , have been scaled up for commercial production by process and equipment marketers such as takai tofu & amp ; soymilk equipment co ., izumi food machinery co ., ltd ., and ta ti hsing machinery company ltd . in my reasoning , unpressed extra soft silken tofu provides a low - fat and high - moisture base for incorporating other frozen dessert ingredients , while pressed firm tofu contributes the high soy solids and protein for satisfying textural and minimum protein needs . unlike taketsuka &# 39 ; s patent application , in which he relied on only one single variety of tofu for formulating his frozen desserts , which made composition formulation inflexible , now a mixture of the two kinds of tofu will provide sufficient versatility in meeting operational and nutritional requirements . tofu , to be processed further into frozen desserts as per generic steps outlined in paragraph [ 0030 ], can be made from the prepared soymilk described in example 1 , as follows : for unpressed extra soft silken tofu , an aqueous mixed - coagulant solution containing 22 % glucono - delta - lactone ( gdl ) and 8 % magnesium chloride ( both ingredients supplied by univar canada ltd , weston , ontario , canada ) was mixed into the cooled soymilk as prepared in example 1 , at a dosage of 1 %. the covered mixture was heated in a water bath at 80 to 85 ° c . for 50 minutes to allow for coagulation to complete . the coagulated extra soft silken tofu , if not used immediately for the preparation of frozen desserts comprising tofu puree , was refrigerated at 1 to 4 ° c . until later use . this unpressed , custard - like , extra soft silken tofu contained about 8 . 5 % solids , 4 . 4 % protein , 2 . 1 % fat , 1 . 2 % carbohydrate , and 0 . 9 % ash . for pressed firm tofu , the hot soymilk at 80 to 85 ° c . was poured into a stainless steel container containing an aqueous mixed - coagulant slurry , comprising 20 % calcium sulfate , 12 % gdl , and 8 % magnesium chloride ( all three ingredients supplied by univar canada ltd .) and used at 1 % of the quantity of soymilk , and mixed by stirring for about 20 to 25 seconds . the mixture was covered and left to stand for about 30 minutes to allow for complete coagulation , after which the curd was broken up and transferred to a stainless steel forming box with drain holes and already lined inside with an oversized cheesecloth with triangular flaps completely overhanging the four sides of the box . after filling the forming box with curd , the overhanging flaps of the cheesecloth were folded across the surface of the curd , and an insert lid befitting the internal dimension of the box was put on top of the curd mass . the curd mass was then subjected to stepwise - increasing mechanical pressure to facilitate curd matting and whey separation , through added weights placed on the lid , initially at 20 g / cm . sub . 2 pressure for 10 minutes , then at 40 g / cm . sub . 2 for another 10 minutes , and followed by 80 g / cm . sub . 2 for an additional 10 minutes . at this point the net weight of the curd corresponded to about half the weight of the soymilk started out with . the pressed firm tofu was then cut into cakes , and , if not used immediately for the preparation of frozen desserts comprising tofu puree , was refrigerated at 1 to 4 ° c . until later use . this pressed firm tofu contained about 16 . 5 % solids , 8 . 7 % protein , 4 . 6 % fat , 2 . 4 % carbohydrate , and 0 . 9 % ash . the generic steps in the preparation of frozen desserts comprising principally of tofu puree , starting with tofu , are described in the following paragraphs , with examples . while the invention has been described with reference to the specific embodiment of the examples , it will be obvious to a person skilled in the art that variations and modifications can be made within the scope of the invention as defined in the claims . generic step ( 1 ): “ coarse ” homogenizing dispersion of tofu , including other pre - weighed base ingredients , to yield coarse mash comprising principally of tofu puree : for the purpose of this invention , tofu puree is prepared by the homogenizing dispersion of tofu , which is either processed straight after tofu - making , or has been kept fresh at a temperature between 1 and 4 ° c ., prior to the operation . the conversion of tofu to tofu puree may be done independently of adjunct ingredients , which are then added and blended into the tofu puree to yield the coarse mash . alternatively or more efficiently operation - wise , the adjunct ingredients can be added to the tofu before initiating the first homogenizing dispersion , so that in one single step the adjunct ingredients may be simultaneously combined with the “ liquefied ” tofu to form the coarse mash , which is comprised principally of tofu puree . the conversion of tofu and adjunct ingredients to coarse tofu - puree mash may be achieved by various means , such as by mechanical , sonic , ultrasonic , or any other means of homogenizing dispersion , or any combination of means thereof , but is preferably done by an “ in - tank ” mechanical homogenizing - dispersing mechanism employing a device such as the silverson high shear batch mixer or disintegrator , with a square hole high shear screen , supplied by silverson machines , inc . on a small scale , the silverson l4rt laboratory mixer is the mechanical device of choice , using the square hole high shear screen with 2 - mm holes . this powerful mixer assembly , when activated at 1000 rpm or higher , preferably 2000 to 4000 rpm , for 30 seconds or more , preferably for 2 to 6 minutes , is capable of converting tofu into tofu puree , or tofu with adjunct ingredients into coarse tofu puree mash . such conversion involves changing the tofu from a custard - like or cheese - like consistency to a liquefied , pumpable dispersion of suspended particles . this high shear operation also ensures the proper hydration and dispersion of the adjunct materials in the tofu puree . for scaling up to commercial production , the preferred mechanical device for this “ coarse ” first homogenizing dispersion is the silverson high - shear in - tank top - entry batch mixer equipped with square hole high shear screen , or , even more preferably , the silverson high - shear in - tank bottom - entry mixer , like the silverson disintegrator 2500 , equipped with square hole high shear screen , designed to fit into the bottom or side of a mixing vessel , and used in conjunction with a slow speed scraper unit to handle the high viscosity contents . the bottom entry mixer provides high shear homogenization while the scraper distributes the homogenized output uniformly throughout the vessel . preferably , the system , whether top - entry or bottom - entry , is coupled with a self - pumping high - shear in - line mixer to ensure complete dispersion before downstream operation . preparation of coarse mash comprising principally of tofu puree from tofu and adjunct ingredients designated for aerated “ ice - cream - like ” vanilla - flavored frozen desserts a mixture of tofu varieties , either straight from tofu - making and still warm , or kept at 1 to 4 ° c . after cooling , comprising 1 . 21 kg unpressed extra soft silken tofu , prepared as described in example 2 , and 0 . 54 kg pressed firm tofu , prepared as described in example 3 , was subjected to high - shear homogenizing dispersion using the silverson l4rt laboratory mixer , equipped with the square hole high shear screen with 2 mm holes , at 3000 rpm for 3 minutes , to reduce it to tofu puree . to this tofu puree was added adjunct ingredients , including 223 g glycerin ( 96 %, supplied by univar canada ltd . ), 1 . 6 g sucralose solution ( 25 %, supplied by tate & amp ; lyle , decatur , ill . ), 2 . 8 g mono - and di - glycerides ( supplied by danisco canada inc . ), and a dry pre - mix comprising 2 . 5 g salt , 15 . 0 g calcium lactate gluconate ( supplied by purac america , inc ., lincolnshire , ill . ), 2 . 6 g regular non - resistant maltodextrin ( supplied by univar canada ltd . ), 2 . 0 g guar gum ( supplied by univar canada ltd . ), 1 . 3 g locust bean gum ( supplied by univar canada ltd . ), 0 . 9 g carboxymethylcellulose ( supplied by danisco canada inc . ), and 0 . 4 g carrageenan ( supplied by univar canada ltd . ), and the mixture was subjected to further high - shear homogenizing dispersion at 3000 rpm for an additional 3 minutes , to complete the coarse - mashing step . this high shear operation reduced the tofu in the coarse mash to tofu puree particles , which appeared mostly spheroidal and not exceeding 50 μm in diameter under optical measuring microscopy . the mean particle size , estimated based on martin &# 39 ; s diameter or taken here as the length of the line ( in the direction of the horizontal reticle line ) dividing the particle area in two equal areas , applied to a total of 625 particles in random fields , was 27 μm . the observation of particle shape and size was made on the spin - dried dispersion on a glass microscope slide , using a meiji techno measuring microscope mc - 40t at 1000 times total magnification with transmitted light from a halogen light source and equipped with an eyepiece micrometer cross - line reticle with 0 . 1 mm graduations ( meiji techno america , santa clara , calif .). preparation of coarse mash comprising principally of tofu puree from tofu and adjunct ingredients designated for aerated “ ice - cream - like ” chocolate - flavored frozen desserts a mixture of tofu , either straight from tofu - making and still warm , or kept at 1 to 4 ° c . after cooling , comprising 1 . 12 kg unpressed extra soft silken tofu , prepared as described in example 2 , and 0 . 50 kg pressed firm tofu , prepared as described in example 3 , was subjected to high - shear homogenizing dispersion using the silverson l4rt laboratory mixer , equipped with the square hole high shear screen with 2 mm holes , at 3000 rpm for 3 minutes , to reduce it to tofu puree . to this tofu puree was added adjunct ingredients , including 16 . 0 g glycerin , 2 . 8 g mono - and di - glycerides , and a dry pre - mix comprising 280 g xylitol ( supplied by danisco canada inc . ), 2 . 5 g salt , 15 . 0 g calcium lactate gluconate , 16 . 0 g inulin ( supplied by orafti active food ingredients , malvern , pa . ), 38 . 0 g extra brute cocoa powder ( supplied by barry callebaut , st . albans , vt . ), 2 . 6 g regular non - resistant maltodextrin , 2 . 0 g guar gum , 1 . 3 g locust bean gum , 0 . 9 g carboxymethylcellulose , and 0 . 4 g carrageenan , and the mixture was subjected to further high - shear homogenizing dispersion at 3000 rpm for an additional 3 minutes , to complete the coarse - mashing step . this high shear operation reduced the tofu in the coarse mash to tofu puree particles , which appeared mostly spheroidal and not exceeding 50 μm in diameter under optical measuring microscopy . the mean particle size , estimated based on martin &# 39 ; s diameter or taken here as the length of the line ( in the direction of the horizontal reticle line ) dividing the particle area in two equal areas , applied to a total of 625 particles in random fields , was 29 μm . the observation of particle shape and size was made on the spin - dried dispersion on a glass microscope slide , using a meiji techno measuring microscope mc - 40t at 1000 times total magnification with transmitted light from a halogen light source and equipped with an eyepiece micrometer cross - line reticle with 0 . 1 mm graduations . preparation of coarse mash comprising principally of tofu puree from tofu and adjunct ingredients designated for aerated “ ice - cream - like ” strawberry - flavored frozen desserts a mixture of tofu varieties , either straight from tofu - making and still warm , or kept at 1 to 4 ° c . after cooling , comprising 0 . 95 kg unpressed extra soft silken tofu , prepared as described in example 2 , and 0 . 66 kg pressed firm tofu , prepared as described in example 3 , was subjected to high - shear homogenizing dispersion using the silverson l4rt laboratory mixer , equipped with the square hole high shear screen with 2 mm holes , at 3000 rpm for 3 minutes , to reduce it to tofu puree . to this tofu puree was added adjunct ingredients , including 60 g strawberry puree ( single - strength , seedless , aseptic , supplied by mondi foods nv , rijkevorsel , belgium ), 113 g glycerin , 2 . 8 g mono - and di - glycerides , and a dry pre - mix comprising 180 g fructose ( supplied by tate & amp ; lyle , decatur , ill . ), 2 . 5 g salt , 15 . 0 g calcium lactate gluconate , 2 . 6 g regular non - resistant maltodextrin , 2 . 0 g guar gum , 1 . 3 g locust bean gum , 0 . 9 g carboxymethylcellulose , and 0 . 4 g carrageenan , and the mixture was subjected to further high - shear homogenizing dispersion at 3000 rpm for an additional 3 minutes , to complete the coarse - mashing step . this high shear operation reduced the tofu in the coarse mash to tofu puree particles , which appeared mostly spheroidal and not exceeding 50 μm in diameter under optical measuring microscopy . the mean particle size , estimated based on martin &# 39 ; s diameter or taken here as the length of the line ( in the direction of the horizontal reticle line ) dividing the particle area in two equal areas , applied to a total of 625 particles in random fields , was 28 μm . the observation of particle shape and size was made on the spin - dried dispersion on a glass microscope slide , using a meiji techno measuring microscope mc - 40t at 1000 times total magnification with transmitted light from a halogen light source and equipped with an eyepiece micrometer cross - line reticle with 0 . 1 mm graduations . this is a thermal pasteurization or sterilization step by heating the coarse tofu puree mash to a temperature of at least 82 . 2 ° c . for a minimum of 10 seconds , preferably 85 ° c . for 30 seconds for pasteurization , or , for uht sterilization , to at least 138 ° c . for 2 seconds , preferably 140 ° c . for 4 seconds , not only to make the product safe microbiologically , but also to effectively activate the stabilizer system amongst the adjunct ingredients . on a small scale , this thermal pasteurization or sterilization is simply achieved batch - wise by heating the mash to and holding at pasteurization temperature , with constant stirring , in a stainless steel vessel jacketed by hot water , to achieve the desired results of microbiological safety and stabilizer activation . and the heating temperature is monitored by thermometer . sterilization , however , is not an option with such a basic setup . for scaling up to commercial production , a scrape - surface heat - exchanger setup , like that supplied by invensys apv ( getzville , n . y .) or tetra pak inc . ( vernon hills , ill . ), with automated temperature and holding - time controls , is preferred for pasteurizing or sterilizing a mash of thick consistency at a high commercial volume and to achieve long , continuous runs . the option for sterilization opens up the opportunity for eventually packaging the sterilized base mix or finished mix aseptically , like in aseptic bag - in - box , tetra pak , or combibloc containers , for cost - effective , refrigeration - free distribution to franchised premises equipped with suitable freezers , equipment , and materials , for conversion to soft - serves , hard packs , and / or frozen novelties on site . pasteurization of coarse tofu puree mash designated for aerated “ ice - cream - like ” frozen desserts each coarse tofu puree mash prepared as per examples 4 , 5 , and 6 , about 2 kg , was put into a stainless steel container and placed in a hot water bath kept at about 90 ° c . the mash was stirred until the temperature reached 82 . 2 ° c ., and was held for 30 seconds before transferred to the cooling step . on a small scale , this cooling of the pasteurized coarse mash is done by constantly stirring the mash in a stainless steel vessel jacketed by ice water , until the desired temperature of below 10 ° c ., preferably between 1 to 4 ° c ., is reached . and the cooling temperature is monitored by thermometer . similar to the pasteurization or sterilization step , for scaling up to commercial production , a scrape - surface heat - exchanger setup , like that supplied by invensys apv or tetra pak inc ., with automated temperature and holding - time controls , is preferred for cooling a mash of thick consistency at a high commercial volume . the benefit of such a setup is that heating and cooling are coupled seamlessly , and with energy regeneration , so important today when energy conservation is such a high priority . cooling of pasteurized coarse tofu puree mash designated for aerated “ ice - cream - like ” frozen desserts each coarse tofu puree mash , pasteurized as per example 7 , about 2 kg , in stainless steel container , was placed in an ice water bath kept at close to 0 ° c . the mash was stirred until the temperature dropped to 1 to 4 ° c ., and then transferred to the aging step . the pasteurized or sterilized coarse mix , now chilled preferably to between 1 to 4 ° c ., is aged for a minimum of 4 hours , preferably 8 to 12 hours , while being kept cool . this aging maximizes the effectiveness of the hydrocolloids . on a small scale , the batch - pasteurized coarse mix is aged and kept cool in a refrigerator at 1 to 4 ° c . for scaling up to commercial production , the pasteurized coarse mix may be aged and kept cool in a chilled or otherwise well - insulated stainless steel tank prior to the “ fine ” homogenizing dispersion . if the coarse mix is uht - sterilized and meant subsequently to go into aseptic packaging , the cooled coarse mix may be aged in an insulated aseptic tank . the aseptic tank may be supplied by niro soavi ( bedford , n . h . ), invensys apv , or tetra pak inc . aging of cooled , pasteurized coarse tofu puree mash designated for aerated “ ice - cream - like ” frozen desserts each pasteurized coarse tofu puree mash , cooled as per example 8 , about 2 kg , in stainless steel container , was allowed to age for 10 hours in a cooler at 1 to 4 ° c ., before subjected to “ fine ” homogenizing dispersion . the mash set into a soft - gel - like mass after aging . generic step ( 5 ): “ fine ” homogenizing dispersion for particle - size reduction of aged coarse mash to base mix : the particle - size refining of the aged coarse mash , now set into a soft - gel - like mass , to the base mix is done through a second homogenizing - dispersing operation . while this “ fine ” homogenizing dispersion may be done through mechanical , sonic , ultrasonic , or any other effective means of homogenizing dispersion , or combination of means thereof , it is preferably done , on a small scale , using a silverson l4rt “ in - tank ” top - entry high - shear batch mixer , equipped with square hole high shear screen with 2 mm holes , to effect the desired particle - size reduction of the coarse mash gel to base mix . this powerful mixer assembly , when activated at 4000 rpm or higher , preferably 5000 to 6000 rpm , for 5 minutes or more , preferably for 8 to 10 minutes , is capable of finely homogenizing the dispersion down to the target particle - size range of 0 . 1 to 27 μm . after the “ fine ” homogenizing dispersion , the base mix is chilled to 1 to 4 ° c . for further processing . for scaling up to commercial production , this “ fine ” homogenizing dispersion can be done using the silverson high - shear in - tank top - entry batch mixer equipped with square hole high shear screen , or , even more preferably , the silverson high - shear in - tank bottom - entry mixer , like the silverson disintegrator 2500 , equipped with square hole high shear screen , designed to fit into the bottom or side of a mixing vessel , and used in conjunction with a slow speed scraper unit to handle the high viscosity contents . the bottom entry mixer gives high shear homogenization while the scraper distributes the homogenized output uniformly through the vessel . preferably , the system , whether top - entry or bottom - entry , is coupled with a self - pumping high - shear in - line mixer to ensure complete dispersion before downstream operation . alternatively , this operation of “ fine ” homogenizing dispersion can be done through a high - pressure mechanical homogenizer , like that supplied by niro soavi , invensys apv , or tetra pak inc . if aseptic packaging of base mix or finished mix is desired , the mechanical device chosen must be an aseptic homogenizer , like that supplied by niro soavi , invensys apv , or tetra pak inc ., installed between the sterilizer and another aseptic tank that immediately precedes the aseptic filling and packaging system . the aseptic filling and packaging system , if aseptic cartons are desired , may be provided by tetra pak inc . or sig combibloc inc . ( chester , pa . ), and if aseptic bag - in - box is desired , by scholle packaging ( northlake , ill .) or rapak ( romeoville , ill .) “ fine ” homogenizing dispersion of aged , pasteurized coarse mix designated for aerated “ ice - cream - like ” vanilla - flavored frozen desserts a silverson l4rt “ in - tank ” top - entry high - shear batch mixer , equipped with square hole high shear screen with 2 mm holes , was sanitized by blending about 2 . 5 liters of a 100 - ppm chlorine sanitizing solution in a 4 - liter stainless steel container at 1000 rpm for 1 minute , after which the chlorine solution was discarded . the silverson assembly was then rinsed , twice , by similarly blending 2 . 5 liters of previously boiled and cooled water at 1000 rpm for 1 minute and discarding that water . then the aged , pasteurized coarse mix , prepared as per example 9 , about 2 kg , in a 4 - liter stainless steel container , was subjected to “ fine ” homogenizing dispersion using the pre - sanitized silverson mixer , at 5000 rpm for 8 minutes . this high shear operation reduced the principally tofu puree particles in the coarse mash to fine particles which appeared mostly spheroidal and not exceeding 30 μm in diameter under optical measuring microscopy . the mean particle size , estimated based on martin &# 39 ; s diameter or taken here as the length of the line ( in the direction of the horizontal reticle line ) dividing the particle area in two equal areas , applied to a total of 625 particles in random fields , was 16 μm . the observation of particle shape and size was made on the spin - dried dispersion on a glass microscope slide , using a meiji techno measuring microscope mc - 40t at 1000 times total magnification with transmitted light from a halogen light source and equipped with an eyepiece micrometer cross - line reticle with 0 . 1 mm graduations . “ fine ” homogenizing dispersion of aged , pasteurized coarse mix designated for aerated “ ice - cream - like ” chocolate - flavored frozen desserts a silverson l4rt “ in - tank ” top - entry high - shear batch mixer , equipped with square hole high shear screen with 2 mm holes , was sanitized by blending about 2 . 5 liters of a 100 - ppm chlorine sanitizing solution in a 4 - liter stainless steel container at 1000 rpm for 1 minute , after which the chlorine solution was discarded . the silverson assembly was then rinsed , twice , by similarly blending 2 . 5 liters of previously boiled and cooled water at 1000 rpm for 1 minute and discarding that water . then the aged , pasteurized coarse mix , prepared as per example 9 , about 2 kg , in a 4 - liter stainless steel container , was subjected to “ fine ” homogenizing dispersion using the pre - sanitized silverson mixer , at 5000 rpm for 8 minutes . this high shear operation reduced the principally tofu puree particles in the coarse mash to fine particles which appeared mostly spheroidal and not exceeding 30 μm in diameter under optical measuring microscopy . the mean particle size , estimated based on martin &# 39 ; s diameter or taken here as the length of the line ( in the direction of the horizontal reticle line ) dividing the particle area in two equal areas , applied to a total of 625 particles in random fields , was 17 μm . the observation of particle shape and size was made on the spin - dried dispersion on a glass microscope slide , using a meiji techno measuring microscope mc - 40t at 1000 times total magnification with transmitted light from a halogen light source and equipped with an eyepiece micrometer cross - line reticle with 0 . 1 mm graduations . “ fine ” homogenizing dispersion of aged , pasteurized coarse mix designated for aerated “ ice - cream - like ” strawberry - flavored frozen desserts a silverson l4rt “ in - tank ” top - entry high - shear batch mixer , equipped with square hole high shear screen with 2 mm holes , was sanitized by blending about 2 . 5 liters of a 100 - ppm chlorine sanitizing solution in a 4 - liter stainless steel container at 1000 rpm for 1 minute , after which the chlorine solution was discarded . the silverson assembly was then rinsed , twice , by similarly blending 2 . 5 liters of previously boiled and cooled water at 1000 rpm for 1 minute and discarding that water . then the aged , pasteurized coarse mix , prepared as per example 9 , about 2 kg , in a 4 - liter stainless steel container , was subjected to “ fine ” homogenizing dispersion using the pre - sanitized silverson mixer , at 5000 rpm for 8 minutes . this high shear operation reduced the principally tofu puree particles in the coarse mash to fine particles which appeared mostly spheroidal and not exceeding 30 μm in diameter under optical measuring microscopy . the mean particle size , estimated based on martin &# 39 ; s diameter or taken here as the length of the line ( in the direction of the horizontal reticle line ) dividing the particle area in two equal areas , applied to a total of 625 particles in random fields , was 16 μm . the observation of particle shape and size was made on the spin - dried dispersion on a glass microscope slide , using a meiji techno measuring microscope mc - 40t at 1000 times total magnification with transmitted light from a halogen light source and equipped with an eyepiece micrometer cross - line reticle with 0 . 1 mm graduations . generic step ( 6 ): finishing by adding flavoring ( s ), acidulant ( s ), and / or coloring ( s ) to convert base mix to finished mix , if necessary : tofu is noted for its blandness . frozen desserts comprising principally of tofu puree will taste bland unless some characterizing flavor is blended into the base mix . for example , dark cocoa powder , green tea , almonds , strawberries , or blueberries may form part of the adjunct ingredients to give the resulting frozen dessert a characterizing flavor . and in most cases , the product flavor is further enhanced by incorporating one or more food flavoring ( s ), preferably natural flavoring ( s ), to round up the overall flavor impact , or to inject the desired “ top notes ” or complementary flavor ( s ). for example , a natural mint flavoring is added to a dark - cocoa base mix to produce a dark chocolate mint finished mix , a natural vanilla flavoring is added to round up the harsh taste of a dark chocolate finished mix , and a natural strawberry flavoring is added to a strawberry base mix to enhance the top notes of the strawberry - flavored frozen dessert . for fruit - flavored frozen desserts , one or more acidulants , like citric acid , or other food - grade acids , may be added to boost the fruity taste . in some cases , food coloring material ( s ), preferably natural coloring material ( s ), may be necessary to improve the esthetic attractiveness of the frozen dessert . for example , a natural red beet colorant is used to enhance the color of the strawberry - flavored frozen dessert comprising tofu puree . liquid flavorings , acidulant solutions , and / or coloring solutions are preferred for ease of homogeneous blending , and , if an aseptic finished mix is desired , adaptability to microfiltration aseptic dosing . aseptic dosing equipment may be supplied by tetra pak inc . at the stage of base mix or finished mix , the refrigerated , pasteurized product may be packaged for eventual freezing elsewhere into the finished frozen dessert . whereas the sterilized product , if aseptically handled throughout after sterilization , also lends itself to aseptic packaging into aseptic cartons like those of tetra pak or sig combibloc , or aseptic bag - in - box like that of scholle packaging or of rapak . the aseptically - packed base can then be shipped without the need for refrigeration to licensed locations equipped with proper freezers , equipment , and materials , for conversion into soft - serves , hard packs , and / or frozen novelties on premise . finishing of finely - homogenized base mix designated for aerated “ ice - cream - like ” vanilla - flavored frozen desserts the finely - homogenized base mix , prepared as per example 10 , about 2 kg , was converted to finished mix by stirring into it 12 ml of natural vanilla flavor ( supplied by givaudan flavors , bridgeton , mo .). the finished mix was kept at 1 to 4 ° c . before freezing into frozen dessert . finishing of finely - homogenized base mix designated for aerated “ ice - cream - like ” chocolate - flavored frozen desserts the finely - homogenized base mix , prepared as per example 11 , about 2 kg , was converted to finished mix by stirring into it 2 ml of natural chocolate flavor and 5 ml of natural vanilla flavor ( both supplied by givaudan flavors , bridgeton , mo .). the finished mix was kept at 1 to 4 ° c . before freezing into frozen dessert . finishing of finely - homogenized base mix designated for aerated “ ice - cream - like ” strawberry - flavored frozen desserts the finely - homogenized base mix , prepared as per example 12 , about 2 kg , was converted to finished mix by stirring into it 3 . 0 g of a 50 %- solution of citric acid ( anhydrous , supplied by tate & amp ; lyle , decatur , ill . ), 1 ml of red beet natural colorant ( supplied by d . d . williamson , louisville , ky . ), and 5 ml of natural strawberry flavor ( supplied by givaudan flavors , bridgeton , mo .). the finished mix was kept at 1 to 4 ° c . before freezing into frozen dessert . generic step ( 7 ): freezing of base mix or finished mix with aeration to achieve an “ ice - cream - like ” texture with overrun , folding in mix - ins or bulky inclusions where desired ; and soft - serving the product without hardening , for immediate consumption on - premise ; or packaging and hardening the product for subsequent storage , distribution , and consumption : the cooled finished mix is now ready for freezing with aeration into “ ice - cream - like ” frozen dessert , whether for soft - serving on premise , depositing into molds or receptacles for novelties , or hardening into hard - pack . the aeration can be done immediately prior to or simultaneously with the freezing operation , and is preferably done simultaneously and conveniently in a dasher - equipped freezer . on a small scale , for the on - premise soft - serve approach , a countertop batch - type soft - serve machine like the model uc - 711 by carpigiani ( supplied by carpigiani corporation of america , winston - salem , n . c . ), is preferred , and the product is drawn at about − 7 to − 8 ° c . for the hard - pack or frozen novelty approach , a batch - type ice - cream freezer , like the model lb - 1002 by carpigiani , is preferred , and the product is drawn at about − 3 to − 4 ° c . the subsequent hardening of the filled packs or deposited novelties , at − 40 ° c ., is done in a flash hardener , like that by kelvinator ( supplied by national consolidated industries , inc ., honea path , s . c .). the hard - pack or frozen novelty approach also lends itself to mix - ins or bulky inclusions , like dark chocolate chips or chunks , fruit pieces like pineapple tidbits , or nuts like walnuts or almonds , being folded in while the frozen mass drawn from the freezer is still pliable . the hardened packs and frozen novelties are stored in storage freezers kept at − 18 ° c . or below , preferably at about − 25 ° c ., until consumption . for the scaled - up commercial production of soft - serves on premise , a floor machine like the carpigiani uf - 820 e is preferred . for scaling up to the commercial production of hard - packs or frozen novelties , a continuous freezer coupled to a downstream system comprising filling and packaging , hardening , and frozen storage , like the equipment by hoyer ( supplied by tetra pak hoyer , lake geneva , wis . ), is preferred . the frozen desserts comprising principally of tofu puree have a gelato - like texture and exhibit excellent flavor and physical stability during proper frozen storage , and command at least a 6 - month shelf life in frozen storage at − 25 ° c . freezing of finished mix designated for aerated “ ice - cream - like ” vanilla - flavored frozen desserts the finished mix , prepared as per example 13 , about 10 kg , was fed into a batch - type ice - cream freezer , like the carpigiani - coldelite model lb - 1002 , and set to freeze for about 4 . 5 minutes , after which the semi - frozen mass was dispensed into lidded one - liter containers . the overrun was about 28 %. the containers were hardened in a flash hardener , like that supplied by kelvinator , to a temperature of − 40 ° c . after hardening , the containers were stored in a storage freezer , like that supplied by kelvinator , at a temperature around − 25 ° c ., until evaluation time . freezing of finished mix designated for aerated “ ice - cream - like ” chocolate - flavored frozen desserts the finished mix , prepared as per example 14 , about 10 kg , was fed into a batch - type ice - cream freezer , like the carpigiani - coldelite model lb - 1002 , and set to freeze for about 4 . 5 minutes , after which the semi - frozen mass was dispensed into lidded one - liter containers . the overrun was about 25 %. the containers were hardened in a flash hardener , like that supplied by kelvinator , to a temperature of − 40 ° c . after hardening , the containers were stored in a storage freezer , like that supplied by kelvinator , at a temperature around − 25 ° c ., until evaluation time . freezing of finished mix designated for aerated “ ice - cream - like ” strawberry - flavored frozen desserts the finished mix , prepared as per example 15 , about 10 kg , was fed into a batch - type ice - cream freezer , like the carpigiani - coldelite model lb - 1002 , and set to freeze for about 4 . 5 minutes , after which the semi - frozen mass was dispensed into lidded one - liter containers . the overrun was about 25 %. the containers were hardened in a flash hardener , like that supplied by kelvinator , to a temperature of − 40 ° c . after hardening , the containers were stored in a storage freezer , like that supplied by kelvinator , at a temperature around − 25 ° c ., until evaluation time . the frozen desserts prepared as per examples 16 , 17 , and 18 were subjected to a scoring preference test by a taste panel made up of 25 panelists , all regular consumers of soy foods and liking frozen desserts , against comparable flavors of commercial soy frozen dessert brands , namely , so good ®, so delicious ®, and purely decadent ®, all bought at retail . so good ® is a registered trademark of soyaworld inc ., vancouver , b . c ., canada , and its soy frozen dessert products are made primarily with isolated protein , without tofu . on the other hand , so delicious ® and purely decadent ® are registered trademarks of turtle mountain llc , eugene , oreg . ; both their branded lines of soy frozen dessert products are made primarily with organic soymilk , again without tofu . panelists , pre - screened as consuming soy foods regularly ( at least once a month ) and liking frozen desserts , were each seated individually in a partitioned booth and each presented with a score sheet and pen and a tray holding four frozen dessert samples of the same described flavor in randomly numbered 2 - oz paper cups with taster spoons , a glass of water for rinsing in - between samples , and an empty glass to hold rinse wastes . the four samples comprised the three said commercial brands of the same described flavor , and the corresponding test sample of this invention prepared as per example 16 , 17 , or 18 , all blind to the panelists , and were randomly sequenced in the order of presentation . the panelists were asked to taste the samples , rinse the palate in - between samples , and check against a liking statement against each sample number on a score sheet . the liking statements were based on a 9 - point hedonic scale verbalized as “ like extremely ,” “ like very much ,” “ quite like it ,” “ somewhat like it ,” “ neither like nor dislike ,” “ somewhat dislike it ,” “ quite dislike it ,” “ dislike very much ,” and “ dislike extremely ,” translated to a numerical score stepwise from 9 to 1 , in descending order respectively , in eventual data analysis . the preference scores were subjected to one - way analysis of variance , followed by post hoc analysis using tukey &# 39 ; s hsd . the results , summarized in tables 1 , 2 , and 3 , clearly indicated the liking viability of the three flavors of frozen desserts comprising principally of tofu puree prepared as per examples 16 , 17 , and 18 described in this invention , as compared with the same described flavors of the commercial brands : the caloric values of the test - sample frozen desserts prepared in examples 16 , 17 , and 18 were compared against those of comparable flavors of commercial soy frozen dessert brands , namely , so good ®, so delicious ®, and purely decadent ®, in table 4 . obviously , the products as per examples 16 , 17 , and 18 described in this invention were more than 25 % lower in calories compared with any of the reference products of the same flavor , or compared with the average of the same flavor of the three commercial brands . the nutrition - related attributes of the test - sample frozen dessert products prepared as per examples 16 , 17 , and 18 described in this invention were compared against the nutrition - related objectives defined earlier in paragraph [ 0022 ], and are summarized in table 5 as follows : * caloric comparison made against the average of the same flavor of three commercial soy frozen dessert brands including so good ®, so delicious ®, and purely decadent ® by the results presented in tables 1 , 2 and 3 , because the test - sample frozen desserts pertaining to this invention were rated with definitely positive liking scores either at par with or significantly better than the corresponding versions of the top commercial brands of soy frozen desserts , it would be safe to conclude that the frozen desserts so prepared according to this invention were enjoyable . and by the results presented in tables 4 and 5 , because the test - sample frozen desserts pertaining to this invention appeared to have met all nutritional - related attribute expectations as stated in paragraph [ 0022 ], it would be safe to conclude that the frozen desserts so prepared according to this invention were healthy . hence , it would appear appropriate to conclude that the aerated frozen desserts so prepared , comprising more than eighty percent tofu puree , were indeed healthy and enjoyable , as per the stated object of this invention . | the frozen desserts include aerated “ ice - cream - like ” frozen desserts , comprising more than 80 . 0 percent , preferably 80 . 5 to 87 . 1 percent , by weight of tofu puree , containing particles . such frozen desserts include , but are not limited to , products that contain , per 100 grams of product , 3 grams or less of fat , 130 or fewer calories , 140 milligrams or less of sodium , 300 milligrams or more of calcium , 1 gram or less of saturated fat , 20 milligrams or less of cholesterol , and / or 5 grams or more of soy protein without additionally requiring the use of isolated soy protein or any other soy - protein - containing material . |
the present invention provides a pharmacologically effective substance ( ptc ) and process for isolating it . the ptc has an excellent cardiovascular effect especially in reducing myocardial oxygen demand and increasing coronary effects . the treatment of angina and other manifestations of myocardial ischemia is based on reduction of myocardial oxygen demand and increase of coronary blood flow to the ischemia myocardium to restore the balance between myocardial oxygen supply and demand . until ptc has been invented , there is no any drug which can reduce myocardial oxygen demand and simultaneously increase of coronary blood flow . meanwhile ptc is safe drug or health food , other cardivascular drugs have a certain degree side effect as mentioned above . ptc can be administered to patients in the form of capsules containing a powdered mixture of the active ingredients in appropriate proportions . alternatively , tablets can be prepared comprising the active ingredients and pharmaceutically acceptable binders , excipients , lubricants , sweeteners and coatings . a syrup or elixir may be prepared by dissolving ptc in alcohol and water together with suitable preservatives , sweeteners , dyes and flavoring agents . ampules or vials for injection may likewise be prepared , with the ptc as prepared for oral administration being purified through further recrystallization and sterilization and the addition thereto of distilled water and other suitable solvents and additives known in the pharmaceutical art . the ptc dosage units prepared according to the invention can be administered to patients . ptc is nontoxic . the compositions of the present invention all include as their active component ptc , which as indicated previously , consists of a mixture of five plant extracts : the following specific examples will provide detailed illustrations of methods of producing ptc according to the present invention and pharmaceutical dosage units containing ptc . moreover , examples will be given of pharmaceutical testing performed with ptc which demonstrates its effectiveness in cardiovascular effects . these examples are not intended , however , to limit or restrict the scope of the invention in any way , and should not be construed as providing conditions , parameters , reagents , or starting materials which must be utilized exclusively in order to practice the present invention . puerarin was extracted from pueraria lobata ( willd .) ohwi or pueraria thomsanii benth . the roots of pueratia lobata ( willd .) ohwi or pueraria thomsanii benth dried and powdered . one kilogram ( 1 kg ) of powder was dipped in 5 liters 95 % ethanol . the extraction was repeated twice with fresh 95 % ethanol . extract combined . extract was concentrated to syrup under reduced pressure and ethanol was recovered . syrup dry at 70 ° c . drying - syrup was chromatographed on alumina using water - saturated butanol as the developing solvent to separate into ten color bands which was seen under ultraviolet light ( u . v .). then using butanol - pyridine as the developing solvent systems . from the fifth band ( from the bottom ) colorless columnar crystals , m . p . 187 ° c ., were obtained after recrystallization from 50 % ethanol . the final product was pueratin and derivatives thereof . danshensu and danshenketone were extracted from salvia miltiorrhiza bunge , salvia przewalskii maxim or salvia trijuga diels . 10 liter of water was added to 1 kg of dry powder . the solution was heated to boil and simmered for one or one - half hours after boiling . this water extraction was repeated once and the two extracts combined and filtered . the filtrate was concentrated under reduced pressure to approximately 300 ml and 2 , 000 ml 95 % ethanol was added with constant stirring to a final ethanol concentration of 75 %. clear solution of ethanol was withdrew . clear solution of ethanol and the residue saved . 2 , 000 ml 90 % ethanol was added to residue with stir . the extraction was repeated twice by collecting the ethanol , replacing it with an equal volume of fresh 90 % ethanol . ethanol was combined with clear solution of ethanol and distilled to 200 ml under reduced pressure . 200 ml water added to 200 ml ethanol solution with stir and distilled to 200 ml under reduced pressure . alternate extraction was repeated with water and ethanol . final solution concentrated to 85 ml under reduced pressure . the concentrated solution was allowed to stand at 4 ° c . colorless needle crystals , m . p . 198 °- 200 ° c ., were obtained . crystals washed with diethyl ether . final product was danshensu . 5 liter of 95 % ethanol was added to 1 kg of dry powder in a water bath at 50 ° c . for 6 hours . the extraction was repeated twice by collecting the alcohol , replacing it with an equal volume of fresh 95 % ethanol and refluxing it with an equal volume of fresh 95 % ethanol for 6 hours . the extraction of ethanol was cooled and filtered . the filtrate combined with the extract filtrate . ethanol was then recovered by reduced pressure distillation and residue obtained . 1 , 000 ml of benzene was added to the residue and refluxing in water bath of 50 ° c . for 6 hours . benzene was concentrated under reduced pressure . residue was chro matographed on alumina using benzene as the developing solvent to separate into violet , orange and dark - red color bands . violet - band was cuted and continuously chromatographed using benzene as the developing solvent . benzene was collected and concentrated under reduced pressure . dark - red crystals were obtained and mother solution was concentrated continuously . red - needles were crystallized . red - needles , m . p . 202 °- 204 ° c ., were obtained after recrystallization from ethanol . the red - needles were daidzeiketone . tetramethyl pyrazine was extracted from ligusticum chuanxiong hort or ligusticum wallichii franch . 2 , 000 ml of 95 % ethanol was added to 1 , 000 g of powdered root and stem of as mentioned above plants and refluxed in a water bath for 2 hours . the extraction was repeated twice with fresh ethanol and further refluxing . the ethanol was recovered by concentration under reduced pressure . the residue was dissolved in warm water , cooled to room temperature and extracted twice with equal volumes of petroleum ether . the ether phase was then extracted with an equal volume of 1n hcl . the sodium carbonate was added to the water phase until its ph was 9 - 10 , and the water phase was then extracted with an equal volume of chloroform . the chloroform phase was collected and chloroform recovered under reduced pressure . the residue gel was dissolved in petroleum ether . the ether was evaporated under reduced pressure and the residue dissolved in a mixture of petroleum ether and chloroform ( 8 : 2 ). the solvent was then evaporated under reduced pressure and the solid residue dissolved in warm water . the solution was cooled to room temperature and the ph adjusted to 8 - 9 with saturated naoh . after distillation and cooling , needle crystals formed which were then dissolved in warm water and filtered . the product was recrystallized once by repeating the above procedure . the final tetramethyl pyrazine product was dried under vacuum and was found to have a melting point of 87 . 5 °- 88 . 8 ° c . a . polysaccharides of dangshen was extracted from the roots of codonopsis pilosula nannf . 2 , 000 ml of 95 % ethanol was added to 1 kg of dried powder and allowed to stand for one day at room temperature . the solution was filtered and the extract filtrate saved . 2 , 000 ml of ethanol was added to the residue and refluxed in a water bath for 6 hours . the refluxing was repeated twice by collecting the ethanol , replacing in with an equal volume of fresh 95 % ethanol and refluxing for 6 hours . the refluxed ethanol was collected and filtered . the filtrate combined with the extract filtrate . for the sake of convenience , solution comprising mixtures of the above filtrate and extract filtrate will hereinafter be refereed to as solution ( 1 ). the solution ( 1 ) was used for extraction of saponin of dangshen . the residue of all process combined for extraction of polysaccharides . residue was grind . 3 , 000 ml of water was added to the residue . the solution was heated to boil and simmered for 3 hours after boiling . filtered . cooled . precipitated . the white precipitate was discarded . the supernatant ( 1 ) solution was collected . centrifugaltion ( approximately 1 , 000 rpm ) carefully collect supernatant layer ( 2 ). the two volumes of fresh 95 % ethanol was added to supernatant layer ( 2 ). the ethanol was recovered by distillation under reduced pressure . the residue was dissolved in warm water . cooled to room temperature . the two volumes of fresh 95 % ethanol was added to cooled solution . the precipitate was collected . the product was dried by vacuum , and the resulting powder was polysaccharides of dangshen . the solution ( 1 ) was used for extraction of saponin of dangshen . solution ( 1 ) was then recovered by reduced pressure distillation and the residue dissolved in 300 ml of distilled water . the lipid component of water solution was removed with 5 changes of 1 , 000 ml diethyl ether to water solution for extraction . an equal volume of water - saturated butanol was added to the final water phase and the butanol was then distilled under reduced pressure . the residue powder was dissolved in 300 ml of ethanol and 2 , 000 ml of acetone was added to the ethanol with constant stirring while a precipitate formed . the precipitate was washed twice each with acetone and other with ether and dried under vacuum . the resulting white or light yellow powder was the final product , i . e ., saponin of dangshen . ______________________________________ preferred weight percent weight percent______________________________________puerarin 10 - 50 % 25 % danshenu or 10 - 50 % 25 % danshenketonetetramethyl pyrazine 10 - 50 % 25 % polysaccharides of dangshen 5 - 25 % 12 . 5 % saponin of dangshed 5 - 25 % 12 . 5 % ______________________________________ the dry ingredients or derivate of ingredients prepared in accordance with the present invention , may be incorporated tablets , capsules , syrups or other form by conventional methods . crude php is extracted from as mentioned above plants by ethanol . ______________________________________ weight preferred percent weight precent______________________________________pueraria lobata ( willd .) ohwi or 10 - 50 % 25 % pueraria thomsanii benth : salvia miltiorrhiza bunge , 10 - 50 % 25 % salvia przewalskii maxim orsalvia trijuga diels : ligusticum chuanxion hort or 10 - 50 % 25 % ligusticum wallichii franch : codonopsis pilosula nannf , 10 - 50 % 25 % codonopsis tangshen oliver orcodonopsis clematidea clarke : ______________________________________ tissues of plant were dried and powdered . 5 liter distillatory water was added 1 kg of dried powder . the solution was heated to boil and simmered for one hour after boiling . this water extraction was repeated two times . combined and filtered . the filtrate was concentrated under reduced pressure to approximately 500 ml . then 1 , 000 ml 95 % ethanol was added to 500 ml water solution . stirred . stilled . filtered . residue and filtrat ( a ) was obtained . 1 , 000 ml 90 % ethanol was added to residue . stirred . extracted . 90 % ethanol extraction was repeated two times . extraction of 90 % ethanol was combined . filtered . filtrate ( b ) was obtained . combined filtrate ( a ) with ( b ). then total filtrate was concentrated to syrup under reduced pressure distillation . ethanol was recovered . syrup dried under vacuum drying . granulated to final powder . weight of every capsule and table is about 100 - 200 mg . crude - ptc is similar to fine - ptc in pharmacological property . male rats ( 280 to 320 g body weight ), maintained on a standard diet , were used in these experiment . the rats were lightly anaesthetized with diethyl ether . the left femoral vein was exposed and heparin ( 200 iu ) was administered intravenously . one minute ( min ) after administration of heparin , the heart was excised and placed in ice cold perfusion medium until contraction had ceased . the heart was then mounted on the perfusion apparatus . bicarbonate ( ph 7 . 4 ) buffer was the standard perfusion fluid . the perfusion fluid was maintained at 37 ° c . and in aerobic studies , the fluid was equilibrated with o 2 + co 2 ( 95 : 5 ). aortic o 2 partial pressure was over 600 mm hg . the heart was perfused after mounting immediately for a 5 min wash - out period . the preparation was then converted into working heart system for a 15 min period ( standard perfusion medium plus 11 mm glucose ). flow meter calibrate for flow ( 5 to 70 ml / min ) at 37 ° c . was used to measure aortic flow rates . the drug was included separately in perfusion medium thoughout the experimental time course . statistical comparison between control and ptc group was made by student &# 39 ; s t - test with the significance level being p & lt ; 0 . 05 . values given are means ± standard error ( s . e . m .). table 1______________________________________ coronary flow number of ( ml / min ) samples______________________________________pretreatment 6 . 7 ± 0 . 6 10after treatment 1 &# 39 ; 10 . 6 ± 0 . 9 10of ptc ( min ) 3 &# 39 ; 10 . 4 ± 0 . 8 10 5 &# 39 ; 0 . 3 ± 0 . 9 10 10 &# 39 ; 6 . 9 ± 0 . 5 10 15 &# 39 ; 6 . 7 ± 0 . 4 10 20 &# 39 ; 6 . 7 ± 0 . 5 10p & lt ; 0 . 01______________________________________ the effect of ptc on myocardial nutrious blood flow in mice in the present example the effect of the myocardial uptake of 86 rb ( rubidium ) used as the index of myocardial nutrious blood flow . the male mice weight 18 - 22 g were used in the experiments and were divided into treated ( ptc ) and control group . the dosage of ptc was 50 mg / kg injected intraperitoneally . the control mice were injected with same volume of normal saline . these injections were repeated daily for four days . on the last day , both ptc and control group 86 rb 50 μ / kg body weight was administered by tail vein , the injections to be completed within 3 seconds for every mouse . 30 seconds after administration of 86 rb the heart was excised . the heart was then dissected and weighted after the removal of auricles and blotted with filter paper quickly . the heart was digested by 1 . 25n naoh in a boiled water bath . then dry digested solution with infrared drier . the 86 rb uptakes were determined on a scintillator . the coronary blood flow was expressed as the per minute per gram heart weight in pulse to amount of 86 rb given ( cpm / g ). table 2______________________________________ control pdc______________________________________cpm / g 138 . 0 ± 10 212 . 5 ± 11 . 6number of sample 20 20p & lt ; 0 . 01______________________________________ the male rats ( 280 to 320 g body weight ) maintaine on a standard diet , were used in these experiments . the rats were lightly anacethetized with diethyl ether , the left femoral vein was exposed and heparin ( 200 iu ) was administered intravenously . 1 minute after administration of hepairin the heart was excised and placed in ice cold perfusion medium until contraction had ceased . the heart was then mounted on the perfusion apparatus . left atrial filling pressure was maintained at 7 . 5 mm hg and aortic resistance was maintained by 70 mm hg in aortic outflow tract . langendorff perfusion for an initial 10 min period , the perfusion was continued as a working preparation for an additional 30 min . the hearts were all electrically paced at between 265 and 275 beats / min during working perfusion . this work load resulted in 60 % to 75 % of maximal , maintainable peak systolic pressure . the perfusate was krebs - henseleit bicarbonate buffer gassed with 95 % oxygen and 5 % carbon dioxide . this perfusate contained 11 mm d - glucose during the langendorff perfusion , and 11 mm d - glucose plus 1 . 4 mm palmitate bound to 3 % bovine serum albumin . aortic pressure , heart rates , coronary flows and aortic outputs were monitored during perfusion . at the end of the perfusion period , the hearts were frozen cooled to the temperature of liquid nitrogen , while still being perfused . the frozen hearts were stored in liquid nitrogen until assayed for metabolic intermediates . the tissue sample was extracted in ice - cold 10 % trichloroacetic acid and centrifuged at 10 , 000 × g for 15 min at 4 ° c . the precipitates of trichloroacetic acid were washed with 1 % trichloroacetic acid and subsequently used for determining levels of lactate . the data were expressed per gram of non - collagen protein ( ncp ). chemical colorimetric methods had been used in the analysis of lactate levels in heart tissue . during the anoxic perfusion period , atmospheric gas contamination of the heart was prevented by completely enclosing the heart in a waterjacketed ( 37 ° c .) chamber which was continuously gassed with a mixture of n 2 + co 2 ( 95 : 5 ). in addition , to prevent diffusion of oxygen into the perfusion fluid , all silicone rubber tubing , connecting reservoirs and the heart , was replaced by glass delivery tubing . perfusion medium was equilibrated with n 2 + co 2 ( 95 : 5 ). example 9 is similar to example 7 in methods of animal . the lactate concentrations in heart of control group increased markedly , whereas lactate concentrations of ptc group did not increase . the data of lactate of ptc can be meant to reduce the degree of myocardial infarct . table 3______________________________________ normal control ptc______________________________________number of sample 10 10 10lactate 3 . 2 ± 0 . 2 5 . 1 ± 0 . 3 3 . 3 ± 0 . 2 ( mols / g ncp ) p -- & lt ; 0 . 01______________________________________ adult male guineapigs ( 300 - 450 g ), maintained on a standard diet , were used in these experiments . the guineapigs were lightly anaesthetized with diethyl ether , then each guineapig was killed by a sharp blow on the head and blod out , the heart was excised immediately and placed in dish containing oxygenated krebs - henseleit solution at 29 ° c . ______________________________________ nacl 118 nahco . sub . 3 25 cacl . sub . 2 2 . 52 kcl 4 . 7 mgcl . sub . 2 1 . 2 nah . sub . 2 po . sub . 4 1 . 18 glucose 5 . 55______________________________________ intact right and left atria was dissected out in a piece , free from ventricular and connective tissues , maintained on a krebe - henseleit solution at 32 ° c . krebs - henseleit solution was equilibrated with 5 % co 2 + 95 % o 2 gas mixture . isolated cardiac muscles were subjected to a resting tension of 0 . 75 g and left to equilibrate in the bath until the rate and amplitude of spontaneous contractions were stable . then isolated cardiac muscles were treated with ptc , ptc was administered to the bath fluid in a cumulative manner . the cardiac muscles were treated with ptc repeatedly at intervals of 20 minutes after the last washing . the spontaneous amplitude and rate of contractions as well as the ptc evoked responses of cardiac muscles were recorded isometrically by mean of devices forcedisplacement transducers , preamplifier and two - channel heat sensitive pen recorder . ptc was determined at a paper speed of 10 mm sec . table 4______________________________________inhibined percent age % chronotropic inotropicrate of contractions responses responses______________________________________80 μl / ml 54 . 9 % 49 . 0 % 38 . 7 % p & lt ; 0 . 01 & lt ; 0 . 1 & lt ; 0 . 1______________________________________ effect of ptc on the oxygen consumption rate and survival percentage of mice under hypoxia the male mice weighy 18 - 20 g were used in the experiments and were divided into ptc and control group . the dosage of ptc was 50 mg / kg injected intraperitoneally . the control mice were injected with same volume of normal saline . these injections were repeated daily for four days . on the last day , bath ptc and control group mice have been placed in airtight box . oxygen of box was measured with bare - tip platinum electrode . atmospheric pressure of airtight box was reduced to 180 mm hg with air pump . ptc group resulted in a prolongation of survival time and elevation of survival percentage of the mice under hypoxia . in ptc group the residual content of oxygen more than the control at 16 min after reduced pressure . it illustrats that ptc might improve the oxygen utilization during hypoxia . table 5______________________________________ residual o . sub . 2survival time survival percentage in ( min ) percentage (%) atmospheric (%) ______________________________________control 16 ± 2 0 6 . 4 ± 0 . 4ptc 58 ± 5 84 8 . 4 ± 0 . 5p & lt ; 0 . 01 & lt ; 0 . 001 & lt ; 0 . 01______________________________________ blood was collected from veins of humans using a needle attached to a plastic disposal syringe . the blood was immediately transtered into siliconized glass tube containing 0 . 1 volume of 3 . 13 % sodium citrate . platelet - rich plasma ( prp ) was obtained by centrifugation of the whole blood at 1 , 000 rpm for 10 min at room temperature . platelet - poor plasma ( ppp ) was prepared by centrifugation of the remaining blood at 3 , 000 rpm for 10 min . platelet aggregation was performed using in aggregameter at 37 ° c . human platelet studies were carried out at constant platelet number ( 3 × 10 8 / ml ). with regards to determination of platelet aggregation , the maximum aggregation induced by adenosine diphosphate ( adp ) in a final concentration of 2 μm was obtained by the light transmission method . 0 . 4 ml prp of each subject was introduced into each of 24 tubes and divided into 2 groups . then to the 12 tubes of each group were added 50 μl of saline and 50 μl php ( 0 . 5 mg / ml ) respectively . after incubation of 3 min at 37 ° c ., to each of 12 tubes of each group were added 50 μl of 2 μm adp . a 5 min aggregation curve for each tube was plotte . table 6______________________________________ rate of aggregation percent inhibition of platelet of aggregation______________________________________control 67 . 5 ± 5 . 0 -- pto 19 . 8 ± 1 . 5 70 . 6 % p & lt ; 0 . 01______________________________________ 1 inject 2 ml of normal saline into the peritoneal cavity of mouse for control group and 50 mg / kg ptc for ptc group daily . 3 inject 2 - 5 ml of tissue culture medium into the peritoneal cavity and gently press the abdomen to bring the cells into suspension . 4open the abdominal skin of the mouse and hold up the centre of the peritoneum with forceps . 5 make a small hole in the peritoneum and remove the medium with a pipe . 6 finally open the mouse fully and suck out all the medium . 7 estimate the number of phagocytes by the uptake of a 1 % neutral red solution ( haemocytometer count ). add 0 . 02 ml of 5 % washed chick red blood cell suspension to 0 . 5 ml of the peritoneal exudate , shake gently to mix and incubate at 37 ° c . for 5 minutes . dip two coverslips , close to each other , in the above mixture and incubate for 30 minutes for the migration of the macrophages along the cover slips , fix and stain with sharma stain . examine microscopically for : phagocytic rate -- number of macrophages with phagocytized chick red blood cells per 100 macrophages counted . table 7a______________________________________ normal ptc______________________________________phagocytic percent + sd (%) 35 . 10 ± 2 . 01 50 . 4 ± 4 . 10number of sample 12 12p & lt ; 0 . 01______________________________________ method -- counted the number of macrophages in the peritoneal exudate of mice and adjusted to 1 × 10 7 cell / ml with normal saline . added 0 . 1 ml of the macrophage suspension i . e . 1 × 10 6 cells to each well on the plastic plate for the test . labelled the chick red blood cell with 53 cr , suspend the label chick red blood cell and adjusted to 1 . 5 × 10 8 / ml , added 0 . 1 ml , i . e . 1 . 5 × 10 7 , to each well . incubated at 37 ° c . for 30 min ., washed to remove the free chick red blood cells . counted each well in a γ - counter . table 7b______________________________________ normal ptc______________________________________cpm 1089 ± 341 3041 ± 401number of sample 12 12p & lt ; 0 . 0001______________________________________ the above data of phagocytosis illustrated that ptc can increase immune function in mice . the male rats ( 280 to 320 g body weight ) were killed by decapitation and the hearts were immediately removed , opened , and washed in cold m / 30 phosphate buffer . the buffer was m / 30 potassium phosphate and was adjusted to ph 7 . 4 . the hearts then were homogenized in cold buffer containing one of the following substrates , depending upon the experiment being performed : glucose or pyruvate . the homogenates were prepared so that 1 cc . contained 100 mg of fresh tissue . one cubic centimeter of homogenate was added to iced warburg vessels containing 1 . 3 cc . of buffer in the main compartment , 0 . 5 cc . of 100 μm ptc or buffer in the sidearm , and 0 . 2 cc . of 10 % koh plus a pleated strip of no . 41 filter paper in the center well . the gas phase was air and the temperature of the bath was 37 ° c . after a ten - minute equilibration period the sidearm contents were tipped into the main compartment , the manometers were closed and the oxygen consumption was read after one hour . the ph of all solution was adjusted to 7 . 4 before use . for each experiment eight rats were used and several flasks were run simultaneously with homogenate from each rat . the experimental results are listed in the following table 8 . table 8__________________________________________________________________________concentration of substratenone 0 . 011m glucose 0 . 015m pyruvatecontrol ptc control ptc control ptc__________________________________________________________________________oxygen30 ± 2 . 7 19 . 5 ± 1 . 0 45 ± 3 . 0 31 . 5 ± 2 . 5 160 ± 11 96 ± 8 . 1uptakenumber8 8 8 8 8 8samplep & lt ; 0 . 01 & lt ; 0 . 1 & lt ; 0 . 001__________________________________________________________________________ 10 % solution of ptc was administered intraperitoneally in mice . no reactions were observed . the acute ld 50 was found to be 918 mg / kg . each dose for an adult is 50 mg . using 50 kg as the average weight of an adult the dosage is 1 mg / kg , therefore it is very safe . it will thus be shown that there are provided compositions and methods which achieve the various objects of the invention , and which are well adapted to meet the conditions of practical use . as various possible embodiments might be made of the above invention , and as various changes might be made in the embodiments set forth above , it is to be understood that all matters herein described are to be interpreted as illustrative and not in a limiting sense . | the new pharamaceutical composition and process are provided for treating and preventing cardiovascular disease . the fine - ptc is composed of following ingredients : puerarin or derivate of puerarin ; danshensu or danshenketone ; tetramethyl pyrazine ; polysaccharides and ssponin of dangshen . the composition is nontoxic . |
the foregoing and other features , aspects , and advantages of the present invention will be more apparent from the following detailed description , which illustrates exemplary embodiments of the present invention . referring now to fig1 , there is illustration of an exemplary embodiment of a fluid delivery device 100 constructed in accordance with some of the embodiments of the present invention , also referred to as a patch unit , which may be adherable to a patient &# 39 ; s body , and a remote control unit ( not shown ), which communicates with the patch unit 100 . the patch unit may comprise a disposable portion 10 , which is detachably connectable to a reusable portion 12 . the configuration of the fluid delivery device comprising such a patch unit is disclosed in applicants israel patent application no . 171813 as well as in u . s . patent application ser . no . 11 / 397 , 115 , both disclosures herein incorporated by reference in their entireties . one of the advantageous of such a fluid delivery device 100 configuration is that the relatively expensive components may be deployed within the reusable portion 12 while less expensive components might be accommodated within the disposable portion 10 . by virtue of this provision , the use of the device is significantly more economical for the patient . reusable portion 12 of a fluid delivery device 100 may be removably coupled to a disposable portion 10 in operative association , as shown in fig1 . in fig2 , only the disposable portion 10 of the fluid delivery device is shown . the disposable portion 10 may include a u - shaped housing defined by lateral walls lw 1 and lw 2 , by bridging section bs and by butt ends be 1 and be 2 . one of ordinary skill in the art would recognize that the u - shaped housing may vary in shape in perspective to a non - formal u - shape . additional components of the disposable portion 10 may include a reservoir 14 situated between lateral walls and butt end be 2 . the reservoir 14 preferably includes a therapeutic fluid , e . g . insulin . the reservoir 14 is in fluid communication with a delivery tube 16 , terminating by an outlet port 18 . through this port the fluid can be delivered to a cannula ( not shown ), which is subcutaneously inserted in a patient . the reservoir 14 can be filled with the therapeutic fluid through an inlet port 20 , which may be made in butt end be 2 . the butt end be 2 may include a rectangular configuration terminating by a face 22 . a sealing cover 24 preferably seals the inlet port 20 . in accordance with the design of the patch fluid delivery device unit 100 , a portion of the delivery tube 16 , which extends along the bridging section bs may be placed between a stator plate and wheels of a peristaltic pump of the reusable portion 12 ( not shown ). when these wheels rotate , they depress the tube 16 to the plate and squeeze it . accordingly , the fluid is periodically pumped from the reservoir 14 to exit port 18 and further to the cannula . with reference to fig3 - 5 adapter 26 of the invention is generally illustrated , which may be suitable for connecting the reservoir 14 with a syringe filled with a therapeutic fluid . preferably , the adapter 26 is configured as an elongated tubular structure made of a plastic suitable for medical use , which in a preferred embodiment is of inexpensive material . the adapter 26 may include a first connecting end 28 , and may also include an opposite second connecting end 30 , with an intermediate body portion 32 . the first connecting end 28 may be attachable to a needle - less syringe 50 , as seen in fig8 . the second connecting end 30 may be releasably attachable either to a circular neck of container for therapeutic fluid or to an end ( e . g ., rectangular butt end be 2 ) of a housing of a fluid delivery device ( e . g ., that of the patch unit 100 ). the second connecting end 30 may be provided also with an abutment wing 34 , which may be used to rest on lateral wall lw 2 of the housing when the second connecting end 30 is connected to the butt end be 2 of the housing . referring to fig4 and 5 , it is seen that the second connecting end 30 may be provided with a border wall 36 delimiting a depression . the contour of the border wall 36 comprises a circular portion 38 and a non - circular portion 40 . the non - circular portion 40 may be a rectangular shape or any other shape which would be understood by one of ordinary skill in the art . the circular portion 38 of the border wall 36 may define a circular region d 1 of the depression . this region d 1 is preferably intended for receiving the circular neck of the fluid container . the non - circular portion 40 of the border wall may define a non - circular region d 2 of the depression . this region d 2 can be used for receiving butt end be 2 of the housing . the circular 38 and non - circular 40 regions may be configured and dimensioned to allow a tight fit with the received items irrespective whether it is circular neck of the fluid container or butt end of the housing . circular portion of the border wall is provided with gaps g 1 , g 2 , g 3 , to provide a discontinuous arrangement , which preferably provides a degree of elasticity . it is understood by one of ordinary skill in the art that the number of gaps g 1 - g 3 may vary accordingly between alternative embodiments . seen in the center of the region d 1 is a sharpened end 42 of a penetrating member , which is secured at the first connecting end of the adaptor 26 . the sharpened end is preferably fully concealed within depression delimited by the border wall 36 and therefore is preferably not accessible . by virtue of this provision inadvertent puncture may be prevented . as shown in fig6 , the first connecting end 28 may be provided with a core 44 , in which a cavity 46 may be provided . the shape of the core and of the cavity may be selected to constitute a female half of luer slip connector . a hollow penetrating member 48 is secured within the core such that sharp end 42 of the penetrating member protrudes inside region d 1 of the depression made in the second connecting end 30 of the adapter 26 . by virtue of this provision , fluid communication is provided between cavity 46 and the depression in the second connecting end 30 . as a suitable penetrating member , one can use a hollow needle or a cannula , according to one embodiment . instead of dedicated core with cavity 46 , one can use ready - to - use female half of luer connector , which would be suitably embedded in the first connecting end 28 . referring to fig7 and 8 it is shown how a needle - less syringe 50 is connected to the first connecting end 28 of the adapter 26 . it is seen that male half 52 of luer slip connector provided at the syringe 50 is inserted within female half 46 of the luer connector associated with the first connecting end 28 . referring to fig9 a and 9b it is shown how the second connecting end 30 may be attached to a fluid container 54 . it is seen in fig9 b , that when a neck 56 of the container is fully received within circular depression region d 1 of the second connecting end 30 , the penetrating member 48 pierces a cover 58 of the container and protrudes inside the container . one of skill in the art can readily appreciate that since there is provided fluid communication between the first 28 and second 30 connecting ends , the therapeutic fluid could be withdrawn from the container through the penetrating member into the syringe 50 . referring now to fig1 a and 10 b it is shown the second connecting end 30 of the adapter 26 being attached to rectangular butt end be 2 of the housing , while first connecting end 28 is attached to syringe 50 such that reservoir 14 can be filled or replenished by the therapeutic fluid from the syringe 50 . it is seen that the butt end be 2 is received within depression in the second connecting end 30 such that it is embraced by non - circular portion 38 of the border wall and by abutment wing 34 juxtaposed with lateral wall lw 2 of the housing . in this position piercing member 48 pierces sealing cover 24 of the reservoir 14 such that therapeutic fluid can be delivered through inlet port 20 to the reservoir from syringe 50 . below is an exemplary method , according to some embodiments of the present invention , of how a reservoir of a fluid infusion device can be filled with the aim of adapter of the invention . when filling the reservoir of the fluid infusion device , the first connecting end of the adapter may be attached to the male half of luer connector of a needle - less regular syringe as illustrated in fig7 . typically , such syringes are supplied with separate therapeutic fluid containers in a pharmacy store . the second connecting end of the adapter may then be firmly attached to the fluid container until circular portion of the border wall engages the orbicular neck of the fluid container and piercing member pierces sealing cover of the container . in one embodiment , in order to eliminate entering of air into syringe , the syringe connected to adapter is held in a vertical position whereas the second connecting end is on top , as illustrated in fig8 a . by pulling the syringe &# 39 ; s plunger backward , fluid from the container can be withdrawn through the piercing member into the syringe . when the syringe is filled with the desired dose , the fluid container is detached from the second connecting end . it is worth noting that entrapment of air bubbles during the withdrawing process should preferably be prevented . for this purpose , according to an embodiment of the invention , air is primed from the syringe before withdrawal of the medicament fluid . during the priming , the syringe is preferably held in a vertical position whereas the second connecting end is on top . then , the plunger of the syringe may be slightly pushed inwardly until a first drop ( s ) of the fluid appears at the tip of the penetrating member . after the syringe is filled with the fluid , the second connecting end of the adapter may be separated from the container and then attached to the housing of the disposable portion of the fluid infusion device as illustrated in fig1 a and fig1 b . the therapeutic fluid can be now transferred from the syringe to the reservoir of the fluid infusion device . it is worth noting that during attachment and filling of the reservoir , the adapter and the housing are preferably held in a vertical position such that the outlet port of the housing is on top . then , the plunger may be slowly pushed inwardly until first drop ( s ) of fluid appears at the outlet port , indicating that reservoir is full and that air in delivery tube was primed . the adapter can then be detached from the housing and the fluid infusion device is ready to operate . although particular embodiments have been disclosed herein in detail , this has been done by way of example for purposes of illustration only , and is not intended to be limiting with respect to the scope of the appended claims , which follow . in particular , it is contemplated that various substitutions , alterations , and modifications may be made without departing from the spirit and scope of the invention as defined by the claims . other aspects , advantages , and modifications are considered to be within the scope of the following claims . the claims presented are representative of the inventions disclosed herein . other , unclaimed inventions are also contemplated . the applicant reserves the right to pursue such inventions in later claims . | medical devices and methods for delivering therapeutic fluids transcutaneously to a body of a patient via a fluid delivery device and an adapter is provided . a luer slip connector is provided at a first connecting end of the adapter . a therapeutic fluid container is connected with the second connecting end such that the container &# 39 ; s neck is received in the second connecting end and a hollow penetrating member provided in the adapter punctures the septum of the container to admit the therapeutic fluid into a needle - less syringe from the container . after , fluid emerges from the tip of the penetrating member , the second connecting end of the adapter is attached to the fluid delivery device , thereby filling the reservoir with the fluid and pushing the syringe plunger forward to inject fluid into reservoir . |
basic components of a fire fighting vehicle in accord with the invention are illustrated in fig1 wherein the vehicle includes an internal combustion engine 10 driving a transmission 12 through a conventional clutch within clutch housing 14 . the vehicle includes rear drive wheels 16 mounted upon a rear axle including differential 18 , and the differential is driven by the transmission output through shaft 20 . usually , the transmission 12 will be of the manual , multi - speed type , but it is within the concept of the invention that the transmission be of the automatic variety . the vehicle also includes water pumps 22 and 24 , the pumps being mounted upon opposite sides of the drive shaft 20 , and pump 22 includes a drive shaft 26 , while pump 24 includes a drive shaft 28 , the pump drive shafts being substantially parallel to the vehicle drive shaft , and extending in a forward direction from the associated pump . the plumbing associated with the pumps includes an inlet manifold 30 , and an outlet manifold 32 , both manifolds being mounted transversely across the vehicle and having ends located adjacent the vehicle lateral sides , as will be described . the transmission 12 is substantially conventional , and includes a rotating shaft 34 which will rotate at all times that the engine 10 is operating except when the clutch within clutch housing 14 is disengaged from the engine . therefore , it is to be understood that the shaft 34 will rotate regardless of whether the vehicle wheels 16 are being driven , or the vehicle is stationary , as long as the transmission clutch is engaging the engine output and the engine is operating . a third speed counter - gear 36 is mounted upon the shaft 34 , and the gear 36 is in alignment with openings 38 defined in the transmission casing , fig2 and 3 . the openings 38 constitute power take - off openings , and the transmission casing includes bosses 40 about the openings which are drilled and tapped for receiving bolts 42 for the attachment of power take - off units to the casing in alignment with gear 36 . a power take - off unit is fastened to each side of the transmission casing , and the power take - offs are generally indicated at 44 and 46 . the power take - offs are similar in construction , being of right hand and left hand construction , and the following description will be with respect to power take - off unit 44 , similar components of unit 46 being indicated by primed reference numeral . the power take - off 44 includes an output shaft 48 rotatably mounted within suitable bearings upon the casing 50 , the output shaft being substantially parallel to the vehicle length , and an output gear 52 is mounted upon the output shaft and is of an axial length approximately twice that of the gear 36 , as will be appreciated from fig3 . a transfer gear 54 is mounted within casing 50 upon rotatable shaft 56 , and the teeth of the transfer gear mesh with the teeth of output gear 52 . the transfer gear 54 is axially slidably displaceable upon the shaft 56 , and includes a groove 58 defined by the gear and flange 60 for receiving the shifting yoke 62 , as will be later described . the teeth of the transfer gear 54 are selectively engageable with the teeth of the transmission drive gear 36 , and in fig3 transfer gear 54 &# 39 ; is illustrated as being out of mesh with the teeth of drive gear 36 , while transfer gear 54 is shown as meshing with the drive gear 36 . a cover plate mounted upon the power take - off casing by bolts cover the opening 66 , and serves as the support for the rotatable shifting shaft 68 . the inner end of the shaft 68 includes a lever 70 and the yoke 62 which is received within the associated transfer gear groove 58 , and the outer end of the shaft 68 has the shifting lever 74 fixed thereon whereby oscillation of the shifting lever rotates shaft 68 and positions yoke 62 to axially displace the associated transfer gear 54 with respect to the drive gear 36 . the lever 74 , shaft 68 , yoke 62 and transfer gear 54 all form a part of clutch structure for the associated power take - off unit 44 whereby the power take - off output shaft 48 may be selectively driven by the transmission shaft 34 and gear 36 . the shifting levers 74 and 74 &# 39 ; are operated remotely through rods or cables 76 and 76 &# 39 ; attached thereto , and actuating means for the rods and cables are located upon the vehicle adjacent an appropriate control panel or console , as is well known in the fire fighting vehicle art . the power take - off output shaft 48 is directly connected to the pump drive shaft 28 , and the power take - off output shaft 48 &# 39 ; is directly connected to the pump drive shaft 26 . of course , the location of the pumps on the vehicle may necessitate the utilization of universal joints in the drive train between the pumps and the associated power take - off unit , but it is to be appreciated that each pump is directly connected to a separate power take - off unit and the pump operation is controlled by the associated power take - off unit . the plumbing associated with the pumps 22 and 24 is best illustrated in fig4 and 5 , and as previously described , includes an inlet manifold 30 , and an outlet manifold 32 . each pump includes an inlet port 78 to which an inlet conduit 80 is attached , and the inlet conduits 80 each communicate with the inlet manifold . the inlet manifold 30 extends transversely across the width of the vehicle , and at each end includes a fitting 82 for receiving a suction hose . the fittings 82 normally close the associated end of the inlet manifold , and an auxiliary valved suction fitting 84 communicates with the inlet manifold whereby an additional suction hose may be attached thereto , if desired . the vehicle also includes a water storage tank 86 , fig1 and the water storage tank includes a valved outlet 88 communicating with the inlet manifold 30 whereby water may be supplied to the pumps from the tank 86 if the water supply of the vehicle is to be utilized . the outlet manifold 32 also extends transversely of the vehicle length , and includes a valved discharge fitting 90 at each end . the outlet manifold is supplied with pressurized water from the pump outlets through conduits 92 and check valves 94 . a hose manifold 96 communicates with the outlet manifold , and valves 98 and 100 are illustrated as mounted thereon in communication with the hose manifold , the hose on valve 98 communicating with the tank of the vehicle to permit filling , and the hose on valve 100 providing the supply to the vehicle hose reel . additional connections are defined upon the hose manifold , and a fitting 102 communicating with the outlet manifold 32 extends rearwardly for attachment to a rear discharge , if desired . the outlet manifold also includes a relief valve 104 which communicates with conduit 106 connected to inlet manifold 30 whereby water will be recirculated when the pumps are operating , and the valves associated with the outlet manifold are closed . the aforedescribed structure permits each of the pumps 22 and 24 to be individually driven by the gear 36 within transmission 12 . either pump may be energized or deactivated , and merely by operating the control cables 76 complete individual control of the pumps is achieved . as the drive gear 36 is located within the regular transmission 12 additional expensive transmission gearing is not required , and the described plumbing connections permit the desired individual pump operation without creating air locks or other disabling conditions . while each pump 22 and 24 is rated at 250 gallons per minute , the torque requirement for operating both pumps to produce a 500 gpm output is 210 ft lb ., as compared with apparatus using a single 500 gpm pump which requires 500 ft . lb . of torque . further advantages of the invention are derived from the ability of the system to be concisely installed upon the vehicle as compared with single pump systems of equal pumping capacity . as the inlet manifold may be directly supplied from the vehicle tank 86 , either one or both pumps may be supplied with water while the vehicle is in motion , and such &# 34 ; pump and roll &# 34 ; capacity is highly desirable when the vehicle is used with grass or forest fires . the apparatus permits pumping capacity even in the event that the drive train from the transmission to the differential fails , and should a pump drive shaft failure occur the disengagement of that pump from the transmission still permits the other pump to operate wherein the apparatus will still remain at a 50 % capacity , an advantage not achieved with the usual fire fighting vehicle pumping system employing a single power take - off and pump driving system . the apparatus in accord with the invention , as compared with more conventional vehicle pumping systems of equivalent capacity , occupies only two - thirds of the space , is only three - quarters as expensive , and is approximately 10 % lighter in weight than a comparable 500 gpm system . it is appreciated that various modifications to invention may be apparent to those skilled in the art without departing from the spirit and scope thereof . | a pumping system for fire fighting vehicles wherein a pair of power take - off units mounted on the vehicle transmission engages with a drive gear within the transmission to separately drive water pumps . the power take - offs are each provided with a clutch wherein selective independent and simultaneous pump operation is possible , and it is also possible to operate one or both of the pumps while the vehicle is moving wherein a &# 34 ; pump and roll &# 34 ; capacity is achieved . the vehicle includes a water storage tank selectively communicating with an inlet manifold communicating with the pump inlets , and an outlet manifold receives the pumps &# 39 ; discharge . the manifolds are provided with hose fittings at each vehicle lateral side , and the two pump system of the invention is readily installable in medium size vehicles . |
in the following description of preferred embodiments , reference is made to the accompanying drawings which form a part hereof , and in which it is shown by way of illustration specific embodiments in which the invention can be practiced . it is to be understood that other embodiments can be used and structural changes can be made without departing from the scope of the embodiments of this invention . although embodiments of the invention may be described and illustrated herein in terms of whiteboards , and particularly smart boards , it should be understood that embodiments of this invention are not so limited , but are additionally applicable to any support system . for example , features of the present invention may be used with chalk boards or bulletin boards . furthermore , although embodiments of the invention may be described and illustrated herein in terms of educational tools , including whiteboards , it should be understood that embodiments of the invention are also applicable to other industries , such as electronic controls and displays , including audio / video equipment mounting systems . fig1 illustrates a whiteboard mounting system 100 according to an exemplary embodiments of the present invention . in an exemplary embodiment , the mounting system 100 may have a top rail 110 that is attached to a wall or support surface ( not shown ) for the whiteboard ( not shown ). it is contemplated that at least one mounting arm 120 is removably attached to the top rail 110 . however , in an exemplary embodiment , a plurality of mounting arms 120 may be removably attached to the top rail 110 . the top rail 110 may include a support protrusion 112 that is configured to mate with an attachment portion 122 of the mounting arm 120 . it is contemplated that at least one , and alternatively , a plurality of support rails 130 may connect to the mounting arms 120 and support the attached whiteboard . in an embodiment , the whiteboard ( not shown ) may be removably attached directly to the support rail 130 or may utilize a support feature 132 on the support rail 130 . the support rails 130 may be positioned along the mounting arms 120 at a plurality of heights to vertically adjust the whiteboard location . additionally , the board may be supported at a plurality of positions on the support rails 130 which may permit horizontal adjustment of the board relative to the support rails 130 . the mounting arm 120 may have at least a first end 119 and a second end 123 . it is contemplated that the second end 123 of the mounting arm 120 , which is located opposite to the attachment portion 122 and the first end 119 of the mounting arm 120 , may include a leveling foot 124 that may adjust the distance from the wall which may ultimately assist in properly aligning the mounting system 100 relative to the wall . in an exemplary embodiment , the mounting arms 120 may be contoured to fit over an existing wall feature . it is contemplated that the mounting arms 120 may have a convex and / or concave portion which may hold the whiteboard away from the supporting surface , such that a user may install the whiteboard over an existing blackboard . moreover , the mounting arms 120 may be constructed to be longer than the height of the whiteboard , to permit greater placement options for the whiteboard on the mounting arms 120 . further the extended length of the mounting alms 120 may permit the mounting arms 120 to span and if necessary , exceed the height of the underlying black board ( not shown ). however , it should be understood that the mounting arms 120 may alternatively be configured to not have any convex or concave portion , and alternatively be flat against the support wall or within the frame of the whiteboard , to provide different aesthetic and special options . fig1 a illustrates a close up of the support rail 130 whereby the support rail 130 attaches to the mounting arm 120 . in an exemplary embodiment , the support rail 130 may attach to the mounting arm 120 at a plurality of locations to permit the vertical adjustment of the whiteboard relative to the mounting arm 120 . the support rail 130 may be attached to the mounting arm 120 by any of screws , rivets , pull - pins , friction sliders , and the like . for example , as seen in fig1 b , mounting arm 120 includes a plurality of screw holes 126 to allow for attachment of the support rail 130 to the mounting arm 120 via screws 134 . in an exemplary embodiment , a plurality of holes are provided to permit a user to adjust the height of the whiteboard . the support rail 130 may include a support feature 132 that may engage a corresponding feature on the whiteboard . for example , as shown in fig1 a , the support feature 132 is a cleat similar to the support protrusion 112 of the top rail 110 . in an exemplary embodiment , the support feature 132 may be a cleat that resembles an upside down , half u - shaped hook that engages a corresponding feature on the back of the whiteboard ( not shown ). the whiteboard may include an upper edge including a lip projected outward then downward to create a mating hook for the support feature 132 . in another exemplary embodiment , the support feature 132 of the support rail 130 and the corresponding feature of the whiteboard ( not shown are configured to permit the whiteboard to easily slide in a horizontal direction . a stop may be provided along the support rail 130 or the corresponding feature of the whiteboard to prevent the board from sliding out of its rail or overbalancing the mounting system . it should be understood that a cleat is provided to removably attach the board to the support rail , however , a plurality of different attachment means may be utilized to attach same . in another alternate embodiment , the mounting system may utilize hook and loop fasteners that may be used in place of the support feature on at least one of the support rails 130 . for example , the mounting system 100 may include two support rails 130 a and 130 b , as seen in fig1 . the upper support rail 130 a may be attached to the whiteboard with a support feature 132 , as described above , while the lower support rail 130 b may be attached to the whiteboard with a hook and loop fastener . in this case , the surface of the support rail 130 b may have a hook or loop fastener , while the back of the whiteboard has the corresponding loop or hook fastener . the hook and loop fastener may be attached to the support rail or whiteboard by taping , gluing , adhering , bonding , stapling , or other device . alternatively , for a more permanent connection , the support rail may be adhered to the whiteboard directly through taping , gluing , adhering , bonding , or other device . fig1 b illustrates the lower corner of the mounting system 100 including the mounting arm 120 and leveling foot 124 . in an exemplary embodiment , the mounting arms 120 includes a leveling foot 124 to adjust the angle of the mounting system 100 . the leveling foot 124 may be an adjustable pad 128 . the height of the leveling foot 124 may be adjusted utilizing devices , such as a sliding extension , a screw extension , or the like . the leveling foot 124 may be attached to the mounting arm 120 or another embodiment may be integrally formed with the mounting arm 120 . in an exemplary embodiment , the leveling foot may be a cap portion that may be fit over the end portion 131 of the mounting arm 120 . the adjustable pad 128 may be adjusted to properly align the whiteboard mounting system 100 . fig1 c illustrates cut away view of the lower corner of the mounting system 100 , including the leveling foot 124 and finger cleat 140 , according to an exemplary embodiment of the invention . in an exemplary embodiment , a finger cleat 140 may be mounted to the support surface ( not shown ) to additionally secure the leveling foot 124 and potentially add further support to the mounting system 100 . the finger cleat 140 includes an indention 142 to fit around a neck 129 of the leveling foot 124 between the adjustable pad 128 and the mounting arm 120 . the finger cleat 140 may be positioned so that the indention 142 in horizontal , and therefore , locks the mounting system 100 in place once installed . the finger cleat 140 may optionally be installed so the indention 142 faces upwards , and therefore , permits the mounting system 100 to be removed and replaced , repeatedly sliding into the indention from the top side while fitting the mounting system to the top rail . the finger cleat 140 may be secured to the support surface by a screw or nail 144 through hole 146 . other securing devices may be used , such as taping , anchoring , adhering , gluing , bonding , and the like . in an exemplary embodiment , the system may utilize hook and loop fasteners that may be added to the mounting system 100 for additional stability . the adjustable pad 128 located on the leveling foot 124 of the mounting arm 120 may include a hook or loop fastener surface . a corresponding loop or hook fastener may be adhered to the mounting surface for attaching to its corresponding hook and fastener on the mounting arm 120 . the hook and loop fasteners may be adhered , bonded , glued , or otherwise attached to the respective locations . it is contemplated that the top rail 110 may be made of any sufficiently strong material to support the whiteboard . in an exemplary embodiment , the top hanging rail 110 may be constructed of aluminum that may be sufficiently rigid to support the attached board , but still light in weight to reduce the additional burden on the wall or supporting surface to which the system is attached . the mounting arms 120 may be constructed of steel to provide adequate support strength for the board . the support rails 130 may also be constructed of aluminum to reduce the weight of the mounting system 100 . other materials , for each component , may include metals or metal alloys , such as aluminum , aluminum alloy ( e . g . 6063 - t5 ), steel ( 18ga steel ). strong plastics or other materials may alternatively be used . it should be understood that a plurality of different materials may be utilized , and each component of the system 100 may be constructed of the same or different materials . fig2 illustrates the mounting system 200 in the unassembled state , according to exemplary embodiments of the invention . in an exemplary embodiment , the mounting system 200 may be provided in a complete kit form which may include an aluminum top rail 210 , two 18ga steel mounting arms 220 with steel hanger clips 226 , leveler inserts 224 , and two aluminum support rails 230 . additionally , the system 200 may include mounting equipment and instructions for assembling the system 200 . the mounting system 200 may be designed to secure a smart board to a wall over an existing black board or whiteboard . to install the top rail 210 , the user would place the top rail above the existing chalk board ( not shown ), and secure the top rail 210 in the desired location . the top rail 210 may be attached to a wall ( not shown ) with wall anchors , nails , screws , or other securing devices , depending on the wall characteristics . then , the support rails 230 may be removably attached to the mounting arms 220 . the mounting arms 220 may include a plurality of holes 226 at set intervals , for example , one inch , to permit incremental adjustment in height . the support rails 230 may be attached to the mounting arms 220 by self - tapping screws . other coupling devices may provide screws , rivets , plugs , and the like . the support rails 230 may be attached with cleat 232 facing outward , away from the wall . preferably , the first and second support rails 230 a and 230 b are utilized and preferably spaced the maximum distance apart to increase stability of the system 200 . once the mounting system 200 is fully assembled , the board may be hung from cleat 232 of the upper support rail 230 a . in an exemplary embodiment , the board may hang from the upper support rail 230 a by corresponding features included on the top of the whiteboard . the lower support rail 230 b may be attached to the board with double - faced tape . once the position of the support rails 230 and mounting arms 220 are in the desired location . double - faced tape is adhered between the lower support rail 230 b and the whiteboard . the board is then pressed firmly to the lower support rail 230 b to properly secure the connection . alternatively , hook and loop fasteners may be used in place of the adhesive for a secure , but non - permanent coupling . further , other fastening means may be employed to removably attach the board to the support rails 230 a and b . in an exemplary embodiment , hook and loop fasteners may be utilized used to increase the connection between the mounting system 200 and the supporting wall . coin - shaped , hook fasteners may be adhered to the supporting wall or existing blackboard with double - faced tape , while the corresponding loop fastener may be adhered to the leveling foot 224 . the hook and loop fasteners may be adhered by taping , gluing , bonding , or some other device . in yet another exemplary embodiment , finger cleats ( not shown in fig2 ) may be utilized to secure the base of the mounting system 200 to the supporting wall . once the mounting system 200 is hung , assembled , and positioned , the finger cleat may slide around the leveling foot 224 and be secured to the supporting wall . the finger cleat is secured to the wall using the appropriate wall anchor and screw 234 , depending on the support wall characteristics . the finger cleat may also be adhered to the supporting wall , or existing chalkboard , such as by taping , bonding , gluing , and the like . another exemplary embodiment may include a permanently affixed wall mounted rail system 200 for interactive whiteboards . the system 200 is composed of a top hanging rail 230 and two support rails , two mounting arms 220 with leveling feet and mounting clip . the rail system semi - permanently attaches an interactive whiteboard to a wall . the top hanging rail 230 is permanently mounted to a wall with the appropriate fasteners . the mounting arms 220 are hung from the hanging rail 226 on the clip affixed to the top of the mounting arm 220 . the two remaining support rails are attached to the mounting arms 220 with screws . the interactive whiteboard mounts to a cleat on the top support rail . two hook and loop tabs 224 are attached with double - face tape to the leveling feet at the bottom of the mounting arms 220 and secured to the wall . two hook and loop tabs 226 are attached to the bottom support rail 210 and secured to the back of the interactive whiteboard . in one embodiment , the mounting arm 220 includes a series of screw holes 234 to allow for height adjustment . although embodiments of this invention have been fully described with reference to the accompanying drawings , it is to be noted that various changes and modifications will become apparent to those skilled in the art . such changes and modifications are to be understood as being included within the scope of embodiments of this invention as defined by the appended claims . | the mounting system may be used to support a display on a support surface . the mounting system may include a top rail secured to the support surface . the mounting , system may also include a mounting arm hung from the top rail and a support rail attached to the mounting arm that supports the whiteboard . the mounting system may provide permanent or removable attachment to the support surface that may interchangeably accommodate a variety of displays . |
in the following description , certain details are set forth so as to provide a thorough understanding of the present embodiments disclosed herein . however , it will be understood by those skilled in the art that the present disclosure may be practiced without such specific details . in many cases , details concerning such considerations and the like have been omitted inasmuch as such details are not necessary to obtain a complete understanding of the present disclosure and are within the skills of persons of ordinary skill in the relevant art . the definitions and explanations as set forth herein are meant and intended to be controlling in any future construction unless clearly and unambiguously modified in the following description or when application of the meaning renders any construction meaningless or essentially meaningless . in cases where the construction of the term would render it meaningless or essentially meaningless , the definition should be taken from webster &# 39 ; s dictionary , 3rd edition . definitions and / or interpretations should not be incorporated from other patent applications , patents , or publications , related or not , unless specifically stated in this specification or if the incorporation is necessary for maintaining validity . other than in the operating examples , or where otherwise indicated , all numbers expressing quantities of components used herein are to be understood as modified in all instances by the term “ about ”. the present disclosure pertains to methods of forming antimicrobial resin compositions that comprise in situ generated silver nanoparticles . in some embodiments , the invention provides a method of making an antimicrobial resin composition containing silver nanoparticles , by selecting a silver - containing material , an acrylic resin monomer and a solvent that is miscible with the silver - containing material and with the acrylic resin monomer ; combining the acrylic resin monomer with a silver binding compound , combining the silver - containing material with the solvent to form a silver - containing material solution ; mixing the silver - containing material solution with the mixture of the acrylic resin monomer and silver binding compound in situ to form an acrylic resin monomer solution ; forming silver nanoparticles within the acrylic resin monomer solution by curing the acrylic resin monomer solution , wherein the curing process converts the acrylic resin monomer to a polymer ; and forming an antimicrobial , resin composition . other embodiments of the present disclosure provide antimicrobial resin compositions produced by the claimed methods . as used herein , the term , “ antimicrobial ” means that the article exhibits one or more of the following properties : the inhibition of the adhesion of bacteria or other microbes to the article ; the inhibition of the growth of bacteria or other microbes on the article ; and / or the killing of bacteria or other microbes on the surface of the article or in an area surrounding the article . for purposes of this invention , adhesion of bacteria or other microbes to the article , the growth of bacteria or other microbes on the article and the presence of bacterial or other microbes on the surface of the article are collectively referred to as “ microbial colonization .” in various embodiments , the articles of the present disclosure exhibit varying levels of inhibition of viable bacteria or other microbes . such bacteria or other microbes include but are not limited to pseudomonas aeruginosa , acanthamoeba species , staphyloccus aureus , escherichia coli , staphyloccus epidermidis , serratia marcesens , acinetobacter baumannii and / or the like . as used herein , the term “ patient ” means and refers to a human or animal . suitable examples include , but are not limited to a human or an animal ( e . g ., a dog , a cat , a horse , a bird , a reptile , an amphibian , a fish , a turtle , a guinea pig , a hamster , a rodent , a cow , a pig , a goat , a primate , a monkey , a chicken , a turkey , a buffalo , an ostrich , a sheep , a llama ). as used herein , the term “ chemically feasible ” refers to a connectivity of atoms such that the chemical valency of each atom is satisfied . for example , an oxygen atom with two bonds and a carbon atom with four bonds are chemically feasible . as used herein , the term “ nanoparticle ( s )” means and refers to small particles ranging from small visible particles to particles on the nano - scale . as used herein , the term “ metallic nanoparticle ( s )” means and refers to nanoparticles that contain one or more metals , such as silver . as used herein , the term “ polymeric ” means and refers to a composition ( s ) that comprises one or more monomers , oligomers , polymers , copolymers , or blends thereof . suitable examples of polymers include , but are not limited to , polyvinyl alcohol , poly ethylene glycol , ethyl cellulose , polyolefins , polyesters , nonpeptide polyamines , polyamides , polycarbonates , polyalkenes , polyvinyl ethers , polyglycolides , cellulose ethers , polyvinyl halides , polyhydroxyalkanoates , polyanhydrides , polystyrenes , polyacrylates , polymethacrylates , polyurethanes , polypropylene , polybutylene terephthalate , polyethylene terephthalate , nylon 6 , nylon 6 , 6 , nylon 4 , 6 , nylon 12 , phenolic resins , urea resins , epoxy resins , silicone polymers , polycarbonates , polyethylene vinylacetate , polyethylene ethyl acrylate , polylactic acid , polysaccharides , polytetrafluoroethylene , polyvinylidenes , polyphosphazines , chlorinated polyethylenes , polysulfones and copolymers and blends thereof . applicants also note that the terms “ polymeric ”, “ polymer ” and “ resin ” may be used interchangeably in the present disclosure . as used herein , the term “ water soluble ” or use of the term “ miscible in water ” means and refers to a level of solubility such that when a composition is placed in water , greater than about 2 . 0 percent by weight of the composition dissolves . for example , methyl methacrylate ( mma ) is considered substantially non water soluble , yet has a water solubility of about 1 . 6 g in 100 g of water . as used herein , the term “%” is intended to refer to % by weight or wt %, unless otherwise indicated . currently , polymeric materials , such as polymethyl methacrylate ( pmma ), are used in many industries for numerous purposes . for instance , polymeric resin materials are used in dentistry , orthopedics and craniofacial surgery . however one major problem with the utilization of polymeric resin materials is the occurrence of infections ( e . g ., caries in dentistry ). for example , but not by way of limitation , approximately 10 % of soldiers returning from various battlefields develop infections after receiving craniofacial implants . likewise , failure of orthopedic implants is often due to the periprosthetic infections of the pmma bone cement . current therapies to treat the more severe cases of infections involve the use of local and systemic antibiotics . however , antibiotic therapy poses the problem of generating resistant strains of bacteria . in the military , this is of special concern because many troops returning from various battlefields are infected with acinetobacter baumannii , a multi - antibiotic resistant bacteria . resin compositions of the claimed invention are also applicable in dental applications such as dental cements , luting agents and restorative materials . furthermore , resin compositions of the claimed invention can be used in non - medical commercial applications as well . accordingly , antimicrobial agents have been added to many polymeric materials in order to prevent infections during their various uses . for instance , silver salts have been used in human healthcare and medicine as an antiseptic for post surgical infections . silver salts have also been used as an anti - microbial agent for various purposes in dental devices , wound therapy , medical devices , and / or the like . specifically , silver nitrate has been used to prevent ophthalmic neonatorum in newborns . however , as discussed previously , silver particle - containing polymers tend to have a “ yellow ” to “ amber ” color at low concentrations and / or tend to darken or blacken during storage and thus , tend to lose their aesthetic appeal . accordingly , the claimed invention provides novel methods of forming antimicrobial polymeric materials and novel resulting products and compositions of matter that have improved color profile relative to existing silver containing resin compositions and also exhibit a more gradual release of silver from the resin . in some embodiments , the present disclosure provides methods of forming an antimicrobial resin composition that comprises a silver nanoparticle . such methods generally comprise : ( 1 ) combining a silver - containing material with a resin in situ , wherein the resin monomer is first combined with a silver - binding compound ; and ( 2 ) curing the resin mixture in the presence of the silver - containing material . as explained below , numerous metal containing materials and resins may be used in various embodiments of the present disclosure likewise , various curing methods may be used to form the polymeric materials of the present disclosure . a person of ordinary skill in the art will recognize that various silver containing materials may be used with the methods and compositions of the present disclosure . specific examples include silver - containing materials ( e . g ., silver , silver alloys , silver oxides , silver carbides , silver nitrides , silver borides , silver borate , silver sulfides , silver myristates , silver stearates , silver oleates , silver gluconates , silver adipates , silver silicates , silver phosphides , silver halides , silver hydrides , silver nitrates , silver carbonates , silver sulfadiazines , silver acetates , silver lactates , silver citrates , alkali silver thiosulphates ( e . g ., sodium silver thio sulphate , potassium silver thio sulphate )). in some embodiments , the silver containing materials are soluble in organic solvents and acrylic monomers . in more specific embodiments , metal containing materials may be silver oleates , silver gluconates , silver adipates , silver sulfadiazines , silver acetates , silver benzoate and the like . in further embodiments , the metal containing material is silver benzoate . a person of ordinary skill in the art will also recognize that various resins may be used with the methods and compositions of the present disclosure . non - limiting examples include acrylic resins . acrylic resins include , but are not limited to , any resin containing an acrylate group (═ cr — coor ′), where r and r ′ can be hydrogen , methyl , ethyl , butyl , benzoyl , or any alkyl or aryl group that is chemically feasible . other examples of resins that may be used with various embodiments of the present disclosure includes poly ( methyl methacrylate ) ( pmma ) resins ( an oil - based acrylic resin ), other oil - based resins , water soluble resins , and / or the like . more specific examples of resins that can be used with various embodiments of the present disclosure include , without limitation : bis - gma ( bisphenol glycidyl methacrylate ) based resins ; tegdma ( triethylene glycol dimethacrylate ) based resins ; hema ( 2 - hydroxyethyl methacrylate ) based resins ; pmdm ( pryomellitic acid diethylmethacrylate ) based resins ; pmgdm ( pyromellitic acid glycerol dimethacrylate ) based resins ; udma ( urethane dimethacrylate ) based resins ; methacrylate based resins ; dimethacrylate based resins ; hydrophobic resins ; hydrophilic resins ; and hardenable monomers suitable for dental and orthopedic applications . generally , oil - based resins are not soluble in water or have limited solubility in water such that less than about 2 . 0 % by weight of the resin dissolves when placed in water . there are many types of oil - based resins that are suitable for the present disclosure . specific examples of acrylic resins include , but are not limited to : a person of ordinary skill in the art will also recognize that various methods may be used to cure resins in the present disclosure . desirably , the curing occurs in situ in the presence of one or more metal containing materials in order to form polymeric materials with metallic nanoparticles . in some embodiments , curing occurs by treating a resin with a chemical ( i . e ., chemical curing ). in more specific embodiments , the resin is treated with one or more initiators , desirably in the presence of one or more metal containing materials . non - limiting examples of suitable initiator systems include benzoyl peroxide ( bpo ) and dimethylparatoluidine ( dmpt ), and allyl thiourea ( t ) and cumene hydroperoxide ( ch ). initiators may be used at various concentrations and ratios for chemical curing . for instance , in some specific embodiments , chemical curing may consist of treating resins with allyl thiourea ( t ) and cumene hydroperoxide ( ch ). in other embodiments , chemical curing may consist of treating resins with benzoyl peroxide ( bpo ) and dimethylparatoluidine ( dmpt ). in other embodiments , curing can occur by treating resins with a light source , such as ultraviolet and blue light ( i . e ., light curing ). in other embodiments , curing may entail both light curing and chemical curing . other methods of curing resins can also be envisioned by a person of ordinary skill in the art . fig1 shows the effect of adding silver and bismuth oxychloride ( boc ) on the color of resins . as the silver concentration increases so does color , but as boc concentration increases the color decreases . this is clearly seen when the silver benzoate concentration is at 0 . 01 % and at 0 . 05 %. increasing the concentration of boc decreases the color of the resin . fig2 shows the effect of adding a phosphate - containing monomer ( p ) on the color of resins . as the phosphate - containing monomer concentration increases , the color of the resin decreases . increasing the concentration of phosphate - containing monomer from 5 % to 10 % causes a perceptible decrease in color of the resin . fig3 shows a four ( 4 ) month release profile of silver from a silver - containing resin composition prepared in accordance with the claimed methods . a person of ordinary skill in the art will recognize that the methods of the present disclosure can be used in various embodiments to form numerous anti - microbial resin compositions . for instance , in some embodiments , the methods of the present disclosure can be used to generate polymeric materials with silver nanoparticles ( agnp ) by curing pmma in the presence of a silver - binding compound and silver benzoate ( agbz ). an embodiment of the invention is directed to a method of making an antimicrobial resin composition containing silver nanoparticles , by selecting a silver - containing material , an acrylic resin monomer and a solvent that is miscible with the metal - containing material and with the acrylic resin monomer ; combining the acrylic resin monomer with a silver binding compound ; combining the silver - containing material with the solvent to form a silver - containing material solution ; mixing the silver - containing material solution with the mixture of the acrylic resin monomer and the silver binding compound in situ to form an acrylic resin monomer solution ; forming silver nanoparticles within the acrylic resin monomer solution by curing the acrylic resin monomer solution , wherein the curing process converts the acrylic resin monomer to a polymer ; and forming an antimicrobial , resin composition . in certain embodiments of the invention , the synthesized resin may be a dual cure resin or a self - cure resin that may be prepared using various combinations of resin monomers and suitable initiators . in various embodiments , herein disclosed are self - cure and dual - cure resins with silver nanoparticles that exhibit one or more of reduced color , reduced color shift , and / or reduced degree of self polymerization . in certain embodiments , compositions of the present invention comprise a camphorquinone ( cq ) and 2 - dimenthylaminoethyl methacarylate ( dmaema ). in other embodiments of the invention , other photo initiators and co - initiators such as iodomium initiators may also be used . in order to achieve a final resin composition that has a desirable color and exhibits a gradual release of silver , the resin monomer is mixed with a compound that is capable of binding silver ions present in the silver containing material . in an embodiment of the invention , the silver binding compound comprises an anionic group . in another embodiment of the claimed invention , the silver binding compound is bismuthoxychloride and / or a phosphate - containing acrylic resin . following the mixing of the silver - binding compound with the resin monomer , the silver containing material is added to the resin mixture in order to generate silver particles in situ . in addition to preventing the typical blackening or darkening color observed in silver containing resins , the addition of the silver binding compound to the resin monomer prior to the addition of the silver containing material , reduces the rate at which the silver is released from the resin . both of these observations , i . e ., the reduced darkening of the silver containing resin and the reduced rate of release of silver from the polymeric resin , are likely due to the fact that the chloride ions from the bismuthoxychloride and / or the phosphate ions from the phosphate - containing monomers bind the silver ions in the silver containing material ( prior to polymer formation ) and to the silver generated during the curing of the monomer . from the foregoing detailed description of specific embodiments of the invention , it should be apparent that novel antimicrobial polymeric materials and novel methods of making such materials have been disclosed . although the invention has been described with reference to specific embodiments , these descriptions are not meant to be construed in a limiting sense . various modifications of the disclosed embodiments , as well as alternative embodiments of the invention will become apparent to persons skilled in the art upon reference to the description of the invention . it should be appreciated by those skilled in the art that the conception and the specific embodiment disclosed may be readily utilized as a basis for modifying or designing other structures for carrying out the same purposes of the present invention . it should also be realized by those skilled in the art that such equivalent constructions do not depart from the spirit and scope of the invention as set forth in the appended claims . it is therefore contemplated that the claims will cover any such modifications or embodiments that fall within the true scope of the invention . | methods of forming antimicrobial resin compositions comprising silver nanoparticles are disclosed . such methods generally comprise : combining a silver - containing material with a resin in situ in the presence of a silver - binding compound ; and curing the resin . antimicrobial polymeric resin compositions formed by said methods have a lighter color than control compositions and also display a slower release of silver ions over time . |
2α - methyl - 19 - nor - 20 ( s )— 1α , 25 - dihydroxyvitamin d 3 ( referred to herein as 2amd ) was synthesized and tested . structurally , this 19 - nor analog is characterized by the general formula i previously illustrated herein . the preparation of 2α - methyl - 19 - nor - 20 ( s )- 1α , 25 - dihydroxyvitamin d 3 having the basic structure i can be accomplished by a common general method , i . e . the condensation of a bicyclic windaus - grundmann type ketone ii with the allylic phosphine oxide iii to the corresponding 2 - methylene - 19 - nor - vitamin d analog iv followed by selective reduction of the exomethylene group at c - 2 and deprotection at c - 1 and c - 3 in the latter compound : in the structures ii , iii , and iv groups y 1 and y 2 are hydroxy - protecting groups , it being also understood that any functionalities that might be sensitive , or that interfere with the condensation reaction , be suitably protected as is well - known in the art . the process shown above represents an application of the convergent synthesis concept , which has been applied effectively for the preparation of vitamin d compounds [ e . g . lythgoe et al ., j . chem . soc . perkin trans . i , 590 ( 1978 ); lythgoe , chem . soc . rev . 9 , 449 ( 1983 ); toh et al ., j . org . chem . 48 , 1414 ( 1983 ); baggiolini et al ., j . org . chem . 51 , 3098 ( 1986 ); sardina et al ., j . org . chem . 51 , 1264 ( 1986 ); j . org . chem . 51 , 1269 ( 1986 ); deluca et al ., u . s . pat . no . 5 , 086 , 191 ; deluca et al ., u . s . pat . no . 5 , 536 , 713 ]. hydrindanones of the general structure ii are known , or can be prepared by known methods . for the preparation of the required phosphine oxides of general structure iii , a new synthetic route has been developed starting from a methyl quinicate derivative which is easily obtained from commercial ( 1r , 3r , 4s , 5r )-(-)- quinic acid as described by perlman et al ., tetrahedron lett . 32 , 7663 ( 1991 ) and deluca et al ., u . s . pat . no . 5 , 086 , 191 . the overall process of the synthesis of compound i is illustrated and described more completely in u . s . pat . no . 5 , 945 , 410 issued aug . 31 , 1999 and entitled “ 2 - alkyl - 19 - nor - vitamin d compounds ” the specification of which is specifically incorporated herein by reference . the introduction of a methyl group in the 2α - position of the 20 ( s ) isomer of 19 - nor - 1 , 25 -( oh ) 2 d 3 had little or no effect on binding to the porcine intestinal vitamin d receptor . this compound bound equally well to the porcine receptor as compared to the standard 1 , 25 -( oh ) 2 d 3 ( fig1 ). it might be expected from these results that this compound would have equivalent biological activity . surprisingly , however , the 2α - methyl and 20 ( s ) substitutions produced a highly selective analog with its primary action on bone . fig2 shows that 2amd is extraordinarily effective in building bone mass in ovariectomized rats as compared to the native hormone without increasing serum calcium concentration . this is as yet an unprecedented new finding for a vitamin d compound . fig3 illustrates that 2amd is 50 - 100 times more potent than 1 , 25 ( oh ) 2 d 3 on hl - 60 differentiation , making it an excellent candidate for the treatment of psoriasis and cancer , especially against leukemia , colon cancer , breast cancer and prostate cancer . table 1 illustrates that 2amd is very effective in restoring bone of ovariectomized , old female rats at 32 pmol given 2 times per week as compared to 1 , 25 ( oh ) 2 d 3 given at high doses 3 times per week . note : 2amd also increases % ash in the femur . table 2 shows that 2amd increases breaking strength in the femurs ( cortical strength ) and crushing strength in the vertebra ( trabecular strength ) of animals shown in table 1 . competitive binding of the analogs to the porcine intestinal receptor was carried out by the method described by dame et al ( biochemistry 25 , 4523 - 4534 , 1986 ). the differentiation of hl - 60 promyelocytic into monocytes was determined as described by ostrem et al ( j . biol . chem . 262 , 14164 - 14171 , 1987 ). 2amd is about as active as 1 , 25 ( oh ) 2 d 3 in binding to the vitamin d receptor ( fig1 ). however , it is between 10 - 100 times more active than 1 , 25 -( oh ) 2 d 3 in causing differentiation of the promyelocyte , hl - 60 , into the monocyte ( fig3 ). this result suggests that 2amd will be very effective in psoriasis because it has direct cellular activity in causing differentiation and in suppressing growth . it also indicates that it will have significant activity as an anti - cancer agent , especially against leukemia , colon cancer , breast cancer and prostate cancer , or as an agent in the treatment of psoriasis . the most important result , however , is that 2amd is extremely effective not only in restoring bone mass of ovariectomized , old female breeder rats as shown in fig2 and tables 1 and 2 , but it causes an increase in bone mass above that of sham - operated controls . this illustrates that 2amd is very likely having an anabolic effect on bone or increasing bone formation . importantly , the increased bone mass provided by 2amd translates into marked increases in bone strength . this increased strength to fracture in femur shows cortical strength while increased strength to crush fractures of vertebra illustrates trabecular bone strength ( table 2 ). interestingly , even the percent ash is unexpectedly increased further by 2amd . of great importance is that at the dosage levels used in this study , there was no change in serum calcium of animals that showed the marked elevation of bone mass . this argues that a window of safety exists between the use of 2amd to increase bone mineral content and the action of 2amd in elevating serum calcium . when given for 7 days in a chronic mode , the most potent individual compound tested was 2α - methyl 19 - nor - 20s1 , 25 -( oh ) 2 d 3 ( table 3 ). when given at 130 pmol / day , the activity of this compound on bone calcium mobilization ( serum calcium ) was much higher than that of the native hormone , possible as high as 10 or 100 times higher . under identical conditions , twice the dose of 1 , 25 -( oh ) 2 d 3 gave a serum calcium value of 6 . 6 ± 0 . 4 mg / 100 ml , while 2α - methyl - 19 - nor - 20s - 1 , 25 -( oh ) 2 d 3 gave a value of 8 . 3 ± 0 . 7 mg / 100 ml of serum calcium at the 1 . 30 pmol dose . when given at 260 pmol / day , 2α - methyl - 19 - nor - 20s - 1 , 25 -( oh ) 2 d 3 produced the astounding value of 10 . 3 ± 0 . 11 mg / 100 ml of serum calcium at the expense of bone . to show its selectivity , this compound also produced a significant change in intestinal calcium transport at both the 260 pmol and the 130 pmol dose levels while having a strong bone calcium mobilizing activity . at the higher dose , the 2α - methyl - 20 ( s ) compound did produce a significant intestinal transport response but also gave an enormous bone mobilization response . with respect to the 2β - methyl - 19 - nor - 20 ( s ) compound , the data in table 3 show it has little , if any , intestinal calcium transport activity , and little , if any , bone mobilization activity . thus , the 2α - methyl - 19 - nor - 20 ( s )- derivative showed strong preferential bone calcium mobilizing activity . these results illustrate that the 20 ( s )- 2α - methyl derivative of 19 - nor - 1 , 25 -( oh ) 2 d 3 is selective for mobilization of calcium from bone . these results illustrate that 2amd is an excellent candidate for an anti - osteoporosis therapy and that it may be useful in a number of other circumstances such as autoimmune diseases , cancer , and psoriasis . with respect to the data in table 3 , male weanling rats were obtained from sprague dawley co . ( indianapolis , ind .) and fed a 0 . 47 % calcium , 0 . 3 % phosphorus vitamin d - deficient diet for 1 week and then given the same diet containing 0 . 02 % calcium 0 . 3 % phosphorus for 2 weeks . during the last week they were given the indicated dose of compound by intraperitoneal injection in 0 . 1 ml 95 % propylene glycol and 5 % ethanol each day for 7 days . the control animals received only the 0 . 1 ml of 95 % propylene glycol , 5 % ethanol . twenty - four hours after the last dose , the rats were sacrificed and intestinal calcium transport was determined everted sac technique as previously described and serum calcium determined by atomic absorption spectrometry on a model 3110 perkin elmer instrument ( norwalk , conn .). there were 5 rats per group and the values represent mean ± sem . for treatment purposes , the compound of this invention defined by formula i may be formulated for pharmaceutical applications as a solution in innocuous solvents , or as an emulsion , suspension or dispersion in suitable solvents or carriers , or as pills , tablets or capsules , together with solid carriers , according to conventional methods known in the art . any such formulations may also contain other pharmaceutically - acceptable and non - toxic excipients such as stabilizers , anti - oxidants , binders , coloring agents or emulsifying or taste - modifying agents . the compound may be administered orally , topically , parenterally or transdermally . the compound is advantageously administered by injection or by intravenous infusion or suitable sterile solutions , or in the form of liquid or solid doses via the alimentary canal , or in the form of creams , ointments , patches , or similar vehicles suitable for transdermal applications . doses of from 0 . 1 μg to 10 μg per day of the compounds are appropriate for treatment purposes , such doses being adjusted according to the disease to be treated , its severity and the response of the subject as is well understood in the art . since the compound exhibits specificity of action , each may be suitably administered alone , or together with graded doses of another active vitamin d compound — e . g . 1α - hydroxyvitamin d 2 or t ) 3 , or 1α , 25 - dihydroxyvitamin d 3 — in situations where different degrees of bone mineral mobilization and calcium transport stimulation is found to be advantageous . compositions for use in the above - mentioned treatment of psoriasis and other malignancies comprise an effective amount of the 2α - methyl - 20 ( s )- 19 - nor - vitamin d compound as defined by the above formula i as the active ingredient , and a suitable carrier . an effective amount of such compound for use in accordance with this invention is from about 0 . 01 μg to about 50 μg per gm of composition , and may be administered topically , transdermally , orally or parenterally in dosages of from about 0 . 1 μg / day to about 10 μg / day . the compound may be formulated as creams , lotions , ointments , topical patches , pills , capsules or tablets , or in liquid form as solutions , emulsions , dispersions , or suspensions in pharmaceutically innocuous and acceptable solvent or oils , and such preparations may contain in addition other pharmaceutically innocuous or beneficial components , such as stabilizers , antioxidants , emulsifiers , coloring agents , binders or taste - modifying agents . the compound is advantageously administered in amounts sufficient to effect the differentiation of promyeloytes to normal macrophages . dosages as described above are suitable , it being understood that the amounts given are to be adjusted in accordance with the severity of the disease , and the condition and response of the subject as is well understood in the art . the formulations of the present invention comprise an active ingredient in association with a pharmaceutically acceptable carrier therefore and optionally other therapeutic ingredients . the carrier must be “ acceptable ” in the sense of being compatible with the other ingredients of the formulation &# 39 ; s and not deleterious to the recipient thereof . formulations of the present invention suitable for oral administration may be in the form of discrete units as capsules , sachets , tablets or lozenges , each containing a predetermined amount of the active ingredient ; in the form of a powder or granules ; in the form of a solution or a suspension in an aqueous liquid or non - aqueous liquid ; or in the form of an oil - in - water emulsion or a water - in - oil emulsion . formulations for rectal administration may be in the form of a suppository incorporating the active ingredient and carrier such as cocoa butter , or in the form of an enema . formulations suitable for parenteral administration conveniently comprise a sterile oily or aqueous preparation of the active ingredient which is preferably isotonic with the blood of the recipient . formulations suitable for topical administration include liquid or semi - liquid preparations such as liniments , lotions , applicants , oil - in - water or water - in - oil emulsions such as creams , ointments or pastes ; or solutions or suspensions such as drops ; or as sprays . for asthma treatment , inhalation of powder , self - propelling or spray formulations , dispensed with a spray can , a nebulizer or an atomizer can be used . the formulations , when dispensed , preferably have a particle size in the range of 10 to 100 μ . the formulations may conveniently be presented in dosage unit form and may be prepared by any of the methods well known in the art of pharmacy . by the term “ dosage unit ” is meant a unitary , i . e . a single dose which is capable of being administered to a patient as a physically and chemically stable unit dose comprising either the active ingredient as such or a mixture of it with solid or liquid pharmaceutical diluents or carriers . | this invention provides pharmaceutical uses for 2α - methyl - 19 - nor - 20 - 1α , 25 - dihydroxyvitamin d 3 . this compound is characterized by high bone calcium mobilization activity demonstrating preferential activity on bone . this results in a novel therapeutic agent for the treatment of diseases where bone formation is desired , particularly osteoporosis . this compound also exhibits pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti - cancer agent and for the treatment of skin diseases such as psoriasis . this compound also increases both breaking strength and crushing strength of bones evidencing use in conjunction with bone replacement surgery such as hip and knee replacements . |
referring to fig1 - 4 an angioplasty and stent delivery catheter system generally indicated at 10 includes a balloon catheter 12 having a balloon 14 on a distal end portion generally indicated at 16 . fig1 shows a proximal portion of the catheter at 12 a and a distal portion 12 b in enlarged view . fig2 and 3 show the distal end portion 16 in an even more enlarged view . the illustrative catheter 12 is of the type known as a rapid exchange or single operator catheter . however , other types of catheters may be used , such as over the wire and fixed wire types . the balloon 14 is fixed to the catheter 12 by standard means . the balloon is shown in its contracted state in fig1 - 3 . in fig1 and 2 the catheter is shown prepared for performing angioplasty and in fig3 it is prepared for stent implantation . in fig1 and 2 , an axially movable mounting body 30 is shown in a position proximal to the end portion 16 of the catheter where a stent may be mounted . the catheter includes at its proximal end a manifold , generally designated 13 , as is known in the art . the manifold includes an inflation port 15 as is known in the art . a wire 31 is attached to body 30 to enable remote ( from the proximal catheter end ) advancement and retraction of it axially on inner lumen 26 over which it slides . in the retracted position shown in fig1 and 2 , the catheter has a low profile for performing angioplasty . this position is a retracted position and is selected by operation of a pull wire 31 . the retracted position of the mounting body may vary . to maximize the low profile of the distal end 16 of the catheter , the retracted position may be within the outer member 24 . after such a procedure , the balloon is deflated , the catheter is withdrawn and the mounting body is advanced by means of wire 31 to the stent mounting position shown in fig3 . a stent 18 may then be fixed about the deflated balloon by crimping it thereto . as can be seen in fig3 , the enlarged mounting body may be , as in this instance , substantially the same length as the stent . the stent has a larger expanded diameter which is obtained when the balloon is again expanded in the known manner . that is , the stent is released from the catheter upon expansion of the balloon as shown in fig4 to be placed in a vessel at the desired location . when the balloon is then again deflated , removal of the balloon and catheter may be accomplished , leaving the stent in place . exemplary dimensions for the inner 26 are a diameter of ½ mm and for body 30 a diameter of ¾ mm . as is known in the art the balloon is either bonded at its ends by adhesive 20 and 22 , respectively to the outer member 24 of the catheter and to the inner member 26 of the catheter in the manner as shown , or is made one - piece with the outer member as is known in the art . the catheter balloon may be inflated by fluid ( gas or liquid ) from an inflation port extending from a lumen 28 ( seen in fig2 and 3 ) contained in the catheter shaft and opening into the balloon as shown , or by other known arrangements , depending on the design of the catheter . the details and mechanics of balloon inflation and specific overall catheter construction will vary according to the particular design involved in any given instance , and are known in the art per se . such details are only shown schematically herein . all variations are acceptable for use with this invention . any balloon expandable stent may be used with this invention . many are known in the art including plastic and metal stents . some are more well known such as the stainless steel stent shown in u . s . pat . no . 4 , 735 , 665 ; the wire stent shown in u . s . pat . no . 4 , 950 , 227 ; another metal stent shown in european patent application ep0 707 837 a1 and that shown in u . s . pat . no . 5 , 445 , 646 , or u . s . pat . no . 5 , 242 , 451 . all of these patents are incorporated herein by reference . also , shape memory metal stents may be used . as already indicated the stent of pct application 960 3092 a1 is particularly preferred . the stent is typically for example about 16 mm long , while the balloon may be 20 mm long for example . these dimensions , however , are merely representative for illustrative purposes only and are not meant to be limiting . the stent is positioned over the balloon portion of the dilatation catheter and gently crimped onto the balloon either by hand or with a tool such as a pliers or the like to be mounted for delivery as shown in fig3 . the crimping may be readily accomplished by the physician during the procedure . in accordance with this invention , mounting body 30 , best seen in fig2 and 3 , is included inside balloon 14 to provide a cushion and / or substrate of enlarged diameter relative to the stent to support and hold the stent and secure it during crimping and the delivery procedure . the mounting body may be axially movable proximally or distally from the position shown in fig3 , proximally being preferred . in the embodiment shown in fig1 - 3 , mounting body 30 is cylindrical in form and takes the shape of a sleeve axially and slidably carried on inner lumen 26 , providing an enlarged area or portion for receiving the balloon and stent when the latter is crimped to the balloon . marker band 34 may also be included on inner 26 as shown . any radiopaque material such as gold is useful for this purpose . a stop member 36 of generally conical shape or any other shape may also be included on the marker band 34 as shown to provide additional resistance to stent movement during delivery and to protect the leading edge of the stent during delivery . polyethylene or the like is suitable for the stop member . other marker arrangements and stop arrangements may be used as well . although , the material of the mounting body may be hard , it is preferably of any deformable thermoplastic material , preferably an elastomer material and more preferably of a relatively resilient elastomer material , e . g ., lower durometer silicone . a preferred deformable thermoplastic material is high density polyethylene ( hdpe ). a preferred lower durometer silicone is in the form of tubing . the deformation of the resilient material of the mounting body when the stent / balloon is crimped to it causes a radial outward force on the stent / balloon increasing the friction therebetween despite any recoil of the stent . during stent delivery , the balloon catheter is advanced through and positioned in a patient &# 39 ; s vasculature so that the stent is adjacent to the portion of the vessel where treatment is to take place . the balloon is inflated to expand the stent to an enlarged diameter . when the stent has reached the desired diameter , the balloon is deflated so that the catheter may be removed leaving the stent in place . another embodiment of the invention is shown in fig5 . in this embodiment mounting body 30 is a spiral cut elastomer or other suitable material , such as a rigid or flexible plastic , to provide separation for flexibility in that portion of the catheter , allowing more easy movement or tracking around bends . the spiral cut may be only partly through the mounting body or may be all the way through as shown in fig5 . also , while stop member 36 is shown at the distal end portion of the catheter in this embodiment , no stop member may be used . another similar version is shown in fig6 which includes a cylindrical mounting body 30 made up of a plurality of separate adjacent rings 30 a held together by wire 31 which extends therethrough as shown with stops 29 to secure the rings together . rings 30 a may be individual bodies carried on the sheath or bodies cut from a cylinder to partially separate them or fully separate them . suitable arrangements may be made to wire 31 at each end of the body 30 to hold the rings together , as shown . at least one separation may be present between the rings . the at least one separation may be exposed to a portion of the medical balloon which located along a radial line which extends from the center axis and through the separation . thus , nothing extends between the separation and the portion of the medical balloon to which it is exposed , the portion being located along a radial line which extends from the center axis and through the separation . the embodiment shown in fig7 includes another feature based on the geometry of the mounting body for further securing the stent upon crimping . this feature is referred to herein as “ interlocking ”. that is , the stent may be interlocked to the mount so that the stent cannot slide proximally or distally on the balloon unless it is deformed , such as by expansion . this can be seen by perusing the structure shown in fig7 which includes the inner 26 having a two - piece mounting body made up of spaced mounting bodies 30 a and 30 b . these bodies are connected to each other by connection means 33 which may be a separate or integral cylindrical body of lesser diameter or may be one or two or more relatively rigid wire members as shown . the spacing between bodies 30 a and 30 b allows portions of the stent 18 and balloon 14 to be depressed or inserted between the bodies upon crimping of the stent thus forming an interlock against sliding of the stent axially or longitudinally before the stent is released . the interlock formation or crimping is readily accomplished by any suitable means such as a two - piece die 40 shown in fig8 or the like . fig9 demonstrates that more than a two - piece mounting body arrangement may be used if desired . in this embodiment , the mounting body is comprised of three spaced interconnected bodies 30 a , 30 b and 30 c on the inner 26 . preferably in the embodiments of fig7 and 9 , the mounting bodies will be ring - like in shape or cylindrical in shape although other configurations will be readily apparent to those familiar with this art . referring now to fig1 , another embodiment of a movable mounting body 30 is shown in the form of a rigid coil of plastic , metal or the like having a control wire 31 , preferably integral therewith . when in the metal form , the coil may be coated with a polymer such as polyethylene or ptfe or enclosed in a polymeric sheath of similar material . the coil may be slidably received on the inner 26 similar in arrangement to that shown in the preceding figures . as already indicated , an alternate arrangement may be used in which the mounting body , instead of being movable , is designed to be enlargeable and reducible or collapsible , while remaining in a fixed position in the stent mounting area of the catheter . fig1 and 12 are directed to such an arrangement . in fig1 , an inner balloon 50 of smaller diameter than outer balloon 14 is mounted on the inner 26 . balloon 50 may have a separate inflation conduit 52 inside inner 26 , preferably including a valving arrangement 54 . valve 54 may be a one - way valve allowing only inflation of balloon 50 if desired . however , inner 26 may serve as the inflation conduit as well . in addition to fully inflate the balloon , inner balloon 50 may also be partially inflated . fig1 shows a modification to fig1 in which two inner balloons 50 a and 50 b are included . fig2 shows a modification in which two inflation valves 54 a and 54 b are included . fig2 shows a full arrangement of inner balloon 50 in which a syringe 120 is inserted into the distal end of the liner 26 of the catheter . the syringe has at its ends blocks 122 and 124 to enable local pressurization of inner 26 to inflate balloon 50 . fig1 and 18 show an inner balloon 50 similar to the arrangement of fig1 but the balloon 50 in fig1 has a narrow center portion and wide ends to provide a mounting shape similar to that of fig7 . in fig1 , balloon 50 is inflated and balloon 14 is partially inflated . in fig1 , balloon 50 is inflated and balloon 14 is uninflated ready for stent loading . balloon material is preferably a polyethylene or urethane elastomer such as tecoflex or tecothane from thermedics . referring to fig1 , an alternate embodiment is shown in which the proximal portion of the inner 26 is axially movable while the distal portion 26 b is fixed with respect to the catheter . in between portion 26 a and portion 26 b is a coil spring 60 inside a flexible sheath 62 of ptfe or the like . portion 26 b of the inner is attached to balloon 14 at the very distal end portion of the catheter . portion 26 a is movable axially within the outer 22 . thus , if 26 a is pushed in the distal direction and held to compress coil 60 , the coil will enlarge in diameter to provide an enlarged mounting area for a stent . twisting the inner to twist the coil will enhance enlargement . alternatively , coil spring 60 may be replaced by a braided element . also , by providing different pitch over the length of the coil it can be made to enlarge more in some regions than in others . for example , if the coil windings are closer together in the center portions than in the end portions , when the coil undergoes compressing , the two end portions will enlarge in diameter more than the center portion to provide a mount similar to that of fig7 . referring now to fig1 and 14 , another embodiment is shown which is alternative to the earlier described embodiments which are inside the balloon on the catheter . in this embodiment a sheath 80 is carried on the outside of the catheter . sheath 80 is elastomeric and is axially movable from a stent mounting position as shown in fig1 to a position remote from the stent mounting position , such as the retracted position as shown in fig1 . in the position shown in fig1 , balloon 14 may be inflated and deflated . in the position shown in fig1 , balloon 14 will be deflated for low profile . sheath 80 when over the balloon as in fig1 acts to increase the profile of the catheter to facilitate crimping a stent thereto during deployment of the stent , sheath 80 will expand with balloon 14 to facilitate inflation and during deflation the elastomer sheath will return to its original dimension . an elastomer material which is presently preferred is tecothane , a tradename for a thermoplastic polyurethane available from thermedics , inc ., of woburn , mass . it may be about 0 . 003 inches thick , for example . with respect to fig1 and 16 , a further embodiment of the invention is shown in which inner 26 carries a mounting body 30 , the distal end 100 of which is secured or fixably attached to inner 26 , as by any suitable adhesive . the remainder of body 30 is slidable over inner 26 as by the application of compression in the distal direction at the proximal end 102 . this may be accomplished by push wire 104 which extends to the proximal end of the catheter for remote manipulation as is known in the art . mounting body 30 is accordion folded with more widely spaced folds at the end portions 106 , than at the central portion 108 . thus , as can be seen in fig1 , a relatively low profile is provided without compression for normal angioplasty use . when a stent is to be mounted ( not shown ), compression by means of push wire 104 will result in a configuration of enlarged diameter of body 30 as shown in fig1 to provide a mount similar to that of fig7 in general configuration . if the spring is uniform over the body , it sill enlarge uniformly , similar to the inner balloon of fig1 . the figures are schematic in form but the concept can be readily appreciated . as an alternative to a folded construction , the body may be of braided construction to achieve the same operation . also , this form of body 30 may be inserted into a two piece inner 26 similar to the arrangement shown in fig1 . in all of these arrangements , the accordion folded body material may be of any suitable polymer , such as polyethylene . for example , tubing having a wall thickness of about 0 . 002 inches may be used . the accordion folds or pleats may be readily formed in such tubing by means of a pressure mold containing spaced blades placed in a heated chamber . the above examples and disclosure are intended to be illustrative and not exhaustive . these examples and description will suggest many variations and alternatives to one of ordinary skill in this art . all these alternatives and variations are intended to be included within the scope of the attached claims . those familiar with the art may recognize other equivalents to the specific embodiments described herein which equivalents are also intended to be encompassed by the claims attached hereto . | an angioplasty and stent delivery system to facilitate introduction and placement of a stent , including a catheter having an expandable distal portion constructed and arranged for expanding the outer diameter of the catheter from a contracted state to an expanded state : a stent positioned around the distal portion of the catheter having a contracted condition and being expandable to an expanded condition , and being sized in the contracted condition to closely surround the catheter in the contracted state , the expandable distal portion of the catheter including a balloon within which or over which there is included on a catheter shaft at least one axially movable or enlargeable body of a diameter larger than the catheter shaft to which the stent and balloon are fitted , as by crimping , for holding the stent in place until it is released therefrom by expansion of the balloon . |
the mechanical components comprising preferred embodiments of an exemplary dispenser 10 will first be described . referring first to fig1 - 3 , dispenser 10 preferably includes housing 11 and removable front cover 13 . in the embodiment , dispenser 10 is configured for mounting on a vertical wall surface ( not shown ) permitting a user to easily access dispenser 10 . housing and cover 11 , 13 may be made of any suitable material or materials such as formed sheet metal , plastic and the like . frame 15 is mounted within housing 11 as shown in fig2 - 3 . frame 15 may be a unitary part made of plastic or other suitable material and secured with respect to housing 11 in any suitable manner . frame 15 supports drive roller 17 , springs 19 , 21 and diverter 23 . drive roller 17 may also be referred to by some in the industry as a “ drum .” preferably , dispenser 10 is adapted to dispense sheet material in the form of a sheet material roll ( not shown ). as is well known , sheet material in roll form comprises a hollow cylindrically - shaped tubular core ( not shown ) and sheet material in the form of a web 25 of sheet material ( fig1 - 15 ) wrapped around the core . the core is typically a hollow tube made of cardboard , plastic or the like . the dispenser shown can accommodate a stub roll ( not shown ) and a reserve roll ( not shown ) of the sheet material . the stub roll may be supported within frame 15 on stub roll holders 27 , 29 mounted on frame 15 . each end of the tubular core of the stub roll is mounted on a respective roll holder 27 , 29 with the respective roll holder inserted into the hollow core . holders 27 , 29 are preferably made of a resilient material so that they may be spread apart to receive the stub roll between them . the stub roll is free to rotate when mounted on holders 27 , 29 . the reserve roll is supported by support arms 31 , 33 and web roll support cups 35 , 37 mounted on respective arms 31 , 33 . each end of the tubular core of the reserve roll is mounted on a respective cup 35 , 37 with the respective cup inserted into the hollow core . arms 31 , 33 are preferably made of a resilient material so that they may be spread apart to receive the reserve roll core between them . as will be appreciated , any type of support structure may be utilized to support the stub and reserve rolls . for example , the stub roll may simply rest on bottom wall 39 of frame 15 without holders 27 , 29 . by way of further example , holders 27 , 29 and support arms and cups 31 , 33 , 35 , 37 could be replaced with a rod inserted through the hollow roll core . such a rod may be supported at its ends by housing 11 . there is no particular requirement with respect to the number of sheet material sources which may be dispensed from dispenser 10 . dispenser 10 could dispense , for example , from single or plural rolls of material depending on the intended use of dispenser 10 . a drive mechanism 41 is provided for discharging web 25 from dispenser 10 . drive mechanism 41 comprises drive roller 17 , tension roller 43 , tension springs 19 , 21 , diverter 23 and the related components as hereinafter described and as shown particularly in fig2 - 15 . preferred drive roller 17 may be a drum - shaped member which is generally - cylindrical in appearance . drive roller 17 may comprise first and second sections 45 , 47 , first and second ends 49 , 51 and outer surface 53 . sections 45 , 47 may be made of plastic or any other suitable material and may be joined by use of adhesives or fasteners 55 ( fig6 ). drive roller 17 is preferably mounted on frame 15 along axis 56 . drive roller 17 is preferably mounted for bidirectional rotatable movement by stub shafts 57 , 59 which extend axially outward from a respective drive roller end 49 , 51 . stub shafts 57 , 59 are received in a respective bearing 61 , 63 . bearing 61 is seated in opening 65 of cam 67 and bearing 63 is seated in opening 68 of frame 15 . bearings 61 , 63 are preferably made of nylon or a similar low - friction material . referring to fig3 - 4 , 6 , and 10 - 15 , eccentric arm 69 is seated on stub shaft 57 and is secured to stub shaft by fastener 71 . arm 69 co - rotates with drive roller 17 . a spring - attachment member 73 is rotatably mounted to end 75 of arm 69 by fastener 77 . member 73 includes arms 79 , 81 for attachment to a respective spring 19 , 21 as described herein . referring to fig1 - 2 and 5 - 6 , a hand wheel 83 linked to drive roller 17 may optionally be provided . hand wheel 83 is provided to permit manual rotation of drive roller 17 , such as to feed web 25 out from dispenser 10 through discharge opening 85 at the time web 25 is loaded into dispenser 10 . hand wheel 83 is linked to drive roller 17 at end 51 by means of a hand wheel post 87 keyed to fit into corresponding female opening ( not shown ) in stub shaft 59 and secured by fastener 89 . as shown in fig2 - 8 , drive roller outer surface 53 preferably includes one or more friction surfaces 91 for engaging and gripping web 25 . friction surfaces 91 are provided to ensure that the drive roller outer surface 53 has sufficient frictional contact with the web 25 so that drive roller 17 will rotate as web 25 positioned across drive roller 17 is pulled from dispenser 10 by a user . the plural friction surfaces 91 ( fig2 - 6 ) may be in the form of sheet - like strips adhered to drive roller outer surface 53 with a suitable adhesive ( not shown ). however , such friction surfaces 91 could be provided in other manners , such as by forming such friction surfaces directly in outer surface 53 . further , the friction surfaces 91 need not be limited to the plural strip - like material shown and could comprise any appropriate configuration , such as a single sheet of material ( not shown ). friction surfaces 91 may consist of any suitable high - friction material , such as grit or rubberized material . an over molded thermoplastic elastomer may also be applied to drive roller 17 out surface 53 . such an elastomer is applied directly to the surface 53 and sets to form a gripping surface similar to friction surfaces 91 . fingers 92 of guard 94 extend into corresponding annular grooves 96 in drive roller 17 to separate web 25 from drive roller 17 so that web 25 does not become adhered to the drive roller 17 ( such as by static electricity ) and to ensure that web 25 is properly directed out of dispenser 10 through discharge opening 85 . guard 94 may be attached across frame 15 by any suitable means well known in the art . drive roller 17 preferably further includes a longitudinal opening 93 through which a cutting blade 95 of a cutting mechanism 97 extends to perforate the web 25 as hereinafter described . tension roller 43 urges web 25 against outer surface 53 of drive roller 17 . tension roller 43 preferably is a generally cylindrically - shaped member having first and second axial stub ends 101 , 103 . roller axial stub ends 101 , 103 fit rotatably in respective slots 109 , 111 provided in frame 15 . as shown in fig3 - 6 , torsion springs 113 , 115 urge tension roller 43 against drive roller 17 . tension roller 43 is generally coextensive with drive roller 17 and is mounted along an axis 117 parallel to axis 56 . tension roller 43 may be provided with annular gripping surfaces 119 seated in a respective annular seat 121 and positioned to abut a respective drive roller friction surface 91 . such gripping surfaces 119 are preferably made of a tactile material such as rubber , or the like . drive roller 17 and tension roller 43 form a nip 123 at the interface of drive roller 17 and tension roller 43 . web material 25 is drawn from a respective stub or reserve roll through nip 123 , against outer surface 53 of drive roller 17 and out of dispenser via discharge opening 85 as described in detail below . drive mechanism 41 further includes springs 19 , 21 and diverter 23 . each spring 19 , 21 is preferably a tension spring . each spring 19 , 21 may be identical to each other , but this is not required . springs 19 , 21 are loaded , or energized , by rotation of drive roller 17 resulting from user web pulling . loaded springs 19 , 21 then power further rotation of drive roller 17 and operation of the cutting mechanism 97 ( as the springs are unloaded ) to complete a dispense cycle . as is well illustrated in fig3 - 5 , 6 , 10 , 10 a - 10 c and 11 - 15 , spring 19 has ends 127 , 129 . end 127 is secured to frame 15 at post 131 and may be secured to post 131 by fastener 133 . the other spring 19 end 129 is attached to arm 79 of spring - attachment member 73 . spring 21 had ends 135 , 137 . spring end 135 is secured to frame 15 at post 139 and may be secured to post 139 by fastener 141 . the second spring 21 end 137 is attached to arm 81 of spring - attachment member 73 . referring further to fig3 - 5 , 6 , 10 , 10 a - 10 c and 11 - 15 , diverter 23 is provided to contact spring 21 and to bend spring 21 when spring 21 is in the rest position of fig1 . preferably , diverter 23 contacts spring 21 between ends 135 , 137 . diverter 23 is secured to frame 15 by adhesive or other suitable fastener 181 ( fig1 b ). referring again to fig1 , 10 a - 10 c and 11 - 15 , diverter 23 may include a guide surface 143 . guide surface 143 preferably includes a groove , or recess , in which spring 21 is fully or partially seated when in the rest position of fig1 . guide surface 143 groove serves as a guide to keep spring 21 in place during the dispense cycle . diverter 23 may be made of materials such as plastics . diverter 23 could be an integral component of frame 15 . in the preferred rest position of fig1 , spring 19 has a generally axial orientation which is retained generally throughout a dispense cycle . spring 21 has a generally axial segment 145 between end 135 and diverter 23 and a generally axial segment 147 between diverter 23 and end 137 . axes 146 , 148 are shown on fig1 b . spring 21 has a segment 149 therebetween which is bent as it contacts diverter 23 . segments 145 , 147 are axial only in the sense that they represent generally straight spring portions about diverter 23 when at rest as in fig1 . put another way , spring 21 is bent by the diverter . the bend preferably includes a radius as shown in fig4 , 10 a , 10 b and 10 - 15 . the position and orientation of segment 147 , in particular , will change as spring 21 bends and is moved during a dispense cycle as is well - illustrated in fig1 - 15 . thus , diverter 23 acts on spring 21 such that segments 145 , 147 are not co - axial when in the rest position of fig1 . it is preferred but not required that springs 19 , 21 are essentially co - planar along plane 146 . by way of further example , spring 21 segment 147 could be arranged such that it lies outside of plane 146 in which springs 19 , 21 are arranged ( fig1 ). diverter 23 advantageously permits use of a spring 21 which may be identical to spring 19 , particularly in length and spring force . and , diverter 23 enables this result in a housing 11 which is more compact than if diverter 23 were not present . more specifically , if diverter 23 were not present , it would be necessary to use a spring which would be relatively shorter than spring 21 with the spring end 135 secured to frame 15 at a location proximate the point where diverter 23 contacts spring 21 in fig1 . such a point is identified by reference number 163 in fig1 . it is desirable , however , that the spring selected for use as spring 21 is a relatively longer spring because the relative extension of such a longer spring is less than that of a relatively shorter spring . as a result , the spring rate of the longer spring is more moderate and consistent throughout the full range of spring movement than that of a relatively shorter spring having a relatively more rapid rebound and more powerful spring force . use of a relatively longer spring 21 , therefore , desirably provides for more consistent and smooth operation of drive roller 17 . a relatively shorter spring may be more likely to fail because of the tensile forces applied to it thereby requiring the use of more costly high tensile springs . use of a relatively longer spring provides the manufacturer with the option to use springs made with less costly materials thereby minimizing cost while extending service life of the dispenser . while a relatively longer spring 21 could be used in dispenser 10 without a diverter 23 , such spring 21 end 135 would be required to be mounted below bottom wall 39 of frame 15 ( at approximately point 164 ) to power rotational displacement of drive roller 17 in the same manner as shown in fig1 - 15 . a larger housing 11 would be required to accommodate this mounting location and such a larger housing 11 may be unacceptable for some applications where space is at a premium or a more compact housing 11 and dispenser 10 appearance is desired . referring to fig2 - 15 , a preferred cutting mechanism 97 for cutting web 25 is illustrated . the cutting mechanism 97 is preferably provided to cut fully through web 25 positioned against drive roller 17 outer surface 53 as drive roller 17 rotates under the force applied by user web pulling and springs 19 , 21 . the exemplary cutting mechanism 97 comprises blade 95 , blade carrier 151 , arm 162 , follower 165 , cam 67 and the related components . as shown in fig6 - 8 , blade 95 may be provided with serrated teeth 150 secured to blade carrier 151 by fasteners 153 . blade carrier 151 is pivotally mounted to respective ends 49 , 51 of drive roller section 45 by means of pin 155 seated in bearing 157 and stub shaft 159 seated in bearing 161 . bearings 157 , 161 are seated in respective drive roller ends 49 , 51 . pivoting action of carrier 151 enables blade 95 to extend outward from drive roller 17 to cut web 25 and further enables blade 95 to retract inward to drive roller 17 following cutting . in the embodiment , serrated teeth 150 cut completely through web 25 so that a single sheet 179 of web 25 is provided during user web pulling . arm 69 is attached at one end to blade carrier 151 and supports rotatable cam follower 165 at its other end . arm 69 and cam follower 165 are positioned for mounting outside of first drive roller section 45 end 49 so that cam follower 165 may be positioned in cam track 167 of stationary cam 67 as is well shown in fig9 and 10 - 15 . fig6 , 9 and 10 - 15 illustrate exemplary cam 67 . cam 67 is preferably mounted to frame 15 with fasteners 168 so that cam track 167 extends through frame opening 170 and faces drive roller 17 and cam follower 165 . cam track 167 provided in cam 67 includes inwardly arcuate portion 169 and outwardly arcuate portion 171 . cam follower 165 follows cam track 167 as the drive roller 17 rotates during a dispense cycle . cam track 167 is eccentric relative to stub shaft 57 and axis 56 and is structured and arranged such that the action of cam track 167 on cam follower 165 and arm 162 , urges carrier 151 to pivot such that blade 95 extends to cut web 25 and retracts during each revolution of drive roller 17 as described more fully below . tail 172 of web 25 of the reserve roll may be manually loaded into nip 123 when the stub roll is fully depleted . alternatively , an automatic transfer mechanism may be incorporated into dispenser 10 to automatically transfer tail 172 of web 25 of reserve roll to the nip 123 when the stub roll is fully depleted or very near full depletion ., such an automatic transfer mechanism is the subject of commonly owned u . s . pat . no . 6 , 460 , 798 , the entire contents of which are incorporated herein by reference . to provide a frame of reference for location of transfer mechanism , a transfer arm 173 as described in u . s . pat . no . 6 , 460 , 798 and which urges web 25 of reserve roll into nip 123 is shown in fig2 - 6 . other transfer mechanism structure is not shown . operation of exemplary dispenser 10 will now be described particularly with respect to fig1 - 15 . it will be understood that fig1 - 15 illustrate representative positions of drive roller 17 and other dispenser 10 components during a dispense cycle . the operational description will center on drive mechanism 41 and cutting mechanism 97 . web 25 may be supplied by a single roll , a stub roll or a reserve roll . the reader is again referred to u . s . pat . no . 6 , 460 , 798 , incorporated herein by reference , for a description of the structure and operation of exemplary transfer mechanisms suitable for use in supplying web 25 to nip 123 upon depletion of the stub roll . fig1 represents dispenser 10 in a rest , or ready , position prior to commencement of a dispense cycle . web 25 is positioned between drive roller 17 and tension roller 43 through nip 123 . ( tension roller 43 is not shown in fig1 - 15 .) to facilitate threading of web 25 into nip 123 during loading of web 25 , drive roller 17 may be manually rotated in the direction of arrow 175 ( i . e . counterclockwise in the example shown ) by means of hand wheel 83 . as drive roller 17 is rotated , friction surfaces 91 engage web 25 which is urged against such friction surfaces by tension roller 43 and , potentially , by the action of user web pulling . web 25 is drawn through nip 123 as drive roller 17 rotates in the direction of arrow 175 and tension roller 43 rotates in the opposite direction . after exiting nip 123 , web 25 is guided toward discharge opening 84 by arcuate guide wall 177 . web 25 is positioned over a portion of drive roller 17 outer surface 53 friction surfaces 91 . pulling of web 25 by a user draws web 25 tightly across the portion of friction surfaces 91 , as shown in fig1 - 15 . guard 94 fingers 92 extend into corresponding annular grooves 96 of drive roller 17 to separate web 25 from drive roller 17 to facilitate movement of web 25 out of dispenser 10 through discharge opening 85 . web tail 172 is then extended from discharge opening 85 by rotation of hand wheel 83 to an appropriate length for gripping by a user . web 25 is now positioned for dispensing from dispenser 10 . in the rest , or ready , position of fig1 , springs 19 , 21 are partially loaded , or energized , and springs 19 , 21 bias drive roller 17 and arm 69 to the position shown in fig1 . at the beginning of a dispense cycle , blade 95 is preferably retracted within drive roller 17 also as shown in fig1 . dispenser 10 is now ready for use . fig1 represents dispenser 10 shortly after commencement of a dispense cycle . the dispense cycle is initiated by user web pulling of web 25 tail 172 . the tension , or pulling , force of web 25 against drive roller 17 outer surface 53 friction surfaces 91 causes drive roller 17 to rotate in the direction of arrow 175 . springs 19 , 21 are partially extended and are loaded ( i . e ., energized ) as drive roller 17 rotates under the influence of web 25 . fig1 represents a further position of dispenser 10 after commencement of a dispense cycle . spring 19 is near fully extended and loaded ( i . e ., energized ) at a centered position . spring 21 is further partially extended and is being loaded ( i . e ., energized ) as drive roller 17 rotates further under the influence of web 25 . blade 95 begins to move toward web 25 to perforate web 25 as cam 67 cam track 167 urges follower 165 and arm 162 to pivot blade carrier 151 . fig1 represents yet a further position of dispenser 10 after commencement of a dispense cycle . spring 19 is past the near centered position of fig1 and powers rotation of drive roller 17 as the spring is unloaded by release of stored energy . spring 21 segment 147 is now in approximately a centered position and spring 21 is fully loaded ( i . e ., energized ) as shown . spring 21 is just starting to power drive roller 17 rotation at this point in the dispense cycle . blade 95 moves further toward web 25 to perforate the web as cam 67 cam track 167 urges follower 165 and arm 162 to pivot blade carrier 151 . spring 19 provides energy required to extend blade 95 . fig1 represents yet another position of dispenser 10 after commencement of a dispense cycle . springs 19 , 21 are both past their centered positions and combine to power rotation of drive roller 17 as the springs are unloaded and stored energy is released . blade 95 moves fully toward web 25 to completely cut web 25 as follower 165 enters inward portion 169 of cam track 167 . springs 19 , 21 provide energy required to fully extend blade 95 to completely cut web 25 . the result is a single sheet 179 of web 25 being provided to the user . fig1 illustrates a further position of dispenser 10 near completion of a dispense cycle . springs 19 , 21 are both past their centered positions and combine to power rotation of drive roller 17 as stored energy is released . blade 95 begins to retract as follower 165 exits inward portion 169 of cam track 167 . spring 21 is the primary provider of energy required to retract blade 95 and return drive roller 17 to the resting position following web 25 cutting . finally , drive roller 17 is returned to the rest , or ready , position of fig1 . tail 172 of web 25 is extended from discharge opening 85 and is ready to be grasped and pulled by a user . the dispenser 10 is now ready to initiate a new dispense cycle . dispenser 10 and its component parts may be made of any suitable material or combination of materials as stated above . selection of the materials will be made based on many factors including , for example , specific purchaser requirements , price , aesthetics , the intended use of the dispenser and the environment in which the dispenser will be used . while the principles of this invention have been described in connection with specific embodiments , it should be understood clearly that these descriptions are made only by way of example and are not intended to limit the scope of the invention . | apparatus and methods for dispensing sheet material from a sheet material dispenser are described . a drive mechanism powered at least in part by one or more springs discharges sheet material from the dispenser . a diverter redirects at least one of the springs enabling use of a relatively longer spring in a more compact and space - efficient dispenser housing . the dispenser may include a cutting mechanism powered at least in part by the one or more springs . |
fig1 shows the natural upper teeth of an adult including the second bicuspids 11 , the first molars 13 , and the second molars 15 . referring now to fig2 and 4 , wherein the same parts are indicated by like numbers , there are shown certain artificial upper teeth constructed according to the present invention . these include : upper left and right second bicuspid 10 and 12 , upper left and right first molar 14 and 16 , and upper left and right second molar 18 and 20 . from these figures it can readily be seen that a bladed insert 22 is always located on the lingual cusp of each tooth . specifically , the bladed insert 22 conforms to the normal shape of the cusp that is replaced . the upper teeth shown in fig2 and 4 are opposed by lower plastic or acrylic teeth of conventional anatomic design . as can be seen in fig5 and 7 each of the bladed inserts 22 includes a head portion 40 including blades 42 and 44 which together form an arched cruciform structure conforming approximately to the envelope of a normal lingual cusp . this structure is quite strong mechanically and able to resist forces from any direction . blades 42 and 44 are not intended to be razor - sharp , but instead have a rounded edge . this design of the cutting blade represents a compromise between the very sharp blade , which creates a risk of damage to the lingual and buccal tissues and which is less strong and , at the other extreme , a very blunt blade which would be considerably less effective for cutting , shearing and shredding food . the bladed insert 22 further includes a post 46 to provide a means of anchoring the insert to an artificial tooth 26 . from fig5 and 7 it can be seen that the shape of the insert 22 varies slightly depending on whether it is intended for use in a bicuspid , first molar , or second molar . in the preferred embodiment , the insert 22 is attached to the tooth in the following manner . the pre - cast bladed insert 22 is placed and held within an empty mold in which the artificial tooth is cast . this insures that the bladed insert 22 necessarily lies within the envelope of the artificial tooth . with the insert thus held in position , the acrylic resin in fluid form is introduced to the tooth mold , and upon curing , the resin adheres to the post 46 thereby securely anchoring the metal insert 22 to the artificial tooth . the artificial tooth thus produced may then be mounted into a denture in the usual manner . although the insert of the preferred embodiment is placed at the mesial lingual cusp of the molars , placement at the distal lingual cusp or at other cusps is also possible in other embodiments . likewise , the use of one , two or three metal teeth is possible , depending on the wishes of the dentist and patient . the inserts can be placed in either upper or lower teeth . in a preferred embodiment , the blade insert 22 is made of a chrome stainless steel . it would , of course , be obvious to use another material , particularly one whose color more nearly matches that of the artificial tooth . other means of attaching the bladed insert to the artificial tooth would be obvious to those skilled in the art . these include the use of a screw instead of post 46 of fig4 or the use of cement or other adhesive to anchor the bladed insert to an artificial tooth . the arched cruciform blade configuration of the tooth of the preferred embodiment has been found to be effective in practice because it is a strong structure . it has adequate sluicing , thereby preventing clogging by food . the effective area actually in contact with the food is small , greatly increasing the effective pressure exerted on the food . this in turn , permits a great improvement in the ability of edentulous patients to cut , shred and tear their food . other blade configurations are conceivable , including a single blade and three intersecting blades . the foregoing detailed description is illustrative of one embodiment of the invention , and it is to be understood that additional embodiments thereof will be obvious to those skilled in the art . the embodiments described herein together with those additional embodiments are considered to be within the scope of the invention . | an anatomical artificial tooth , used for complete or partial dentures , is provided with a metal insert located on a lingual cusp of the tooth , the insert having a blade configuration on its occlusal surface for the efficient cutting , shearing and shredding of food . |
according to the illustrations of fig1 - 3 , the device 1 to fix metal guides and balloon catheters of the present invention , intended for vascular interventions , mainly to treat damage and bifurcation , is formed by a base or a platform 11 and , on its narrow proximal end 15 , has two pins 13 and a jaw 14 to support the y connector 40 as appropriate for bifurcation , wherein the pins 13 are located so to fix the distal portion of the y connector 40 , while the jaw 14 fixes the proximal portion of said y connector 40 . more specifically , pins 13 are converging prismatic structures projecting from the base 11 and having a recess able to couple the distal portion of the y connector 40 . the jaw 14 is a full prismatic element provided on its upper portion with two opposed holding arms , limiting a seat with similar shape to the external cylindrical shape of the proximal portion of the y connector 40 . concerning the valve connector or y connector 40 , this is an element known in the art , intended to direct the guide catheter and , within that and as per the case , the balloon catheter and the balloon catheter with stent over metal guides ( not shown ), for which reason we do not need to make a detailed description of their operation . in any case , the y connector 40 has a basically triangular body with rounded edges . from its proximal portion 48 , a cylindrical structure is projected to guide and support the elements ( balloon catheter , balloon catheter with the stent and metal guides , respectively ) to be inserted in the patient by percutaneous route . on its distal or proximal portion , the y connector 40 has a route 41 to inject contrast agent and determine the intravascular pressure , as well as , in this case , two inlets , of which a first inlet 42 is intended to introduce a metal guide and a balloon catheter ( not shown ) for the main vessel and the second inlet 43 intended to introduce the metal guide and balloon catheter ( not shown ) for the secondary or side vessel . returning to the device 1 of the invention , below each one of the inlets 42 , 43 of the y connector 40 , a respective hole 12 , 12 ′ intended to the flow of blood is located . furthermore , on the distal edge 16 of the base 11 of the device 1 , preferably wider than the proximal edge 15 of the same base 11 , two pairs of fixers 17 , 17 ′ and 18 , 18 ′ are located , wherein the first pair of fixers 17 , 17 ′ is located aligned over the inlet 42 of the y connector 40 to the main vessel , while the second pair of fixers 18 , 18 ′ is located aligned with the inlet 43 of the y connector 40 to the secondary or side vessel . specifically , any one of the fixers 17 , 17 ′, 18 , 18 ′ is a trunk - pyramidal structure made of a rigid material , projecting from the base 11 of the device 1 . on its upper portion , any one of the fixers 17 , 17 ′, 18 , 18 ′ has a graft 5 , made of a liable material and provided with a lengthwise gutter 6 composing a seat intended to receive and retain a metal guide , a balloon catheter or a balloon catheter with stent ( not shown ). particularly and according to the present invention , to receive means to receive with no lacks and keep it in position not allowing side deflections or displacements , involving or not a given compression of the material composing the gutter 6 ; while to retain means to keep in position , not allowing movements back and forth of the element as retained over the respective fixer , due to the friction between the internal face of the gutter 6 and the external face of the element to be retained within said fixer . preferably , the graft 5 has a prismatic shape with crosswise section in half - circle , but , in other embodiments , the crosswise section of the graft 5 may have another appropriate shape . in an alternative form of embodiment of the present invention , as shown by fig7 , the device 2 is intended to receive and facilitate the use of a y connector 40 ′ intended for use in vascular interventions to treat simple damage . therefore , said y connector 40 ′ has only one inlet 42 intended to introduce a metal guide and a balloon catheter ( not shown ) for the main vessel , as well as a route 41 for injection of contrast agent and determination of the intravascular pressure . specifically , the device 2 of the invention is composed by a base 21 having a narrow proximal end 25 and a distal end 26 opposed to the first one . similarly to the disclosures above , the proximal end 25 has two pins 13 and a jaw 14 to support the y connector 40 ′, wherein the pins 13 are located so to fix the distal portion of the y connector 40 ′, while the jaw 14 fixes the proximal portion of said y connector 40 ′. on the distal direction , opposed to the y connector 40 ′, four fixers 17 , 17 ′, 17 ″ and 17 ″′ are intended , related and aligned to the inlet 42 of the y connector 40 ′, being one nearer fixer 17 , two intermediate fixers 17 ′ and 17 ″ and one fixer 17 ″′ on the distal portion 26 of the base 21 , as opposed to said y connector 40 ′. furthermore , and below the final position taken by the main inlet 42 of the y connector 40 ′, an orifice 12 is located , intended to the flow of blood . in another alternative form of embodiment of the present invention , as shown by fig8 , the device 3 is intended to receive and facilitate the use of a y connector 40 ″ intended for use in vascular interventions to treat trifurcation damage . therefore , said y connector 40 ″ has a main inlet 42 intended to introduce the metal guide and the balloon catheter ( not shown ) for the main vessel , two inlets 43 and 44 intended to introduce the metal guide and the balloon catheter in the secondary or side vessels , indistinctively , as well as a route 41 for the injection of contrast agent and determination of intravascular pressure . the base 31 of the device 3 has a narrow proximal end 35 and a distal end 36 opposed to the first one . similarly to the disclosures above , the proximal end 35 has two pins 13 and a jaw 14 to support the y connector 40 ″, wherein the pins 13 are located so to fix the distal portion of the y connector 40 ″, while the jaw 14 fixes the proximal portion of said y connector 40 ″. in the distal direction , opposed to the y connector 40 ′, three pairs of fixers 17 and 17 ′, 18 and 18 ′, 19 and 19 ′ are included , being the first pair of fixers 17 and 17 ′ related and aligned with the main inlet 42 of the y connector 40 ″, while the other pairs of fixers 18 and 18 ′, 19 and 19 ′ are respectively aligned to each one of the other inlets 43 and 44 for the secondary or side vessels . furthermore , and below the final position as assumed by each one of the inlets 42 , 43 and 44 of the y connector 40 ″, respective orifices 12 , 12 ′, 12 ″ intended for the flow of blood are included . in an alternative form of embodiment , as shown by fig9 , the base 11 ′ of the device 4 to fix metal guides and balloon catheters , intended for vascular interventions , and particularly for the treatment of bifurcation damage , has a v - shaped discontinuity 33 formed between the support regions for the fixers 17 , 17 ′ and 18 , 18 ′. therefore , each one of said support regions for the fixers 17 , 17 ′ and the fixers 18 , 18 ′ is present in the form of a projection or leg from the central region of the base 11 ′ of the device 4 . said form of embodiment of the invention allows the quantity of the base material 11 ′ to be reduced , thus making the device 11 ′ become lighter and more practical for its use and transport . in a preferable way of embodiment of the invention , according to fig1 a , 10 b and 10 c and so to enable a more precise evaluation of the extension of the damage or obstruction , the line of fixers 17 , 17 ′, 17 ″, 17 ″′ includes the disposition and / or printing of a millimeter ruler 20 . said rule 20 may be an element incorporated to the base 11 , 11 ′, 21 , 31 , but , preferably , said rule 32 is printed over the base 11 , 11 ′, 21 , 31 . in another possible form of embodiment , the rule 20 may have the form of a sticker with printing over or under a plastic base of a transparent material , as long as the material of the plastic base of the sticker is able to support the device sterilization procedures as required for its use in a surgery room . the inclusion and disposition of said rule 20 over the base 11 , 11 ′, 21 , 31 allows us to evaluate , with relatively higher precision , the effective size of the damage being treated and therefore the size of the balloon and / or stent to be used in the intervention . alternatively , other millimeter rulers 20 , 20 ′ and 20 ″ are also located in any one of the bases 11 , 11 ′, 21 , 31 , respectively the devices 1 , 2 , 3 or 4 , under the axis as defined by the respective pairs of fixers 17 and 17 ′, 18 and 18 ′, as well as 19 and 19 ′. the object of the present invention will now be disclosed as a function of its practical application , particularly in the percutaneous treatment of bifurcation damage , which is made with the support of the device 1 , as shown by fig1 - 3 . however , we should highlight that the use of embodiments as shown by fig7 and 8 is similar , with the only variation in the number of metal guides , balloon catheters and / or balloon catheters with stent ( not shown ) as a function of the type of damage to be treated ( angioplasty or trifurcation , respectively ). in the percutaneous treatment of bifurcation damage , the operator should initially pass or catheterize the vessel with the bifurcation damage with a guide catheter and connect the guide catheter to the appropriate y connector 40 for bifurcation . subsequently , we should fix the y connector 40 in bifurcation to the base or platform 11 , firstly fixing its more distal portion and then its proximal portion or , alternatively , fixing is proximal portion and then its distal portion ( as shown by fig4 to 6 ), so that said connector 40 is stabilized and with its two inlets 42 and 43 related and aligned , respectively , to fixers 17 , 17 ′ and 18 , 18 ′ of the metal guides and balloon catheters . after fixing the connector 40 , the operator should pass a metal guide to the main vessel by means of the inlet 42 of the y connector 40 , which is more aligned with the guide catheter . at that point , and before starting to pass the guide through the obstruction , the operator fixes the directing device ( not shown ) of the metal guide , as commonly used in interventions , at the zero point of the millimeter ruler 20 ( please refer to fig1 a ) as printed at the line of the fixers 17 , 17 ′, thus marking the start of the damage . continuing with the advance of the metal guide and after reaching the end of the obstruction , the operator makes the guide directing device abut the ruler 20 and evaluates the linear displacement of the metal guide , from which it is possible to make a precise estimative of the extension of the damage . based on that value , the operator can then choose the size of the balloon or stent to be used more precisely and safely . the advancement of the metal guide follows to reach the distal bed of the vessel and then the operator fixes the guide to the pair of fixers 17 and 17 ′ which is aligned ; the operator then passes a second metal guide to the side or secondary branch through the other inlet 43 of the y connector , which is more crosswise with the guide catheter and , when reaching the distal bed of said vessel , the operator is fixed in its pair of fixers 18 , 18 ′, similarly to the above description . the operator now has the metal guides as identified , positioned and fixed , as well as a faithful estimative of the extension of the estimated damage . dilatations are then made with balloon catheters at the obstructions of the main and side vessels . to perform this skill , the operator needs to put and position two balloons at the level of obstructions and insufflate them separately or simultaneously , to then release one or two endovascular prostheses or stents . with that purpose , the operator releases the guide of the main vessel of fixers 17 and 17 ′ and passes the balloon catheter over the metal guide and , soon after passing the more proximal portion of the balloon catheter , the operator fixes again the metal guide to said fixers 17 , 17 ′ and then pushes the balloon catheter over the metal guide and , after positioning the balloon at the obstruction level , the operator also fixes the balloon catheter to the fixers 17 , 17 ′ of the corresponding guide , so that they do not go back or forth when a second balloon catheter is introduced into the side or secondary vessel . when a second balloon is required , the operator performs the same procedures as for the first one , releases the metal guide of the fixers 18 , 18 ′, passes the balloon catheter , again fixes the guide into the corresponding fixers 18 , 18 ′ and pushes the balloon catheter until the level of obstruction . in that moment , the operator can handle , at the same time , both balloon catheters and locate them more safely and quickly . after balloon insufflations and de - insufflations , balloon catheters are pulled , keeping fixed metal guides . to take off the balloon catheter , the operator slowly pulls the balloon catheter until its proximal portion reaches the inlet 42 of the y connector . after the injection of contrast agent by the route 41 of the y connector 40 , the operator will decide which skill will be used to treat bifurcation obstructions . in case the operator decides to implant endovascular prosthesis or stents , he / she should follow the same steps as previously disclosed for balloon catheters , since those prosthesis are fixed or clipped to the balloon of balloon catheters . therefore , the operator releases the guide of the main vessel from fixers 17 , 17 ′ and passes the balloon catheter with the endovascular prosthesis over the metal guide , fixes it again to the fixers 17 , 17 ′ and pulls the balloon catheter over the guide until the level of obstructions and , after the balloon is positioned with the endovascular prosthesis , the operator insufflates the balloon , releasing the stent at the place of obstruction . when the second balloon catheter is required at the side or secondary vessel , the operator makes the same procedure as the first one , i . e . he / she releases the guide from the fixers 18 , 18 ′, passes the balloon catheter , fixes it again in the same fixers , pushes the balloon until the level of obstruction and insufflates it alone or simultaneously with the balloon from the main vessel . in case the operator still desires to insufflate the balloons or release the stents at the same time , he / she may simultaneously handle both balloon catheters with stents and position them more quickly and safely . to take off the balloon catheter , the operator slowly pulls the balloon catheter until its proximal portion reaches the inlet 42 or 43 of the y connector . as we can conclude from the above description , the use of any one of the devices 1 , 2 , 3 or 4 , as disclosed above , makes the surgical procedure become easier , faster and safer for the patient , also reducing the quantity of x rays to which patients and doctors are exposed . concerning the operator , devices 1 , 2 , 3 or 4 facilitate handling of guides and their respective catheters , facilitating the identification of each one , thus avoiding eventual prejudicial crossing between guides and catheters , and especially reducing the risk of displacements during the procedure . | a device for fastening metallic guides and balloon catheters for carrying out medical procedures involving percutaneous vascular surgery is described . the device may include a flat base with a proximal end and a distal end . fastening means may be mounted on the tapered proximal end to hold and position a y connector . at least one pair of aligned fasteners may be mounted on the distal end . each pair of fasteners may also be aligned with the respective inlets for the main vessel and for the secondary or lateral vessels . each fastener may have a shape of a truncated pyramid made of a rigid material , may project from the base , and may be provided at the top end with an insert made of a flexible material with a longitudinal groove that defines a receptacle for housing and retaining a metallic guide , a balloon catheter or a balloon catheter with a stent . |
a . 0 . 01 to 10 % by weight of extract of inula racemosa ; and b . 0 . 01 to 10 % by weight of naringin . the term edible composition preferably means a composition which is ingestible by human being . the edible composition preferably comprises 0 . 1 to 10 %, more preferably 1 to 10 %, further more preferably 3 to 10 % and most preferably 5 to 10 % by weight of extract of inula racemosa . inula racemosa is a species of an ornamental plant of the asteraceae family . inula racemosa grows in the temperate and alpine western himalayas , and it is common in kashmir , and also known as “ pushkarmool ”. “ extract of inula racemosa ” herein is to be understood as a composition obtainable by extracting roots of such plants or preferably parts of such roots with liquid and preferably water herein , “ extract of inula racemosa ” is the same as “ inula racemosa extract ”. all the above mentioned percentage is on solid weight basis of the composition . if the composition is having high percentage of water then the percentage of the extract of inula racemosa as mentioned above has to construe accordingly . the edible composition also preferably comprises 0 . 1 to 10 %, more preferably 1 to 10 %, further more preferably 3 to 10 % and most preferably 5 to 10 % by weight of naringin . “ naringin ” herein relates to the molecular structure as set out below , and is chemically known as 4 , 5 , 7 - trihydroxyflavanone 7 - rhamnoglucoside ( chemical formula : c 27 h 32 o 14 , mw = 580 . 54 ), including the edible salts thereof . naringin is a flavanone glycoside naturally occurs in fruits e . g . citrus fruits especially in grapes . it is one of the major flavonoid in grapefruit . the preferred source of naringin for the purpose of the present invention is from citrus fruits mainly grapes . preferably in the composition of the present invention , the ratio of inula racemosa to naringin is in the range of 1 : 0 . 01 to 1 : 10 , more preferably in the range of 1 : 0 . 1 to 1 : 10 and further more preferably in the range of 1 : 1 to 1 : 10 and most preferably in the range of 1 : 1 to 1 : 5 . though the edible composition of the present invention is not limited to any particular edible composition but the preferred composition of the present invention is in the form of a liquid such as a soup or a beverage , a spread , a dressing , a dessert or bread . the term tea based beverage as herein referred to preferably include black tea based beverages , green tea based beverage and oolong tea based beverages . the preferable format may be liquid tea drink , ready - to - drink tea , tea juice etc . both hot and / or cold brew . the edible composition of the present invention may also be in the form of a solid or powdered food supplement . the present invention also provides a process of producing an edible composition comprising the steps of mixing and / or blending 0 . 1 to 10 % by weight of extract of inula racemosa and 0 . 01 to 10 % by weight of naringin with the other ingredients to obtain the edible composition . the term “ other ingredients ” as mentioned above means the compositional ingredients needed for making a targeted edible product e . g . in case of making a soup composition ( targeted edible product ) the term “ other ingredients ” preferably are starch , salt , sugar , yeast extract , fat powder , vegetable pieces , flavour , colour etc . to make the edible composition of the present invention , the inula racemosa extract may be prepared by extracting ( boiling ) the roots of inula racemosa with water at a temperature in the range of 70 to 100 ° c . for 2 - 6 hours followed by cooling . after that the solution is filtered and concentrated . the concentration stage preferably carried out in a rotary evaporator . alternately , commercially available ( if available ) inula racemosa water extract powder may also be used . the composition of the present invention has been primarily developed for preventing and controlling diabetes and more particularly type 2 diabetes . without wishing to be bound by theory it is stated that type - 2 diabetes associated with increasing dpp - 4 ( dipeptidyl peptidase - 4 ) and thereby decreasing glp - 1 ( glucagon - like peptide - 1 ) activity . glp - 1 generally maintains the balance thereby controls blood sugar level . increasing level of dpp - 4 suppress the activity of glp - 1 . the present invention is primarily developed to inhibit dpp - 4 and thereby maintaining the activity of glp - 1 which in turns controls the blood sugar level . the present invention provides the use of a composition for anti - diabetic benefit . the present invention provides the use of a composition for the treatment of type 2 diabetes . the present invention provides the use of a composition according for maintaining glp - 1 activity . the present invention provides the use of a composition for the inhibition of dpp - 4 . the invention will now be demonstrated with the help of examples , which are for the purpose of illustration , and in no way limit the scope of the invention . inula racemosa extract was prepared by using the following procedure : the inula racemosa ( pushkarmool ) plant was bought from the local ( bangalore , india ) market . this was available as a stem size of ˜ 3 - 6 cm which was a combination of roots and stems of pushkarmool . the dried inula racemosa powder was then prepared by a pulverizer ( cutting mill , retsch sm 100 ) attached with a 200 μm size sieve . the extract of the inula racemosa was prepared from dried inula racemosa powder . 100 g of dry inula racemosa root powder was soaked in 800 ml of water for ˜ 14 hours and then boiled at 80 ° c . for 4 hours . it was then cooled down to ˜ 35 ° c . followed by filtering the solution to get a clear solution . the solution was then concentrated to dryness ( moisture content of ˜ 3 %) using rotary evaporator ( heidolph laborota 4002 ). this extract was used for the other experiments as described below . a 96 well plate ( nest biotechnology co . ltd , cat no 701001 ) was taken . in each well of 96 well plate extract of inula racemosa ( as prepared above ), naringin ( sigma , cat . no : n1376 ) and the combination of extract of inula racemosa and naringin were put in varied concentration as per table 1 . in each well , 4 ng of human recombinant dipeptidyl peptidase - iv ( dpp - iv ) enzyme ( prospec israel , cat . no . enz 375 ) was also added . after that , the final volume was made up to 200 μl / well using tris - hcl buffer of ph - 8 . the tris - hcl buffer was prepared by adding 2 . 42 g of tris ( tris hydroxyl methyl amino methane ; supplier : sisco research laboratory ltd , cat no 2044122 ) base , 0 . 372 g of edta ( sigma , cat no e6758 ) and 5 . 644 g of nacl in 900 ml of autoclaved milli - q water ( millipore ® india ) and stirred it till it get dissolved (˜ 30 minutes ). after that the ph of the solution was adjusted to 8 . 0 using hcl acid and then the volume of the solution was made up to 1000 ml with autoclaved milli - q water . the enzyme and combinations of extract of inula racemosa and naringin were mixed for 1 min using microplate reader ( bio - rad lab india , model no . 680 ) and incubated in an incubator ( thermo scientific , model 3111 ; conditions : at 37 ° c .) for 10 minutes . after that the enzymatic reaction was initiated by adding 10 μl / well of the 19 mm of substrate glycine - proline para nitroanilide ( gly - pro p - na ) ( this is equivalent to glp - 1 ). gly - pro - p na is a universally accepted and commercially available substrate for the enzyme dpp - 4 , due to the lack of availability of commercially available chromogenic glp - 1 . we have used gly - pro - p na in the assay which is equivalent to glp - 1 . it has also been reported to use gly - pro - p na instead of glp - 1 ( yogisha et . al ., journal of natural products , vol . 3 ( 2010 ): 76 - 79 ). as controls three different sets of samples were also taken for this assay viz . only substrate ( gly - pro - p na ) at the same concentration used above ( control 1 ), only dpp - 4 enzymes at the same concentration used above ( control 2 ) and other was the combination of gly - pro - p na and dpp - 4 at the same respective concentration used above ( control 3 ). all the above reaction mixture was again incubated for 1 hr in the same incubator under the same condition . then the enzymatic activity was arrested by adding 100 μl / well of citrate buffer . the citrate buffer was prepared adding 2 . 1 g of citric acid monohydrate ( sisco research laboratory ltd , cat no 0348216 ) and 2 . 94 g of sodium citrate tri basic dihydrate ( sisco research laboratory ltd , cat no 1949110 ) in 90 ml of autoclaved milli - q water ( millipore ® india ) and stirred it till it get dissolved (˜ 30 minutes ). after that the ph of the solution was adjusted to 4 . 0 using hcl acid and then the volume of the solution was made up to 100 ml with autoclaved milli - q water . after this the absorbance was measured at a wavelength of 405 nm using microplate reader ( bio - rad lab india , model no . 680 ). to get the % inhibition by inula racemosa and naringin , the absorbance value for the control 3 was considered as 100 % activity of dpp - 4 . the % activities of the dpp - 4 for the other samples were calculated using the following formula : the % inhibitions by the samples were then calculated by subtracting the activity from 100 . the results of the experiments summarized below in table 1 . from the above table it is evident that a combination of inula racemosa and naringin in the ratio inside the scope of the present invention ( example 1 , 2 and 3 ) provides much higher “% inhibition ” than either of inula racemosa or naringin when used alone at the same concentration ( example a , b , c and d ). therefore it is clear that the combination of combination of inula racemosa and naringin provides synergistic benefit when used in particular ratios . the soup composition was made by mixing the dry ingredient according to the following table : the soup was then prepared using 15 g of the above composition in 100 ml of hot water (˜ 90 ° c .) and tasted by a group of professional taster . it was found that the addition of inula racemosa extract and naringin did not alter the taste of the soup . the soup was as delicious as a control soup ( without the addition of inula racemosa aqueous extract and naringin ). | the present invention provides relates to an edible composition for anti - diabetic benefit . diabetes is one of the major and commonly occurring health problems in today &# 39 ; s world . pharmaceuticals companies are very active in this field to develop new medicines for preventing and controlling diabetes . there are several medicines available in the market for the treatment of type 2 diabetes . there are prior arts which describes composition and / or therapies for the prevention of glucose intolerance and / or diabetes . we have found that , though prior art discloses compositions and therapies for treating diabetes , there is not disclose any food composition which is effectively controls glp - 1 activity thereby control diabetes . the present inventors while working extensively for providing an edible composition for preventing diabetes have surprisingly found that a particular combination of inula racemosa and naringin is effective for controlling and / or preventive diabetes thereby satisfying one or more of the aforesaid objects . |
those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described . it is to be understood that the invention includes all such variation and modifications . the invention also includes all of the steps , features , compositions and compounds referred to or indicated in the specification , individually or collectively and any and all combinations or any two or more of the steps or features . other definitions for selected terms used herein may be found within the detailed description of the invention and apply throughout . unless otherwise defined , all other scientific and technical terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the invention belongs . the present invention relates to a device to be used for providing electrical stimulation to the eye . the purpose of providing electrical stimulation is to deliver a therapeutic or neuroprosthetic effect to a diseased eye . a therapeutic effect is an electrical stimulation of the eye that aims in assisting the healing and regeneration of damaged tissue . this will then lead to an improvement in the vision of a patient with diseases of their eyes or other parts of their visual system , and thus prevent the patient &# 39 ; s vision from deteriorating further . a neuroprosthetic effect is electrical stimulation of the eye with the aim of activating cells such as neurons in the eye which can relay signals to the visual centers of the brain . electrical activation of such cells causes a patient to experience the visual phenomenon of a small spot of light in their visual field , called a “ phosphene ”. by eliciting phosphene perception through electrical stimulation the device can restore or improve vision to patients who are blind or have lesser degrees of visual impairment , and thus also prevent further deterioration of vision in patients who have not lost all visual sensation . the aim of a visual prosthesis is to convey to the patient a rudimentary image of the surrounding environment built up of a number of phosphene “ pixels ”. visual prostheses are being developed that electrically stimulate the visual pathway at the level of the retina , the optic nerve and the visual cortex . the present inventors have established the feasibility of an extraocular approach to retinal stimulation . this is the first study of an extraocular retinal prosthesis , an approach to visual prosthesis development for which a device has hitherto not yet been developed ( maynard e m . 2001 , above ), ( margalit et al ., 2002 above ), ( humayun m s , et al ., 2003 above ). the present invention thus discloses devices for electrical stimulation of the eye via electrodes placed on the scleral surface of the eye . as such it is an extraocular device , which achieves electrical stimulation of the eye from electrodes placed in an extraocular location on the external surface of the sclera . unlike devices of the prior art ( eg . fedorov u . s . pat . no . 5 , 147 , 284 ), which discloses a device for electrical stimulation between an electrode on the optic nerve and an electrode on the scleral equator , the devices of the present invention do not have electrodes attached to the optic nerve . the present invention has one or more scleral electrode . the present invention presents unique designs of devices for electrode implantation on the scleral surface of the eye from both therapeutic and visual prosthesis uses . there are considerable advantages to using an extraocular ( scleral ) eye stimulator over epiretinal and subretinal visual prostheses previously disclosed . it does not require intraocular surgery , it does not require placing a chronic foreign body in the intraocular compartment and it does not require cables to be passed in and out of the eye through the sclera as in previously disclosed inventions . the device is much easier to implant and remove than intraocular devices . the device is also much easier to manufacture than intraocular devices . by having the tough yet thin sclera between the device and the retina ; it protects the delicate tissues of the retina from direct mechanical trauma , and heat and charge effects from electrical stimulation with the device , as compared with intraocular epiretinal and subretinal implants . in one form , the extraocular device consists of three components . these components are at least one electrode , a conducting means and a stimulator . preferably , the electrodes are housed in a continuous base ( referred to herein as a base member ), or each electrode is housed in its own base . the conducting means connects the base member or bases to the stimulator . the base member or bases can have a variety of shapes depending on the embodiment of the invention , and there can be from approximately 1 to 1000 electrodes , or more , of varying size , shape and inter - electrode configuration depending on the embodiment . the base member or bases of the device are implanted in the human body on the surface of the eye . after a surgical approach to gain access to the scleral surface of the eye , the device is placed on this surface . in one embodiment , the base member is shaped to conform to the curvature and shape of the external scleral surface of the globe of the eye . the base member is shaped to be placed on the scleral surface of the eye without disrupting the attachment of the optic nerve exiting from the posterior of the globe . the base member is shaped to fit around other structures that attach to the scleral surface of the globe , such as the attachment of the rectus muscles , depending on the objective of the embodiment . examples of suitable attachment means whereby the base member conforms to the outer surface of the sclera include embedding one or more electrodes in a scleral buckle , which are devices that are commonly known in the field . electrode - embedded scleral buckles can be placed on the scleral surface in the same manner as standard scleral buckles , when used for other eye conditions ( eg . retinal detachment ). in an alternative form of the invention , the base member or individual bases of the device of the invention are retained on the scleral surface using a suitable , long - term , bioadhesive glue . suitable examples are well known in the art and include cyanoacrylates ( eg . n - butyl cyanoacrylates ), and fibrin glue . in one form , the device has a base member in which electrodes may be embedded . the electrodes have active surfaces which are directed towards the inner surface of the base member of the device , so that when the base member is applied to the scleral surface of the eye , the base member conforms to the shape of the globe , and the active surfaces of the electrodes come into contact with the scleral surface of the eye . in this embodiment , each electrode has an independent insulated conductor which travels in the substance of the base member and exits the base member at the point where the conducting means is attached to the base member . in this form of the invention , the conducting means attaches to the outer surface of the base member and carries the individual insulated conductors from the electrodes . the conducting means connects the base with the stimulator , which may be implanted in the human body . alternatively the conducting means may exit the body through a percutaneous connection and connect with a stimulator outside the body . in another form , the conducting means may attach to a percutaneous plug , to which an external stimulator can be interfaced . in one embodiment , the stimulator is a device which is implanted in the body in a location that is outside the orbit or inside the orbit . the stimulator produces electrical pulses that are conducted through the conducting means of the stimulator to the electrodes on the bases or base member , which are applied to the outer scleral surface of the eye . the stimulator may be powered by battery and run a pre - programmed sequence of stimulation . alternatively the stimulator may be powered and controlled by an inductive link from a transmission coil that has been placed outside the body . in a further form , the function of the electrical stimulator is replaced with a means for electrically stimulating the one or more electrodes of the device . suitable means for activating electrodes are well known in the art , and include , but are not limited to , laser light or conventional light sources . the base member is suitably composed of a biocompatible material such as , but not limited to , a silicone elastomer . such a suitable biocompatible material will also insulate the the conducting means , and cover the conducting means to its connection with the stimulator . preferably , the electrodes are composed of a material suitable for electrical stimulation such as , but not restricted to , platinum and its alloys . electrical stimulation of the eye may occur through monopolar , bipolar , and multi - polar electrical stimulation of the electrodes on the grid through a variety of different configurations . stimulus parameters will include , but are not limited to , constant - current pulses , of pulse durations between 10 μs and 10 ms and current intensity levels between 1 μa and 10 ma . biphasic or monophasic pulses may be used . trains of stimuli with frequencies between 0 . 01 hz and 250 hz may be used . in a particularly preferred embodiment , the present inventors seek to adapt the neuroprosthetic technology that is available in the nucleus 24 auditory brainstem implant ( cochlear ltd , australia ). this implant has an electrode array of 21 platinum disc electrodes , each of 700 μm diameters , with a 950 μm centre - to - centre inter - electrode spacing , arranged in three rows in a silicone carrier . the present inventors have investigated a number of electrode types , configurations , and stimulus methods to optimize the development of an extraocular retinal implant for the restoration of visual perception to blind patients . an example of an extrocular device according to the invention will now be described with reference to fig1 , which illustrates an overview of the three components of the invention . the base member 6 , forms the main body of the device and preferably consists of a biocompatible insulating material 1 such as a silicone elastomer , in which are embedded the electrodes 3 , whose active surfaces on the inner aspect of the base member are applied to the scleral surface of the eye 2 , after the base member is implanted over the eye . according to this embodiment , extending from the lateral surface of the base member ( when viewed after implantation on the eye ), is the conducting means 4 , which contains independent conductors from all the electrodes in the base . the conducting means 4 , however , may exit from the base at any location that is feasible . in the present examples , the conducting means 4 connects the base with the stimulator 5 . fig2 illustrates a further example of an extraocular device of the invention . in this examples the base member 1 does not extend all around the sclera as in fig1 , but occupies a localised region 6 on the scleral surface . the scleral face of the base member is shown . in this embodiment the base 1 has a circular shape , and as in fig1 , contains multiple embedded electrodes 3 . turning now to fig3 , a further examples of an extraocular device of the present invention is illustrated in which the device consists of multiple bases 1 , each of which have a single electrode 3 and are implanted independently . independent insulated conductors 7 from these bases 1 converge to form the conducting means 4 . examples of the device will now be described with reference to fig4 a and 4b , which show front - on views of the inner scleral surface of the base member 1 . the base member 1 may contain one or many hundreds of electrodes , the electrodes being generally denoted as 3 , or any number in between . the electrodes 3 can be of varying diameters , arrangements or inter - electrode separations . fig4 a shows an extraocular device having a base member with 4 electrodes of 2 mm diameter , one placed in each quadrant . fig4 b shows an extraocular device having a base member with 57 electrodes , each of 700 μm in diameter . turning now to fig5 , there are depicted six exemplary methods of placement of the base member of examples of devices of the invention on the eye . fig5 a shows placement of the device from above the eye ; fig5 b depicts placement of the device from below the eye ; fig5 c illustrates placement of the device from the medial side of the eye ; fig5 d illustrates placements of the extraocular device from the lateral side of the eye ; fig5 e shows placement from behind the eye ; and fig5 f shows placement of the example device from the front of the eye . the base member is slid over the scleral surface of the posterior half of the globe of the eye . the anterior extent of the base member stops behind the attachment of the rectus muscles . this is also the approximate region where the sensory neuroretina ends ( ora serrata ). according to this example , a defect or elongated aperture in the posterior portion of the base member allows passage of the optic nerve and long ciliary vessels . in this example , the base member has a slit at its medial aspect ; this allows it to be slid over the eye from a lateral approach to form a sleeve around the eye . fig6 illustrates an enlarged view of an example of a device of the invention with particular emphasis on the base member 6 of this embodiment , showing its anterior 8 , posterior 10 , and medial 9 defects , which have special relations to its positioning and relation to the anatomical structures of the globe of the eye . the electrodes of the base 6 of the device are generally indicated as 3 . turning now to fig7 , there are illustrated exemplary means of attachment of the extraocular devices of the invention to the scleral surface of the eye . in particular , the electrodes 3 are placed to make contact with the scleral surface of the eye 2 . the base or base member 1 can be secured to the eye either through the use of sutures 12 , or through the use of a suitable bioadhesive glue 11 , as discussed above , between the edges of the base or base member 1 and the scleral surface of the globe . alternatively the base member 1 may stay attached to the scleral surface of the globe without these methods when its shape conforms to the shape of the globe and holds it in position . fig8 shows examples of certain methods for electrical stimulation of the eye with an extraocular device of the invention . a stimulating electrode can be stimulated with respect to a distant ground electrode 3 ( monopolar ); it can be stimulated with respect to another electrode nearby 13 , 14 , ( near - bipolar ). it can be stimulated with respect to a distant electrode 3 ( distant - bipolar ). it can also be stimulated with respect to multiple other electrodes ( multipolar mode ). fig9 a shows a further example of the device in which a perforations 3 in the base member 1 are used to decrease the degree of separation of connective tissues overlying the sclera of the eye from the sclera of the eye . the approximate location of the optic nerve as it exits from an aperture in the extraocular device is generally indicated as 16 . such perforations 3 decrease the thickness profile of the device , and thereby cause a minimal disruption between the scleral surface of the eye and the overlying connective tissue surrounding the globe of the eye , such as the fascia bulbi / tendons of the capsule ( not shown ). a further example of an extraocular device of the invention is shown in fig9 b , in which the base member 1 is in the form of a linear array of electrodes 3 in a strip . yet a further example of an extrocular device of the invention is shown in fig1 , shows the options for termination of the conducting means 19 into the stimulator . the conducting means may connect to an internal stimulator 5 . alternatively , the conducting means may connect to a percutaneous plug 22 by extension of the conducting means 20 , or it may exit the body percutaneously 21 . the internal body compartment is generally indicated as 18 , the external body compartment is generally indicated as 17 . the internal stimulator 5 may be powered and controlled by an inductive link from a transmission coil 23 that has been placed outside the body . in order that the invention may be readily understood and put into practical effect , particular preferred embodiments will now be described by way of the following non - limiting examples . development of a retinal prosthesis for blind patients based on extraocular stimulation of the eye with disc electrodes the present study was undertaken to investigate the feasibility of an extraocular approach to retinal stimulation . this is the first study of an extraocular retinal prosthesis , an approach to visual prosthesis development for which a device has hitherto not yet been developed ( maynard , 2001 , above ; margalit et al ., 2002 , above ; humayan et al ., 2003 , above ). the present inventors intend to adapt the neuroprosthetic technology that is available in the nucleus 24 auditory brainstem implant ( cochlear ltd , australia ). this implant has an electrode array of 21 platinum disc electrodes , each of 700 μm diameters , with a 950 μm centre - to - centre inter - electrode spacing , arranged in 3 rows in a silicone carrier . a number of electrode types , configurations , and stimulus methods were investigated to optimise the development of an extraocular retinal implant for the restoration of visual perception to blind patients . acute experiments were carried out in anaesthetised cats in accordance with the approval and guidelines of the animal ethics committee of the university of new south wales . in adult cats ( n = 6 ) weighing between 2 . 5 kg and 5 . 5 kg , anaesthesia was induced with an intramuscular injection of ketamine ( 20 mg / kg ) and xylazine ( 1 mg / kg ). the animals were given a preoperative dose of subcutaneous atropine ( 0 . 2 mg / kg ) and dexamethasone ( 1 . 5 mg / kg ). after intubation the animals were ventilated , and anaesthesia was maintained with a 70 : 30 mixture of nitrous oxide and oxygen , with 0 . 5 - 1 % halothane . ecg , end - tidal carbon dioxide , and core body temperature monitoring was carried out , and animals were monitored regularly for the absence of reflexes to ensure adequate anaesthesia . at the end of the experiment the cat was euthanased with an intravenous injection of pentobarbital . the cats underwent a bilateral craniotomy of the parietal bones , and the dura was removed to expose the primary visual cortex ( cytoarchitectonic area 17 ) of both hemispheres . the right orbit was approached by removing the bone of the lateral orbital wall and retracting or removing the right temporalis muscle . the cerebral cortex was regularly irrigated with warmed ( 35 ° c .) paraffin oil . recordings of cortical evoked potentials were carried out after placement of the cat in a stereotaxic frame , with platinum or silver ball electrodes placed on the pial surface of the primary visual cortex . cortical potentials were recorded using scope 3 . 6 . 11 software and a powerlab / 4sp data acquisition system connected to a ml135 biopotential amplifier ( adinstruments , australia ). evoked potentials were averaged over 100 - 200 trials , after being filtered to within a frequency range of 10 hz - 5 khz , and a 50 hz notch was used . a differential recording system was used , with an indifferent scalp clip and ground connected to a right thigh subcutaneous pin . a variety of stimulating electrodes and configurations were investigated . this included silver ball electrodes ( 1 mm diameter ), flat platinum disc electrodes of 2 mm and 4 mm diameters ( cochlear ltd , australia ), and a multi - electrode array consisting of 21 platinum disc electrodes each of 700 μm in diameter ( cochlear ltd , australia ), which were embedded in a scleral buckle and implanted in the same manner as standard scleral buckles . in some experiments a contact lens electrode was used as the stimulus return path ( ergjet ; universo , switzerland ). electrical stimuli were rectangular constant - current symmetrical biphasic pulses ( delivered from a 2100 isolated pulse stimulator ; am - systems , usa ) or monophasic pulses ( from a ml180 stimulus isolator ; adinstruments ). biphasic stimuli were also delivered using a nucleus 24 abi ( cochlear ltd , australia ). averaged cortical response to electrical stimulation of the right retina with extraocular electrodes was recorded , and compared a variety of configurations . vep and erg recordings were obtained to confirm the integrity of the neural visual pathway , and trialed surgical implantation techniques for an electrode array . monopolar and bipolar extraocular stimulation of the retina were investigated with silver ball electrodes . in cat a the stimulation electrode was placed on the posterior scleral surface of the eye , 5 mm lateral to the optic nerve attachment , in the horizontal meridian . in this animal a 4 mm platinum disc electrode was implanted on the inferionasal aspect of the globe to serve as the current return path . in cat b , two silver ball electrodes with a 5 mm inter - electrode spacing were placed at the central posterior surface of the globe superio - lateral to the optic nerve head . this is illustrated in fig1 , where the solid circle represents the attachment of the optic nerve to the back of the eye . open circles represent the placement of electrodes . the typical electrical evoked response to cathodal - first biphasic stimulation in a monopolar configuration from cat a , was compared to the response from monophasic stimulation of bipolar electrodes in cat b ( fig1 ). bipolar stimulation in cat b showed a typical negative - positive electrically evoked response ( dawson & amp ; radtke , invest ophthalmol vis sci 1977 ; 16 ( 3 ): 249 - 52 ). however due to a prolonged artifact in cat a , as is typical with monopolar stimulation ( yeomans , principles of brain stimulation . new york : oxford university press , 1990 ), the initial negative component of the cortical response in this cat was obscured ( a comparison with control waves was performed ). the first visible true response in cat a is a positive peak at 38 ms . a second positive peak follows this wave at 54 ms . the average latency of the negative and positive peaks for cat b , and the two positive peaks for cat a are shown in table 1 : by determining the threshold current to elicit a response at the visual cortex , a strength - duration curve was obtained for biphasic monopolar extraocular electrical stimulation of the retina ( fig1 ). for phase durations greater than 200 μs , threshold currents for eliciting a visual cortex response were below 1 . 5 ma . we also determined the peak amplitude of the positive component of the evoked response in cat a for a range of stimulus current levels at a pulse width of 250 μs ( fig1 ). higher response amplitudes were obtained with increasing current up to 5 ma , after which there was a response plateau . the effect of pulse trains on cortical response amplitude was investigated . the amplitude of the positive wave of the electrical evoked response was recorded for 2 ma , 250 μs cathodal - first biphasic stimuli to single pulses and pulse trains of 2 , 3 or 4 pulses presented at 200 hz . these responses were also compared to the amplitude of the cortical potential evoked by a double pulse at 100 hz ( fig5 ). the highest cortical responses were obtained with three pulse trains . for double pulses , a longer interval between pulses evoked a larger cortical response . extraocular stimulation of a localised region of the sclera leads to excitation of a localised region of the retina which evokes localised cortical responses . monopolar extraocular stimulation of the retina was undertaken with a ball electrode placed in the horizontal meridian 5 mm lateral to the attachment of the optic nerve on the globe . biphasic pulses of 250 μs pulse width and 2 ma current intensity were used , and recorded evoked responses at localised points on the primary visual cortex over the posteriomedial regions of the lateral gyri of both hemispheres . using a 1 mm silver ball recording electrode we moved antero - posteriorly in 1 mm steps to record evoked cortical potentials from horsely - clarke co - ordinates a1 to p8 . we recorded from the most medial position of the superior surface of the lateral gyrus that was accessible after a craniotomy preserving a narrow strip of bone overlying the sagital sinus ( fig1 ). cortical responses in cat a were localised in the anterio - posterior plane to horsely - clarke co - ordinates p6 and p7 in the left and right hemispheres respectively . there was a second smaller peak of cortical activity anteriorly in the left hemisphere at p2 , which was not present in the right hemisphere . extraocular stimulation of the retina with flat platinum disc electrodes in 3 different configurations was investigated ( fig1 a ). in cat d , a 2 mm active electrode was sutured under the superior rectus muscle and a 4 mm return electrode was placed anterior to the attachment of the lateral rectus muscle ( fig1 b ). in cat e , a 2 mm active electrode was placed in the inferio - lateral quadrant of the right eye and a 4 mm return electrode was placed anterior to the attachment of the medial rectus muscle . in cat f , a 2 mm platinum disc was applied to the sclera 5 mm lateral to the optic nerve attachment in the horizontal meridian and a contact - lens electrode applied to the cornea was used for the current return path . the strength - duration curve for cortical activation with the electrode configurations in cats d and f is shown in fig1 . electrical stimulation of the eye in cat e produced a right cortex cortical activation map which is shown along with cat a in fig6 . anodal stimulation was more effective than cathodal stimulation at exciting the retina ( cat f ), demonstrated by the upward shift of the strength - duration curve . the strength - duration curves flattened towards rheobase at pulse widths greater than 500 μs . increasing the pulse width of the stimulus up to 1 ms , led only to small decreases in the threshold current required for retinal activation . cathodal stimulation with the electrode configuration of cat f was more effective than the configuration used in cat d . in cat f , it was possible to obtain cortical responses from retinal stimulation with threshold currents of less than 100 μa at pulse widths greater than 400 μs . extraocular retinal stimulation with components of a prototype extraocular retinal prosthesis in two cats was undertaken . in cat c we implanted a 21 - electrode array , embedded in a scleral bukcle , along the horizontal meridian of the posterior sclera of the right globe , and bipolar biphasic pulses were delivered with a bench stimulator . in cat f , extraocular stimulation of the retina was carried out with a nucleus 24 abi , using neural response telemetry ( nrt ) software and the portable programming system ( pps ) ( cochlear ltd , australia ). strength - duration curves for both bench and implant stimulation are shown in fig1 . electrode impedance measurements obtained with the reverse telemetry feature of the implant ( cat f ) gave a reading of 15 . 6 kohms in the monopolar configuration ( single grid electrode active , contact lens electrode as the corneal return ) and 8 kohms in the “ common ground ” configuration ( single electrode active , all other 20 electrodes on the grid shorted to the return path ). using bipolar stimulation ( bench ) of the electrode array , threshold currents were lower than 1 ma for pulse durations greater than 300 μs . stimulation levels with the implant are programmed in device units up to “ 255 ”, which is the strongest stimulation level using the unit , and equal to approximately 1 . 75 ma . pulse widths up to the device maximum of 400 μs were investigated . monopolar stimulation was more effective than common ground mode stimulation . no responses could be elicited with a pulse width below 400 μs in common ground mode . in monopolar configuration , using pulse widths of 100 μs and 200 μs , stimulation intensities at the upper limits of the device were required . electrical stimulation of the retina can elicit visual perceptions in blind patients 9 , commonly described as small spots of light termed “ phosphenes ”. major efforts are underway to develop a retinal prosthesis that will hopefully restore a level of visual perceptions that will be functionally useful to blind patients ( rizzo et al ., 2001 ; margalit et al ., 2002 ; humayun et al ., 2003 ; eckmiller , ophthalmic res 1997 ; 29 ( 5 ): 281 - 9 ; jensen et al ., 2003 ). a medical device for this purpose must be surgically feasible ( walter et al ., retina , 1999 ; 19 ( 6 ): 546 - 52 ), be physically biocompatible to the body ( majji et al ., invest ophthalmology & amp ; vis sci 1999 ; 40 ( 9 ): 2073 - 81 ), utilize safe stimulation parameters ( mccreery et al ., ieee transactions on biomedical engineering 1990 ; 37 ( 10 ): 996 - 1001 ; agnew & amp ; mccreery , epilepsia 1990 ; 31 ( suppl 2 ): s27 - 32 ), and give the highest possible number of stable , reproducible and resolvable phosphene sensations ( humayun . 2001 , above ). the present inventors believe that an extraocular approach to retinal prosthesis development will be better than current attempts at epiretinal prostheses ( margalit et al ., 2002 , above ; humayun et al ., 2003 , above ), for fulfilling these goals in the development of a clinically viable visual prostheses for blind patients in the short term . in six cats it was possible to record evoked responses at the visual cortex to electrical stimuli applied to the retina with electrodes placed on the posterior surface of the globe ( fig1 ). we investigated electrical stimulation with different electrode types in a variety of configurations ( fig1 a ), all of which were able to evoke visual cortex responses . as it has been postulated that activity at the primary visual cortex is correlated to conscious perception ( lamme et al ., vision res 2000 ; 40 ( 10 - 12 ): 1507 - 21 ), the activity evoked in the visual pathway through this method of stimulation will most probably evoke phosphene perception in human patients . the feasibility of implanting both electrode arrays , and single electrodes , on the surface of the sclera was also investigated . in the cat shown in fig1 b , the disc electrode was slipped under the superior rectus muscle , and the electrode tail was then sutured to this muscle , and then again to the periorbita with a purse - sting suture . local paralysis of the extraocular muscles to prevent movement will be necessary in future chronic implantations . it would also be possible in the future to use biological adhesives or sutures to fix the silicone base carrying the electrode directly to the sclera . the placement of extraocular electrodes does not require any intraocular surgery , or the intraocular placement of foreign bodies against the delicate retinal tissues . it also does not require complicated methods of attachment of electrode arrays to the retinal surface such as tacks ( humayun et al ., 2003 , above ). extraocular electrodes have a better surgical feasibility profile than intraocular electrodes . the minimum thresholds for eliciting cortical evoked responses with extraocular electrodes were examined . current thresholds were variable amongst cats with different electrode configurations . the lowest thresholds were found with a 2 mm electrode placed on the posterior of the globe , and stimulated with respect to a contact lens electrode placed on the cornea . the threshold for eliciting an evoked response was as low as 100 μa ( fig1 ) at a pulse duration of 400 μs ( 0 . 04 μc per phase ). this translates to a charge - density at the electrode surface of 1 . 27 μc / cm2 , which is well within safe charge injection levels in human studies for chronic neural stimulation ( gordon et al ., electroenceph & amp ; clin neurophysiol 1990 ; 75 ( 5 ): 371 - 7 ). higher thresholds occurred with monopolar stimulation using the nucleus 24 abi ( fig1 ). a threshold of 225 device units ( 255 units = 1 . 75 ma ) was obtained when using 400 μs cathodal - first biphasic pulses . with extraocular stimulation , the electrodes are not applied directly on top of the delicate retinal tissue . the firm scleral base for extraocular electrodes avoids mechanical trauma to the retina , and decreases the likelihood of pathological effects due to charge transfer and heat generation ( jayaker , advances in neurology 1993 ; 63 : 17 - 27 ). the ability of extraocular stimulation to produce localised phosphenes was assessed , by investigating whether extraocular stimulation produces localised activation at the primary visual cortex . the medial edge of the lateral gyrus ( cytoarchitectonic area 17 ) contains a retinotopically mapped representation of the visual field ( tusa et al ., j comp neurol 1978 ; 177 ( 2 ): 213 - 35 ). in cat a the cortical response was localised posteriorly at a similar anterio - posterior coordinate in both hemispheres ( fig1 ). studies of pulse summation will aid in the identification of optimal stimulus parameters for an extraocular retinal prosthesis . ideal frequencies for pulse trains were investigated with multi - pulse studies . higher cortical responses were obtained with paired pulses at 100 hz than at 200 hz . for 200 hz stimuli , peak responses were obtained with 3 pulse trains ( fig1 ). as expected , anodal stimuli were less effective than cathodal stimuli in eliciting extracellular stimulation of retinal tissue ( fig1 ) ( yeomans , 1990 , above ; jayakar , advances in neurology 1993 ; 63 : 17 - 27 ). a basic feasibility study of adapting technology in the nucleus 24 abi for extraocular retinal stimulation was undertaken . this device is composed of an array of 21 platinum disc electrodes in a silicone carrier , and a stimulator implant which can be powered and controlled transcutaneously . the electrode array could elicit stimulation of the sclera under a variety of electrode configurations . the stimulator implant itself was able to evoked visual cortex responses with single biphasic pulses ( fig1 ). an extraocular retinal implant will overcome many of the difficulties of using epiretinal stimulation for a visual prosthesis ( rizzo et al ., 2001 , above ). the present inventors have shown the feasibility of such an approach by demonstrating an ease of surgical implantation , safe current thresholds for evoking cortical responses , and localised activation of the primary visual regions in the brain . adaptation of the technology in the nucleus 24 abi will provide a basis for developing an extraocular prosthesis for human trial . it will provide a higher number of drivable electrodes ( dawson & amp ; radtke , 1977 , above ), and hopefully resolvable phosphenes , than the epiretinal prostheses currently undergoing clinical trial ( humayun et al ., 2003 , above ). establishment of suitable threshold , strength - duration and evoked response amplitude data for electrical stimulation of the retina with an extraocular device acute experiments were carried out in anaesthetised cats , with adherence to the arvo statement for the use of animals in ophthalmic and vision research , the nih principles of laboratory animal care and in accordance with the guidelines of the animal ethics committee of the university of new south wales . in adult cats ( n = 3 ), anaesthesia was induced with an intramuscular injection of ketamine ( 20 mg / kg ) and xylazine ( 1 mg / kg ). the animals were given a preoperative dose of subcutaneous atropine ( 0 . 2 mg / kg ) and dexamethasone ( 1 . 5 mg / kg ). the pupils were dilated with atropine ( 1 %) and phenylephrine ( 10 %) eye drops . after intubation , the animals were ventilated and anaesthesia was maintained with a 70 : 30 mixture of nitrous oxide and oxygen , with 0 . 5 - 1 % halothane . ecg , end - tidal carbon dioxide , and core body temperature monitoring was carried out , and animals were monitored regularly for the absence of reflexes to ensure adequate anaesthesia . at the end of the experiment the cat was euthanased with an intravenous injection of pentobarbital . two extraocular electrodes ( manufactured for the study by cochlear ltd , australia ) were implanted on the right eye of each cat , one laterally and one superiorly . the extraocular electrode consists of a 2 mm diameter platinum disc ( surface area 0 . 0314 cm 2 ) embedded on the surface of a silicone base shaped to conform to a portion of the outer scleral surface . a silicone tail was connected to the edge of the base within which was a helically wound ( strain relief ) electrode lead that was bonded to the inactive side of the platinum disc . in each cat the right superio - lateral orbital wall was removed , and the periorbita in the horizontal plane laterally and vertical plane superiorly was incised 1 cm posterior to the limbus . the lateral and superior rectus muscles were removed to gain access to the sclera , and the electrodes were placed on the sclera and centred on points 13 mm posterior to the limbus with their tails pointing posteriorly . using a 7 - 0 vicryl spatula tip ( ethicon , usa ), the extraocular electrode was attached to the sclera with 4 interrupted sutures distributed around its circumference , biting the silicone rim 1 mm from its edge . the periorbita and skin over the lateral orbit was then closed with the tails exiting through the posterior aspects of the wounds . after implantation of the electrodes the cats were placed in a stereotaxic frame and a craniotomy of the right posterio - medial parietal bone was performed . the dura was removed to expose the posterio - medial lateral gyrus , over which the primary visual cortex is located . the exposed pial surface of the cerebral cortex was bathed in a well of warmed ( 35 ° c .) paraffin oil . recordings of cortical evoked potentials were made with a 2 mm silver / silver chloride ball electrode . this was placed on the most medially accessible region of the pial surface of the lateral gyrus at horsely - clarke co - ordinates p2 or p3 , the location of cytoarchitectonic area . a differential recording system was used with the indifferent electrode connected to a posterior scalp clip , and ground connected to a right thigh subcutaneous pin . cortical potentials were recorded using scope 3 . 6 . 11 software and a powerlab / 4sp data acquisition system connected to a ml135 biopotential amplifier ( all from adinstruments , australia ). evoked potentials were averaged over 200 trials , were filtered to within a frequency range of 10 hz - 5 khz , and a 50 hz notch was used . stimuli were generated with a powerlab / 4sp and were fed through a model 2200 analog stimulus isolator ( am - systems , usa ). stimulation was performed with single biphasic charge - balanced constant - current pulses . a half - pulse of phase duration between 200 μs and 1000 μs was followed by an identical half - pulse of opposite polarity with an interphase interval of 100 μs . current intensities between 10 μa and 3 ma were used . stimuli were delivered at 2 hz . bipolar stimulation was performed between the lateral and superior extraocular electrodes , the polarity of the stimulus determined by the electrode polarity during the first phase of the stimulus . monopolar stimulation occurred between the lateral extraocular electrode and a contact lens electrode ( erg - jet ; universo , switzerland ), which was used as the current return path . stimulation was performed in the light - adapted eye . flash visual evoked potentials ( veps ) were recorded from the right eye after implantation of the electrodes . flash stimuli were delivered from a botex sp - 106mr super strobe ( n . c . w ., hong kong ) at 1 hz , and the visual evoked response was averaged over 100 trials , with similar filter settings to those used for electrically evoked potential recording . the electrically evoked potential ( eep ) to extraocular retinal stimulation is a complex wave consisting of early and late components . fig2 shows the cortical response to subthreshold ( 0 . 15 ma ) and suprathreshold ( 3 ma ) bipolar lateral - cathodal stimuli in cat 1 . random cortical activity follows a subthreshold stimulus . an evoked wave was considered to be an eep if its amplitude was at least twice the amplitude of the average baseline activity to subthreshold stimuli , and exhibited typical eep latencies . the early component of the eep consists of a positive - negative wave which begins soon after the electrical artifact generated by the stimulus . the positive peak of this wave ( ep1 ) had an average positive peak latency of 8 . 39 ms and its negative trough ( en1 ) had an average latency of 16 . 32 ms , as shown in table 2 : the late component of the eep was a negative - positive wave with the average latency of its negative trough ( en2 ) being 33 . 28 ms , and its positive peak being 56 . 97 ms . fig2 compares the response latencies of the four eep components to bipolar lateral - cathodal stimuli across the three cats . eeps , as analysed by component latency , were consistent both within cats and between cats . however the relative amplitudes of the early or late components of the eep were variable between cats . the highest amplitude component of the vep recorded to flash stimulation was a negative - positive wave ( vn2 - vp2 ) which occurred after 70 ms ( table 2 ). the vep was compared with the eep to extraocular retinal stimulation . the late wave of the eep ( en2 - ep2 ) had a smaller amplitude and a shorter latency as compared to the vn2 - vp2 component of the vep . this would be expected as electrical stimulation bypasses the time needed for photoreceptor processing by directly depolarizing the retinal neurons . the en2 component of the eep occurs 67 . 12 ms earlier than the vn2 component of the vep . a smaller positive - negative wave vp1 - vn1 was also identified in the vep , which may be the vep correlate of the ep1 - en1 wave of the eep as it occurs at a similar latency shift to the en2 and vn2 components of the eep and vep respectively . the current intensity for eliciting a threshold ( an early or late wave amplitude greater than twice the baseline noise level ) eep was measured for bipolar lateral - cathodal biphasic stimuli at phase durations between 20 μs and 1000 μs to determine strength - duration relationships in the three cats . these have been plotted in fig2 , along with the threshold charge - density curve averaged across all cats . threshold decreased with increasing phase duration . the lowest current thresholds were obtained in cat 1 . it was possible to evoke visual cortex responses with stimuli of 500 μa when using 800 μs per phase pulses . the lowest charge - density threshold for an eep was 8 . 92 μc / cm2 , and was obtained in cat 1 at a phase duration of 200 μs and a current intensity of 1 . 4 ma . the amplitude of the ep1 - en1 wave of the eep to bipolar lateral - cathodal stimuli was recorded in relation to changes in phase duration and current intensity levels in all cats . stimuli of similar current level , but longer phase duration evoked higher amplitude eeps ( fig2 ). using stimuli at a constant phase duration , increases in the current intensity of the pulses evoked higher amplitude eeps . in cat 1 , the increase in eep amplitude started to plateau at current levels greater than 1 . 8 ma . eep amplitudes were higher in cat 1 compared to cats 2 and 3 for stimuli at a similar phase duration . a third - order polynomial curve was fitted to the eep responses from stimulus pulses with a 1000 μs phase duration obtained in cat 1 , and this was extrapolated to the x - axis ( fig2 ). this intersects the x - axis at a current level of 300 μa , which is the lowest threshold for an eep that could be projected from the available data . monopolar and bipolar stimuli , and the effects of polarity reversal were investigated by comparing strength - duration curves and eep amplitudes . bipolar lateral - cathodal stimulation was compared with monopolar lateral - cathodal stimuli . both these stimulus configurations produced a similar profile of cortical response ( fig2 a ), reaching rheobase at a current level of 500 μa . monopolar lateral - cathodal stimulation was compared with monopolar lateral - anodal stimulation . cathodal extraocular monopolar stimulation consistently evoked higher amplitude eeps than anodal stimulation ( fig2 b ). bipolar lateral cathodal stimulation was compared with bipolar lateral anodal stimulation . these produced overlapping strength - duration curves , with lateral - anodal stimulation being more effective than lateral - cathodal stimulation at phase durations greater than 800 μs ( fig2 c ). extraocular stimulation is a possible approach to developing a visual prosthesis to aid in the rehabilitation of blind patients . this study has demonstrated the feasibility of implanting electrodes on the sclera , and has evaluated their ability to evoke visual cortex responses from single pulse stimulation in the cat . the electrodes for this prototype prosthesis have been constructed from platinum and silicone , materials which have a good biocompatibility profile in human tissue . access to the sclera can be gained through a simple surgical approach , and the extraocular electrode can be securely sutured or affixed by the shape of the extraocular device on the globe , its silicone base insulating the electrode from direct contact with overlying tissues or muscle . an extraocular device avoids the risks and complications associated with the more invasive surgery that would be needed for an epiretinal or subretinal implant , and avoids the placement of a foreign body intraocularly . as larger electrodes are used for extraocular stimulation as compared with epiretinal implants , and the extraocular electrodes are further away from the target neurons in the retina , an extraocular device may not be able to match the potential resolution of a high - density intraocular implant , should such a device become a reality . however an extraocular device may be able to provide simple low resolution visual sensations to aid blind patients in their mobility and orientation . due to the surgical and mechanical simplicity of an extraocular device , this may be a more clinically feasibly short - term goal than the restoration of more complex visual perception with intraocular implants . a number of controls were performed to ensure that the responses were generated by localized electrical stimulation of the retina through the scleral electrodes , and were not the results of electrical artifact or stimulation through the cornea . reversing the polarity of the stimulus did not invert the shape of the cortical response shown in fig2 . the eep occurred at a shorter latency to the vep , and at a similar latency shift to that shown in other studies . the amplitudes of the eeps are significantly less than that of the vep ( fig2 ), therefore only partial activation of the retina is occurring , favouring localised activation at the scleral electrode . stimulation is occurring at the sclera and not through the cornea , as bipolar stimulation between two scleral electrodes evoked similar responses to monopolar stimulation using an erg electrode as the return path ( fig2 a ). if stimulation was occurring through the cornea , bipolar stimulation would not evoke cortical responses , and the strength - duration curves for bipolar and monopolar stimulation would be very different . extraocular stimulation of the retina produces eeps with early and late components . the eep has a shorter latency than the vep ( table 2 ) as would be expected if extraocular stimulation was bypassing the time required for photoreceptor processing by directly exciting neural cells in the retina . due to the short latency of the eep ( fig2 ), direct stimulation of the ganglion cells or their axons is probably occurring . the late ( en2 - ep2 ) wave of the eep occurs at a similar latency to the eeps described by dawson and radtke in the cat ( dawson & amp ; radtke , 1977 , above ), and humayun and colleges in human studies ( humayun et al ., 1996 , above ). however , the early wave ( ep1 - en1 ) of the eep recorded in this study with extraocular retinal stimulation has not been previously described . due to its shorter latency , evaluation of this response may give a more direct indication of the effects of different stimulus parameters on retinal activation than the late wave of the eep . the eeps that were recorded exhibited the typical characteristics of a physiologic response . alternating the polarity of the stimulus did not alternate the polarity of the recorded waveform . the eep components had similar latencies within and between cats ( fig2 ), and when using different electrode configurations . increasing the stimulus pulse width lowered the current threshold for a response , to produce typical strength - duration relationships . also , the amplitude of the cortical evoked response saturated above certain current levels and did not show a linear increase ( fig2 ), which is more typical of a physiologic rather than artifactual response . retinal activation was possible at current and charge - intensity levels that were well within safe limits for chronic neural stimulation with platinum electrodes . the threshold charge - density for evoking a cortical response in all cats , and across the range of phase durations investigated ( fig2 ) were well below charge injection limits for platinum electrodes of 100 μc / cm2 10 , and within the safety limit of 52 μc / cm2 established for chronic human brain stimulation . we recorded thresholds as low as 500 μa with extraocular retinal stimulation ( fig2 ). when extrapolating from curves of eep amplitude as a function of current intensity , thresholds as low as 300 μa were calculated ( fig2 ). the 2 mm diameter electrodes that were used in this study had a surface area of 0 . 0314 cm2 , which is much larger than the electrode surface area in most epiretinal implants . we recorded threshold charge - densities as low as 8 . 92 μc / cm2 ( fig2 ). studies in animals with photoreceptor degenerations are expected to display stimulus thresholds may be increased for diseased retinas . a number of experiments were carried out to compare different electrode configurations for extraocular stimulation . bipolar stimulation produced similar responses to monopolar stimulation ( fig2 a ). as would be expected , cathodal stimulation is more effective than anodal stimulation at exciting the neural tissue in the retina ( fig2 b ). the large surface area of the sclera available posterior to the ora serrata will allow easy implantation of an array of at least about 20 electrodes of 1 - 2 mm diameter in extraocular devices . 1 . sharma r k , & amp ; ehinger b . management of hereditary retinal degenerations : present status and future directions . survey of ophthalmology 1999 ; 43 ( 5 ): 427 - 44 . 2 . chong n h & amp ; bird a c . management of inherited outer retinal dystrophies : present and future . british journal of ophthalmology 1999 ; 83 ( 1 ): 120 - 2 . 3 . mitchell r n , & amp ; cotran r s . chapter 3 : repair : cell regeneration , fibrosis , and wound healing . in : kumar v , cotran r s , robbins s l , eds . basic pathology . 6 ed . philadelphia : w . b . saunders , 1997 . 4 . scarlatis g . optical prosthesis : visions of the future . jama 2000 ; 283 ( 17 ): 2297 . 5 . larkin m . artificial - vision research comes into focus . lancet 2000 ; 355 ( 9209 ): 1080 . 6 . veraart , et al . visual sensations produced by optic nerve stimulation using an implanted self - sizing spiral cuff electrode . brain research 1998 ; 813 ( 1 ): 181 - 6 . 7 . maynard e m . visual prostheses . annual review of biomedical engineering 2001 ; 3 : 145 - 68 . 8 . brindley g s & amp ; lewin w s . the sensations produced by electrical stimulation of the visual cortex . journal of physiology 1968 ; 196 ( 2 ): 479 - 93 . 9 . humayun et al . visual perception elicited by electrical stimulation of retina in blind humans . archives of ophthalmology 1996 ; 114 ( 1 ): 40 - 6 . 10 . dobelle w h . artificial vision for the blind by connecting a television camera to the visual cortex . asaio journal 2000 ; 46 ( 1 ): 3 - 9 . 11 . grumet et al . multi - electrode stimulation and recording in the isolated retina . journal of neuroscience methods 2000 ; 101 ( 1 ): 31 - 42 . 12 . humayun m s . intraocular retinal prosthesis . transactions of the american ophthalmological society 2001 ; 99 : 271 - 300 . 13 . humayun , et al . pattern electrical stimulation of the human retina . vision research 1999 ; 39 ( 15 ): 2569 - 76 . 14 . chow a y , & amp ; chow v y . subretinal electrical stimulation of the rabbit retina . neuroscience letters 1997 ; 225 ( 1 ): 13 - 6 . 15 . stett , et al . electrical multisite stimulation of the isolated chicken retina . vision research 2000 ; 40 ( 13 ): 1785 - 95 . 16 . rizzo , et al . retinal prosthesis : an encouraging first decade with major challenges ahead . ophthalmology 2001 ; 108 ( 1 ): 13 - 4 . 17 . margalit , et al . retinal prosthesis for the blind . survey of ophthalmology 2002 ; 47 ( 4 ): 335 - 56 . 18 . chow , et al . subretinal artificial silicon retina microchip implantation in retinitis pigmentosa patients : long term follow - up . arvo meeting abstracts 2003 ; 44 ( 5 ): 4205 -. 19 . chapin & amp ; moxon . neural prostheses for restoration of sensory and motor function . boca raton : crc press , 2001 . 20 . humayun et al . visual perception in a blind subject with a chronic microelectronic retinal prosthesis . vision res 2003 ; 43 ( 24 ): 2573 - 81 . 21 . dawson & amp ; radtke . the electrical stimulation of the retina by indwelling electrodes . invest ophthalmol vis sci 1977 ; 16 ( 3 ): 249 - 52 . 22 . yeomans j s . principles of brain stimulation . new york : oxford university press , 1990 . 23 . eckmiller r . learning retina implants with epiretinal contacts . ophthalmic research 1997 ; 29 ( 5 ): 281 - 9 . 24 . jensen et al . thresholds for activation of rabbit retinal ganglion cells with an ultrafine , extracellular microelectrode . invest ophthalmol vis sci 2003 ; 44 ( 8 ): 3533 - 43 . 25 . walter et al . successful long - term implantation of electrically inactive epiretinal microelectrode arrays in rabbits . retina 1999 ; 19 ( 6 ): 546 - 52 . 26 . majji , et al . longterm histological and electrophysiological results of an inactive epiretinal electrode array implantation in dogs . investigative ophthalmology & amp ; visual science 1999 ; 40 ( 9 ): 2073 - 81 . 27 . mccreery et al . charge density and charge per phase as cofactors in neural injury induced by electrical stimulation . ieee transactions on biomedical engineering 1990 ; 37 ( 10 ): 996 - 1001 . 28 . agnew & amp ; mccreery . considerations for safety with chronically implanted nerve electrodes . epilepsia 1990 ; 31 ( suppl 2 ): s27 - 32 . 29 . lamme et al . the role of primary visual cortex ( v1 ) in visual awareness . vision res 2000 ; 40 ( 10 - 12 ): 1507 - 21 . 30 . gordon et al . parameters for direct cortical electrical stimulation in the human : histopathologic confirmation . electroencephalography & amp ; clinical neurophysiology 1990 ; 75 ( 5 ): 371 - 7 . 31 . jayakar p . physiological principles of electrical stimulation . advances in neurology 1993 ; 63 : 17 - 27 . 32 . tusa et al . the retinotopic organization of area 17 ( striate cortex ) in the cat . j comp neurol 1978 ; 177 ( 2 ): 213 - 35 . | a medical device for use on the human eye is described . the device is placed in an extrocular location in a patient and delivers an electrical current that stimulates the retina of patients who are blind or have vision disorders . it has at least one electrode that makes contact with the scleral surface of the eye , the electrode typically being activated by an electrical stimulator . the device produces electrical pulses which pass through the electrodes on the scleral surface of the eye , to activate the retina of the eye , which causes the patient to experience improved vision , visual sensations or the prevention of deterioration of vision . by this means , sight can be restored or improved where patients have disorders of their retina or other parts of their visual system . |
the preferred embodiment and best mode of the invention is shown in fig1 through 8 . “ batter ” as used herein in the application is meant to encompass cake batter , dough , malleable ice cream , gelatin or a malleable dessert which sets up in a rigid or semi - rigid shape . referring to the figures , a molding or baking assembly 20 according to the invention is adapted to shape or mold cake batter , other compositions ofbaking goods or complimentary desserts such as ice cream , gelatins , puddings into a concentric dual bundt cake shape . the outer pan 22 is typically symmetrical with a ring shape and a domed cross section taken across one segment of the ring . the outer pan is constructed with a ring shaped body 24 having a domed or curved closed bottom 26 , and side walls 27 and 28 forming an interior chamber or cavity 29 with an open end 30 . the side wall 28 forms an interior reverse funnel shaped structure 31 with an upper ring shaped planar surface 33 which defines a central aperature 37 as seen in fig1 and 8 . the open end 30 is formed with a curved or rolled outer lip or rim 32 as shown in fig2 and has two handles 34 secured to the exterior of the sides the outer pan surface under the rim 32 extending outward from the rim or outer circumference ofthe pan opposite each other . each handle 34 has a downwardly turned tab member 36 , each tab member being located on different ends of the respective handles . the outer lip 32 is curved in a bead or circular configuration and preferably has a diameter of about 0 . 25 inches and sits inside of rim 63 of the inner pan cover assembly . while the ring body provides a suitable seat for baking , ifdesired , a base support member ( not shown ) may be secured to the bottom surface 26 of the ring body 24 to provide a flat base surface during working and / or cooking . the base support member is preferably constructed of 22 gage c1018 cold rolled steel with ring shape having a bell shaped exterior surface having a side wall with a curved bottom edge forming a planar plane which seats the outer pan . the base support member is secured to the base section of the ring shaped body 24 by welding or braising . if desired , a bimetallic thermometer can be attached to the base support member which thermometer would turn an appropriate color upon reaching the desired cooking temperature allowing the cook to ascertain that the desired temperature has been reached . the outer pan body 24 and optional base support member is preferably integrally constructed of sheet steel or stainless steel but can be constructed of copper , aluminum , cast iron , pyrex , glass , porcelain , ceramic or any type of microwaveable material at a uniform desired thickness commonly used for baking pans and containers . if desired , the outer ring pan body can have its external surface coated with a non - corroding material such as tin or chromium . the outer ring pan body 24 therefore may be constructed of a single sheet of metal formed into the desired shape . the inside surface of the ring cavity 29 is preferably coated with one or more nonstick coatings , as for example teflon ® ( i . e ., fluorocarbon polymers ), ( e . g ., tetrafluroethlene and fluorinated ethylene propylene ). the interior surface ofthe outer pan 24 , which contacts the batter or dessert composition , is covered with teflon ® in the preferred embodiment to ease the removal ofthe baked or chilled product from the bowl . the radial sloping of the inner surfaces further eases removal of the final dessert composition . it will be appreciated by those skilled in the art that other shapes and geometries of pan assemblies are possible , and that the specifics of material of which it is made can be changed without departing from scope of the invention . the mold may be formed or stamped from a solid piece of material or spun from aluminum instead of formed from a sheet . a cover assembly 50 has an integral ring shaped pan 52 as shown in fig1 and 7 . the inner pan 52 is typically ring shaped with a segment of the ring having a dome shaped cross section . the inner pan is constructed with a curved closed bottom surface 54 , side walls 55 and 56 forming a cavity or chamber 58 and an open end 60 . a lip 61 extends above the plane of cover skirt 62 . the ring body 52 has a smaller width and depth so that it will be seated in cavity 29 of the outer ring pan 24 . the cover assembly 50 is substantially circular or of a ring shape with handles 64 opposing each other . the handles 64 are shaped to fit over the outer pan handles 34 as shown in fig4 and 8 and a lower downwardly extending rim 65 which sits just outside of outer lip 32 of the outer pan when the components are locked together . the area 62 between the lip 61 and rim 65 is planar and forms a concentric circular area or skirt which covers the cavity 29 or open end 30 of the outer pan ring pan 24 . the handles 64 are rolled or bent in a “ c ” configuration to hold handles 34 so that the bottom portion 66 fits under the lower surface of handles 34 of the outer ring pan and when rotated , locks the outer ring pan and cover assembly 50 in a fixed position as shown in fig8 . one end of each handle is provided with an outwardly extending tab 68 which allows the handle to be easily rotated on the handle 34 and removed . the inner side wall 56 forms an internal center support structure 57 which fits over the inner structure 31 formed by side 28 . the center support structure 57 has a upper circular planar surface 59 and indentation 159 which rests on structure 31 . the planar bottom surface of the indentation 159 defines a aperture 160 which is axially aligned with circular aperture 37 of structure 31 when the two component pans are mounted to each other . preferably the planar cover area or skirt 62 is provided with a number ofthroughgoing holes 70 as shown in fig1 and 6 which allow steam to escape from the batter in the outer pan 22 while it is cooking . alternatively , the cover assembly 50 and inner ring pan 52 can be constructed of porous material such as high temperature teflon coated high temperature fiberglass ranging from 5 to 10 mils in thickness or a stainless steel wire cloth also teflon coated on both sides , both of which are breathable an allow an air flow of 50 cfm which vents moisture during baking without batter coming through . the porous material has a sieve opening for the stainless steel wire cloth ranging from 0 . 0165 + or − 0 . 0005 and the stainless steel is stme 1187 . the inside and outside surfaces of the inner ring pan 52 are preferably coated with one or more nonstick coatings , such as for example teflon ® ( i . e ., fluorocarbon polymers ), ( e . g ., tetrafluroethlene and fluorinated ethylene propylene ). alternately the bowl body can be constructed of sheet steel , stainless steel , copper , aluminum , cast iron , pyrex , glass , porcelain , ceramic or any type of microwaveable material at a uniform desired thickness commonly used for baking pans and containers . the interior and exterior surfaces of the inner pan 52 , which contacts the batter or dessert composition is smooth and is preferably covered with teflon ® in the preferred embodiment to ease the removal of the baked or chilled product from the bowl . the radial sloping ofthe inner walls further eases removal of the final dessert composition . it will be appreciated by those skilled in the art that other shapes and geometries of pan assemblies are possible , and that the specifics of material of which it is made can be changed without departing from scope of the invention . the inner pan 52 is mounted in the ring shaped outer pan cavity 29 by placing the cover assembly 50 on the rim 32 so that the handles 64 are offset from the outer bowl handles 34 is adjacent rim 32 . the cover assembly 50 is then rotated by applying force to tabs 68 so that the ends 65 of the handles 64 engage the outer ring pan handles 34 with the bottom portion 66 of the cover assembly handles being positioned under the bottom surface of outer pan handles 34 engaging a downwardly projecting handle rim support 35 as shown in fig8 . in operation cake batter is poured , about ⅔ to ¾ full , in the pan cavity 24 up to the embossed guide line or lines and the cover assembly 50 and its integral inner ring shaped pan 52 is placed in chamber or cavity 29 of the outer pan 22 and the cover rotated so that both handles are aligned and locked . a second cake batter of a different flavor as for example , chocolate , is poured in the cavity 58 of pan 52 about ⅔ to ¾ of the depth of the cavity . after the batter is molded and baked by the application of heat to the pans , with steam being conveyed by holes 70 , the cover assembly 50 is removed and the inner ring pan 52 is taken out of its nesting position cavity 29 in the outer pan 24 leaving a cavity in the cake or mold . the teflon ® coating of the interior and exterior surface of the cover assembly 50 and inner ring pan 52 facilitates removal of the mold without tearing or damaging the final baked product . the baked cake is then removed from the inner ring pan 52 , the teflon ® coating ofthe interior surface of the cavity of the inner pan facilitating the dessert removal . the result is a baked goods , which has concentric ring shaped portions , preferably ofdifferent flavors and / or composition and is ready to eat . the teflon ® coating of the interior surface of the outer pan mold 24 facilitates removal of the baked product without tearing or damaging the final baked product . the interior cake or other optional filling is placed in the cavity formed by inner ring pan 52 and the composite assembly is inverted onto a serving area for frosting , icing or other decoration preparatory to being served . the result is a dual composition bundt cake or dessert which is ring shaped and ready to eat . the baked goods or molded foodstuffs may be filled or coated with ice cream , pudding , icing or other sweet filling for a dessert pastry . although aluminum , sheet steel and / or stainless steel is preferred for the outer pan body , any suitable structural material could be used in its place , as for example , alloyed steel , copper , brass , cast iron or even glass or ceramic , such as stoneware . the inner bowl body has the same structural body as that of the outer pan body . the principles , preferred embodiments and modes of operation ofthe present invention have been described in the foregoing specification . however ; the invention should not be construed as limited to the particular embodiments which have been described above . instead , the embodiments described here should be regarded as illustrative rather than restrictive . variations and changes may be made by others without departing from the scope of the present inventions defined by the following claims . | an apparatus assembly for forming a compound dessert in a predetermined compound ring shape including a first outer ring shaped pan defining a cavity , the cavity having a dome shaped cross section with a closed circular end and an open end . a cover including a second dome ring shaped pan of a smaller width and depth and a surrounding circular skirt is mounted to the outer ring shaped pan with the second inner ring shaped pan extending into a cavity of the first outer ring shaped pan . |
before describing these inventive ideas , it is worth explaining the principles behind thermactive materials . the basic idea is similar to the more familiar metallic “ bimetal ” strips . two materials of different thermal expansion are bonded ( laminated ) together . this structure constrains the laminated face of each film to be the same length , at all temperatures . however , if one film has a significantly larger expansion coefficient than the other ( and is stiff enough not to compress ), that film will try to grow longer when heated . the only way to accommodate this relative expansion is to curl . as is well known , on a racetrack the inner lane covers a shorter distance than the outer lane . in the same way , the film with the higher expansion coefficient ( e . g . longer ) will be on the outside of a curled film when heated , and on the inside when cooled . the film will be straight ( e . g . not curled ) at one intermediate temperature , called the “ lay flat temperature ”. the lay flat temperature can be adjusted during the lamination process , and in the case of a thermactive flower , would typically be in the range of 70 - 80 degrees , so the flower petals are flat in a normal office or home environment . note “ heating ” the flower can be accomplished by many means . clearly , one means is simple thermal contact with warm or cold air . alternatively , a flower petal in the sun or under and incandescent bulb will absorb some of the light &# 39 ; s heat ( more if darkly colored , less if brightly colored ). the exposed petal may heat by 20 c more than the surrounding air . thermactive materials can be made symmetric with respect to temperature — that is , it curls one way when cold , and the other direction when heated . so , one could assemble a flower out of a multitude of petals with the low expansion layer oriented towards the center of the bud . thus , when heated ( whether in the sun or a warm room ) the petal will curl towards the center of the flower , and not bloom . however , when cooled ( say in the shade or a refrigerator ) the flower will bloom . such a flower either mimics real night blooming species ( such as the moon flower ipomoea alba ) or could be associated with a fictional story . for example , a flower that blooms at night might be an appropriate gift from a vampire . since the flower only opens at a particular temperature ( either hot or cold ), one could create a small , “ secret ” storage niche in the center of the flower to hide or store a precious memento . for example , a girl might keep a boy &# 39 ; s lock of hair in the flower . or a man might propose to a woman by storing a ring in the flower , and having it open in the sun during a proposal . while these inventive flowers may bloom in direct sunlight , on partly sunny days or in an interior room there may be insufficient light to heat the petals faster than they cool to the environment . for example , the flower may be placed on a windowsill in winter , and the cold air near the window will prevent sunlight from warming the petals sufficiently for motion . our solution is to provide a removable or integrated greenhouse - like cover . such a cover is shown in fig1 . referring to fig1 , there is shown , a vacuum - formed double walled plastic bell jar 10 that fits over the flower 12 and flowerpot 14 . or a simple clear plastic bag that is slipped over an open wire frame . advantageously , the bell jar 10 or bag has provisions to vent out excessive heat on particularly sunny days . for example , the bag could be furled or the bell jar lifted above the flowerpot 14 , or the bell jar split and hinged vertically ( like a tambour door on a roll - top desk ). note , in one example , the flower could be sold in a hanging package , contained within a thin clear “ blister ”. this blister package could perform “ double duty ” as the greenhouse . in some cases , the flower 12 might be desired to bloom on demand . for example , when placed in a vase . in this case , the flower &# 39 ; s stem could be fashioned from a heat pipe ( a technology well known in the art ), and the flowerpot 14 filled with hot water . the heat pipe will conduct the water &# 39 ; s warmth within the thermactive flower bud , causing it to open . by evaporating or otherwise depositing a thin , high electrical resistance layer on the thermactive material , a thin - film heater is produced in intimate contact with the plastic . by attaching electrodes to the resistive metal , and passing current through the metal , heat is produced and very efficiently coupled into the thermactive material . this combination of thermactive and resistive materials would allow a thermactive flower to bloom simply by attaching a battery and flipping a switch . or , the flower could be linked , via a usb cable , to a computer . the flower might bloom whenever the weather report indicates clear skies , or close on bad news in the stock market . previous flower designs disclose only very simple petal arrangements — typically just a single ring of diamond - like flaps . real flowers exhibit a much broader range of petal shapes . as the flower blooms , each petal may unfold in a unique way — some curl to the side , others bend directly away from the stamens . we have discovered a much more realistic and pleasing flower can be created by systematically mixing different petal types in one flower head . we have discovered that the flower petal &# 39 ; s thermactive behavior is sensitively dependent on the axis of the petal relative to the axis of curl of the thermactive film 18 . referring to fig2 , it can be seen that the petals 20 a , 20 b , 20 c might be aligned and cut along the thermactive &# 39 ; s axis of curl ( zero degrees , in the middle petal 20 b ); perpendicular to the curl direction ( ninety degrees , in petal 20 a ), or at a bias ( forty five degrees , in petal 20 c ) referring to fig3 and fig2 , it can be seen that after the petals 20 a , 20 b , 20 c are cut from the film 18 , and viewed from the tip of the petal towards the stem , it is clear the “ 0 ” degree petal 20 b follows the simple curl of the original film , the “ 90 ” degree petal 20 a is only slight bowed in the perpendicular direction , but is basically flat , and “ 45 ” degree petal 20 c is twisted . when heated or cooled , each of these petals 20 a , 20 b , 20 c move in entirely different , but predictable , ways . for example , the “ 0 ” degree petal 20 b will curl when cooled lower than the lay flat temperature , but will flatten above , and barely curl in the opposite direction . the “ 90 ” petal 20 a exhibits the reverse behavior . and the “ 45 ” petal 20 c will twist one way when cooled , and the opposite direction when heated ( at very high excursions above or below the lay flat temperate , all petals 20 a , 20 b , 20 c curl into a twisted ribbon . these varied behaviors are of particular advantage in a thermactive flower . for example , the inner petals of a rose can be assembled from the 45 degree petals 20 c , while the calyx petals along the exterior are cut along the 90 degree petals 20 a . when heated , the tight rose bud would open into a mass of curled petals , while the calyx petals bend directly away from the stem — as in an actual rose . in addition to carefully mixing different petals in one flower , there are advantages to mixing petals made from films with varied lay flat temperatures . for example , in the sun a black petal will bend much more quickly than a white petal , because it absorbs significantly more heat . if it is desired to have both black and white petals bend at the same time , a higher lay flat temperature thermactive film is used for the darker petal . conversely , it may be desired to extend the temperature range over which the flower blooms . so , one might select petals made from a low lay flat temperature for the outer petals , and higher lay flat temperatures , for the inner petals . then , as the day &# 39 ; s temperature climbs , the bloom slowly transitions across the flower bud &# 39 ; s radius . if a petal is attached to a support , and that support is curved , the petal ( at the lay flat temperature ), will follow the curve and form a partial cylinder . this cylindrical shape stiffens the petal ( as it does with any thin sheet ), and before the petal can bend , it must overcome the shape - induced rigidity . so , when a curved petal is exposed to the sun , nothing happens until so much compressive energy is stored in the film , it suddenly bends over . while curved mounting of a petal is typically disadvantageous , the phenomena can be harnessed advantageously . in fig4 , there is shown a venus flytrap thermactive flower 24 . here , the two halves of the flytrap flower 24 are joined along a curved common axis , forming two intersecting cupped petals . when heated , the petals cannot bend easily . but at a high enough temperature , they will suddenly bend and snap shut . decoratively , a small plastic fly may be glued to one petal . or , as part of a game the player must try to dangle a fly in the trap at exactly the right time to be caught . | an artificial flower and the associated method of its manufacture . to produce the artificial flower , two films of material are laminated . the films of material have markedly different coefficients of thermal expansion . the laminate is formed into a curve shape . petals and leafs are cut from the laminate . the petals and leafs are cut at different orientations across the curved shape . accordingly , various petals and leaves change shape in different manners in response to changes in temperature . the various petals and leafs are then formed into an artificial flower . |
the new variety was noted in test plantings wherein approximately 100 , 000 seeds , seedlings and cuttings had been test planted under agricultural conditions on a total of 2 . 5 acres following over ten ( 10 ) years of study of salt - tolerant plants . the purpose of these large plants was specifically to discover new grain and plant varieties with commercial potential and to learn their agronomic requirements . the new variety , yensen 2a , was derived from a plant produced from a bed seedling . the new plant which first produced the new grain variety was first noted for its vigorous growth and ideal form and later for its high yield of grain on relatively short stalks . the stalks are erect and the grain heads are of a suitable height for combine harvest . plants which yield the new grain variety , yensen 2a , are being reproduced via rhizomes in tucson , ariz ., where a number of other plant and grain varieties are also being observed . parentage : a grain variety by plant variety yensen 2a , a plant variety of distichlis palmeri . the harvested caryopses from which the yensen 1a variety emerged were among literally millions of harvested caryopses which were then selected for size and weight . while approximately 100 , 000 caryopses have been so selected and test planted , the particular test planting from which yensen 1a emerged had approximately 3 , 000 caryopses . this test planting was in plot number 2 . . . of 9 test plots planted at tucson , ariz . these test plots were subjected to various stresses , e . g . water , temperature , salts , etc . such that only 0 . 1 % to 1 % of the caryopses reached maturity . the plants that survive this rigorous selection process are often phenotypically similar . this may be true in part due to similar genetic combinations that can survive the same rigorous selection process , and in part to the harvested caryopses being frequently derived from a few phenotypically similar parents . due to ( 1 ) the nature of the selection process wherein massive numbers of caryopses are utilized , and ( 2 ) the heavy selection pressures , it is not practical to follow individual caryopses and their lineages . grain : 6 - 11 mm in length ( including the bifurcation style ), length decreasing slightly apically on the spikelet , 1 - 2 mm in width , 1 - 2 mm in height ; embryo cover 2 - 4 mm in length ; ventral surface indented with a longitudinal groove ( except in unusually well - filled caryopses ); anterior seed coat longitudinally wrinkled and posterior portion wrinkled into two rounded ventral keels and one rounded dorsal keel which extends to the bifurcation of the styles ; surface texture with numerous longitudinal striae and light vertical rugae , glabrous , colored a brown and may be darker anteriorly and lighter posteriorly . propagation : to date all grain described herein . it is expected that at least 90 % of the grain progeny of the yensen 2a grain will be phenotypically similar to the characteristics of the initial grain variety as they are described herein . it is acknowledged that the new grain variety is undoubtedly genetically heterozygous at a number of loci and no claim is made herewith for genetic homozygosity . culms : rigid , erect , occasionally branched , glabrous , 20 - 50 cm high depending on rhizome age at inflorescence , 2 - 3 mm in diameter . the color of the culms is not significantly different from some other varieties . blades : firm , rigid , ascending , pointed and pungent , involute ( especially upon drying ), distichous , glabrous to slightly puberulent , 3 - 5 mm basal width , 20 - 30 veins at base , typically 30 - 80 mm in length . sheath : glabrous to slightly puberulent , with a tuft of wooly hairs at either side of the mouth , ligule smooth with pubescence apically . panicle -- erect , compoundly branched ( often branched in two &# 39 ; s ), 4 - 8 cm in length and does not extend beyond the leaves ; spikelet -- with 5 - 9 flowers , subtending &# 34 ; bracts &# 34 ; infertile , 20 - 40 mm in length , 6 - 10 mm in width ; florets -- lemma 10 - 15 mm in length decreasing slightly apically on the spikelet , 4 - 6 feint veins on either side of a weak keel ; palea 9 - 11 mm in length , length decreasing slightly apically on the spikelet . | a grain variety , yensen 2a , of distichlis palmeri , which are characterized by vigorous growth in salty soils , high grain yield and ideal form for harvest . this grain variety has excellent taste qualities . |
the invention in its basic form comprises a central bowl portion 10 having tapered skirt - like sides 12 , the bowl and skirt preferably being molded as a single plastic unit . a lid 14 is attached to one edge of the bowl by a hinge 16 which could be of conventional construction as shown or simply a piece of permanent tape adhered to the lid and upper rim of the bowl . the lid is preferably made of transparent plastic to be relatively light in weight and permit the status of the food supply to be determined at a glance . the lid is provided with an extended upwardly curved tab 17 by which the pet can lift the lid with his nose , and to prevent the lid from swinging over the center so that it will fall closed automatically when the animal is finished , a slight protrusion 19 is provided at the hinged edge of the lid to strike the edge of the bowl prior to the lid achieving the vertical position . an annular moat or trough 18 is disposed around the bowl 10 to serve as a prophylactic against crawling insects and to provide water for the pet . the moat could be an integral part of the bowl portion , or a separate piece having a tapered inner wall 20 which mates flushly with the skirt 12 of the bowl and is held in place by gravity . as shown in fig6 and 7 , the central food bowl is elevated somewhat above the water trough to provide easier access thereto by the pet . to accomodate pets of different sizes , and to keep up with a growing dog , the dish should have means of elevation to various heights . this can be accomplished in several different ways . as shown in fig6 the skirt of the bowl mates snugly in an annular shoulder 22 of the uppermost section 24 of a pedestal 26 which is comprised of as many sections as are required , each of these frustoconical sections mating with adjacent sections as the bowl 10 mates with section 24 . a slight variation of the sectional pedestal is shown in fig7 wherein shoulders are not provided and the sections nest on each other due to their frustoconical shape . in a modified embodiment illustrated in part in fig1 and 2 , the dish 10 is supported on a tripod arrangement of telescopic legs 28 having sleeve sections 30 which are maintained in place by a brace 32 , and extensible feet portions 34 which telescope within the sleeves and are maintained at the desired length of extension by screwtype detents 36 or other suitable means , such as plural holes in the sleeves and legs through which pins are inserted . the upper ends of the legs are crimped flat as at 38 , and in the illustrated embodiment the skirt 12 of the bowl has been deleted and replaced by a flange or lip 40 so that the bowl is supported by this lip on the legs . the trough 18 rests snugly on the crimped portions of the sleeves as shown in fig2 . clearly the bowl 10 complete with the skirt could also be used in this embodiment with slight modification . a further embodiment illustrated in fig3 and 4 incorporates an elongated bowl portion 42 which is integrally molded with the surrounding water trough 44 . this dish will simultaneously feed two or more without the mutual jealousy which is often incurred during simultaneous feeding from the same dish . to accomplish this , a pair of lids 44 are commonly hinged at 46 across the center of the dish , each of the lids having an extended tab 50 which in this instance may extend across the trough to be easily liftable by the pets . as shown in phantom in fig4 the lids will swing open independently , and to prevent over - the - center movement the opposite edges of each lid are provided with a protrusion 52 near the hinge area which strikes one of the studs 54 projecting from opposite sides of the food bowl portion of the dish . elevation of the elongated dish may be accomplished by one of the methods already described , or a common tray support assembly can be used as shown in fig4 wherein two inverted u - shaped leg member 56 are fastened by their crossbars 58 in clips 60 such that the legs 62 cross and are pinned together as at 64 through any pair of the holes 66 provided therein , so that elevation may be varied according to the holes chosen . the entire structure as thus described is relatively cheap to manufacture , and effectively prevents access to pet food by either airborn or terrestrial pests , and offers food at a convenient height to pets of any size . | an anti - pest variable height pet dish having a central food bowl with a pet - operable lid and an annular moat - type water trough removably or fixedly mounted around the central bowl , the moat and bowl being elevatable by means of telescopic legs or a tapered sectional pedestal having removable sections . |
according to the embodiment ( s ) of the present invention , various views are illustrated in fig1 - 11 and like reference numerals are being used consistently throughout to refer to like and corresponding parts of the invention for all of the various views and figures of the drawing . fig1 illustrates a hair extension weaving device 1 constructed according to the teachings of the present invention . the hair extension weaving device 1 may be used for attaching wefts of real or manufactured , artificial hair to an individual &# 39 ; s braided hair . the individual &# 39 ; s braided hair may be embodied as , for example , a cornrow , or braid . the device aims to reduce the amount of time required to attach the wefts of hair . the weaving device 1 consists of an upper body member 5 and a lower body member 10 which are selectively engageable with one another . the upper body member 5 is preferably shaped like a cone frustum . in various embodiments , the size and shape of upper body member 5 may be modified to make the hair extension weaving device 1 easier to hold and grip . the upper body member 5 is preferably made out of plastic . however other materials such as metal , ceramic , wood , and rubber are contemplated and foreseeable herein . the upper body member 5 preferably includes a securing member 15 that in the present embodiment is embodied as a blunt screw . the securing member 15 may be inserted into an aperture 20 and preferably extends into the upper body member 5 ( see fig2 ). the securing member 15 preferably secures a needle member 25 within the upper body member 5 . to do so , the needle member 25 is first preferably inserted substantially into a receiver 30 that is embodied as a tunnel shaped bore that channels downwardly through the upper body member 5 ( see fig3 ). in some embodiments , a sheathing device may further be provided to secure and protect the needle member 25 . the sheathing member may even include a mechanism for retracting when the device 1 is in use . the securing member 15 may then be inserted and subsequently screwed using a common threading technique into the aperture 20 . in the preferred embodiment , the securing member 15 is tightened until it abuts the needle member 25 , thus securing the needle member 25 substantially in its position emerging upwardly from the upper body member 5 , and perpendicular to the securing member 15 . however , other securing mechanisms are contemplated and foreseeable . the upper body member 5 preferably includes a cylindrical inner portion 35 ( shown in fig2 and 4 ) that has a circumference slightly smaller than that of the rest of the upper body member 5 . the cylindrical inner portion 35 has a circumference that is also just smaller than that of the lower body member 10 so that when the upper body member 5 is inserted into the lower body member 5 , the cylindrical inner portion 35 forms a friction fit within the lower body member 10 . a bottom surface 40 of the cylindrical portion 35 also includes an opening 45 for receiving and securing a rod member 50 extending upwardly from within the lower body member 10 . the lower body member 10 is preferably substantially barrel - shaped so that it can better hold a spool of thread . the lower body member 10 may take on a different size and / or shape to ensure the hair extension weaving device 1 is easier to hold and grip . additional shapes , dimensions , and sizes of the lower body member 10 are contemplated and foreseeable . lower body member 10 is preferably made out of plastic , but other materials such as metal , ceramic , wood , and rubber may also be used . the lower body member 10 preferably includes a cavity 55 for receiving a spool of thread ( not illustrated ). the rod member 50 is housed within the cavity 55 and preferably receives and secures the spool of thread . as set forth above , when the lower body member 10 and the upper body member are selectively engaged , the inner cylindrical member 35 is releasably secured within the cavity 55 such that a lip 60 that circumscribes the upper body member 5 abuts a lip 65 that circumscribes the lower body member 10 . turning now to fig5 , the lower body member 10 further preferably includes a slit - like slot member 70 for dispensing thread ( not illustrated ). at an upper end 75 of the slot member 70 , the slot member 70 preferably includes a throat 80 that allows for a greater range of motion and reduces fraying and breaking of the thread . the throat 80 is shown and illustrated as having rounded edges 85 to reduce fraying and breaking . lower body member 10 further also preferably includes a cutting member 90 . the cutting member 90 may be used to sever thread , as described in greater detail below . the cutting member 90 may be placed anywhere on the device 1 , preferably near the bottom of lower body member 10 where it will not interfere with other components of the device 1 . the cutting member 90 may be screwed , glued , or nailed onto the hair extension weaving device 1 . other methods of attaching the cutting member 90 are contemplated and foreseeable . however , the cutting member 90 does not have to be a separate piece attached to the hair extension weaving device 1 . fig6 provides an elevation view of a preferred embodiment of a needle member , needle member 95 . the needle member 95 is spiral shaped , and the illustrated needle member 95 completes a full turn . the spiral shape of the needle member 95 preferably makes it easier for a hairstylist to push the needle 95 through an existing hair track or braid , and thus it may reduce the time required to attach hair extensions . other types of needles , including straight and curved , are contemplated and foreseeable . the needle members 25 , 95 are preferably made out of stainless steel , but other materials are contemplated and foreseeable . when a spool of thread is placed onto the rod member 50 inside the cavity 55 of the lower body member 10 , a tail end of the thread can then be pulled from the cavity 55 of the lower body member 10 through the slot member 70 . turning now to fig7 - 10 , the hair weaving device 1 is shown at various stages of sewing an extension weft 100 to a braided track 105 . prior to beginning to sew the weft 100 onto the track 105 , a tail end of the thread 110 may be threaded through an eye 115 of the needle member 25 in a known manner . the thread 110 should be knotted at its tail end so that it cannot be pulled through a base ( not illustrated ) of the weft 100 . the weft 100 may be placed on top of the track 105 , and the knotted thread pulled through a base ( not shown ) of the weft 100 . the weft 100 is preferably attached to the braided hair track 105 via slip knots 115 so the weft 100 can be easily removed by simply cutting the thread once , as shown in fig7 . this allows the remaining thread 110 to unravel quite easily . to form the slip knots 115 that are used to attach the weft 100 to the track 105 , the threaded needle member 25 should be guided upwardly under the track 90 as shown in fig8 , between the track 105 and the head itself ( not illustrated ). with the excess thread between the needle member 25 and the hair weaving device 1 , a loop 120 should be formed that has an arch or rainbow - like shape ( see fig8 ). the loop 120 should be held with the hand not holding the hair extension weaving device 1 . the loop 120 may be pulled downwardly over the track 105 , so the loop 120 is inverted to be u - shaped in front of the track 105 , as shown in fig9 . the needle member 25 may then be pushed through the u - shaped loop 120 as shown in fig1 , and then again guided between the head and the track 105 . this motion , repeated several times , forms the slip knots shown in fig7 that allow the weft 100 to be firmly attached to the track 105 . after every stitch , the thread 110 should be pulled until the stitch is tight against the base of the weft 100 . these steps should be repeated until the entire weft 100 is sewn onto the track 105 . once at the end portion ( not illustrated ) of the weft 100 , the thread should be knotted to prevent the weft 100 from becoming detached from the braid 105 . fig1 shows an illustration of another embodiment of a hair extension weaving device 125 that may be smaller and more efficiently used than the device 1 described above . the hair extension weaving device 125 may be fixedly or releasably attached to a strap 130 worn by a hairstylist on his or her wrist . the weaving device 125 may include a slot member 135 through which thread 140 may be dispensed in a manner substantially similar to the manner described above . in the embodiment shown in fig1 , the weaving device 125 includes an upper lid member 145 that is releasably engageable to a lower body member by a screw - top mechanism . other means for engaging the upper lid member 145 and lower body member 150 to one another are contemplated and foreseeable . the manner in which the thread 140 is used to secure a braid and weft to one another may be substantially similar as set forth above . from the foregoing , it will be seen that the various embodiments of the present invention are well adapted to attain all the objectives and advantages hereinabove set forth together with still other advantages which are obvious and which are inherent to the present structures . it will be understood that certain features and sub - combinations of the present embodiments are of utility and may be employed without reference to other features and sub - combinations . since many possible embodiments of the present invention may be made without departing from the spirit and scope of the present invention , it is also to be understood that all disclosures herein set forth or illustrated in the accompanying drawings are to be interpreted as illustrative only and not limiting . the various constructions described above and illustrated in the drawings are presented by way of example only and are not intended to limit the concepts , principles and scope of the present invention . thus , there have been shown and described several embodiments of a novel hair extension weaving device . as is evident from the foregoing description , certain aspects of the present invention are not limited by the particular details of the examples illustrated herein , and it is therefore contemplated that other modifications and applications , or equivalents thereof , will occur to those skilled in the art . the terms “ having ” and “ including ” and similar terms as used in the foregoing specification are used in the sense of “ optional ” or “ may include ” and not as “ required ”. many changes , modifications , variations and other uses and applications of the present constructions will , however , become apparent to those skilled in the art after considering the specification and the accompanying drawings . all such changes , modifications , variations and other uses and applications which do not depart from the spirit and scope of the invention are deemed to be covered by the invention which is limited only by the claims which follow . | a hair extension weaving device is provided that is able to efficiently attach wefts to braided hair tracks , reducing the time necessary to add hair extensions and prevent both pain and damage to the hair stylist . the hair extension weaving device includes an upper body member and lower body member that may be releasably attached to one another . the upper body member may secure a needle member thereto that is used to sew the weft to the hair track . the lower body member may include a cavity for containing a spool of thread therein that is threaded through the needle member . |
referring now to the drawings , wherein like reference numerals indicate identical or similar parts throughout the several views , fig1 - 23 show a preferred embodiment of the present invention . referring now to fig1 , the large square bale stacker 100 is shown in perspective view . the tongue 110 is used to draw the bale stacker 100 behind a baler equipped with a bale accumulator , as well as behind any source of motive power . a plurality of ground engaging wheels 120 support the stacker 100 and its load . a roller bed 130 , having a plurality of rollers 135 , provides a surface onto which large square bales 400 ( see , for instance , fig4 a ) are slid in organized fashion . transition rollers 115 are attached to the tongue 110 and aid in transferring bales 400 into the bale stacker 100 irrespective of the tongue &# 39 ; s 110 position . a cable lift mechanism 140 is used to raise bales 400 to make room for more bales 400 below . gates 150 , opened and closed by hydraulic cylinders 160 , hold the bales 400 in place until an unloading operation is initiated . the following terms are hereby defined for the purposes of this document , including the claims . an arrow 170 indicates a forward direction . this is the direction of travel when the bale stacker 100 is in use . front is forward - most when the bale stacker 100 is pulled in its forward direction . back or rear is opposite that of the front and behind is defined as in back of or rear of something . left is defined as the left side when viewed from the rear , that is , when an observer is facing in the forward direction . right is defined as the right side when viewed from the rear , that is , when an observer is facing in the forward direction . up or upward is a direction opposing gravity , while down or downward is opposite that of up . in particular , the verb , raise , implies movement in the upward direction while the verb , lower , implies movement in the downward direction . all these terms all have their usual and customary meanings . fig2 a and 2 b depict the adjustable angle , θ , of the bale stacking mechanism 200 . the bale stacking mechanism 200 is pivotable about a pin 220 defining a substantially horizontal axis 340 ( see fig3 a ) by virtue of the hydraulic cylinders 210 . the adjustment of the angle , θ , of the bale stacking mechanism 200 allows the bale stacker 100 to be pulled behind baler accumulators ( not shown ) of varying heights . by adjusting the angle , θ , bales 400 may transition smoothly from the baler into the bale stacker 100 . the frame 300 for the bale stacker 100 features an adjustable position tongue 110 as shown in fig3 a - 3 c . the adjustable hitch makes it possible to pull the bale stacker 100 behind a baler utilizing either a two - or three - bale accumulator . this is because the bale stacker mechanism 200 may be laterally positioned directly behind any set — for instance , a pair — of bales 400 to be transferred from the bale accumulator to the bale stacker 100 as shown in fig4 a - 4 c . lateral positioning is effected by pivoting the tongue 110 about a substantially vertical axis 310 through the actuation of a pair of hydraulic cylinders 320 . note that , here as well as elsewhere in this document , a hydraulic cylinder may be replaced by a pneumatic cylinder , linear electric actuator , screw actuator , etc . the present invention is not limited to hydraulic cylinders . by actuating the cylinders 320 , the tongue 110 is offset , angularly , from a longitudinal axis 330 . the tongue 110 may be shifted left , as shown in fig3 b , or right , as shown in fig3 c , both from a perspective from the rear of the bale stacker 110 . the right and left offsets of the tongue 110 are greater than a minimum required to align with the bales 400 as they are received from the bale accumulator . this is so an operator can adjust how the bale stacker 100 trails the baler and the bale accumulator on a side - hill and when turning . position sensors may be placed on the tongue 110 and programed to follow the motions of the baler to maintain optimal alignment with the bale accumulator . in fig4 a , the tongue 110 of the bale stacker 100 is disposed symmetrically on the bale stacker 100 to be pulled directly behind a hitch on the baler ( not shown ). this provides the narrowest configuration for transport on roads , through gates , etc . in this configuration , none of the bales 400 can enter the bale stacking mechanism 200 , directly . in fig4 b , the bale stacker 100 is shown aligned with a right - offset — that is , the tongue 110 has been shifted left — to permit two of the bales 410 , 420 to enter the bale stacking mechanism 200 . the bale stacker 100 can then be shifted , giving it a left - offset as shown in fig4 c . in this position , the bale stacking mechanism 200 is aligned to allow two more bales 430 , 440 to enter it . details of the bale accumulator are well known to those skilled in this art . a disclosure of a bale accumulator is provided by branson in u . s . pat . no . 5 , 829 , 238 , hereby incorporated in its entirety by reference . the first step in the bale stacking process is depicted in fig5 . the adjustable position tongue 110 is shifted right , aligning the bale stacking mechanism 200 with the two leftmost bales 430 , 440 on the accumulator . the roller bed 130 is in its lowest position , as evidenced by a retracted hydraulic cylinder 510 in the cable lift mechanism 140 . the bale stacking mechanism 200 has been angled back relative to the tongue 110 . no bales 400 are present in the bale stacker 100 . fig6 shows the bale stacker 100 receiving the two leftmost 430 , 440 bales onto the roller bed 130 from the accumulator . the two bales 430 , 440 are disposed in their lowest position in the bale stacker 100 . the hydraulic cylinder 510 is now extended in fig7 indicating the cable lift mechanism 140 has raised the roller bed 130 and the two bales 430 , 440 now residing on the roller bed 130 . the first two bales 430 , 440 are raised to make room for two more bales 400 beneath the first two bales 430 , 440 . fig8 depicts the bale grasping mechanism 810 gripping the now raised first bales 430 , 440 . the first bales 430 , 440 are gripped between two bars or grippers 820 . the adjustable position hitch 110 is shifted left aligning the bale stacker 100 with the two rightmost bales 410 , 420 on the accumulator . in fig9 , the cable lift mechanism 140 is shown returning the now empty roller bed 130 to its lowest position by retracting the hydraulic cylinder 510 . another bale 400 has been received on the bale accumulator . fig1 , the bale stacker 100 receives the two rightmost bales 410 , 420 from the accumulator onto the roller bed 130 . the second two bales 410 , 420 presently reside beneath the first two bales 430 , 440 . a single bale 400 remains on the three - wide bale accumulator . in fig1 and 12 , the bale accumulator again fills , including the third two bales 1110 , 1120 . fig1 shows the cable lift mechanism 140 raising the roller bed 130 and the second two bales 410 , 420 now residing on the roller bed 130 until the second two bales 410 , 420 touch the underside of the first two bales 430 , 440 , being held by the bale grasping mechanism 810 . the bale grasping mechanism 810 releases the first two bales 430 , 440 in its grasp . the first two bales 430 , 440 are now supported by the second two bales 410 , 420 , which continue to lift with the cable lift mechanism 140 and the extension of the hydraulic cylinder 510 . the bale stack residing on the roller bed 130 now contains four bales 400 , two wide by two high . the bale grasping mechanism 810 now grips the second two bales 410 , 420 in fig1 to maintain the entire stack of bales 410 , 420 , 430 , 440 in an elevated position , making room for additional bales 400 under the second two bales 410 , 420 . the roller bed 130 has been returned to its lowest position in fig1 , preparing the bale stacker 100 to receive the third two bales 1110 , 1120 . the third two bales 1110 , 1120 have been received into the bale stacker 100 in fig1 . this completes the stack for the stacker configuration shown in the figures . the next step in the process is to prepare to eject the completed bale stack 1710 from the back of the bale stacker 100 , as shown in fig1 . the hydraulic cylinders 160 for each of the two gates 150 are contracted to open the gates 150 , at which time , the completed bale stack 1710 will eject , as shown in fig1 , under the force of gravity due to the tilt of the bale stacking mechanism 200 . if the angle , θ , is insufficient at the time of the gate 150 opening , or if the bale stacker 100 is facing downhill , the angle , θ , may be increased by extending the hydraulic cylinders 210 . fig1 illustrates the cable lift mechanism 140 for the roller bed 130 in the down position . a slider 1900 is actuated by the hydraulic cylinder 510 , which is retracted in this lowest roller bed 130 position . the fixed length cables 1920 are attached at one end to the roller bed 130 and at the other end to a stationary frame member 1930 . via a system of pulleys 1940 , the cables are disposed downward at the corners of the bale stacker 100 , as best seen in fig2 and 22 . in fig2 , the cable lift mechanism 140 for the roller bed 130 is in its uppermost position . the roller bed 130 is raised as the hydraulic cylinder 510 extends , and the slider 1900 is pushed to its extreme forward position . extending the cylinder 510 increases the distance between stationary frame member 1930 and the slider 1900 . the fixed length cables 1920 move with the slider 1900 and raise the roller bed 130 . fig2 illustrates the bale grasping mechanism 810 . in this figure , the bale grasping mechanism 810 is in its open position , that is , it is not gripping any bales in this position . hydraulic cylinders 2110 are used to actuate the bale grasping mechanism 810 . these hydraulic cylinders 2110 are , here , retracted so the bale grasping mechanism 810 is in its open position . in fig2 , the bale grasping mechanism 810 is shown in rear elevation in its closed position . in the closed position , the hydraulic cylinders 2110 are extended and a set of bales 400 may be gripped . the tongue weight may be adjusted by repositioning an adjustable spindle 2310 , shown in fig2 . the spindle is operatively affixed to a large plate with multiple adjustment holes , permitting the spindle to be disposed in more forward or more rearward positions to alter the balance of the bale stacker 100 . all functions of the bale stacker 100 of the present invention may be automated using feedback from position sensors and a controller area network ( can ) bus system . this will free up the baler operator to concentrate on controlling the baler functions . those skilled in the art will recognize that a wide variety of modifications , alterations , and combinations can be made with respect to the above described embodiments without departing from the spirit and scope of the invention , and that such modifications , alterations , and combinations are to be viewed as being within the ambit of the inventive concept as expressed by the attached claims . | a method of and apparatus for producing stacks of large square bales . bales are received from the baler via a bale accumulator and formed into a stack , a plurality of bales high . the resulting bale stacks may be dropped in the field for pickup later . |
referring now to the drawings , it is seen that the aquarium cleaning system of the present invention , generally denoted by reference numeral 10 , is comprised of a housing 12 that is a hollow tubular member having an open top 14 and an open bottom 16 . advantageously , although not necessarily , the housing 12 , which is made from appropriate material such as plastic , is clear so that a user can visually observe the actions within the housing 12 whenever the aquarium cleaning system 10 is operational . a pair of opposed openings 18 is located on the housing 12 approximately midway up the height of the housing 12 . attached to the bottom 16 of the housing 12 is a base 20 that has a rubber boot 22 encompassing the lower periphery of the base 20 . a series of angled openings 24 are located on the base 20 such that whenever the housing 12 is attached to the base 20 ( which may be simply by friction fitting the housing 12 into the top of the base 20 , or the housing 12 may be adhered to the base 20 ), the housing 12 does not cover these openings 24 . these openings 24 are substantially smaller relative to the openings 18 on the housing 12 . it is understood that the housing 12 and the base 20 can be formed as an integral , even a monolithic unit , however , for ease of manufacture as well as to provide structural rigidity to the aquarium cleaning system 10 , a two section housing 12 and base 20 combination is preferred . a reducing coupling 26 is attached to the top 14 of the housing 12 either via friction fit or via adhesion , etc . a relatively small diameter siphon hose 28 is attached to the reduced distal end of the reducing coupling 26 via an appropriate hose fitting 30 of any appropriate design . one or more valves 32 , either manual or electric ( electric version not illustrated ) with a control button is located proximate the housing 12 . again it is understood that the housing 12 and the reducing coupling 26 can be formed as an integral , even a monolithic unit , however , for ease of manufacture as well as to provide structural rigidity to the aquarium cleaning system 10 , a two section housing 12 and reducing coupling 26 combination is preferred . the base 20 and the reducing coupling 26 may be made from any appropriate material such as plastic , pvc , etc . protruding through each opening 18 on the housing 12 is an inlet tube 34 , each connected to one end of a t - fitting 36 . located on the protruding end of each inlet tube 34 is a screen 38 to help prevent ingestion of large objects into the tubing system of the aquarium cleaning system 10 . attached to the downwardly facing base leg 40 of the t - fitting 36 is a rotator coupling 42 . rotatably attached to the opposing end of the rotator coupling 42 is a spray bar assembly 44 which is basically a t - fitting having a base leg 46 that is rotatably coupled to the rotator coupling 42 ( appropriate seals are provided ( not illustrated ) to help prevent small sand and other particles from entering the connection area , which particles could interfere with proper rotation of the spray bar assembly ) and a pair of extension arms 48 extending outwardly from the base leg 46 . an opening 50 is located on each extension arm 48 , each opening 50 facing in opposite direction relative to the other opening 50 . one or more riser arm assemblies 52 , of any appropriate design , are attached to the aquarium cleaning system 10 , advantageously to the base 20 and to the reducing coupling 26 . the riser arm assemblies 52 provide a retractable riser arm 54 that helps hold the rubber boot 22 of the base 20 off of the bottom b of the aquarium a as more fully explained below . in order to use the aquarium cleaning system 10 of the present invention , the sump of the aquarium a is turned off . the distal end of the siphon hose 28 is positioned into an appropriate fluid receiving vessel 56 located gravitationally below the aquarium a . the valve 32 on the siphon hose 28 is closed . the housing 12 is placed into the aquarium a and positioned over an area to be cleaned with the rubber boot 22 just above the bottom b of the aquarium a . if provided , the riser arms 54 of the riser arm assemblies 52 are extended to help hold the aquarium cleaning system 10 in this position above the bottom b . the valve 32 is opened and a siphon is established via the siphon hose 28 in any appropriate fashion ( purely manually , mechanical assist , electric device assist , etc .,), so that water w flows through the housing 12 , through the reducing coupling 26 and through the siphon hose 28 into the fluid vessel 56 . this water w flow causes the substrate g to be ingested into the housing 12 . sufficient substrate g is so ingested until a bare spot at the bottom b of the aquarium a occurs , which bare spot is slightly larger than the outer diameter of the rubber boot 22 . thereafter , the housing 12 is lowered ( riser arms 54 retracted , if used ) until the rubber boot 22 is sitting on the bare bottom b of the aquarium a . once the rubber boot 22 sits upon the bottom b of the aquarium a , the aquarium cleaning system 10 is sealed to the bottom b at the rubber boot 22 and a suction is formed thereat . as such , water w rushes into the housing 12 via its two openings 18 , the water w flowing through the inlet tubes 34 and into the t - fitting 36 , and down into the spray bar assembly 44 . the water flows out of the two openings 50 on the extension arms 48 of the spray bar assembly 44 with sufficient force to cause the spray bar assembly 44 to rotate about the rotator coupling 42 . the spinning spray bar assembly 44 causes the water exiting the openings 50 to form a vortex causing agitation of the substrate g which is suspended as a slurry , or fluidized bed within the upward flowing water w inside the housing 12 of the device . the interior cross section of the siphon hose 28 is on the order of about 4 - 5 times greater relative to the combined cross sections of the interior of the tubing system of the agitation subsystem ( inlet tubes 34 , t - fitting 36 and spray bar assembly 44 ) in order to achieve sufficient rotation of the spray bar assembly 44 . coincidentally , water w also rushes into the housing 12 via the small openings 24 on the base 20 . these openings 24 are angled so that the incoming water w flow is in opposite direction relative to the vortex created by the water w flowing out of the openings 50 of the spray bar assembly 44 , resulting in a counterflow vortex . these two colliding vortexes cause increased turbulence within the housing 12 and thus increased substrate g particle collisions . such collisions increase the amount of the particulate organic carbon layer that is removed from the surface of the substrate g . after being bled off by collisions with other particles g , excess kinetic energy is then further depleted as the particle g rises inside the more gentle laminar flow in the upper portion of the housing 12 . this slowing of the particle g allows gravity to carry it back toward the bottom of the housing 12 before it can be lost through the reducing coupling 26 at the top 14 of the housing 12 . particulate organic carbon material c , with its lesser specific gravity is then drawn out of the upper portion of housing 12 through the siphon tube 28 and is allowed to flow down to the vessel 56 below the aquarium a for either disposal ( during water - change ) or sedimentation - filtration and return to the aquarium system in a separate step of the substrate cleaning operation . once the aquarium cleaning system 10 has been operational for a sufficient amount of time , say on the order of 30 to 60 seconds or so , the siphon hose control valve 32 is closed , thereby breaking the seal of the base 20 to the bottom b of the aquarium a returning the newly cleaned substrate material g to the bottom of the aquarium a . the aquarium cleaning system 10 is lifted up and moved to a different location within the aquarium a wherein the process is repeated . the user performs several such cleaning iterations until the aquarium a is sufficiently cleaned . if the volume of water w lost in this cleaning process exceeds the amount of water w to be changed then the contents of the vessel 56 in which most of the particulate matter c has settled is siphoned back into the sump of the aquarium a through a fine - mesh filter - bag . new water may be siphoned or pumped into the sump of the aquarium a and the circulation pump is started to refill the aquarium a itself . as seen in fig4 - 6 an alternate embodiment of the aquarium cleaning system of the present invention , generally denoted by reference numeral 110 , is comprised of a housing 112 that is a hollow tubular member having an open top 114 and an open bottom 116 . advantageously , although not necessarily , the housing 112 , which is made from appropriate material such as plastic , is clear so that a user can visually observe the actions within the housing 112 whenever the aquarium cleaning system 110 is operational . a pair of opposing openings 118 is located on the housing 112 approximately midway up the height of the housing 112 . attached to the bottom 116 of the housing 112 is a base 120 that has a rubber boot 122 encompassing the lower periphery of the base 120 . the housing 112 may be attached to the base 120 by simply friction fitting the housing 112 into the top of the base 120 , or the housing 112 may be adhered to the base 120 . it is understood that the housing 112 and the base 120 can be formed as an integral , even a monolithic unit , however , for ease of manufacture as well as to provide structural rigidity to the aquarium cleaning system 110 , a two section housing 112 and base 120 combination is preferred . a reducing coupling 126 is attached to the top 114 of the housing 112 either via friction fit or via adhesion , etc . a relatively small diameter siphon hose 128 is attached to the reduced distal end of the reducing coupling 126 via an appropriate hose fitting 130 of any appropriate design . again it is understood that the housing 112 and the reducing coupling 126 can be formed as an integral , even a monolithic unit , however , for ease of manufacture as well as to provide structural rigidity to the aquarium cleaning system 110 , a two section housing 112 and reducing coupling 126 combination is preferred . one or more valves ( not illustrated for brevity and clarity ), either manual or electric with a control button is located proximate the housing 112 . the base 120 and the reducing coupling 126 may be made from any appropriate material such as plastic , pvc , etc . protruding through each opening 118 on the housing 112 is an inlet tube 134 , each connected to one end of a cross - fitting 136 . located on the protruding end of each inlet tube 134 is a screen 138 to help prevent ingestion of large objects into the tubing system of the aquarium cleaning system 110 . attached to the downwardly facing base leg 140 a of the cross - fitting 136 is a rotator coupling 142 while a second rotator coupling 142 is attached to the upwardly facing base leg 140 b . rotatably attached to the opposing end of each rotator coupling 142 is a spray bar assembly 144 which is basically a t - fitting having a base leg 146 that is rotatably coupled to its respective rotator coupling 142 ( appropriate seals are provided ( not illustrated ) to help prevent small sand and other particles from entering the connection area , which particles could interfere with proper rotation of the spray bar assembly ) and a pair of extension arms 148 extending outwardly from the base leg 146 . an opening 150 is located on each extension arm 148 , each opening facing in opposite direction relative to the other opening 150 such that the openings 150 on the lower spray bar assembly are 180 degrees out of phase relative to the openings 150 of the upper spray bar assembly . one or more riser arm assemblies ( not illustrated for brevity and clarity ), of any appropriate design are attached to the aquarium cleaning system 110 , advantageously to the base 120 and to the reducing coupling 126 . the riser arm assemblies provide a retractable riser arm that helps hold the rubber boot 122 of the base 120 off of the bottom b of the aquarium a as more fully explained below . in order to use the aquarium cleaning system 110 of the present invention , the sump of the aquarium a is turned off . the distal end of the siphon hose 128 is positioned into an appropriate fluid receiving vessel ( not illustrated ) located below the aquarium a . the valve 132 on the siphon hose 128 is closed . the housing 112 is placed into the aquarium a and positioned over an area to be cleaned with the rubber boot 122 just above the substrate g located on the bottom b of the aquarium a . if provided , the riser arms of the riser arm assemblies are extended to help hold the aquarium cleaning system 110 in this position above the substrate g . the valve 132 is opened and a siphon is established via the siphon hose 128 in any appropriate fashion ( purely manually , mechanical assist , electric device assist , etc .,), so that water w flows through the housing 112 , through the reducing coupling 126 and through the siphon hose 128 into the fluid vessel . the housing 112 is then lowered ( riser arms retracted , if used ) until the rubber boot 122 is sitting on the bare bottom b of the aquarium a . during device penetration through the substrate g , the housing 112 can be tilted slightly to help move the substrate g in order to provide a “ clean ” bottom surface for the rubber boot 122 to sit upon . once the rubber boot 122 sits upon the bottom b of the aquarium a , the aquarium cleaning system 110 is sealed to the bottom b at the rubber boot 122 and a suction is formed thereat . as such , water w rushes into the housing 112 via its two openings 118 , the water w flowing through the inlet tubes 134 and into the cross - fitting 136 , and into each of the spray bar assemblies 144 . the water flows out of the two openings 150 on the extension arms 148 of each of the spray bar assemblies 144 with sufficient force to cause each spray bar assembly 144 to rotate about its rotator coupling 142 . as the openings 150 of the lower spray bar assembly 144 are 180 degrees out of phase relative to the openings 150 of the upper spray bar assembly 144 , the two spray bar assemblies 144 rotate in opposite directions relative to one another . each spinning spray bar assembly 144 causes the water w exiting its openings 150 to form a vortex causing agitation of the substrate g . as the two spray bar assemblies 144 each rotate in opposing directions , each produces a vortex of opposite direction relative to the other vortex . these two colliding vortexes cause increased turbulence within the housing 112 and thus increased substrate g particle collisions . such collisions increase the amount of the sediment layer that is removed from the surface of the substrate g . after being bled off by collisions with other particles g , excess kinetic energy is then further depleted as the particle g rises inside the more gentle laminar flow in the upper portion of the housing 112 . this slowing of the particle g allows gravity to carry it back toward the bottom of the housing 112 before it can be lost through the reducing coupling 126 at the top 114 of the housing 112 . particulate organic carbon material c , with its lesser specific gravity is then drawn out of the upper portion of housing 112 through the siphon tube 128 and allowed to flow down to the vessel below the aquarium a for either disposal ( during water - change ) or sedimentation - filtration & amp ; return to the aquarium system in a separate step of the substrate cleaning operation . the interior cross section of the siphon hose 128 is on the order of about 4 - 5 times greater relative to the combined cross sections of the interior of the flow tubes of the agitation subsystem ( inlet tubes 134 , cross - fitting 136 and spray bar assemblies 144 ) in order to achieve sufficient rotation of the spray bar assembly 144 . once the aquarium cleaning system 110 has been operational for a sufficient amount of time , say on the order of 30 to 60 seconds or so , the siphon hose control valve 132 is closed , thereby breaking the seal of the base 120 to the bottom b of the aquarium a . the aquarium cleaning system 110 is lifted up and moved to a different location within the aquarium a wherein the process is repeated . the user performs several such cleaning iterations until the aquarium a is sufficiently cleaned . if the volume of water w lost in this cleaning process exceeds the amount of water w to be changed then the contents of a vessel in which most of the particulate matter c has settled is siphoned back into the sump of the aquarium a through a fine - mesh filter - bag . new water may be siphoned or pumped into the sump of the aquarium a and the circulation pump is started to refill the aquarium a itself . while the invention has been particularly shown and described with reference to embodiments thereof , it will be appreciated by those skilled in the art that various changes in form and detail may be made without departing from the spirit and scope of the invention . | an aquarium cleaning system uses a housing that seals to the bottom of the aquarium . water is siphoned out of the top of the housing into a vessel . as a result of the siphoned off water , additional water enters the housing via a tube assembly wherein a spray bar assembly rotates and discharges water out of a pair of opposing openings , such discharge causing a vortex . a counterflow vortex is created either by a second counterrotating spray bar assembly or via angled inlet jets on the base proximate the rotating spray bar assembly . the colliding vortexes cause substrate within the aquarium to collide and thereby clean itself . lighter waste material is carried out of the housing by the laminar water flow of the siphon with the substrate loosing sufficient kinetic energy from the laminar flow so as to gravitationally settle back toward the base of the housing . |
the present invention comprises a headband 5 with one or more protective inserts 10 . the headband 5 may be made of any suitable material as is known in the art , including cotton , polyester , rayon , nylon , wool , velvet , velour , canvas , leather , neoprene , etc ., and may have elasticity as is known in the art . the inserts 10 may be attached directly to the headband 5 ( e . g ., with tape , velcro , or light glue ), or may be enclosed ( at least partially ) in pouches 15 which in turn are attached directly to the headband 5 . pouches 15 and / or inserts 10 may be emblazoned with team logos , advertising , or other graphics or text . pouches 15 may be permanently attached to the outer or inner surface of the headband 5 ( e . g ., by sewing ), such that there are designated areas for receiving the inserts 10 . pouches 15 may alternatively be attached by velcro , tape , light glue , or other suitable means to allow for quick maintenance , replacement , repair , and even alternating use of graphics for various occasions . likewise , in embodiments without pouches 15 , the surfaces of the inserts 10 to be attached to the headband 5 may be velcro , tape , light glue , or other suitable means , for quick and easy attachment / removal . for example , if the outer surface of the headband 5 is primarily velcro , pouches 15 with mating velcro backings ( or inserts 10 with such backings ) may be precisely positioned as needed , and efficiently replaced during time - outs , on the sidelines between plays , during breaks , or even while actively sporting , such as jogging , cycling , etc . the same applies if the outer surface of the headband 5 has a substantially smooth surface for receiving tape - backed pouches 15 and / or inserts 10 . the inserts 10 are made of a hard yet flexible material , such as polypropylene , plastic , polycarbonate , polyurethane , foam padding , or any combination thereof . the material should be thick enough to absorb a measurable amount of force from impact , yet thin enough to fit securely in the headband pouches 15 and / or mating profiles 35 of a helmet 30 , if applicable . each insert 10 may be a single solid molded , stamped , or extruded piece , or for more flexibility upon impact , may be perforated at one or more locations ( see , e . g ., 20 in fig3 a ), segmented , corrugated , or otherwise constructed of multiple pieces . multiple - piece inserts 10 also allow for the option of using only a portion thereof for a particular pouch 15 , depending on the comfort or other needs of the athlete . each insert 10 may be uniformly thick , or may have varying thicknesses . a typical range of thickness ( either uniformly or variable ) is about 2 mm - 8 mm , 2 mm - 9 mm , or 2 mm to 10 mm , but other ranges are about 2 - mm - 7 mm , 2 mm - 6 mm , 2 mm - 5 mm , 2 mm - 4 mm , 2 mm - 3 mm , 3 mm - 8 mm , 3 mm - 7 mm , 3 mm - 6 mm , and 3 mm - 5 mm , 3 mm - 4 mm , 4 mm - 8 mm , 4 mm - 7 mm , 4 mm - 6 mm , and 4 mm - 5 mm . the thickest portion of an insert 10 may be as thick as 10 mm or even 20 mm , especially if the insert 10 includes a padded portion . each insert 10 may be substantially flat , or may be curved ( i . e ., have a degree of concavity ) to substantially conform to the shape of the corresponding portion of the athlete &# 39 ; s head against which the insert 10 will lie . such shapes may be standard , customized for a particular athlete , and / or come in various sizes corresponding to various size headbands 5 . the inserts 10 may be aerated as shown at 25 in fig3 b , to allow for easier evaporation of sweat . additionally and / or alternatively , the inserts 10 may have a rough or coarse surface such as ridges , bumps , sandpaper texture , etc ., as a friction element to help keep the headband 5 in place . a preferred embodiment of the headband 5 does not cover the top of the head , i . e ., like a baseball cap , helmet , or beanie hat would . this provides for better comfort ( especially on hot days ) and style ( especially when used without a helmet ). if the headband 5 has pouches 15 , however , the pouches 15 should be positioned so the inserts 10 therein at least partially cover at least two of the following regions of the athlete &# 39 ; s head when worn : the frontal ; left parietal ; right parietal ; left sphenoidal ; right sphenoidal ; left temporal ; right temporal ; and occipital . in one embodiment , the headband 5 includes pouches 15 positioned so the inserts 10 therein at least partially cover each of the frontal , two parietal , two sphenoidal , two temporal , and occipital regions of the athlete &# 39 ; s head . typically , the headband 5 may be worn underneath a helmet 30 as seen in fig6 . in such instances , the athlete may opt to include only some of the inserts 10 depending on the athlete &# 39 ; s needs . for example , an athlete may prefer to include only the occipital insert to guard against an extra vulnerable injury due to a recent injury in the same area . or a soccer player may prefer to include only the frontal insert since most of contact with his or her head during a typical game will be at the frontal area of his or her head . in one embodiment of the present invention , the headband 5 may be attachable ( and detachable ) from a helmet 30 , or may be attached to the helmet 30 using friction gel , tape , buttons , snaps , latches , velcro , laces , elastic bands , or other means , or any combination thereof . similarly , the headband 5 or portions thereof may be aligned to mate with mating profiles 35 such as slots , recesses , cavities , indents , notches , etc ., on the inside of the helmet , as seen e . g ., in fig4 . doing so could facilitate a snug fit with the helmet 30 without requiring the headband 5 to be physically attached to the helmet 30 . typically the alignment should coincide with one or more of the protective inserts 10 . in some embodiments , the headband 5 may be both attached to the helmet 30 , and mated with profiles of the helmet 30 . another embodiment of the present invention includes a headband 5 as described above , with a top portion 40 that covers the top of the head . the top portion 40 may include a protective insert 10 as well , and this insert 10 may be shaped to cover the top portion of the head . in this embodiment , the headband 5 may be one - piece or two - piece . in the one - piece embodiment as seen in fig7 , the headband 5 has an integrated top portion 40 , either with or without a pouch or pouches 15 . in the two - piece embodiment as seen in fig8 , the top portion 40 is separate from the rest of the headband 5 ( again with or without a pouch or pouches 15 ), and may be attachable / detachable by buttons , snaps , velcro , tape , tabs / slots , glue , or any other suitable means ( not shown ). although particular embodiments of the present inventions have been shown and described , it will be understood that it is not intended to limit the present inventions to the preferred embodiments , and it will be clear to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the present inventions . thus , the present inventions are intended to cover alternatives , modifications , and equivalents , which may be included within the spirit and scope of the present inventions as defined by the claims . | a headband with one or more protective inserts . the inserts may be strategically positioned to provide protection for specific areas of a person &# 39 ; s head that are most vulnerable to impact , depending on the sport or other activity . the inserts may be directly attached to the headband , or may be enclosed in pouches which are directly attached to the headband . the headband may be worn with or without additional headgear , and may be configured to cooperate with the additional headgear as to form , fit , and functionality . |
following is a description by way of example only and with reference to the accompanying drawings of a manner of constructing and using the cushioning shoe inserts . example embodiments are provided to fully convey the scope of this disclosure to those skilled in the art . the present disclosure may have additional embodiments , may be practiced without one or more of the details described for any particular described embodiment , or may have any detail described for one particular embodiment practiced with any other detail described for another embodiment . numerous specific details are set forth as examples and are intended to provide a thorough understanding of embodiments of the present disclosure . it will apparent to one skilled in the art that these specific details need not be employed , that example embodiments may be embodied in many different forms , and that neither should be construed to limit the scope of the disclosure . in some example embodiments , well - known processes , well - known device structures , and well - known technologies are not described in detail . referring now to the drawings , fig1 - 5 illustrate various views of a cushioning shoe insert 10 in accordance with a first embodiment of the present disclosure . the cushioning shoe insert 10 includes a pad 12 having an inner surface 14 and an outer surface 16 . the cushioning shoe insert 10 may include one or more layers of adhesive 18 disposed over at least a portion of the outer surface 16 wherein the adhesive layers 18 are each covered by a flexible nonstick cover 20 having a tab 22 attached thereto . in some embodiments , there may be a single tab 22 attached to one or more flexible nonstick covers 20 whereas in other embodiments there may be one tab 22 for each flexible nonstick cover 20 . the tab ( s ) 22 is ( are ) configured to protrude from an inner portion of a shoe 21 such that a user may pull upon the tab ( s ) 22 thereby exposing the layers of adhesive 18 while the cushioning shoe insert , and more particularly the pad 12 , is maintained at an optimal location . the pad 12 may be made of low - resilience polyurethane , heat sensitive viscoelastic closed - cell polyurethane , any other type of foam or memory foam , gel , or any another suitable material for use as a cushioning shoe insert . preferably , the pad 12 is memory foam . the pad may further comprise one or more antimicrobial agents and one or more absorbent layers such as , for example , nonwoven fabric . if such an absorbent layer is included in any particular embodiment , it is preferably adhered to the inner surface 14 of the pad 12 as a lining element for increased comfort . as can be seen in fig2 - 5 , it is an intended purpose of the shoe insert disclosed herein to enable a user to insert the shoe insert into a shoe prior to exposing the layers of adhesive 18 . enabling a user to insert the shoe insert 10 into a shoe prior to exposing the layers of adhesive 18 quite clearly will enable the user to insert and remove the shoe insert 10 any number of times without compromising the integrity or adhesive capabilities of the layers of adhesive 18 . thus , a user is empowered with the ability to place the shoe insert 10 into an inner portion of a shoe 21 along with one of the user &# 39 ; s feet in order to determine what , if any , customization of the shoe insert 10 will be needed . for example , a user may wear the shoe insert 10 as she normally would with the exception of the layers of adhesive 18 being non - exposed , and then adjust the shoe insert 10 until it is in an optimal location , and then mark one or more portions of the shoe insert 10 , e . g . the pad 12 , for trimming , and subsequently remove the shoe insert 10 from the inner portion of the shoe 21 and trim the pad 12 . continuing with this example , the user may then re - insert the shoe insert 10 into the shoe , with the layers of adhesive remaining non - exposed ( i . e . covered by the flexible nonstick covers 20 ), re - adjust the shoe insert 10 into an optimal location , and finally pull upon each tab 22 thereby peeling off the flexible nonstick cover 20 from the layers of adhesive 18 . fig3 illustrates the first embodiment of the shoe insert 10 after the user has removed one of two flexible nonstick covers 20 exposing the layer of adhesive 18 which thus adheres the shoe insert 10 to the inner portion 21 of the depicted shoe . with particular reference to fig4 - 5 , the side cross - sectional views taken along the line a - a of fig2 illustrates various features of the cushioning shoe insert 10 and , more particularly , illustrates the preferred embodiment for attaching the tab ( s ) 22 to the flexible nonstick covers 20 . as used herein , distal refers to further from the body and proximal refers to closer to the body . as can be seen , the tab ( s ) 22 attach to the flexible nonstick cover ( s ) 20 at generally the distal most region of the flexible nonstick cover 20 . as the user pulls upon the tab 22 , the flexible nonstick cover 20 is peeled off generally along a fold region 28 which moves generally in the direction of distal to proximal ( as indicated by the arrow labeled 29 in fig5 ) until the nonstick cover 20 is completely removed and can be discarded appropriately . as can be seen with particular clarity in fig5 , in some embodiments the tab 22 and flexible nonstick cover 20 features are comprised within a single material , e . g . a single sheet of peel off backing may be used to as accomplish both features . in such embodiments , the material may be folded such that a single continuous surface of the material comes into contact with itself thereby defining the boundary between the flexible nonstick cover 20 , which is the portion of the peel off backing in contact with any portion of a layer of adhesive 18 , and the tab 22 . suitable peel off backing materials will be sufficiently tear resistant to allow for the user to remove the material notwithstanding the material being essentially squeezed between the inner portion of the shoe and the pad 12 . the suitable peel off backing materials will be one or more flexible sheets 23 which preferably comprise at least one release surface ( not labeled in figs .). the release surface may comprise either silicone or polytetrafluoroethylene or any other suitable material , many of which are well known in many arts . as used herein , the term release surface intended to refer merely to the topology of the flexible sheet and is not to be interpreted as requiring discrete layer over the flexible sheet material . while in a preferred embodiment the flexible sheet 23 is coated with silicone , in other embodiments the material of the flexible sheet itself comprises sufficient topological characteristics to serve independently as the non - stick layer . in preferred embodiments , the pad 12 includes at least a lower portion 30 for cushioning a plantar region of a foot , a front region 32 for cushioning a distal region of a foot ; and an upper portion 34 for cushioning a dorsal region of a foot . most preferably , the pad 12 additionally includes an inner portion 31 for cushioning a medial region of a foot and an outer portion 33 for cushioning a lateral portion of a foot . as used herein , medial means towards the center line of the body and lateral means away from the center line of the body . in some embodiments , the lower portion 30 extends generally from past a distal most portion 36 of a user &# 39 ; s foot to slightly more proximal than a metatarsal region 38 of a user &# 39 ; s foot and is intended to generally spread out vertical forces over the plantar region of a foot . in some embodiments , the front portion 32 generally fills in inner portion 21 of a shoe , wherein the inner portion 21 would otherwise be left generally void in the absence of the cushioning shoe insert 10 . for example , typically when a woman wears pointed women &# 39 ; s fashion shoes her toes do not fill the entire front inner portion 21 of the shoe which results in a relatively small area of the woman &# 39 ; s foot coming into contact with the top line 44 of the shoe . moreover , a typical women &# 39 ; s fashion shoe includes a high heel 46 causing a steep slope 48 down which the user &# 39 ; s foot tends to slide thereby causing the relatively small area of the woman &# 39 ; s foot in contact with the top line 44 to experience high pressures which often result in blistering or bunions or both . with the inclusion of the front portion 32 the forces normally concentrated along the top line 44 are transferred , at least partially , to the portion of the user &# 39 ; s foot contacting the inner surface 14 of the front portion 32 . the upper portion 34 is preferable for similar reasons to the front portion 32 in that both reduce the amount of pressure concentrated along the top line 44 . referring particularly to fig2 - 3 , it can be seen here that although the pad 12 does not extend past the top line 44 of the shoe in the illustration the tabs 22 are sized such that a user would easily be capable of scribing the outer surface of the pad 12 adjacent to the top line 44 such that the pad 12 can be accurately customized for a specific shoe if such customization were needed , e . g . if the pad 12 extended past the top line 44 over the users foot . in some embodiments , the tabs 22 comprise an accordion like sequential fold structure allowing the entire tab 22 to be folded down flat without protruding out of the inner portion of the shoe 21 whilst a user scribes the outer surface of the pad 12 . in other embodiments , including the one shown in fig1 - 5 , a user may also simply fold the tab forward over the front or distal region of the foot as opposed to backward such that the tab does not block the user from scribing any portion of the outer surface of the pad . referring particularly to fig4 - 5 , it can be seen that the upper portion 34 for cushioning a dorsal region of a foot is of generally constant thickness . however , in many embodiments the thickness of this portion will vary substantially . preferably , the most distal part of the upper portion 34 will have a larger thickness than the more proximal part of the upper portion 34 . most preferably , the upper portion comprises a maximum thickness generally above the toes region which then tapers into a thinner constant thickness area over the top of the foot proximal of the toes . the constant thickness area is preferably between roughly 1 - 3 millimeters so that this area can be trimmed just distal from the top line 44 without created a visible gap between the upper foot and the top line 44 . a second embodiment of the shoe insert 60 is illustrated in fig6 - 8 . this embodiment comprises a pad 62 having an inner surface 64 configured for cushioning a foot and an outer surface 66 for attachment to an inner portion of a shoe 68 . moreover , this embodiment comprises one or more layers of adhesive ( not shown ) covered by one or more flexible nonstick covers ( not shown ) and a means ( not shown ) for removing the flexible nonstick cover while the pad 62 is compressed against the inner portion of the shoe 68 . the means ( not shown ) may comprise a peel off backing material in accordance with the first embodiment . alternatively , it may comprise a solution in which the nonstick cover is not folded but rather slides off of the adhesive when pulled upon . the second illustrated embodiment , preferably , comprises a foot chock 76 which protrudes generally upwardly from the inner surface 64 and provides support to a metatarsal region of a foot . as used herein , metatarsal refers generally to the region of the foot below the metatarsal bones or just distal of the metatarsal bones . in the preferred embodiment , the foot chock 76 is located just forward of the metatarsal heads of the foot such that support is provided directly to the metatarsal heads from the foot chock 76 thereby reducing the pressure on the toe region of the foot at or near the opening of the shoe . the principle of the foot chock 76 is similar to that of the commonly known tire chock which is simply a wedge or block placed against a tire object to prevent it from moving . as shown in fig7 , the foot chock 76 may be configured to generally fill the volume 79 under the location where a user &# 39 ; s toes meet the rest of the foot . due to the already discussed problem of a shoe wearer &# 39 ; s toes often being jammed into the inner portion of a shoe , it is easily recognizable that the foot chock 76 , by supporting the foot at a location more proximal than the toes , will reduce the pressure and discomfort experienced by a shoe wearer . especially when a type of shoe or activity causes the user &# 39 ; s foot to be forced toward or into the front of the shoe , e . g . sliding down a high heel and being jammed into the front of the shoe . a third embodiment of the shoe insert 80 is illustrated in fig9 - 11 . this embodiment comprises a pad 82 having an inner surface 84 and an outer surface 86 . as illustrated , the pad 82 of this embodiment might not comprise an inner portion for cushioning a medial region of a foot and an outer portion for cushioning a lateral portion of a foot . there are at least two reasons why the shoe insert 80 might exclude an inner portion and an outer portion . first , this enables the shoe insert 80 to be constructed simply by cutting a shape out from a flat sheet of pad material and then fold the flat shape into a shoe insert shape 80 so as to create at least a lower portion 88 for cushioning a plantar region of a foot , a front portion 90 for cushioning a distal region of a foot ; and an upper portion 92 for cushioning a dorsal region of a foot . fig9 illustrates a “ blank ” of such a material having been cut out from a flat sheet of material . second , because many shoes , and especially women &# 39 ; s fashion shoes , have pointed toe regions and therefore narrow toe regions , it may be preferable to maximize space around the sides of the user &# 39 ; s foot to decrease pressures . this third embodiment may also comprise one or more layers of adhesive 94 disposed over at least a portion of the outer surface 86 of the shoe inset 80 , the adhesive 94 being covered by a nonstick cover 96 . as in other embodiment , the nonstick cover 96 is easily removed by pulling upon a tab 98 . the nonstick cover may be exposed while the shoe insert is within an inner portion of a shoe 100 with or without a user &# 39 ; s foot . while preferred and alternate embodiments have been illustrated and described , as noted above , many changes can be made without departing from the spirit and scope of the cushioning shoe insert . accordingly , the scope of the cushioning shoe insert is not limited by the disclosure of these preferred and alternate embodiments . instead , the scope of the cushioning shoe insert should be determined entirely by reference to the claims . | this application discloses shoe inserts which are configured such that a user may expose one or more adhesive layers while the cushioning shoe insert is maintained at an optimal location within a shoe , thereby securing the cushioning shoe inserts precisely at the optimal location . moreover , this application discloses shoe inserts which are designed to distribute necessary support forces , e . g . through a foot chock , thereby mitigating or eliminating uncomfortable levels of localized pressure . |
as shown in fig1 a preferred embodiment of the invention comprises a self - contained vibrator and data storage unit 1 which is about 4 inches long , 3 . 5 inches wide , and 0 . 5 inches thick , which may be hand - held . for convenience , and to prevent loss during sleep , the unit 1 is provided with a strap loop 2 through which the hand 3 is slipped so as to hold the unit firmly in the palm of the hand . a response button 4 , such as a spring loaded micro switch , is conveniently located at one end of the unit so that it can be readily activated by the thumb 5 . it will , of course , be appreciated that the location and design of the response button is merely a matter of design choice and numerous alternatives will be readily apparent to those skilled in the art . as shown in fig2 the housing 1 contains a power source for a patient response sensor 11 , a timing circuit 7 , an electro tactile vibrating unit 8 ( such as a tactile vibrator , supplied by audiological engineering corp ., summerville , mass .) and a microprocessor 9 , which is provided with a signal output 10 which should be compatible with a computer interface . the power source 6 is conveniently , but not essentially , a conventional long - life dry cell which provides sufficient power to operate the timing circuit , the vibrator and the microprocessor . it will be appreciated that while preferred , it is by no means essential that power source 6 be internal to unit 1 . an external power source with appropriate lead in wires is also within the scope of this invention . the vibrator 8 is preferably an electro tactile vibrator which provides a 20 - 40 hz bandwidth at the selected frequency of 160 - 200 hz and preferably 180 hz . the timer may be set to trigger the vibrator on either a random basis or , more usually , on a timed basis of the order of a 0 . 5 second pulse every 5 - 10 minutes . the vibrations are of sufficiently low amplitude that they are unlikely to provoke any sleep disturbance in a sleeping patient . the time of each vibratory event whether or not the patient makes a response to that event and the time taken to make that response may be recorded in the microprocessor data storage device . the stored data may be recovered for later analysis using a conventional computer interface . twelve healthy , volunteer , young , female subjects who were medication free were recruited to compare the vibratory stimulus unit to standard polysomnographic monitoring during a single night of sleep monitoring . before going to sleep the subjects had electrodes attached as described above for electrophysiological monitoring : the resulting sleep records were scored according to standard criteria . they then had the vibratory stimulus device 1 described above fitted to their preferred hand . the subjects were instructed to sleep normally and press switch 4 whenever they felt a vibratory stimulus . the stimulus was a 180 hz vibration administered with a maximum peak - to - peak output of 1150 mv for 0 . 5 seconds at an average inter - stimulus interval of 7 . 5 minutes . a polysomnographic recording classifies sleep in several stages systematized by an international committee ( recht - schaffen & amp ; kales , 1968 . &# 34 ; a manual of standardized terminology , techniques and scoring system for sleep stages in human sleep subjects . brain information service / brain research institute , los angeles ). the major characteristics are summarized in table 1 . table 1______________________________________table of the major characteristics of the stage of sleepstage major characteristics______________________________________awake alpha activity and / or low voltage , mixed frequency eeg . stage 1 relatively low voltage , mixed frequency eeg . highest voltage is about 50 - 75 μv and tends to occur in bursts mostly towards the latter position of the stage . stage 2 defined by the presence of sleep spindles and / or k complexes and the absence of sufficient high voltage , slow activity to define slow wave sleep . stage 3 . sup . b a record in which at least 20 % of the epoch con - sists of waves of 2 cps . sup . a or slower and ampli - tudes greater than 75 μv peak - to - peak . stage 4 . sup . b an eeg record in which more than 50 % of an epoch consists of waves of 2 cps . sup . a or slower and with amplitudes greater than 75 μv peak - to - peak . rem the appearance of low voltage , mixed frequency eeg activity , and episodic rapid eye movements ( rems ). mt a record in which at least 50 % of a page ( corres - ponding to 30 seconds ) is characterized by an increase in emg activity . ______________________________________ . sup . a cycles per second . sup . b stages 3 and 4 are commonly referred to as slow wave sleep ( sws ) the correspondence between behavioural and polysomnographic definitions of sleep onset was assessed by comparing mean differences among a number of different polygraphic and and behavioural definitions of sleep onset . both the behavioural and physiological definitions of sleep onset are presented in table 2 . table 2______________________________________table of physiological and behavioural definitionsdefinition definition of sleep onset______________________________________physiological1 first epoch of stage 12 first epoch of stage 1 leading to stage 23 first epoch of stage 24 first epoch of stage 2 followed by & gt ;= 8 min . sleep in next 10 min . 5 first minute of stage 2 followed by & gt ;= 8 min . sleep in next 9 min . behavioural6 first missed response7 two consecutive missed responses______________________________________ the criterion of the first missed response to the vibratory stimulus was chosen as an intuitively plausible measure of behaviourally defined sleep onset . similarly , two consecutive missed responses was chosen to identify the onset of a consolidated sleep period . the polysomnographic criteria were selected to include a variety of definitions employed in the existing literature . briefly , these definitions range from the least stringent criterion of the appearance of the first epoch of stage 1 to a more stringent consolidated criterion requiring the subject to have entered the first minute of stage 2 sleep that is followed by nine consecutive minutes of sleep ( stage 2 , 3 , or 4 ) interrupted by no more than one minute of awake . lying somewhere in the middle is the most widely used definition of sleep onset , that is the appearance of the first epoch of stage 2 sleep . these definitions may be roughly grouped into those requiring little or no consolidation ( 1 - 3 ) and those requiring a definite degree of consolidation ( 4 and 5 ). mean sleep onset latencies corresponding to each of the behavioural and physiological definitions are presented in fig3 . sleep onset latencies defined by the seven criteria were compared in an analysis of variance in which the definition of sleep onset was extracted as a within subjects factor . a significant effect of definition was found ( f ( 6 , 66 )= 8 62 ; p & lt ; 0 . 0013 ). as can be seen in fig3 this was due mainly to differences between the mean latency defined by the physiological criterion of the first appearance of stage 1 and the two consolidated sleep onset latency definitions and both of the behavioural definitions of sleep onset latency . statistical analysis indicates that the estimates of sleep onset latency provided by the vibratory stimulus device do not differ significantly from those provided by the consolidated physiological definitions of sleep onset . this suggests that the behavioural criteria define consolidated sleep and can serve as accurate indicators of the onset of polygraphically defined consolidated sleep . the mean percent of stimuli responsed to in each sleep stage is illustrated in fig4 . as anticipated , the highest level of responding was seen in wakefulness ( aw ). during sleep a higher level of responding occurred in the ` lighter ` stages of sleep ( stage 1 and stage 2 ), while little or no responding was seen in the ` deeper ` stages ( stages 3 and 4 ). an intermediate level of responding was found during rem sleep . the relationship between the behavioural measure and polysomnographic recording was also examined by correlating the total percent responding of the subjects with various polygraphic measures of sleep . these correlations are presented in table 3 . over the whole night , a significant correlation was found between behavioural responding and both total sleep time ( r ( 10 )=- 0 . 777 ; p & lt ; 0 . 003 ) and sleep efficiency ( r ( 10 )=- 0 . 819 ; p & lt ; 0 . 001 ). thus , those subjects who responded more frequently during the night slept significantly less than subjects who responded less frequently , and their sleep efficiency ( calculated by dividing the total sleep time by the total recording time and multiplying by 100 ) was also significantly reduced . table 3______________________________________table of pearson product moment correlation between meanpercent responding and sleep variablessleep variable r p______________________________________total time recorded ( ttr ) 0 . 298 n . s . total sleep time ( tst ) - 0 . 777 & lt ; 0 . 003sleep efficiency ( se ) - 0 . 819 & lt ; 0 . 002sleep onset latency ( sol ) 0 . 568 n . s .% awake ( peraw ) 0 . 838 & lt ; 0 . 001 % stage 1 ( per1 ) 0 . 727 & lt ; 0 . 01 % stage 2 ( per2 ) - 0 . 747 & lt ; 0 . 006 % stage 3 ( per3 ) - 0 . 371 n . s .% stage 4 ( per4 ) - 0 . 250 n . s .% rem ( perrem ) - 0 . 682 & lt ; 0 . 05 % mt ( permt ) 0 . 117 n . s . rem latency ( reml ) 0 . 614 & lt ; 0 . 05no of rem periods ( nremp ) - 0 . 463 n . s . shifts to awake ( shaw ) - 0 . 672 & lt ; 0 . 02shifts to stage 1 ( sh1 ) 0 . 501 n . s . shifts to mt ( shmt ) 0 . 146 n . s .% sws ( persws ) - 0 . 593 & lt ; 0 . 05shifts to aw + 1 + mt ( shaw1mt ) 0 . 664 & lt ; 0 . 02______________________________________ mean percent responding over the night was also correlated with the different stages of sleep . it was found that , in general , wakefulness ( r ( 10 )= 0 . 838 ; p & lt ; 0 . 0007 ) and stage i ( r ( 10 )= 0 . 727 ; p & lt ; 0 . 008 ) correlated positively with behavioural responding , while ` deeper ` stages of sleep ( stages 3 and 4 ) correlated negatively . this suggests that the more frequently subjects responded , the more time they spent awake and in stage 1 , and the less time they tended to spend in sws ( r ( 10 )= 0 . 592 ; p & lt ; 0 . 05 ). the amount of time spent in stage 2 sleep was also found to be significantly correlated with percent responding ( r ( 10 )=- 0 . 746 ; p & lt ; 0 . 005 ). subjects who responded with greater frequency to the stimulus spent significantly less time in stage 2 sleep . a significant correlation was also found between mean percent responding and shifts to awake ( r ( 10 )= 0 . 672 ; p & lt ; 0 . 02 ), indicating that more frequent responding was associated with more shifts to awake . a significant negative correlation was also found between mean percent responding and percentage of rem sleep ( r ( 10 )=- 0 . 682 ; p & lt ; 0 . 01 ). subjects who responded more often to the vibratory stimulus had significantly less rem sleep than those subjects who responded less frequently . finally , percent responding was found to be significantly correlated with rem latency ( r ( 10 )= 0 . 614 ; p & lt ; 0 . 03 ), which is defined as the interval of time between sleep onset and the beginning of the first rem period . thus , rem latency was significantly longer for those subjects who responded more frequently to the vibratory stimulus . it is evident that a substantial relationship exists between sleep assessed behaviourally and polygraphically . although the parameters of the stimulus presentation were chosen so as to minimize the possibility of disturbing the subjects &# 39 ; sleep , the extent to which sleep might differ from that usually experienced was assessed in two ways : by examining the subjects &# 39 ; subjective appraisal of their experience and their polysomnographically defined sleep . it is generally known that sleeping in a new environment produces a ` first night effect `, that is sleep may be more disturbed than that which occurs in an environment which is familiar . in the morning subjects were asked a number of questions to obtain information on their own experience during the study . on average subjects estimated that they experienced 8 vibrations a night while , in fact , they received an average of about 50 per night . half the subjects indicated that their sleep was the same as a ` normal ` night &# 39 ; s sleep at home and half indicated that it was worse , a finding that it is typically obtained after the first night in a sleep laboratory . a number of polygraphic parameters were compared with a sample of approximately the same age who were also spending their first night in the laboratory but who were allowed to sleep undisturbed . the results indicated differences in stage 1 , stage 2 , slow wave sleep ( stages 3 and 4 ) and movement time . overall the degree of disturbance averaged slightly over 4 percent of the total night &# 39 ; s sleep . overall , by both subjective and polygraphic criteria , the sleep of the subjects was disturbed to some degree by the vibratory units . however , the amount of disturbance appears to be quite small and insufficient to invalidate the general conclusions regarding the efficacy of this device . | a vibrating stimulus - response device and method to monitor sleep behaviour is described . the self - contained portable device can be used in a home environment as a preliminary screen before a more extensive polysomnographic examination . |
fig1 shows a screen image from a game show having a display with an underlying image . the title of the game , e . g ., “ 60 $ econd millionaire ” optionally involves a time limit and a time display . as shown , the time displayed is 45 seconds . an underlying image is obscured by one or more overlying images . as shown in fig1 , a 5 × 5 array of overlying obscuring images obscures the underlying images . as shown , there are three pairs of initials , at in the upper left hand corner of the array , ct in the first row , third column and ht in the second row , third column . as the caller is presented with questions , they may answer and , if their answer is correct , the overlying obscuring piece corresponding to that answer or question is then removed , thereby reviewing the underlying image in the region where the overlying obscuring portion had previously been presented . various interactive game show formats and methods for game play are provided . in one embodiment , a second or ancillary game is played in parallel with a first or primary game . by way of example , in association with a first game comprising a lottery number ball draw , a second game may involve a selected player &# 39 ; s guessing whether the next ball draw will be of a higher or lower number , or odd or even or the like . various aspects of enhanced game play and novel game are disclosed . in a first aspect , the game play method and system provides for the playing or running of a parallel game or ancillary game along with a first or primary game . for example , during the real time ball draw for a lottery , the improved game play would involve running a parallel or ancillary game along with the ball draw . one implementation would involve a first ball draw , followed then by game play by a contestant such as predicting whether the next ball drawn would be of a higher or lower number , or would be odd or even . in one implementation , the master of ceremonies would advise the player which of these options had a better probability of being the outcome , thereby making the ancillary game more a game of chance as opposed to a game of skill . optionally , scoring may be done , such as where one player or audience participant is scored or ranked relative to another player or participant . in yet another aspect , the game play includes the use of contestant game play to determine lottery numbers . for example , a contestant may be blindfolded or otherwise be made unable to see various options . the person then selects from among the various options as the means by which the random lottery numbers are drawn . one example could comprise a blindfolded contestant selecting objects . in yet another aspect , this invention relates to an interstitial game show . main or regular programming , such as is broadcast on a given evening during prime time on a broadcast network would additionally include multiple interspersed , typically short , segments relating to game play . in the preferred embodiment , the game play would be for a relatively short period of time , for example , 1 to 2 minutes . for example , at 8 : 00 an initial round may be played prior to the beginning of prime time programming . normal programming would then resume through the remainder of the 8 : 00 hour . at 9 : 00 , a second short segment may be played . the play may continue at later times , such as to culminate at a show at 11 : 00 . preferably , the short segments would not necessarily be shown at a predetermined or predeterminable time as far as the audience was concerned . in that way , viewers who wish to see the progression of the game segments would need to continue viewing that channel , or at least , return to the channel fairly frequently . optionally , the game play may be progressive from one interstitial game segment to another . players may be presented with the option of stopping play or continuing . in yet another game format , the show would include a display having an underlying image , with that image being at least partially obscured by overlying image regions which differ from the underlying image region . a contestant would be given a time limit in which they would be presented with information relating to a suggestion or a clue relating to an overlying image region , which if the player responded correctly , would be removed so as to reveal that portion of the underlying image which was below the overlying image . the suggestion or clues may be related to the underlying image or may merely be unrelated suggestions or clues with respect to that particular overlying image region . yet another embodiment of game play provides for the repurposing of an existing taped game show . the previously recorded game show would be segmented into subsets of issues , for example , presentation of questions or answers ( as in the case of jeopardy ), those issues would be presented to one or more players , a response would be received from those players , and the answer would be compared to the correct answer . scoring would then rank players relative to one another or to indicate the amount of the prize . in yet another game play implementation , one or more contestants would be presented with multiple images upon which predetermined data had been assembled . for example , images of five actresses may be presented to the player and the associated data would comprise opinion polling information as to whom the audience thought was the most attractive . the players would then play against each other to eliminate the images which they believe do not correspond to the most popular or number one response . the players would alternate until one player remained . in a second round , individual play , as opposed to play between contestants is utilized . again , the player attempts to eliminate those answers which were other than the most popular answer of the audience . in yet another aspect of enhanced game play , audience participation via an interactive video display , such as a computer connected over the internet , or via an interactive television arrangement , may participate in the program . the following comprises a detailed description of one implementation of a weekly game show utilizing various inventive aspects described herein . fig3 shows a depiction of a possible set for the game show . generally , two contestants and a master of ceremonies ( mc ) are placed at podiums . large displays are provided on the set such that the in - studio audience may view the images . optionally , the players may be additionally provided with monitors or other displays to aid in their viewing of the images . a display may be provided , such as to show the amount of money then available to be won , or to display other data , such as the number of participants still remaining . such would be useful where there is significant audience participation , or participation by others via the internet or other computer based network . each week the show starts out with the introduction of the two contestants that will compete against each other and eventually have a chance to win , perhaps , the largest game show jackpot in television history . we have thousands of telephone players that are also competing from home for their share of the money . these players have all called our telephone number during the week , and qualified to play on the program . on stage is a readout that shows the prize money building up , even during the broadcast . the phone players that remain in the game until the end of the show are patched in “ live - on - tape ” and have a shot at the money . for this example , let &# 39 ; s assume that 25 , 000 people have qualified to participate in this week &# 39 ; s show and the jackpot is up to $ 1 . 6 million . the object of the studio game is to be the first player to reach $ 25 , 000 dollars . that player will go on to the end game for a chance to win thousands more , and perhaps hit the big jackpot ! the first round starts with the in - studio players being asked an opinion question with 5 possible answers . each of the 5 answers is displayed on a large video wall in a semi - circle onstage which creates the backdrop of our set . the first question is worth $ 1 , 000 dollars to the winner . for example : sandra bullock , elizabeth hurley , catherine zeta jones , julia roberts , nicole kidman . the phone players vote for their favorite answer . the in - studio players take turns trying to eliminate the answers that they think are not the number 1 answer . the game is quite simply a kind of reverse “ family feud .” if a player mistakenly picks the number 1 answer , the opposing player will receive the $ 1 , 000 dollars . additionally , if a player can successfully pick the last answer , leaving the number one answer , that player will receive the $ 1 , 000 dollars . the phone players who selected the number 1 answer are still in the game , and the others are eliminated . the studio players are shown another question worth $ 2 , 000 dollars and play continues in the same manner as before . six questions in total are asked in the first round with the value going up by $ 1 , 000 dollars each time . the phone players are gradually whittled down to a few thousand by the end of the six questions . this time the questions are played individually by a player instead of alternating between players . the player that is behind goes first . as before , a player must eliminate everything but the number 1 answer . for the first question , we stake a bank with $ 1 , 000 dollars . every successful elimination will add $ 1 , 000 dollars to the bank . if the player eliminates every answer but the number 1 answer , they receive the money that has been built up in the bank . at any point the player mistakenly picks the number 1 answer , his / her opponent will get the money in the bank . the 2 nd question starts with a $ 2 , 000 dollar stake in the bank and each successful elimination adds $ 2 , 000 to the bank . the 3 rd question starts with 3000 and so on and so forth . the player that crosses the $ 25 , 000 dollar goal first will win the competition . the losing player gets parting gifts and does not keep the money accumulated during the game . like the previous round , phone players who have picked the number 1 answer in this round will advance to the next round . the speed round is played by the winning player . the player tries to answer as many questions as they can in sixty seconds . the questions always have two possible answers . for example : as before , the phone players that give the majority answer will stay in the game . the first successful answer is worth $ 10 , 000 dollars to the in - studio player . if he / she gets the next question right , it is worth an additional $ 20 , 000 dollars , the next an additional $ 30 , 000 and so on . if the player guesses incorrectly , the total amount of money that they have accumulated up to that point is cut in half , and the next question starts back at the $ 10 , 000 dollar base amount . the player must then try to build back up his / her money . let &# 39 ; s assume , for example sake that at the end of the sixty seconds , the player has built up $ 120 , 000 dollars . we will also assume that there are 5 phone players left in the game . at this point , the player is faced with a decision . he / she is shown a final question . for example : the question was posed to a previously selected group in order to get the results . the player can either stop and keep the money , or try for the jackpot . all the player must do is simply pick the number 1 answer . if the player stops , he / she keeps 50 % of the money that they have accumulated so far and we will split the remaining 50 % amongst the phone players . we will speak to some of the players on the phone to find out whether they think the player should go for it or not . if the player decides to play for the jackpot , the phone players must also decide if they want to go for it too . any phone player that does not wish to play can opt out of the game and keep their share of the money won thus far . after the player decides what answer he / she believes is the number 1 answer , the host starts dramatically revealing the other answers one at a time until we get down to a 50 - 50 shot of winning . then we see the players answer . if the player wins , he / she will win 50 % of the jackpot and the remaining phone players will win 50 %. if the player loses , he / she will lose everything along with the phone players that participated and they will all receive parting gifts . the jackpot will then roll over to next week &# 39 ; s show . when the jackpot is not hit for several weeks , the excitement level for the viewers and players will be incredible ! although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity and understanding , it will be readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims . | a variety of games and methods for enhancing game play are provided . in one aspect , a secondary or ancillary game is played in parallel with a first game , such as a lottery ball draw . yet another game involves the selection of items which a player or participant believes had been selected by an audience as not being the most popular . in yet another aspect , an interstitial progressive sequencing of programming is provided , such as where a series of short segments are presented at differing times throughout an evening of prime time programming . audience participation may be enhanced by permitting internet access to the game system , and to permit remote users to play along as if they were in studio participants or part of the studio audience . |
referring initially to fig1 , a medicament delivery device is shown , and is generally designated 10 . as shown , the device 10 includes a first reservoir member 12 interconnected with a second reservoir member 14 . structurally , the reservoir members 12 , 14 define an inner chamber 16 . further , the first reservoir member 12 forms an inlet 18 to the chamber 16 , while the second reservoir member 14 forms an outlet 20 from the chamber 16 . as shown , the inlet 18 is connected to a fluid source 22 via a tube 24 . also , a valve 26 is positioned along the tube 24 to control the flow rate of fluid from the fluid source 22 . in fig1 , it can be seen that the outlet 20 is connected to a nozzle 28 via a tube 30 . as shown , the nozzle 28 may direct fluid 32 from the fluid source 22 , through the chamber 16 , to selected tissue 34 , such as oral tissue , for medical treatment . in fig2 , it can be seen that the chamber 16 defines a chamber axis 36 . further , the engagement between the tube 24 , reservoir members 12 , 14 , and the tube 30 is illustrated more clearly . as shown , the device 10 includes an anchor member 38 defining a channel 40 interconnecting the inlet 18 of the first reservoir 12 with the lumen 42 of the tube 24 . structurally , the anchor member 38 extends axially from a proximal end 44 to a distal end 46 . at its proximal end 44 , the anchor member 38 forms a threaded bore 48 radially spaced from a protrusion 50 extending axially in the proximal direction . between the threaded bore 48 and the protrusion 50 , the anchor member 38 forms a cylindrical void 52 . as shown in fig2 , the distal end 54 of the tube 24 is forced into the cylindrical void 52 to connect the lumen 42 of the tube 24 with the channel 40 of the anchor member 38 . as shown , the tube 30 is flexible and is deformed as it engages the anchor member 38 . still referring to fig2 , it can be seen that the distal end 46 of the anchor member 38 also forms a threaded bore 56 and protrusion 58 that define a cylindrical void 60 . as shown , the inlet 18 of the first reservoir member 12 is received within the cylindrical void 60 . in order to ensure a fluid tight engagement , the inlet 18 is provided with tabs 62 that extend radially outward to engage with the threaded bore 56 . the first reservoir member 12 also includes radially outward extending threads 64 at its distal end 66 . further , the second reservoir member , 14 includes reciprocating , radially inward extending threads 68 at its proximal end 70 . with this cooperation of structure , the reservoir members 12 , 14 may be connected and disconnected . in fig2 , the outlet 20 of the second reservoir member 14 is shown in engagement with the tube 30 . specifically , the outlet 20 is fit inside the tube 30 to frictionally engage the second reservoir member 14 and the tube 30 and provide fluid communication between the chamber 16 and the lumen 71 of the tube 30 . because the tube 30 is flexible , it can deform to engage the outlet 20 . when the lumen 42 , channel 40 , chamber 16 and lumen 71 are interconnected , a passageway 72 from the fluid source 22 to the nozzle 28 ( both shown in fig1 ) is created . further , when the reservoir members 12 , 14 are connected , as in fig2 , the chamber 16 formed is able to hold medicaments . structurally , the volume of the chamber 16 increases diametrically from the inlet 18 toward the distal end 66 of the first reservoir member 12 . then , the volume of the chamber 16 decreases diametrically from the proximal end 70 of the second reservoir member 14 to the outlet 20 . in fig2 , shown positioned in the chamber 16 is a medicament 74 , specifically , a selected anti - microbial agent . for the present invention , the anti - microbial agents 74 may be in different physical forms , including pills , capsules , gels , and powders , and may be bacteriocidal or bacteriostatic . more specifically , the anti - microbial agents 74 may include metallic salts ( sodium chloride , bicarbonate or soda , povidone iodine , sodium hypochlorite , or other anti - microbial agents effective against porphyromonas gingivalis , prevotella intermedia , bacteroides forsythus , fusobacterium , selenomonas , centipeda periodontii , spirochetes , peptostreptococcus micros , eubacterium , actinobacillus actinomycetemcomitans , eikenella corrodens , capnocytophaga , campylobacter rectus , enteric rods / pseudomonads , staphylococcus , enterococcus faecalis , candida , protozoans ( amoebae and trichomonads ), and viruses . as further shown in fig2 , a filter 76 is positioned adjacent to the outlet 20 to prevent the medicament 74 from blocking the outlet 20 . also , in order to seal the components of the device 10 , each interface between device components may be provided with resilient o - rings 78 . for purposes of the present invention , the first reservoir member 12 and the second reservoir member 14 are selected from a plurality of reservoir members 12 and 14 . for instance , a small chamber 16 formed by a first reservoir member 12 and a second reservoir member 14 may have an axial length of 1¾ inches ( 1 . 75 in .) and a maximum diameter of ⅝ inches ( 0 . 616 in .). further , a medium chamber 16 may have an axial length of 2⅜ inches ( 2 . 745 in .) and a maximum diameter of 1 inch . also , a large chamber 16 may have a length of 2⅛ inches ( 2 . 116 ) and a maximum diameter of 1¼ inches ( 1 . 30 in .). for each reservoir member 12 , 14 , the diameter of the inlet 18 and the diameter of the outlet 20 may be selectively varied as well , though the diameter of the inlet 18 is preferably ¼ inch ( 0 . 30 in .) and the diameter of the outlet 20 is preferably 3 / 24 inches ( 0 . 2675 in .). further , for each reservoir member 12 , 14 , the length of the outlet 20 may be selectively varied . with the provision of reservoir members 12 , 14 having chambers 16 , inlets 18 and outlets 20 ( and tubes ) of varying diameters and lengths , a range of flow rates through the passageway 72 can be provided . for instance , given a flow rate from the fluid source 22 , the selected length and diameters of the inlet 18 , reservoir members 12 , 14 , and outlet 20 can determine a maximum flow rate through the passageway 72 . as a result , the device 10 provides for proper treatment of selected tissue 34 with any desired medicament 74 . for instance , proper treatment with metallic salts , iodine , etc . may require the application of these various agents over a period of time no longer than five minutes and at appropriate concentrations . after the dissolving rate of the topical agents is determined , and with the volume of the medicament 74 , the maximum concentration of the medicament 74 , and the period of application for the medicament 74 known , reservoir members 12 , 14 having a properly dimensioned chamber 16 , inlet 18 and outlet 20 may be selected . in this manner , the device 10 provides for the proper application of a wide range of medicaments 74 . in operation , the micro - organisms are identified , and a treatment plan is identified and implemented . specifically , the medicament 74 is identified , the amount of medicament 74 is chosen , and the amount of time for the application of the medicament 74 is selected . as a result , an optimal flow rate for the fluid 32 is ascertained . in view of these determinations , the appropriate first reservoir member 12 and second reservoir member 14 are selected . after the components of the device 10 are interconnected , and the medicament 74 is positioned in the chamber 16 , the water source 22 is activated to flow the water 32 through the passageway 72 . the valve 26 and fluid source 22 may be manipulated to achieve the desired flow rate in view of the selected reservoir members 12 , 14 . as the water 32 passes the medicament 74 , it dissolves or otherwise picks up some of the medicament 74 and carries the medicament 74 out of the nozzle 28 to irrigate the selected tissue 34 . after the treatment is performed , the water source 22 is turned off . then another medicament 74 may be positioned in the chamber 16 of the same reservoir members 12 , 14 , or in the chamber 16 of different sized reservoir members 12 , 14 , and the device components reconnected . when the device 10 is ready , the water source 22 is again activated and the water is adjusted to a desired flow rate . this process may be repeated for multiple medicaments 74 , as desired . while fig1 illustrates the use of the device 10 on oral tissue 34 , the device 10 may be used on any type of tissue infected with micro - organisms . while the particular dental / medical oral irrigation system as herein shown and disclosed in detail is fully capable of obtaining the objects and providing the advantages herein before stated , it is to be understood that it is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims . | a method and device delivers a medicament to a selected tissue for treatment of the tissue , plaque and biofilm included . in the device , a first reservoir member is used to connect to a fluid source . further , a second reservoir member engages the first reservoir member to define a chamber for receiving the medicament . structurally , the second reservoir member includes an outlet . attached to the outlet is a tube that extends to a nozzle . when connected , the first reservoir member , second reservoir member , and tube define a passageway from the fluid source to the nozzle . during use , a flow rate for a fluid is established through the passageway to deliver the medicament from the passageway through the nozzle to the selected tissue . |
the best mode for carrying out the invention is presented in terms of its preferred embodiment , herein depicted within the fig1 through 4 . referring now to fig1 , an overall pictorial representation of the video game system auxiliary cover system 10 shown in an utilized state upon a video game console 15 is depicted , according the preferred embodiment of the present invention . the video game system auxiliary cover system 10 is an overall cover which encapsulates the video game console 15 on multiple sides . the video game console 15 is depicted as a generic game console for the purposes of illustration . it is envisioned that specifically designed models of the video game system auxiliary cover system 10 would be produced for all past , current and future home video gaming consoles , including systems 10 for x - box ®, playstation ® consoles , ninetendo gamecube ® and others . the dimensions and associated tolerances are such that the video game system auxiliary cover system 10 would be held in place on the video game console 15 via friction fit along with the aid of first snap clips 20 , which grip the bottom corners and side surface of the video game console 15 . two of four first snap clips 20 are visible in this view for purposes of clarity . the number and placement of the first snap clips 20 would vary dependent on the shape of the video game console 15 and as such is not intended to be a limiting factor of the present invention . a pair of connector openings 25 are provided on the front of the video game system auxiliary cover system 10 to allow access to connectors 30 , such as those provided for game controllers . in a similar manner , a pair of switch openings 35 provides access to a set of switches 40 , such as those provided for power or ejecting of the gaming media . finally , also located on the front of the video game system auxiliary cover system 10 , is a media tray opening 45 which allows access to a media tray 50 , such as those for a compact disc ( cd ), digital versatile disc ( dvd ) or other proprietary media . in a similar manner , although not visible in this view , are openings for a power cable 55 which provides electrical power into the video game console 15 and a monitor cable 60 which provides video and audio signals to a monitor system . a set of multiple vent openings 65 are provided on the side of the video game system auxiliary cover system 10 or at any location vents are provided by the manufacturer of the video game console 15 . in this manner , it is ensured that any heat producing components located inside of the video game console 15 can be allowed access to outside ambient air . first graphic displays 70 are provided on the top surface of the video game system auxiliary cover system 10 , in this case a graphic representation of flames is provided . the first graphic displays 70 can be virtually anything and is envisioned to be related to specific games played on the video game console 15 , sport teams , children &# 39 ; s themes , adult themes , fantasy themes , and the like . additional furnished graphic images 75 such as holographic images , photographic images and the like may also be furnished . finally , user supplied images 80 such as stickers and the like can be added to blank space area 85 furnished on the top of the video game system auxiliary cover system 10 by the final user . referring next to fig2 , an exploded isometric view of the video game system auxiliary cover system 10 and the video game console 15 is disclosed . this fig . more clearly depicts the attachment method between the video game system auxiliary cover system 10 and the video game console 15 and the simple method of installation . no tools are required to remove or install the video game system auxiliary cover system 10 . a simple friction fit is all that is necessary . proper alignment of the connector openings 25 with the connectors 30 and the media tray opening 45 with the media tray 50 along with all other openings is assured dependent on the make and model of the video game console 15 . it is envisioned that in addition for providing customization of the video game console 15 , the video game system auxiliary cover system 10 can also be used to provide physical protection as well against dirt , dust , scratches and the like . additionally , the user can apply stickers and other graphic images to the video game system auxiliary cover system 10 in lieu of the video game console 15 , thus not reducing the value and subsequent resale value of the video game console 15 . finally , should an existing video game console 15 be damaged , scratched or cracked , the user can install the video game system auxiliary cover system 10 to provide a like new appearance . this fig . also provides a different type of first graphic displays 70 , such as fireworks . it is also envisioned that this type of first graphic displays 70 would utilize integral fiber optic strands 90 to produce display points 95 of light . the light would be produced by light - emitting diodes ( led &# 39 ; s ) as will be described in greater detail herein below . electrical power for the led &# 39 ; s will be provided by a power pigtail cable 100 which would connect to the power input point of the power cable 55 ( as shown in fig1 ). in such a manner , the top surface of the video game system auxiliary cover system 10 will light up in a dark room with a multi - colored display , thus making playing video games at night or in low - light conditions an exciting event . referring now to fig3 , a sectional view of the video game system auxiliary cover system 10 as seen along a line i — i shown in fig2 is disclosed . a light emitting diode ( led ) 110 is embedded in the top surface of the video game system auxiliary cover system 10 ( and / or the game controller cover 115 ) the long life nature of the video game system auxiliary cover system 10 , coupled with their low heat dissipation and small size allow them to be sealed within the plastic structure of the video game system auxiliary cover system 10 without need for replacement . a set of multiple strands from the fiber optic strands 90 is aligned with the video game system auxiliary cover system 10 and similarly embedded within the top surface of the video game system auxiliary cover system 10 . the fiber optic strands 90 are then routed outward and spread out where they turn upwards and penetrate the top surface of the video game system auxiliary cover system 10 . it is envisioned that multiple light emitting diode ( led ) 110 of different colors such as red , green , white , yellow , and blue could be used with overlapping and intertwined fiber optic strands 90 to produce words , pictures and the like . referring finally to fig4 , an exploded isometric view of a game controller cover system 115 as used with a game controller 120 is disclosed . the game controller cover system 115 consists of a game controller top half 125 and a game controller bottom half 130 as shown . the game controller 120 is intended to be a generic representation of any one of the multitude of manufacturers as aforementioned described . the game controller 120 is provided with a multitude of joysticks 135 , pushbuttons 140 , and paddle switches 145 as commonly expected . the game controller top half 125 is then provided with a multitude of openings 150 that match abovementioned protrusions . the game controller top half 125 is provided with a set of second snap clips 155 that align with a matching set of receiving clips 160 on the game controller bottom half 130 . the game controller bottom half 130 provides a basically concave form to encompass the bottom of the game controller 120 . a set of second graphic displays 165 on the game controller top half 125 would match the first graphic displays 70 on the video game system auxiliary cover system 10 ( as shown in fig1 and fig2 ). the game controller top half 125 and the game controller bottom half 130 can be applied and removed by hand without the use of tools or excessive force . in a manner similar to the video game system auxiliary cover system 10 ( as shown in fig1 ), the game controller cover system 115 provides physical protection for the game controller 120 or can cover surface or cosmetic damage that may be existing on the game controller 120 . it is further envisioned that the game controller cover system 115 includes a plurality of leds or a plurality of fiber optic strands are embedded in the system 115 to provide additional aesthetic lighting to the system 115 , either standing apart from the leds or fiber optic strands of the cover system 10 or as a compliment to the cover system 10 , thus providing a lighted visual effect . the led or fiber optic arrangement or configuration may be similar to the that disclosed in relation to the cover system 10 , or may include an arrangement different to accommodate the remoteness of the controller from the console itself . it is envisioned that other styles and configurations of the present invention can be easily incorporated into the teachings of the present invention , and only one particular configuration shall be shown and described for purposes of clarity and disclosure and not by way of limitation of scope . the preferred embodiment of the present invention can be utilized by the common user in a simple and effortless manner with little or no training . after purchase or procurement of the video game system auxiliary cover system 10 it must be applied to the video game console 15 and corresponding game controller 120 . to begin the installation process , the user would unplug all power cable 55 , all monitor cable 60 , all controller cables , and any other device which may protrude from the video game console 15 . next , the video game system auxiliary cover system 10 is simply slid over the video game console 15 and attached to the base of the video game console 15 by use of the first snap clips 20 . in a similar manner , the game controller top half 125 and the game controller bottom half 130 are snapped around the game controller 120 and secured using the second snap clips 155 in the receiving clips 160 . next , any power cable 55 , any monitor cable 60 , any controller cables , and any other device that was aforementioned removed , must be reinstalled . if the video game system auxiliary cover system 10 should be equipped with a light emitting diode ( led ) 110 and fiber optic strands 90 , the user would connect the pass through power connector 105 of the power pigtail cable 100 to the power cable 55 before it connects to the video game console 15 . at this point the video game system auxiliary cover system 10 is ready for use . during the actual use of the video game console 15 equipped with the video game system auxiliary cover system 10 , nothing is readily different nor is the actual game playing activity modified . however , the additional aesthetic value provided by the video game system auxiliary cover system 10 coupled with the internal lighting afforded by the fiber optic strands 90 and the light emitting diode ( led ) 110 , if so equipped , will provide additional entertainment value . if the user wishes to remove the video game system auxiliary cover system 10 for the purposes of applying a different one , or applying to a new video game console 15 , or if selling the video game console 15 , it can be removed easily be snapping it off . the foregoing descriptions of specific embodiments of the present invention have been presented for purposes of illustration and description . they are not intended to be exhaustive or to limit the invention to the precise forms disclosed , and obviously many modifications and variations are possible in light of the above teaching . the embodiments were chosen and described in order to best explain the principles of the invention and its practical application , to thereby enable others skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated . it is intended that the scope of the invention be defined by the claims appended hereto and their equivalents . therefore , the scope of the invention is to be limited only by the following claims . | a system by which interchangeable covers are provided for video game consoles and controllers to provide a wide variety of appearances is disclosed . it is envisioned that the system would be customized to work with popular video game consoles . to change the appearance of an existing console , the user would simply snap the new cover over or on the existing manufacturer &# 39 ; s cover . the cover would be specifically designed to accommodate all access panels , buttons , cooling vents , connection ports and the like . the new covers would be specifically designed to go with a specific game or be of a more generally styled theme . the game controller covers are two halves that snap around the controller yet expose all control buttons and surfaces . it is also envisioned that an led lighting system could be embedded in the controller case cover to add an interesting artistic touch by way of case illumination . |
while the invention described is susceptible of embodiment in many different forms , they are shown in the drawing , specification and herein described in the detailed specific embodiments and is not intended to be limited to the specific embodiments illustrated . referring to fig1 the seat pad 1 of the present invention is constructed of a first upper panel 10 , and a second lower panel 15 comprising a semi - rigid or resilient fabric like material . the first upper panel 10 , and second lower panel 15 may provide different materials , colors , textures or a design that may be provided by other conventional methods . a third side panel component 20 is provided between the first upper panel 10 , and second lower panel 15 to be attached at least a portion of the outer perimeter of upper panel 10 , and lower panel 15 . the third side panel 20 may be fixedly attached to the upper panel 10 , and lower panel 15 , to at least a portion of the outer periphery to form a three dimensional shape . an optional alternative fourth side panel component 25 , may be fixedly attached to the third side panel 20 , and separatively divided about the midsection and having the top outer edge fixedly attached to the edge of the first upper panel 10 , and the lower opposing edge attached to the edge of the second lower panel 15 , and to receive a third anti - slip gripping component 30 fixedly attached around the midsection of the third or fourth said side panel component 20 , and 25 of the said seat pad assembly . a filler opening 35 located between the upper panel 10 , and lower panel 15 , to load and unload the seat pad 1 , with filler material . the filler opening 35 may be secured by a mechanical fastening means for loading and unloading the filler material or otherwise permanently fastened . the seat pad 1 can be constructed in various shapes and sizes to accommodate a stool , chair , or bench type seat . the seat pad 1 , material can be made from fabric like materials such as woven , non - woven , flax , wool , cotton , polycotton , vinyl , polyvinyl chloride , nylon olefins , rubber and other synthetic and non - synthetic materials or combination thereof . the seat pad 1 , and anti - slip component 30 securely fastened between the upper panel 10 , and lower panel 15 with the ability to pivotably rotate about the midsection and upper panel 10 , and opposing lower panel 15 with a secure rotatable , reversible means . however it is understood that panels may be combined or may vary in size , shape and length to accommodate various designs and manufacturing methods without deviating from the scope of the invention . referring to fig2 , the seat pad 1 , shown in perspective exploded view , in one embodiment having an upper panel 10 , and a lower panel 15 fixedly connected by a third side panel component 20 , and an optional fourth side panel component 25 , split somewhere about the midsection 26 to attach an anti - slip gripping component 30 having the ability to be reversible and rotatable about the width of the seat pad 1 . the fourth side panel 25 may be eliminated to reduce cost in the assembly by using the third side panel 20 to securely attach the upper panel 10 , and lower panel 15 having the anti - slip gripping component 30 fixedly attached somewhere about the midsection of the width of the said third side panel 20 . a filler material 40 , made of synthetic or non synthetic materials not limited to but including , recycled paper , polyurethane foam , polyester fiber , tempurpedic foam ( heat sensitive foam ) or a combination of polyurethane and tempurpedic foam ( heat sensitive foam ). the seat pad 1 , assembly can be constructed by stitching , mechanical fastening , radio frequency or heat welding . the seat pad 1 , upper panel 10 , and lower panel 15 , may comprise of a non woven backing material , reflective foil material , to add functional material properties and benefits to the seat cushion , reducing the effect of radiant heat , enabling the user to stay cool , or retain heat inside their body when sitting on the pad in adverse temperature conditions . aluminum reflective foil reflects radiant heat and therefore minimizes the temperature effects on the pad . in addition to stabilizing internal temperatures of the seat pad , the reflective foil radiates heat back to the human body to minimize heat loss when in use . other common materials can be used to fill the volumetric three - dimensional structure . alternative phase change materials may be utilized as a filler material to stabilize the temperature of the seat pad and minimize adverse effects of various temperature conditions . referring to fig3 a , another variation of a cushioned filler material 41 is shown with a series of thru - holes 42 passing through the body of the cushioned filler material 41 that provide a means to reduce the filler material &# 39 ; s volume of material and provide a desired firmness when a thin airtight member 43 made of film or fabric like material and affixed by adhesive 44 to trap air in the holes 42 of the cushion filler material 41 providing an enhanced cushion effect . when the seat pad assembly 1 of fig1 is rotated , the opposite effect is present , where the filler material 41 offers a less dense comfortable seat pad allowing the air to evacuate from the seat pad . when utilizing the filler material 41 , the seat pad 1 may be selectively rotated 180 ° degrees so that the holes 42 are in close proximity to an individual seated . by selectively rotating the seat pad , the user can change the firmness or cushioning effect of the seat pad cushion . a visual indicator or graphics may be applied to the seat pad to indicate firmness , or other effects when rotated to the desired position . referring to fig3 b , cushioned filler material 41 , as shown in a side view with a series of holes 42 exposed upwardly away from the seating surface , where the filler material 41 is coupled to a thin member 43 with bonding adhesive 44 . the effects may be variable with changes in the respective size or diameter of the holes 42 , and also provide additional benefits minimizing materials for cost effective construction of seat pads . referring to fig3 c , bladder 46 , containing a resilient filler material 47 , including a series of holes 49 , airtight semi - rigid member 50 , with perforated holes 51 . the bladder 46 , having a valve 53 , and orifice 54 , that enables the bladder 46 to receive air when the valve 53 is open . the spring 52 assists the bladder 46 to increase in size to the maximum height , with maximum air capacity . the valve 53 can remain open to exhaust air from the bladder , and upon closing the valve 53 , the seat pad will remain at the desired height with the bladder holding a constant volume of air . the materials for construction may be desirable as a resilient air sealable sheet film or fabric like material . the bladder 46 may be fabricated of resilient pvc ( polyvinyl chloride ), polymers , thermoplastic elastomer , urethanes , polyester , or other like films . the airtight semi - rigid member 48 and semi - rigid member 50 can be fabricated from plastic , film extrusions , using radio frequency welding , heat sealing or alike . referring to fig4 seat pad shown in a bottom view , having an anti - slip material 61 , closely held to the surface of the lower panel 62 , covering less than sixty percent of the seating surface area minimizing the cost of materials , and providing sufficient anti - slip material surface area contact to securely position a pad on a seating surface . the pad 60 may be fabricated in various shapes and sizes . referring to fig5 seat pad 60 , shown in a top view , having a top surface area defined by the upper panel 63 , that may provide an alternative design or material than the lower panel 62 , as shown in fig4 , is constructed with an anti - slip material 61 that partially covers the lower panel 62 , and part of the side wall panels 64 , as shown in fig6 . the seat pad 60 may comprise of various shapes , sizes and patterns to accommodate the consumer , fashion and market demands . the anti - slip material 61 preferably should be of a high coefficient of static friction , made of rubber mesh like material , latex or alike . an optional liner material 68 can be coupled to the seat pad 60 on the surface that may come in contact with the user or opposing surfaces as desired . the liner material 68 may comprise of an individual sheet or stacked layer of disposable liners . referring to fig6 a rear side view of the seat pad 60 , having an upper panel 63 , gripping member 61 , and side panel 64 , where the side panel 64 is coupled to the gripping member 61 . the gripping member 61 is fixedly attached to a portion of the outside perimeter of the seat pad 60 , and may include a filler opening 65 to insert the filler material into the three dimension structure and can be permanently closed or selectively fastened by means of a zipper , thread , hook and loop , or other mechanical means . the filler opening 65 is not limited to the mentioned side panel and various configurations may require different fill methods . the methods and various configurations shall be noted but not limiting the scope of the said invention . referring to fig7 another preferred embodiment of the said invention , seat pad 70 shown in a perspective top view , illustrates a non - slip member 71 fixedly attached to approximately the midsection 75 of side panel 74 . the non slip member 71 , defined by a portion of the shape of the seat pad 70 , is fixedly attached on three sides held in close proximity to the lower panel 73 surface area , where the space between the non slip member 71 , and the lower panel 73 define a pocket 72 that has the capacity to store articles within the seat pad 70 assembly . small articles such as papers , photos , magazines and alike can be stored within the assembly and conveniently removed and inserted without the need for other storage devices . the need for a pocket or pouch is more commonly used in travel , outdoor events , or sports and alike games . referring to fig8 a and 8 b the seat pad cushion 80 is shown as an assembly , the assembly main components comprising of a lower panel 83 , a gripping member 81 , on fig8 a , and another embodiment shown of the gripping member 85 on fig8 b . the anti - slip material used on gripping members 81 and 85 are shown with a reduction in material weight for lowering the manufacturing cost of the seat pad 80 . the gripping member 85 as shown in fig8 b can also be utilized as a handle to enable the consumer to carry the seat pad 80 , or securely hold onto in the event of an emergency . the seat pad 80 , and the gripping member 85 , are constructed for use as one component , with a resilient means to turn or flip the gripping member 85 around the seat pad 80 for multi - use purposes . referring to fig9 a illustrates an alternative design within the scope of the invention . as illustrated in fig9 a a perspective view of seat pad 90 , in use on a stool 91 , where the gripping member 93 is in contact with the stool seating surface 92 allowing the consumer to sit securely on the upper panel 94 surface area resisting movement . the stool 91 , and support leg ( s ) 95 , provide an unstable surface for chair pads and cushions . the need for a non - slip seat pad with minimum parts and no assembly is desired . as illustrated in fig9 b a seat pad 96 , is shown in perspective view on a bench seat 100 . the bench seat 100 comes in contact with the seat pad 96 , and two areas are disclosed showing the anti - slip gripping members 97 and 98 , respectively . the prior descriptions and embodiments are shown within the scope of the invention for a bench seat design . the bench seat design may offer one side of the upper panel 99 being water resistant and the opposite side having a different texture or fabric design . the bench seat 100 , and seat pad 96 with anti - slip gripping members 97 at one end and 98 at the other end illustrate how the description of one embodiment may be applied to another within the scope of the invention disclosed . referring to fig1 , an exploded assembly view of one embodiment is shown seat pad 110 , having a first panel 111 comprising a reflective foil material , a second panel 113 fixedly attached to at least a portion of the said first panel 111 , a third panel 115 fixedly attached to a second panel 113 or subsequent sub assembly in connection to the first said panel 111 to form a three dimensional shape . the three dimensional shape includes a filler material 114 , and also may include an anti - slip gripping member 116 fixedly attached between the said first panel 111 , and the said third panel 115 , where the gripping member 116 , is pivotably rotatable around the width of the seat pad 110 , to selectively use either side of the seat pad 110 for various features . a visual indicator 112 may be used to indicate a feature or provide instructions for use or even provide temperature indicia for the consumer in various temperature environments . it should be understood that the proceeding is merely a detailed description of one embodiment of this invention and that numerous changes to the disclosed embodiment can be made in accordance with the disclosure herein without departing from the spirit or the scope of the invention . | an improved seat pad and integrated gripping member is provided , which prevents the pad from slipping when placed between a seating surface and individual . the gripping member is permanently attached to the seat pad along its edge and covers a portion of either side of the seating surface . the gripping member is reversible therefore either side of the seat pad may be selectively exposed during use . this allows both seat pad sides to be constructed of different materials , colors , or patterns and be interchangeable when desired by the user . |
fig1 shows an end on view of a kernel cracking assembly ( also known as a crop processor ) as used in forage harvesters for cracking kernels of maize . the kernel cracking assembly is arranged downstream of the main cutter ( not shown ) of the forage harvester in the crop flow path , just prior to the blower which urges the crop up a discharge chute and into a suitable vessel normally driven alongside the forage harvest . in reference to fig1 , the assembly 10 consists of two frames 12 and 14 pivotable relative to one another about a pivot pin 16 . each frame supports one of two rollers 18 and 20 along their axial end . an arrow on fig1 and 2 indicates the path of the crop flow between the two rollers 18 and 20 . the rollers 18 and 20 rotate relative to one another at different speeds so that crop passing between them is sheared causing any remaining kernels unaffected by the main cutter to crack open releasing their nutrient . the separation of the rollers is related to the size of the kernels and maintaining this separation is important to the efficient operation of the kernel cracking assembly . in the embodiment shown in fig1 and 2 , the separation of the frames 12 and 14 , and hence the rollers they support 18 and 20 , is determined by actuators , in this case wedges 22 and 24 . at respective axial ends of the rollers 18 and 20 , the wedges 22 and 24 are sandwiched between the frames 12 and 14 , the latter being urged towards one another by means of springs 38 . the wedges 22 and 24 are pivotally attached by means of cranks 30 and 32 to a transition shaft 34 . the crank 30 is further pivotally attached to hydraulic ram 36 , which serves to raise or lower both wedges 22 and 24 simultaneously by virtue of their connection through the cranks 30 and 32 and the transition shaft 34 . the wedges 22 and 24 , have tapering ramp surfaces 26 and 28 , respectively . as the ram 36 forces the wedges to translate relative to a plane containing the axes of the rollers 18 and 20 , the ramp surfaces 26 and 28 push against bearings 40 arranged on the frame 12 , forcing the frame 12 to separate against the action of the springs 38 . thus , the vertical position of wedges 22 and 24 , governs the separation of the roller 18 with regard to roller 20 . in order to determine the position of the wedges or actuators , the wedge 24 is pivotally connected via a tie rod 42 to sensor arm 44 . as the wedge 24 translates , tie rod 42 causes sensor arm 44 to rotate relative to the frame 14 . this rotation is monitored by a rotational sensor 46 and is indicative of the separation of the rollers . the position of the hydraulic ram 36 , and hence the separation of the rollers 18 and 20 , is controlled by the feedback circuit shown in fig3 . the hydraulic fluid used to power the ram 36 is provided by hydraulic pump 58 , which is connected via control valve 54 to hydraulic cylinder 56 . this may be a dedicated pump , or as is more likely to be the case , a pressurized oil supply already employed in the vehicle for other purposes . a control unit 50 , having a control panel located for easy access by the vehicle operator , is connected to rotational sensor 46 and control valve 54 . the control valve 54 is biased into a central position in which no fluid can flow into or out of cylinder 56 of the hydraulic ram 36 . thus , in the absence of any signal from the control unit 50 , the position of the ram 36 , and thus the separation of the rollers 18 and 20 , remains constant . the rotational sensor 46 delivers a signal to the control unit indicative of the position of the rollers . at any point the control unit 50 is preset with a desired separation input by the operator of the vehicle . the control unit 50 creates an error signal from the difference between the desired and measured separation of the rollers . the control unit then operates the control valve 54 to minimize this error . as with any closed loop feedback system , a dead band must be programmed into the control unit 50 in order to prevent the system from oscillating . the dead band dictates the margin of error permitted by the control unit . the dead band has little effect on the accurate placement of the rollers 18 and 20 due to the mechanical advantage provided by the shape of the actuator 24 , be it a screw , wedge or cam . their use in this application ensures that a significant amount of movement is required by the hydraulic ram 36 in order to produce a relatively small movement in the rollers . the mechanical advantage also means that a relatively small ram 56 will suffice to overcome the force of the springs 38 urging the rollers together . if the position of the hydraulic ram 36 should change as a result of some leakage of hydraulic fluid past the piston of the ram 56 , the resulting movement of the rollers will be detected by the rotational sensor 46 and automatically be compensated for by the feedback circuit . though the actuators 22 , 24 limit the distance that the rollers can move toward one another , they do not inhibit separation of the rollers . thus , if a stone should be present in the crop , the two frames will pivot to increase the distance between the rollers to allow the stone to pass without causing permanent damage to the kernel cracking assembly . | a kernel cracking assembly comprises two frames each supporting a respective one of two rollers between which kernels are crushed . a hydraulically operated actuator acts to move the frame relative to frame to set the separation of the rollers . a position sensor coupled to the actuator forms part of a closed - loop feedback circuit which serves to maintain a predetermined separation of the rollers . |
a surgical instrument for endoscopic dissection of vessels for cabg surgery as known in the art generally comprises a concave working head , a shaft , and a handle . the instrument is typically fitted with an endoscope inserted through a handle and the shaft so that an operator may view into a working space created by concave working head . in operation the surgeon introduces the concave working head and a portion of shaft through a surgical incision and manipulates surgical instrument alongside the saphenous vein in order to free the vein from surrounding tissues and to isolate side branches of the vein that must be ligated prior to removal of the vein from the patient &# 39 ; s leg . the concave working head may be made from a clear plastic so that the operator may visualize tissue structures adjacent to it as well as inside the working space . u . s . pat . no . 5 , 928 , 138 also discloses how surgical instrument may be used with other surgical instruments for dissecting and harvesting a vein . the present invention reduces the time required to perform the evh procedure ( and subsequent trauma to tissue ) due to fewer exchanges of these additional instruments into incision . referring now to fig1 a surgical instrument is illustrated therein generally referred to by reference number 2 . the present invention includes at least one dissecting element ( shown in fig2 - 14 ), which is either movably connected or fixed to a concave working head , also referred to as a spoon retractor 10 . the spoon retractor 10 is useful for dissection of tissue such as is required for separating the saphenous vein from surrounding tissues during an evh . surgical instrument 2 may be used with an endoscope 18 in order to view inside the working space . in the descriptions that follow , several variations of the spoon retractor 10 and dissecting elements are described . for the embodiments shown , the spoon retractor 10 is preferably attached to an elongated shaft 1 and a handle 3 , similar to the surgical instrument of the prior art . [ 0038 ] fig2 is a front view and fig3 is a side sectional view of a spoon retractor 10 of the present invention . spoon retractor 10 is an improvement of concave working head of the prior art . in this implementation , spoon retractor 10 is symmetrically shaped with a proximal end 17 attached to the distal end of a shaft 1 . spoon retractor 10 tapers to a distal end 19 so that an operator 4 may easily use spoon retractor 10 to separate tissue layers and isolate a vein 6 from surrounding tissues . spoon retractor 10 is preferably made of a medical grade , injection moldable plastic such as polycarbonate and is optionally clear for endoscopic viewing of tissue both inside the working space and adjacent to spoon retractor 10 . in the implementation of fig2 and 3 , spoon retractor 10 includes a retractable , flexible arm 12 . an upper layer 14 and a lower layer 16 of spoon retractor 10 define a channel that extends partially between distal end 19 and proximal end 17 , and slidably retains flexible arm 12 . an operator 4 may position flexible arm 12 at an extended position such as shown in fig2 and 3 , at a retracted position , as shown in fig4 and 5 , or at any position between the extended and retracted positions . a control ( not shown ) for moving flexible arm 12 is preferably located on a portion of the surgical instrument 2 that remains external to the patient during the procedure , such as on the proximal end 50 of shaft 1 or on handle 3 , as may be easily envisioned by those skilled in the art . in the retracted position , the flexible arm 12 lies above the level of the endoscope 18 , and portions which are located outside of the spoon retractor 10 may lie on the shaft 1 . flexible arm 12 may be made of a medical grade , injection moldable plastic such as high - density polyethylene . a distal end of flexible arm 12 comprises two opposing curved portions 11 for a traumatically sliding along the sides of an elongate tissue structure such as a vein 6 in order to free the vein 6 from surrounding tissues . curved portions 11 define an arm 13 that extends distally to an outer edge 15 to assist in separating the vein 6 from the connecting tissues . [ 0040 ] fig6 shows a bottom view of spoon retractor 10 and corresponds with fig4 and 5 for when flexible arm 12 is in the retracted position . lower layer 16 ( see fig3 ) comprises two guide rails 22 to support flexible arm 12 . guide rails 22 connect to an inside surface of spoon retractor 10 . the guide rails 22 also serve to insure that the flexible arm 12 does not restrict the field of view of the endoscope 18 . [ 0041 ] fig7 and 8 are a front view and a side view of a first variation of a spoon retractor 10 , respectively , with a left curved edge 30 and an opposing right curved edge 31 extending from a bottom edge 29 on each side of spoon retractor 10 . in this implementation , a left middle section ( not shown ) and a right middle section 34 blends with the curvation on each side of spoon retractor 10 . as can be seen in fig7 left curved edge 30 , right curved edge 31 and spoon retractor 10 approximately surround the longitudinal axis of spoon retractor 10 , thus allowing an operator to place spoon retractor 10 near a vessel with left curved edge 30 and right curved edge 31 on opposing sides of the vessel . the operator 4 may then slide spoon retractor 10 back and forth along the vessel to free the vessel from surrounding tissue . [ 0042 ] fig9 and 10 show a second variation of the spoon retractor 10 of the present invention . fig9 is a front view and fig1 is a side view , showing a wireform dissecting element 37 comprising a left side rail 38 and a right side rail 39 fixed to spoon retractor 10 . wireform dissecting element 37 preferably has a curved distal end 36 joining left side rail 38 and right side rail 39 . wireform dissecting element 37 further comprises a pair of proximal ends 44 , which are fixedly connected to spoon retractor 10 . cavity 48 of spoon retractor 10 retains and supports curved distal end 36 . wireform dissecting element 37 is made from a medical grade material such as stainless steel wire having a diameter approximately in the range of one to two millimeters . the operator 4 may position left side rail 38 and right side rail 39 and on either side of a vessel and move spoon retractor 10 slowly forward and back to separate vein 6 from the connecting tissue layers . fig1 - 14 show a third variation of the spoon retractor 10 of the present invention . fig1 and 12 show front and side views , respectively , of spoon retractor 10 , and include a movable arm 50 shown in a first position . an extended portion 46 at a proximal end 42 of the spoon retractor 10 rotatably retains a shank 54 of movable arm 50 . an operator 4 moves movable arm 50 between the retracted first position and a second position ( fig1 and 13 , respectively ) by actuating a rotation control ( not shown ) preferably located on the proximal end of shaft 1 or on handle 3 ( see fig1 ). actuation of a distal element of a surgical element by a control rod is well known in the art . movable arm 50 includes a tip 52 for dissecting tissues . shank 54 preferably lies directly below endoscope 18 . movable arm 50 is preferably made from a stainless steel wire having a diameter approximately in the range of one to two millimeters . movable arm 50 may rotate in either direction about the axis defined by the shank and may also rotate a full 360 degrees . the operation of the surgical instrument 2 of the present invention will now be discussed with reference to the figures . the surgical instrument 2 of the present invention has a particular ability in dissecting vessels from tissue in a patient however , such a use is given by way of example only and does not limit the scope or spirit of the present invention . once a device comprising at least one of the dissection elements discussed above is provided , the surgeon determines the location of the vessel to be dissected , and makes an incision in the patient . the spoon retractor is inserted into the incision and blunt dissection of the tissue surrounding the vessel 6 is performed . for extraction purposes , it is preferable to dissect as much tissue from the vessel as possible . the initial insertion of the spoon retractor 10 creates a working space 7 in the tissue of the patient near the vessel 6 being dissected . this working space provides a location where the operator may utilize the various dissection elements , discussed above to dissection the vessel from the surrounding tissue . finally the dissection elements need to be manipulated by the user to further dissect tissue surrounding the vessel 6 being dissected . the dissection of the vessel 6 is accomplished by moving the spoon retractor 10 along the vessel and separating the tissue from the vessel . to assist in the dissection there are various forms of dissection elements which can be provided , as discussed above . each of the various dissection elements can be incorporated into the method described here with some variation of the manipulation step . one of the dissection elements which may be provided is shown in fig7 and 8 . the dissection element comprises the spoon retractor 10 having curved edges 30 , 31 extending from the bottom edge on each side of the spoon retractor . the dissection element is used by orienting the vessel 6 between the two curved edges 31 . once the vessel is so oriented the spoon retractor 10 is moved along the vessel 6 . this movement causes the curved edges 30 , 31 to dissect the vessel from the tissue located on either side . another dissection element provided comprises a rigidly attached wireform 37 having left and right side rails 38 , 39 , and these rails are connected at the distal end of the wireform 37 . such a dissection element 37 is used by orienting the left side rail 38 , on a first side of the vessel 6 , and the right side rail 39 on a second side of the vessel 6 . the vessel is captured by the wireform by operation of the u - shape connection point of the dissection element . after the vessel 6 is captured , the spoon retractor 10 and wireform 37 are slid along the length of the vessel . the left side rail dissecting on the first side of the vessel and the right side rail dissecting the right side of the vessel . the u - shaped connection assists in the dissection of tissue on the top surface of the vessel . yet another dissection provided is one having a movable arm 50 having an extended portion and a shank 44 as shown in fig1 - 14 . the dissecting element is movably connected to the spoon retractor 10 , and the manipulation comprises rotating the movable arm 50 about an axis defined by the shank 44 . sliding the spoon retractor 10 and attached movable arm 50 along the vessel , and simultaneously rotating the movable arm 50 about the vessel tissue , dissects on all sides of the vessel from the surrounding tissue . additionally , when the movable arm 50 is in the position shown in fig1 , the dissection element can slidingly engage the tissue along the axis defined by the shank to dissect it from the vessel . the movable arm 50 can be forced along one side of the vessel 6 while the spoon retractor 10 is moved along another surface of the vessel 6 . upon projecting the spoon retractor a certain distance , the movable arm can be rotated to dissect tissue from the vessel by the circumferential movement of the movable arm around the vessel 6 . still another dissection element provided is one having a flexible arm 12 slidably retained in said spoon retractor , and movable between an extended position and a retracted position , as shown in fig2 - 8 . the distal end of the flexible arm 12 defines at least one curved portion 11 . the curved portion 11 further defining an arm 13 which extends to an outer edge of the flexible arm 12 . this dissection element is manipulated by extending the flexible arm from the retracted to the extended position , and sliding the spoon retractor 10 and attached flexible arm 12 along the vessel 6 , at the same time the curved portion 11 of the flexible arm 12 is placed on at least one side of the vessel 6 to dissect the vessel 6 from the surrounding tissue . typically , the flexible arm 12 has two curved portions 11 and will be used to dissect the tissue from one side of the vessel 6 and then a second side of the vessel 6 . during the dissection the curved portion 11 slides along the surface of the vessel 6 . the arm 13 facilitates the dissection on the underside of the vessel 6 . those skilled in the art will appreciate that the methods of the present invention do not require the insertion multiple dissection tools to perform procedure . nor do they require multiple tool exchanges . accordingly , the procedure as a whole is far easier , and efficient that those previously known . as a result the stress on the patient is reduced . although only a few exemplary embodiments of this invention have been described in detail above , those skilled in the art will readily appreciate that many modifications are possible without materially departing from the novel teachings and advantages of this invention . accordingly , all such modification are intended to be included within the scope of this invention as defined in the following claims . | a surgical instrument for dissecting a vessel in a patient . the surgical instrument includes a spoon retractor having a proximal end and a distal end , said spoon retractor defining a working space in the tissue of a patient , a dissecting element proximate to the spoon retractor for dissecting tissue from a vessel , and a handle for manipulating the spoon retractor near the vessel . also provided is a method for dissecting a vessel including the steps of providing the surgical instrument for dissecting a vessel in a patient described above . making an incision in a patient . inserting the spoon retractor into the incision . creating a working space in the tissue of the patient near the vessel being dissected , and manipulating the dissecting element to further dissect tissue surrounding the vessel being dissected . |
the following examples , while not limiting the scope of the invention , will enable those of ordinary skill in the art to make and use the invention . carotene is a common ingredient used in commercial colored oleomargarine to impart a yellow color . a typical useage level is five ( 5 ) milligrams beta - carotene per pound of oleomargarine , or 0 . 0011 %. at this level , the color is light yellow . at 0 . 011 % the color is still yellow . at 0 . 11 %, the color is orange - brown and at 1 . 1 %, the color is reddish - brown . this illustrates the fact that where the concentration of carotene is substantially increased beyond recommended base levels , a very objectionable off - color is produced . annatto is another common ingredient used to impart yellow color to butter and colored oleomargarine . a typical useage level , for imparting yellow color is 0 . 01 %. at a base level of 0 . 006 %, the color is pale yellow . at 0 . 06 %, the color is golden . at 0 . 6 %, the color is reddish - brown . at 6 . 0 %, the color is deep red . this illustrates that where the concentration of annatto is substantially increased beyond recommended base levels , a very objectionable off - color is produced . another commercial annatto product contains a small amount of turmeric blended in with the annatto . at a base level of 0 . 006 %, the color is light yellow . at 0 . 06 %, the color is golden . at 0 . 6 %, the color is orange - brown . at 6 . 0 %, the color is deep red . results are thus substantially the same as with annatto alone . turmeric oleo resin by itself , at 0 . 025 % concentration imparts a light yellow color but with a greenish cast . at 0 . 25 %, the yellowish color was enhanced and so was the greenish cast . at 2 . 5 %, a golden color , with greenish cast , results while at 25 . 0 %, a dark brown color is produced . these results illustrate that where turmeric is used to impart a yellow color , a noticeable greenish cast is produced . paprika oleo resin by itself imparted colors not useful for oleomargarine : run concentration color______________________________________a 0 . 05 % very light peachb . 5 % medium peachc 1 . 0 % very light oranged 2 . 5 % light orange______________________________________ the discovery was made that adding paprika oleo resin to the turmeric oleo resin already present overcomes the greenish cast and allows an attractive and appealing yellow - gold color to come through , suitable for oleomargarine even at very high and very deep levels . __________________________________________________________________________run concentration color__________________________________________________________________________a 0 . 25 % turmeric light yellow color , greenish castb &# 34 ; + 0 . 01 % paprika * light yellow color , lt . greenish castc &# 34 ; + 0 . 03 % paprika light yellow color , no greenish castd &# 34 ; + 0 . 05 % paprika lt . med . yel . color , good oleo - margarine color , no greenish caste &# 34 ; + 0 . 10 % paprika med . yel . color , good oleo margarine color , no greenish castf &# 34 ; + 0 . 25 % paprika slightly darker yellow color than run e , no greenish cast__________________________________________________________________________ * paprika concentration is given in examples in weight % based on weight o oleomargarine these results illustrate that paprika oleo resin overcomes the greenish cast caused by the turmeric and permits an appealing yellow - gold color to come through . the amount of paprika should not , however , generally exceed the amount of turmeric since such excess amounts of paprika introduce a reddish off - color . the minimum amount of paprika needed to offset the greenish cast of the turmeric is generally about 10 %. the following results are obtained with 2 . 5 % oleo resin of turmeric : run concentration color______________________________________a 2 . 5 % turmeric medium yellow color , greenish castb &# 34 ; + 0 . 1 % paprika medium yellow color , lt . green - ish castc &# 34 ; + 0 . 3 % paprika medium yellow color , no greenish castd &# 34 ; + 0 . 5 % paprika medium yellow / gold color , good oleomargarine color , no greenish caste &# 34 ; + 1 . 0 % paprika deep yellow gold color - light orange castf &# 34 ; + 2 . 5 % paprika light orange cast______________________________________ these results show that very high concentrations of turmeric may be used to provide good yellow color with no objectionable off color . the results also show that at higher concentrations of turmeric , it is preferred to use generally lower concentrations of paprika than may be employed at lower turmeric concentrations . where the turmeric concentration exceeds about 2 %, it is therefore preferred to keep the paprika concentration at from 10 % to 50 % of the turmeric concentration . the following runs are made using 25 % oleo resin of paprika based on the amount of oleo resin of turmeric , the concentration of the latter being based on the margarine . ______________________________________run turmeric concentration color______________________________________a 0 . 125 % light yellow color - no greenish castb 0 . 25 % medium yellow color - no greenish castc 0 . 50 % light golden color - no greenish castd 1 . 0 % deep golden color - no greenish caste 2 . 0 % very deep golden color - no greenish castf 3 . 0 % very deep golden color - orange castg 4 . 0 % light orange color______________________________________ these results show that the maximum amount of turmeric for suitable yellow color is up to about 3 % by weight , based on the margarine weight . as indicated above , the amount of turmeric can be increased to very high levels without objectionable off - color according to the invention . this has the three fold advantage of : ( 1 ) providing an alternative yellow food colorant to those presently commercially available which could become scarce and costly due to any number of unforseen circumstances ; ( 2 ) allowing increased colorant concentrations to produce deep golden yellow color without introducing off - color ; and ( 3 ) permitting greater latitude in formulating . the last mentioned advantage is best understood with reference to the small quantities of colorants generally used . for example , a formulating error of an increase by a mere 5 milligrams in the amount of carotene colorant can double the amount of colorant in the margarine . since off - colors are produced at higher carotene content , it follows that generally small formulating errors may result in an off - color product . much greater latitude is achieved with the present invention since good color is produced at very high colorant levels . | a yellow coloring agent for foodstuffs such as oleomargarine . oleo resin of turmeric and oleo resin of paprika , in an amount of about 10 % to 100 % by weight based on the weight of the turmeric , is a yellow colorant for foodstuffs . the turmeric is used in an amount sufficient to impart a desired yellow color , and paprika is added in an amount sufficient to eliminate the greenish cast which would result from the use of the turmeric alone . |
the example embodiments in general relate to a pullup exercise assembly that includes rotatable handle assemblies and a pivotable bar assembly which can be oriented and secured into various positions between two vertical surfaces , such as the doorposts or sides of a door frame . the example exercise assembly can combine the pullup and chin - up exercise , and can be used for performing core exercises such as an inverted pushup ( known as an “ australian pullup ”), standing row exercise and a dip exercise , for example . fig1 is a perspective view of an exercise assembly in accordance with the example embodiments . the pullup exercise assembly , hereafter “ exercise assembly 1000 ”, is shown positioned between vertical surfaces 305 of a frame 300 . the exercise assembly 1000 includes a bar assembly 200 comprising a central bar 205 connected between a pair of side arm assemblies 250 . the central bar 205 may include a rubber overmold grip , for example . one or more handle assemblies 100 can be affixed to the central bar 205 via a j - hook 110 that forms part of the handle assembly 100 . the handle assembly 100 includes a j - hook 110 , a rotation assembly 120 , and a handle 130 . the j - hook 110 grips the central bar 205 . the j - hook 110 is connected to the rotation assembly 120 , which in turn is connection to the handle 130 . the j - hook 110 remains fixed in place as the handle 130 can be rotated around the axis of the j - hook 110 via the rotation assembly 120 . each side arm assembly 250 includes a vertical side strut 252 connected to a horizontal end stub 254 . the end stub 254 can be welded to the side strut 252 . the side struts 252 extend along the vertical surface 305 between an upper hook mount 215 ( which receives the portion of the side - arm assembly where the end stub 254 is attached to the side strut 254 ) and a lower mount 251 which includes a pivot pin 255 that extends through a slotted aperture 253 in the side strut 252 . the bar assembly 200 can pivot about the pivot pins 255 . in an example , the bar assembly 200 is first lifted out of the upper hook mounts 215 to unlock the pivot pin 255 , such that the pin 255 slides down into the wider part of the slotted aperture 253 . the bar assembly 200 can then be rotated to a desired angle from vertical to perform a different exercise such as a dip , standing row , inverted pullup , etc . as shown in fig1 , the bar assembly 200 includes a central hollow metal bar 205 , which can be covered with an overmold grip , as previously described . the central bar 205 is dimensioned so that its inner diameter is slightly larger than the outer diameter of the end stubs 254 . accordingly , the end stubs 254 are received within the central bar 205 , and may be secured via retaining rings 210 . fig2 is a perspective view of the handle assembly in accordance with the example embodiments . the handle assembly 100 is a standalone component ; in other words it is freely removable from the bar 205 and is not fixed to the central bar 205 by a connection means which requires assembly / disassembly , such as a pin , screw or actuation mechanism which locks and unlocks the handle assembly 100 from the central bar 205 . the j - hook 110 includes an upper curved portion 112 , an elongate intermediate body that is generally semi - circular in shape and which forms a circular shape at a base 116 of the hook 110 . the j - hook 110 may be made of a metal material such as steel ( which may be painted for stylistic purposes ), and alloy thereof , aluminum , etc . the handle 130 is connected to the rotation assembly 120 at a neck 139 . the handle 130 includes a metal u - bracket 132 having a grip member 138 secured therein by way of threaded fasteners 134 . the u - bracket 132 may be made of a medium or heavy gauge impact plastic such as acrylonitrile butadiene styrene ( abs ), or of a metal material such steel , and alloy thereof , cast aluminum , etc . the fasteners 134 may be pins for example . fig3 is an exploded view of the handle assembly of fig2 to illustrate components in greater detail . the rotation assembly 120 includes a generally circular or cylindrical bearing 119 which is positioned between a washer 125 and an internally threaded plug 118 . the bearing 119 permits the handle 130 to be rotated 360 degrees in either direction around a vertical axis of the j - hook 110 that is perpendicular to the bar 205 during exercise . the plug 118 receives a hex bolt 126 such that the external threads on bolt 126 mate with internal threads within plug 118 to connect the j - hook 110 with handle 130 . the plug 118 has a hex head shape that is a standard profile for an allen wrench , and fits into a bore 117 formed in base 116 . as can be seen in fig3 , bolt 126 extends through neck 139 , washer 125 and bearing 119 , to be threaded into the plug 118 . the rotation assembly 120 includes a rubber bellow 128 between the hook 110 and the neck 139 of the handle 130 . at its top , the rubber below 128 attaches to the base 116 of the j - hook 110 . the rubber bellow 128 mates with the neck 139 of handle 130 at its bottom so that a portion of the neck 139 contacts an interior surface of the bellow 128 . the rubber below 128 encloses the washer 125 and a portion of the bolt 126 extending there through . the handle 130 includes a hollow metal shaft 137 overlaid with or sheathed within grip member 138 . shaft 137 may be composed of chrome steel or aluminum , for example , and is secured to arms of the u - bracket 132 via insertion of fasteners 134 through holes 133 in the u - bracket 132 . the grip member 138 may be made of a foam rubber or suitable elastomeric material and has a wider or thicker center portion which tapers down to the end portions of the grip member 148 . the bearing 119 has an opening for receiving the bolt 126 . when the handle assembly 100 is assembled , the bearing 119 fits up into a bore 117 formed within the base 116 of the j - hook 110 , contacting an underside surface of plug 118 . fig4 is a front view of the handle assembly of fig2 , and fig5 is a cross - section view of the handle assembly in fig4 taken across a line a - a . referring to fig4 and 5 , the relationship between moving and fixed components with rotation assembly 120 can be seen in greater detail . the bearing 119 is designed to rotate around the fixed bolt 126 with the hook 110 being fixed on the central bar 205 and the user swiveling or rotating the handle 130 around the rubber bellow 128 such that the neck 139 and bearing 119 rotate together . thus , the bearing 119 and handle 130 rotate together for desired rotational movement in either direction . fig6 is a partial exploded view of the bar assembly 200 to illustrate components in greater detail , and fig7 is a partial exploded view of the bar assembly 200 to illustrate connection thereof between vertical surfaces . referring to fig6 and 7 , the outer ends of each end stub 254 are attached to corresponding upper ends of the side struts 252 . the portion of the side - arm assembly 250 shown in circle b of fig7 is received into the upper hook mount 215 . the upper hook mount 215 includes a channel 216 to receive the end of end stub 255 and top of side strut 252 at the intersection thereof . thus , the channel 216 has a sufficient width to accommodate the upper portion of the side - arm assembly 250 , as shown best in fig7 . the upper hook mount 215 is secured to a vertical surface 305 of a door frame 300 for example by suitable fasteners 217 ( such as wood screws ) through holes 219 formed in the upper hook mount 215 . a lower pivot mount 251 is provided to enable the bar assembly 200 to be pivotable , once the top of the assembly 200 is lifted out of the channels 216 of the hook mounts 215 . the lower pivot mount 251 is secured to the vertical surface 305 by suitable fasteners 258 ( such as wood screws ) through holes 259 formed in the lower pivot mount 251 . the lower pivot mount 251 contains the pivot pin 255 . the pivot pin 255 has a post with a mushroom head 257 that is configured to extend into the larger opening of the slotted aperture 253 . once the desired location of the bar assembly 200 is set , i . e ., the assembly 200 has either ( a ) been set for conventional pullup / chin - up exercises , or ( b ) has been pivoted to some desired angle from vertical for another exercise , the mushroom head 257 captures surfaces of the side struts 252 . for example , once the bar assembly 200 has been pushed downward so that the pivot pin 255 rides up the narrower channel 256 of slotted aperture 253 , the mushroom head 257 of the pivot pin 255 captures surfaces of the side struts 252 along the slotted aperture 253 . exercising may begin . in one example , the bar assembly 200 can be removed from the channels 116 of the upper hook mounts 215 and rotated up to 180 degrees to a lower dimension , pivoting around the lower pivot mounts 251 so as to permit one to perform inverted pushup exercises from the ground up , a standing rowing exercise , a dip exercise etc . fig8 illustrates a user performing a conventional pullup or chin - up exercise on the exercise assembly 1000 . since the handle assemblies 100 swivel , the user &# 39 ; s hands can rotate as the user is moving up and down , engaging additional muscle groups . fig9 illustrates a user performing an australian pullup on the exercise assembly 1000 . in this example , the fitness trainer has oriented the exercise assembly 1000 such that the side struts 252 and central bar 205 have been rotated downward approximately 180 degrees from vertical . in this orientation , the trainer can perform a reverse pushup ( australian pullup ) to work different muscles than can be achieved with a conventional pullup / chin - up bar . fig1 illustrates a user performing a standing row on the exercise assembly 1000 . in this example , the fitness trainer has oriented the exercise assembly 1000 such that the side struts 252 and central bar 205 have been rotated downward approximately 120 degrees from vertical . in this orientation , the trainer can perform a rowing exercise to work the core abdominal muscles , in addition to working the biceps , deltoids , pectorals and other back muscles . fig8 through 10 are merely example orientations of the exercise assembly 1000 to perform exercises other than standard pull - ups or chin - ups . it would be evident to one or skill in the art to re - position the side - arm assemblies 250 and central bar 205 to perform exercises other than shown in fig8 - 10 . therefore , unlike traditional pullup or chin - up bars that limit the user &# 39 ; s range of motion , the example exercise assembly 1000 includes twisting handles 130 on adjustable swing arms 250 which attach to the central bar 205 to maximize muscle motion . the handle assemblies 100 incorporate bearings 119 to enable 360 degree rotation . this permits the user &# 39 ; s arms to move naturally , reduces strain on joints , and engages additional muscle groups as compared to the standard pullup bar . the example exercise assembly 1000 thus may combine the standard pullup and chin - up exercises into one , and can facilitate additional workouts to core and abdominal muscle groups . the example embodiments being thus described , it will be obvious that the same may be varied in many ways . such variations are not to be regarded as departure from the embodiments of the present invention . all such modifications as would be obvious to one skilled in the art are intended to be included within the following claims . | an exercise assembly for performing a wide array of exercises including pull - ups and chin - ups is provided which includes a bar connected between rotatable swing arm assemblies . the swing arm assemblies extend along vertical faces of a frame and are adapted to rotate the bar from one position between the vertical faces to another position . the exercise assembly includes at least one handle assembly removably grasping the central bar and having a handle adapted to rotate 360 degrees during exercise . |
reference will now be made in detail to the present preferred embodiment of the invention , an example of which is illustrated in the accompanying drawings . while the invention will be described in connection with a preferred embodiment , it will be understood that it is not intended to limit the invention to that embodiment . on the contrary , it is intended to cover all alternatives , modification and equivalents as may be included within the spirit and scope of the invention defined in the appended claims . making reference first to fig1 the overall game apparatus is depicted from the perspective of the participant . the curved zig - zag or serpentine path incorporated into table 10 has a front to rear slope and is mounted within a support structure 50 which comprises a front panel 55 , side panels 56 , a rear panel 57 and bottom support panel 80 . a scoreboard 60 can be mounted on rear panel 57 . a base member 136 sits flush with the ground or flooring supporting the structure 50 . at the top of the front panel 55 is provided a steering wheel mount or transmission housing 31 upon which a steering wheel 30 is mounted . within the steering wheel mount 31 , depicted in fig5 is a set of two or more gears . top gear 68 turns on upper shaft 20 and lower gear 69 turns on lower shaft 24 . additionally , there is an axle 53 depicted in fig3 and 4 which provides linkage between steering wheel 30 and the curved zig - zag path 10 . while the preferred embodiment has been depicted with a steering wheel 30 , any implement capable of effecting rotational motion , such as a radial handle or lever 22 shown in fig2 can be employed . the curved zig - zag path 10 has a point of beginning 11 near the steering wheel 30 and , at the other end or rear of the zig - zag path 10 , an objective 12 . a curved zig - zag path 10 is generally planar and slopes from the upper point of beginning 11 to the lower objective 12 . the rail 13 is adapted to surround the zig - zag path from the point of beginning 11 down along the first portion 14 of the curved zig - zag path 10 . a ball 15 placed at or near the point of beginning 11 will , as a result of the force of gravity roll down the path 10 generally towards the objective 12 . while rolling along the first portion 14 of the path 10 the side rails 13 will keep the ball 15 on the path . after the ball 15 has passed the first portion 14 of the path 10 it will enter the last portion 16 of the curved zig - zag path 10 . at this point , the ball will leave the path 10 unless the participant ( not depicted ) can manipulate the rotation of the plane of the path 10 so as to prevent the ball 15 from rolling off of the path 10 . the successful participant will be able to manipulate the rotation of the path 10 until the ball reaches the objective 12 . fig1 also depicts the game enclosed in a clear cover cabinet 70 . the cabinet 70 , as depicted , has a front panel 71 . the steering wheel 30 or lever 22 has a shaft 29 connecting through panel 71 for insertion into insert 26 or 27 respectively . a ball drop hole 42 is located in front panel 71 to drop ball 15 onto table 10 . the bottom support panel 80 connects the cabinet panels 55 , 56 and 57 . strut 52 is mounted on a top surface of panel 80 . this support panel 80 could ( but need not ) be sloped down from the rear panel 57 to the front panel 55 so that a ball 15 which falls off the curved path 10 rolls down to the front panel 55 . by further adapting the support panel 80 with a channel 28 shown in fig1 or a low point adjacent to the front panel 55 , the ball 15 can be caused to roll to a designated point 83 along the front panel 55 which can be further adapted with a gate 85 for selectively retrieving the ball 15 through the front panel 55 at that point 83 . also located in front panel 55 is an optional ticket dispenser 40 . it should be noted that the principles of the invention do not require the use of any cabinet at all . in order to practice the game , it is only necessary to be able to mount a steering wheel 30 or control mechanism 22 in front of the path 10 and to pivotally support the rest of the path in a downward slope . accordingly , the support or mounting structure could be dispensed with altogether or could , alternatively , be in any shape or configuration which properly orients and supports the path 10 and control means . additionally , a single support structure could be built to house a series of such paths 10 side by side . additionally , the cabinet could be made in some manner other than with the substantially rectangular panels described and depicted herein . for instance , an elongated elliptical panel could be used ( not depicted ) with the planar path housed within the ellipse and the steering mechanism mounted at the oblong end proximate to the path point of beginning . any form of housing which would accommodate supporting the inclined orientation of the path and permit the rotation of the path would be satisfactory and within the spirit and scope of the invention as hereafter claimed . it should also be noted that the game may be automated . by adapting the gate 85 to be controlled with a coin activation device 86 a player could obtain access to a ball 15 without the need for an attendant by depositing the appropriate coin , token , ticket , or bill for play . once the ball 15 falls off of the path 10 , the ball 15 will automatically return to the gate 85 for the next plays as a result of the slope of the support panel 80 and any channel built therein . a coin activation mechanism is shown in fig1 . any such device capable of detecting the deposit of the correct combination of coins or tokens and energizing a relay would be satisfactory . this automatic feature is also presented as an optional enhancement of the game and is not necessary to make or practice a device incorporating the principles of the invention . making reference now to fig2 the relevant support structure of the path 10 can be seen . it is first noted that the curved zigzag path 10 from the side view is seen to be planar . it is also noted that the objective point 12 , may , but need not , be adapted with a net 18 to catch a ball which has been successfully manipulated to the objective point . the curved zig - zag path 10 is supported by an axle rod 53 which is axially connected to shaft 24 . at a point near the objective 12 a strut 52 supports the curved path 10 . the strut 52 is further adapted with a freely pivoting mount 59 as seen in fig7 - 8 , which permits the zig - zag path 10 to be rotated either clockwise or counter - clockwise . the axle rod 53 is in geared communication with the steering wheel 30 . the steering wheel 30 can be used to manipulate the rotation of the curved path 10 in either a clockwise or counter - clockwise direction . such rotation is in no way impeded by the pivoting mount 59 . referring to fig9 the steering wheel shaft 29 can be inserted into either the insert 27 for upper shaft 20 or the insert 26 for lower shaft 24 . a locked pin 62 locks the steering wheel shaft 29 in place within either insert 27 or 26 . a bushing 64 is inserted into holes 54 and 58 in the front wall 66 of the transmission housing 31 . shaft 20 fits through the bushing 64 and hole 54 to engage top gear 68 . shaft 24 fits through the bushing 64 and hole 58 to engage bottom gear 69 . a pin 90 locks the shaft 20 through hole 92 to gear 68 and another pin 90 locks the shaft 24 through hole 96 to gear 69 . the axle 53 of shaft 24 engages the universal joint 32 and is held in place by pin 122 . shaft 20 passes through bushing 98 and hole 100 in the back wall 102 of the transmission housing 31 . in like manner , shaft 24 passes through bushing 104 and then through hole 106 in back wall 102 . a bushing 108 , a spacer 110 , a washer 112 and acorn nut 114 terminate the threaded end 116 of shaft 20 . shaft 24 passes through bushing 116 , spacer 118 and washer 120 before engaging the universal joint 32 with axle 53 . pin 122 holds the axle 53 in place in the universal joint 32 . the universal joint 32 is connected to a plate 124 screwed to the bottom 126 of table 10 . if the steering wheel 30 is connected to lower shaft 24 , then as the player turns the wheel 30 in a clockwise direction the table 10 tilts in a clockwise direction . to make the game more difficult the wheel 30 can be connected to upper shaft 20 so that as the player turns the wheel in a clockwise direction the board 10 tilts in a counterclockwise direction . a threaded eye hook 128 is screwed by its threaded end into the bottom of gear 69 as seen in fig5 and 6 . the other end of the eye hook engages a pair of springs 130 which are engaged to separate eye hooks 132 and 134 bolted to the base member 80 joined to panels 55 , 56 and 57 . as see in fig9 an adjustable limiter device 138 is inserted into a hole 140 in the side portion of rear panel 102 . threads 142 on device 138 allow it to be adjusted to control its penetration through the side portion of rear panel 102 to act as a stop on gear 69 . the end of limiter device 138 has a rubber tip 162 to prevent damage to gear 69 . optionally , lights 144 can be attached along the periphery of curved path 10 to make the game more attractive in a night environment . in addition , a coin operating device as seen in fig1 can be added . this device has a solenoid 146 that is activated by a dropping coin . the solenoid causes arm 148 to lift plate 150 and allow a ball 15 to pass to the player . a spring 152 retains the plate 150 in a locked position by holding one end 154 of plate 150 . the plate pivots at point 156 when the arm 148 overcomes the pressure from spring 152 . a stopper pin 158 prevent plates 150 from being pulled too far by spring 152 . fig3 depicts the axle rod 53 as it is connected to the beginning portion of the curved zig - zag path 10 . as depicted , it can be seen that the universal joint 32 is used to permit tilting of table 10 . fig4 is a cut - out view showing how two gears 68 and 69 are built into the steering wheel mount 31 in order to translate the rotation of the steering wheel to the axle 53 of the path . with two gears ( one connected to the steering wheel translating rotation to the axle ) the steering wheel rotation will be opposite that of the axle 53 . three gears in series ( not depicted ) would result in the same direction of rotation . additionally , the gears could be made of different sizes in order to require more or less steering wheel rotation in order to achieve a given degree of path rotation . it finally should be noted that the steering control means could be in direct axle connection with the path axle ( such as with the universal joint of fig3 ) and no gears used at all . a micro switch 160 as shown in fig2 can be mounted on bottom surface 126 near objective 12 to indicate when a ball 15 has dropped into the objective 12 . this switch 160 can activate a digital musical recording , a light or bell . modification and variation can be made to the disclosed embodiments without departing from the subject and spirit of the invention as defined in the following claims . such modifications and variations , as included within the scope of these claims , are meant to be considered part of the invention as described . | a carnival or amusement park game in which a player is challenged to keep a rolling ball to its objective descending , planar , zig - zag path by manipulating the rotation of the plane of the path . the game may be further enhanced by providing rotational steering alternatives , providing for coin operation , or by providing a device to record or signal the event of a successful play . |
the present invention relates to novel methods of treating depression in a mammal in need of such treatment . the treatment comprises administering in unit dosage form an effective amount of a compound of formula ## str2 ## wherein r 1 is hydrogen or a lower alkyl and n is 4 , 5 , or 6 or a pharmaceutically acceptable salt thereof . the term lower alkyl includes straight or branched chain alkyl groups of up to eight carbon atoms . preferred compounds of formula i above include but are not limited to 1 - aminomethyl - 1 - cyclohexane - acetic acid , ethyl 1 - aminomethyl - 1 - cyclohexane - acetate , 1 - aminomethyl - 1 - cycloheptane - acetic acid , 1 - aminomethyl - 1 - cyclopentane - acetic acid , methyl 1 - aminomethyl - 1 - cyclohexane - acetate , n - butyl 1 - aminomethyl - 1 - cyclohexane - acetate , methyl 1 - aminomethyl - 1 - cycloheptane - acetate , n - butyl 1 - aminomethyl - 1 - cycloheptane - acetate , toluene sulfonate , 1 - aminomethyl - 1 - cyclopentane - acetate , benzene - sulfonate , and n - butyl 1 - aminomethyl - 1 - cyclopentane - acetate . pharmaceutical compositions of the compound of the present invention or its salts are produced by formulating the active compound in dosage unit form with a pharmaceutical carrier . some examples of dosage unit forms are tablets , capsules , pills , powders , aqueous and nonaqueous oral solutions and suspensions , and parenteral solutions packaged in containers containing either one or some larger number of dosage units and capable of being subdivided into individual doses . some examples of suitable pharmaceutical carriers , including pharmaceutical diluents , are gelatin capsules ; sugars such as lactose and sucrose ; starches such as corn starch and potato starch , cellulose derivatives such as sodium carboxymethyl cellulose , ethyl cellulose , methyl cellulose , and cellulose acetate phthalate ; gelatin ; talc ; stearic acid ; magnesium stearate ; vegetable oils such as peanut oil , cottonseed oil , sesame oil , olive oil , corn oil , and oil of theobroma , propylene glycol , glycerin ; sorbitol ; polyethylene glycol ; water ; agar ; alginic acid ; isotonic saline , and phosphate buffer solutions ; as well as other compatible substances normally used in pharmaceutical formulations . the compositions of the invention can also contain other components such as coloring agents , flavoring agents , and / or preservatives . these materials , if present , are usually used in relatively small amounts . the compositions can , if desired , also contain other therapeutic agents . the percentage of the active ingredient in the foregoing compositions can be varied within wide limits but for practical purposes it is preferably present in a concentration of at least 10 % in a solid composition and at least 2 % in a primary liquid composition . the most satisfactory compositions are those in which a much higher proportion of the active ingredient is present . routes of administration of the subject compound or its salts are oral or parenteral . for example , a useful intravenous dose is between 100 and 800 mg and a useful oral dosage is between 200 and 800 mg . a unit dosage form of the instant invention may also comprise other compounds useful in the therapy of depression . a typical dose is , for example , from 600 to 2400 mg per day given in three individual doses . a skilled physician will be able to determine the appropriate situation in which subjects are susceptible to or at risk of minor or major depression for administration by methods of the present invention . the advantages of using the compounds of formula i , especially gabapentin , in the instant invention include the relatively nontoxic nature of the compound , the ease of preparation , the fact that the compound is well tolerated , and the ease of iv administration of the drug . further , the drug is not metabolized in the body . the usefulness of compounds of formula i above and the salts thereof as agents for depression is demonstrated in the following case reports . note that the patients undergoing treatment for epilepsy using gabapentin appear to be better dressed and to take better care of themselves , children are doing better in school ; patients were more alert and some were more active . ______________________________________beneficial effect of gabapentin studypatient age sex day effect______________________________________1 51 m 78 less sluggish - able to perform better2 34 f 10 brighter and happier3 30 f 14 less depressed ; more energy4 38 m 28 more cheerful5 39 f 202 feels more positive about life6 25 f 28 much more alert and playful ; increased activity , borders on hyperactivity behavior at best since childhood7 27 f 29 improved mood8 32 f 119 better attitude______________________________________ examples of formulations of the subject compound of salts thereof are illustrated by the following examples . the compound or a suitable salt thereof is dissolved in water and passed through a 0 . 2 - micron filter . aliquots of the filtered solution are added to ampoules or vials , sealed and sterilized . combine the compound and the lactose in a tumble blend for two minutes , blend for one minute with the intensifier bar , and then tumble blend again for one minute . a portion of the blend is then mixed with the sterotex powder , passed through a # 30 screen and added back to the remainder of the blend . the mixed ingredients are then blended for one minute , blended with the intensifier bar for 30 seconds , and tumble blended for an additional minute . the appropriately sized capsules are filled with 141 mg , 352 . 5 mg , or 705 mg of the blend , respectively , for the 50 mg , 125 mg , and 250 mg containing capsules . combine the corn starch , the cellulose , and the compound together in a planetary mixer and mix for two minutes . add the water to this combination and mix for one minute . the resulting mix is spread on trays and dried in a hot air oven at 50 ° c . until a moisture level of 1 to 2 percent is obtained . the dried mix is then milled with a fitzmill through a # rh2b screen , and added back to the milling mixture and the total blended for five minutes by drum rolling . compressed tablets of 150 mg , 375 mg , and 750 mg , respectively , of the total mix are formed with appropriate sized punches the 50 mg , 125 mg , or 500 mg containing tablets . | the instant invention is a novel use of known cyclic amino acids . such compounds , including gabapentin , are useful for treating major and minor forms of depression . |
in fig1 there can be seen the preferred embodiment of the apparatus of the present invention designated generally by the numeral 10 . fig2 is a side view of apparatus 210 and fig3 is a side view of apparatus 310 . face mask release apparatus 10 can be used , for example , with a rounded contact sports helmet 11 which has forehead 12 and left 13 and right 14 temple areas . a face mask 15 in the form of a grid - like cage includes left and right side portion 16 and a central attachment 18 . thus , a three point attachment is defined for affixing the mask 15 to the helmet 11 , as shown generally in fig1 - 3 . each side 13 , 14 of helmet 11 provides a plurality of posts , preferably arranged in closely spaced pairs , which are placed on the helmet in various configurations , as shown in fig1 and 3 . in fig1 the right temple area 14 of the helmet 11 bears a pair of posts 20 which are spaced apart and define a line which forms a 45 ° angle with horizontal if the line connects the two posts . in fig2 the two posts 20 are shown on the left temple area 13 of helmet 11 , and in the embodiment of fig2 the posts 20 are arranged along a line which is horizontal . in fig3 the posts 20 are likewise arranged in an angular position with respect to horizontal , preferably 45 ° with respect to horizontal , however , in fig3 the rear post is in a lower position , whereas in fig1 the rear post is in a high position . in each embodiment of fig1 and 3 , the left and right connection 16 , 216 , 316 portions of masks 15 , 215 , 315 are provided with brackets which register with and form connections to the pair of spaced apart posts 20 , as shown in the drawings . in fig1 bracket 21 is generally s - shaped and could be , for example , manufactured of a rounded cross - section which corresponds to a narrowed grooved area of each post , as will be described more fully hereinafter . the bracket 21 includes a first portion 22 which wraps around the top side of posts 20 , a central section 23 which passes between the posts 20 in fig1 and a portion 24 which extends around the rear upper posts in fig1 to form the &# 34 ; s &# 34 ; pattern as shown . one skilled in the art will recognize that the force applied to mask 15 in a direction , as shown by arrow 25 , namely , a forwardly application of force as would normally occur , results in a retention of the mask to the helmet as is desirable . however , force applied in either direction along the line indicated by the force arrow 26 , or in a sideways direction , perpendicular to the force arrow 26 , will cause the bracket 21 to rotate off the posts 20 because the posts 20 would be manufactured of a slightly flexible but resilient material , such as hard rubber , plastic , or the like ( see fig8 and 9 ). in the configuration of fig2 the end connections 217 are connected to brackets 225 which include a first portion 226 that wraps around the top of the forwardly position of posts 20 , a central section 27 which passes between the posts 20 and a rear section 28 which wraps under the rearmost of the posts 20 . in fig3 the mask 315 provides bracket 29 that are generally c - shaped and affixed to the ends 316 of face mask 315 with a first portion 30 that extends along the forward edges of posts 20 and a bottommost portion 31 that wraps around the underside of the lower posts 20 , shown in fig3 while a third portion 32 of the bracket 29 extends around the upper and forward portion of the uppermost posts 20 , as shown in fig3 . the connection between mask 15 and the forehead 12 portion of helmet 11 includes a center post 19 provided on mask 15 which interlocks with a forehead support bracket 35 mounted on the foreward or forehead area 12 of helmet 11 , as shown in fig1 . bracket 35 would preferably have a socket 36 receptive of ball 37 , as best shown in fig4 and 4a . in the embodiments of fig1 a and 10b , a preloaded , adjustable socket 40 is seen receptive of ball 37 , the socket 40 including a bore 41 carrying a compression spring 42 that biases a curved follower plate 43 into engagement with ball 37 . the lowermost end portion 44 of socket 40 provides a knurled inner edge 45 in the form of a reduced diameter area that prevents curved follower plate 43 from exiting bore 41 , thus retaining it in that position . however , ball 37 also is retained within socket 40 , and more particularly , occupies a position within the confines of bore 41 , held in position by the knurled edge 45 , as shown in fig1 a and 10b . the follower plate 43 applies pressure to the ball which is adjustable by means of adjustment screw 46 and upper moveable stop 47 . the stop 47 is threadably attached to threaded shaft 48 of screw 46 and one skilled in the art will recognize that rotation of the screw 46 will cause the plate 47 to move upwardly and downwardly , as shown by the direction arrow 49 in fig1 a . by moving the plate 47 upwardly or downwardly , the force applied by the curved follower plate 43 to the ball 37 is varied , thus providing a preloaded value to the force applied to ball 37 , thus defining a release value for ball 37 from socket 40 . with players of lesser ability or younger players wherein injury might be more a problem , the socket could be preloaded with a very small release value so that a lower application of force to face mask 15 will cause the ball 37 to release from socket 40 . a similar adjustability to the release value of mask 15 , 215 and 315 from helmet 11 is provided between the attachment of mask 15 , 215 , and 315 to helmet 11 at posts 20 , and more particularly , the connection of brackets 21 , 225 , and 29 , to posts 20 . fig8 and 9 illustrate the variable release which can be made of face mask 15 to helmet 11 . in fig8 a single post 20 is shown as mounted upon helmet 11 . the attachment of posts 20 to helmet 11 can be , for example , by gluing , an adhesive , or by screws , or as shown in fig8 the posts can be integral with the helmet . the post is generally cylindrical providing a central longitudinal axis 20x , as shown in the drawings . the brackets 21 could be , for example , round in cross - section throughout the particular bracket 21 and when force is applied to the face mask 15 , the brackets 21 would simply roll off the posts 20 as shown by the phantom lines in fig8 . each post 20 provides a narrowed portion 50 of post 20 . this is provided at the joint between post 20 and helmet 11 . the narrowed portion is defined by an annular groove 52 that preferably extends 360 ° around post 20 , as shown in fig6 and 9 . the narrowed portion 50 of post 20 thus defines an outer enlarged head 53 portion which can provide a rounded outer surface 54 , as shown in fig8 . however , enlarged portion 953 can provide a downwardly extending lip 55 , as shown in fig9 so that the enlarged head portion 953 , extends substantially around the particular bracket 21 confining it so that release of bracket 21 from post 20a is more difficult than with the configuration of fig8 . further , the resiliency of post 20 could be varied so that a desired durometer reading for a particular rubber or plastic could be selected for post 20 . in this manner , a more flexible material would be used for post 20 in the case of children , and less experienced athletes , or with athletes in less physical condition . likewise , face mask brackets 21 , 225 , 29 could also be manufactured of a more flexible material having a flexibility which enhances release of face mask 15 from post 20 . from the above , one skilled in the art will recognize that by varying the configuration of post 20 and of annular recess 52 and of enlarged head 53 , and or by changing the resiliency of post 20 and or the resiliency of brackets 21 , 225 , 29 , a broad range of release values can be achieved as desired depending upon whether the player is highly skilled or a young beginner . fig5 and 5a illustrate additional embodiments for retaining mask 515 to the side 13 , 14 temple areas of helmet 11 which include a side ball and socket 550 type attachment of mask side end portions 516 to helmet 11 . in the preferred embodiment , the face mask 15 can be manufactured of any conventional structural material typically used in the manufacture of face masks , such as for example , any number of plastics ( such as polycarbonate alloy ) or a metal wire of round configuration covered with plastic . similarly , helmet 11 could be manufactured of any suitable commercially available helmet material such as any a number of plastics well known in the art , including for example , polycarbonate , polycarbonate alloy , fiberglass . posts 20 could be manufactured , for example , of hard rubber or of plastic and the posts could be manufactured integrally with the helmet , as shown in the embodiments of fig8 and 9 . however , posts 20 could be retrofitted to existing helmets using attachments , such as bolted connections , screwed connections , adhesive , rivets or the like . the foregoing description of the invention is illustrative and explanatory thereof , and various changes in the size , shape and materials , as well as in the details of the illustrated construction may be made without departing from the spirit of the invention . | a face mask release apparatus for a contact sports helmet includes a face mask having a three point attachment to the left and right respective side portions of the helmet and to the forward forehead area of the helmet . the attachment includes a plurality of posts , positioned in pairs on each respective side of the helmet in the temple areas and a ball and socket connection in the forehead area . each post includes a grooved area formed around the post defining a narrowed diameter section and a bracket carried at the ends of each side of the face mask forms a releasable connection with the posts in virtually all directions away from the helmet and along the helmet so that the user is protected from head and neck injury when force is applied to the mask in any of one of a plurality of directions . |
the following description of the preferred embodiment is merely exemplary in nature and is in no way intended to limit the invention , its application , or uses . for example , the present invention may be used during any meal , such as breakfast , brunch , lunch , dinner , supper , a picnic , or at any time a conversation or a discussion between dining partners is encouraged . moreover , the present invention may find utility in various applications such as residential , commercial , corporate , cruise , and the like . for purposes of this description , the term “ tableware ,” “ tableware piece ,” or “ dining - piece ” shall each include any plate , saucer , charger , bowl , cup , glass , goblet , napkin holder , napkin , placemat , table utensil , table decoration , party favor , and / or any other piece or item used in setting a table for a meal , such as breakfast , brunch , lunch , dinner , supper , a picnic , and the like . the terms “ tableware ,” “ tableware piece ,” or “ dining - piece ” may be used interchangeably . this tableware shall be made of conventional materials , such as china , earthenware , stoneware , porcelain , plastic , glass , silver , gold , steel , paper , expanded rigid polystyrene plastic such as styrofoam ™, or any other material or composition commonly used in manufacturing formal , everyday , or disposable tableware products . referring to fig1 - 3 , a conversation - generating apparatus 10 includes at least one tableware piece 12 defining a top or exposed surface 14 and a bottom or unexposed surface 16 . exposed surface 14 is generally exposed to the view of the user when tableware piece 12 is placed on a table and , in terms of a plate , would be the side in which food or other tableware is placed . on the other hand , unexposed surface 16 is generally concealed from the view of the user when tableware piece 12 is placed on a table and , again in terms of a plate , would be the non - food side that is placed downwardly . it is anticipated that conversation - generating apparatus 10 may include any number of tableware or dining pieces . each tableware piece 12 includes an open - ended question or command 18 printed on a surface thereof or otherwise affixed thereto . in the interest of brevity , open - ended question or command 18 will be referred to as open - ended question 18 unless otherwise noted . however , it should be appreciated that a command that instructs a guest to describe an experience , situation , opinion , or the like is within the scope of this invention . preferably , open - ended question 18 is printed on unexposed surface 16 of tableware piece 12 to prevent a user from reading the question or command prior to a discussion or conversation . however , open - ended question 18 may also be printed on exposed surface 14 of tableware piece 12 to be preferably covered by food or other tableware . it is anticipated that open - ended question 18 is printed on or affixed to tableware piece 12 in a known manner , such as by forming the lettering under a coating applied to the tableware piece either during or after the manufacturing process . this printing method would allow for a smooth , unobstructed , durable finish on the surface thereof . such printing of open - ended question 18 in this manner also prevents the lettering from contaminating any food items placed on or in tableware piece 12 . however , it should be appreciated that any printing or affixing method known to one skilled in the art may be used . open - ended question or command 18 is generally defined as a question or command that allows for a spontaneous , unstructured response that typically has no right or wrong answer . open - ended questions or commands commonly allow a respondent to elaborate on their own personal thoughts , opinions , feelings , or experience relating to a specific topic . preferably , open - ended question or command 18 is chosen from topics relating to politics , history , movies , theatre , sports , children , marriage , dating , religion , famous people , television , education , alma maters , space , general matters , personal experiences , festive occasions , and the like . it should be noted that open - ended question 18 may be any question which allows for a spontaneous , unstructured response . by way of non - limiting example , the following open - ended questions represent a varied cross - section of possible alternatives that are believed to elicit a spontaneous , unstructured response : 1 .) if you could invite a person in history to have dinner with you , who would it be 2 .) which relative or acquaintance makes you want to “ run for cover ,” when they 1 .) which u . s . political figure has made the most important contribution to our 2 .) which top five inventions have made the most impact on our culture ? 1 .) if you could spend a weekend “ on location ” during the filming of a movie with 2 .) what movie should be a requirement for all children to see ? 1 .) choose a sport and describe how certain aspects of the sport mimic life and its 2 .) which american athlete presents the best qualities of a role model for youth 1 .) what did you do to receive the most memorable punishment of your life ? 2 .) you are getting ready to leave for school , what do you hear your mom or dad 2 .) what physical characteristics do you appreciate most in a potential date ? 1 .) you are talking to a young person about to marry , what three pieces of advice 2 .) what was the funniest event that occurred during your wedding and / or on your 1 .) which verse provides you with the most inspiration for dealing with life &# 39 ; s 2 .) you and god are dining , what do you say to him and what does he say to preferably , each guest receives at least one tableware piece 12 . this tableware piece would include a unique open - ended question 18 that is unlike any of the remaining open - ended questions . the use of conversation - generating apparatus 10 will now be described in further detail . as set forth above , the present invention may be used for a variety of entertaining situations . however , in the interest of brevity , the use of conversation generating apparatus 10 will be described with reference to a dinner party environment or other formal occasion . place settings for formal dinner parties typically include the largest number of individual tableware pieces , such as plates , saucers , chargers , bowls , cups , glasses , goblets , napkin holders , napkins , placemats , table utensils , table decorations , party favors , and the like and , thus , provide the opportunity for the most complete description of the preferred embodiment . however , this detailed description shall not be interpreted to limit this application in that this invention may be used with a single tableware piece with a single open - ended question or command printed thereon . to use conversation - generating apparatus 10 , each guest or dining partner randomly receives a complete set of tableware defining a single place setting . preferably , each piece of tableware 12 may include open - ended question or command 18 printed on unexposed surface 16 . the printing of open - ended question or command 18 on unexposed surface 16 prevents each guest from knowing his / her questions . this prevents each guest from knowing and preparing a response to the open - ended question beforehand . consequently , the intent of eliciting spontaneous , unstructured answers and opinions is maintained . however , it is anticipated that in the alternative , open - ended question or command 18 may be printed on exposed surface 14 of tableware 12 . when these questions or commands are printed on exposed surface 14 , they may be obscured from view by food or beverage or may be revealed to the guest upon sitting at the table . the specific time at which the open - ended questions or commands are revealed to the guest may be determined by the host and may be tailored to suite the desired atmosphere of the social gathering . at a time to be determined by the host , each guest or dining partner is asked to uncover , if necessary , the open - ended question or command that is printed on a specific piece of tableware and read it aloud to the remaining dining partners . this is preferably done prior to the serving of the next course . the guest then answers the open - ended question or command aloud , thereby sharing with the remaining dining partners their own thoughts , opinions , feelings , and / or experiences relating to the topic . the remaining dining partners are then engaged in a group discussion relating to the open - ended question or command and / or the answer ( s ) provided by their fellow dining partner ( s ). once the group discussion is substantially exhausted or at a time determined by the host , another guest is asked to read aloud and answer aloud the open - ended question or command printed on one of their specific pieces of tableware and the process is repeated for each guest . alternatively , one guest may read the open - ended question or command , while another guest responds to the question or command . it is important to note that there may be variations to this method that are within the scope of this application which still provide for eliciting a spontaneous , unstructured response to facilitate conversation among guests . by providing each guest with multiple tableware pieces having a different open - ended question or command printed thereon , each guest may have multiple turns of reading aloud and answering aloud their specific questions or command . it is also anticipated that the present invention may be used by two or more dining partners . for example , the present invention may be particularly useful in quickly getting to know the personal opinions and / or experiences of someone that one is dating or seeking to employ . the invention being thus described , it will be obvious that the same may be varied in many ways , such as with some editions centered on a certain theme and / or limits on production volumes . such variations are not to be regarded as a departure from the spirit and scope of the invention . such variations or modifications , as would be obvious to one skilled in the art , are intended to be included within the scope of the following claims . | tableware capable of facilitating conversation between guests and a method of using the same is provided that includes : a ) providing a set of open - ended questions or commands each being separately printed on a surface of a dining - piece ; b ) distributing one or more of the dining - pieces to each dining partner ; c ) having each dining partner read aloud the open - ended question or comment printed on their dining - piece ; d ) having one of the dining partners answer the open - ended question ; and e ) engaging all of the dining partners in open discussion of alternate answers to the question . |
with reference to fig1 , an embodiment of the ball bat 10 of the present invention is shown having an end cap 12 , a barrel 14 , a transition region 16 , a handle 18 , and a knob 20 . the barrel 14 is a hollow tube and , in one embodiment , has an inner diameter of about 2 . 0 inches ( 5 . 08 cm ). as shown in fig2 a - b , the end cap 12 includes a central ring 22 stabilized by a plurality of ribs 24 . in one embodiment , the central ring 22 has an inside diameter of about 0 . 625 inches ( 1 . 59 cm ). the end cap 12 may be secured to the barrel 14 by any suitable method , such as , for example , bonding with an adhesive , a friction fit , or a mechanical lock where an end cap ridge and corresponding barrel channel , or vice versa , secure the end cap 12 via mechanical interference . the end cap 12 may be manufactured using common manufacturing techniques , as known in the art . with reference to fig3 b , 4 , and 6 , the ball bat includes a central tube 26 coaxially positioned within the barrel 14 . the central tube 26 extends along a longitudinal axis 40 and includes an end 28 sized to snugly fit within the central ring 22 . the end 28 may be retained within the central ring 22 by any suitable means , such as , for example by bonding with an adhesive and with a pin 44 . in one embodiment , as shown in fig6 , corresponding central tube holes 46 and central ring holes 48 are formed , such that a split pin 44 may be inserted through the holes 46 , 48 , mechanically locking the end 28 within the central ring 22 . the central tube 26 may be constant diameter or variable diameter . in one embodiment , as shown in fig3 , the end 28 has an outer diameter of about 0 . 625 inches ( 1 . 59 cm ), remaining constant for a length of about 0 . 755 inches ( 1 . 92 cm ). the diameter of the central tube 26 then increases over a length of about 0 . 47 inches ( 1 . 19 cm ) to a diameter of about 0 . 875 inches ( 2 . 22 cm ), which remains generally constant for a length of 5 . 9 inches ( 15 . 0 cm ). the total length of the central tube 26 is about 7 . 125 inches ( 18 . 1 cm ). the central tube 26 may be made of any suitable material , such as , for example , composite fiber . the central tube 26 includes at least one restriction member 50 capable of limiting the deformation experienced by the ball bat 10 upon impact of a ball . the at least one restriction member 50 is a generally washer - shaped member with a restriction member central channel 42 . the at least one restriction member 50 is positioned coaxially around the central tube 26 , with the central tube 26 positioned within the restriction member central channel 42 of the at least one restriction member 50 . the outer diameter of the at least one restriction member 50 is less than the inner diameter of the barrel 14 , creating a void 90 between the at least one restriction member 50 and the inner surface of the barrel 14 . in the embodiments shown in fig4 and 5 , the outer diameter of the at least one restriction member 50 may be 75 - 95 % the inner diameter of the barrel 14 or , preferably , 85 - 92 % the inner diameter of the barrel 14 . the at least one restriction member 50 is composed of a resilient material capable of resisting deformation , such as aluminum or pre - impregnated composite fiber (“ pre - preg ”). in a preferred embodiment , the at least one restriction member 50 is composed of 7075 aluminum or laminated graphite pre - preg . in one embodiment , as shown in fig3 , the central tube 26 includes a first restriction member 30 . in this embodiment , the first restriction member 30 has an outer diameter 51 of about 1 . 75 inches ( 4 . 45 cm ), 87 . 5 % the inner diameter of the barrel 14 , and a length 53 of about 0 . 11 inches ( 2 . 8 mm ). the first restriction member 30 is located along the length of the central tube 26 at about the same longitudinal station as the center of the optimal hitting area or “ sweet spot ” of the ball bat 10 . in this embodiment , the first restriction member 30 is located about 6 . 5 inches ( 16 . 5 cm ) from the end of the ball bat 10 . in this embodiment , the central tube 26 further includes a second restriction member 32 . the second restriction member 32 has an outer diameter of about 1 . 70 inches ( 4 . 32 cm ), 85 % the inner diameter of the barrel 14 , and a length of about 0 . 11 inches ( 2 . 8 mm ). the second restriction member 32 is located along the length of the central tube 26 at a position between the first restriction member 30 and the end cap 12 . in this embodiment , the second restriction member 32 is located about 5 . 0 inches ( 12 . 7 cm ) from the end of the ball bat 10 . in other embodiments , the central tube 26 may include a single restriction member , two , three , or more restriction members . the maximum performance of a ball bat 10 may be precisely controlled by varying the number of restriction members and the diameter , length , and location of each . the ball bat 10 preferably includes a support 34 , as shown in fig4 . the support 34 is generally cylindrical and sized to snugly fit within the barrel 14 . the support 34 includes a support central channel 36 sized to snugly accept the central tube 26 . in one embodiment , the support 34 has a diameter of about 2 . 0 inches ( 5 . 08 cm ) and the support central channel 36 has a diameter of about 0 . 875 inches ( 2 . 22 cm ) and snugly accepts the 0 . 875 inch ( 2 . 22 cm ) diameter section of the central tube 26 . the central tube 26 extends at least partially through the support central channel 36 . preferably , the support 34 is placed coaxially around the central tube 26 at a longitudinal station where the support 34 contacts at least one restriction member 50 . in an embodiment with a first restriction member 30 and second restriction member 32 , the support 34 is preferably placed coaxially around the central tube 26 between the first restriction member 30 and second restriction member 32 , as shown in fig4 . preferably , the support is of sufficient length to contact both the first restriction member 30 and second restriction member 32 . in an embodiment where the first restriction member 30 is located about 6 . 5 inches ( 16 . 5 cm ) from the end of the ball bat 10 and the second restriction member is located about 5 . 0 inches ( 12 . 7 cm ) from the end of the ball bat 10 , the support 34 has a length of about 1 . 39 inches ( 3 . 53 cm ), which places the support 34 in contact with both the 0 . 11 inch ( 2 . 8 mm ) long restriction members . in an embodiment with a third or more restriction members , the present invention preferably includes additional supports 34 positioned between each pair of restriction members . in an embodiment with a single restriction member , as shown in fig5 , the support is preferably placed coaxially around the central tube 26 on a side of the restriction member opposite the end cap 12 , such that the central tube 26 extends partially through the support central channel 36 . the support 34 may be made of any suitable material , such as , for example , foam , or preferably , expanded polyproplyene (“ epp ”) foam with a density between 1 . 0 and 2 . 0 lb / cu . ft . ( 16 . 0 - 32 . 0 g / l ), ideally about 1 . 3 lb / cu . ft ( 20 . 8 g / l ). by contacting at least one restriction member 50 , the support 34 serves to dampen any vibration of the at least one restriction member 50 and the central tube 26 that occurs as a result of an impact between the ball bat 10 and a ball . for example purposes only , a central tube 26 may be made by rolling at least one flat sheet of pre - preg around an appropriately shaped mandrel , thereby making a variable diameter tube as described above . in a preferred embodiment , the sheet of pre - preg comprises six layers of graphite pre - preg with fibers angled +/− 20 degrees from the longitudinal with each layer orientated at a negative angle to the previous layer . each layer has a height of about 0 . 005 inches ( 0 . 127 mm ), providing a central tube 26 with a thickness of about 0 . 03 inches ( 0 . 76 mm ). at least one restriction member 50 is positioned on the central tube 26 at the appropriate longitudinal station . the central tube 26 is then placed in a mold conforming to the shape of the central tube 26 including the at least one restriction member 50 . the mold includes at least one pair of hollows where excess composite fiber may be added . for each pair of hollows , one hollow is located adjacent to and on the end cap 12 side of a restriction member 50 and the other hollow is located adjacent to and on the knob 20 end side of the same restriction member 50 . upon curing , the excess composite fiber in each hollow forms a protrusion on the central tube 26 extending perpendicular to the longitudinal axis 40 of the central tube 26 . each protrusion has a height of about 0 . 11 inches ( 2 . 8 mm ). each pair of protrusions creates and defines a groove 38 extending perpendicular to the longitudinal axis 40 of the central tube 26 . each groove 38 is sized such that it may secure and retain a restriction member 50 by mechanical interference . in one embodiment , each groove 38 has a length of about 0 . 11 inches ( 2 . 8 mm ). in an embodiment including a plurality of restriction members , as shown in fig3 b and 4 , the central tube 26 includes a plurality of grooves 38 , whereby each groove 38 accepts and secures one restriction member 50 at the desired longitudinal station . after curing , the central tube 26 is positioned within the support central channel 36 . in a preferred embodiment , a slit is introduced into the support 34 , such that the support 34 may be opened in a clamshell fashion to receive the central tube 26 . the handle 18 is a mostly constant diameter hollow tube . the handle 18 may be manufactured using common manufacturing techniques . for example purposes only , a composite handle 18 may be made by rolling at least one flat sheet of pre - preg around a mandrel , thereby making a tube with an outer diameter appropriately sized for a ball bat handle . in a preferred embodiment , the sheet of pre - preg comprises two layers of graphite pre - preg with fibers angled +/− 15 degrees from the longitudinal with one layer orientated at a negative angle to the other layer . two layers of pre - preg with a height of about 0 . 005 inches ( 0 . 127 mm ) and fibers angled 90 degrees from the longitudinal are wrapped around the last 7 . 87 inches ( 20 . 0 cm ) of the handle 18 at the end opposite the knob 22 . the barrel 14 is a mostly constant diameter hollow tube that tapers through a transition region 16 to the handle 18 . in one embodiment , the barrel 14 is made of composite material . the composite barrel 14 may be manufactured using common manufacturing techniques . for example purposes only , a composite barrel 14 may be manufactured by spirally rolling 24 layers of high aspect ratio parallelogram - shaped pieces of pre - preg , each layer having a height of about 0 . 005 inches ( 0 . 127 mm ), on a rolling mandrel with the fibers oriented longitudinally , thereby making a tube with an outer diameter appropriately sized for a ball bat barrel . the parallelograms are rolled up such that each layer has a butt joint with itself and such that on one end all the layers stop at the same longitudinal station but on the other end , each layer is about 2 . 54 inches ( 1 . 0 cm ) shorter than the previous layer , creating a tapered end . in one embodiment , the layers are angled +/− 37 degrees from the longitudinal with each layer orientated at a negative angle to the previous layer . after being rolled up , a tapered mandrel is added to one end of the rolling mandrel immediately after where the lay - up ends on the tapered end . rubber bands are placed around the lay - up on this end , then the entire assembly is partially slid off the rolling mandrel and onto the tapered mandrel , forming a tapered transition region 16 . in one embodiment , the transition region 16 is about 8 . 0 inches ( 20 . 3 cm ) in length . the barrel 14 is removed from the mandrels and a portion of the handle 18 is inserted . an inflatable bladder is inserted into the ball bat 10 assembly and a standard knob 20 is applied using techniques common in the industry . the bladder is inflated , expanding the barrel 14 and handle 18 . the assembly then is placed into a ball bat - shaped mold under pressure and heated to cure the ball bat , using standard techniques known in the art . after curing , the end cap 12 and central tube 26 are inserted into the ball bat 10 . fig5 depicts a second embodiment of the ball bat 110 of the present invention wherein the at least one restriction member 50 is a single restriction member 130 . in this embodiment , the single restriction member 130 has a diameter of about 1 . 75 inches ( 4 . 45 cm ) and a length of about 0 . 11 inches ( 2 . 8 mm ). the single restriction member 130 is located along the length of the central tube 26 at about the same longitudinal station as the center of the optimal hitting area or “ sweet spot ” of the ball bat 10 , about 6 . 5 inches ( 16 . 5 cm ) from the end of the ball bat 10 . in this embodiment , the central tube 126 includes a single groove 138 which secures and retains the single restriction member 130 . the support 134 is preferably positioned around the central tube 126 on a side of the single restriction member 130 opposite the end cap 12 . in this embodiment , the 1 . 39 inch ( 3 . 53 cm ) long support 134 will extend past the central tube 26 , as shown in fig5 . in alternative embodiments , a shorter support 134 may be used such that the support 134 does not extend past the central tube 26 . in a third embodiment of the present invention , as shown in fig7 a - b , 8 a - b , 9 a - b , and 10 , a ball bat 210 may include at least one resilient member 252 disposed about at least one of the at least one restriction member 250 . as previously discussed , when the ball bat 210 impacts a ball , the barrel 214 transiently deforms until the inner surface of the barrel 214 contacts the at least one restriction member 250 . the resilient member 252 increases the effective diameter of the at least one restriction member 250 , which provides a smaller void 290 between the at least one restriction member 250 and the inner surface of the barrel 214 , which can further limit the performance of the ball bat 210 . use of at least one resilient member 252 has also been found to affect the sound upon impact between a ball and the ball bat 210 . in one embodiment , the at least one resilient member 252 is a rubber ring encircling or otherwise disposed about the at least one restriction member 250 , as shown in fig9 a - b . in a preferred embodiment , the resilient member 252 is a rubber ring with a hardness of about 90 - 95 shore a . in embodiments including a plurality of restriction members 250 , resilient members 252 may be disposed about none , less than all , or all of the plurality of restriction members 250 . referring now to fig7 a - b , the at least one restriction member 250 of the third embodiment is preferably shaped to retain the resilient member 252 about the at least one restriction member 250 . in one embodiment , where the inner diameter of the barrel 214 is 2 . 28 inches ( 5 . 79 cm ), the at least one restriction member has a diameter of about 2 . 124 inches ( 5 . 38 cm ) and includes a restriction member central channel 242 with a diameter of about 0 . 875 inches ( 2 . 22 cm ). the at least one restriction member 250 , at a position adjacent of the restriction member central channel 242 , has a length of about 0 . 3 inches ( 7 . 6 mm ) and maintains this length from a diameter 0 . 875 inches ( 2 . 22 cm ) to about 1 . 148 inches ( 2 . 92 cm ). the length of the at least one restriction member 250 is about 0 . 08 inches ( 2 . 0 mm ) from a diameter of about 1 . 148 inches ( 2 . 92 cm ) to about 1 . 752 inches ( 4 . 45 cm ). the length of the at least one restriction member 250 increases at about a 45 degree angle from 0 . 08 inches ( 2 . 0 mm ) to 0 . 3 inches ( 7 . 6 mm ) as the diameter increases from about 1 . 752 inches ( 4 . 45 cm ) to about 1 . 86 inches ( 4 . 72 cm ). the at least one restriction member 250 maintains the length to a diameter of about 2 . 114 inches ( 5 . 37 cm ), then , on either end of its length , decreases on a curve with a radius of 0 . 01 inches ( 0 . 25 mm ) to a maximum diameter of 2 . 124 inches ( 5 . 38 cm ). the diameter of the at last one restriction member 250 then decreases at about a 15 degree angle to a diameter of 2 . 07 inches ( 5 . 26 cm ), forming a restriction member groove 254 about 0 . 25 inches ( 6 . 4 mm ) in length bounded by a pair of projections 256 . other designs for shaping the at least one restriction member 250 to retain the at least one resilient member will be apparent to individuals skilled in the art . the resilient member 252 in this embodiment has a inner diameter 258 of about 2 . 07 inches ( 5 . 26 cm ) and an outer diameter 260 of about 2 . 25 inches ( 5 . 72 ). the resilient member 252 is sized to fit within the restriction member groove 254 and preferably includes a length about equal to or less than the length of the restriction member groove 254 . as shown in fig9 a and 9b , the resilient member 252 encircles the at least one restriction member 250 , and is retained within the restriction member groove 254 by the projections 256 . in this embodiment , where the inner diameter of the ball bat is 2 . 28 inches ( 5 . 79 cm ), there is a 0 . 03 inch ( 0 . 76 mm ) void 290 between the resilient member 252 . the outer diameter 260 of the resilient member 252 may 90 - 99 . 5 % the inner diameter of the barrel 214 , or preferably 94 - 99 % the inner diameter of the barrel 214 . in this particular embodiment , the outer diameter 260 of the resilient member 252 is 98 . 7 % the inner diameter of the barrel 214 and the length of the resilient member is about 0 . 236 inches ( 6 . 0 mm ). in the third embodiment , as shown in fig1 , the central tube 226 includes a first restriction member 230 . in this embodiment , the inner diameter of the barrel 214 is 2 . 28 inches ( 5 . 79 cm ) and the total length of the ball bat 210 is 32 inches ( 81 . 3 cm ). in this embodiment , the first restriction member 230 has a diameter of about 2 . 03 inches ( 5 . 16 cm ) to the surface of the restriction member groove 254 , and a diameter of about 2 . 08 inches ( 5 . 28 cm ) to the tips of the projections 256 . a first resilient member 262 is disposed about the first restriction member 230 in the restriction member groove 254 , and has an outer diameter 260 of about 2 . 21 inches ( 5 . 61 cm ). the second restriction member 232 has a length of about 0 . 3 inches ( 7 . 6 mm ). the first restriction member 230 is located along the length of the central tube 26 at about the same longitudinal station as the center of the optimal hitting area or “ sweet spot ” of the ball bat 210 . in this embodiment , the first restriction member 230 is located about 6 . 75 inches ( 17 . 1 cm ) from the end of the ball bat 210 . in this embodiment , the central tube 226 further includes a second restriction member 232 . the second restriction member 232 has a diameter of about 2 . 07 inches ( 5 . 26 cm ) to the surface of the groove 254 , and a diameter of about 2 . 12 inches ( 5 . 38 cm ) to the tips of the projections 256 . a second resilient member 264 is disposed about the second restriction member 232 in the restriction member groove 254 , and has an outer diameter 260 of about 2 . 25 inches ( 5 . 72 cm ). the second restriction member 232 has a maximum length of about 0 . 3 inches ( 7 . 6 mm ). the second restriction member 232 is located along the length of the central tube 26 at a position between the first restriction member 230 and the end cap 12 . in this embodiment , the second restriction member 232 is located about 5 . 25 inches ( 13 . 3 cm ) from the end of the ball bat 210 . the foregoing detailed description is given primarily for clearness of understanding and no unnecessary limitations are to be understood therefrom for modifications can be made by those skilled in the art upon reading this disclosure and may be made without departing from the spirit of the invention . | industry regulatory organizations have created performance restrictions for ball bats . the present invention relates to a ball bat with an internal impact dampening means . more particularly , the present invention relates to a ball bat with a handle , a barrel , and a central tube positioned coaxially within the barrel . the central tube includes at least one restriction member capable of limiting the deformation experienced by the ball bat upon impact of a ball . precisely limiting the deformation of the ball bat allows the present invention to achieve , but not exceed , performance substantially equal to the maximum performance allowed by industry regulatory organizations and maintain that level of performance over a substantial length of the ball bat . |
the present invention is directed to a variety of hair pre - treatment compositions . in some embodiments , the hair pre - treatment compositions comprise ( or consist essentially of , or consist of ) a combination of ( 1 ) one or more hydrophilic water - soluble polymers in combination with ( 2 ) one or more nonionic lipophilic oil soluble polymers together with selected ( 3 ) water - and ( 4 ) oil - soluble antioxidants or reducing agents in ( 5 ) an acceptable cosmetic base . the hair pre - treatment compositions and method of use are effective for protecting hair from damage caused by antibacterial and / or oxidizing agents normally employed in treated pools ( e . g ., swimming pools ). these consist of , but are not limited to , ionic salts containing an oxidized ionic species , such as halogens , consisting of mainly chlorine - and bromine - containing oxidizing agents such as sodium hypochlorite , etc ., oxygen bleaches such as sodium perborate , and organic containing oxidants such as isocyanurates . the hydrophilic water - soluble polymers employed in the hair pre - treatment compositions of the present invention are desirably cationic modified polysaccharides or synthetic polymers , which carry a net cationic charge . the foregoing includes known industrial compounds , which are commercially available from cosmetic suppliers . these include , but are not limited to , guar hydroxypropyl trimonium chlorides ( ghptcs ) such as jaguar ® and aquacat ® products commercially available from aqualon corporation ( wilmington , de . ); cationic modified cellulosics such as polyquaternium 10 ( i . e ., cellulose 2 -( 2 - hydroxy - 3 -( trimethylammonio ) propoxy ) ethyl ether ), one of a series of celquat ® products from akzo nobel ( amsterdam , netherlands ); and diallyl dimethyl ammonium chloride / acrylamide copolymer such as merquat ® products ( e . g ., ( polyquaternium - 7 ) commercially available from nalco company ( naperville , ill .). the charge density of the cationic polymers may be modified to balance substantivity with removal to avoid build - up on hair . the charge density , related to the amine functional cationic groups , is typically from about 0 . 01 meq / gram to 10 meq / gram , and preferably , from about 0 . 2 to about 7 meq / gram , and most preferably , between about 0 . 18 to about 0 . 36 meq / gram . the cationic polymers , which can used alone or in combination , are typically employed at a total cationic polymer ( s ) level of from about 0 . 1 to about 10 % by weight , and preferably from about 0 . 5 to about 6 % by weight , and most preferably from about 1 to about 3 % by weight . the lipophilic nonionic polymers suitable for use in the present invention include , but are not limited to , the following classes of compounds : polyvinyl stearyl ethers commercially available under the trade designation giovarez ® from phoenix chemical , inc . ( sommerville , n . j . ), pvp / eicosene copolymers commercially available under the trade designation ganex ® from international specialty products ( wayne , n . j . ), and hydrogenated castor oil / sebacic acid copolymers commercially available under the trade designation crodabond ® from croda ( edison , n . j . ), a di - behenyl imidazolinium product such as quaternium 91 from croda . the lipophilic nonionic polymers may be used alone or in combination to achieve optimal wash off / water resistance during use . the total level of lipophilic nonionic polymer ( s ) employed may be from about 1 to about 15 % by weight , preferably , from about 2 to about 10 % by weight , and most preferably , from about 4 to about 8 % by weight . the ratio of hydrophilic cationic polymer ( s ) to lipophilic nonionic polymer ( s ) may be from about 1 : 10 to about 10 : 1 , and a preferred ratio is from about 1 : 7 to about 7 : 1 by weight in the final composition . the oil - soluble antioxidants employed by the present invention include , but are not limited to , tocopherol ( e . g ., alpha tocopherol ), tocotrienol ( e . g ., alpha tocotrienol ), and carotenoids . the oil - soluble antioxidants , which can used alone or in combination with one another , are typically present at a total amount of oil - soluble antioxidant ( s ) of from about 0 . 1 to about 10 % by weight of the formula , and preferably , at about 1 to about 5 % by weight , and most preferably , from about 1 to about 3 % by weight . the water - soluble antioxidants suitable for use in the present invention include , but are not limited to , sulfur containing amino acids such as cysteine or methionine , their analogs , and di - or tri - peptides containing at least one cysteine or methionine moiety in the amino acid sequence ; sodium thoisulfate ; butylhydroxytoluene ( bht ); butylhydroxyanisole ( bha ); sodium bisulfate ; sodium metabisulfite ; and bis - phenol extracts of plant origin . the water - soluble antioxidants may be used alone or in combination with one another . the water - soluble antioxidants are typically present in a total amount of one or more water - soluble antioxidants of from about 0 . 1 to about 5 % by weight , and preferably , at about 1 to about 3 % by weight in the finished product . the above - described active ingredients may be incorporated in a cosmetic base , which exhibits both ( i ) compatibility with the above - described active ingredients , and ( ii ) acceptable aesthetics on the treated hair . the cosmetic base components may include , but are not limited to , deionized water ; cationic surfactants ; fatty alcohols such as cetearyl alcohol ; nonionic emulsifiers ; rheology modifiers ; preservatives ; chelators ( e . g ., edta and its salts , such as disodium edta ); dyes ; fragrances ( e . g ., mentha spicata , coconut , rose oil , sandlewood oil , etc . ); ph control agents ; and buffers . humectants , such as glycerin and glycols ( e . g ., butylene glycol ), and oils of mineral or plant origin may be used alone or in combination with any of the above - mentioned cosmetic base components as desired . exemplary cationic surfactants suitable for use in the present invention may include , but are not limited to , mono - and di - dimethyl ammonium chlorides , benzalkonium chlorides , and di - steary - di - methyl ammonium chloride . exemplary fatty alcohols suitable for use in the present invention may include , but are not limited to , c10 - c22 carbon chain alcohols ( straight or branched ), and stearyl alcohol . exemplary nonionic emulsifiers suitable for use in the present invention may include , but are not limited to , sorbitan esters , ethoxylated fatty alcohols , and polysorbate 20 . exemplary rheology modifiers suitable for use in the present invention may include , but are not limited to , hydroxyalkyl celluloses , zanthan and guar gums , modified starches , and peg 150 distearate . exemplary preservatives suitable for use in the present invention may include , but are not limited to , 5 - chloro - 2 - methyl - 1 , 2 - thiazol - 3 - one , 2 - methyl - 1 , 2 - thiazol - 3 - one , 1 , 3 - dimethylol - 5 , 5 - dimethylhydantoin , 3 - iodo - 2 - propynyl butyl carbamate kathon ™ cg commercially available from sigma - aldrich , inc . ( st . louis , mo .) and glydant plus commercially available from lonza , ltd . ( basil , switzerland )), and parabens such as methylparaben and propylparaben . exemplary dyes suitable for use in the present invention may include , but are not limited to , fd & amp ; c and d & amp ; c approved dyes such as d & amp ; c yellow # 10 . exemplary ph control agents suitable for use in the present invention may include , but are not limited to , citric acid , and potassium hydroxide . exemplary buffer agents suitable for use in the present invention may include , but are not limited to , sodium phosphates , mono -, di -, and tribasic ; and potassium citrates , mono -, di -, and tribasic . exemplary oils of mineral or plant origin suitable for use in the present invention may include , but are not limited to , johoba oil , camellia oleifera leaf extract , green tea extract and white tea extract . the hair pre - treatment compositions of the present invention may comprise up to about 95 % by weight of deionized water . typically , deionized water is present in an amount of from about 45 to about 90 % by weight , more typically , from about 65 to about 85 % by weight , and even more typically , from about 65 to about 80 % by weight , based on a total weight of the hair pre - treatment composition . other cosmetic base materials , such as any cationic surfactant , fatty alcohol , nonionic emulsifier , rheology modifier , preservative , chelator ( e . g ., edta or sodium salt thereof ), dye , fragrance , ph control agent , buffer , humectants , and / or oil of mineral or plant origin may each independently be present in the hair pre - treatment compositions of the present invention in an amount of up to about 10 % by weight , based on a total weight of the hair pre - treatment composition . typically , each of the above - listed cosmetic base materials ( other than deionized water ), when present , are each independently present in an amount of from greater than 0 to about 5 . 0 % by weight , more typically , from about 0 . 0001 to about 3 . 0 % by weight , and even more typically , from about 0 . 01 to about 1 . 0 % by weight , based on a total weight of the hair pre - treatment composition . the ph of the resulting hair pre - treatment compositions typically ranges from about 4 to about 7 , desirably ranging from about 4 to about 6 , more desirably ranging from about 4 to about 5 . it should be noted that the hair pre - treatment compositions of the present invention may comprise , consist essentially of , or consist of any one the above - mentioned composition components or any combination of two or more of the above - mentioned composition components . in one exemplary hair pre - treatment composition of the present invention , the exemplary hair pre - treatment composition comprises ( or consists essentially of , or consists of ) at least one hydrophilic cationic polymer comprising guar hydroxypropyltrimonium chloride ( ghptc ); at least one lipophilic nonionic polymer comprising ( i ) a polyvinyl stearyl ether , ( ii ) a vinylpyrrolidone - eicosene copolymer , or ( iii ) a combination of ( i ) and ( ii ); one or more water - soluble antioxidants or reducing agents comprising cysteine , methionine , or any mixture thereof ; one or more oil - soluble antioxidants or reducing agents comprising a tocopherol , a tocotrienol , beta carotene , or any mixture thereof ; and one or more of the following components : deionized water , cetearyl alcohol , peg 40 castor oil , stearalkonium chloride , hydrogenated castor oil / sebacic acid copolymer , di - behenzyl imidazolinium , cetrimonium methosulfate , cetearyl alcohol , a polyoxyethylene ether of cetyl / stearyl alcohol , butylene glycol , isopropyl myristate , citric acid , an acrylate / aminoacrylate / c10 - 30 alkyl peg - 20 itaconate copolymer , trisodium edta , amidomethicone , cetrimonium chloride , 2 - tridecoxyethanol , camellia oleifera leaf extract , camellia sinensis ( white tea ) extract , methylchloroisothiazolinone , methylisothiazolinone , and a fragrance . in another exemplary hair pre - treatment composition of the present invention , the exemplary hair pre - treatment composition comprises ( or consists essentially of , or consists of ) at least one hydrophilic cationic polymer comprising guar hydroxypropyltrimonium chloride ( ghptc ); at least one lipophilic nonionic polymer comprising ( i ) a polyvinyl stearyl ether , ( ii ) a vinylpyrrolidone - eicosene copolymer , or ( iii ) a combination of ( i ) and ( ii ); one or more water - soluble antioxidants or reducing agents comprising cysteine , methionine , or any mixture thereof ; one or more oil - soluble antioxidants or reducing agents comprising a tocopherol , a tocotrienol , beta carotene , or any mixture thereof ; and all of the following components : deionized water , cetearyl alcohol , peg 40 castor oil , stearalkonium chloride , hydrogenated castor oil / sebacic acid copolymer , di - behenzyl imidazolinium , cetrimonium methosulfate , cetearyl alcohol , a polyoxyethylene ether of cetyl / stearyl alcohol , butylene glycol , isopropyl myristate , citric acid , an acrylate / aminoacrylate / c10 - 30 alkyl peg - 20 itaconate copolymer , trisodium edta , amidomethicone , cetrimonium chloride , 2 - tridecoxyethanol , camellia oleifera leaf extract , camellia sinensis ( white tea ) methylchloroisothiazolinone , methylisothiazolinone , and a fragrance . it should be noted that the hair pre - treatment compositions of the present invention comprise , consist essentially of or consist of one or more composition components , discussed above , that are not present in other hair treatment compositions , for example , shampoos and / or conditioners . in addition , the hair pre - treatment compositions of the present invention typically do not contain composition components found in shampoos and / or conditioners . composition components that are typically found in shampoos and / or conditioners , but are not typically present in the hair pre - treatment compositions of the present invention , include , but are not limited to , anionic surfactants . the present invention is described above and further illustrated below by way of examples , which are not to be construed in any way as imposing limitations upon the scope of the invention . on the contrary , it is to be clearly understood that resort may be had to various other embodiments , modifications , and equivalents thereof which , after reading the description herein , may suggest themselves to those skilled in the art without departing from the spirit of the present invention and / or the scope of the appended claims . 2 — pre - melt part b in separate vessel and heat to 70 ° c . 5 — adjust ph to 5 - 6 with 50 % citric acid in deionized water the following hair pre - treatment composition components were mixed as described below . 2 — pre - melt part b in separate vessel and heat to 70 ° c . 5 — adjust ph to 5 - 6 with 50 % citric acid in deionized water the following examples consist of compositions made via the procedure outlined in examples 1 and 2 above . a series of six measurements were taken on swimmers after 2 - 4 hours immersion in a swimming pool in north carolina . the object was to determine the efficacy regarding control of residual chlorine on swimmers hair with and without pre - treatment using the composition of example 7 in the foregoing examples . the composition of 7 above was applied to the hair and rinsed using tap water prior to swimming . the amount of product was judged in relation to length and fullness of the hair . the controls received no pre - treatment prior to pool immersion . the pool ph together with total and free chlorine was monitored using indicator strips during the measurements for consistency . results are shown below . while the specification has been described in detail with respect to specific embodiments thereof , it will be appreciated that those skilled in the art , upon attaining an understanding of the foregoing , may readily conceive of alterations to , variations of , and equivalents to these embodiments . accordingly , the scope of the present invention should be assessed as that of the appended claims and any equivalents thereto . | compositions for treating hair are disclosed . methods of making and using compositions for treating hair are also disclosed . |
as seen in fig1 a safety harness 10 , for a hunter 18 , or wearer , climbing a tree 32 , generally comprises a strap 12 , affixed by a buckle 14 into an annular belt 19 about the waist 16 , or torso 17 , of a wearer 18 . the harness 10 further comprises a safety line assemblage 21 attached to the strap 12 , generally including a cord 22 with a ring 24 attached at a first end 26 of the cord , and a hook assembly 28 attached at a second end 30 thereof . these elements help secure the wearer 18 by the strap 12 to a tree 32 , as further explained below . the strap 12 of the preferred embodiment is an elongated piece of material or webbing 34 which , in operation , is secured about the wearer 18 into an annular belt 19 by the buckle 14 . preferably , the strap 12 is of a size to encircle a wide range of wearer waists 16 or torsos 17 . the strap 12 is preferably made of a strong , lightweight , abrasion resistant and stretch - resistant material and / or weave design so as to be : conveniently portable over harsh terrain ; durable ; and stable under operating conditions , as explained below . man - made fibers such as nylon , polypropylene , or polyethylene , will offer the advantages of being lighter than a comparable size and strength leather belt , showing little or no stretch whether wet or dry , and have the additional advantage of being heat sealable for the repair of snags , runs , trimming to size the strap 12 etc . it is also preferable for physical reasons to provide a strap 12 whose width is sufficient to distribute the loading forces of harness 10 operation over a broad enough area on the wearer 18 so as to not cause discomfort to the wearer 18 . it will be appreciated that a variety of fabrics or materials , man - made or natural , woven or non - woven ; may be used in accordance with the present invention to supply a strap 12 of a variety of dimensions . as an alternative to the single broad strap illustrated in the drawings , it is envisioned that a narrow strap having a load bearing pad ( not shown ) located thereon could also be used . as seen in fig5 the buckle 14 is made from aluminum alloy or other suitably surface - hard and strong materials adequately to the task of securing the strap 12 about the wearer 18 during climbing operations . the buckle 14 generally comprises a rectangular frame 40 having first , second , third , and fourth coplanar frame legs 36 , 42 , 44 , 46 , respectively , which define a central opening 48 within the boundaries of the frame 40 . a first &# 34 ; u &# 34 ;- shaped side flange 50 extends perpendicularly from the fourth frame leg 46 . the side flange 50 , is attached to the fourth frame leg 46 by the arms 54 , 56 of the &# 34 ; u &# 34 ; so as to define a race 58 within the buckle 14 for slidably retaining a first end 59 of a tensioning bar 60 . a second &# 34 ; u &# 34 ;- shaped side flange 52 , substantially identical to the first flange 50 , is attached to the second frame leg 42 in a like manner to define a second race 57 for retaining a second end 62 of the tensioning bar 30 . the tensioning bar 60 is an annular rod 66 having a knurled surface 64 thereon to aid in grasping the strap 12 , as further explained below . the first and second tension bar ends 59 , 62 , respectively , are flattened so as to more easily slide within the races 57 , 58 of the buckle 14 . an aperture 68 is formed in the third frame leg 44 of the buckle 14 . a ribbon 70 , as seen in fig2 is fastened through the aperture 68 to provide an easily utilized single - hand means for releasing the strap 12 from the grasp of the buckle 14 , as further explained below . as seen in fig2 and 5 , a buckle 14 , is secured to the strap 12 by passing the strap 12 over a first buckle frame leg 36 , folding the strap 12 back onto itself to form a loop ( not shown ) around the first frame leg 36 , and securing the strap 12 in this position by stitching 38 , adhesive , or other known fastening means . as seen in fig3 a hook 28 , ring 24 and cord 22 are combined in a safety line assemblage 21 so as to be connected to the strap 12 through the ring 24 . the cord 22 functions as a safety line attaching the wearer 18 to a tree 32 ( see fig1 and 4 ) to prevent a plummet therefrom by the wearer 18 . the cord 22 is preferably made of a strong , lightweight , abrasion resistant , and nonstretching material such as multifilament polypropylene and / or weave design , such as diamond - braiding , so as to provide advantages of portability , durability and good operating characteristics , as cited above for the strap 12 . the cord 22 in the preferred embodiment is a rope 72 of man - made material , such as nylon , having a length sufficient to encircle a tree 32 having a circumference adequate to support a tree stand 74 and the wearer 18 . the first end 26 of the cord is fastened about the ring 24 by a knot 76 formed thereabout by the cord 22 . as an added safety feature , in the preferred embodiment , the cord first end 26 is fastened back upon the cord 22 by a crimped metal band 78 to ensure the knot 76 stays fastened about the ring 24 . the ring 24 is a closed loop 80 which in the preferred embodiment is &# 34 ; d &# 34 ;- shaped . such rings are commonly referred to as &# 34 ; d &# 34 ;- rings . the ring 24 is formed of a strong , hard , material such as steel or the like and has a smooth surface to prevent wearing of the cord 22 . the ring 24 will preferably be of a size to allow passage of the strap 12 through the ring 24 without bending the strap 12 . the second end 30 of the cord 22 is passed through the body 82 of the hook assembly 28 in a first direction 29 as further explained below . the second end 30 of the cord 22 has a knot 81 formed therein after passing through the hook assembly 28 to prevent the cord 22 from traveling in a second , opposite , direction 31 back through , and out of , the hook assembly 28 . the hook assembly 28 is , preferably , made of cast aluminum or the like and generally comprises the body 82 , the cam 84 , and the cam follower 86 . the hook assembly 28 , in and of itself , is a known design and , per se , does not form a part of the invention , but will be briefly described for purposes of clarity and exposition . the body 82 has a first end 88 defining a cylindrical channel ( not shown ) for admitting the cord 22 therethrough . a hollow central portion 90 of the body is defined by two parallel side walls , such as at 92 . a second end 94 of the body is formed in a hook 96 capable of substantially surrounding the cord 22 . the cam 84 and cam follower 86 are pivotally fitted within the hollow central portion 90 by a pin 98 passing through the side walls 92 . the cam 84 is spring loaded ( not shown ) to a closed position . the cam has a knurled or toothed surface ( not shown ) for gripping the cord 22 and preventing its travel in the second direction 31 out of the body 82 . the cam follower 86 has a surface ( not shown ) opposing the cam knurled surface within the body 82 . the cam follower surface ( not shown ) and the cam knurled surface ( not shown ) define therebetween a variable width channel for unopposed cord passage in the first direction 29 and selective cord passage in the second direction 31 , therethrough . a cam flange 102 affixed to the cam 84 is operable by finger pressure for channel width selection as further explained below . the cam follower 86 has a flange or armature 100 thereon placed so as to substantially close the mouth 103 of the hook 96 when the cam 84 is in its normally closed position . in use , the strap 12 is passed through the ring 24 . the strap 12 is then placed about the waist 16 or torso 17 of the wearer 18 and secured thereabout into the annular belt 19 in a comfortably snug fashion by passing the free end 13 of the strap 12 through the buckle central opening 48 and over the tensioning bar 60 and drawing the strap 12 through the buckle 14 to attain a proper fit . as seen in fig1 and 2 , the cord 22 is thereby attached at the first end thereof through the ring 24 to the strap 12 . the cord 22 is then passed around the circumference of the tree 32 and fastened by the hook assembly 28 back onto the ring 24 . thus , the wearer 18 is secured to the tree 32 in such a fashion that the wearer 18 may ascend the tree 32 by the use of foot pegs , one of which is shown at reference no . 104 . these foot pegs 104 are commonly mounted to the tree 32 in serial order by the wearer 18 as he ascends the tree 32 , thus requiring the use of the hands 106 the wearer 18 . the wearer 18 has therefore only to lean back against the safety harness 10 and the previously secured foot pegs 104 to allow his hands 106 the freedom to mount the pegs 104 or the tree stand 74 , fig2 ; while also being saved from a precipitous plunge from the tree 32 should a foot 108 slip from a peg 104 . as seen in fig4 once the wearer 18 has attained his position on the tree stand 74 the hook assembly 28 may be detached from the ring 24 and refastened over the cord 22 to allow the safety harness 10 to act as a tether to the tree 32 allowing the wearer a range of movement while still securing the wearer 18 to the tree 32 . should the strap 12 need loosening about the waist 16 the wearer 18 may tug on the ribbon 70 to move the buckle frame 40 relative to the tensioning bar 60 therein allowing the strap 22 to let out slack from the free end 13 thereof . should the cord 22 need tightening about the tree 32 , the cord second end 30 may be pulled through the hook assembly 28 in the first direction 29 with no resistance from the cam 84 . conversely , the cam 84 will not allow loosening of the cord 22 ; i . e ., movement in the second direction 31 through the hook assembly 28 ; unless pressure is applied to cam flange 102 to release the grip of the cam 84 on the cord 22 , by opening the channel width between the cam 84 and cam follower 86 . thus , the present invention provides a lightweight , durable , inexpensive , safety harness for a tree stand hunter which will greatly reduce the risk of injuries associated with climbing of trees and hunting from tree stands . | a safety harness especially for hunters who use tree stands is disclosed . the harness comprises a web belt with a buckle for the hunter . attached to the belt by a &# 34 ; d &# 34 ;- ring is a safety rope which is fastened around the tree and back onto the &# 34 ; d &# 34 ;- ring by a cammed - hook assembly to secure the hunter from falling . the harness is easily portable and is usable both as a climbing harness and as a tether while the hunter is on the tree stand . |
fig1 shows one of many different flying insect traps which may be made in accordance with the present invention . the flying insect trap shown includes a glueboard 10 , a housing 30 , three ultraviolet light sources 56 , 57 and 58 , a removable pan 80 , and a removable cage 82 . the removable cage 82 prevents people from inadvertently coming into contact with and being potentially burned by the light sources 56 , 57 and 58 while at the same time permitting ingress of flying insects into the caged area . glueboards 10 of the type used may be of a variety of shapes . as shown in the drawings , the glueboard 10 is rectangular in shape having a first edge 12 parallel to a second edge 14 and a third edge 16 parallel to a fourth edge 18 extending between first and second surfaces . the first or back surface has no adhesive coating . the second or front surface 20 has a peripheral section 22 adjacent the edges 12 , 14 , 16 and 18 and a center section 24 . the center section 24 is coated with a suitable adhesive for immobilizing the pests to be captured by the pest control device . the peripheral section 22 is typically not coated with such an adhesive to promote ease of handling . fig5 also shows a release paper 26 which covers the adhesive layer of the center section 24 during shipping and handling to prevent unintended items from sticking to the center section 24 . the release paper 26 is removed at the time the glueboard 10 is placed into service as illustrated in fig1 and 6 - 8 . as best shown in fig2 and 6 , the housing 30 includes a space 32 in which a glueboard 10 is received and retained . as shown in the drawings , the space 32 is defined by a first channel 34 , a second channel 40 , and a support surface 46 . alternatively , a single u - shaped channel could be employed . the first channel 34 has at least one open end 36 and a lip 38 for retaining edge 18 of the glueboard 10 . the second channel 40 has at least one open end 42 and a lip 44 for retaining edge 16 of the glueboard 10 . the dimensions of the lips 38 and 44 and the peripheral section 22 are such that the adhesive coating of the glueboard 10 never comes into contact with lips 38 and 44 . when the glueboard 10 is located within the space 32 , the front surface 20 of the glueboard 10 and adhesive coating over the center section 24 face away from a support surface 46 of the housing 30 . as such , the back surface of the glueboard 10 , which is not coated with adhesive , is in face - to - face registration with the support surface 46 . as shown in fig1 - 3 and 6 - 8 , the housing 30 also includes electrical fittings 50 - 55 for physically and electrically coupling three ultraviolet ( uv ) light sources 56 - 58 to the housing . the uv light sources , when energized , give off uv light which is known to be attractive to insects . as shown , the uv light sources 56 - 58 are positioned in front of and spaced from the channels 34 and 40 and the glueboard 10 and extend across the support surface 46 and glueboard 10 . when the uv light sources 56 - 58 are illuminated , insects attracted by the uv light will fly about the light sources 56 - 58 , come into contact with the adhesive and adhere to the glueboard 10 . of course , if the glueboard 10 is not replaced regularly , the adhesive can dry out and loose its adhesive properties in which case any dead insects will fall into pan 80 . while the drawings show uv light sources being employed , other types of attractants can be employed either in lieu of or in addition to such light sources . the drawings also show a pair of guides 60 and 62 . as shown , each guide includes a first bearing 64 and a second bearing 66 which support opposite end sections of an axle 68 . mounted along each axle 68 between the two bearings 64 and 66 are narrow wheels 70 and a plurality of stops 72 . the stops 72 prevent the axle 68 from unintentionally becoming disconnected from the bearings 64 and 66 and the wheels from sliding along the axle . the wheels 70 have an axis of rotation along the same longitudinal line as the axle 68 . the wheels 70 can either be fixed to the axle 68 , in which case the bearings 64 and 66 permit the axle to rotate , or the wheels can rotate about the axle 68 . the wheels 70 terminate in a narrow outer edge to ensure the adhesive of the glueboard 10 does not cause the wheels 70 to stick to the glueboard 10 . the wheels 70 of guide 60 provide at least two very important functions when the edges 16 and 18 of a replaceable glueboard 10 are being inserted into or removed from the channels 34 and 40 of the housing 30 . specifically , the wheels 70 guide the glueboard 10 so the edges 16 and 18 enter the channels 34 and 40 . the wheels 70 also prevent the adhesive - coated center section of the glueboard from coming into contact with the outer surfaces of bulbs 56 - 58 or other surfaces of the housing 30 . guides having other configurations can also provide this function without deviating from the invention so long as any edge of the guide coming into contact with the adhesive coating is thin enough to prevent an adhesive bond from being formed between the glueboard and the guide . a second guide 62 may be added at the opposite end of space 32 and channels 34 and 40 for additional security . when a second guide 62 is provided , the guides 60 and 62 cooperate with the lips 38 and 44 of the channels 34 and 40 to ensure the glueboard 10 does not move , warp or otherwise change position in a fashion which could permit the adhesive of glueboard 10 to come into contact with the outer surfaces of light sources 56 - 58 or other surfaces of the housing 30 . from the drawings , it should be appreciated that the thickness of the glueboard 10 , at least at the peripheral section 22 , should be less than the distance between the lips 38 and 44 and the support surface 46 so the edges 12 and 14 of the glueboard 10 can be slid between the lips 38 and 44 and the support surface 46 . as noted above , the depth of the lips 38 and 44 and the peripheral section 22 of the glueboard 10 should be dimensioned so adhesive from the glueboard 10 does not come into contact with the lips 38 and 41 . the axles 68 may also be made of a flexible yet resilient material to allow for variations in the thickness of the replaceable glueboard 10 and provide a slightly - pinching force against the glueboard 10 between the wheels 70 and the support surface 46 . the drawings and the description provided above are designed to meet the disclosure requirements of the patent laws , but the invention is not limited to the embodiment disclosed . variations can be made without deviating from the invention . by way of example , a different number or type of lights may be employed as the pest attractant . pest attractants other than light sources may be employed including , but not limited to , pheromones and other odorous materials embedded in the glueboard or positioned adjacent to the glueboard . the housing may also include various grills , grates or decorative panels to prevent people from coming into contact with the adhesive coating of glueboard 10 , to prevent viewing of the glueboard 10 and any pests trapped by the glueboard 10 , or to prevent people from coming into contact with either the glueboard or light sources . also , the housing 30 and glueboard 10 may have a variety of different shapes without deviating from the invention . thus , it is intended that the invention only be limited by the language of the claims which are intended to cover what the claims literally describe and a fair range of equivalents . | a pest control device uses a replaceable glueboard to immobilize pests attracted to the pest control device . a unique guide is provided to help prevent the adhesive surface of the glueboards from coming into contact with other surfaces of the pest control device during installation and removal of such glueboards . |
a description of the preferred embodiments of the present invention will now be presented with reference to fig1 - 10 . as used herein , the words “ tubes ” or “ tubing ” refer to supply lines for providing water and / or nutrients . as will be appreciated by one of skill in the art , such “ tubes ,” “ tubing ,” or “ pipe ” do not necessarily need to be cylindrical , but may be of any suitable shape , and no limitation is intended by the use of these words , which can also more broadly be described as “ solution - channeling devices .” described herein are a system and method of supplying water and / or nutrients to the roots of growing plants wherein the water and / or nutrients are released to the plants as needed by the individual plants . herein the term “ plants ” should be construed broadly , and can include , for example , grasses . although not intended as a limitation on the invention , it is believed that when under water stress , plant roots can emit exudates or surfactants that promote the release of water and / or nutrients stored under the conditions described below . specifically , the plants are supplied water and / or nutrients from supply lines or feeder tubes , at least portions of which are hydrophilic . in some embodiments , the tubing may include a plurality of holes that are covered by hydrophilic membranes ; in other embodiments , the entire tubing , the below surface portion thereof , or a significant portion thereof is hydrophilic . in yet other embodiments , the system may include a surface tube that is water impermeable or hydrophobic , the tube being connected to a plurality of hydrophilic tubes that can be inserted into a support medium for supplying the roots . one or more hydrophilic tubes may be inserted into a quantity of support medium such that the tubes are at least partially below the surface of the support media . the support media may be selected from any suitable medium or mixture of media suitable for supporting growing plants and roots . examples , which are not intended as limitations , of such support media can include sand , soil , rockwool , polyurethane foam , fleximat ™, sri cellulose - based growth media , and the like . other suitable media known in the art , such as continuous - fiber growth media , may also be used . in particular embodiments , plants are planted in the support medium and the respective tubes are connected to reservoirs containing water , nutrients , or a mixture thereof . in some embodiments , two tubes may feed a row of plants : a water tube and a nutrient tube . as discussed above , it has previously been shown that the plants are capable of distinguishing between these tubes . alternatively , nutrient ( s ) can be added to a water reservoir for distribution through a unitary tube . thin - walled microporous hydrophilic tubes are not known at present to be commercially available for use as irrigation tubing . in a particular embodiment , hydrophilic materials , including cell force ™ and flexi sii ™, may be made into hydrophilic tubes . such tubes , while relatively easy to construct , can be fragile and difficult to use in applications requiring structural integrity . alternatively , some existing hydrophobic thin - walled tubes can be made hydrophilic by a process that uses a water - insoluble hydrophilic polymer ( e . g ., polyhydroxystyrene , u . s . pat . no . 6 , 045 , 869 , incorporated herein by reference ; structure illustrated in fig6 ) as a surface coating . such solutions applied as a coating to and impregnated into microporous hydrophobic plastic tubing have been shown not to clog the pores and to remain hydrophilic for many years . thus continuous tubes of a material such as tyvek ® ( a microporous polyethylene material made from very fine , high - density polyethylene fibers , dupont , richmond , va .) in a radius of 5 - 10 mm ( irrigro international irrigation systems ) have been used after being made hydrophilic and have been shown to act as a membrane that is responsive to the roots of plants in a subsurface irrigation system . tyvek ® is available in a plurality of styles , each having different properties . although not intended to be limiting , two particular types have been found to be most beneficial for use in the present invention : 1059b and 1073b . alternative means of forming a solution - channeling device can comprise , for example , joining lateral ends of a sheet comprising a hydrophilic material to form a tube having a lumen therethrough ; introducing an alcohol solution of a hydrophilic polymer to a microporous hydrophobic sheet and joining lateral ends of the sheet to form a tube ; making a tube hydrophilic , the tube having a lumen therethrough and comprising a microporous polyethylene material comprising fine , high - density polyethylene fibers ; and creating a substantially planar , microporous film comprising a hydrophilic polymer and joining opposed sides of the film to form a tube having a lumen therethrough , although these methods and the devices resulting therefrom are not intended as limitations . as discussed above , it has been shown that hydrophilic membranes can become hydrophobic over time owing to organic impurities in the water adsorbed onto the membrane . because of the variability of the impurities in water , we have added organic substances to the water which can be adsorbed onto the exit pore walls , making the membrane hydrophobic , and thereby reducing the flow of water or nutrient solution through the membrane . examples of suitable organic substances include , but are by no means limited to , humic acid , kerosene , turpentine , pinene , paraffin , and hexadecane . in other embodiments , other suitable c8 - c16 saturated hydrocarbons may be used . the amounts added ranged from 10 ppb to 10 ppm to the irrigating medium . as will be appreciated by one of skill in the art , in some embodiments , the addition of the organic substance may not be essential , depending on the quality of the water . when growing crops in soil , the addition of nutrient on a continuous basis is not essential ; however , when growing crops in sand , fleximat ™, or rockwool , a nutrient solution , for example , any suitable nutrient solution known in the art such as those commonly used in hydroponic systems , e . g ., hoegland solution , peter &# 39 ; s solution , miracle - gro ®, or other less dyed fertilizer such as schultz export may be added to the water supply or may be fed directly to the plants in a separate tube , as described above , and thus the roots of the plant can be allowed to take as much water and nutrient as required . however , for growth in artificial media the inclusion of nutrients and micronutrients is generally important . fig1 a and 1b illustrate a system 10 that uses twin irrigation tubes 11 , 12 for delivering water and nutrient solution to plants 13 growing in a growing medium 14 . in this embodiment 10 , the tubes 11 , 12 are running through the root systems 15 of the plants 13 . it has been found in experiments in both sand and potting soil that the higher the concentration of nutrients used , the smaller the volume of the nutrient solution that is released to the roots 15 , which is illustrative of the water conservation achieved by the current invention . it will be understood by one of skill in the art that the tubes 11 , 12 could be provided as a single composite double - lumen tube without departing from the spirit of the invention . the diameters of the two portions could be in a proportion commensurate with a plant &# 39 ; s requirements for water versus nutrient , for example , double the size for the water tube , although this is not intended as a limitation . in some embodiments , since subsurface thin - walled microporous tubing can be collapsed if sufficient pressure is applied , a spiral 60 comprising , for example , plastic , can be incorporated into a tubing such as tubing 11 or 12 to form a tube 61 that is more resistant to collapsing ( fig1 c ). fig2 illustrates a system 20 for the irrigation of grass 21 where the subsurface tubes 22 are spaced 1 - 2 feet apart and are substantially continuously fed with water under low constant pressure , with nutrients added to the aqueous solution as desired . the irrigation systems and methods described herein are believed superior to any other watering system currently in use , and further are independent of atmospheric pressure , making them usable for astroculture or micro - gravity conditions , as well as others . in one embodiment of the invention 30 ( fig3 ), for example , a continuous fiber growth medium 31 such as rockwool or the spongy fleximat ( from grow tech ) can be used to support the plants 32 and their roots 33 . in this embodiment 30 , both of the reservoirs 34 comprise a container 35 that has an interior space 36 for holding the water and nutrient solution therein . the containers 35 are formed similar to a bellows , and are movable between an expanded state when containing solution and a retracted state when solution has been removed . the containers 35 also comprise a filling inlet 37 that is in fluid communication with the containers &# 39 ; interior space 36 for adding solution thereto . distribution tubes 38 are also in fluid communication with the containers &# 39 ; interior spaces 36 and with inlets 39 of the hydrophilic tubes 40 . this arrangement provides solution to the tubings &# 39 ; lumina 40 . the distribution tubes 38 also have check valves 41 therein for preventing backflow of solution from the tubes 40 toward the containers &# 39 ; interior spaces 36 . support for plants and their roots can be provided for in the present system under zero gravity , for example , with the use of a monolithic contiguous material such as rockwool or fleximat ™, a spongy hydrophilic porous material made by grow - tech ( lisbon falls , me .) or the newly developed artificial sponge such as , for example , agrilite ( sri enviro - grow systems , ontario , canada ). by using these materials to surround twin microporous hydrophilic irrigating tubes , one supplying water while the other supplying a nutrient solution , it is possible to achieve complete conservation of water and nutrients supplied to growing plants . such a system can also be applied to arid or desert environments where water conservation is desirable . early laboratory tests showed that using nutrients in water , it was possible to grow tomatoes in sand with amerace a10 membranes 42 ( 50 % silica gel in polyethylene ) glued over holes 43 in a subsurface pvc tube 44 ( fig4 ). the holes 43 in the pvc tube 44 were 12 mm in diameter , spaced 10 cm apart , drilled in 17 - mm - id rigid pvc tubing . the holes 43 are believed to have limited the amount of water and nutrient available to the growing plant , and the system proved to be inadequate when the plants began to bear fruit and needed more membrane area to supply the plants &# 39 ; requirements . increasing the total surface area of the membrane by drilling and covering more holes improved the system . however , a best mode of practicing the invention at the present time favors the use of a continuous tube . because of the brittle nature of amerace , membrane tubes made of this material tended to crack and leak . tyvek ® ( dupont ) in tube form has been used for irrigation purposes under elevated water pressure for gardens and row crops . however , the hydrophobic nature of the polyethylene material permits it to act as a drip source of water for plants without any control by the exudates of the plant roots . the conversion of a hydrophobic surface to hydrophilic has been described ( u . s . pat . no . 6 , 045 , 869 ) and can be used to make tyvek ® tubing hydrophilic and responsive to the water and / or nutrient needs of the plant . when the tubing has been made hydrophilic by coating and impregnating it with an alcohol solution of polyhydroxystyrene , the tubing was found to be permeable to water at much lower pressures , and showed a decrease in water permeability as the organic compounds in water are adsorbed onto the exit pore walls . this can be considered a “ conditioning phase ,” during which permeability can be decreased by as much as 80 % by the addition of hydrocarbons to the tap water . the present invention is believed to be the first to provide a plurality of feeding tubes arranged to extend beneath the surface of a support medium to feed a plurality of plants or a row of plants . furthermore , a clear advantage of tubes comprising a hydrophilic material is that a greater area of the support medium is fed water and nutrients compared to a single horizontal membrane . the invention will now be described by way of examples ; however , the invention is not intended to be limited by these examples . a 4 ft . length of tyvek ® tubing (# 1053d ) was made hydrophilic with an alcoholic solution of polyhydroxystyrene and submerged in a 4 . 5 ft by 13 cm wide by 10 cm deep planter , covered with soil and connected to a constant supply of nutrient solution at a constant head of 35 cm of water . ten cherry tomato ( lycopersicon sp .) seedlings were planted at even distances next to the tube where water and nutrients were supplied . fluorescent lighting was supplied to the plants for 18 hours per day . the average consumption of water was 75 ± 10 ml / hr when the plants were 15 cm high and 125 ± 20 ml / hr when the plants were 25 cm high . when rainfall was simulated by spraying the bed with 100 ml of water , the consumption of water dropped to zero for 2 hours and slowly over the next 3 hours returned to the normal rate . the plants grew to two feet in height , and numerous tomatoes were harvested . at the end of the experiment , the system was examined to determine if there was any competition between the plants for space on the membrane . an examination of the root system indicated that the roots encircled the membrane only within about 1 - 2 inches from the plant stem . this indicates that it should be possible to increase the density of plant growth to an extent that would only be limited by the photochemical flux available and mutual interference . when a dual - tube system was used to supply both water and nutrient separately , the ratio of water consumed to nutrient solution consumed was approximately 2 . 5 to 1 for 8 cherry tomato plants in sand . again , little or no fluctuations were observed when the size of the plants reached a height of 35 cm . a continuous irrigation tube can be unnecessary for plants such as grape vines or kiwi vines that are spread apart from each other by distances as much as 20 to 40 cm . in these situations 50 , it is more practical to use a main flexible surface distributing tube 51 of from 20 - 30 mm id , out of which are drawn satellite tubes 52 that feed a short length of from 10 to 30 cm , depending of the size of the vine , of thin - walled microporous hydrophilic irrigating tube 53 , closed at its end 54 , surrounding the roots 55 of the vine or bush 56 , as illustrated in fig5 a and 5b . a tomato plant was planted in potting soil , into which was also placed two 20 - cm - long microporous hydrophilic tubes of 1 cm radius . the tubes were connected to reservoirs of water and nutrient which were kept full . the soil remained dry while the plant grew to produce numerous tomatoes . another experiment was conducted with tyvex ® tubing (# 1053b ), 1 . 25 m long and 1 cm radius . the tubing was sealed at one end that was made hydrophilic with a 3 % solution of polyhydroxystyrene ( novolac grade from triquest ) in ethanol . the tubing was submerged in a 1 . 4 - m planter , covered with soil , and connected to a supply of nutrient solution at a constant head of 35 cm of water . ten cherry tomato ( lycopersicon sp ) seedlings were planted at even distanced next to the tube , by which water and nutrients were supplied . the plants grew during the conditioning phase while exposed to fluorescence lighting for 16 hr / day . the average consumption of water was 75 ± 10 ml / hr when the plants were 15 cm in height and 125 ± 20 ml / hr when the plants were 25 cm in height . rainfall was simulated by spraying the bed with 100 ml water , following which the consumption of water dropped to zero for 2 hours and then slowly , over the next 3 hours , returned to the normal rate . the plants grew to 60 cm in height , and an abundance of tomatoes was harvested . at the completion of the experiment , the system was examined to determine if there had been any competition between the plants for space on the membrane . an examination of the root system indicated that the roots encircled the membrane only within about 2 . 5 - 5 cm from the plant stem . this finding would seem to indicate that it should be possible to increase the density of plant growth to a level only limited by the light flux available and mutual interference . it has also been shown that different plants requiring different rates of water and nutrient can grow together with each being satisfied individually without monitoring . when a dual membrane system was used to supply both water and nutrient separately , the ratio of water consumed to nutrient solution consumed was approximately 2 . 5 to 1 for 8 cherry tomato plants in sand . once again , there was little or no fluctuation observed when the size of the tomato plants reached a height of 35 cm . a planter 115 cm long , 13 cm wide , and 10 cm deep , was set up in a greenhouse with dual - feed membrane tubes for water and nutrient through the center of a bed comprising 50 cm of flexmat and 50 cm of rockwool separated by 15 cm of polyurethane foam . the seeds or seedlings of canola ( brassica sp ), beans ( phaseolus sp ), corn ( zea mays sp ), and tomatoes ( lycopersicon sp ) were planted in each of their respective media and their growth patterns observed . growth , which was favored in the fleximat , proceeded normally , except for the polyurethane foam , with each crop growing at its own rate under a light flux of 50 - 60 mw / cm 2 . root crops such as carrots ( daucus carota var sativa sp ), radishes ( raphanus sativus sp ), beets ( beta vulgaris sp ), and onions ( allium sp ) were grown in soil and peat , while potatoes ( solanum tuberosum sp ), parsnips ( pastinaca sativa sp ), and parsley ( petroselinum sativum var tuberosum sp ) were grown successfully in vermiculite . a cellulose material ( sri petrochemical co .) can also be used as an artificial growth medium . it was determined that grass ( gramineae sp ) can be successfully irrigated for 3 successive years with submerged tubular membranes spaced 40 - 50 cm apart . in another case , two hydroponic planters ( 30 × 30 × 30 cm ) were fitted with a membrane tube for a water / nutrient solution approximately 7 cm from the bottom . the media comprised a soil - less mixture approximately 25 - 26 cm deep in the planters . this depth allowed the root crops to produce straight tap roots , which is of concern to consumers when purchasing vegetables . one planter was seeded with parsnips ( daucus carota var . sativa sp .). the other planter was seeded with parsley ( petroselinum sativum var . tuberosum var . tuberosum sp . ), a dual - purpose crop of foliage and root stocks . plant competition controlled the over - seeding issue with each planter . the plants received only natural sunlight , reducing the risk of “ bolting .” extreme warm temperatures were a concern for the health of the plants . the parsnip roots were straight in growth , and produced a total weight of 38 . 9 g . the texture and flavor were excellent . the parsley produced straight tap roots , giving a total weight of 38 . 3 g . the foliage produced had longer petioles than usually purchased , yet the total weight was 58 . 9 g . it will be appreciated by one of skill in the art that plants with varying water requirements can be satisfied by the embodiments of the present invention , wherein one continuous porous hydrophilic irrigating tube is used to allow each plant to take its water requirements independently of the other plants . such requirements are often needed in greenhouses , where many different plants are cultivated under one roof . it has also been shown that a hydrophilic irrigation tube with two channels , one for water and the other for nutrients , can fully satisfy the plants &# 39 ; requirements and also increase the density of the plants , limited only by the sunlight available . it has also been shown that commercially available thin - walled microporous hydrophobic tubes can be converted to hydrophilic tubes and thereby become responsive to plants and their roots . such tubes may include , but are not intended to be limited to , high - pressure irrigation hoses , although their use in the present invention does not require the use of high pressure . it has also been shown how a dual - membrane tube can be incorporated into a container for one or more plants so that the plants can be fed on demand both water and nutrients from separate reservoirs and thereby require no attention or supervision as long as there is water available in the tube reservoirs . in a particular embodiment , a diametric ratio of 3 : 1 for the water tube over the nutrient tube is optimal , although this is not intended as a limitation , and obviously is dependent upon nutrient concentration and plant type . it has additionally been shown that water systems that are free of contaminated organic substances and unresponsive in the irrigation system can , by the addition of trace amounts of one or more hydrocarbons to the water supply , become responsive to the irrigation system . it has also been shown that the irrigation system of the present invention can be used to replace the emitter in a drip irrigation system , thereby making the release of water and / or nutrient responsive to the roots . in a particular embodiment , a factor of from 100 to 500 has been found for the difference in water volume used between the known drip irrigation systems and that of the present invention . in yet another embodiment 70 ( fig9 ), a pressure regulating device , such as a float flow control valve 71 ( fig1 ), is interposed between the reservoirs 72 , 73 and the tubing 74 , 75 . in addition , an inline filter 76 may be added to filter out particulate matter . in a particular embodiment , the float control 71 is operative to regulate the pressure between 1 and 3 psi , although these values are not intended as limitations . the pressure value is adjustable , for example , by setting the float flow control valve at a desired level above the tubing 74 , 75 , for example , 28 inches for a particular tubing material and system . the exemplary float control valve 71 of fig1 , a water inlet 77 feeds into a top end 78 of a chamber 79 and is affixed to a float 80 that floats on a maintained water level 81 . water exits via an outlet 82 at a bottom 83 of the chamber 79 , and an air vent 84 is supplied to maintain atmospheric pressure . the irrigation tube 74 , 75 is shown positioned beneath ground level . the height 85 above the tube &# 39 ; s level can be adjusted , and the chamber &# 39 ; s volume can be selected based upon desired flow rates through the system 70 , for example . it has been found that the addition of the float flow control valve 71 permits minimal operating pressures to be maintained , and that maximum pressures are not exceeded . whether the tubing 74 , 75 be uniform or non - uniform , a minimum pressure is required for liquid to pass through . if too much pressure is applied , the liquid passes through the pores of the tubing 74 , 75 irrespective of the presence or absence of surfactant root exudate . this system 70 permits the maintenance of pressures without the use of other , more expensive , types of pressure regulators , electronic valves , or flow regulators . the system 70 is easily concealed for landscaping applications , and yet is sufficiently robust for agricultural applications . sectors of grass are known to be grown substantially in isolation , for example , on golf courses wherein the greens are formed within soil - filled depressions in the ground and continuously or at predetermined intervals fed with water and nutrients . in such an arrangement , the system of the present invention can ideally provide water and nutrients to the grass roots on an on - demand basis , thereby saving both water and nutrients , and also ensuring optimal sustenance of the greens . the following tables 1 - 4 include data on experiments conducted indoors ( table 1 ) and outdoors ( table 2 ), and the flow rates for water and nutrient ( table 3 ) and for watering results in series and for single plants ( table 4 ). a planter with two tubes , one for water ( w ), the other for nutrient solution ( n ). the reservoirs were interchanged periodically to cancel any membrane effects . flow rates in ml / hr ; experiment time march 18 to july 16 . another aspect of the invention is directed to the making of tubing for use with a “ water - on - demand ” system . in one method , sheets of a low - porosity substance are coated with the aforementioned polyhydroxystyrene , and formed into cylinders by , for example , thermal , ultrasonic , or impulse means . although not intended as a limitation , a possible explanation of the operation of the polyhydroxystyrene polymer ( fig6 ) will now be presented . first , how the polyhdroxystyrene attaches to the membrane : polyhydroxystyrene has two groups , an hydroxyl ( oh ), which is hydrophilic and can hydrogen bond with water , and the styrene groups , which include a benzene ring (— c6h4 -) attached to an ethylene group (═ ch — ch2 -), both of which are hydrophobic and can stick to the hydrophobic polyethylene membrane , leaving the hydrophilic ( oh ) group , which forms a weak hydrogen bond with water . as discussed above , the polymer can act as a capillary through the membrane . it has been shown that organic impurities in water are 105 - 106 times more likely to stick at the exit end wall of the capillaries , where there is a gas - liquid - solid equilibrium ( i . e ., air - water - membrane ). the organic impurities are in equilibrium along the walls of the capillary , where the equilibrium is only between liquid and solid . thus the surface of the exit pores become hydrophobic due to the adsorption of the trace organic impurities in water and / or nutrient solution . when a plant is in need of water , it emits chemicals called exudates that can include a surfactant that removes the adhering organic compounds at the exit wall and liquid from the irrigation tube now is allowed to flow . this has been shown for two different membranes in the prior art , as discussed above with reference to fig7 - 8l . high - purity water is free of organic impurities . some domestic water supplies are often purified to such an extent that very little organic impurities remain . this would result in pore closure only after a large , and usually unnecessary , volume of water had passed through the membrane . the result would not be suitable because of the time delay between the removal of the organics and their deposition onto the membrane and the closure of the pores . on the other hand , too much organic content in the water could result in a delay in opening the closed pores because of the limited amount of surfactant that is released by the roots . it has been found that in general the membrane area needed for a plant is best supplied by a tube of diameter equal to about a 1 - cm radius , with a thickness of 0 . 5 mm maximum and pore sizes of from 0 . 1 to 5 μm , with a preferred average of 0 . 4 μm , although this is not intended as a limitation , and other porosity values can be used . this segment of the membrane is to be in contact with the roots of the plant . short segments of membrane tubing can be supplied with water and / or nutrient solution by smaller diameter tubing , but care must be taken to prevent air locks in the line . tubing of 1 - cm id would not be considered too large . since the feed lines are exposed to light ( sunlight or artificial lighting ), it is necessary to use opaque tubing , or the solar active light will result in algae formation that can eventually block the pores . it is believed that the coating of the hydrophobic membrane is primarily to allow the resulting hydrophilic surface to become hydrophobic and to close the pores . leaving the inner pore uncoated would restrict the flow of water through the membrane . in the foregoing description , certain terms have been used for brevity , clarity , and understanding , but no unnecessary limitations are to be implied therefrom beyond the requirements of the prior art , because such words are used for description purposes herein and are intended to be broadly construed . moreover , the embodiments of the apparatus illustrated and described herein are by way of example , and the scope of the invention is not limited to the exact details of construction . having now described the invention , the construction , the operation and use of preferred embodiments thereof , and the advantageous new and useful results obtained thereby , the new and useful constructions , and reasonable mechanical equivalents thereof obvious to those skilled in the art , are set forth in the appended claims . | a system and method for efficiently delivering an aqueous solution to plants includes a hydrophilic solution - channeling device having a delivery portion positionable adjacent a root system of a plant . the solution - channeling device has a lumen therethrough for channeling a solution from an inlet to the delivery portion . at least a portion of the delivery portion has a porosity adapted for permitting a flow of the solution therethrough when acted upon by at least one of a surfactant root exudate and negative root pressure generated by the plant roots , for example , when experiencing water stress and / or a need for nutrients . the system also includes a pressure regulating device for providing at least a minimum pressure value to permit fluid to flow through the lumen and at most a maximum pressure value above which fluid flows through the lumen even in the absence of surfactant root exudate or negative root pressure . |
in fig1 a phototherapeutic apparatus 10 is shown including a housing 12 having a plurality of light diffusing loops 14a , 14b which can be expanded out of , or retracted back into , the instrument housing 12 by control wire 16 . as shown , the apparatus 10 can further include a radio opaque region 18 which facilitates location of the instrument by radiographic means . although the apparatus is illustrated with only two loops , in some applications it can be desirable to have a great number of loops in fig2 a - 2c , the deployment of loop elements 14a and 14b is shown schematically . fig2 a illustrates a fully retracted mode in which most of the loop elements are withdrawn into the housing 12 . in fig2 b , a control wire 16 has been moved partially forward and a larger portion of diffusive loop elements 14a and 14b projects outward from the housing 12 . in fig2 c , the control wire has been slid forward even further and the loop elements 14a , 14b now are nearly fully deployed . in fig3 a , a truncated , cross - sectional view of a diffusive loop element 14 is shown connected to two optical fibers 13a and 13b , each having a light transmissive core 20a , 20b and a cladding / buffer coating 29 . the end face of each fiber core 20a , 20b is inserted into a housing 28 which contains a scattering medium 24 with optional individual scatterer particles 25 . preferably , the medium 24 has a greater refractive index than the housing 28 . fig3 b is a graph of intensity vs . radial distance for two fibers as shown in fig3 a . the curve 21a illustrates the intensity of diffused radiation vs . axial length of one fiber while curve 21b represents a similar intensity distribution for a second fiber which has been deployed in an opposite configuration . the cumulative intensity distribution of these two fibers are shown by curve 23 . by employing pairs of fibers that are joined in opposite directions , one can thus achieve nearly uniform distribution of the diffusive radiation . a similar radiation distribution pattern can be achieved by employing a reflective end cap on each loop , as shown in fig4 . in this figure , a truncated , cross - sectional view of a diffusive loop element 14 is shown having an optical fiber 13 with a light transmissive core 20 and a cladding / buffer coating 29 . the end face of fiber core 20 is inserted into a housing 28 which contains a scattering medium 24 with optional individual scatterer particles 25 . preferably , the medium 24 has a greater refractive index than the housing 28 . at the distal end of the housing 28 an end plug 26 is disposed . optionally , the end plug may also be fitted with a mirror reflector 40 to create a distribution pattern like that shown in fig3 b . light propagating through the optical fiber core 20 is transmitted into the scatterer medium and scattered in an cylindrical pattern along the length of the assembly 14 . each time the light encounters a scatterer particle , it is deflected and , at some point , the net deflection exceeds the critical angle for internal reflection at the interface between the housing 28 and the medium 24 . when this happens the light will exit . the housing can either be made sufficiently long to ensure that virtually all of the light entering it is eventually scattered and diffused in a single path , or as noted above , a reflective mirror can be fitted to the distal end of each diffuser assembly . when a mirror is employed , light propagating through the medium 24 will be at least partially scattered before it reaches mirror 40 . light which does not exit during this initial pass through the tip will be reflected by mirror 40 and returned through the tip assembly . during the second pass , the remaining radiation ( or at least a major portion of this returning radiation ) again encounters the scatterers which provide further circumferential diffusion of the light . an exemplary manufacturing process suitable for joining a diffuser assembly to a glass - clad or polymer - clad optical fiber having an outer diameter of about 50 to about 1000 micrometers can begin by stripping off the buffer from the end of the optical fiber , e . g ., exposing about two or three millimeters of the inner fiber core and its cladding . ( it is not necessary to strip the cladding away from the core .) prior to stripping , the fiber end face preferably should be prepared and polished as known in the art to minimize boundary or interface losses . a transparent tubular structure which will form the housing for the scatterer medium is then slipped over the prepared fiber end and , preferably slid beyond the fiber end . for example , if a tip assembly of about 20 millimeters is desired , the tubing can be about 100 millimeters long and slid over about 75 millimeters of the fiber , leaving an empty lumen of about 25 millimeters in front of the fiber end face . in one preferred embodiment , the housing is teflon ® fep tubing , available , for example , from zeus industries ( raritan , n . j .). the assembly is then injected with a scatterer - loaded material , such as a silicone , epoxy or other polymeric material ( if a solid diffuser is desired ) or a suitable liquid , such as water or a deuterium oxide solution , containing colloidal scatterer particles , such as silica , alumina , or titania , ( if a liquid diffuser is desired ). one exemplary scatterer medium can be formulated by mixing 70 parts of clear silicone , mastersil ™ formula 151 - clear ( available from masterbond , inc . of hackensack , n . j .) with one part of titania filled silicone , mastersil ™ formula 151 - white ( also available from masterbond ), and a conventional silicone curing or hardening agent . the tube lumen should be completely filled with the silicone , epoxy or other carrier mixture to avoid entrapment of air bubbles . the reflector ( e . g ., an aluminum , gold or other reflector - coated plug ) is inserted into the distal end of the tube . the reflector at the distal end of the scatterer tube can be a deposited metal or dielectric coating . in one preferred embodiment , a room temperature hardening agent is used and the diffuser assembly is simply allowed to solidify overnight . it should be clear that the manufacturing processes described above are merely illustrative , and various alternative techniques can be practiced to construct the fiber tip assemblies of the present invention . for example , automated extrusion methods and / or injection molding approaches can be employed to mass produce fibers with integral diffusive tip assemblies . the amount of scatterer incorporated into the diffusive tip assembly will vary with the carrier and the desired length , and can therefore be adjusted to meet particular applications . different scatterers may be more or less useful in particular applications . table 1 below illustrates certain relevant characteristics of three different scatterer compositions : table 1______________________________________scatterer characteristicsscatterer density transmission spectrumcomposition ( grams / cc ) ( wavelength in micrometers ) ______________________________________tio . sub . 2 4 . 0 . 45 - 11sio . sub . 2 2 . 1 . 2 - 7al . sub . 2 o . sub . 3 3 . 6 . 2 - 9______________________________________ in certain applications , it may be desirable to mix two or more scatterer compositions together to achieve blended characteristics . liquid scatterer compositions can be used to extend phototherapy into the ultraviolet ( uv ) and infrared ( ir ) regions of the spectrum . in particular , structures employing deuterium oxide and other heavy water solutions are useful to transmit ir light with low losses and minimal tip heating . distilled water suspensions of scatterers or simply water or acetic acid can be useful in uv light delivery . the above - described manufacturing techniques were used to produce diffusing tips joined to fibers ranging from about 100 to about 600 micrometers in diameter . when fiber bundles are joined to the diffuser tip , the individual fibers can be even smaller , e . g ., as small as 25 micrometers in diameter . the cylindrical light - diffusing assemblies can be used to produce axial exposure patterns of about 2 cm to about 4 cm in length and nearly spherical exposure patterns . the devices of the present invention can be used for various therapeutic purposes . one application is photodynamic therapy ( pdt ), a form of light - activated chemotherapy . in this approach , photosensitive dyes are delivered by injection or other vehicles such that the dye is preferentially accumulated in cancer cells . when the cells which have taken up the dye are irradiated at an appropriate wavelength ( e . g ., with red light ), a photochemical reaction occurs that yields radicals ( usually singlet oxygen ) which poison the cell . thus , the present invention further encompasses the use of diffused radiation to activate photosensitive dyes . one advantage of the present invention is that it permits pdt at remote treatment sites via a catheter , trocar , hollow needle or other hand held instrument in a minimally invasive manner because diffusive fiber tip assemblies can now be constructed with outer diameters on the order of only a few hundred micrometers . the invention is particularly useful in illuminating spherical or hollow organs such as the bladder , stomach or uterus . the present invention also encompasses the use of diffuse radiation in photocoagulation and / or hypodermic therapy of tumors and hyperplasia . for example , the phototherapy apparatuses described above can be used to treat liver , pancreatic or prostate tumors , or benign prostate hyperplasia . the application of diffuse radiation to heat prostate tissue can be used in lieu of transurethral resection of the prostate , balloon dilatation of the prostate or ultrasonic hyperthermia . in particular , the directional probes described above can be especially useful in improving the outcome of prostate treatment by heating more tissue directly in less time , and in distributing irradiation over a larger volume of prostatic tissue , thus increasing the therapeutic heating effects while reducing the risk of overheating damage to surrounding tissue structures such as the sphincter . the invention further permits interstitial laser coagulation of hepatic and pancreatic tumors . the desired effects are achieved by thermal destruction of cancerous tissue by depositing laser radiation via a diffusive fiber tip carrier by a hypodermic needle or similar instrument inserted percutaneously into the tumor . in each of these procedures , therapy can be delivered while the patient is awake ; general anesthesia as well as open surgery are avoided . in heat - based phototherapy techniques , the diffusive fiber tip assemblies of the present invention allow for the formation of large distributed heat sources within the target tissue . the invention significantly alters the rate of heat deposition in tissue , especially in the regions immediately surrounding the fiber tip , where tissue overheating and / or carbonization would limit the effectiveness and inhibit efficient heat transfer . since the radiation is distributed by the diffuser assembly over a larger volume of tissue , more tissue is heated directly and there is less need to rely on convective or conductive heat transfer through nearby tissue to reach the periphery of the tumor . moreover , the materials disclosed herein for the diffusive tips and jackets further enhance the therapeutic effects by permitting high radiation transmission and low absorption , thereby ensuring the tip assembly itself does not overheat during usage . in addition , the use of teflon ® tubes and / or coatings further improve the procedures by avoiding the problem of tip fusion or contact - adhesion between the tip assembly and biological tissue during usage . it has been found that teflon ® fep materials ( polyperfluoroethylene - propylene copolymers ) are preferable for most applications because they do not discolor if they are etched prior to loading with the scatterer medium , although teflon ® pfa materials ( polytetrafluoroethylene polymers with perfluoroalkoxy side chains ) and teflon ® ptfe ( polytetrafluoroethylene ) and other fluoropolmers may also be useful . in fig5 the loop diffuser apparatus of the present invention 10 is shown schematically in operation . the diffuser apparatus 10 is coupled to a source of phototherapeutic radiation 36 ( e . g ., a laser ) and positioned within a patient &# 39 ; s body to provide phototherapy . as shown in fig5 the diffuser assembly can be designed to fit within the instrument channel of an endoscope 32 . the endoscope can further include viewing means 34 and / or at least one additional channel 38 for the introduction of irrigation saline or therapeutic solutions . alternatively , the diffusing assemblies of the present invention can be incorporated into catheter - type instruments that are introduced into the patient &# 39 ; s body without the assistance of an endoscopic channel . in fig6 an outer jacket ( e . g ., of teflon ® material ) is shown disposed about the apparatus to encase the fiber 12 and loop diffuser assembly 14 . the outer sheath surrounds the entire optical transmission apparatus and ensures that the radiation - generating components do not come into direct contact with the patient &# 39 ; s body and , thereby , permits reuse of the instrument . only the outer sheath 50 needs to be disposed after each use . | methods and apparatus are disclosed for diffusing radiation from a optical fiber to provide a larger exposure area for phototherapy and to provide a substantially uniform energy distribution to a major portion of the exposure area . the invention is especially useful in constructing and implementing circumferential and / or sideways - emitting diffusive tip assemblies , or quasi - spherical diffusive tip assemblies for optical fibers to direct laser radiation in a radially outward pattern relative to the fiber &# 39 ; s axis . in one aspect of the invention , a plurality of optically - transmissive fiber tip assemblies are employed to act as diffusers . the two or more fiber tip assemblies are deployed as loops which create a uniform illumination pattern . by &# 34 ; looping &# 34 ; or &# 34 ; folding &# 34 ; the fibers , a plurality of fibers can be deployed in conjunction with one another to create geometric exposure patterns with increased energy density while still avoiding &# 34 ; hot spots .&# 34 ; |
preferred embodiments of the present disclosure will be described hereinbelow with reference to the accompanying drawings . in the following description , well - known functions or constructions are not described in detail to avoid obscuring the present disclosure in unnecessary detail . referring to the drawings and particularly fig1 , a punching bag and suspension system is illustrated and generally designated by the reference character 10 . the system includes a punching bag 12 and a suspension member 14 . the punching bag 12 may be supported on a generally horizontal suspension member 14 held by a first connection mechanism 16 on one side of the suspension member 14 and a second connection mechanism 18 on the other side of the suspension member 14 . in one embodiment , the connection mechanisms 16 , 18 are self - adjustable to adjust a length of the suspension member 14 . the connection mechanisms 16 , 18 may be latches , hooks , a noose , etc . as shown in fig2 , the first connection mechanism 16 is attached to a fixed structure 20 , e . g ., a vertical post or support , and the second connection mechanism 18 is attached to another fixed structure 22 , e . g ., a vertical post or support , and can be adjustable to any length , for example , between about 4 feet to about 30 feet . when attached to the fixed structures 20 , 22 , the suspension member 14 is generally horizontal and enables the punching bag 12 to travel horizontally thereon as indicated by the arrows . the punching bag and attachment system 10 may be connected to structures other than structures 20 , 22 shown in fig2 , for example , a wall , a fence , a part of a boxing ring , etc . the punching bag 12 is suspended in the air by the suspension member 14 . the suspension member 14 can be made of , but not limited to , a rope , a bungee , a nylon cord , etc . in one embodiment , the suspension member 14 is flexible , e . g ., a bungee cord , which increases the movement of the punching bag forward and backward relative to a user in addition to moving side to side . as shown in fig3 , the punching bag 12 has a cylindrical tube 24 ( shown in broken lines ) through its core with an opening on one side 26 and an opening on the other side 28 . the ends of the cylindrical tube 24 meet the outer circular openings 26 , 28 of the punching bag 12 flush . these openings 26 , 28 allow the tube 24 to slide along suspension member 14 . the tube 24 may be made of metal , plastic , a magnetic material , a ferromagnetic material , etc . as shown in fig4 , an outer membrane 13 of the punching bag 12 may include a rubber material , an ethylene vinyl acetate ( eva ) material , or an alternate material . the punching bag 12 may include a bladder 30 that could be filled with air , gas , foam , a soft material , etc . in one embodiment , the tube 24 is composed of metal , a ferromagnetic material , plastic , etc . in an alternate embodiment , the tube 24 is magnetized . in yet another alternate embodiment as shown in fig5 , the punching bag 12 contains a tube 124 that contains ball bearings 32 in a wall 33 of the tube 124 to help the tube slide easily over the suspension member 14 . in a further embodiment as shown in fig6 , the tube 224 contains a wheel 34 with an attached coil spring 36 located inside a terminal 38 , also known as a recoil mechanism , shown on both ends . when the punching bag 12 is in motion , the wheel 34 contacts the suspension member 14 and winds up the internal coil spring 36 and is eventually propelled back by the coil spring 36 in the opposite direction it was moving , hence bringing it back to its original position . although the embodiment in fig6 illustrates two wheels 34 , coil springs 36 , and terminals 38 , i . e ., two recoil mechanisms , it is to be appreciated that other embodiment may include only one recoil mechanism , two recoil mechanisms or more than two recoil mechanisms . as shown in fig7 , in one embodiment , there is a weight 40 coupled to the suspension member 14 and deposed in the approximate center of the suspension member 14 . it is to be appreciated that the weight 40 may be coupled to the suspension member 14 in various ways . for example , the weight 40 may be a sleeve slid over the suspension member 14 , the weight may be compressed onto the suspension member 14 , the suspension member 14 may be coupled to the ends of the weight 40 , etc . it is further to be appreciated that the weight 40 will be configured to allow the tube 24 to travel over the weight 40 , e . g ., the weight is configured in a generally cylindrical shape . due to gravity , the weight 40 creates a point that is closer to the ground than any other area on the suspension member 40 as shown by arrow a , therefore directing the punching bag 12 to the center where the weight 40 is disposed . in another embodiment , the weight 40 is magnetized and disposed in the approximate center of the suspension member 14 that creates a point that is closer to the ground than any other area as shown by arrow a , therefore directing the punching bag 12 to the center . the magnetism of the weight 40 produces a locking effect when contact is made with the tube 24 , 124 , 224 when the tube is made of a predetermined material , e . g ., metal , a ferromagnetic material , etc . since the magnetic weight 40 attracts the tube 24 , 124 , 224 , the punching bag will tend to come to rest at the weight 40 instead on continuing to travel along the suspension mechanism past the weight 40 . in an alternate embodiment , there is a metal weight 40 in the direct center of the suspension member 14 . the weight 40 may be composed of metal or a ferromagnetic material produces a locking effect when contact is made with the magnetized tube 24 , 124 , 224 creating an orientation point and return point for the punching bag 12 . in yet another embodiment , the tube 24 , 124 , 224 could be plastic or an alternate material , and the weight 40 may be made of metal or an alternate material . as shown in fig8 , when the punching bag 12 is struck on the right side , as shown by arrow b , the punching bag 12 travels along the suspension member 14 , as shown by arrow c , until the punching bag 12 comes to rest . upon rest , the punching bag 12 then returns to its orientation point over the weight 40 , as shown by arrow d . as shown in fig9 , when the punching bag 12 is struck on the left side , as shown by arrow e , the punching bag 12 travels along the suspension member 14 , as indicated by arrow f , until the punching bag 12 comes to rest . upon rest , the punching bag 12 then returns to its orientation point over the weight 40 , as shown by arrow g . in one embodiment , the weight 40 is composed of metal and produces a locking effect when contact is made with the magnetized tube , 24 , 124 , 224 , thus preventing the punching bag 12 from extending past the weight 40 . in another embodiment , the tube 24 , 124 , 224 is composed of metal and produces a locking effect when contact is made with the magnetized weight 40 , thus preventing the punching bag 12 from extending past the weight 40 . in yet another embodiment , the tube 24 , 124 , 224 could be made of plastic , rubber , a ferromagnetic material , etc . and the weight 40 could be made of a metal , a ferromagnetic material , a non - metal material , etc . it is to be appreciated that the various features shown and described are interchangeable , that is a feature shown in one embodiment may be incorporated into another embodiment . while the disclosure has been shown and described with reference to certain preferred embodiments thereof , it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the disclosure . furthermore , although the foregoing text sets forth a detailed description of numerous embodiments , it should be understood that the legal scope of the invention is defined by the words of the claims set forth at the end of this patent . the detailed description is to be construed as exemplary only and does not describe every possible embodiment , as describing every possible embodiment would be impractical , if not impossible . one could implement numerous alternate embodiments , using either current technology or technology developed after the filing date of this patent , which would still fall within the scope of the claims . it should also be understood that , unless a term is expressly defined in this patent using the sentence “ as used herein , the term ‘ ______ ’ is hereby defined to mean . . . ” or a similar sentence , there is no intent to limit the meaning of that term , either expressly or by implication , beyond its plain or ordinary meaning , and such term should not be interpreted to be limited in scope based on any statement made in any section of this patent ( other than the language of the claims ). to the extent that any term recited in the claims at the end of this patent is referred to in this patent in a manner consistent with a single meaning , that is done for sake of clarity only so as to not confuse the reader , and it is not intended that such claim term be limited , by implication or otherwise , to that single meaning . finally , unless a claim element is defined by reciting the word “ means ” and a function without the recital of any structure , it is not intended that the scope of any claim element be interpreted based on the application of 35 u . s . c . § 112 , sixth paragraph . | a punching bag and suspension system is a boxing training device that is orientated horizontally , which permits the punching bag to move vertically , horizontally , diagonally , as well as a 360 degree range of motion . the punching bag has a plastic or metal cylindrical tube running through its core . the tube contains an opening on both sides extending to the outer circumference of the punching bag . these openings allow the tube , and therefore the punching bag , to slide along suspension member . at the center of the suspension member there is a weight that through gravitational pull , creates an orientation and return point for the punching bag . |
referring now to the various figures , a detailed description of the preferred embodiment of the present invention will be presented . various complex dielectric permittivity , temperature and distribution pattern studies of microwave heated teeth and simulations of specific absorption rate distribution have been conducted as part of the research into the present invention . the complex permittivity was measured on different types of dental tissues , using extracted teeth , including enamel , dentin and caries . reflective coefficients have been obtained using a network analyzer . the characteristics of enamel caries and dentin are different . the dielectric loss factor of caries is fairly higher than that of normal healthy parts particularly in the millimetric wave in the frequency between 12 ghz to 25 ghz . when the tooth is exposed to millimetric microwaves in this range , caries are preferentially heated . temperature rise can kill the microorganisms in caries . control and or extinction of microorganism slows or stops the progress of caries , permitting previously carious tissue to recalcify by biological latent support of the pulp . temperature distribution measurement with microwaves heating reveals that the temperature of caries is higher than that of normal tooth tissue . these properties are used with the provisions of this invention for the diagnostic and treatment of teeth having caries and subsequent internal heat conditioning and or curing of provided dental restorative materials . when dielectric loss factor is higher , the absorption of microwave is better and local temperature is higher . microwave energy heats by radiation and is able to penetrate through various substances including desiccated tissue and thus can create an addressed effect . to understand the details on which the preferred embodiment is based , it is helpful to understand how microwave energy is generated and absorbed . the microwave energy absorbed by a given dental materials is governed by the following equation : this equation shows that in order to determine the microwave energy in terms of the incident microwave power level absorbed by a dental article , both the applied electric field strength and the dielectric material characteristics must be known . one of the difficulties in properly evaluating this equation is that when a curable dielectric resinous material is polymerized , its microwave absorption is drastically reduced because the dielectric constant of the material changes as a result of the polymerization process . similarly , when microwave energy is directed to a tooth containing a carious lesion , the absorption of the microwave energy changes . the present invention utilizes this difference in absorption as a mechanism for identifying carious lesions with the same hand - held dental tool that can be used to non - invasively treat those caries , in one embodiment as shown in fig7 a system of caries control in a non invasive atraumatic way , without surgical burs entry and with a reduced risk and necessity of exposing the dental pulp organ comprise , a hand held microwave applicator with a sufficient microwave power delivery capability is provided to heat the dental tissues or restorative materials . the electronic circuit diagram of fig7 is designed to suit small microwave generators such as an oscillation source coupled with a rf power amplifier or impatt diodes or similar solid state or transistorized microwave emitters with an output power of about 2 to 5 watts which requires usually an electrical voltage of about 60 dc . the bias voltage is applied through a high impedance line ( 56 ) in order to limit the perturbation of electromagnetic signals . a power supply module is provided with a current and voltage limiting mean to permit the polarization of the impatt diode in the specific limits with a resonant circuit ( 57 ), such as a 50 ohms line , having a length preferably equal to the half of the length of the selected frequency . the length of the line may be calculated with the following equation : l = 3 × 10 8 / 2fε cff ½ . one end of the “ resonator ” is connected to the impatt diode ( 58 ) and the other end of it is coupled ( 59 ) to a transmission line including an isolator ( 60 ) to provide isolation of the microwave source from the rest of the circuit in order to avoid frequency variations , caused by a mismatch of the output ( 61 ). a coupler ( 62 ) having a coupling of about − 15 db permit a sampling of the signal emitted by the microwave generator in order to measure the incident and reflected power levels . the couplers should be perfectly matched at both extremities to permit precise measurements . matching circuit ( 63 ) at the input and the output as well as load resistors permit achievement of an adaptation at each ends , equal or better than − 15 db . detecting diodes ( 64 ) rectify the radio frequencies signal in order to convert the power to a dc voltage which can advantageously be subsequently transmitted to a micro controller or a “ adc ” analog digital converter which converts this voltage to a digital signal for an appropriate processing of the acquired information and the precise monitoring and the control of the microwaves energy delivered to the dental target . the controller is a means of setting the power level , exposure cycles , processing modes , and may also be used in the selection of the frequency of microwave generation . as shown in fig2 the control of the microwave source is preferably made by a selector ( 65 ), located on the device , allowing the operator to set different power levels and modes . between the tip antenna and the microwave source or amplifier , a shielded cable ( 66 ) or wave guide , as short as possible is used to operatively transmit the microwave power to the head antenna . a suitable connector preferably permits the interchange of different provided head antennas to match different applications and enhance energy transmission and deposition on the dental target . a means of electrical supply ( 67 ), such as a shielded cable , connects the mobile applicator to the power supply . the hand held applicator may be equipped with a water cooling system ( 68 ) and a digital display ( 69 ). one head antenna ( 70 ) as shown in fig4 is provided for therapeutic purposes to target teeth and treat , heat or detect dental caries , and is made of a highly conductive metal such as copper , platinum or gold , plated or not , having the format of a rectangular or a loop shaped band of which one end is connected to the inner and the outer conductors of the transmission line . one provided monopole head antenna has the form of an i as shown in fig5 . this applicator is made for example by stripping the outer jacket and the outer conductor of a coaxial shielded cable , the inner conductor and dielectric ( teflon ) constitute the applicator . to increase the directivity of the radiating microwave energy , a loaded i - applicator ( 71 ) having an increased forwarding effect may be made by placing a platinum ring over the outer conductor of the coaxial cable and soldering a platinum rod on the inner conductor of the antenna . another provided head antenna ( 72 ) as shown in fig6 is made of a microstrip which may be made of miscible polymeric or other conductive materials , having the format for example of a square metal skin is positioned on a dielectric substrate with a ground plane on its back . an electrically shielded temperature probe may be embedded in the head of the hand held applicator antenna to provide a means of monitoring the temperature of the heated target for judging the efficiency of tissue heating and to avoid sudden temperature rises . the provided head antenna designs help in achieving good impedance matching and effective delivery of microwave for internal heat conditioning of dental targets . as shown in fig3 a means of safely containing any leakage of microwave energy close to the irradiation space can be used such as the disclosed head antenna choke ( 73 ), made of microwave absorbing materials . preferably , the antennas are made with a portion that is strong and flexible enough to be used as a positioning and compression tool for the pasty resin matrix for the dental composite . the loop and patch antenna may preferably carry negative dental molds to aid in the formation of the dental composite . alternatively , a minaturized version of a manual resin injector , such as previously described in connection with fig1 may be provided to deliver the pasty resin matrix for the dental composite as part of the hand - held tool . while the hand - held tool is preferably used in an intra - oral application with dental composites , it will be recognized that the hand - held tool can also be used in the dental office , for example , to accomplish repairs or welds of dental prosthetics devices as well . in one embodiment as shown in fig1 an economic manual fluid resin pressurization and injection device ( 46 ) is provided to remove the need of being connected to an external pressurized fluid source . a mechanical force accumulator such as a spring ( 47 ) is compressed by turning the internally threaded cylinder ( 48 ) while holding the device handle ( 49 ). a force boosting piston ( 50 ) is especially useful for molding and filling of composite curable dental materials . the injection nozzle and the piston acts as previously described . when under a hydraulic pressure , the piston ( 39 ) forces the material from its compartment through the injector ( 40 ). the piston ( 39 ) is advantageously equipped with sealing joints ( 44 ). this embodiment can be minaturized and employed with the hand - held intra - oral microwave applicator . in general , various polymer based material compositions are useful for the construction of dental devices . these compositions may be used in the filling of teeth and the construction of appliances used for replacing teeth and other oral structures . one preferred composition for dental composites suited to be formed and hardened in accordance with the providing of this invention consists of a polymerizable mixture including one or a selection from the large family of polyfunctional methacrylate esters , and oligomers including the compound prepared from one molecule of bisphenol a and two molecules of glycidyl methacrylate called 2 , 2bis [ 4 ( 2 - hydroxy - 3 methacryloyloxy - propyloxy )- phenyl ] propane , known as bis - gma for its lower degree of shrinkage and / or 2 , 2 - bis [ 4 - methacryloxyethoxy ) phenyl ] propane for its good water resistance properties . other monomers , such as triethyleneglycol dimethacrylate for viscosity reduction , urethane dimethacrylates , spiro orthocarbontes , etc are advantageously employed in admixture with silanized inorganic fillers and organic fillers , coupling agents , microwave sensitive cure initiation system including organic peroxides and amines and color pigments are advantageously added . the weight of the fillers as an overall weight of the composite is preferably in the range of 30 to 90 % and include silanized silicon dioxide particles . in one embodiment , compositions specially suitable for making dental removable appliances such as dentures is provided which comprise a liquid and a powdery component . the liquid component in accordance with the invention contains preferably from 40 % to 90 % of mono -, di -, tri , or multifunctional acrylic monomer , a cross - linking agent , a plasticizer , a stabilizer . an accelerator and color pigments . the mono -, di , tri , or multifinctional acrylic monomer in accordance with the invention are within the scope of the formula : where r1 in accordance with the invention is hydrogen , alkyl , substituted alkyl group , cyclic hydrocarbon , benzyl , ether , hydroxyalkyl and r2 is hydrogen , halogen , alkyl , substituted alkyl or cyclic hydrocarbon group . monomers within the scope of the following formula are also particularly suitable to the invention : wherein r is an acrylic - free organic moiety , r 1 is hydrogen , hologen , halogen , alkyl , substituted alkyl or cyano radical and n is an integer from 1 to 20 and m is an integer from 1 to 1000 . these monomers may be used alone or in admixture . the microwave sensitive initiators in accordance with the invention includes benzoyl and peroxide , dilauroyl peroxide up to 2 , 5 %. the polymerization accelerator in accordance with the invention is a quaternary ammonium chloride , which is easily soluble in the methacrylate monomers and reacts with barbituric acid derivatives . a preferred compounds are the quatemary ammonium with an alkyl of 1 to 20 carbons , such as , dodecyltrimethylammonium . these quaternary ammonium chlorides may be added in alone or in admixture from 0 , 09 to 1 , 5 %. the crosslinking agent in accordance with the provided microwave hardening material compositions is a polyfunctional monomer wherein at least two carbon - carbon double bonds , such as 1 , 3 - butanediol dimethacrylate , 1 , 4 - butanediol dimethacrylate , 1 , 4 - butanediol divinyl ether , di ( ethylene glycol ) dimethacrylate , di ( ethylene glycol ) divinyl ether , pentaerythritol diacrylate monostearate , ethylene glycol dimethacrylate , trimetylolpropane trimethacrylate , pentaerythritol triacrylate , pentaerythritol tetraacrylate , trimetylolpropane triacrylate . the crosslinking agents may be used alone or in admixture . polymerization promoters for the monomers of the provided curable material compositions for the present invention are useful because they rapidly react with the quaternary ammonium chloride to produce radicals , which promotes a rapid and uniform polymerization in the composition and a higher degree of conversion . the barbituric acid derivative in accordance with the invention include 1 , 3 , 5 - trimethylbarbituric acid , 1 , 3 - dimethyl - 5 - isobutylbarbituric acid , 1 , 3 - dimethyl - 5 - phenylbarbituric acid , 5 - n - butylbarbituric acid , 5 - ethylbarbituric acid , 1 - cyclohexyl - 5 - ethylbarbituric acid and 1 - benzyl - 5 - phenylbarbituric acid . these acid derivatives may be used alone or in admixture in very small amounts . the polymerization stabilizers comprise hydroquinone , hydroquinone monomethyl ether or 4 - ethoxyphenol which are usually added to the liquid component of dental compositions ( up to 4 %). the plasticizer in accordance with the invention is generally a low molecular weight ester , such as dibutyl phthalate or phosphates . the composition for a one component microwavable curable material system in accordance with this invention is approximately the same as the one for the two component materials with some variations mainly in the initiation system . preferred initiators for a one component dental composition for denture or such need to be thermally stable at room or higher temperatures such as 50 ° c . and initiate polymerization at higher temperatures such as benzopinacole , tert - butyleperbenzoate , and 2 , 2 ′ dichlorobenzopinacol . the powder component in accordance with the invention includes from 20 % to 80 % of mono - di - tri , or multifunctional acrylic or acrylate ester polymer . the powder may advantageously include from 5 % to 40 % of a copolymer . the powder component in accordance with the invention may advantageously include from 0 , 1 % to 3 % of an initiator for radical polymerization including organic peroxides such as benzoyl peroxide and dilauroyl peroxide . the powder component in accordance with the invention can include up to 1 % of a barbituric acid derivative to promote chemical reaction . the mono -, di , tri , or multifunctional acrylic polymer used in denture base in accordance with the invention are : where the r1 in accordance with the invention is hydrogen , alkyl , substituted alkyl group , cyclic hydrocarbon , benzyl , ether , hydroxyalkyl , r2 is hydrogen , halogen , alkyl , substituted alkyl group and n is an integer at least equal to 2 . the copolymer in accordance with this invention are mainly composed of methyl methacrylate polymer or a mixture of methyl methacrylate polymer and an methacrylate polymer other than methyl methacrylate polymer . inorganic and organic fillers may be added into the compositions of one or two components denture base . useful inorganic fillers include glass , metal ceramics , silicon dioxide in powdery or fiber format , which are preferably silanized with coupling agent , such as 3 - methacryloxloxypropyltrimethoxy . organic fillers include splinter or bead polymers of high molecular weight , or fibers such as aramide fibers , polyacrylate fibers , polyamide fibers and polyacrylonitrile fibers . organic fillers may be used alone or mixed with inorganic fillers . thermoplastic compounds such as poly functional methacrylate , polycarbonate , polysulfone , fluoropolymers , elastomers , polyurethanes , impression compound , wax , gutta percha , polycaprolactone and mixture of thermoset and thermoplastics are advantageously heat processed with the provided method and permit dental rehabilitation . microwave absorbing substances can advantageously be incorporated into disclosed thermoplastic and thermohardening material compositions , to decrease internal heat generation of compositions which does not have sufficient dielectrical loss when microwaved nor does they have sufficient heatability for a desired speed of heating . these microwave absorbants are also useful when the employed polymeric material has only a low microwave absorption behavior at low temperatures such as many thermoplastic polymers including polycarbonate and also for substantially increasing the speed and the addressability such as in welding and joining functions . these absorbers may be powdery , hollowed , coated and comprise ferromagnetics , metallic oxides or speciality ceramics . microwave absorbant materials and or sterilants can be advantageously utilized with the intra - oral embodiment of the present invention to increase the speed and addressability of heating the dental composite and to increase the effectiveness of the sterilization of the targeted caries . the following tables set forth several examples in accordance with the various aspects of the present invention . all ratio for materials are expressed in weight . | a hand - held microwave system for intra - oral dentistry utilizes microwave energy to cure polymer materials intra - orally so as to produce dental composites having improved physical characteristics , and also utilizes microwave energy to detect the presence of and to preferentially heat caries or cavities , thereby disinfecting and therapeutically treating the caries in a potentially non - invasive manner . the intra - oral polymerization process can be accomplished with less overall energy and with composite - matrices that maximally absorb the microwave energy so as to reduce heating of adjacent tissue . the antenna of a hand - held version of the intra - oral microwave system is also advantageously designed to detect the presence of and to preferentially heat caries or cavities , thereby disinfecting and therapeutically treating the caries in a potentially non - invasive manner . a method and product by process for the system are also disclosed . |
referring to the drawings in detail and to fig1 in particular , reference character 10 generally designates a warning device constructed in accordance with the present invention . the warning device 10 may be built into durable medical equipment , such as a walker , a cane , or a wheelchair . similarly , as shown in fig1 the device may be mounted in a case 12 , so it may be added to an existing ambulatory aid . when the warning device 10 is mounted in a case , such as case 12 , preferably the case 12 includes a back plate 14 , a left side plate 16 , and a right side plate 18 . a cover ( not shown ) may be provided to enclose the remainder of the case . the warning device 10 includes a power source 22 , the power source may be any electrical storage device , but preferably is a battery with a large storage capacity such as the nine volt battery , shown in fig1 . the device also includes a warning indicator 24 ( such as a buzzes , light or vibrator ), and one or more gravity sensitive switches , such as mercury switches . shown in fig1 are sight mercury switch 30 , left mercury switch 34 , rear mercury switch 36 , and front mercury switch 38 . the warning device 10 may also include an on / off switch , such as on / off switch 26 . it should be noted that a single switch would warn the user of the most common misuse . for example , a single switch could activate a warning if a walker , wheel chair or other device was tilted to the rear . it should also be noted that although four switches are preferable , three switches could be used to activate the warning when a device is tilted in any direction . in addition , more than four switches could be used to activate the warning device . electrical leads connect the power source 22 , the warning indicator 24 and the gravity sensing switches 30 , 34 , 36 & amp ; 38 such that when any gravity sensing switch is closed , the warning indicator 24 is activated . as shown in fig1 an on / off switch 26 may be placed at any point in the electrical circuit so that the device may be shut down to conserve power when not in use . the gravity sensing switches should be designed and positioned in such a manner that tilting the warning device 10 in any direction , beyond a specified degree , will close the circuit and activate the warning indicator 24 . preferable , the gravity sensing switches are a plurality of mercury switches connected parallel such that the closing of any individual mercury switch will activate the warning indicator 24 . as shown in fig1 each mercury switch 30 , 34 , 36 and 38 may be mounted in a mounting block 28 . right mercury switch 30 is mounted at an angle 32 , such that when the warning device 10 is tilted to the right , beyond the angle 32 , the circuit closes and activates the warning device 24 . in a similar manner , left mercury switch 34 , is mounted at an angle 32 , to activate the warning indicator when the warning device is tilted to the left , beyond the angle 32 . rear mercury switch 36 and front mercury switch 38 are also mounted at angles to activate the warning indicator when the warning device 10 is tilted either to the rear or to the front beyond angle 32 . the warning device 10 shown in fig2 is attached to a walker 40 . the walker has a front 42 , a rear 44 and a top 46 . when the walker 40 is tilted at an angle 48 to the rear , or in any other direction , the warning device activates , indicating to the operator that an unsafe condition of the walker exists . one or more pressure switches 50 may be attached to the legs of the walker 40 and to the warning device 10 to prevent the warning device from activating when all four legs are firmly placed on the ground . in this way , the walker 10 will not give a false warning when it is used on an incline slope , such as a handicap ramp . however , it should be noted that the angle 48 of activation of the warning device 10 should be such that it would not activate when used on a properly installed handicap ramp . in an alternative embodiment , the gravity switches 30 , 34 , 36 , and 38 , could be eliminated and replaced with pressure switches , such as switch 50 on each of the four legs of the walker . the pressure switches should be wired , such that when any two legs of the walker 40 are in contact with the surface of the ground and the remaining two are not in contact with the surface of the ground , the warning device 10 would activate . the proper use of a walker includes lifting the walker vertically without tilting the walker , then moving it horizontally away from the user and placing it down . when used properly , the walker should never be tilted , thus the warning indicator 24 would not activate unless the walker was used improperly . fig3 shows a cane 66 having the warning device 10 attached thereto . the cane 66 disclosed in fig3 is a quad cane , but it should be noted that the warning device may be used with any multi legged cane , that is , any cane having a plurality of legs . the quad cane 66 of fig3 has cane legs 62 ( only one being designated by reference numeral 62 therein ), a handle 64 and a front 60 . the warning device 10 may be attached to the cane or to the cane legs , so long as it is securely attached and maintains its position relative to the cane 66 . fig4 shows the warning device attached to a wheelchair 70 . it should be noted that when attached to a wheelchair , it is not necessary for the warning device 10 to active when the wheelchair 70 is tilted either to the left or to the right , however , the warning device 10 should activate whenever the wheelchair is tilted to the rear . this is because one common , unsafe use of a wheelchair is tilting rearward , which may cause the operator to fall over backwards . fig5 shows a perspective view of the walker 40 , with different types of warning indicators attached to the warning device 10 . for example , a vibrator 80 may be placed inside the handle of the walker 40 to warn the user by vibrating the walker &# 39 ; s handle . another indicator which may be used , either in conjunction , with the vibrator 80 , or separately , is a warning light 82 . the light 82 should be attached to the walker 40 , along the front portion thereof , so that it is clearly visible to the user , when using the walker 40 . the warning light 82 and the vibrator 80 may be used in conjunction with a horn or buzzes . it should be understood that any of the warning indicators may be used alone or in conjunction with one or more of the other warning indicators . as shown in fig5 pressure switches may also be added as an additional safety device , to either indicate when one or more legs are in contact with the ground , and the remaining legs are not in contact . additionally , the pressure switches 50 may be used in conjunction with the various warning indicators and gravity switches to activate only when the gravity switches indicate an unsafe position and one or more pressure switches are not in contact with the ground . fig6 shows an improved mercury switch , which may be used with the current invention . a baffled mercury switch 90 includes a sealed tube , such as glass tube 92 , containing mercury 94 . a first electrical lead 96 and a second electrical lead 98 extend into the glass tube and may be connected to the warning device , such that it would complete a circuit , when the mercury 94 travels from the first end 104 to the second end 106 . one or more baffles 100 placed inside the glass tube 92 , between the first end 104 and the second end 106 , may be provided to prevent the mercury 94 from bouncing from the first end 104 to the second end 106 . in this way , the baffles 100 dampen the movement of the mercury 94 , such that minor jars and jolts do not cause the mercury 94 to complete the contact between the first lead 96 and the second lead 98 . a suitable baffle such as baffle 100 , includes a disc mounted inside the glass tube 92 at an intermediate point between the first end 104 and the second end 106 . wherein the disc 100 includes a plurality of apperatures 102 . there should be sufficient number of baffles 100 with large enough apperatures 102 to allow the mercury 94 to easily move from the first end 104 to the second end 106 whenever the second end 106 is lower than the first end 104 . another possible baffled switch would include ridges or other protrusion which extend from the sides of the tube to dampen the movement of the mercury . the mercury switches of the present invention may be mounted permanently in the case , or ambulatory aid , however , it has been found that it is advantageous to mount the mercury switches so that they may be adjusted to set the angle of activation and to calibrate the warning device 10 so that each mercury switch activates at a similar angle . one method for accomplishing this is to mount the mercury switches on separate adjustable mercury switch mounts , such as switch mount 110 , shown in fig7 . switch mount 110 includes a base plate 112 , having attachment holes 122 therein . the base plate 112 may be screwed , tacked , glued , welded , or otherwise secured to the warning device case or ambulatory aid . the switch mount 110 also includes pivotal plate 114 . plate 114 is pivotally connected to the base plate 112 by pivotal connection 116 . connection 116 may be a screw , rivet , or other means of attachment as long as the pivotal plate 114 may pivot relative to the base plate 112 . locking screw 118 may be provided , to attach the opposite end of the pivotal plate 114 . in this way , locking screw 118 may be loosened and pivotal plate 114 may be pivoted to set the angle of activation of the mercury switch . the mercury switch should be attached to the pivotal plate by a suitable means . preferably the mercury switches are attached by means such as holding prongs 120 . in this way the mercury switch may be removed and replaced if damaged . fig8 shows an alternative gravity switch which may be used in place of the plurality of mercury switches in the warning device 10 . the alternative gravity switch 130 , includes a conductive loop 132 , connected to a lead 134 to the warning device . a flexible conductor 136 is provided ( or a rigid or semi - rigid conductor may be used as long as it is hinged at hinge point 138 or in a similar manner ). the flexible conductor 136 is electrically connected to the power supply through lead 140 . a weight 142 is attached to the lower end of the flexible connection . in this way whenever the alternative gravity switch is tilted , the flexible lead will come in contact with the conductive loop 132 , thereby completing a circuit . changes may be made in the combinations , operations and arrangements of the various pairs and elements described herein without departing from the spirit and scope of the invention as defined in the following claims . | an ambulation aid warning device for warning the uses when an ambulation aid is about to be used improperly . the device includes one or more gravity sensitive switches to activate an auditory , visual and / or sensory alarm when the ambulation aid is tilted beyond a specified angle . |
the posterior stabilized knee replacement 100 consists of a femoral component 200 , a bearing 300 , a control arm assembly 400 and a tibial platform 500 as shown in fig1 . the femoral component 200 , as shown in fig2 and 3 , contains a cam box 201 with box sidewalls 202 and femoral cam 203 . the femoral cam 203 includes a cam surface 204 that faces inferiorly at full extension , as shown in fig1 . in the embodiment of fig1 - 19 , the femoral cam surface 204 is a single concave surface . in other embodiments , the cam surface could be a compound curve with convex surfaces separated by a concave surface . the cam box 201 also includes an anterior wall 211 . the femoral component 200 is similar to that described in u . s . pat . no . 5 , 702 , 466 except for the addition of the cam box 201 detail and a modular post for accepting an extensions to provide enhanced fixation . more particularly , the femoral component 200 includes a pair of convex condyles 206 that face inferiorly for articular bearing engagement with the bearing 300 , as explained below . the bearing 300 , as shown in fig4 - 6 , contains a posterior notch 301 , a dovetail guide slot 302 and a stop recess 303 with a bearing stop surface 304 . the control arm assembly 400 , as shown in fig7 - 9 , comprises a control arm 410 , a post 420 and a conical bearing 430 . the post 420 has medial and lateral side surfaces 421 , an inferior recess 422 , a post cam surface 423 and an anterior stop surface 424 . the control arm 410 comprises a post support pin 412 , a dovetail guide 413 , a conical bearing support 414 , a control arm boss 415 with control arm stop surfaces 416 and a stop pin 417 . the post 420 and conical bearing 403 preferably are formed from plastic and are assembled to the control arm 410 by pressing them on the post support pin 412 and conical bearing support 414 respectively . during assembly the inferior recess 422 of the post 420 engages the boss sidewalls 417 of the control arm 410 to prevent rotation of the post 420 on the post support pin 412 . the tibial platform 500 has a superior bearing surface 501 and contains a conical hole 502 into which the conical bearing 403 of the control arm assembly 400 is placed on implantation . the tibial platform 500 can be the same as that described in u . s . pat . no . 5 , 702 , 466 . the embodiment shown here is a version used where an extension is added to the distal end of the platform to enhance fixation where needed . the femoral component 200 , the control arm 410 and tibial platform 500 preferably are made of titanium alloy coated with ultracoat ® tin coating as disclosed in u . s . pat . no . 5 , 702 , 448 . however , these components can also be made of co — cr alloy . the bearing 300 , post 420 and conical bearing 403 preferably are made of uhmwpe . implantation is illustrated in fig1 - 14 . the tibial platform 500 is implanted into the tibia 600 and the femoral component assembly 900 consisting of the femoral component 200 with an attached extension 800 is inserted onto the femur 1000 in the usual fashion . the dovetail guide slot 302 of bearing 300 is engaged with the dovetail guide 413 of the control arm assembly 400 to produce a subassembly 350 as shown in fig1 . the subassembly 350 then is assembled onto the tibial platform 500 as shown in fig1 and 13 with the knee 700 flexed to about 100 °. the bearing 300 then is pressed digitally in a posterior direction until the bearing 300 is seated under the femoral component as shown in fig1 and 14 . there are two means of valgus - varus stability . under load bearing conditions the normal compressive load will press the femoral condyles 206 against the matching articular bearing surfaces 310 . the match is such that under compression any rotation of the femoral component 200 , in the plane of fig1 must occur around an axis 207 through the center of curvature 208 of the femoral condyle 206 . rotation about axis 207 produces impingement between the medial and lateral surfaces 421 and box sidewalls 202 . this contact produces a reaction force that resists any valgus - varus moment applied to the joint . thus , bending of the post 420 and post support pin 412 need not occur to resist the applied moment . the outer medial and lateral side surfaces 421 may be made to slope outward distal so as to increase contact area with cam box 201 . during non - load bearing phases where any valgus - varus moment is quite small , the post may be subject to small bending loads since joint compression may not occur . the post support pin 412 must be strong enough in bending to resist such moments . the cooperative action of the cam box 201 and post cam surface 423 are illustrated in fig1 - 21 . these figures show the outer posterior condyle 206 of the femoral component 200 broken away and the bearing in cross - section so as to show the action of the cam surfaces and the posterior bearing stop means . in full extension , as shown in fig1 , the cam box surface 204 and post cam surface 423 need not be in contact . at such flexion angles they do not act to prevent anterior - posterior dislocation in the absence of load bearing . under load bearing the shape of the femoral articular surface 210 pressing against the tibial articular surface 310 provides stability and position . as flexion progresses , as shown in fig1 - 21 , the anterior wall 211 of the box cam 201 of the femoral component 200 moves away from the post 420 of the control arm assembly 400 . this allows play or translation , as limited by various surfaces of the cam box 201 and post 420 , the stop pin 417 and stop recess 303 or the stop surfaces 304 and 416 . the femoral cam surface 204 will engage the post cam surface 423 at about 45 °. at flexion below 450 the post cam surface 423 plays no role in providing roll back . roll back up to about 7 . 5 mm nevertheless can occur at such low flexion with the subject invention . this roll back can be generated by the action of tension in the patella tendon , which tends to pull the tibia anteriorly . the 7 . 5 mm play allowed is relatively normal and certainly less than the play that is present in most current prosthetic knee designs . translation motion of the bearing 300 is limited to about 7 . 5 mm and roll back after about 120 ° of flexion produces some acceptable amount of climb so as to limit excess posterior motion of the bearing 300 , which might otherwise produce impingement with posterior structures of the knee , thereby inhibiting flexion . fig1 - 21 show that at the full illustrated range of flexion angles , the contact between the femoral cam 203 and the post cam surface 423 is always concave - to - convex , thus allowing for moderate contact stress . this differs from convex - to - convex or convex - to - planar contact which would produce substantially higher contact stresses . fig2 shows that the illustrated embodiment enables 1550 of flexion . this value is significantly greater then needed for most western peoples , and is sufficient for deflection preferred by asian people where sitting style may require high degrees of flexion . the cooperative action of the box cam 201 and post cam surface 423 for an alternate embodiment are illustrated in fig2 - 31 . in full extension , as shown in fig2 , the box cam surface 204 and post cam surface 423 need not be in contact . at such flexion angles they do not act to prevent anterior - posterior dislocation in the absence of load bearing , as is the case in the first embodiment . under load bearing the shape of the femoral articular surface 210 pressing against the tibial articular surface 310 provides stability and position as shown in fig2 . full extension in the normal knee also produces anterior - posterior stability due to the tightening action of the cruciate ligaments at full extension . thus this design produces normal full extension stability against translation . as shown in fig2 there is no anterior - posterior slop in full extension since the femoral component and bearing are trapped between the contact of post face 424 and wall 211 and the contact of stop pin 417 and bearing stop surface 304 . as flexion progresses , as shown in fig2 , wall 211 moves away from the post 420 . this allows “ slop ” or translation as limited by various surfaces of the cam box 201 and post 420 , or stop pin 417 and bearing stop surface 304 or stop surfaces 415 and 306 . at flexion below 350 the post cam surface 423 plays no role in providing rollback . rollback up to about 7 . 5 mm can still , however , occur at such low flexion with the disclosed embodiment as is shown in fig2 . ( all distances given are for the size 3 ( standard ) size knee . other size distances are proportional .) this rollback can be generated by the action of the tension in the patella tendon , which tends to pull the tibia anteriorly when it is acting . the 7 . 5 mm of play allowed is only moderately in excess of normal ( 0 - 5 mm ) and certainly less than that present in most current knee designs . translation motion of the bearing is limited to about 7 . 5 mm and rollback after about 75 ° of flexion produces some small , admissible amount of climb so as to limit excess posterior motion of the bearing . this excess posterior motion could increase impingement with posterior structures of the knee inhibiting flexion . as flexion progresses further , as shown in fig2 - 31 , the box cam surface 204 will engage the post cam surface 423 at about 350 if the femur has not moved posteriorly as the result of muscle , or other , forces . flexion beyond 35 ° will then force the femoral component 200 posteriorly as shown in fig2 . the compressive force on the bearing and its concave shape of its articulating surface will cause the bearing 300 to move posteriorly with the contact point between femoral component 200 and the bearing 300 . this posterior movement , or femoral rollback , improves quadriceps effectiveness as is well known . this rollback is present for normal load bearing activity likely to be performed by a knee replacement patient requiring a posterior stabilizer device . at 45 ° to 60 ° rollback is about 6 . 5 mm , at 90 ° rollback is about 9 . 5 mm and at 120 ° about 10 . 5 mm . at the maximum flexion of 162 ° rollback is also maximum and is about 13 mm . slightly beyond 75 ° of flexion it may be desirable to prevent additional posterior motion of the bearing to prevent this motion from being excessive . avoiding this excessive motion avoids the slop associated with it and also reduces impingement between the posterior aspect 305 of the bearing and posterior tissues , which may inhibit flexion . this is accomplished in this embodiment by having stop surface 415 engage posterior stop surface 306 as shown in fig2 . additional rollback would then be accompanied by some “ climb ” of the femoral component over the articular surface of the bearing . in the embodiment here this effect is small . at 90 ° of flexion there is about 2 mm posterior translation of the femur on the bearing surface . this produces an additional shearing force of about 16 % of body weight ignoring the effects of friction that tends to reduce this added force . at 120 ° of flexion , rollback on the bearing is about 3 mm and produces an additional shearing force of about 24 %. this latter rollback represents a lift of only about 0 . 12 mm . such flexion is infrequently encountered and the force increase is moderate . at the maximum of 162 ° of flexion climb on the bearing is about 5 mm with a small lift of 0 . 4 mm . such flexion is , however , passive and thus there is no significant loading associated with it . the embodiment of fig2 - 31 has several other advantageous features . in particular , as flexion progresses a gradual clearance develops which allows about 7 . 5 mm of rollback . thus rollback approaching normal is available at 30 ° of flexion . at 35 ° the femoral cam 203 engages the post cam surface 423 and begins the development of forced rollback . thus significant rollback starts much earlier than the 70 ° typical of the earlier designs . additionally , for all load bearing flexion angles the contact between femoral cam 203 and post cam surface 423 is always concave to convex thus allowing for moderate contact stresses in a contact where contact stresses in earlier designs are always excessive . the height of the post is significantly greater improving posterior dislocation resistance . although conventional posterior stabilizer devices reduce such dislocation they do not eliminate it . the embodiment disclosed herein is superior in its posterior dislocation resistance due to this increased height as well as the action of the femoral box wall 211 . this wall also resists anterior dislocation at low and moderate flexion angles . this embodiment allows 162 ° of flexion a value significantly greater than needed for use by western peoples and sufficient for asiatic peoples . additionally rollback at moderate flexion angles , where the most frequent activities occur , does not produce any significant “ climb ” in the disclosed prosthetic device . at such flexion angles , rollback approaching normal is available without any significant increase in shearing forces associated with such climb . rollback is significantly greater at very deep flexion than in moderate flexion . here climb does occur to some degree , but the increase in shear loading is moderate for active flexion . rollback is greatest at angles associated with passive flexion where the knee is not load bearing . this additional rollback is important in obtaining greater flexion by increasing anterior movement of the tibia relative to the femur reducing posterior tissue impingement restricting flexion . | a knee joint prosthesis includes femoral and tibial components , a bearing and a control arm . the bearing includes an inferior surface in sliding bearing engagement with the tibial component and a superior surface in articular bearing engagement with the femoral component . a notch extends into the posterior end of the bearing and a groove extends anteriorly from the notch in the inferior surface of the bearing . the posterior portions of the femoral component define a cam box having medial and lateral walls and a cam extending therebetween . the control arm is slidably engaged in the groove of the bearing and pivotally engage on the tibial component . the control arm further includes a post that extends into the cam box . the post includes a cam surface that engages the femoral cam to generate roll back of the femoral component on the bearing during flexion . |
the polypeptides to be delivered by intrapulmonary absorption are growth factors and cytokines . growth factors or hormones are polypeptides that induce the proliferation or enlargement of target cells . such factors or hormones , hereafter referred to as hormones for convenience , may incidentally increase the respiratory rate or metabolism of the target cells , but in the absence of increased cell mitosis or enlargement a polypeptide is not to be considered a growth hormone for the purposes of this application . most growth hormones exhibit a molecular weight of about from 5 kd to 75 kd and a pi ranging from about 4 to 8 . specific examples include growth hormone ( somatropin ), thymosin , somatomedins such as igf - 1 or igf - 2 , transforming growth factors - a and b , nerve growth factor , platelet - derived growth factor , ovarian growth factor , fibroblast growth factor , myoblast growth factor , epidermal growth factor and the like , but excluding insulin . these substances are well known to those skilled in the art and , in many cases , have been cloned and expressed in recombinant organisms . the preferred growth hormone for use herein is somatropin or its n - terminal methionylated variant ( somatrem ) described below . cytokines are the polypeptide secretory products of cells constituting the immune system , e . g . lymphocytes such as b - cells and t cells , including helper and suppressor t cells , macrophages and neutrophils . cytokines serve as effectors in that they induce changes in the activity or secretory products of other immune cells , or as direct acting proteins in that they induce a change in a target non - immune cell . furthermore , many cytokines , e . g . thymosin or gamma interferon , may be considered growth hormones as well in that they induce the proliferation of specialized immune target cells . typically , cytokines have molecular weights of about from 5 kd to 30 kd and pi of about from 4 to 8 . examples of cytokines include the interleukins , tumor necrosis factors , interferons and immune suppressor factors . preferred cytokines for use herein are tumor necrosis factors - a and b , and interferons - a , b and g . the terms growth hormone and cytokine are to be considered to include amino acid sequence , glycosylation and other variants of the native molecules . these variants may exhibit enhanced levels of the normal biological activity of the native molecules or may , on the contrary , act antagonistically towards the native molecule . alternatively , variants are selected for improved characteristics such as stability to oxidation , extended biological half - life , and the like . such variants as are known or will be developed in the future are suitable for use herein . for example , n - terminal methionyl human growth hormone ( somatrem ) is an example of a common variant produced in recombinant cell culture wherein a methionine residue not found in the native analogue is covalently bound to the normal n - terminal amino acid residue . the polypeptides administered in accordance with this invention are first placed into a particulate dispersed form . this is accomplished by preparing an aqueous aerosol or solid particles which contain the polypeptide . ordinarily , an aqueous aerosol is made by formulating an aqueous solution or suspension of the desired polypeptide together with conventional pharmaceutically acceptable carriers and stabilizers . the carriers and stabilizers will vary depending upon the requirements for each polypeptide , but typically include nonionic surfactants ( tweens , pluronics or polyethylene glycol ), innocuous proteins like serum albumin , sorbitan esters , oleic acid , lecithin , amino acids such as glycine , buffers , salts , sugars or sugar alcohols . the formulations also can include mucolytic agents such as those described in u . s . pat . no . 4 , 132 , 803 , as well as bronchodilating agents . the formulations will be sterile . aerosols generally will be prepared from isotonic solutions . the particles optionally include normal lung surfactant proteins . it is within the scope of this invention to form aerosols of particles in aqueous or nonaqueous , e . g . fluorocarbon propellant , suspension . such particles include , for example , intramolecular aggregates of the polypeptides or liposomal or microcapsular - entrapped polypeptides . the aerosols should be free of lung irritants , i . e . substances which cause acute bronchoconstriction , coughing , pulmonary edema or tissue destruction . however , nonirritating absorption enhancing agents are suitable for use herein . sonic nebulizers preferably are used in preparing aerosols . sonic nebulizers minimize exposing the polypeptides to shear , which can result in degradation of the molecule . a suitable device is the bird micronebulizer . however , it is also within the scope of this invention to employ other atomizing or nebulizing systems or intratracheal delivery systems , e . g . u . s . pat . no . 3 , 915 , 165 , the aerosol generator - inhalator described in ep 166476 , the jet nebulizers described by newman et al . “ thorax ” 40 ( 9 ): 671 - 676 ( 1985 ), metered dose inhalers ( m . berenberg , 1985 , “ j . asthma - usa ” 22 ( 2 ): 87 - 92 ), or other devices ( sears et al ., 1983 “ n . z . med . j .” 96 : 743ii ; o &# 39 ; reilly et al ., 1983 , “ br . med . j .” 286 : 6377 ; or j . stander et al ., 1982 , “ respiration ” 44 ( 3 ): 237 - 240 ), so long as they are compatible with the protein to be administered and are capable of delivering particles of the desired size . particulate aerosol suspensions are essentially fine dry powders containing the polypeptides . they are prepared by any number of conventional procedures . the simplest method of producing them is to micronize polypeptide , e . g . crystals or lyophilization cakes , and suspend the particles in dry fluorocarbon propellants . in these formulations the polypeptides do not dissolve in the hydrophobic propellants ( which evaporate after the suspension is released from the pressurized device into the air ). rather , the polypeptides are suspended in the fluorocarbon . in an alternate embodiment the polypeptides are stored in a compartment separate from the propellant . discharge of the propellant withdraws a predetermined dose from the storage compartment . the devices used to deliver drugs in this manner are known as metered dose inhalers ( mdis ) ( p . r . byron , 1986 , “ drug development and industrial pharmacy ” 12 : 993 ). the size of the aerosols or particles generally will range about from 0 . 5 mm to 4 mm , preferably about 0 . 5 to 1 mm . smaller particles are less acceptable because they tend not to be deposited but instead are exhaled . larger particles are not preferred because in large measure are unable to be deposited at the level of the alveoli , being removed by impaction within the nasopharyngeal or oral cavities ( byron , 1986 , “ j . pharm . sci .” 75 : 433 ). obviously , most aerosol or particulate compositions will be heterogenous in size distribution , although heterogeneity can be reduced by known methods , e . g . the screening unit described in ep 135390a . heterogeneity will not be disadvantageous unless the proportion of particles having an average mean diameter in excess of about 4 mm is so large as to impair the delivery of a therapeutic dose by pulmonary inhalation . suspensions containing greater than about 15 % of particles within the 0 . 5 - 4 mm range can be used , but generally the proportion of particles having an average mean diameter larger than 4 mm should be less than about 25 %, and preferably not greater than 10 %, of the total number of particles . the diameters recited refer to the particle diameters as introduced into the respiratory tract . the particles may or may not bear a net charge . the presence of a net charge is desirable for minimizing particle aggregation in the airways since the particles will repel one another electrostatically . charged particles are made by removing water from solutions of the polypeptides at a ph other than the isoelectric point , e . g . ordinarily about from 0 . 5 to 2 ph units on either side of the isoelectric point . on the other hand , dewatering of polypeptides at a ph other than the isoelectric point may result in precipitation or denaturation of the protein , so the desirability of use of such a ph will depend upon the known characteristics of the polypeptide to be administered . a suitable system for inhalation delivery of the polypeptides herein is illustrated in fig1 . a source of compressed air 1 communicates with a nebulizer shown generally at 4 by way of a conduit 2 . the flow of compressed air is controlled by valve 3 . the nebulizer 4 contains a capillary tube 7 which extends down into the solution of growth hormone or cytokine in reservoir 8 . the end of capillary 7 which is distal to solution reservoir 8 terminates immediately adjacent to the orifice 5 of conduit 2 . an impaction sphere 6 is adjustably positioned opposite orifice 5 . the orifice 5 , capillary 7 and sphere 6 serve as the dispersing means for forming the aerosol of the polypeptide disposed in reservoir 8 . nebulizer 4 also includes serrated output baffles shown generally at 9 , downstream of which is a conduit 10 communicating with a respirator mouthpiece 12 for sealably engaging the mouth of the patient ( not shown ). the passage of aerosol 15 through conduit 10 is controlled by valve 11 , which also operates valve 3 through circuit 13 and control device 14 . in operation , compressed air is valved by valve 3 on demand as determined by programmed control device 14 . the control device is actuated on demand from valve 11 . compressed air passes through conduit 2 and out the orifice 5 . the flow of air over the end of capillary 7 draws the solution of polypeptide from reservoir 8 into the stream of air where , together with collision on the impaction sphere 6 , an aerosol of the solution is formed . the stable aerosol suspension is forced out by air pressure through baffles 9 and down conduit 10 upon demand from valve 11 as activated by the patient . the baffles are selected of appropriate size , dimension and composition to remove the bulk of particles greater than about 4 mm . the seating of mouthpiece 12 will ensure that the patient inhales substantially only the delivered mixture of air and aerosolized polypeptide with each breath . the method herein is illustrated by way of the following examples , which are not to be construed as limiting the invention . an adult baboon weighing 24 kg was anesthetized with intravenous pentobarbital , a tracheal intubation performed and the animal allowed to breathe normally until and between dosing . a bird micronebulizer in line with a bird mark 7 respirator was charged with 5 - 10 ml of a solution of 12 mg / ml protropin r brand of met - hgh ( somatrem ) in mannitol / phosphate buffer . the micronebulizer then was used to simultaneously ventilate and dose the animal at 22 cm h 2 o at a rate of 1 . 8 mg / hgh /- min . for 30 min . at this pressure the animal ventilated at approximately normal inspiratory volume . the animal was allowed to exhale normally after each ventilated breath and was positioned supine for dosing . after the first dosing period the animal was allowed to breathe normally for another 20 minutes , after which a second dosing was performed in the same way as the first . blood plasma samples were taken at the initiation time of the first dose and thereafter as shown by the data points in fig2 . the baboon completely emerged from anesthesia 8 hours after the last pentobarbital injection . radioimmunoassays of met - hgh in these sera showed that intrapulmonary delivery in accord herewith produced a blood level that is greater than twice that which is considered an acceptable therapeutic dose when administered intramuscularly . the radioimmunoassay employed in this example also will cross - react with normal baboon growth hormone , so it is believed that some of the hgh detected at 28 hours after the commencement of dosing may represent a circadian or stress induced increase in baboon growth hormone , probably similar to the levels in rhesus monkeys ( 10 ng / ml ). since the normal detectable gh levels in primates typically fall within the 10 - 20 mg / ml range , the method of this invention made it possible to deliver far in excess of a systemic therapeutically effective dose of hgh for a period exceeding 28 hours . this was particularly surprising since the general view is that long term drug delivery (& gt ; 12 hr ) is not achievable by intrapulmonary inhalation ( byron , op cit . ). adult rats were anesthetized and tracheal intubations performed on each animal . solutions of human recombinant gamma interferon and human recombinant tumor necrosis factor were injected into the trachea of test animals until a dosage of 3 mg / kg and 378 mcg / kg , respectively , was delivered . serum samples were withdrawn from each test animal at the times indicated in fig3 - 4 and assayed for the appropriate polypeptide . the results , shown in fig3 - 4 , clearly demonstrate effective system delivery of these two cytokines . | polypeptides selected from the group of growth factors and cytokines are administered by intrapulmonary inhalation . disclosed are novel compositions and devices for effecting the intrapulmonary administration of these polypeptides . |
the following detailed description is merely exemplary in nature and is not intended to limit the described embodiments or the application and uses of the described embodiments . as used herein , the word “ exemplary ” or “ illustrative ” means “ serving as an example , instance , or illustration .” any implementation described herein as “ exemplary ” or “ illustrative ” is not necessarily to be construed as preferred or advantageous over other implementations . all of the implementations described below are exemplary implementations provided to enable persons skilled in the art to practice the disclosure and are not intended to limit the scope of the appended claims . moreover , the illustrative embodiments described herein are not exhaustive and embodiments or implementations other than those which are described herein and which fall within the scope of the appended claims are possible . furthermore , there is no intention to be bound by any expressed or implied theory presented in the preceding technical field , background , brief summary or the following detailed description . as used herein , relative terms such as “ upper ”, “ lower ”, “ front ” and “ back ” are used to describe exemplary positions of various components relative to each other in exemplary use of the prosthetic devices and are not intended to be construed in a limiting sense . referring initially to fig1 - 6 of the drawings , an illustrative embodiment of the prosthetic devices having electronic display , hereinafter prosthetic device , is generally indicated by reference numeral 1 . the prosthetic device 1 may be designed to be fitted on the residual limb 30 below the knee , as illustrated , or alternatively , on the residual limb above the knee ( not illustrated ) of a wearer 32 to replace a portion of or most of the wearer &# 39 ; s natural limb which was lost or is missing due to injury , illness or congenital deformity , for example . in some embodiments , the prosthetic device 1 may include an upper leg portion 2 which receives the residual limb 30 of the wearer 32 . a lower leg portion 24 may include a support pylon 26 which extends from the upper leg portion 2 . in the case of an above the knee prosthesis , the lower leg portion 24 may include a knee component ( not illustrated ). a foot portion 27 may be provided on the support pylon 26 . it will be recognized and understood that the prosthetic device 1 which is illustrated in fig1 - 6 is merely one example of a prosthetic device design which is suitable for implementation of the prosthetic device 1 . as will be hereinafter further described , at least one display 20 is provided on or in at least one of the upper leg portion 2 and the lower leg portion 24 of the prosthetic device 1 . in some embodiments , the display may be provided on the front , side and / or rear portion of the upper leg portion 2 . a control module 10 may be connected to each display 20 , such as via control wiring 8 , and / or via wireless signals 29 ( fig9 a ), for example and without limitation , for selective control of the display 20 , as will be hereinafter described . the control wiring 8 may be embedded in a prosthesis wall 3 of the prosthetic device 1 . in some embodiments , the control module 10 may be attached to the exterior surface of the upper leg portion 2 or the lower leg portion 24 . in other embodiments , the control module 10 may be embedded inside the lamination of the prosthesis wall 3 , the support pylon 26 or a wireless transmitter ( not illustrated ) which is part of the control module 10 , for example and without limitation . techniques which are suitable for attaching the control module 10 to the prosthesis wall 3 include but are not limited to hook and loop fasteners , magnets , brackets , adhesives and mechanical fasteners . in other embodiments , the control module 10 may be recessed in a control module recess , cavity or void ( not illustrated ) provided in the exterior surface or lamination of the upper leg portion 2 or the lower leg portion 24 . as illustrated in fig3 - 5 , the upper leg portion 2 ( and / or the lower leg portion 24 in some embodiments ) may have a generally annular prosthesis wall 3 . the prosthesis wall 3 may include an outer wall sheet / layer 4 and an inner wall sheet / layer 5 . each of the outer wall sheet / layer 4 and the inner wall sheet / layer 5 of the prosthesis wall 3 may be fabricated using materials and methods which are well - known in the fabrication of prosthetic devices . for example and without limitation , the outer wall sheet / layer 4 and the inner wall sheet / layer 5 may include plastic , fiberglass , carbon fiber and / or other material which is fabricated on a mold ( not illustrated ) from multiple sheet / layers of woven reinforced and non - reinforced materials and a curable plastic resin material , as is known by those skilled in the art . in some embodiments , at least one coating layer 9 may be provided on the outer wall layer 4 . the coating layer 9 may include at least one clear coating and / or sealing layer which may coat the outer wall layer 4 , the control module housing 11 of the control module 10 and the display 20 . the outer wall sheet / layer 4 , the inner wall sheet / layer 5 and the coating layer 9 of the prosthesis wall 3 can be applied using any technique which is known by those skilled in the art and is consistent with the material of construction of each layer . these application techniques include but are not limited to silk screening , screen printing , painting and spraying . as illustrated in fig4 - 6 , a wiring space 6 may be provided in the prosthesis wall 3 . the wiring space 6 may be formed between the outer wall sheet / layer 4 and the inner wall sheet / layer 5 . in some embodiments , the wiring space 6 may accommodate the control wiring 8 as the control wiring 8 extends from the control module 10 to the display 20 . in some embodiments , a display cavity 7 may be provided in the outer surface of the prosthesis wall 3 . the display cavity 7 may be sized and configured to accommodate the display 20 , as will be hereinafter described . in some embodiments , it may be desirable to position the display 20 in a highly - visible location and the control module 10 in a less visible location on the prosthesis wall 3 . for example and without limitation , in some embodiments , the display 20 and the control module 10 may be provided at the front and rear , respectively , of the prosthesis wall 3 , in substantially opposite or 180 - degree relationship to each other on opposite sides of the upper leg portion 2 or the lower leg portion 24 . in other embodiments , the relative positions of the display 20 and the control module 10 may be reversed . accordingly , the control wiring 8 may extend from the control module 10 to the display 20 through the wiring space 6 on opposite sides of the prosthesis wall 3 . in some embodiments , the display cavity 7 may be omitted and the display 20 may be attached to the exterior surface of the prosthesis wall 3 according to the knowledge of those skilled in the art . as illustrated in fig9 , in some embodiments , the control module 10 may include a control module housing 11 . the control module housing 11 may have any desired shape . in some embodiments , the control module housing 11 may have a concave surface which is generally complementary to the convex curvature of the exterior surface of the prosthesis wall 3 . a microprocessor , cpu or other controller , hereinafter controller 14 , may be provided in the control module housing 11 . display controls 16 and at least one battery 18 may electrically interface with the controller 14 . the display 20 may be connected to the controller 14 through the control wing 8 . in some embodiments , at least one solar panel ( not illustrated ) may interface with the controller 14 or with the battery 18 to provide a source of electrical power . the controller 14 may be adapted to present at least one image 21 ( fig1 ) on the display 20 . the image 21 may include a favorite sports team emblem , a business logo , a slogan , a symbol and / or any other image or images which a wearer of the prosthetic device 1 desires to display on the display 20 . the image 21 may include a static image ( an unchanging size , shape and / or color ) and / or a dynamic image ( a changing size , shape and / or color ) and may be a single color or various colors . in some embodiments , the controller 14 may be adapted to present multiple images 21 in the form of video , animation and / or other visual effects on the display 20 . in some embodiments , the display 20 may include an lcd ( liquid crystal display ), led ( light emitting diode ) or aoled ( active organic light emitting diode ) screen , for example and without limitation . in other embodiments , the display 20 may include at least one electric light which is formed or shaped into the desired image 21 to be displayed . as further illustrated in fig9 , in some embodiments , at least one port 17 such as a standard usb port or other type of port interfaces with the controller 14 and is provided on the exterior of the control module housing 11 and may be wireless in some embodiments . the controller 14 may be loaded with software , code or other programming which enables the wearer 32 to upload selected image and / or video data files from an external device ( not illustrated ) to the controller 14 via the port 17 such as in the conventional manner . the controller 14 may be programmed to present or display images and / or video encoded by the loaded image or video data files on the display 20 by manipulation of the appropriate display controls 16 on the control module 10 . in some embodiments , the control module 10 and the display 20 may be retrofitted to an existing prosthetic device 1 according to the knowledge of those skilled in the art . as illustrated in fig9 a of the drawings , in some embodiments of the control module 10 , a transmitter 23 may interface with the controller 14 . a receiver 22 may interface with the display 20 . the transmitter 23 communicates with the receiver 22 through wireless signals 29 . accordingly , the controller 14 is adapted to transmit image and / or video data to the display 20 via the transmitter 23 , wireless signals 29 and receiver 22 . as illustrated in fig2 , in some embodiments , the display controls 16 for the image 21 on the display 20 may include a power switch 16 a which controls flow of electrical current from the battery 18 ( fig9 ) to the display 20 ; a blink control switch 16 b which facilitates selective blinking of the image or images 21 on the display 20 ; and / or a dimmer switch 16 c which facilitates selective dimming and brightening of the image or images 21 on the display 20 . in application of the prosthetic device 1 , the upper leg portion 2 receives the residual limb 30 of the wearer 32 . the wearer 32 can selectively display one or more of the selected images 21 on the display 20 by appropriate manipulation of the display controls 16 ( fig9 ) on the control module 10 . for example and without limitation , the wearer 32 may selectively turn the display 20 on and off by manipulation of the power switch 16 a ( fig2 ); control blinking of the images 21 on the display 20 by manipulation of the blink control switch 16 b ; and control the brightness or the images 21 by manipulation of the dimmer switch 16 c . accordingly , as the wearer 32 dons the prosthetic device 1 , the images 21 on the display 20 provide a means of self - expression to observers . additionally or alternatively , the images 21 on the display 20 may provide a means of displaying information and / or variables measured by the controller 14 and / or sensors ( not illustrated ) such as temperature sensors , for example and without limitation , which may interface with the controller 14 in some embodiments . it will be recognized and understood that the prosthetic device 1 is equally applicable and adaptable to alternative prosthetic device designs which are known by those skilled in the art . for example and without limitation , in some embodiments the prosthetic device 1 may include a covering portion ( not illustrated ) which receives the upper leg portion or a remaining portion of the residual limb 30 of the wearer 32 according to the knowledge of those skilled in the art . the covering portion ( not illustrated ) may include the display 20 , wiring 8 and control module 10 and / or other functional components . referring next to fig7 and 8 of the drawings , an illustrative arm embodiment of the prosthetic devices with electronic display is generally indicated by reference numeral 101 . in fig7 and 8 , elements which are analogous to the respective elements of the prosthetic device 1 which was heretofore described with respect to fig1 - 6 are designated by the same reference numeral in the 100 series . the prosthetic device 101 may include an arm , or alternatively , forearm portion 102 which is adapted to be fitted on the residual arm or residual forearm ( not illustrated ) of a wearer to replace a portion or most of the wearer &# 39 ; s natural arm which was lost or is missing due to injury , illness , or congenital deformity , for example . in some embodiments , a wrist portion 134 having a hand 135 may extend from the forearm portion 102 . at least one display 120 may be provided on the exterior surface of the forearm portion 102 , as illustrated , and / or on the forearm portion 134 . as illustrated in fig8 , a control module 110 may be provided on the exterior surface of the forearm portion 102 and / or the wrist portion 134 . the control module 110 may be electrically connected in the display 120 via control wiring 108 , which may extend through a wiring space ( not illustrated ) or may otherwise be embedded in the prosthesis wall 103 as was heretofore described with respect to the prosthetic device 1 . operation of the display 120 of the prosthetic device 101 may be as was heretofore described with respect to the prosthetic device 1 in fig1 - 6 . in some embodiments , the control module 110 and the display 120 may be retrofitted in an existing prosthetic device 101 according to the knowledge of those skilled in the art . referring next to fig8 a of the drawings , an exemplary cosmetic prosthetic glove according to an illustrative embodiment of the prosthetic device with electronic display , hereinafter glove , is generally indicated by reference numeral 60 . the glove 60 may be adapted to be fitted over a prosthetic device such as the prosthetic device 101 which was heretofore described with respect to fig7 and 8 , for example and without limitation , for cosmetic purposes . the glove 60 may include a backhand glove surface 61 , a palm glove surface 62 , glove fingers 63 and a glove thumb 64 . a control module 110 and a display 120 may be provided at selected positions on the glove 60 . in some embodiments , the display 120 may be provided on the backhand glove surface 61 and the control module 110 may be provided on the palm glove surface 62 , as illustrated . in other embodiments , the positions of the control module 110 and the display 120 may be reversed or may both be provided on the backhand glove surface 61 or the palm glove surface 62 . the glove 60 is adapted to be placed on the prosthetic device 101 typically for cosmetic purposes , as is known by those skilled in the art . the control module 110 may be operated to present at least one image 121 on the display 120 , as was heretofore described . referring next to fig1 , a flow diagram of an illustrative embodiment of an exemplary method of fabricating a prosthetic device with electronic display is generally indicated by reference numeral 1000 . in block 1002 , a positive model may be formed . the positive model may be an arm cast or a leg cast . in block 1004 , a plastic bag may be placed over the positive model and secured . in block 1006 , an interior sheet / layer may be placed over the plastic bag . the interior sheet / layer may include a woven sheet or layer of material such as fiberglass or carbon fiber , for example and without limitation . in block 1008 , a wiring sheet / layer in which control wiring is embedded may be placed over the interior sheet / layer . in block 1010 , an exterior sheet / layer may be placed over the wiring sheet / layer . the exterior sheet / layer may be similar in construction to the interior sheet / layer . in block 1012 , a display opening may be cut in the exterior sheet / layer . in block 1014 , resin may be distributed through the exterior sheet / layer , the wiring sheet / layer and the interior sheet / layer by application of vacuum to the resin . in block 1016 , the resin may be cured using conventional resin curing techniques . in block 1018 , cured resin may be cut and / or otherwise removed from the display opening in the exterior sheet / layer . in block 1020 , a display may be connected to control wiring in the wiring sheet / layer and secured in the display opening . in block 1022 , a control module may be connected to the control wiring in the wiring sheet / layer . the control module may be attached to the prosthetic device using suitable attachment techniques . it will be appreciated by those skilled in the art that the prosthetic devices of the disclosure are amenable to a variety of embodiments . for example and without limitation , referring again to fig3 , in some embodiments , the control module 10 may be inserted inside the upper leg portion 2 and may be secured therein using magnets , clips , clamps and / or other attachment technique . in other embodiments , the control module 10 may be attached to the exterior surface or the prosthesis wall 3 using a suitable attachment technique . in some embodiments , an inner transparent or translucent layer or sheet of plastic may be thermoformed on a positive model of the leg . one or more electroluminescent wires and / or panels may be placed against the inner layer or sheet and arranged in the form of a squiggle , line , logo or pattern , for example and without limitation . an outer transparent or translucent layer or sheet of plastic or clear protective coating may be thermoformed on the inner layer or sheet with the electroluminescent wires or panels sandwiched between the sheets or layers . the electroluminescent wires or panels may be connected to the control module 10 to facilitate flow of electrical current through the electroluminescent wires or panels to illuminate the wires and the pattern which is formed by the wires or panels . referring next to fig1 a of the drawings , a flow diagram of an illustrative embodiment of a method of retrofitting an electronic display and control module to an existing prosthetic device is generally indicated by reference numeral 1000 a . in block 1002 a , an existing prosthetic device is provided . in some embodiments , the prosthetic device may be adapted to be fitted on a residual limb corresponding to an upper or lower leg of a wearer . in other embodiments , the prosthetic device may be adapted to be fitted on a residual limb corresponding to an upper or lower arm of a wearer . in block 1004 a , a display is attached to the prosthetic device . in block 1006 a , a control module is attached to the prosthetic device . in block 1008 a , a communication interface is provided between the display and the control module . in some embodiments , the communication interface may include wiring or other electrical communication pathway or contact . in other embodiments , the communication interface may include a wireless interface . referring next to fig1 and 12 of the drawings , an alternative illustrative embodiment of the prosthetic devices with electronic display is generally indicated by reference numeral 201 . in the prosthetic device 201 , elements which are analogous to the respective elements of the prosthetic device 1 that was heretofore described with respect to fig1 - 9a are designated by the same numeral in the 201 - 299 series in fig1 and 12 . while the prosthetic device 201 in fig1 . is presented as a leg embodiment , in other embodiments the prosthetic device 201 may be an arm embodiment as was heretofore described with respect to fig7 . the prosthetic device 201 may include an electroluminescent lamp ( el ) display 220 . as illustrated in fig1 , the el display 220 may include an encapsulant layer 240 . the encapsulant layer 240 may include a protective encapsulant such as clear coat , for example and without limitation . in some embodiments , the encapsulant layer 240 may include uv cure ink 5018 / a / g or solvent - based 7165 which is available from the dupont corp . ( www . dupont . com ). in some embodiments , the encapsulant layer 240 may be attached to the exterior surface of the prosthesis wall 203 of the prosthetic device 201 using bonding techniques known by those skilled in the art . in other embodiments , the encapsulant layer 240 may be provided within a cavity or void ( not illustrated ) in the exterior surface of the prosthesis wall 203 . in some embodiments , the encapsulant layer 240 may be laminated within the prosthesis wall 203 of the prosthetic device 201 according to the knowledge of those skilled in the art . in some embodiments , 5018 / a / g screen printable uv cure inks or 7165 solvent ink , both available from dupont corp ., may be used as the encapsulant layer 240 in order to provide electrical insulation and extra protection of the components of the prosthetic device 201 against humid environments . the uv encapsulants may not adhere well to ito - sputtered film , so in some embodiments it may be desirable to limit the print area of the 5018 / a / g to that of the underlying dielectric layer 242 . 7165 solvent ink adheres well to ito film but may only be usable in a single print . in more complex embodiments of the el display 220 , two layers of 5018 / a / g may be used as an effective insulator in the encapsulant layer 240 where conductor crossovers are present . it may be desirable to print the first uv encapsulant layer over the entire lamp area to prevent cracking over the dielectric where local crossovers are printed . in some embodiments , a thick , single print of 7165 solvent ink encapsulant may be used as an option . a rear electrode 241 may be provided on the encapsulant layer 240 . the rear electrode 241 may include any electrically - conductive material which is suitable for the purpose . in some embodiments , the rear electrode 241 may include 9145 silver and / or 8144 carbon which is available from the dupont corp ., for example and without limitation . at least one dielectric layer 242 may be provided on the rear electrode 241 . in some embodiments , at least two prints of dielectric layers 242 (& lt ; 25 microns total dried thickness ) may be provided over the rear electrode 241 . in some embodiments , at least three prints of dielectric layers 242 (& gt ; 25 microns total dried thickness ) may be provided over the rear electrode 241 for optimum yield and reliability . a phosphor layer 243 may be provided on the dielectric layer or layers 242 . the phosphor layer 243 may include an inorganic phosphor such as a zinc sulfide compound , for example and without limitation . the phosphor particles of the phosphor layer 243 may be selected and arranged to define at least one desired pattern , image or symbol on the el display 220 in application of the prosthetic device 201 which will be hereinafter described . a front electrode 244 is provided in electrical contact with the rear electrode 241 through an ac voltage power source 248 and bus bar 249 . the front electrode 244 may include any electrically - conductive material which is suitable for the purpose . in some embodiments , the front electrode 244 may include translucent conductor 7162 which has ato ( antimony - doped tin oxide ) and is available from the dupont corp . in el display designs with small - lit areas , screen - printable translucent conductive ink may be used as the front electrode 244 . the as - printed resistivity of translucent conductors can be around 100 times that of ito film . consequently , lit areas should be kept small so that good uniformity of illumination is achieved . el displays 220 may be fabricated with an area of 10 cm × 5 cm without noticeable darkening towards the center of the displays ( powered at 100v / 400 hz ). higher frequency operations may cause darkening towards the center of the displays ; thus . use of frequencies below about 800 hz may be optimum in some embodiments . the bus bar 249 may include a printed electrically - conductive material such as silver , for example and without limitation . it may be desirable to print a silver bus bar close to the lit area around the perimeter of the translucent conductor front electrode 244 . this expedient may improve the light uniformity by lowering the contact resistance and minimizing the voltage drop across the surface of the front electrode 244 instead of using a carbon electrode . a printed silver bus bar 249 along the perimeter of the el display 220 may be used for large areas in order to provided more even illumination of the el display 220 . a base substrate layer 245 may be provided on the phosphor layer 243 . in some embodiments , the base substrate layer 245 may include polyester film sputtered with ito ( indium tin oxide ) or coated with an electrically - conductive polymer or other suitable material . accordingly , the base substrate layer 245 may be obtained with an ito transparent conductor sputter - coated on one side . polyester thickness of between 100 - 175 μm and resistivities ranging from 50 to 300 ω / sq can be used . heat - stabilized film may be recommended as drying temperatures of up to 130 degrees c . may be used in some fabrication methods . non - ito coated films may be used for high resistivity applications ( from about 1000 ω / sq to about 3000 ω / sq ). in some embodiments , the base substrate layer 245 may include a screen - printed conducting translucent ink on a clear base substrate . in other embodiments , the base substrate layer 245 may include heat - stabilized , print - treated polyester . in still other embodiments , the base substrate layer 245 may include any material or combination of materials which is consistent with the functional requirements of the base substrate layer 245 in the el display 220 . it will be recognized and understood that the encapsulant layer 240 , the rear electrode 241 , the dielectric layer or layers 242 , the phosphor layer 243 , the front electrode 244 and the base substrate layer 245 can be applied using any technique which is known by those skilled in the art and is consistent with the material of construction of each layer . these application techniques include but are not limited to silk screening , screen printing and spraying , for example and without limitation . the controller 14 ( fig9 ) of the control module 210 may communicate with the bus bar 249 of the through control wiring 208 ( fig1 ) as was heretofore described with respect to fig9 . alternatively , the controller 14 may communicate with the bus bar 249 through a transmitter 23 , wireless signals 29 and a receiver 22 as was heretofore described with respect to fig9 a . accordingly , operation of the control module 210 establishes flow of electrical current between the rear electrode 241 and the front electrode 244 of the el display 220 . application of an ac voltage across the rear electrode 241 and the front electrode 244 generates a changing electric field within the phosphor particles of the phosphor layer 243 , causing the phosphor particles to emit light 250 through the base substrate layer 245 . the phosphor particles in the phosphor layer 243 may be selected by color and arranged in position to emit light 250 of different wavelengths and form at least one selected light pattern or image . in some embodiments , an inverter ( dc - ac converter ) may be used as the power source 248 . the inverter may generate 60 ˜ 115v and frequencies in the region of about 50 ˜ 1000 hz . for signage applications , much higher frequencies can be used to increase the brightness of the el display 220 . output of the light 250 from the el display 220 may gradually decay with time as the luminescent efficiency decreases . the presence of any moisture in the phosphor layer 243 may accelerate this decline . the phosphor particles used in the phosphor layer 243 may be micro - encapsulated to hinder the penetration of moisture and thus , prolong the useful life of the el display 220 . application of the prosthetic device 201 may be as was heretofore described with respect to the prosthetic device 1 in fig1 - 9a . the control module 210 can be selectively operated to facilitate emission of light 250 from the el display 220 to form at least one selected single - color or multi - colored image which may be defined by the pattern of phosphor particles in the phosphor layer 243 . referring next to fig1 - 17 of the drawings , an exemplary sequential fabrication technique for the el display 220 is illustrated . in fig1 , a front electrode 244 may be provided over a base substrate layer 245 ( fig1 ). in fig1 , a phosphor layer 243 may be provided over the front electrode 244 . in fig1 , at least one dielectric layer 242 may be provided over the phosphor layer 243 . in fig1 , a rear electrode 241 may be provided over the dielectric layer or layers 242 . a bus bar 249 may connect the rear electrode 241 to the front electrode 244 . in fig1 , an encapsulant layer 240 may be provided over the rear electrode 241 . a power source 248 ( fig1 ) may be electrically connected to the bus bar 249 . the power source 248 of the el display 220 may interface with the control module 210 ( fig1 ) as was heretofore described with respect to fig9 or fig9 a . referring next to fig1 and 24 of the drawings , an alternative illustrative embodiment of the prosthetic devices with electronic display is generally indicated by reference numeral 301 in fig2 . in the prosthetic device 301 , elements which are analogous to the respective elements of the prosthetic device 201 that was heretofore described with respect to fig1 are designated by the same numeral in the 301 - 399 series in fig1 and 24 . while the prosthetic device 301 in fig1 is presented as a leg embodiment , in other embodiments the prosthetic device 301 may be an arm embodiment as was heretofore described with respect to fig7 . the prosthetic device 301 may include an electroluminescent lamp ( el ) display 320 . as illustrated in fig1 , the el display 320 may include an encapsulant layer 340 . in some embodiments , the encapsulant layer 340 may be attached to the exterior surface of the prosthesis wall 303 of the prosthetic device 301 using bonding techniques known by those skilled in the art . in other embodiments , the encapsulant layer 340 may be provided within a cavity or void ( not illustrated ) in the exterior surface of the prosthesis wall 303 . in some embodiments , the encapsulant layer 340 may be laminated within the prosthesis wall 303 of the prosthetic device 301 according to the knowledge of those skilled in the art . a rear electrode 341 may be provided on the encapsulant layer 340 . at least one dielectric layer 342 may be provided on the rear electrode 341 . a phosphor layer 343 may be provided on the dielectric layer or layers 342 . a front electrode 344 is provided in electrical contact with the rear electrode 341 through an ac voltage power source 348 and bus bar 349 . a base substrate layer 345 may be provided on the phosphor layer 343 . the encapsulant layer 340 , the rear electrode 341 , the dielectric layer or layers 342 , the phosphor layer 343 , the front electrode 344 and the base substrate layer 345 may have the same materials of construction as those respective components in the el display 220 heretofore described with respect to fig1 . the controller 14 ( fig9 ) of the control module may communicate with the bus bar 349 of the through control wiring 308 ( fig2 ) as was heretofore described with respect to fig9 . alternatively , the controller 14 may communicate with the bus bar 349 through a transmitter 23 , wireless signals 29 and a receiver 22 as was heretofore described with respect to fig9 a . referring next to fig1 - 23 of the drawings , an exemplary sequential fabrication technique for the el display 320 is illustrated . in fig1 , an encapsulant layer 340 is provided . in some embodiments , the encapsulant layer 340 may be part of the prosthesis wall 303 of a prosthetic device . in other embodiments , the encapsulant layer 340 may be attached to the exterior surface of the prosthesis wall 303 or may be provided in a cavity or void ( not illustrated ) in the exterior surface of the prosthesis wall 303 . the encapsulant layer 340 may be applied to the prosthesis wall 303 as a translucent conductive ink , although alternative substrate types and materials may be used . in fig2 , a rear electrode 341 and bus bar 349 may be provided on the encapsulant layer 340 . in fig2 , at least one dielectric layer 342 may be provided on the rear electrode 341 . in fig2 , a phosphor layer 343 may be provided on the dielectric layer or layers 342 . in fig2 , a base substrate layer 345 may be provided over the phosphor layer 343 . application of the prosthetic device 301 may be as was heretofore described with respect to the prosthetic device 301 in fig1 - 9a . the control module 310 can be selectively operated to facilitate emission of light 350 from the el display 320 to form a selected single - color or multi - colored image which is defined by the pattern of phosphor particles in the phosphor layer 343 . while the embodiments of the disclosure have been described above , it will be recognized and understood that various modifications can be made and the appended claims are intended to cover all such modifications which may fall within the spirit and scope of the disclosure . | a prosthetic device includes a prosthesis wall , at least one display carried by the prosthesis wall in spaced - apart relationship to the at least one display and interfacing with the at least one display , the control module adapted to present at least one image on the at least one display . |
in the following detailed description , reference is made to the accompanying drawings , which form a part hereof . in the drawings , similar symbols typically identify similar components , unless context dictates otherwise . the illustrative embodiments described in the detailed description , drawings , and claims are not meant to be limiting . other embodiments may be utilized , and other changes may be made , without departing from the spirit or scope of the subject matter presented here . it will be readily understood that the aspects of the present disclosure , as generally described herein , and illustrated in the figures , can be arranged , substituted , combined , and designed in a wide variety of different configurations , all of which are explicitly contemplated and made part of this disclosure . fig1 a illustrates an imprinter 100 that comprises a retainer 110 with retainer sides 113 , a grip 119 , at least one lock 150 , which in one embodiment includes a first lock 150 a and a second lock 150 b at opposing ends 106 of the retainer . the imprinter 100 may be made of any suitable material , for example , plastic . the retainer 110 of the imprinter 100 may receive at least one press piece 180 . the imprinter 100 may be any color . in addition , the imprinter 100 may be transparent or opaque , and the press piece 180 may be transparent or opaque . in a preferred embodiment , the imprinter 100 and at least one press piece 180 may be transparent . the press piece 180 may be made of any suitable material , for example , plastic . the retainer 110 and the press piece 180 may be made of different materials . referring now to fig1 a - c , the imprinter 100 includes a retainer 110 . the retainer 110 includes a retainer body 111 . the retainer body 111 maybe substantially planar . extending from the retainer body 111 are a first retaining portion 113 a and a second retaining portion 113 b . in one embodiment , the first retaining portion 113 a extends from a first edge of the retainer body 111 parallel with the longitudinal axis of the retainer body 111 . a second retaining portion 113 b extends from a second edge , opposite the first edge , of the retaining body parallel with the longitudinal axis of the retainer body 111 . the first retaining portion 113 a and second retaining portion 113 b may extend perpendicular to the plane of the retainer body 111 . in one embodiment , each of the first retaining portion 113 a and the second retaining portion 113 b include a corresponding groove 114 a , 114 b for receiving a portion of the press piece 180 . the grooves 114 may be formed as a recess in the respective first retaining portion 113 a and second retaining portion 113 b or may be formed by the presence of a flange on the respective first retaining portion 113 a and second retaining portion 113 b . referring now to fig2 a - d , in one exemplary embodiment , a press piece 180 includes a deck 181 having a design 182 extending therefrom and sides 183 . the press piece 180 further includes a back surface 184 ( illustrated in fig2 d ). when the press piece 180 is assembled with the retainer 110 , the back surface 184 is adjacent to the retainer body 111 and the design 182 extends away from the retainer 110 . the press piece 180 includes a retained portion 183 that is configured to engage with the retainer 110 to hold the press piece 180 to the retainer 110 . in one embodiment , the retained portions 183 are sides of the press piece 180 configured to slide into sides 113 of retainer 110 . in one embodiment , the retained portions 183 may substantially fill the short axis ( height ) of the grooves 114 such that the press piece 180 may be removed from the retainer 110 but when engaged with the retainer 110 is snugly fit so as to prevent substantial movement vertically when the retainer 110 is operated . the design 182 of fig2 a is alphanumeric . in another exemplary embodiment , the design 182 may be ornamental ( see fig2 b ). the press piece 180 is removable from the retainer 110 for easy cleaning and for customizing combinations of designs to be imprinted with the imprinter 100 . with reference to fig1 a , the first lock 150 a and the second lock 150 b are engageable with the retainer 110 . the first lock 150 a and the second lock 150 b each includes a lock retaining portion 151 and a lock deck 152 , which may be tab - shaped as shown in fig3 a . in one embodiment , the retainer 110 is attached to a grip 119 for use in positioning the imprinter 100 over a surface . the grip 119 assists decorators in imprinting the design 182 at precise locations and angles for decorating . the retainer 110 has sides 113 between which at least one press piece 180 may slide into the retainer 110 . the lock deck 152 of first lock 150 a and second lock 150 b may be turned toward the design 182 to secure the press piece 180 in place . the first lock 150 a and the second lock 150 b are configured to slide between sides 113 of retainer 110 and are disposable at opposing ends 106 of the retainer 110 . the first lock 150 a and the second lock 150 b are configured to secure at least one press piece 180 . the first lock 150 a and the second lock 150 b may be configured to release at least one press piece 180 and allow for movement within the retainer 110 and removal from the retainer 110 . placement of the first lock 150 a and the second lock 150 b on opposing ends 106 of the retainer 110 sandwiches at least one press piece 180 between the first lock 150 a and the second lock 150 b . when the lock deck 152 of each lock is oriented to project perpendicularly to the retainer 110 , contents of the retainer 110 are unlocked and may shift slightly within the retainer 110 during imprinting . in a preferred embodiment , first lock 150 a and second lock 150 b are both locked to inhibit movement during imprinting and are unlocked to facilitate easy removal of the press piece 180 and easy insertion of the press piece 180 into the retainer 110 . the exemplary embodiments described above do not limit the types of designs that may be used in the imprinter 100 . for example , other designs that may be used in conjunction with imprinter 100 include symbols , curlicues , embellishments , illustrations , adornments , and artwork . in one embodiment , the press piece 180 features a design 182 that is scroll - like ( see fig2 b ). moreover , in other embodiments , impressions may be made of combinations of different types of designs . referring now to fig3 a - b , the lock 150 includes a lock deck 152 and a lock retaining portion 151 . in one embodiment , the lock retaining portion 151 is positioned at one end of the lock 150 and configured to engage the groove . in one embodiment , the lock retaining portion 151 comprises a cylinder . the lock retaining portion 151 may be a cylinder that extends at least the width of the lock deck 152 or may be in two parts with a first cylinder extending from one side of the lock deck 152 and a second cylinder extending from the other side of the lock deck 152 . the lock retaining portion 151 comprises a major axis 158 and a minor axis 159 , the major axis 158 corresponding to the longest diameter and the minor axis 159 to the shortest diameter . in one embodiment , the major axis 158 is perpendicular to the plane of the lock deck 152 . the major axis 158 is equal to or greater than the height of the groove 114 while the minor axis 159 is less than the height of the groove 114 . thus , the locking retaining portion 151 may slide along the groove 114 while the major axis 158 is not aligned perpendicular to the longitudinal axis of the retainer 110 ( and its groove 114 ). the lock 150 may be slid into the groove 114 while it is non - parallel with the retainer 110 . the lock 150 may be rotated , while the lock retaining portion 151 is in the groove 114 , to rotate the relative positions of the major axis 158 and minor axis 159 with respect to the groove 114 . due to the size of the major axis 158 , the rotation of the lock 150 will result in the lock retaining portion 151 becoming wedged within the groove 114 to secure the lock 150 in place relative to the retainer 110 . in one embodiment , the lock retaining portion 151 is shaped to provide a bi - stable structure , wherein the lock 150 is stable when substantially perpendicular — and free to slide in the groove 114 — to the retainer 110 . in such a perpendicular position , the lock 150 would extend from the retainer 110 and interfere with the imprinting . the lock 150 is also stable when substantially parallel — and unable to slide without substantial force relative to the groove 114 — with the retainer 110 . when in such a parallel position , the lock 150 does not extend from the retainer 110 sufficient to interfere with imprinting . in one implementation , the lock retaining portion 151 is an elliptical cylinder . in another implementation , illustrated in fig3 b , the lock retaining portion 151 includes one or more ridges 153 . the ridges 153 provide a larger effective diameter than where the lock retaining portion 151 lacks ridges 153 . in such an embodiment , the ridges engage the retainer 110 to secure the lock 150 when the lock 150 is positioned parallel to the retainer 110 . in one embodiment , the lock 150 has a ledge 154 bordering the lock deck 152 and extending from the lock deck 152 such that the ledge 154 is adjacent to the retainer body 111 when the lock 150 is parallel with the retainer 110 . in one embodiment , illustrated in fig3 a , two ledges 154 are provided such that each ledge 154 abuts and runs perpendicular to the lock retaining portion 151 . each ledge 154 protrudes from the lock deck 152 to interfere with sides 113 of retainer 110 to ensure that first lock 150 a and second lock 150 b fasten at least one press piece 180 between the sides 113 of retainer 110 . the ledge 154 may serve as a stop to limit rotation of the lock 150 with respect to the retainer 110 . for example , the ledge 154 may prevent the lock 150 from rotating past the point where the major axis 158 is when the lock deck 152 is oriented in a first position to parallel retainer 110 , and interference is created between each ledge 154 and sides 113 of retainer 110 to inhibit movement . when the lock deck 152 is oriented to be in a second position to be perpendicular to the design 182 and to retainer 110 , movement is allowed . the lock deck 152 has a width , and , in one embodiment , the lock retaining portion 151 has a width that exceeds the width of lock deck 152 . the width of lock deck 152 is less than the distance between the opposing grooves 114 to allow the lock 150 to rotate relative to the retainer 110 . the press piece 180 has a design 182 projecting in a first direction away from the retainer 110 and towards a surface to be imprinted ( see fig1 c ). a press piece 180 comprising a back 184 may be oriented in the retainer 110 so that the design 182 contacts the desired surface while the back 184 of the press piece 180 faces towards retainer 110 ( see fig5 ). as illustrated in fig4 a , the grip 119 projects from the retainer 110 in a second direction opposed to the first direction . sides 113 of the retainer 110 project in the first direction . the grip 119 allows for manual positioning of imprinter 100 at a desired location . the grip 119 is approximately equidistant between sides 113 of retainer 110 and provides for imprinter 100 to be used comfortably and safely . referring now to fig1 c , sides 183 of press piece 180 extend in a second direction opposite to the first direction that the design extends along . sides 183 of press piece 180 are configured to be inserted between sides 113 of retainer 110 . fig5 illustrates an embodiment when viewed from the surface to be imprinted . an embodiment formed of transparent material removes guesswork from positioning the imprinter to create impressions in a surface at a desired location because a decorator can view the position of at least one press piece 180 within the retainer 110 prior to applying force to the imprinter 100 . in one embodiment , the imprinting tool may include only a first lock 150 a . the first lock 150 a may be engageable at one end of the retainer 110 , with the second end of the retainer 110 retaining the press pieces 180 such that a second lock 150 b is not necessary to retain the press pieces 180 . in one embodiment , the first lock 150 a and the second lock 150 b are chiral , being non - superimposable mirror images of each other and are designed to only secure the retainer 110 from their respective ends . in another embodiment , the first lock 150 a and the second lock 150 b are identical and may be interchanged to secure the retainer 110 from either end . in one embodiment , a lock 150 may positioned between two press pieces 180 such as to serve as a spacer . in such embodiment , the lock 150 does not extend from the retainer 110 sufficiently to leave an imprint when the imprinter 100 is used . thus , the lock 150 may serve to additionally secure press pieces 180 other than from an end and may also serve as a spacer , such as where a decorator wishes to form works from letters on press pieces 180 . in one embodiment , the press piece 180 may be inserted into the retainer 110 with the design 182 facing outward , i . e . away from the retainer , or inward , i . e . disposed between the deck 181 and the retainer body 111 . in this embodiment , storage of the press piece 180 with the design inwardly facing can protect the design 182 from damage , such as during travel . further , press pieces 180 that are inserted into the retainer 110 facing inward may be used as spacers between outwardly facing press pieces 180 to provide spaces between imprinted designs . in one embodiment , the retainer 110 includes a plurality of retaining portions . in this embodiment , a plurality of grooves 114 each for receiving a portion of the press piece 180 are disposed to permit rows of press pieces 180 to be stacked in the retainer 110 . in such embodiment , imprinter 100 can imprint at least one design 182 , and resulting impressions on a surface of a desired location can surpass the design 182 of the press piece 180 in height and width . in this embodiment , the retainer body 111 comprises pairs of grooves 114 parallel to each other . press pieces 180 can be disposed horizontally and vertically relative to each other to permit rows and columns of imprinted designs . a method of using imprinter 100 is now described . referring to fig1 - 5 , at least one press piece 180 with a design 182 is selected . each press piece 180 is inserted into a retainer 110 to be oriented parallel to a desired location for imprinting . a first lock 150 a and a second lock 150 b are positioned on opposing ends 106 of the retainer 110 . a tab - shaped portion of each lock of first lock 150 a and second lock 150 b is turned in a first position parallel to the design 182 to secure each press piece 180 . a grip 119 is used to position imprinter 100 over a surface at a desired location . force is applied to imprinter 100 so that the design 182 of at least one press piece 180 is impressed on the surface . the imprinter described above provides several advantages . the decorator can readily imprint designs on the surface of a desired location accurately and with consistent results . a plurality of combinations of designs are achievable . the grip 119 and the retainer 110 allow for placement of designs directly on the surface without manually positioning the press piece at the desired location . the method of imprinting described above may be more sanitary as there may be less contact with the decorator &# 39 ; s hands and higher precision of design location and angle . embodiments comprising translucent materials may allow the decorator to see the surface at the desired location , reducing delay and improving decoration speed and quality . with respect to the use of substantially any plural and / or singular terms herein , those having skill in the art can translate from the plural to the singular and / or from the singular to the plural as is appropriate to the context and / or application . the various singular / plural permutations may be expressly set forth herein for the sake of clarity . the foregoing description of illustrative embodiments has been presented for purposes of illustration and of description . it is not intended to be exhaustive or limiting with respect to the precise form disclosed , and modifications and variations are possible in light of the above teachings or may be acquired from practice of the disclosed embodiments . it is intended that the scope of the invention be defined by the claims appended hereto and their equivalents . | an imprinter for creating impressions of designs in media such as buttercream , fondant , gum paste , modeling dough , and cookie dough for decoration . the imprinter includes a retainer having a retainer body and at least one retaining portion and a lock configured to be received by the retainer . the lock has a lock retaining portion engageable with the retaining portion of the retainer to selectably secure the lock to the retainer . |
the present invention provides a new class of lipid molecules , which lipid molecules are provided with one or more nitric - oxide containing groups . the nitric - oxide containing groups comprises one or more of the following moieties : as is well known in the art , pendant s - nitroso -, n - nitroso - and o - nitroso - groups groups can be made , for example , from pendant thiols , amines and alcohols . because many naturally occurring lipid compounds do not contain thiol groups , in some embodiments of the present invention ( for example , those in which an s - nitroso moiety is formed ), it is desirable to provide a lipid species with pendant thiol groups from a lipid species having one or more pendant nucleophilic groups , such as alcohols or amines . these pendant nucleophilic groups can be converted to pendant thiol groups by methods known in the art , such as those disclosed in gaddell and defaye , angew . chem . int . ed . engl . 30 : 78 ( 1991 ) and rojas et al ., j . am . chem . soc . 117 : 336 ( 1995 ), the teachings of which are hereby incorporated into this application by reference . in these methods , primary alcohols are thiolated preferentially over secondary alcohols . moreover , u . s . pat . no . 5 , 770 , 645 , the entire disclosure of which is hereby incorporated by reference , teaches that a polythiolated species can be prepared by reacting a polyhydroxylated species , and preferably primary alcohol groups of a polyhydroxylated species , with a reagent that adds a moiety containing a free thiol or protected thiol to the alcohol . in one example the polysaccharide is reacted with a bis isocyanatoalkyldisulfide followed by reduction to functionalize the alcohol as shown in structural formula ( i ): conditions for carrying out this reaction are found in cellulose and its derivatives , fukamota , yamada and tonami , eds . ( john wiley & amp ; sons ), chapter 40 , ( 1985 ), the disclosure of which is incorporated herein by reference . methods for producing thiol groups from alcohol groups are also disclosed in u . s . pat . no . 4 , 466 , 914 , the disclosure of which is incorporated herein by reference . lipids with thiol groups are also available commercially . one example is phosphatidylthioethanol available from avanti polar lipids , 700 industrial drive , alabaster , ala . 35007 . once a lipid with one or more pendant thiol groups is provided , these compounds can be reacted with a nitrosylating agent under conditions suitable for nitrosylating the free thiol groups . appropriate procedures are discussed , for example , in u . s . pat . no . 5 , 770 , 645 . nitrosylating agents disclosed as suitable include acidic nitrite , nitrosyl chloride , compounds comprising an s - nitroso group ( s - nitroso - n - acetyl - d , l - penicillamine ( snap ), s - nitrosoglutathione ( snog ), n - acetyl - s - nitrosopenicillaminyl - s - nitrosopenicillamine , s - nitrosocysteine , s - nitrosothioglycerol , s - nitrosodithiothreitol and s - nitrosomercaptoethanol ), an organic nitrite ( e . g . ethyl nitrite , isobutyl nitrite , and amyl nitrite ), peroxynitrites , nitrosonium salts ( e . g . nitrosyl hydrogen sulfate ), oxadiazoles ( e . g . 4 - phenyl - 3 - furoxancarbonitrile ) and the like . for more information , see u . s . pat . no . 5 , 770 , 645 . similar procedures are known in the art for the formation of other groups , including n - nitroso - groups ( see , e . g ., u . s . pat . no . 5 , 185 , 376 , the disclosure of which is incorporated herein by reference ) and n - nonoates ( see , e . g ., u . s . pat . nos . 5 , 721 , 365 , 5 , 698 , 738 and 5 , 519 , 020 , the disclosures of which are incorporated herein by reference ). using the above as well as other well - known procedures , a wide range of s - nitroso -, n - nitroso - and o - nitroso - lipids can be produced from appropriate precursor molecules in accordance with the present invention , several of which are discussed below . exemplary precursor molecules appropriate for the practice of the present invention include lipids having a sphingosine base as a backbone . by “ a sphingosine base ” is meant sphingosine as well as related bases known in the art such as dihydrosphingosine , phytosphingosine , 4 , 8 - sphingadiene , and so forth . in addition to sphingosine bases themselves , other lipids having a sphingosine base as a backbone are appropriate for the practice of the present invention , including n - alkyl - substituted sphingosine bases such as n , n , n - trimethylsphingosine . n , n , n - trimethylsphingosine is known to inhibit platelet activation , s . d . kennedy , y . igarashi and t . s . keckler , 1997 “ measurement of in vitro p selectin expression by flow cytometry ,” am . j . clin . pathol ., 1 : 107 , pp . 99 - 104 , the disclosure of which is hereby incorporated by reference . it also prevents leukocyte - endothelial interactions and preserves cardiac contractile function following myocardial ischemia and reperfusion , b . campbell and y . k . shin , r . scalia and a . m . lefer , 1998 , “ beneficial effects of n , n , n - trimethylsphingosine following ischemia and reperfusion in the isolated perfused rate heart ,” cardiovasc . res . 2 : 39 , pp . 393 - 400 , the disclosure of which is hereby incorporated by reference . it further inhibits tumor growth and protein kinase c . still other lipids having a sphingosine base as a backbone are appropriate for the practice of the present invention and include the sphingolipids , which are complex lipids containing three characteristic building block components : ( 1 ) a polar head group , ( 2 ) a fatty acid molecule , and ( 3 ) a sphingosine base as a backbone . exemplary groups of sphingolipids appropriate for the practice of the invention include sphingomyelins , neutral glycosphingolipids ( including cerebrosides ) and acidic glycosphingolipids . acidic glycosphingolipids , also known as gangliosides , are present in neurological tissue . sphingolipids contain , for example , — oh groups for nitrosylation , with the glycosphingolipids having an abundant supply of — oh groups as they contain saccharide moieties within their head groups . phosphoglycerides are other precursor molecules appropriate for the practice of the present invention . preferred phosphoglycerides are those having one or more — oh groups in the polar head ( for example , phosphatidylinositol , phosphatidylglycerol and cardiolipin ), those with amine groups in the polar head ( for example , phosphatidylcholine , phosphatidylethanolamine and phosphatidylserine ) and those with both — oh and amine groups in the polar head ( for example , 3 ′- o - lysylphosphatidylglycerol ). of these , phosphatidylinositol ( which is an important intracellular signaling lipid ) and phosphatidylcholine are highly preferred . where r is a branched aliphatic chain of eight or more carbon atoms , are also appropriate as precursor molecules for the practice of the present invention . a preferred sterol is cholesterol . other precursor molecules appropriate for the practice of the present invention include monoacylglyerols ( monoglycerides ), diacylglycerols ( diglycerides ), and glycosylacylglycerols , each of which has one or more pendant — oh groups . each of the above precursor molecules has one or more groups , typically amine , hydroxyl and / or thiol groups , which allow them to be converted , using the procedures discussed above , into the s - nitroso - n - nitroso - and / or o - nitroso - compounds of the present invention . as a specific example , an s - nitroso - n , n , n - trimethylsphingosine molecule is formed by first forming a thiol group at one or more of the hydroxyl groups of n , n , n - trimethylsphingosine , for example , using techniques such as those discussed above . the thiolated compound is subsequently nitrosylated using nitrosylating agents such as those described above . upon delivery to the body ( e . g ., to the vasculature ) the s - nitroso - n , n , n - trimethylsphingosine of the present invention releases nitric oxide , which has numerous beneficial therapeutic effects as noted above . since it contains n , n , n - trimethylsphingosine , this compound also inhibits platelet formation and prevents leukocyte - endothelial interactions , even after the release of no from the compound . one advantage that the s - nitrosylated , n - nitrosylated and o - nitrosylated lipids of the present invention have over other organic no donors and inorganic no donors is that they can be readily incorporated into cell membranes , promoting tissue uptake and enhancing tissue retention time . similarly , the s - nitrosylated , n - nitrosylated and o - nitrosylated lipids of the present invention have an affinity for lipid deposits in the body , for example , those lipid depositions within atherosclerotic plaques . this affinity allows for targeted no release within such regions . as another example , and as discussed further below , they can also be provided within liposomes , which are also effectively incorporated into cell membranes and lipid deposits . as a specific example , where genetic material such as dna or rna is incorporated into liposomes comprising the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid of the present invention , the no released from the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid would act to dilate capillaries , enhancing tissue uptake of the liposomes and increasing the amount of liposome ( and hence genetic material ) that is delivered across the cell membrane and into the cytoplasm . moreover , specific cell types can be targeted , for example , by forming liposomes from lipids that further contain cell - binding domains directed to , for example , protein receptors on the cell surface . the s - nitrosylated , n - nitrosylated and o - nitrosylated lipids of the present invention can be delivered to the body by essentially any vehicle appropriate for delivery of therapeutic agents . for instance , in some embodiments of the present invention , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids of the present invention are simply adsorbed as a monolayer on the surface of polymer , metal or silica - based materials , with polymer materials being more preferred . in general a very smooth surface is required for the lipid groups to orient in a head - to - tail orientation ( or vice versa ) on a material surface . such a surface can be achieved , for example , by machining the material of interest with a polisher or grinder . in other embodiments , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids of the present invention are added to a liquid delivery vehicle that is based on one or more lipophilic and / or hydrophilic solvents . in general , a solvent system is selected to disperse or dissolve the lipid of the present invention . the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids of the present invention are typically soluble in lipophilic solvents . lipophilic solvents appropriate for the practice of the present invention include ethanol as well as other biocompatible lipophilic solvents such as dimethylsulfoxide ( dmso ), methylpyrrolidone , methanol , isopropyl alcohol and so forth . one drawback associated with lipophilic solvents , however , is that they commonly have some degree of cytotoxicity . hydrophilic solvents , particularly water , can also be used in connection with the present invention . in some instances , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids are also sufficiently amphiphilic such that they are dissolved or dispersed in the hydrophobic solvent at the desired concentration . alternatively , to assist with the dissolution / dispersion of the lipids of the present invention , emulsifying agents or other surfactants may be added , allowing lipid to be dispersed in the solvent system . in other instances , liposomes or micelles are formed which contain the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids of the present invention . micelles are formed in the appropriate solvent at a high , critical concentration of lipid in solution as is known in the art . for example , liposomes ( lipid vesicles ) are formed when thin lipid films or lipid cakes are hydrated and stacks of liquid crystalline bilayers become fluid and swell . the hydrated lipid sheets detach during agitation and self - close to form large , multilamellar vesicles ( lmv ) which prevents interaction of water with the hydrocarbon core of the bilayer at the edges . once these particles have formed , reducing the size of the particle requires energy input in the form of sonic energy ( sonication ) or mechanical energy ( extrusion ). disruption of an lmv suspensions using sonic energy ( sonication ) typically produces small , unilamellar vesicles ( suv ) with diameters in the range of 15 - 50 nm . lipid extrusion is a technique in which the lipid suspension is forced through a filter with a defined pore size to yield particles having a diameter near the pore size of the filter used . such methods for preparing and handling liposomes are well known and are found , for example , in the avanti polar lipids , inc . catalog , edition iv , the disclosure of which is hereby incorporated by reference ( see also http :// avantilipids . com ). in other embodiments of the present invention , a polymer matrix is provided as a delivery vehicle and the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid of the present invention is provided within the polymer matrix . the polymer matrix may be either biodegradable or non - biodegradable . numerous matrix materials exist in the art and a list of preferred polymers follows : polycarboxylic acids , including polyacrylic acid , available as hydroplus ® ( boston scientific corporation , natick , mass .) and described in u . s . pat . no . 5 , 091 , 205 , the disclosure of which is hereby incorporated herein by reference , gelatin , polyvinylpyrrolidone , cross - linked polyvinylpyrrolidone , polyanhydrides including maleic anhydride polymers , polyamides , polyvinyl alcohols , polyvinyl ethers , polyvinyl aromatics , polyethylene oxides , glycosaminoglycans , polysaccharides , polyesters including polyethylene terephthalate , polyacrylamides , polyethers , polyether sulfone , polycarbonate , polyalkylenes including polypropylene , polyethylene and high molecular weight polyethylene , polyvinyl acetates , halogenated polyalkylenes including polytetrafluoroethylene , polyurethanes , polyorthoesters , proteins , polypeptides , silicones , siloxane polymers , polylactic acid , polyglycolic acid , polycaprolactone , polyhydroxybutyrate valerate , coatings from polymer dispersions such as polyurethane dispersions ( bayhdrol ®, etc . ), fibrin , collagen and derivatives thereof , polysaccharides such as celluloses , starches , dextrans , alginates and derivatives such as cellulose acetate and cellulose nitrate , and hyaluronic acid . blends and copolymers containing the above - listed polymers are also appropriate for the practice of the invention . some exemplary copolymers include copolymers of vinyl monomers such as eva ( ethylene - vinyl acetate copolymer ) and poloxamers , which are also known as polyethylenepolypropylene glycols . a diversity of administrative routes can be used for the delivery of the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids to the patient &# 39 ; s body . patients include animal patients , preferably mammals , and more preferably humans . preferred administrative routes are topical routes , direct injection routes , intravascular routes and implantation routes . topically , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids can be administered in the form of a spray , solution , lotion , gel , cream , ointment or other topical delivery vehicle known in the art . patches or bandages are also contemplated . for example , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid can be dissolved or suspended in a liquid delivery vehicle ( including solutions , dispersions , lotions , gels , creams , ointments , etc .) and applied to a patch or bandage . alternatively , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid can be directly adsorbed to the patch or bandage surface , or the lipid can be disposed within a polymer matrix ( such as those set forth above ) disposed on the patch or bandage . the above sprays , lotions , gels , creams , ointments , patches or bandages can be applied to intact skin ( for example , to effect transdermal delivery of the lipids , which can result in , for instance , skin warming due to the resultant vasodilatation ). they can also be applied to broken skin ( for example , to enhance wound healing ). the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids can also be provided within the body using a number of additional administrative routes , including implantation , intravascular delivery and direct injection . for instance , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids can be provided in the form of an implant , which can serve to locally or systemically deliver the lipid . implants appropriate for use in connection with the present invention include soft tissue implants , bone implants and so forth . for example , the implant can consist entirely of a matrix material , such as those set forth above , or it can consist of a substrate coated with such a matrix material , or it can consist of a base material upon which the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid is adsorbed . the implant is preferably bioresorbable following no release . for direct injection , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid can be provided in the form of a solution or dispersion . suitable liquid media for this purpose include both lipophilic - and hydrophilic - solvent - based systems with hydrophilic - solvent - based systems being preferred . for intravascular delivery , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid can be provided in connection with a variety of intravascular delivery devices , including vascular catheters ( for example , balloon catheters , injection catheters or infusion catheters ), guide wires , balloons , filters ( for example , vena cava filters ), stents , stent grafts , vascular grafts , aneurysm fillers ( including gdc ( guglielmi detachable coils )) and intraluminal paving systems . in some embodiments , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid is directly adsorbed to the surface of the intravascular device ( e . g ., a stent , catheter , etc .). surfaces appropriate for adsorption of the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid include those listed above . in other embodiments , the intravascular device includes a matrix that is loaded with the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid . the matrix can be , for example , one of the matrices listed above , with biocompatibility being an important consideration . if of sufficient structural integrity , the matrix can constitute the entire device . alternatively , the matrix can constitute a portion of the device ( such as a device component , a portion thereof , or a coating on the device ). in other embodiments , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid is provided in a liquid medium that is injected from the intravascular device into the vascular wall . suitable injection media are discussed above . devices suitable for intravascular injections include needle injection catheters . in still other embodiments , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid is expressed in liquid form from an intravascular device such that it comes into contact with the vascular wall or blood . suitable liquid media for this purpose include both lipophilic - and hydrophilic - solvent - based systems with hydrophilic - solvent - based systems being preferred . suitable devices include infusion catheters . one beneficial effect associated with providing the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid of the present invention on the surface of an implant or intravascular medical device , it that the surface of the device is rendered less thrombogenic ( and preferably non - thrombogenic ), due to the release of nitric oxide . moreover , using these devices , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids can be administered locally to the blood and / or tissue surrounding the device or implant , leading to one or more of the beneficial tissue effects noted herein . in other embodiments of the present invention , an auxiliary therapeutic agent in addition to the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid is provided . this provides , for example , a “ double - edged ” therapy in which one therapeutic effect is provided by the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipid , and another effect is provided by the auxiliary therapeutic agent . a wide variety of auxiliary therapeutic agents , including genetic therapeutic agents , non - genetic therapeutic agents , and cells , can be used in conjunction with the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids of the present invention : anti - thrombotic agents such as heparin , heparin derivatives , urokinase , and ppack ( dextrophenylalanine proline arginine chloromethylketone ); anti - inflammatory agents such as dexamethasone , prednisolone , corticosterone , budesonide , estrogen , sulfasalazine and mesalamine ; antineoplastic / antiproliferative / anti - miotic agents such as paclitaxel , 5 - fluorouracil , cisplatin , vinblastine , vincristine , epothilones , endostatin , angiostatin , angiopeptin , monoclonal antibodies capable of blocking smooth muscle cell proliferation , and thymidine kinase inhibitors ; anti - coagulants such as d - phe - pro - arg chloromethyl ketone , an rgd peptide - containing compound , heparin , hirudin , antithrombin compounds , platelet receptor antagonists , anti - thrombin antibodies , anti - platelet receptor antibodies , aspirin , prostaglandin inhibitors , platelet inhibitors and tick antiplatelet peptides ; vascular cell growth promoters such as growth factors , including platelet - derived growth factor , transcriptional activators , and translational promoters ; vascular cell growth inhibitors such as growth factor inhibitors , growth factor receptor antagonists , transcriptional repressors , translational repressors , replication inhibitors , inhibitory antibodies , antibodies directed against growth factors , bifunctional molecules consisting of a growth factor and a cytotoxin , bifunctional molecules consisting of an antibody and a cytotoxin ; angiogenic factors including growth factors such as acidic and basic fibroblast growth factors , vascular endothelial growth factor , epidermal growth factor , transforming growth factor α and β , platelet - derived endothelial growth factor , platelet - derived growth factor , tumor necrosis factor α , hepatocyte growth factor and insulin like growth factor , thymidine kinase (“ tk ”) and other agents useful for interfering with cell proliferation , and the family of bone morphogenic proteins (“ bmp &# 39 ; s ”), including bmp - 2 , bmp - 3 , bmp - 4 , bmp - 5 , bmp - 6 ( vgr - 1 ), bmp - 7 ( op - 1 ), bmp - 8 , bmp - 9 , bmp - 10 , bmp - 11 , bmp - 12 , bmp - 13 , bmp - 14 , bmp - 15 , and bmp - 16 . currently preferred bmp &# 39 ; s are any of bmp - 2 , bmp - 3 , bmp - 4 , bmp - 5 , bmp - 6 and bmp - 7 . these dimeric proteins can be provided as homodimers , heterodimers , or combinations thereof , alone or together with other molecules . alternatively or , in addition , molecules capable of inducing an upstream or downstream effect of a bmp can be provided . such molecules include any of the “ hedgehog ” proteins , or the dna &# 39 ; s encoding them . viral vectors such as adenovirus ( av ), adenoassociated virus ( aav ) and lentivirus cells include cells of human origin ( autologous or allogeneic ), including stem cells , or from an animal source ( xenogeneic ), which can be genetically engineered if desired to deliver proteins of interest . the lipid compounds of the present invention are useful in providing the following effects , based on the following known actions of nitric oxide : anti - thrombotic effects . nitric oxide is known to inhibit platelet activation , preventing thrombus formation . as a result , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids of the present invention are useful in the treatment of peripheral vascular disease and coronary disease ( atherosclerosis ) where clot formation is a problem . vasodilation effects . nitric oxide causes smooth muscle cells to relax , dilating arteries and other blood vessels . this is important in maintaining proper blood flow during myocardial infarction , stroke , impotence , and peripheral circulation diseases ( e . g ., arising as complications of diabetes ). anti - inflammatory effects . nitric oxide prevents white blood cell adhesion ( anti - platelet activity also contributes to this effect ), rendering the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids of the present invention good candidates in the treatment of inflammatory disease , including psoriasis ( and other skin disorders ), septic shock , arthritis , atherosclerosis , stroke , and so forth . cytotoxic effects . at high dosages , nitric oxide is cytotoxic and can be used to reduce populations of undesirable cells , such as cancer cells , bacterial cells ( see , e . g ., u . s . pat . no . 5 , 814 , 666 ) and cells present in atherosclerotic lesions . nitric oxide prevents inflammation and promotes good blood circulation . nitric oxide is also important in the formation of collagen in wound healing ( see , e . g ., m r schaffer et al ., “ nitric oxide regulates wound healing ”, j surg res june 1996 ; 63 ( 1 ): 237 - 40 , the disclosure of which is hereby incorporated by reference ). if nitric oxide synthesis is prevented , wounds have few proliferating cells , and little collagen formation and capillary formation , thereby delaying the healing response ( see , e . g ., m n ackay et al , “ effect of nitric oxide synthase inhibitor on experimentally induced burn wounds ”, j trauma august 2000 ; 49 ( 2 ): 327 - 30 , the disclosure of which is hereby incorporated by reference ). as a result , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids of the present invention provide a good means of delivering nitric oxide to a wound or to a diseased site associated with a dermatological condition . dermatological conditions of interest include impetigo , epidermolysis bullosa , eczema , neurodermatitis , psoriasis , pruritis , erythema , hidradenitis suppurativa , warts , diaper rash , jock itch , and combinations thereof . see , e . g ., u . s . pat . no . 5 , 869 , 104 , “ method for treating dermatological conditions including impetigo ” and wo 00 / 53193a1 entitled “ pharmaceutical composition containing nitrate source and an acidifying agent for treating skin ischaemia ”, the disclosures of which are hereby incorporated by reference . nitric oxide is also useful in promoting proper healing after angioplasty procedures . for example , lower dosages of nitric oxide are known to promote smooth muscle cell relaxation , reduce smooth muscle cell proliferation , promote endothelial cell health , prevent platelet activation , and reduce inflammation , all of which effects tend to promote vascular health and proper healing ( e . g ., healing without the advent of restenosis ), for example , in the wake of angioplasty procedures . as noted above , the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids of the present invention have an affinity for lipid deposits in the body , such as those within atherosclerotic plaques , allowing for targeted no release within such regions . the lipids of the present invention can be supplemented by lipases , which are delivered to affect the lipid metabolism of the artery wall ( see , e . g ., k hirata et al ., “ regulated expression of endothelial cell - derived lipase ”, biochem biophys res commun 2000 may 27 ; 272 ( 1 ): 90 - 3 , the disclosure of which is hereby incorporated by reference ). the lipids of the present invention can also be supplemented by plaque degrading enzymes agents such as metalloproteinases , including collagenases , elastases and other enzymes that degrade the extracellular matrix . conversely , since the action of matrix degradation is important in the migration of smooth muscle cells , the s - nitrosylated , n - nitrosylated and / or o - nitrosylatedlipids of the present invention can also be combined with inhibitors of the metalloproteinases ( for example , halofuginone which inhibits matrix metalloproteinase - 2 expression and collagen expression ). in this way , restenosis following angioplasty can be hindered by inhibiting the migration of smooth muscle cells . as a treatment for restenosis following stent implantation or angioplasty ( as well as other purposes ), numerous auxiliary therapeutic agents can be supplied along with the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids of the present invention . these include the following ( several of which are also found in the above list of auxiliary therapeutic agents ): s - nitroso compounds including low molecular weight compounds ( e . g ., s - nitroso derivatives of captopril , glutathione and n - acetyl penicillamine ), high molecular weight compounds ( e . g ., s - nitroso derivatives of proteins , peptides , oligosaccharides , polysaccharides , synthetic polymers / oligomers and natural polymers / oligomers ) heparinoids such as heparin , low molecular weight heparin , dextran sulfate and β - cyclodextrin tetradecasulfate cyclooxygenase pathway inhibitors such as aspirin , ibuprofen , flurbiprofen , indomethacin and sulfinpyrazone hmg - coa reductase inhibitors such as lovastatin , pravastatin , fluvastatin , simvastatin and cerivastatin free - radical scavengers / antioxidants such as probucol , vitamins c and e , ebselen , trans - retinoic acid and sod mimics fgf pathway agents such as bfgf antibodies and chimeric fusion proteins igf pathway agents including somatostatin analogs such as angiopeptin and ocreotide tgf - β pathway agents such as polyanionic agents ( heparin , fucoidin ), decorin , and tgf - β antibodies egf pathway agents such as egf antibodies , receptor antagonists and chimeric fusion proteins thromboxane a2 ( txa2 ) pathway modulators such as sulotroban , vapiprost , dazoxiben and ridogrel protein tyrosine kinase inhibitors such as tyrphostin , genistein and quinoxaline derivatives antimetabolites such as purine analogs ( e . g ., 6 - mercaptopurine , thioguanine ), pyrimidine analogs ( e . g ., cytarabine and 5 - fluorouracil ) and methotrexate nitrogen mustards , alkyl sulfonates , ethylenimines , antibiotics ( e . g ., daunorubicin , doxorubicin ), nitrosoureas and cisplatin agents affecting microtubule dynamics ( e . g ., vinblastine , vincristine , colchicine , paclitaxel and epothilone ) matrix deposition / organization pathway inhibitors such as halofuginone or other quinazolinone derivatives and tranilast dosages of the s - nitrosylated , n - nitrosylated and / or o - nitrosylated lipids of the present invention , as well as any ancillary therapeutic agents , will depend , for example , upon the lipids / therapeutic agents selected , upon the route of delivery , upon the condition being treated / prevented , upon the age of the patent , and so forth . it is well within the skill of those of ordinary skill in the art to make such determinations . although various embodiments are specifically illustrated and described herein , it will be appreciated that modifications and variations of the present invention are covered by the above teachings and are within the purview of the appended claims without departing from the spirit and intended scope of the invention . | novel nitric - oxide releasing lipid molecules are provided which comprise a lipid molecule selected from phosphoglycerides , lipids having a sphingosine base as a backbone , monoacylglyerols , diacylglycerols , glycosylacylglycerols , wherein the lipid molecole is provided with a nitric - oxide contianing group which comprises a a — s — n ═ o moiety , a — o — n ═ o moiety , or a moiety . also provided are methods of forming such nitric oxide releasing lipid molecules . various pharmaceutical compositions , topical liquids and drug delivery systems comprising the ntric - oxide releasing lipid molecules are also described . further provided are methods for therapeutically administering nitric oxide to patients , methods for treating or preventing various conditions , methods for promoting wound healing and methods for reducing the cells present in an atherosclerotic lesion which methods utilize the nitric - oxide releasing lipid molecules . |
the figures and corresponding text below describe several exemplary embodiments of the invention . however , it should be understood that the present disclosure is only exemplary of the invention and is not intended to be limiting and that the claims below should be referred to for a full understanding of the scope of the invention . referring to fig1 the present invention relates to work vehicles such as agricultural work vehicles that employ one or more markers that can be raised or lowered with respect to the ground and an additional implement ( or toolbar of an implement ) that also can be raised or lowered with respect to the ground . in the embodiment shown in fig1 an exemplary work vehicle , in this case an agricultural work vehicle , is shown to be a tractor 10 that tows a planter 20 . the tractor 10 can , for example , be a mx series magnum tractor manufactured by cnh global nv of racine , wis ., while the planter can be , for example , a pivot - transport planter also manufactured by cnh global nv . as shown , the planter 20 towed behind the tractor 10 includes left and right marker assemblies 30 , 40 that are attached to left and right sides 50 , 60 of the planter respectively . each of the left and right marker assemblies 30 , 40 has outer and inner markers 151 , 161 , and 51 , 61 , respectively ( see also fig2 ). additionally , the planter includes a toolbar 70 that is attached to the remainder of the planter 20 ( the planter can also be termed an implement ). in accordance with the present invention , each of the markers 151 , 161 , 51 and 61 and the toolbar 70 can be raised and lowered with respect to the ground . in fig1 the right outer marker 51 is shown to be in a raised position , while the left outer and inner markers 151 , 161 are shown to be in lowered positions . in addition to the toolbar 70 , the planter 20 additionally includes several other components that are known in the art , including a plurality of hoppers 80 and a liquid fertilizer tank 90 . the toolbar 70 can include a variety of elements including , for example , seed discs , furrow opening and closing mechanisms , and press wheels , as are known in the art . although fig1 shows the tractor 10 and planter 20 , the present invention is intended to apply to any agricultural or other work vehicles that include one or more markers , as well as include a toolbar , implement or other device , where it is necessary to be able to raise and lower all of these devices . although the planter 20 is shown to be towed by the tractor 10 , the present invention also is intended to be applicable to any agricultural or other work vehicle on which one or more raisable / lowerable marker ( s ) and toolbar / implement are employed , regardless of whether all of these components are positioned on a single vehicle portion , or on multiple vehicle portions ( e . g ., where one marker is on the tractor , another marker is on a towed device other than the planter , and the toolbar / implement along with possibly yet another marker are on the planter itself .) the present invention further would relate to a work vehicle having only a single marker assembly , e . g ., a right marker assembly , or having more than two marker assemblies , as well as to a vehicle on which one or more of the marker assemblies had only a single marker , or more than two markers . referring to fig2 ( a )- 2 ( c ), the right marker assembly 40 is shown in three positions , namely , a first position in which each of the right outer and inner markers 51 , 61 is in its lowered position ( fig2 ( a )), a second position in which the outer marker is raised but the inner marker is lowered ( fig2 ( b )), and a third position in which each of the outer and inner markers is raised ( fig2 ( c )). as shown , the right marker assembly 40 includes a shoulder hinge 42 by which the marker assembly 40 is connected to the right side 60 of the planter 20 . in addition to the shoulder hinge 42 , the right marker assembly 40 includes an upper arm portion 43 , an elbow hinge 44 , a lower arm portion 45 , a wrist hinge 46 , and an outer extension 47 , which are connected to one another in succession . the right outer marker 51 is formed primarily by elements 44 - 47 and is supported by the right inner marker 61 , which is formed primarily by elements 42 and 43 . marking devices such as marking rings can be coupled to an outer tip 48 of the outer extension 47 and to an outer end 58 of the upper arm portion ( see fig1 for an exemplary marking ring 49 ). the right inner marker 61 is actuated by a right inner marker cylinder 62 while the right outer marker 51 is actuated by a right outer marker cylinder 52 ( see fig2 ( a ) and 2 ( b )). as shown , when the outer marker cylinder 52 is expanded , this causes the lower arm portion 45 to raise . because the outer extension 47 is hingedly connected to the lower arm portion 45 by the wrist hinge 46 , the outer extension falls due to gravity as the lower arm portion 45 is raised such that the lower arm portion 45 and the outer extension 47 retract in upon one another as shown in fig2 ( b ). conversely , when the right outer marker cylinder 52 is retracted , the lower arm portion 45 is lowered . because a lever 41 attached to the outer extension 47 proximate the wrist hinge 46 is hingedly coupled to a pull 53 that in turn is coupled to the outer end 58 , the outer extension 47 swings outward as the lower arm portion 45 is forced outward , and thus the right outer marker 51 becomes fully extended as shown in fig2 ( a ). fig2 ( a ) and 2 ( b ) show the right inner marker 61 in its lowered position . that is , the right inner marker 61 can remain in its lowered position regardless of whether the right outer marker 51 is lowered or not . as shown in fig2 ( a ) and 2 ( b ), the right inner marker 61 is lowered when the right inner marker cylinder 62 is retracted . however , as shown in fig2 ( c ), when the right inner marker cylinder 62 is extended , the upper arm portion 43 becomes raised and the right inner marker 61 therefore is raised . as is evident from fig2 ( c ), when the right inner marker 61 is in its raised position , the right outer marker 51 must also be in its raised position . although not shown in fig2 ( a )- 2 ( c ), the left marker assembly 30 in the present embodiment has a similar design to that of the right marker assembly and , in particular , the outer and inner markers 151 , 161 of the left marker assembly are actuated by a left outer marker cylinder 152 and a left inner marker cylinder 52 , respectively ( see fig3 ). referring to fig3 components of a hydraulic system 100 capable of being implemented on the tractor 10 and the planter 20 to raise and lower the markers 51 , 61 , 151 and 161 and the toolbar 70 is shown . in particular , the hydraulic system 100 includes a pump 110 that is powered by an engine 120 of the tractor 10 , and that is hydraulically coupled to a reservoir 130 from which it receives hydraulic fluid . the hydraulic fluid is then communicated to first and second toolbar cylinders 140 , 142 that govern the raising and lowering of left and right halves of the toolbar 70 , to the left and right outer marker cylinders 152 and 52 , respectively , and to the left and right inner marker cylinders 162 and 62 , respectively , by way of first and second control valves 170 and 172 , and a control circuit 174 . the right inner and outer marker cylinders 62 , 52 are those discussed above with reference to fig2 ( a )- 2 ( c ) while the left inner and outer marker cylinders 162 , 152 , though not shown with reference to fig1 or 2 ( a )- 2 ( c ), serve the same purposes with reference to the left marker assembly 30 as marker cylinders 62 and 52 serve with reference to the right marker assembly 40 . in fig3 the control valves 170 , 172 are shown to be located on the tractor 10 so that the valves can be actuated by a tractor operator ( e . g ., using control levers within a cab of the tractor ), while the control circuit 174 is shown to be located on the planter 20 ; however , the exact positioning of these components can vary depending upon the embodiment . as shown , the first control valve 170 specifically governs the provision of hydraulic fluid and hydraulic fluid pressure to ports s and r of the control circuit 174 , while the second control valve 172 specifically governs the provision of hydraulic fluid and hydraulic fluid pressure to ports s 1 and r 1 of the control circuit . each of the first and second control valves 170 , 172 has four possible positions or states , namely : a raise position in which hydraulic fluid is directed from the pump 110 to a respective one of the ports s , s 1 and from the a respective one of the ports r , r 1 to the reservoir 130 ; a lower position in which hydraulic fluid is directed from the pump 110 to a respective one of the ports r , r 1 and from a respective one of the ports s , s 1 back to the reservoir ; a neutral position in which fluid flow between the corresponding ports s , r or s 1 , r 1 and the pump and reservoir is precluded ; and a float position in which both of the ports s , r or s 1 , r 1 corresponding to the control valve are coupled to the reservoir 130 . as shown , each of ports s , r , s 1 , and r 1 is a port of the control circuit 174 . in addition , the port s is coupled to head portions 144 of each of the toolbar cylinders 140 and 142 , while the port r is coupled to rod portions 146 of each of those cylinders . consequently , whenever the first control valve 170 is switched to the raise position , hydraulic fluid flow is provided to the head portions 144 of the cylinders 140 , 142 , which causes the cylinders to expand and thus raises the left and right halves of the toolbar 70 . ( in alternate embodiments , only one cylinder can be used to raise the toolbar 70 or a portion thereof or another movable element , or more than two cylinders can be used to raise more than two segments of the toolbar or other movable elements .) however , when the first control valve 170 is switched to the lower position , hydraulic fluid flow is directed to the rod portions of the cylinders 140 , 142 and thus causes the toolbar 70 to be lowered . further , when the first control valve is in the neutral position , hydraulic fluid flow cannot occur to or from the first and second toolbar cylinders 140 , 142 from or to the pump or reservoir 110 , 130 , and consequently the position of the toolbar 70 is locked . additionally , when the first control valve 170 is in the float position , the toolbar 70 can lower under the influence of gravity as fluid is passed from the head portions 144 of the toolbar cylinders 140 , 142 to the rod portions 146 ( because the rod portions are smaller in cross - section than the head portions due to the presence of the rods therewithin , some of the fluid leaving the head portions also is directed toward the reservoir 130 ). the hydraulic fluid pressure provided to the ports s and r as determined by the first control valve 170 , in addition to being provided to the cylinders 140 and 142 , also is provided to the control circuit 174 . based upon the status of the control circuit 174 , the hydraulic fluid pressure provided to the ports s and r additionally can determine the upward and downward positioning of the right and left outer and inner marker cylinders 52 , 62 , 152 and 162 which govern the positioning of the corresponding right and left outer and inner markers 51 , 61 , 151 and 161 , respectively . although , depending upon the status of the control circuit 174 , the hydraulic fluid provided to the ports s and r can influence the positions of these marker cylinders 52 , 62 , 152 , and 162 , in accordance with the present embodiment of the invention , the hydraulic fluid provided to the ports s 1 and r 1 as determined by the control valve 172 also can influence the positions of these marker cylinders . that is , the actuation of the marker cylinders 52 , 62 , 152 and 162 and positioning of the markers 51 , 61 , 151 and 161 based upon the actuation of those cylinders can be governed either by way of the first control valve 170 , in which case some or all of the marker cylinders can be actuated simultaneously with the actuation of the toolbar cylinders 140 , 142 , or by way of the second control valve 172 , in which case some or all of the marker cylinders can be actuated independently of any actuation of the toolbar cylinders 140 , 142 . to prevent interaction between the hydraulic pressure provided by the two control valves 170 , 172 , the control circuit 174 serves to isolate the ports s 1 , r 1 from hydraulic fluid pressure being provided at the ports s , r and serves to isolate the ports s , r from hydraulic fluid pressure being provided at the ports s 1 , r 1 . as shown in fig3 the control circuit 174 includes first and second pilot operated check valves 176 , 178 , first and second conventional check valves 180 and 182 , and first and second pilot - to - close check valves 184 and 186 . the first pilot operated check valve 176 is connected between the port s and a first intermediate node 188 , while the second pilot operated check valve is connected between the port r and a second intermediate node 190 . further , the first conventional check valve 180 is coupled between the first intermediate node 188 and the port s 1 , while the second conventional check valve 182 is coupled between the second intermediate node 190 and the port r 1 . except as discussed below with respect to check valves 176 and 178 , each of the check valves 176 , 178 , 180 , and 182 are configured and positioned so as to only allow hydraulic fluid to flow through each respective check valve toward its respective intermediate node , and not from its respective intermediate node back to the corresponding one of the ports s , r , s 1 and r 1 . for example , the first conventional check valve 180 is configured and orientated to allow hydraulic fluid to flow from port s 1 to the first intermediate node 188 , but not in the opposite direction . while the first and second conventional check valves 180 , 182 are designed to always prevent hydraulic fluid from flowing from the intermediate nodes 188 , 190 to ports s 1 and r 1 , and to only allow hydraulic fluid to flow from the ports s 1 and r 1 to the intermediate nodes 188 and 190 , respectively , the first and second pilot operated check valves 176 and 178 , while normally being closed to prevent hydraulic fluid flow from the intermediate nodes 188 , 190 to the ports s and r , can be operated in certain situations to allow hydraulic fluid to flow in that reverse direction . as shown , a first pilot line 192 is coupled between the first pilot operated check valve 176 and the port r , while a second pilot line 194 is coupled between the second pilot operated check valve 178 and the port s . consequently , when hydraulic fluid pressure at the port s exceeds a certain minimum threshold , the second pilot operated check valve 178 enters an alternate state in which it allows hydraulic fluid to flow from the second intermediate node 190 to the port r . similarly , when the hydraulic fluid pressure at the port r exceeds a certain minimum threshold , then the first pilot operated check valve 176 enters an alternate state in which it allows hydraulic fluid to flow from the first intermediate node 188 to the port s . further referring to fig3 a third pilot line 196 couples the first pilot - to - close check valve 184 to the port s , while a fourth pilot line 198 couples the second pilot - to - close check valve 186 to the port r . the first pilot - to - close check valve 184 is coupled in parallel with the first conventional check valve 180 between the port s 1 and the first intermediate node 188 , and the second pilot - to - close check valve 186 is coupled in parallel with the second conventional check valve 182 between the second intermediate node 190 and the port r 1 . each of the pilot - to - close check valves 184 , 186 is designed to normally allow hydraulic fluid to flow in either direction between its respective port s 1 , r 1 and its respective intermediate 188 , 190 . however , when hydraulic pressure at the port s exceeds a minimum threshold , the first pilot - to - close check valve 184 prevents hydraulic fluid from flowing from the first intermediate node 188 back to the port s 1 . similarly , when the hydraulic fluid pressure at the port r exceeds a certain minimum threshold , then the second pilot - to - close check valve 186 prevents hydraulic fluid from flowing from the second intermediate node 190 back to the port r 1 . further as shown in fig3 head portions 157 of each of the right and left outer marker cylinders 52 , 152 are coupled to the first intermediate node 188 by respective right and left solenoid valves 202 , 204 ( which also are included as part of the control circuit 174 as shown in fig3 ), and by a two - way restriction orifice 206 and a one - way restriction orifice 207 . the restriction orifices 206 , 207 are coupled in series with one another and the respective solenoid valves 202 , 204 between the first intermediate node and the head portions of the respective cylinders 52 , 152 . each of the solenoid valves 202 , 204 can be set in one of two positions , a first position in which fluid flow is unrestricted by the solenoid valve and a second position in which fluid can only flow through the solenoid valve towards its respective marker cylinder and not away from its cylinder . the restriction orifices 206 , 207 allow fluid flow both from the first intermediate node 188 to the solenoid valves 202 , 204 and from the solenoid valves 202 , 204 to the first intermediate node ; however , the restriction orifices limit the rates at which fluid can flow . while the two - way restriction orifice 206 restricts flow in both directions , the one - way restriction orifice 207 serves only to restrict flow occurring toward the cylinders 52 , 152 . additionally as shown , respective head portions 208 of the respective right and left inner marker cylinders 62 , 162 are coupled to the first intermediate node 188 by way of respective first and second solenoid valves 210 , 212 , each of which can be set in either a first position in which all fluid flow through the respective solenoid valve is prevented and a second position in which fluid flow through the respective solenoid valve is unrestricted . although not required , in the embodiment shown , the respective solenoid valves 210 , 212 , are connected to the respective head portions 208 of the respective marker cylinders 62 , 162 by respective one - way restriction orifices 211 , which restrict fluid flow toward the head portions but not away from the head portions . further , respective rod portions 214 of the right and left inner marker cylinders 62 , 162 are coupled to the second intermediate node 190 . in the present embodiment , these connections are made by way of respective two - way restriction orifices 216 , although such orifices need not be employed in every embodiment . given the design of the control circuit 174 , the inner and outer marker cylinders 62 , 162 , 52 and 152 can be actuated independently of the actuation of the toolbar cylinders 140 , 142 if hydraulic fluid is applied at the ports s 1 and r 1 by way of the second control valve 172 , and also can be activated simultaneously with the toolbar cylinders 140 , 142 if hydraulic fluid pressure is applied at the ports s and r by way of the first control valve 170 . in the case of simultaneous control , the first control valve 170 is adjusted to either the raise position or the lower position such that hydraulic fluid pressure from the pump 110 is communicated to the port s or to the port r , respectively . at such times , the second control valve 172 is typically in the float position , although this is not necessary . if the hydraulic fluid pressure is provided to the port s , the hydraulic fluid flows through the first pilot operated check valve 176 to the first intermediate node 188 , and in turn is provided to each of the solenoid valves 210 , 212 , 202 , and 204 . consequently , the head portions 157 of the right and left outer marker cylinders 52 , 152 receive hydraulic fluid , which tends to raise the outer markers 51 , 151 and , additionally , if the solenoid valves 210 , 212 are in their second positions such that fluid is communicable therethrough , hydraulic fluid is then provided also to the head portions 208 of the respective right and left inner marker cylinders 62 , 162 , which causes the inner markers 61 , 161 also to raise . further , as hydraulic fluid enters the head portions 208 of the inner marker cylinders 62 , 162 , hydraulic fluid must exit those cylinders from the rod portions 216 , and fluid thus exiting the cylinders is returned to the second intermediate port 190 . because the hydraulic fluid pressure at the port s is at a high level , the second pilot line 194 communicates this pressure to the second pilot operated check valve 178 , which causes that check valve to allow the fluid returning to the second intermediate port 190 to return to the reservoir 130 by way of the port r . additionally , the third pilot line 196 communicates the pressure at the port s to the first pilot - to - close check valve 184 , which causes that valve to close and thus prevent fluid from flowing from the first intermediate node 188 to the port s 1 . also , because the hydraulic pressure applied to the port s is applied to the head portions 144 of the toolbar cylinders 140 , 142 , the toolbar 70 also tends to raise simultaneously as the markers are being raised . alternately , if the control valve 170 is put into the lower position such that the hydraulic fluid pressure from the pump 110 is applied to the port r , then hydraulic fluid flows through the first pilot operated check valve 178 to the second intermediate node 190 . because the pressure at the port r is communicated by way of the pilot line 192 to the first pilot operated check valve 176 , that check valve allows hydraulic fluid to flow from the first intermediate node 188 to the port s and then further to the reservoir 130 by way of the first control valve 170 . consequently , fluid from the head portions 157 of the left and right outer marker cylinders 52 , 152 can flow through the solenoid valves 202 , 204 ( assuming that those solenoid valves are in the first position allowing unrestricted flow therethrough ) and further through the restriction orifices 206 , 207 back to the first intermediate node 188 and finally to the reservoir 130 by way of the port s . the outer markers 51 , 151 corresponding to the outer marker cylinders 52 , 152 are lowered at a controlled pace ( despite the fact that they are lowered under the force of gravity ) due to the restriction created by the restriction orifice 206 . if one or both of the solenoid valves 202 , 204 are in their second position preventing flow away from the cylinders 52 , 152 , then the corresponding markers 51 , 151 are locked in place and cannot lower . also , fluid does not flow from the port r to the port r 1 via the second pilot - to - close check valve 186 since the fourth pilot line 198 communicates the pressure of the port r to that check valve such that the valve precludes such flow . further , as fluid is provided to the second intermediate node 190 by way of the second pilot operated check valve 178 , the fluid is further directed to the rod portions 216 of the inner marker cylinders 62 , 162 . if the solenoid valves 210 and 212 corresponding to the right and left inner marker cylinders 62 , 162 are in their second , fluid - conducting positions , then hydraulic fluid is capable of leaving the head portions 208 of the cylinders and returning by way of the corresponding solenoid valves to the first intermediate node 188 and then , because the first pilot operated check valve 176 is open due to the pressure upon the first pilot line 192 , further able to return to the reservoir 130 by way of the port s . if either of the solenoid valves 210 , 212 happens to be in its first ( closed ) state , then the corresponding marker cylinder 62 or 162 cannot vary in its position . additionally , as hydraulic fluid pressure is applied to the port r , then that fluid pressure is again provided to the rod ends 146 of the toolbar cylinders 140 and 142 , and consequently the toolbar 70 lowers simultaneously with the lowering of the outer markers and / or inner markers as determined by the states of the solenoid valves 202 , 204 , 210 and 212 . in certain embodiments , including the one shown in fig3 a switch 218 ( actuatable by the operator or also by a computer ) governs the positions of the solenoid valves 202 , 204 . in particular , the switch 218 allows an operator to alternate the solenoid valves &# 39 ; positions so that , at a first time , the solenoid valve 202 is in its first position such that it is fully conducting while the solenoid valve 204 is in its second position at a second time , the solenoid valve 204 is in its first position while the solenoid valve 202 is in its second position , and so on . regardless of whether the second control valve 172 is in the neutral state when hydraulic fluid is provided to one or the other of the ports s and r , the circuit 174 nonetheless prevents hydraulic fluid from being communicated to either of the ports s 1 and r 1 . in particular , when the first control valve 170 is in the raise state such that hydraulic fluid pressure is provided to the port s , fluid nevertheless cannot be communicated from the first intermediate port 188 to the port s 1 by way of the first conventional check valve 180 , nor can hydraulic fluid be provided from that intermediate node to the port s 1 by way of the first pilot - to - close check valve 184 . likewise , hydraulic fluid returning to the second intermediate node 190 cannot be provided to the port r 1 by way of either the second conventional check valve 182 or the second pilot - to - close check valve 186 . likewise , when the first control valve 170 is in the lower position , such that hydraulic fluid pressure is provided to the port r , the conventional check valves 180 , 182 and pilot - to - close check valves 184 , 186 prevent fluid flow from the intermediate nodes 190 , 188 toward the ports r 1 and s 1 . thus , the ports s 1 and r 1 are isolated from the hydraulic fluid pressure provided at either of the ports s and r . in the case where the first control valve 170 is in the neutral position but the second control valve 172 is in the raise position or the lower position , the outer marker cylinders 52 , 152 and inner marker cylinders 62 , 162 can be actuated independently of ( e . g ., without the actuation of ) the toolbar cylinders 140 , 142 . in particular , if the second control valve 172 is placed into the raise position , hydraulic fluid pressure is provided from the pump 110 to the port s 1 . the pressure at the port s 1 is initially provided to the first intermediate node 188 by way of both the first conventional check valve 180 and the first pilot - to - close check valve 184 . however , because the first conventional check valve 180 is spring - biased towards being closed , once some of the fluid initially moves from the port s 1 to the first intermediate node 188 , the first conventional check valve tends to close , thus preventing further fluid flow through that valve . consequently , after initially flowing through both the first conventional check valve 180 and the first pilot - to - close check valve 184 , the fluid then continues to flow from the port s 1 to the first intermediate node 188 only by way of the first pilot - to - close check valve . regardless of how the hydraulic fluid reaches the first intermediate port 188 , that fluid then proceeds toward each of the solenoid valves 202 , 204 , 210 and 212 and is capable of actuating the outer and inner marker cylinders 52 , 152 , 62 , and 162 , depending upon the states of those solenoid valves . when the solenoid valves 210 and 212 are in their second , fluid - communicating positions , fluid further returns from the rod ends 216 of the inner marker cylinders 62 , 162 to the second intermediate node 190 and further returns to the port r 1 from that node by way of the second pilot - to - close check valve 186 . alternately , when the second control valve 172 is in the lower position such that hydraulic fluid pressure is provided to the port r 1 , hydraulic fluid flows first to the second intermediate node 190 by way of both of the second conventional check valve 182 and the second pilot - to - close check valve 186 , and then continues to flow to the second intermediate node by way of only the second pilot - to - close check valve . depending upon whether the solenoid valves 210 and 212 are in the fluid communicating positions , hydraulic fluid may or may not flow toward the rod ends 216 of the inner marker cylinders 62 , 162 and then return from the head ends 208 of those cylinders by way of the solenoid valves to the first intermediate node 188 . further , depending upon whether the solenoid valves 202 and 204 are in their fluid communicating positions , fluid also may return to the first intermediate node 188 by way of the respective solenoid valve ( s ) and the restriction orifices 206 , 207 . the fluid returning to the first intermediate node 188 then further can proceed out to the reservoir 130 by way of the port s 1 by way of the first pilot - to - close check valve 184 . assuming that the first control valve 170 is either in the neutral position or the float position while all this is taking place , there is no significant hydraulic fluid pressure at the ports s and r , and consequently neither of the first and second pilot operated check valves 176 , 178 are opened to allow fluid to flow from the intermediate nodes 188 , 190 to the ports s and r . thus , the actuation of the marker cylinders 52 , 152 , 62 and 162 can occur independently of ( typically , without ) any actuation of the toolbar cylinders 140 , 142 . the control circuit 174 shown in fig3 is only one embodiment of several possible embodiments envisioned by the present invention . the control circuit 174 shown in fig3 employs three pairs of different types of check valves 176 and 178 , 180 and 182 , and 184 and 186 in order to allow for the outer markers 51 , 151 to move up and down when in the lowered position to accommodate variation in the terrain encountered by the markers . that is , typically , when the inner and outer markers 51 , 151 , 61 , 161 are in their lowered positions , the second control valve 172 is in the float position such that , as those markers need to vary in their position to account for variations in terrain , hydraulic fluid can freely flow back and forth to the marker cylinders 52 , 152 , 62 and 162 by way of the ports s 1 and r 1 and the pilot - to - close check valves 184 and 186 . however , in alternate embodiments , for example , embodiments in which the marker linkages themselves include compensation features that effectively allow the markers to float without necessitating any movement of hydraulic fluid in relation to the movement of those markers , then the pilot - to - close check valves 184 and 186 can be eliminated and the first and second conventional check valves 180 and 182 can be replaced with pilot operated check valves like the check valves 176 and 178 , with pilot lines coupling those respective new pilot operated check valves to the ports s 1 and r 1 ( in alternating fashion , just as the pilot lines 192 and 194 couple the check valves 176 and 178 to the ports s and r .) the present invention is also intended to encompass a variety of alternate embodiments that employ varying numbers and types of valves in place of or in addition to any of the valves 170 , 172 , 176 , 178 , 180 , 182 , 184 , 186 , 202 , 204 , 210 and 212 , so long as there are two isolated hydraulic actuation paths in which one of the paths actuates one or more marker ( s ) while another of the paths actuates those marker ( s ) plus an additional component such as a toolbar . to apprise the public of the scope of this invention , the following claims are made : | an apparatus and method for controlling positions of an implement and a marker associated with a work vehicle . the apparatus includes a hydraulic circuit coupled to a first cylinder that governs the position of the marker , a first valve coupled to a second cylinder that governs the position of the implement and also coupled to a first port of the circuit , and a second valve coupled to a second port of the circuit . the circuit is configured to isolate the first port of the circuit from secondary pressure supplied to the second port by way of the second valve , and further configured to isolate the primary port of the circuit from primary pressure supplied to the first port by way of the first valve . the primary pressure influences movement of both the marker and the implement , while the secondary pressure influences movement of the marker only . |
preferably , the radicals r 1 , r 2 and r 3 have the following meanings : r 2 , r 3 , independently of one another , are methyl , ethyl . more preference is given to 3 , 3 , 6 - trimethylindan - 1 - one ( r 1 , r 2 and r 3 are all methyl ). it has been found that the 6 - alkylindan - 1 - ones according to the present invention have a leathery odor with woody notes . the compounds according to the present invention are characterized by an intensive odor , particularly high extendability , high odiferous adhesion and a valuable odor character . u . s . pat . no . 4 , 532 , 357 describes 3 , 3 , 7 - and 3 , 3 , 5 - trimethylindan - 1 - one as fragrances . it describes the odiferous properties of the mixture of the two isomers , and the two individual isomers . the sensory properties of the compounds according to the present invention have been investigated with regard to the odor character , the extendability , the intensity and the adhesion compared to the other regio isomers ( see table 1 ). all of the odor tests were carried out by a group of trained experts with at least six participants with concealed and coded samples . 6 - alkylindan - 1 - ones are characterized by a very high odiferous extendability , a high odiferous intensity and very high odiferous adhesion . in addition , 6 - alkylindan - 1 - ones are also characterized by a significant leather odor with spicy notes and differ in this respect from the other isomers in which tobacco and honey notes with floral aspects dominate . to determine the extendability , logarithmically diluted solutions of the compound according to the present invention and of other isomers in diethyl phthalate ( dep ) were prepared , and smelling strips were dipped uniformly into these solutions . these smelling strips were then smelled compared with smelling strips which are immersed in pure and odorless diethyl phthalate . in this way , the last dilution to still have an odor was determined by the group of experts . in this connection , it emerged that 3 , 3 , 6 - trimethylindan - 1 - one has an extendability which is fifty to five hundred times greater than that of other isomers ( table 1 ). this property means that even the very smallest amounts of the compounds according to the present invention can be perceived in odor terms and thus can make a considerable contribution in perfume oils and perfumed products . to determine the odor intensity of the compounds according to the present invention and of the 3 , 3 , 4 -, 3 , 3 , 5 - and 3 , 3 , 7 - trimethyl isomers , the 5 % strength by weight ethanolic solutions were smelled from smelling strips . in this connection , the odor intensity was compared on a scale from 1 ( weak ) to 9 ( very strong ). in this connection , it is found that , for example , the 3 , 3 , 6 - trimethylindan - 1 - one has a significantly higher odor intensity than that of the other isomers ( table 1 ). odor adhesion is the odiferous perception of fragrances over a long period . to evaluate the odor adhesion , the group of experts in each case daily evaluates smelling strips with the compound according to the present invention and the other isomers until a time when no odor , or only a very weak or untypical odor , can be perceived . in this connection , it is found that 3 , 3 , 6 - trimethylindan - 1 - one has a considerably longer odor adhesion than the other investigated isomeric trimethylindan - 1 - ones ( table 1 ). on the basis of the sensory work which has been carried out , it has surprisingly been found that 3 , 3 , 6 - trimethylindan - 1 - one has essential advantages over the other isomers . to assess the individual isomeric trialkylindan - 1 - ones , they were prepared by reacting alkyl - substituted benzoic acid isobutyl esters in polyphosphoric acid . thus , 3 , 3 , 4 -, 3 , 3 , 5 -, 3 , 3 , 6 - and 3 , 3 , 7 - trimethylindan - 1 - ones , for example , were obtained by reacting para -, meta - or ortho - toluic acid isobutyl esters , respectively , in polyphosphoric acid . in a mixture with other isomeric trialkylindan - 1 - ones , such as , for example , 3 , 3 , 4 -, 3 , 3 , 5 - or 3 , 3 , 7 - trimethylindan - 1 - one , the compounds according to the present invention also develop a pleasant leather - like odor which makes a valuable contribution in perfume compositions . surprisingly , the compounds according to the present invention in a mixture with isomeric trimethylindan - 1 - ones impart a particularly intensive odor and produce a particularly high extendability which cannot be achieved by the two isomers alone . this gives rise to considerable advantages when employing the 6 - alkylindan - 1 - ones for use in perfume oils . the compounds according to the present invention can produce surprising enhancing effects in perfume oils either as an individual fragrance , or as a mixture with isomeric trimethylindan - 1 - ones or together with other fragrances . examples of fragrances in perfume oils can be found , for example , in k . bauer , d . garbe and h . surburg , common fragrance and flavor materials , 3 rd . ed ., wiley - vch , weinheim 1997 . extracts from natural raw materials such as essential oils , concretes , absolutes , resins , resinoids , balsams , tinctures , such as , for example , ambergris tincture ; amyris oil ; angelica seed oil ; angelica root oil ; aniseed oil ; valerian oil ; basil oil ; wood moss absolute ; bay oil ; mugwort oil ; benzoin resin ; bergamot oil ; beeswax absolute ; birch tar oil ; bitter almond oil ; savory oil ; bucco leaf oil ; cabreuva oil ; cade oil ; calmus oil ; camphor oil ; cananga oil ; cardamom oil ; cascarilla oil ; cassia oil ; cassia absolute ; castoreum absolute ; cedar leaf oil ; cedarwood oil ; cistus oil ; citronella oil ; lemon oil ; copaiva balsam ; copaiva balsam oil ; coriander oil ; costus root oil ; cumin oil ; cypress oil ; davana oil ; dill herb oil ; dill seed oil ; eau de brouts absolute ; oakmoss absolute ; elemi oil ; estragon oil ; eucalyptus citriodora oil ; eucalyptus oil ; fennel oil ; spruce needle oil ; galbanum oil ; galbanum resin ; geranium oil ; grapefruit oil ; guaiac wood oil ; gurjun balsam ; gurjun balsam oil ; helichrysum absolute ; helichrysum oil ; ginger oil ; iris root absolute ; iris root oil ; jasmine absolute ; calamus oil ; blue camomile oil ; roman camomile oil ; carrot seed oil ; cascarilla oil ; pine needle oil ; spearmint oil ; caraway oil ; labdanum oil ; labdanum absolute ; labdanum resin ; lavandin absolute ; lavandin oil ; lavender absolute ; lavender oil ; lemongrass oil ; lovage oil ; distilled lime oil ; pressed lime oil ; linaloe oil ; litsea cubeba oil ; bayleaf oil ; mace oil ; marjoram oil ; mandarin oil ; massoi bark oil ; mimosa absolute ; musk seed oil ; musk tincture ; clary sage oil ; nutmeg oil ; myrrh absolute ; myrrh oil ; myrtle oil ; clove leaf oil ; clove flower oil ; neroli oil ; olibanum absolute ; olibanum oil ; opopanax oil ; orange - flower absolute ; orange oil ; origanum oil ; palmarosa oil ; patchouli oil ; perilla oil ; peruvian balsam oil ; parsley leaf oil ; parsley seed oil ; petitgrain oil ; peppermint oil ; pepper oil ; pimento oil ; pine oil ; pennyroyal oil ; rose absolute ; rosewood oil ; rose oil ; rosemary oil ; dalmation sage oil ; spanish sage oil ; sandalwood oil ; celery seed oil ; spike lavender oil ; japanese anise oil ; styrax oil ; tagetes oil ; fir needle oil ; tea - tree oil ; turpentine oil ; thyme oil ; tolu balsam ; tonka absolute ; tuberose absolute ; vanilla extract ; violet leaf absolute ; verbena oil ; vetiver oil ; juniper oil ; wine lees oil ; absinthe oil ; wintergreen oil ; ylang oil ; hyssop oil ; civet absolute ; cinnamon leaf oil ; cinnamon bark oil ; and fractions thereof , or ingredients isolated therefrom ; individual fragrances from the group of hydrocarbons , such as , for example , 3 - carene ; α - pinene ; β - pinene ; α - terpinene ; γ - terpinene ; p - cymene ; bisabolene ; camphene ; caryophyllene ; cedrene ; farnesene ; limonene ; longifolene ; myrcene ; ocimene ; valencene ; ( e , z )- 1 , 3 , 5 - undecatriene ; of aliphatic alcohols , such as , for example , hexanol ; octanol ; 3 - octanol ; 2 , 6 - dimethylheptanol ; 2 - methylheptanol , 2 - methyloctanol ; ( e )- 2 - hexenol ; ( e )- and ( z )- 3 - hexenol ; 1 - octen - 3 - ol ; mixture of 3 , 4 , 5 , 6 , 6 - pentamethyl - 3 / 4 - hepten - 2 - ol and 3 , 5 , 6 , 6 - tetramethyl - 4 - methyleneheptan - 2 - ol ; ( e , z )- 2 , 6 - nonadienol ; 3 , 7 - dimethyl - 7 - methoxyoctan - 2 - ol ; 9 - decenol ; 10 - undecenol ; 4 - methyl - 3 - decen - 5 - ol ; of aliphatic aldehydes and 1 , 4 - dioxacycloalken - 2 - ones thereof , such as , for example , hexanal ; heptanal ; octanal ; nonanal ; decanal ; undecanal ; dodecanal ; tridecanal ; 2 - methyloctanal ; 2 - methylnonanal ; ( e )- 2 - hexenal ; ( z )- 4 - heptenal ; 2 , 6 - dimethyl - 5 - heptenal ; 10 - undecenal ; ( e )- 4 - decenal ; 2 - dodecenal ; 2 , 6 , 10 - trimethyl - 5 , 9 - undecadienal ; heptanal diethyl acetal ; 1 , 1 - dimethoxy - 2 , 2 , 5 - trimethyl - 4 - hexene ; citronellyl oxyacetaldehyde ; of aliphatic ketones and oximes thereof , such as , for example , 2 - heptanone ; 2 - octanone ; 3 - octanone ; 2 - nonanone ; 5 - methyl - 3 - heptanone ; 5 - methyl - 3 - heptanone oxime ; 2 , 4 , 4 , 7 - tetramethyl - 6 - octen - 3 - one ; of aliphatic sulfur - containing compounds , such as , for example , 3 - methylth iohexanol ; 3 - methylth iohexyl acetate ; 3 - mercaptohexanol ; 3 - mercaptohexyl acetate ; 3 - mercaptohexyl butyrate ; 3 - acetylthiohexyl acetate ; 1 - menthene - 8 - thiol ; of aliphatic nitriles , such as , for example , 2 - nonenenitrile ; 2 - tridecenenitrile ; 2 , 12 - tridecenenitrile ; 3 , 7 - dimethyl - 2 , 6 - octadienenitrile ; 3 , 7 - dimethyl - 6 - octenenitrile ; of aliphatic carboxylic acids and esters thereof , such as , for example , ( e )- and ( z )- 3 - hexenyl formate ; ethyl acetoacetate ; isoamyl acetate ; hexyl acetate ; 3 , 5 , 5 - trimethylhexyl acetate ; 3 - methyl - 2 - butenyl acetate ; ( e )- 2 - hexenyl acetate ; ( e )- and ( z )- 3 - hexenyl acetate ; octyl acetate ; 3 - octyl acetate ; 1 - octen - 3 - yl acetate ; ethyl butyrate ; butyl butyrate ; isoamyl butyrate ; hexyl butyrate ; ( e )- and ( z )- 3 - hexenyl isobutyrate ; hexyl crotonate ; ethyl isovalerate ; ethyl 2 - methylpentanoate ; ethyl hexanoate ; allyl hexanoate ; ethyl heptanoate ; allyl heptanoate ; ethyl octanoate ; ethyl ( e , z )- 2 , 4 - decadienoate ; methyl 2 - octynoate ; methyl 2 - nonynoate ; allyl 2 - isoamyloxyacetate ; methyl 3 , 7 - dimethyl - 2 , 6 - octadienoate ; of acyclic terpene alcohols , such as , for example , citronellol ; geraniol ; nerol ; linalool ; lavandulol ; nerolidol ; farnesol ; tetrahydrolinalool ; tetrahydrogeraniol ; 2 , 6 - dimethyl - 7 - octen - 2 - ol ; 2 , 6 - dimethyloctan - 2 - ol ; 2 - methyl - 6 - methylene - 7 - octen - 2 - ol ; 2 , 6 - dimethyl - 5 , 7 - octadien - 2 - ol ; 2 , 6 - dimethyl - 3 , 5 - octadien - 2 - ol ; 3 , 7 - dimethyl - 4 , 6 - octadien - 3 - ol ; 3 , 7 - dimethyl - 1 , 5 , 7 - octatrien - 3 - ol ; 2 , 6 - dimethyl - 2 , 5 , 7 - octatrien - 1 - ol ; and formates , acetates , propionates , isobutyrates , butyrates , isovalerates , pentanoates , hexanoates , crotonates , tiglinates , 3 - methyl - 2 - butenoates thereof ; of acyclic terpene aldehydes and ketones , such as , for example , geranial ; neral ; citronellal ; 7 - hydroxy - 3 , 7 - dimethyloctanal ; 7 - methoxy - 3 , 7dimethyloctanal ; 2 , 6 , 10 - trimethyl - 9 - undecenal ; geranylacetone ; and the dimethyl and diethyl acetals of geranial , neral , 7 - hydroxy - 3 , 7 - dimethyloctanal ; of cyclic terpene alcohols , such as , for example , menthol ; isopulegol ; alpha - terpineol ; terpineol - 4 ; menthan - 8 - ol ; menthan - 1 - ol ; menthan - 7 - ol ; borneol ; isoborneol ; linalool oxide ; nopol ; cedrol ; ambrinol ; vetiverol ; guaiol ; and formates , acetates , propionates , isobutyrates , butyrates , isovalerates , pentanoates , hexanoates , crotonates , tiglinates , 3 - methyl - 2 - butenoates thereof ; of cyclic terpene aldehydes and ketones , such as , for example , menthone ; isomenthone ; 8 - mercaptomenthan - 3 - one ; carvone ; camphor ; fenchone ; alpha - ionone ; beta - ionone ; alpha - n - methylionone ; beta - n - methylionone ; alpha - isomethylionone ; beta - isomethylionone ; alpha - irone ; alpha - damascone ; beta - damascone ; beta - damascenone ; delta - damascone ; gamma - damascone ; 1 -( 2 , 4 , 4 - trimethyl - 2 - cyclohexen - 1 - yl )- 2 - buten - 1 - one ; 1 , 3 , 4 , 6 , 7 , 8a - hexahydro - 1 , 1 , 5 , 5 - tetramethyl - 2h - 2 , 4a - methanonaphthalen - 8 ( 5h )- one ; nootkatone ; dihydronootkatone ; alpha - sinensal ; beta - sinensal ; acetylated cedarwood oil ( methyl cedryl ketone ); of cyclic alcohols , such as , for example , 4 - tert - butylcyclohexanol ; 3 , 3 , 5 - trimethylcyclohexanol ; 3 - isocamphylcyclohexanol ; 2 , 6 , 9 - trimethyl - z2 , z5 , e9 - cyclo dodecatrien - 1 - ol ; 2 - isobutyl - 4 - methyltetrahydro - 2h - pyran - 4 - ol ; of cycloaliphatic alcohols , such as , for example , alpha - 3 , 3 - trimethylcyclohexylmethanol ; 2 - methyl - 4 -( 2 , 2 , 3 - trimethyl - 3 - cyclopent - 1 - yl ) butanol ; 2 - methyl - 4 -( 2 , 2 , 3 - trimethyl - 3 - cyclopent - 1 - yl )- 2 - buten - 1 - ol ; 2 - ethyl - 4 -( 2 , 2 , 3 - trimethyl - 3 - cyclopent - 1 - yl )- 2 - buten - 1 - ol ; 3 - methyl - 5 -( 2 , 2 , 3 - trimethyl - 3 - cyclopent - 1 - yl )- pentan - 2 - ol ; 3 - methyl - 5 -( 2 , 2 , 3 - trimethyl - 3 - cyclopent - 1 - yl )- 4 - penten - 2 - ol ; 3 , 3 - dimethyl - 5 -( 2 , 2 , 3 - trimethyl - 3 - cyclopent - 1 - yl )- 4 - penten - 2 - ol ; 1 -( 2 , 2 , 6 - trimethylcyclohexyl ) pentan - 3 - ol ; 1 -( 2 , 2 , 6 - trimethylcyclohexyl ) hexan - 3 - ol ; of cyclic and cycloaliphatic ethers , such as , for example , cineol ; cedryl methyl ether ; cyclododecyl methyl ether ; ( ethoxymethoxy ) cyclododecane ; alpha - cedrene epoxide ; 3a , 6 , 6 , 9a - tetramethyldodecahydronaphtho [ 2 , 1 - b ] furan ; 3a - ethyl - 6 , 6 , 9a - trimethyldodecahydronaphtho [ 2 , 1 - b ] furan ; 1 , 5 , 9 - trimethyl - 13 - oxabicyclo [ 10 . 1 . 0 ] trideca - 4 , 8 - diene ; rose oxide ; 2 -( 2 , 4 - d imethyl - 3 - cyclohexen - 1 - yl )- 5 - methyl - 5 -( 1 - methyl propyl )- 1 , 3 - dioxane ; of cyclic ketones , such as , for example , 4 - tert - butylcyclohexanone ; 2 , 2 , 5 - trimethyl - 5 - pentylcyclopentanone ; 2 - heptylcyclopentanone ; 2 - pentylcyclopentanone ; 2 - hydroxy - 3 - methyl - 2 - cyclopenten - 1 - one ; 3 - methyl - cis - 2 - penten - 1 - yl - 2 - cyclopenten - 1 - one ; 3 - methyl - 2 - pentyl - 2 - cyclopenten - 1 - one ; 3 - methyl - 4 - cyclopentadecenone ; 3 - methyl - 5 - cyclopentadecenone ; 3 - methylcyclopentadecanone ; 4 -( 1 - ethoxyvinyl )- 3 , 3 , 5 , 5 - tetramethylcyclohexanone ; 4 - tert - pentylcyclohexanone ; 5 - cyclohexadecen - 1 - one ; 6 , 7 - dihydro - 1 , 1 , 2 , 3 , 3 - pentamethyl - 4 ( 5h )- indanone ; 5 - cyclohexadecen - 1 - one ; 8 - cyclohexadecen - 1 - one ; 9 - cycloheptadecen - 1 - one ; cyclopentadecanone ; of cycloaliphatic aldehydes , such as , for example , 2 , 4 - dimethyl - 3 - cyclohexenecarbaldehyde ; 2 - methyl - 4 -( 2 , 2 , 6 - trimethyl - cyclohexen - 1 - yl )- 2 - butenal ; 4 -( 4 - hydroxy - 4 - methylpentyl )- 3 - cyclohexenecarbaldehyde ; 4 -( 4 - methyl - 3 - penten - 1 - yl )- 3 - cyclohexenecarbaldehyde ; of cycloaliphatic ketones , such as , for example , 1 -( 3 , 3 - dimethylcyclohexyl )- 4 - penten - 1 - one ; 1 -( 5 , 5 - dimethyl - 1 - cyclohexen - 1 - yl )- 4 - penten - 1 - one ; 2 , 3 , 8 , 8 - tetramethyl - 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 - octahydro - 2 - naphthalenyl methyl ketone ; methyl - 2 , 6 , 10 - trimethyl - 2 , 5 , 9 - cyclododecatrienyl ketone ; tert - butyl 2 , 4 - dimethyl - 3 - cyclohexen - 1 - yl ketone ; of esters of cyclic alcohols , such as , for example , 2 - tert - butylcyclohexyl acetate ; 4 - tert - butylcyclohexyl acetate ; 2 - tert - pentylcyclohexyl acetate ; 4 - tert - pentylcyclohexyl acetate ; decahydro - 2 - naphthyl acetate ; 3 - pentyltetrahydro - 2h - pyran - 4 - yl acetate ; decahydro - 2 , 5 , 5 , 8a - tetramethyl - 2 - naphthyl acetate ; 4 , 7 - methano - 3a , 4 , 5 , 6 , 7 , 7a - hexahydro - 5 or 6 - indenyl acetate ; 4 , 7 - methano - 3a , 4 , 5 , 6 , 7 , 7a - hexahydro - 5 or 6 - indenyl propionate ; 4 , 7 - methano - 3a , 4 , 5 , 6 , 7 , 7a - hexahydro - 5 or 6 - indenyl isobutyrate ; 4 , 7 - methanooctahydro - 5 or 6 - indenyl acetate ; of esters of cycloaliphatic carboxylic acids , such as , for example , allyl 3 - cyclohexyl - propionate ; allyl cyclohexyloxyacetate ; methyl dihydrojasmonate ; methyl jasmonate ; methyl 2 - hexyl - 3 - oxocyclopentanecarboxylate ; ethyl 2 - ethyl - 6 , 6 - dimethyl - 2 - cyclohexenecarboxylate ; ethyl 2 , 3 , 6 , 6 - tetra methyl - 2 - cyclohexenecarboxylate ; ethyl 2 - methyl - 1 , 3 - d ioxolan - 2 - acetate ; of araliphatic alcohols , such as , for example , benzyl alcohol ; 1 - phenylethyl alcohol ; 2 - phenylethyl alcohol ; 3 - phenylpropanol ; 2 - phenylpropanol ; 2 - phenoxyethanol ; 2 , 2 - dimethyl - 3 - phenylpropanol ; 2 , 2 - dimethyl - 3 -( 3 - methylphenyl ) propanol ; 1 , 1 - dimethyl - 2 - phenylethyl alcohol ; 1 , 1 - dimethyl - 3 - phenylpropanol ; 1 - ethyl - 1 - methyl - 3 - phenylpropanol ; 2 - methyl - 5 - phenylpentanol ; 3 - methyl - 5 - phenylpentanol ; 3 - phenyl - 2 - propen - 1 - ol ; 4 - methoxybenzyl alcohol ; 1 -( 4 - isopropylphenyl ) ethanol ; of esters of araliphatic alcohols and aliphatic carboxylic acids , such as , for example , benzyl acetate ; benzyl propionate ; benzyl isobutyrate ; benzyl isovalerate ; 2 - phenylethyl acetate ; 2 - phenylethyl propionate ; 2 - phenylethyl isobutyrate ; 2 - phenylethyl isovalerate ; 1 - phenylethyl acetate ; alpha - trichloromethylbenzyl acetate ; alpha , alpha - dimethylphenylethyl acetate ; alpha , alpha - dimethylphenylethyl butyrate ; cinnamyl acetate ; 2 - phenoxyethyl isobutyrate ; 4 - methoxybenzyl acetate ; of araliphatic ethers , such as , for example , 2 - phenylethyl methyl ether ; 2 - phenylethyl isoamyl ether ; 2 - phenylethyl 1 - ethoxyethyl ether ; phenylacetaldehyde dimethyl acetal ; phenylacetaldehyde diethyl acetal ; hydratropaldehyde dimethyl acetal ; phenylacetaldehyde glycerol acetal ; 2 , 4 , 6 - trimethyl - 4 - phenyl - 1 , 3 - dioxane ; 4 , 4a , 5 , 9b - etrahydroindeno [ 1 , 2 - d ]- m - dioxin ; 4 , 4a , 5 , 9b - tetrahydro - 2 , 4 - dimethylindeno [ 1 , 2 - d ]- m - dioxin ; of aromatic and araliphatic aldehydes , such as , for example , benzaldehyde ; phenylacetaldehyde ; 3 - phenylpropanal ; hydratropaldehyde ; 4 - methylbenzaldehyde ; 4 - methylphenylacetaldehyde ; 3 -( 4 - ethylphenyl )- 2 , 2 - dimethylpropanal ; 2 - methyl - 3 -( 4 - isopropylphenyl ) propanal ; 2 - methyl - 3 -( 4 - tert - butylphenyl ) propanal ; 3 -( 4 - tert - butylphenyl ) propanal ; cinnamaldehyde ; alpha - butylcinnamaldehyde ; alpha - amylcinnamaldehyde ; alpha - hexylcinnamaldehyde ; 3 - methyl - 5 - phenylpentanal ; 4 - methoxybenzaldehyde ; 4 - hydroxy - 3 - methoxybenzaldehyde ; 4 - hydroxy - 3 - ethoxybenzaldehyde ; 3 , 4 - methylened ioxybenzaldehyde ; 3 , 4 - dimethoxy - benzaldehyde ; 2 - methyl - 3 -( 4 - methoxyphenyl ) propanal ; 2 - methyl - 3 -( 4 - methylenedioxyphenyl ) propanal ; of aromatic and araliphatic ketones , such as , for example , acetophenone ; 4 - methylacetophenone ; 4 - methoxyacetophenone ; 4 - tert - butyl - 2 , 6 - dimethylacetophenone ; 4 - phenyl - 2 - butanone ; 4 -( 4 - hydroxyphenyl )- 2 - butanone ; 1 -( 2 - naphthalenyl ) ethanone ; benzophenone ; 1 , 1 , 2 , 3 , 3 , 6 - hexamethyl - 5 - indanyl methyl ketone ; 6 - tert - butyl - 1 , 1 - dimethyl - 4 - indanyl methyl ketone ; 1 -[ 2 , 3 - dihydro - 1 , 1 , 2 , 6 - tetramethyl - 3 -( 1 - methylethyl )- 1h - 5 - indenyl ] ethanone ; 5 ′, 6 ′, 7 ′, 8 ′- tetrahydro - 3 ′, 5 ′, 5 ′, 6 ′, 8 ′, 8 ′- hexamethyl - 2 - acetonaphthone ; of aromatic and araliphatic carboxylic acids and esters thereof , such as , for example , benzoic acid ; phenylacetic acid ; methyl benzoate ; ethyl benzoate ; hexyl benzoate ; benzyl benzoate ; methyl phenylacetate ; ethyl phenylacetate ; geranyl phenylacetate ; phenylethyl phenylacetate ; methyl cinnamate ; ethyl cinnamate ; benzyl cinnamate ; phenylethyl cinnamate ; cinnamyl cinnamate ; allyl phenoxyacetate ; methyl salicylate ; isoamyl salicylate ; hexyl salicylate ; cyclohexyl salicylate ; cis - 3 - hexenyl salicylate ; benzyl salicylate ; phenylethyl salicylate ; methyl 2 , 4 - dihydroxy - 3 , 6 - dimethylbenzoate ; ethyl 3 - phenylglycidate ; ethyl 3 - methyl - 3 - phenylglycidate ; of nitrogen - containing aromatic compounds , such as , for example , 2 , 4 , 6 - trinitro - 1 , 3 - dimethyl - 5 - tert - butylbenzene ; 3 , 5 - dinitro - 2 , 6 - dimethyl - 4 - tert - butylacetophenone ; cinnamonitrile ; 5 - phenyl - 3 - methyl - 2 - pentenenitrile ; 5 - phenyl - 3 - methylpentanenitrile ; methyl anthranilate ; methyl n - methylanthranilate ; schiff bases of methyl anthranilate with 7 - hydroxy - 3 , 7 - dimethyloctanal , 2 - methyl - 3 -( 4 - tert - butylphenyl ) propanal or 2 , 4 - dimethyl - 3 - cyclohexenecarbaldehyde ; 6 - isopropylquinoline ; 6 - isobutylquinoline ; 6 - sec - butylquinoline ; indole ; skatole ; 2 - methoxy - 3 - isopropylpyrazine ; 2 - isobutyl - 3 - methoxypyrazine ; of phenols , phenyl ethers and phenyl esters , such as , for example , estragole ; anethole ; eugenole ; eugenyl methyl ether ; isoeugenole ; isoeugenyl methyl ether ; thymol ; carvacrol ; diphenyl ether ; beta - naphthyl methyl ether ; beta - naphthyl ethyl ether ; beta - naphthyl isobutyl ether ; 1 , 4 - dimethoxybenzene ; eugenyl acetate ; 2 - methoxy - 4 - methylphenol ; 2 - ethoxy - 5 -( 1 - propenyl ) phenol ; p - cresyl phenylacetate ; of heterocyclic compounds , such as , for example , 2 , 5 - dimethyl - 4 - hydroxy - 2h - furan - 3 - one ; 2 - ethyl - 4 - hydroxy - 5 - methyl - 2h - furan - 3 - one ; 3 - hydroxy - 2 - methyl - 4h - pyran - 4 - one ; 2 - ethyl - 3 - hydroxy - 4h - pyran - 4 - one ; of lactones , such as , for example , 1 , 4 - octanolide ; 3 - methyl - 1 , 4 - octanolide ; 1 , 4 - nonanolide ; 1 , 4 - decanolide ; 8 - decen - 1 , 4 - olide ; 1 , 4 - undecanolide ; 1 , 4 - dodecanolide ; 1 , 5 - decanolide ; 1 , 5 - dodecanolide ; 1 , 15 - pentadecanolide ; cis - and trans - 11 - pentadecen - 1 , 15 - olide ; cis - and trans - 12 - pentadecen - 1 , 15 - olide ; 1 , 16 - hexadecanolide ; 9 - hexadecen - 1 , 16 - olide ; 10 - oxa - 1 , 16 - hexadecanolide ; 11 - oxa - 1 , 16 - hexadecanolide ; 12 - oxa - 1 , 16 - hexadecanolide ; ethylene 1 , 12 - dodecanedioate ; ethylene 1 , 13 - tridecanedioate ; coumarin ; 2 , 3 - dihydrocoumarin ; octahydrocoumarin . the preparation of the compounds according to the present invention is described for some compounds . for example , journal of am . chem . soc . 78 , 2622 ( 1956 ) describes the preparation of 3 , 3 , 6 - trimethylindan - 1 - one . this three - stage synthesis is overall unsatisfactory both with regard to the reaction conditions and also the yield ( 40 % of theory over three stages ). it has now been found that the preparation of 1 - indanones is possible in high yields by reacting ( 3 , 3 - alkyl - substituted ) acrylic acid ( 3 ) or esters thereof in a friedel - crafts reaction with ( alkyl -) benzenes ( 2 ), and subsequently cyclizing formed intermediate ( 4 ), polyphosphoric acid being the preferred catalyst for this cyclization . the preparation process according to the present invention can be illustrated by the following reaction scheme : the radicals r , r 1 , r 2 and r 3 can have the following meanings : r 1 is hydrogen , methyl , ethyl , n - propyl , isopropyl , n - butyl , isobutyl , r 2 , r 3 , independently of one another , are h , methyl , ethyl , n - propyl , isopropyl , n - butyl , sec - butyl , isobutyl . preferably , the radicals r , r 1 , r 2 and r 3 have the following meanings : r 2 , r 3 , independently of one another , are methyl , ethyl . more preferably , r = h and r 1 , r 2 and r 3 are all methyl . in the 1 st stage , i . e . the reaction of the ( alkyl -) benzenes ( 2 ) with the acrylic acid derivative ( 3 ), friedel - crafts catalysts are preferably used . the friedel - crafts catalysts which may be used are all catalysts customary for this type of reaction . metal halides , such as , for example , aluminum chloride , iron chloride or zinc chloride , are particularly suitable . aluminum chloride is more preferred . the friedel - crafts reaction can be carried out in a wide temperature range . the friedel - crafts reaction is advantageously carried out at temperatures in the range from − 20 to 100 ° c ., preferably in the range from − 10 to 50 ° c . and more preferably in the range from 0 to 25 ° c . the 1 st stage can be carried out in the presence of nonaromatic solvents , such as , for example , ethers ( e . g . methyl tert - butyl ether , tetrahydrofuran ), cyclic or acyclic hydrocarbons ( e . g . cyclohexane ). the 1 st stage is preferably carried out without a solvent . preference is given to an excess of ( alkyl -) benzene ( 2 ). the resulting intermediates ( 4 ) are of adequate purity to be reacted to give the end product ( 1 ). if required , purification can be carried out , for example by means of distillation . the 2 nd stage , i . e . the cyclization of the intermediate ( 4 ) to give the 6 - alkylindan - 1 - ones ( 1 ) according to the present invention , is preferably carried out in the presence of an acid and a water - binding agent . a preferred catalyst for the 2 nd stage is polyphosphoric acid . preferred amounts are 50 to 250 % by weight , based on substrate used , and preferred polyphosphoric acid contents are 110 - 120 %, based on molar equivalents of phosphoric acid . the cyclization can advantageously be carried out at temperatures in the range from 50 to 180 ° c ., preferably in the range from 80 to 150 ° c . and more preferably in the range from 100 to 130 ° c . 340 g ( 2 . 6 mol ) of aluminum chloride were stirred at room temperature into 300 g ( 3 . 26 mol ) of toluene and cooled to 0 ° c . a solution of 250 g ( 2 . 5 mol ) of 3 , 3 - dimethylacrylic acid in 400 g ( 4 . 34 mol ) of toluene was then metered in at 0 - 5 ° c . over the course of 1 h . when the metered addition was complete , the mixture was after - stirred for a further 10 min , added to 1000 g of dilute hydrochloric acid and extracted with methyl tert - butyl ether . distillation gave 370 g of product with a gc purity of 95 %. yield 77 % of theory . 730 g of polyphosphoric acid ( 115 % based on molar equivalents of phosphoric acid ) were initially introduced and heated to 120 ° c . 370 g ( 1 . 93 mol ) of tolylbutyric acid ( crude product from the 1 st stage , example 1a ) were then metered in over the course of 45 min , and the mixture was after - stirred at 120 ° c . for a further 3 h . the mixture was cooled to 60 ° c . and admixed with 900 g of iced water , extracted with methyl tert - butyl ether and then distilled . 320 g of 3 , 3 , 6 - trimethylindan - 1 - one product with a gc purity of 95 % were obtained . yield 95 % of theory . application examples [ 0072 ] table 2 parts by weight parts by weight name composition 1 composition 2 red berries extract 40 40 bergamot oil bergapten - free 80 80 cardamom absolute 25 25 cyclopentadecanolide ( 1 ) 190 190 cypress oil 5 5 eugenol 50 50 ginger oil synthetic 60 60 methyl dihydrojasmonate 100 100 iso e super ® ( 2 ) 200 200 amarocit ® ( 1 ) 50 50 muscone 50 50 clary sage oil 80 80 stemone ® ( 3 ) 10 10 vertocitral ® ( 1 ) 50 50 vetiver oil 10 10 3 , 3 , 6 - trimethylindan - 1 - one 1 — international flavors & amp ; fragrances , usa , new jersey , union beach givaudan , switzerland , geneva the addition of 3 , 3 , 6 - trimethylindan - 1 - one to perfume composition 1 brings about a significant intensification of the overall odor , with the leathery notes additionally being enhanced . in addition , the perfume composition adopts a significantly sharper character , which is particularly suitable for a man &# 39 ; s scent . [ 0076 ] table 3 parts by weight parts by weight name composition 3 composition 4 ambrarome abs . ® ( 4 ) 2 2 benzoin resin 100 100 bergamot oil bergapten - free 12 12 citral 5 5 civet tincture 10 % in dipropylene 20 20 glycol coumarin 19 19 indole 10 % in dipropylene glycol 5 5 isomethylionone 30 30 linalool 10 10 opoponax oil 5 5 patchouli oil 20 20 tolu balsam resin colourless 2 2 vanilla resin , decolourized , 50 50 10 % in dipropylene glycol 3 , 3 , 6 - trimethylindan - 1 - one 5 — the addition of 3 , 3 , 6 - trimethylindan - 1 - one to perfume composition 3 achieves a harmonization of the overall odor in this orientally floral perfume composition . the perfume composition smells more natural and was clearly preferred over perfume composition 4 in a preference test . [ 0079 ] table 4 parts by weight parts by weight name composition 5 composition 6 clary sage oil synthetic 100 100 davana oil 10 10 benzyl salicylate 100 100 undecavertol ® ( 3 ) 5 5 iris oil synthetic 5 5 irone 2 2 coumarin 80 80 nectarol ® ( 5 ) 2 2 cedarwood oil florida 100 100 andrane ® ( 2 ) 100 100 sclareolide 10 10 ambroxide ( 1 ) 5 5 isomeric mixture of equal parts of 200 — 3 , 3 , 4 -, 3 , 3 , 5 -, 3 , 3 , 6 - and 3 , 3 , 7 - trimethylindan - 1 - one international flavors & amp ; fragrances , usa , new jersey , union beach givaudan , switzerland , geneva the perfume composition 5 has a significantly more intensive odor in which the leathery labdanum note plays a harmonious part in the odor picture . in the case of perfume composition 6 , which has a weaker odor overall , the leathery note is significantly lesser . the perfume composition is clearly more suitable for the perfuming of a care range for men . perfume compositions 1 and 2 were separately incorporated , in an amount in each case of 1 % by weight , into the shampoo formulation given below ( table 5 ), and the shampoo was used to wash hair . the odor evaluation was then carried out by a group of experts on the shampoo composition , the dilute aqueous solution in the hair , the wet rinsed hair and the dry hair . the addition of 3 , 3 , 6 - trimethylindan - 1 - one gives the perfume composition 1 an excellent rounded leather note compared to perfume composition 2 in all evaluation stages for the shampoo . the leathery odor is significantly perceptible particularly on wet and dry hair , and it clearly represents an improvement in the perfume composition . perfume compositions 5 and 6 were incorporated separately , in each case in an amount of 0 . 4 % by weight , into a detergent formulation ( table 6 ). the odor from the powder , of the aqueous solution , of the damp and of the dry laundry was assessed by a group of experts . it was found that perfume composition 5 was generally more preferred and produced a more harmonious scent by virtue of the woody and leathery notes . on the damp and dry laundry , in particular , a significantly more intensive and typical leathery odor was perceived for perfume composition 5 compared with composition 6 . although the invention has been described in detail in the foregoing for the purpose of illustration , it is to be understood that such detail is solely for that purpose and that variations can be made therein by those skilled in the art without departing from the spirit and scope of the invention except as it may be limited by the claims . | the invention relates to the use of 6 - alkylindan - 1 - ones as fragrances , to a process for their preparation , to fragrance mixtures comprising 6 - alkylindan - 1 - ones , and to perfumed products comprising 6 - alkylindan - 1 - ones . |
an improved collar apparatus 4 in accordance with the disclosed and claimed concept is depicted generally in fig1 and 2 . the collar apparatus 4 can to include a collar body 8 and a closure 12 that are connected together in any of a variety of fashions . the collar body 8 is an elongated and flexible belt - like body that is formed of a polymeric material that is photoluminescent . the closure 12 in the depicted exemplary embodiment is a buckle - type closure that includes a buckle 16 having a tang 20 that is mounted to an end of the collar body 8 . the collar body 8 includes a hole 24 formed therein near an end opposite the buckle 16 that is configured to receive the tang 20 therein to place the collar apparatus 4 in a closed condition such as is depicted generally in fig2 . the collar apparatus 4 in the closed condition of fig2 is arranged to have a generally closed loop that receives an animal &# 39 ; s neck therein . the tang 20 is removable from the hole 24 to return the collar apparatus 4 to an open condition wherein the collar body 8 does not form a part of a closed loop . however , it is noted that the closure 12 can be any suitable closure . in one embodiment , as shown in fig3 , the collar body 8 is formed by placing uncured polymeric materials into a mold 28 and by then performing an appropriate curing operation on the polymeric materials to cause the materials to reach a cured state . the collar body 8 can then be removed from the mold 28 and can have the closure 12 attached thereto . the mold 28 is depicted in fig3 as having a cavity 32 that receives uncured polymeric material 44 from a first tap 36 and that receives other uncured polymeric material 48 from a second tap 40 . in the depicted exemplary embodiment , the uncured polymeric material 44 includes a photoluminescent component whereas the uncured polymeric material 48 does not include a photoluminescent component . the result of using two different polymeric materials , one being photoluminescent and the other not being photoluminescent , will result in the collar body 8 having some type of pattern of photoluminescence and non - photoluminescence that may be selected based on various aesthetic and / or functional purposes . for example , the two uncured polymeric materials 44 and 48 can be placed in a camouflage - like arrangement to provide a glow - in - the - dark functionality that appears camouflage - like . alternatively , the uncured material 44 having the photoluminescent component may be applied in a chevron - like pattern in combination with the uncured polymeric material 48 to result in glow - in - the - dark chevron being formed in the collar body . it is understood that the uncured polymeric materials 44 and 48 can be applied in virtually any fashion to the cavity 32 to result in desirable designs , and it is further noted that the first and second taps 36 and 40 are merely exemplary in both nature and quantity and potentially can be robotically controlled to generate repeatable designs . it is further noted that the use of multiple uncured polymeric materials is unnecessary , and rather is expressly noted that the entirety of the collar body 8 can be formed of the same polymeric material having a luminescent component . in use , the collar apparatus 4 and , more particularly , the collar body 8 , is subjected to electromagnetic radiation such as is visible light . such visible light will cause photoexcitation of the photoluminescent component of the polymeric material that is used to form the collar body 8 . such photoexcitation causes the photoluminescent component and thus the collar body 8 itself to emit visible light via photoluminescence . in so doing , it may be necessary to remove the collar apparatus 4 from the animal in order to fully expose the collar body 8 to the electromagnetic radiation , although this need not be the case depending upon the excitation light that is available . the photoexcitation of the photoluminescent collar body 8 can be refreshed or recharged with the use of street lights , house lights , flashlights , and the like without limitation . the improved collar apparatus 4 thus emits visible light via photoluminescence and increases the visibility of the animal to drivers and others , all of which is highly desirable . in one embodiment , photoluminescent component 34 can be thermoplastic rubber ( tpr ), in which a portion of the collar apparatus 4 is made . for example , portions of the collar body 8 and / or the closure 12 can be formed from the photoluminescent component . accordingly , in one embodiment , the closure 12 or portions of the closure 12 are molded using a photoluminescent component 34 . that is , thermoplastic material ( or other suitable material ) is formed or infused with a photoluminescent component prior to the molding or form process . in another embodiment , the photoluminescent component 34 is added to the collar body 8 and / or the closure 12 after the molding process or forming process . it is noted that any suitable photoluminescent component 34 can be disposed on the collar body 8 and / or the closure 12 , including but not limited to glow in the dark tape , glow in the dark paint and any other suitable glow in the dark material . moreover , the photoluminescent component 34 can be disposed on a suitable portion of the collar body 8 and / or the closure 12 , and can include the entire collar body 8 and the closure 12 . additionally , the photoluminescent component 34 can be in various decorative configurations . for example , the photoluminescent component 34 can be in a web shaped configuration , a plurality of circles or other shapes or in any suitable configuration . the photoluminescent component 34 can be the actual design ( e . g ., circles ) or is can be inverse of the design ( e . g ., the background on which the circles are disposed ). further , the photoluminescent component 34 can be solid or in any suitable design . accordingly , the collar described herein increases safety at night due to increased visibility . for example , when an animal is on a leash or simply out at night without a leash , the photoluminescent component will enable higher visibility of the animal to increase the safety of the animal and / or a person walking the animal . while only selected embodiments have been chosen to illustrate the present invention , it will be apparent to those skilled in the art from this disclosure that various changes and modifications can be made herein without departing from the scope of the invention as defined in the appended claims . for example , the size , shape , location or orientation of the various components can be changed as needed and / or desired . components that are shown directly connected or contacting each other can have intermediate structures disposed between them . the functions of one element can be performed by two , and vice versa . the structures and functions of one embodiment can be adopted in another embodiment . it is not necessary for all advantages to be present in a particular embodiment at the same time . every feature which is unique from the prior art , alone or in combination with other features , also should be considered a separate description of further inventions by the applicant , including the structural and / or functional concepts embodied by such features . thus , the foregoing descriptions of the embodiments according to the present invention are provided for illustration only , and not for the purpose of limiting the invention as defined by the appended claims and their equivalents . | a collar apparatus includes a flexible collar body configured to be removably disposed about around a neck of an animal when first and second ends are adjacent each other , and including a photoluminescent component , and a closure situated on the collar body and operable to move the collar body between a closed condition wherein the collar body and the closure form a closed loop and an open state wherein the collar body and the closure do not form a closed loop . |
with reference to the accompanying drawings wherein like elements are designated by like numerals , fig1 illustrates a presently preferred embodiment of the self - feeder of this invention , which is generally designated by the numeral 10 . the self - feeder 10 consists of two main assemblies : the feeding arm assembly 12 and the base assembly 14 . the feeding arm assembly includes an upright support in the form of a vertical tube 16 , a cross arm 18 and a spoon holder assembly 20 . the base assembly includes a base plate 22 which rests on four equal feet 24 of slip - resistant material . the base 22 has a top surface 26 on which is supported a turntable assembly 30 , which includes a slide plate 32 , a slide plate fastener 34 , and a turntable 36 . the base assembly also includes a base post 38 with a mounting flange 42 fastened to the base plate 22 by two screws 44 . a food bowl 25 is supported on turntable 36 . the feeding arm assembly 12 is assembled to the base assembly 14 by a telescoping sliding fit of the vertical tube 16 onto the base post 38 , as best understood from fig2 and 3 . tube 16 is freely rotatable about base post 38 , that is , about the vertical center axis of the base post . rotation of tube 16 is limited , however , by a base flange 46 fixed as by welding to the lower end of tube 16 . base flange 46 has two opposite right and left contact edges 46 a , 46 b each of which contacts a corresponding right and left stop lug 48 a , 48 b fastened to the base plate by screws 44 , as shown in fig5 . the stop lugs are of elongated shape and can be turned about the corresponding screw 44 to provide an adjustable stop for limiting the arc of rotation h of the vertical tube 16 about the base post 38 in either sense of rotation indicated by arrow a in fig1 . the cross arm 18 is a straight beam of rectangular cross sectional shape which includes a top 50 a and two opposite side walls 50 b , 50 c . a first pivot shaft 52 supported between side walls 50 b , c pivots the cross arm 18 for oscillation in a vertical plane to the upper end of the vertical tube 16 by way of a supporting elbow 54 . the lower end of elbow 54 is welded to the tube 16 close to the upper end of the tube . pivot shaft 52 passes through a lower hole 54 a in elbow 54 , as indicated in fig3 and pivotably supports the arm 18 in radially spaced relationship to the center axis of tube 16 . as shown in fig2 the vertical tube 16 contains a damped spring assembly 60 , which as best seen in fig3 includes a damper cylinder 62 and a coil spring 64 , both cooperating to urge a piston rod 66 toward extension from the cylinder 62 at a controlled rate . an end block 68 is threaded to the end 68 a of the piston rod , and the coil spring is compressed between the end block and the cylinder 62 . the end block has a screw hole 68 b which aligns with hole 72 in vertical tube 16 to receive screw 74 . screw 74 supports the spring within tube 16 in spaced relationship above the base post 38 , as best understood by reference to fig2 . the damper cylinder 62 is a one way damper which has a controlled rate of extension of the damper piston rod 66 such that the damper works to control the rate of upward movement of the cross arm under the urging of the coil spring 64 . the damper cylinder is a commercially available unit and has at its top end a threaded shaft 63 . a coupling 65 is threaded onto shaft 63 . a spring transfer arm 67 has a lower end pivoted at 69 to the top of coupling 65 . the upper end of the spring transfer arm is pivoted by pivot shaft 76 to the cross arm 18 approximately along the center axis of tube 16 . the damped spring assembly 60 is compressed between the cross arm 18 and the vertical tube 16 and operates to apply a continuous upward spring bias to the cross arm along a vector approximately aligned with the center axis of tube 16 . this spring bias vector is spaced along cross arm 18 from the first pivot shaft 52 and consequently acts to raise the free end 75 of cross arm 18 towards a maximum elevation determined by an adjustable elevation stop 55 on elbow 54 . elevation stop 55 includes a detent tab 57 slidable along the upright arm of elbow 54 and fixed to the elbow at an adjustable position by means of set screw 59 . the upper edge 53 of detent tab 57 contacts the underside of cross arm 18 to stop downward movement of the cross arm end 73 corresponding to upward movement of the opposite free end 75 of the cross arm . as a result , lowering of detent tab 57 along elbow 54 results in an increase in maximum height of the free end 75 under the urging of spring assembly 60 . conversely , maximum elevation of the cross arm is reduced by raising the position of detent tab 57 on elbow 54 . the spoon holder assembly 20 includes an upper portion or arm 80 pivoted to arm 18 by third pivot shaft 82 supported in holes 82 a in side walls 50 c of the cross arm , and passing through lower hole 82 b in arm 80 of the spoon holder assembly . the upper end of arm 80 is connected by way of cross linkage 84 to the upper end of elbow 54 , by means of pivots 86 a , 86 b respectively . the four pivots 52 , 86 b , 86 a and 82 define a parallelogram arrangement which operates to keep the upper portion 80 of the spoon holder assembly in a constant attitude , e . g . a vertical relationship , to the base 22 during pivotal movement of the cross arm 18 in the vertical plane . turning to fig4 spoon holder assembly 20 also includes a lower portion 88 which is dependent from the upper portion 80 and pivoted at 90 for oscillation in the same vertical plane as the cross arm 18 . oscillation of lower portion 88 is limited , in a clockwise sense , by stop pin 92 which is located so as to stop the lower portion 88 in vertical alignment with the upper portion 80 by contact of pin 92 with the inside edge 94 of the upper portion 80 . counterclockwise oscillation of lower portion 88 is limited by adjustable detent 96 which is displaceable along upper portion 80 and set in a selected position therealong by tightening set screw 98 . the lower portion tends to return under its own weight to a normal condition limited by pin 92 , and must be manually lifted to an elevated or tilted condition such as depicted in fig4 . lifting of the lower portion 88 as suggested by arrow d is aided by handle 100 which has a handle knob 102 and a handle shaft 104 fitted into a handle bore 106 of lower portion 88 and retained in the handle bore by spoon screw 108 . a spoon 110 is removably secured to the underside of lower portion 88 also by spoon screw 108 . the flat spoon handle 109 is captured between the head 112 of screw 108 and the underside of lower portion 88 , with the longitudinal dimension of the spoon transversely to the cross arm 18 , either on the left or the right hand side of the cross arm . for this purpose the spoon handle may have a short slot 113 sized to receive the threaded shaft of screw 108 . the spoon can therefore be easily detached from the feeder for washing or replacement with a different sized spoon simply by loosening the screw 108 . the spoon screw holds the spoon with the bowl 115 of the spoon level when the lower portion 88 of the spoon holder is in its normal lowered position . as earlier explained , the lower portion 88 drops to the lower position under its own weight , so that the spoon attached to the lower portion 88 is self leveling relative to the upper portion 80 of the spoon holder . the upper portion 80 , as also explained , is kept in a vertical condition at all times independently of vertical cross arm movement . the net result of both these actions is that the spoon remains level for any position of the cross arm unless the spoon is deliberately lifted to an inclined condition by the user in the course of self - feeding . turning to fig1 and 2 , the circular turntable 36 is mounted for - free rotation on a slide plate 32 . the slide plate has a slot 114 through which extends a threaded shaft 116 fixed to the base 22 , as suggested in phantom lining in fig2 . a slide plate fastener knob 34 screws onto the upper end of threaded shaft 116 and can be tightened against the slide plate 32 so as to press the slide plate against the base 22 and thus capture and lock by frictional engagement the slide plate against displacement relative to the base 22 . in a normal , tightened condition of fastener 34 the slide plate 32 and consequently the turntable 36 are fixed on the base 22 . however , the position of the turntable relative to the spoon can be adjusted by loosening fastener 34 , which allows the slide plate to be displaced towards or away from the vertical tube 16 along the slot 114 , and also by rotation of the plate 32 about the shaft 116 so as to move the turntable and consequently the food bowl 25 across the base 22 transversely to the cross arm 18 , thereby to optimally position the turntable for a given food bowl size and to suit the preferences of the user . the top surface 35 of the turntable 36 is covered with a sheet of material selected to resist slippage of the food bowl 25 across the turntable . furthermore , the turntable has a relatively high rim 37 to ensure that the food bowl 25 is not pushed off the turntable during self - feeding . the various features described in this paragraph allow interchangeable use of different food bowls to suit the user &# 39 ; s preferences or the particular food being served , and to adapt to use of existing institutional food bowls , so that the self - feeder is not restricted to custom food bowls . for self - feeding use the user is seated at a table or other surface with the feeder 10 placed on the supporting surface directly in front of the user and the cross arm extending left to right in front of the user . the vertical tube 16 is positioned to the left of a right - handed user or on the right hand side of a left handed user to facilitate access by the user &# 39 ; s dominant hand to the spoon holder 20 . the spoon 110 is attached to the lower portion 88 of the spoon holder assembly 20 accordingly , i . e ., extending from the cross arm 18 towards the user regardless of the left or right hand placement of the self - feeder 10 relative to the user . the self - feeder 10 is readily adapted to either right or left hand use simply by reversing the position of the spoon on the spoon holder from one side to the other of the cross arm 18 by loosening spoon screw 108 , turning the spoon about the screw shaft , and tightening the screw . the height adjustment 55 is preset so that the spoon rises to the level of the user &# 39 ; s mouth when the cross arm is released . the two stop lugs 48 a , 48 b are set to prevent the cross arm from swinging further away from the user than is necessary to adequately reach all parts of the food bowl with the spoon , yet allow the cross arm to swing towards the user so as to bring the spoon within comfortable reach of the user &# 39 ; s mouth . the settings of the right and left stop lugs 48 a , 48 b are therefore dependent , among other factors , on whether the self - feeder is being set - up for right or left handed use . in an initial before - use position of the feeder 10 the cross arm 18 will be elevated to the preset maximum height , as depicted in fig2 . a bowl or plate 25 containing a serving or portion of food f is placed on the turntable surface 37 generally underneath - the spoon 110 , as illustrated in fig1 . the user will push down on either on the cross arm 18 or handle 100 to depress the free end 75 while at the same time rotating the cross arm towards or away from him or her self , so as to position the spoon 110 for dipping into the food serving f . the bowl of the spoon 110 is loaded with food by lifting the spoon to a tilted position as shown in fig1 by lifting the handle 100 , and maneuvering the cross arm both in the vertical and the horizontal plane so as to bring the bowl of the spoon into contact with food serving f . the spoon is then lowered through an arc c in fig1 as by pushing down on the handle 100 , to dip the spoon bowl into the food f until the spoon bowl 115 reaches a level position corresponding to a vertical condition of the lower portion 88 of the spoon holder , that is , a condition where further depression of the handle 100 is stopped by detent pin 92 . at this point , the spoon bowl 115 can be lifted from the food serving f , now loaded with a spoonful of food , by releasing the cross arm 18 which then rises away from the food bowl 25 under the upward urging of the spring assembly 60 . the action of the coil spring 64 is damped by the damper cylinder 62 to ensure a relatively slow and steady vertical movement of the cross arm 18 , both up under the urging of spring assembly 60 as well as down under the pressure of the user &# 39 ; s hand . the user typically operates the cross arm 18 and handle 100 with his dominant hand , and may hold onto vertical tube 16 with his or her other hand to further stabilize the self - feeder . alternatively , the dominant hand may operate handle 100 to lower the cross arm and to load food onto the spoon , and the other hand used to swing the cross arm towards and away from the user . as the cross arm rises under spring bias the weight of the spoon keeps the lower portion 88 of the spoon holder in lowered position and the spoon level , as previously explained and shown in fig2 and 3 . the cross arm 18 rises to its maximum preset elevation with the spoon bowl 115 aiming towards the user , who can then bring the spoon bowl 115 towards his or her mouth by swinging the cross arm 18 in a horizontal plane , that is , by turning the cross arm with vertical tube 16 about the base post 38 , into sufficient proximity where the user can comfortably take the bowl of the spoon with the spoonful of food into his or her mouth . once the user has transferred the spoonful of food from the spoon bowl to his or her mouth , the empty spoon is again loaded with another spoonful of food by repeating the aforementioned sequence of steps . it will be appreciated that the self - feeder disclosed above offers three separate degrees of movement of the spoon available to the user ; a ) rotation of the cross - arm about a vertical axis permits horizontal swinging of the cross arm b ) pivotal movement of the cross arm in the vertical plane allows the cross arm to swing up or down vertically , and c ) oscillation of the spoon relative to the cross arm in a direction transverse to both the vertical swing and horizontal swing of the cross arm . these three degrees of freedom , indicated in fig1 by arrows a , b and c respectively , facilitate the self - feeding process . the damped vertical movement of the cross - arm 18 of the self - feeder 10 compensates in large measure for tremors or poor muscular control of the upper extremities , while the upward bias of the cross arm lifts the spoon to a safe height if the user is unable to hold it and lets go of the cross arm during feeding , thereby preventing dropped spoons and spilled food which would likely result if the handicapped user attempted to feed himself or herself in a conventional manner by handholding the spoon without mechanical assistance . while a preferred embodiment of the invention has been shown and illustrated for purposes of clarity and illustration , it must be understood that many changes , substitutions and modifications to the described embodiment will be apparent to those having only ordinary skill in the art , and that the scope of the invention is limited only by the scope of the following claims . | a feeding device for use by persons with limited or no use of their arms , wherein a spoon is mounted on supporting and counterbalancing levers and is associated with a mouth - piece in such a manner that the user can manipulate the spoon to lift food from a dish , can then place the spoon on a fixed support and then adjust the spoon to a position for convenient eating of the food . the spoon mounting includes an adjustable support for a counterbalancing spring . all the parts are mounted on a flat base which is adapted also to support the food dish . |
while this invention is susceptible of embodiments in many different forms , there is shown in the drawings and will herein be described in detail a preferred embodiment of the invention with the understanding that the present disclosure is to be considered as an exemplification of the principles of the invention and is not intended to limit the broad aspect of the invention to embodiments illustrated . as shown in the multiple images of fig1 a through 10k , one use of the pillow is to support neck curvature . maintaining a healthy cervical curvature becomes more important as one gets older . the degeneration of neck curvature occurs more from front to back of the cervical spine compared to the side . current pillows are made to support the c - curvature of the user &# 39 ; s neck while they sleep on their backs , and to maintain the straight alignment of the neck on their side . however , some users sleep on their stomach and cannot change their sleeping posture due to habit . therefore , other pillows can become useless for stomach sleepers . the pillow disclosed herein can be beneficial for users who sleep on their back , side and stomach because it allows for them to receive proper neck support to help them maintain their healthy , c - curvature . the disclosed support systems are designed to maintain the cervical spine for users who have different stages of degeneration . this is made possible by controlling the height of the support surface through attachable supporting panels under the head part . the pillow disclosed herein can be used for neck strengthening exercises while properly supporting their neck curvature . exercises are done with the user laying on a base , such as a table , bed or floor , to stabilize the upper trunk which omits the compensation of upper trunk muscles . stabilizing the upper trunk allows for a more focused exercise of the neck , or other body area , without the necessity of using the upper trunk muscles . while the figures and descriptions are almost exclusively directed to a neck exercise device , it should be understood that the device is also suitable for support during exercise of other body parts , including the lower back and knees . those skilled in the art would fully understand the applicability of the systems to these additional uses from the disclosure provided herein . referring to fig1 - 10 , there is illustrated two embodiments of the exercise support system , generally referenced herein by the number 10 . the first support system 10 is comprised of two distinct bodies , a first body 12 and at least one elevating panel 14 . the second support device system 110 adds a third component , an insertable body portion 16 to allow adjustments to the support . together these two and three body systems , 10 and 110 , are capable of multiple configurations , as will be explained in greater detail below . with respect to the embodiment of fig1 - 5 , a system 10 for supporting a user &# 39 ; s neck ( or other body area ) during exercise is illustrated . the first body 12 preferably has a truncated hemispherical cylinder shape and is comprised of a foamed material , such as a polyurethane . the material used to form the first body 12 should have a consistent density throughout . the first body 12 has a contoured contact surface 20 and a flat bottom or base surface 22 . as shown , the bottom or base surface 22 of the first body 12 includes a cavity , orifice or depression 24 that is constructed and arranged to make the first body 12 more pliable or less stiff as a user puts his or her neck on the pillow comfortably . that is , as a user adds weight to the pillow , the general shape of the space in the cavity 24 will change as the pillow is compressed , and the cavity 24 fills with the upper portion 26 . preferably , the cavity 24 is centered at the base surface 22 and has a depth to the approximate center mass of the first body 12 . however , other locations of the cavity 12 may be possible to produce similar results . as to the elevating panels 14 , these “ bodies ” are used to elevate the first body 12 into a sufficiently supportive configuration . a plurality of elevating panels 14 having substantially identical thicknesses are preferably used to allow incremental increases of the height of the first body 12 . for example , if each elevating panel 14 is only one - inch thick , a total of four panels would be necessary to allow the first body 12 to be raised to four inches by one inch increments , i . e ., one - inch elevated , two - inches elevated , three - inches elevated , and four - inches elevated . however , panels of differing thicknesses ( not shown ) may be used as well . for example , providing just three panels , i . e ., a one - inch panel , a two - inch panel , and a three - inch panel , would allow the first body 12 to be raised one - inch , two - inches , three - inches , four - inches ( 1 ″+ 3 ″ panels ), five - inches ( 2 ″+ 3 ″ panels ) or even six - inches ( 1 ″+ 2 ″+ 3 ″ panels ). further , the elevating panels 14 are also preferably made of a polyurethane foam , but may be constructed of other suitable materials . the elevating panels 14 are preferably rectangular , which is useful for supporting a patient &# 39 ; s head , neck or knee . however , as shown in fig5 , the elevating portions may be semi - elliptical for use in supporting a patient &# 39 ; s lower back during exercise . a second embodiment of the system 110 is illustrated in fig6 - 9 . in this embodiment , system 110 includes the first body 112 and the elevating panels 114 , but also includes insertable body portions 16 . as a means for adjusting the overall density of the first body 112 , the user can add the insertable body portions 16 into the cavity 124 of the head portion . the insertable portions 16 are designed to fit snuggly into the cavity 124 . preferably , the insertable portion 16 will generally be tubular , cylindrical or have a shape which allows it to fit snuggly in the defined cavity 124 . insertable portions 16 are preferably made of polyurethane foam , or other similar material . in an embodiment of the inventive system 10 , there are a plurality of insertable portions 16 , each having a different density . such a system 10 allows multiple adjustments to the overall density of the first body 12 by adding one of the various insertable body portions 16 into the cavity 124 . further , to allow quick identification of the different insertable portions 16 , each may be coded , by a color ( e . g ., red , orange , green , yellow ), a number ( e . g ., 1 , 2 , 3 , . . . ), a letter ( e . g ., a , b , c , . . . ), or a similar identifiers which might represent various degrees of increasing density or hardness . in other variations of the disclosed embodiments , the first body 12 ( or 112 ) may be made using vinyl or other fabric that is filled with buckwheat or other similar materials . preferred embodiments made using a fabric filled with particulate materials would still contain a cavity 24 in the base surface 22 of the first body 12 . additionally , embodiments may also include a cover 30 for the first body 12 ( or 112 ). the cover 30 may be made from vinyl or various types of fabric to keep the first body 12 clean and in place . the cover 30 , if used , may be fastened around the first body 12 using any known means , including hook - and - loop fasteners ( e . g ., velcro ® brand products ), magnets , zippers or snap fasteners . use of fasteners will help keep the contents within the pillow in place . the cover 30 can be bound tightly or loosely , depending on a user &# 39 ; s neck size for example . if the user has a shorter neck , the fastener of the cover 30 may be tightly fastened to compress and reduce the size of the first body 12 within it . if the user has a longer neck , the fastener can be loosely fastened so that it does not compress the first body 12 as much . in some embodiments , the first body 12 may be spray coated with a vinyl based coating to serve as a cover . as for the height adjustment or elevating panels 14 , the system 10 should include at least one or more to increase the ability for use on several different patients or body areas . the panels 14 may be made from the same material as the head portion , or other materials can be substituted to increase or decrease rigidity . in some embodiments , the elevating panels 14 may be fastened to the first body 12 and to other panels 14 using hook - and - loop fasteners ( e . g ., velcro ® brand products ), although other means known in the art , such as snap fasteners , may be used . the elevating panels 14 may also be fastened to the first body 12 and other panels using magnets to make it easier to align the components . magnets can be adhered to the panels 14 and first body 12 , as needed . much like the first body 12 , the elevating panels 14 may have a vinyl cover , or other various type of fabric cover to ensure that the magnets will stay in place . the matter set forth in the foregoing description and accompanying drawings is offered by way of illustration only and not as a limitation . while particular embodiments have been shown and described , it will be apparent to those skilled in the art that changes and modifications may be made without departing from the broader aspects of applicants &# 39 ; contribution . the actual scope of the protection sought is intended to be defined in the following claims when viewed in their proper perspective based on the prior art . | a therapeutic exercise support system for patients helps stabilize a body area , such as a neck , lower back or knee , during exercise . the systems and methods include a first body formed of a compressible material , the body having a substantially rounded support surface , a base surface and a cavity formed therein , the cavity being accessible from a surface of the body . the open cavity allows the density of the first body to be raised to suit different needs . additionally , at least one insertable second body formed of a compressible material and formed to fit within the cavity of the first body , as well as at least one elevating panel formed of a compressible material having a density and attachable to the base surface of the first body to thereby raise a height of the rounded support surface of the first body from a base structure , may be included . |
fig1 shows an exemplary embodiment of a sealing system 1 for sealing between an inner pipe and an outer pipe of a telescoping vacuum cleaner suction pipe p ( an end portion of which is shown in phantom outline ). the sealing system 1 comprises an annular base body 2 , the base body 2 being produced from a first material . the sealing system 1 also comprises an annular sealing body 3 which is located on the base body 2 , the sealing body 3 being produced from a second material . the first material and the second material are different materials which however can originate from the same material super group . the sealing body 3 is located on the base body 2 so that the base body 2 and the sealing body 3 form a unit , specifically the sealing system 1 . the sealing body 3 extends partially on an outer periphery of the base body 2 . both the base body 2 and also the sealing body 3 have an annularly closed contour . the base body 2 on its inner periphery has an inner shoulder 4 so that the sealing system 1 can be slipped onto an inner pipe ( in the direction from the left according to fig1 ). until its end face fits on a stop 5 . the stop 5 results from a shoulder 6 which is made in the outer periphery of the base body 2 and also forms the inner should 4 on the opposite side of stop 5 . the sealing body 3 is located on the shoulder 6 so that the sealing body 3 is located on an outer periphery of the base body 2 . the shoulder 6 constitutes an offset inward relative to the surface of the remaining outer periphery of the base body 2 . the shoulder 6 is arranged here such that it is located in the end region of the base body 2 facing away from the inner pipe in the mounted state . fig2 shows the exemplary embodiment according to fig1 in a perspective view . the sealing system 1 with its base body 2 with the shoulder 4 can be slipped onto an inner pipe until an end surface of the inner pipe fits on the stop 5 . for fixing of the inner pipe , on the shoulder 4 there are catch projections 7 which lock to a recess in the inner pipe in the mounted state . fig3 shows another exemplary embodiment of a sealing system 1 in a cutaway side view . in the outer periphery of the base body 2 , there is a groove 8 , a sealing body 3 being located in the groove 8 . the groove 8 is made to run peripherally in a ring - shape in an outer periphery of the base body 2 . the sealing body 3 in this exemplary embodiment is located as a separate component on the base body 2 , specifically as a separate sealing body 3 — made as a gasket — it is inserted into the groove 8 of the base body 2 and held by form - fit by the flanks of the groove 8 . the sealing body 3 has a sealing surface 9 . the sealing surface 9 in the mounted state of the sealing system 1 flatly adjoins the inner periphery of the outer pipe , forming a seal , and seals the annular gap which arises between the inner pipe and the outer pipe . the sealing body 3 according to fig3 has an essentially rectangular cross section , as a result of which advantageously the sealing surface 9 arises from the width of the sealing body 3 . the width of the sealing body 3 and the width of the sealing surface 9 in this exemplary embodiment correspond roughly to one third of the width of the base body 2 . the height of the sealing body 3 corresponds roughly to half its width . fig4 shows the exemplary embodiment according to fig3 in a perspective view . an inner pipe can be locked with the catch projections 7 and can be inserted into the shoulder 4 in the inner periphery of the base body 2 of the sealing system 1 . the outer contour of the sealing body 3 with its sealing surface 9 is roughly 0 . 2 mm larger than the inner contour of the outer pipe so that in the mounted state the material of the sealing body 3 , especially specifically the sealing surface 9 , is forced away to the left and right by the contact of the outer pipe , as a result of which reliable sealing arises . the outer periphery of the base body 2 which remains next to the groove 8 is used as a spacer and for stabilization between the inner pipe and the outer pipe . fig5 shows another exemplary embodiment of a sealing system 1 in a cutaway side view . in the shoulder 6 of the base body 2 there is a sealing body 3 which has a flexible sealing lip 10 . the flexible sealing lip 10 is sloped in the direction of the base body 2 proceeding from the end region which is shown at the right in fig5 and in the radial direction has a decreasing material thickness . additionally , as also shown in fig5 , the sealing body 3 projects axially beyond the base body 2 so as to form an axial end of the sealing system . the outer contour of the sealing body 3 , especially specifically the sealing lip 10 , also running peripherally in this exemplary embodiment , is roughly 0 . 2 mm larger than the inner contour of the outer pipe so that the sealing lip 10 is pressed to the inside by the inner contour of the outer pipe in the mounted state , as a result of which the sealing lip 10 flexibly adjoins the inner contour of the outer pipe and implements reliable sealing . the base body 2 is produced as polyethylene in this exemplary embodiment , while the sealing lip is produced from a rubber . fig6 shows the exemplary embodiment according to fig5 in a perspective view . this sealing system 1 with its shoulder 4 in the inner periphery of the base body 2 can also be slipped onto an inner pipe so that the inner pipe is pushed into the base body 2 until it reaches the stop 5 and is locked with the catch projections 7 . the sealing lip 10 from an end region in the direction of the base body 2 . the base body 2 has an essentially round shape . the exemplary embodiment according to fig1 & amp ; 2 also has a flexible sealing lip 10 which is located at an angle of 90 ° relative to the bottom of the shoulder 6 or to the outer surface of the base body . the sealing lip 10 tapers in the radial direction — the material thickness decreases continuously , as a result of which advantageous flexibility is achieved . on the side facing away from the base body 2 the sealing lip 10 has a slope which causes the reduction of the material thickness . the outer contour of the sealing body 2 , especially specifically the sealing lip 10 , is roughly 0 . 2 mm larger than the inner contour of the outer pipe so that the sealing lip 10 in the mounted state placed in the outer pipe yields flexibly , preferably in the direction of the base body 2 . | a sealing system for sealing between an inner pipe and an outer pipe of a telescoping vacuum cleaner suction pipe , which ensures maximum possible sealing with simultaneously simple operator controllability of the vacuum cleaner suction pipe , has at least one annular base body of a first material and an annular sealing body of a second material on the base body . |
referring to fig1 - 6 , a tillage apparatus of the present invention is depicted in various configurations . fig1 a and fig1 b depict one embodiment of tillage apparatus 1 of the present invention comprising frame 10 having a plurality of transverse frame - members 11 ( only one labeled ) and longitudinal frame - members 12 ( only one labeled ). the frame includes drawbar 13 extending from the front and hitch 14 at the end of the drawbar for connecting the apparatus to a vehicle . the apparatus rides on eight wheels 20 ( only two labeled ). mounted on the frame are a plurality of secondary tillage tools including a plurality of rolling harrows 15 ( only one labeled ) in one transverse row at the rear of the apparatus , a plurality of tine harrows 16 ( only one labeled ) in three transverse rows just forward the rolling harrows , and a plurality of coulter wheels 17 ( only one labeled ) mounted on the frame by flexible coil elements and arranged in a plurality of transverse rows . the coulter wheels in adjacent rows are staggered ( offset ) so that they do not follow the same longitudinal lines when the apparatus is dragged through a field . also mounted on the frame are three transverse rows of selectively moveable primary tillage shanks having chisel plows mounted thereon . a front row comprises eleven primary tillage shanks 25 ( only one labeled ). a rear row comprises eight primary tillage shanks 27 ( only one labeled ) staggered ( offset ) from the first row of shanks . and , a middle row comprises four primary tillage shanks 26 ( only one labeled ), which make - up for a lack of space in the rear row . the primary tillage shanks are moveable between a lowered soil engaging position and a raised disengaged position by hydraulic cylinders , as more clearly shown in fig3 . the front row of primary tillage shanks is independently moveable from the rear and middle rows . movement of the rear and middle rows is tied so that the shanks in these rows move in tandem . the apparatus depicted in fig1 may be used for various tillage operations , including , for example , primary tillage , secondary tillage and primary tillage with fertilizer application . fig2 depicts three different modes in which the tillage apparatus of fig1 may be used in a method for primary tillage , especially in the autumn . referring to fig2 a and fig2 b , the tillage apparatus 1 as described above being dragged by tractor 30 may have all of its primary tillage shanks 25 , 26 , 27 lowered into soil engaging positions . such an arrangement results in narrower furrow spacing . fig2 b shows a rear view of this arrangement with the wheels and harrows removed for clarity . it can be readily seen from fig2 b that the primary tillage shanks with their chisel plows are equidistantly spaced in a transverse direction , even though eleven are in the front row , four are in the middle row and eight are in the rear row . even furrow spacing is therefore achieved . referring to fig2 c and fig2 d , the tillage apparatus 1 as described above being dragged by tractor 30 may have the front row of primary tillage shanks 25 lowered into soil engaging positions , but the middle and rear rows of primary tillage shanks 26 , 27 are raised in disengaged positions . such an arrangement results in wider furrow spacing than the arrangement in fig2 a and fig2 b . fig2 d shows a rear view of this arrangement with the wheels and harrows removed for clarity . it can be readily seen from fig2 d that the eleven primary tillage shanks 25 with their chisel plows in the soil engaging position are still equidistantly spaced in a transverse direction . even furrow spacing is therefore achieved , but with a wider furrow spacing than in fig2 a and fig2 b . referring to fig2 e and fig2 f , the tillage apparatus 1 as described above being dragged by tractor 30 may have the front row of primary tillage shanks 25 raised in a disengaged positions , but the middle and rear rows of primary tillage shanks 26 , 27 are lowered in soil engaging positions . like the arrangement in fig2 c and fig2 d , such an arrangement results in wider furrow spacing than the arrangement in fig2 a and fig2 b , however , the furrows created by the arrangement in fig2 e and fig2 f are offset from those created by the arrangement in fig2 c and fig2 d . fig2 f shows a rear view of this arrangement with the wheels and harrows removed for clarity . it can be readily seen from fig2 f that the twelve primary tillage shanks 26 , 27 of the middle and rear rows with their chisel plows in the soil engaging position are still equidistantly spaced in a transverse direction . even furrow spacing is therefore achieved , but with a wider furrow spacing than in fig2 a and fig2 b . referring to fig3 , enlarged views are shown of selectively moveable primary tillage shank 25 used in the apparatus depicted in fig2 . primary tillage shanks 26 , 27 from fig2 are identical . fig3 a - 3c show the shank in its lowered soil engaging position while fig3 d - 3 f show the shank in its raised disengaged position . the shank 25 has chisel plow 35 mounted thereon at the soil engaging end of the shank . the shank is fixedly secured at the other end of the shank to shank bracket 36 by a bolt through upper bolt hole 41 in the shank bracket . there are three bolt holes 41 , 42 , 43 in the shank bracket to which the shank may be secured . less soil penetration by the shank and shallower furrows are achieved by securing the shank through upper bolt hole 41 . more soil penetration by the shank and deeper furrows are achieved by securing the shank through lower bolt hole 43 . shank penetration depth may be adjusted in this manner . shank bracket 36 is rotatably mounted on mounting bracket 37 by virtue of pin 38 . further connection shank bracket 36 to mounting bracket 37 is dual - acting hydraulic cylinder 45 . hydraulic cylinder 45 is rotatably attached to shank bracket 36 by virtue of pin 46 and rotatably attached to mounting bracket 37 by virtue of pin 47 . mounting bracket 37 is fixedly secured to frame - member 50 with u - shaped bracket members 39 . in operation , when cylinder arm 44 of hydraulic cylinder 45 is extended , shank bracket 36 rotates on pin 38 and forces shank 25 down into the soil engaging position , as best shown in fig3 a and fig3 c . when cylinder arm 44 of hydraulic cylinder 45 is retracted , shank bracket 36 rotates the other direction on pin 38 and forces shank 25 up out of the soil engaging position into the disengaged position , as shown best in fig3 d and fig3 f . hydraulic cylinder 45 receives and returns hydraulic fluid to a fluid reservoir on the tractor through hydraulic lines connected to cylinder ports 49 . actuation of the hydraulic cylinder is controlled by an operator in the cab of the tractor . referring to fig4 a and fig4 b , the tillage apparatus 1 as described above being dragged by tractor 30 has all of its primary tillage shanks 25 , 26 , 27 lowered into soil engaging positions . this is the same as the arrangement in fig2 a and fig2 b . the arrangement of fig4 a and fig4 b differs from fig2 a and fig2 b in that a different shaped chisel plow is mounted to the primary tillage shank and fertilizer feeder 60 is mounted on the shank in conjunction with the chisel plow , as best shown in fig5 described below . such an arrangement is useful for autumn primary tillage operations in which fertilizer ( e . g . anhydrous ammonia ) is mixed into the soil . referring to fig5 , enlarged views are shown of selectively moveable primary tillage shank 25 used in the apparatus depicted in fig4 . primary tillage shanks 26 , 27 from fig4 are identical . fig5 a - 5c show the shank in its lowered soil engaging position while fig5 d - 5 f show the shank in its raised disengaged position . most of the features are the same as those described in connection with fig3 . however , in fig5 , chisel plow 55 mounted on primary tillage shank 25 is smaller and slimmer than the chisel plow depicted in fig3 . this provides space to mount fertilizer feeder 60 on shank 25 to be used in conjunction with chisel plow 55 . fertilizer ( e . g . anhydrous ammonia ) is fed into feeder 60 through air lines connected to an air cart having a fertilizer hopper mounted thereon ( lines , air cart and hopper not shown ). fertilizer is fed directly from feeder 60 into the furrows created by the primary tillage shanks and chisel plow . referring to fig6 a and fig6 b , the tillage apparatus 1 as described in fig1 being dragged by tractor 30 has all of its primary tillage shanks 25 , 26 , 27 raised into their disengaged positions . this arrangement is a conservation tillage configuration useful for spring seed bed preparation operations . coulter wheels 17 on coiled shanks , harrow tines 16 and rolling harrows 15 are all secondary tillage implements designed for conservation tillage . thus , the apparatus with its primary tillage shanks all selectively raised in the disengaged position can be used purely as a conservation tillage apparatus . fig6 b most clearly shows that all of the primary tillage shanks 25 , 26 , 27 in the front , middle and rear transverse rows are in the raised position . the novel features of the present invention will become apparent to those of skill in the art upon examination of the detailed description of the invention . it should be understood , however , that the scope of the claims should not be limited by the preferred embodiments set forth in the examples , but should be given the broadest interpretation consistent with the specification as a whole . | a tillage apparatus for selective primary tillage and seed bed preparation makes use of a selectively moveable primary tillage shank to provide seasonal , in - field and / or on - the - fly flexibility of tillage operation . the tillage apparatus has a cultivator frame , at least one secondary tillage tool mounted on the frame and a primary tillage shank mounted on the frame , the primary tillage shank selectively moveable between a lowered soil engaging position and a raised disengaged position . in a method of tilling or preparing a seed bed , the tillage apparatus is dragged around a field with the at least one secondary tillage tool engaged with the field when secondary tillage of the field is desired , and the selectively moveable primary tillage shank lowered to be engaged with the field when the field is in need of primary tillage or raised to be disengaged from the field when primary tillage is not desired . |
the present invention provides an apparatus for modifying the mass of a bat for contacting a baseball , softball , or other object . the invention also modifies the performance of a bat by modifying the center of mass for a bat . fig1 illustrates one embodiment of the invention , wherein bat 10 has handle 12 and contact end 14 forming an annular ring about hollow 16 . interior wall 18 of bat 10 defines the perimeter of hollow 16 . weight 20 is releasable attached to interior wall 18 so that weight 20 can be removed from contact with bat 10 . as shown in fig1 , threaded connection 22 attaches weight 20 to interior wall 18 , and weight recess 24 , shown in fig5 , permits a tool ( not shown ) to rotate weight 20 into threaded engagement with bat 10 . alternative , the outer edge of weight 20 can be rotated by a person &# 39 ; s hand to permit installation of weight 20 relative to interior wall 18 . conventional hollowed end bats can be threaded with minimal tooling to provide threaded connection 22 between weight 20 and interior wall 18 . weight 20 has a selected mass , and the added mass of weight 20 selectively increases the mass of bat 10 . weight 20 can be removed from attachment with bat 10 , and a lighter weight can be substituted in place of weight 20 to reduce the overall mass of bat 10 . alternatively , weight 20 can be removed from attachment with bat 10 and a heavier weight can be substituted in place of weight 20 to increase the overall mass of bat 10 . the invention permits selective adjustments in the mass of bat 10 without requiring the replacement of bat 10 . consequently , the invention provides an economic , simple apparatus for adjusting the mass of a bat . by placing increased mass proximate to contact end 14 of bat 10 , relatively small variations in the mass of weight 20 increases the torque acting on bat 10 because of the axial distance between the batter &# 39 ; s hands and weight 20 . a close up of this description can been seen in fig8 and fig9 . significantly , the invention permits the overall center of mass for bat 10 to be moved along the longitudinal axis of bat 10 . when a heavier weight is substituted for weight 20 , the overall center of mass for bat 10 moves away from the batter &# 39 ; s hands . when a lighter weight is substituted for bat 10 , the overall center of mass for bat 10 moves toward the batter &# 39 ; s hands . additionally , weight 20 can be constructed as a composite wherein weight 20 is formed with a combination of materials having different masses . by varying the mass and composition of weight 20 , a batter can adjust the response and performance of the bat while maintaining the same grip in precisely the same position on bat handle 12 . the weight adjustments can be made without modifying the exterior shape of bat 10 , thereby eliminating performances caused by air resistance during the batter &# 39 ; s swing . an alternative embodiment of the invention is disclosed in fig2 , wherein bat 26 is illustrated in attachment with bushing 28 . bushing 28 comprises any fixed or removable liner for attaching weight 30 and bat 26 . bushing 28 can be attached to bat 26 with adhesive material , solder , compression , and / or other conventional techniques . as illustrated , weight 30 has threads 32 which are engaged with matching thread form 34 on bushing 28 . in this embodiment of the invention , different materials can be used for weight 30 and bushing 28 . weight 30 can comprise a metal , plastic , or composite material sufficient to provide the desired mass . bushing 28 can comprise a metal , plastic , or composite material sufficient to facilitate the attachment , retention , and detachment of weight 30 . in one embodiment of the invention , threads 32 and thread form 34 can comprise a material , or can be coated with a friction resistant material which facilitates the attachment and detachment of weight 30 and bushing 28 . other variations to the embodiments disclosed herein can be made to modify the performance of the weight . instead of having a solid center , weights 20 and 30 could have a hollow interior partially filled with a moveable , metallic or non - metallic material such as mercury , lead shot , or steel particles . as the bat is manipulated in an area , the moveable material would move outwardly relative to the bat handle due to centrifugal force . such movement permits the center of mass to be concentrated toward the bat handle during the initial acceleration of the bat , and such movement moves the center of mass away from the bat handle during the bat swing . by moving the center of mass outwardly during the swing , such embodiment utilizes the torque of the bat handle to deliver maximum mass and acceleration to the region of the bat contacted by the bail or other object . in this fashion , the moveable material within the weight increases the efficiency of energy transfer between the bat and the bail or other object . although the invention has been described in terms of certain preferred embodiments , it will be apparent to those of ordinary skill in the art that modifications and improvements can be made to the inventive concepts herein without departing from the scope of the invention . the embodiments shown herein are merely illustrative of the inventive concepts and should not be interpreted as limiting the scope of the invention . | the existing bat cap is removed and the bat is threaded to match the threads on the “ adjustable sports bat plug weight ” and the “ adjustable sports bat plug weight ” is screwed in until tight . the “ adjustable sports bat plug weight ” comes in varying weights measured in half ounce increments to provide a full range of available options . |
the present invention provides a novel vaccine for the generation of cd8 + t cell responses against epitopes contained in ubiquitinatable long peptide sequences . the invention is based upon the principle that long peptide antigens must first be delivered into the cytoplasm , and then into the proteasome of an antigen presenting cell , in order to obtain efficient processing and presentation of mhc - i epitopes . the vaccine of the invention is a combination of the following 3 components : 1 ) a peptide antigen containing both ubiquitinatable and antigenic regions , 2 ) a ph - sensitive liposomal carrier to facilitate uptake and cytoplasmic unloading in apcs , and 3 ) a bilayer - associated immunostimulant ( including , but not limited to , mpl , and cpg oligonucleotides conjugated to membrane - associated components ). the vaccine of the invention , which may be referred to herein as a ubiquisome , or a ubiquisome vaccine , works on the model that long , ubiqutinable peptides can be loaded into antigen - presenting cells for processing and mhc - i presentation , by adjuvanted - liposomal carriers ( fig1 ). this method for eliciting an immune response has not been previously described , and employing an antigen with a proteasome - sorting sequence can circumvent the limitations of the prior art . by selection of the antigenic region of the peptide , the vaccines of the invention can be used in a variety of applications . these include , without limitation , treatment or prevention / delay of cancer , and treatment and prevention of infections and infectious diseases caused by bacteria , viruses and parasites . [ 0022 ] fig2 shows a representation of an exemplary peptide ( seq id no . 1 ). it contains a ubiquitinatable sequence ( seq id no . 2 ) derived from beta actin protein , a linker ( in the figure ggg ), an antigenic portion , in the figure the ovalbumin mhc - 1 restricted epitope siinfeklk ( seq . id no . 3 ). the invention , however , is not limited to the specific ubiquitinatable sequences , linker , or the antigenic portion shown . the ubiquitinatable region of the peptide in the vaccine compositions of the invention may be any ubiquinatable amino acid sequence . other examples include ubiquitin , as described in u . s . pat . no . 5 , 496 , 721 ; the e2f ubiquination domain as described in u . s . pat . no . 6 , 368 , 809 . these patents are incorporated herein by reference . the antigenic portion of the peptide in the vaccines of the present invention is not limited and may comprise any potentially antigenic epitope or sequence . specific examples of suitable antigen portions include : break point regions are amino acid sequences encoded by the fused regions of chimeric oncofusion genes . many oncofusion proteins have been identified and associated with different types of malignancies : disease oncofusion protein acute lymphoblastic leukemia e2a / pbx1 acute promyelocytic leukemia pml / rar chronic myelogenous leukemia bcr / ab1 aveolar rhabdomyosarcoma pax3 / fkhr ewing &# 39 ; s sarcoma ews / fli1 liposarcoma tls / chop synovial sarcoma syt / ssx melanoma of soft parts ews / atf1 sarcoma aspl / tfe3 peptides generated from proteolytic processing of oncofusion protein breakpoint regions , if displayed via mhc - i molecules , can be seen by the immune system as neoantigens . this can result in t cell - mediated immunity against oncogene - expressing cells , thus targeting tumor cells while avoiding an autoimmune response . although these breakpoint regions are ideal targets for immune therapy , they must be processed by the proteasome / mhc i pathway of an antigen presenting cell ( apc ) in order to elicit an immune response . there currently exists no method for the delivery of breakpoint antigens into the proteasome / mhc i pathway of apcs . immunization with dna encoding the breakpoint region is not an option because of the potential for dna recombination , leading to malignant cell transformation . the present invention provides a solution to this problem , by delivering long peptides into the mhc - i processing / presentation pathway of apcs in vivo . 2 . any peptide sequence containing a mhc - i - restricted epitope or mhc - i - restricted heteroclitic epitope ( epitopes engineered for enhanced binding to mhc or tcr ). examples of such peptide sequences include , without limitation those described in u . s . pat . no . 6 , 287 , 569 discussed above , namely , there are many tumor antigens that can be recognized by autologous ctl ( boon , t ., et al . j . exp . med . 183 : 725 - 729 , 1996 ; disis , m . l ., et al . curr . opin . immunol . 8 : 637 - 642 , 1996 ; robbins , p . f ., et al . curr . opin . immunol . 8 : 628 - 636 , 1996b ). such antigens are peptide fragments derived from cell proteins that either are restricted to the type of tissue from which the tumor is derived , are mutated during the course of malignant transformation , are aberrantly expressed by the tumor cell , and / or represent “ neo ” antigens resulting from errors in transcription , rna processing , translation , and / or protein processing due to a mutation ( s ) idiosyncratic to the tumor cell . also , viral antigens are often presented on infected cells and on some tumor cells . there are several examples of antigens that have been found to be recognized by human t cells . these antigens include , but are not restricted to , gp100 ( wolfel , t ., et al . eur . j . immunol . 24 : 759 - 764 , 1994 ; kawakami , y ., et al . j . immunol . 154 : 3961 - 3968 , 1995 ), mart - 1 ( melana ) ( castelli , c ., et al . j . exp . med . 181 : 363 - 368 , 1995 ), tyrosinase ( wolfel , t ., et al . science 269 : 1281 - 1284 , 1995 ; brichard , v . g ., et al . eur . j . immunol . 26 : 224 - 230 , 1996 ; topalian , s . l ., et al . j . exp . med . 183 : 1965 - 1971 , 1996 ), mage - 1 ( traversari , c ., et al . j . exp . med . 176 : 1453 - 1457 , 1992 ; van der bruggen , p ., et al . science 254 : 1643 - 1647 , 1991 ), mage - 3 ( gaugler , b ., et al . j . exp . med . 179 : 921 - 930 , 1994 ), bage ( boel , p ., et al . immunity . 2 : 167 - 175 , 1995 ), cage - 1 , 2 ( van den eynde , b ., et al . j . exp . med . 182 : 689 - 698 , 1995 ), n - acetylglucosaminyltransferase - v ( guilloux , y ., et al . j . exp . med . 183 : 1173 - 1183 , 1996 ), ( robbins , p . f ., et al . j . immunol . 154 : 5944 - 5950 , 1995 ), b - catenin ( robbins , p . f ., et al . j . exp . med . 183 : 1185 - 1192 , 1996a ), mum - i ( coulie , p . g ., et al . proc . natl . acad . sci . u . s . a . 92 : 7976 - 7980 , 1995 ), cdk4 ( kawakami , y ., et al . proc . natl . acad . sci . u . s . a . 91 : 6458 - 6462 , 1994 ), her - 2 ( erbb - 2 )/ neu ( peoples , g . e ., et al . proc . natl . acad . sci . u . s . a . 92 : 432 - 436 , 1995 ; fisk , b ., et al . j . exp . med . 181 : 2109 - 2117 , 1995 ), human papillomavirus - e6 , e7 ( ressing , m . e ., et al . cancer res . 56 : 582 - 588 , 1996 ; alexander , m ., et al . am . j . obstet . gynecol . 175 : 1586 - 1593 , 1996 ), and muc - 1 ( finn , 0 . j ., et al . immunol . rev . 145 : 61 - 89 . the sequences of these antigens are set forth in the &# 39 ; 569 patent . utilizing known techniques of recombinant dna technology , one of ordinary skill in the art could construct peptides which contain these sequences as the antigenic portion for use in the vaccines of the invention . 3 . potentially immunogenic regions of target proteins , which may contain one or more mhc - i - restricted epitopes . such peptide sequences may be found in virtually any region of any target protein of interest . the use of long polypeptides , which extend beyond a single epitope , allows for optimum antigen processing and presentation , regardless of the patient &# 39 ; s mhc - i haplotype . mhc - ii - restricted epitopes can also be included inside of ubiquisomes to provide cd4 + t cell help . the liposomal vaccines of the invention are utilized in the treatment or prevention / delay of cancers , infections and / or infectious diseases by introducing the vaccines to an individual , including a human individual , in need of treatment . introduction of the vaccine in vivo can be carried out by direct injection of the vaccine , for example intramuscular , subcutaneous , subdermal , intravenous , parenteral , and intraperitoneal injection . the amount of liposomal vaccine administered and the frequency of administration will depend on a variety of factors , including the identity of the antigenic species , the tolerance of the individual being treated for the host , and the duration of therapeutic benefit required . furthermore , in many cases , dosage levels reflect a balancing of detrimental side effects or toxicity with the benefits obtained as a result of the treatment . the determination of dosage amounts and schedules , however , is a matter of standard procedure within the skill in the art . the invention will now be further described with reference to the following , non - limiting examples . the model ova peptide antigen ( fig2 seq . id no . 1 ) was encapsulated in mpl - doped liposomes as outlined in fig3 . liposomes were made according to the thin film rehydration technique . for standard ubiquisomes , ph - sensitive bilayers were comprised of 70 mole % palmitoyl - oleoyl - phosphatidylethanolamine ( pope ), 30 mole % cholesteryl hemisuccinate ( chems ) and 0 . 1 - 2 . 0 mole % monophosphoryl lipid a ( mpl ). for ph - stable ubiquisomes , bilayers were comprised of 70 mole % egg yolk phosphatidylcholine , 30 mole % cholesterol , and 2 , 0 mole % mpl . lipid thin films were rehydrated by vortexing following addition of dissolved peptide antigen in pbs ( ph 8 . 5 ). extrusion of liposomes through polycarbonate membranes produced unilamellar vesicles of the desired size . unencapsulated peptide was then removed by dialysis against pbs ( ph 8 . 2 ) or size exclusion chromatography using cl4b resin . an in vitro liposome uptake study was performed . ph - sensitive liposomes encapsulating a quenched concentration ( 50 mm ) of the membrane - impermeable fluorescent dye calcein were added to a fresh splenocyte culture on microscope slides . slides were rinsed 24 or 48 h later and photographed to visualize uptake of liposomes . fluorescence images demonstrated dequenching of fluorescence , indicating unloading of liposomal contents into cells . both punctate and diffuse fluorescence were observed , demonstrating endosomal and cytoplasmic unloading respectively . light microscope images indicated no liposome uptake by non - adherent cells . adherent cells from a splenocyte culture demonstrated enhanced uptake of liposomes compared with non - phagocytic cells , suggesting that phagocytosis may be the mechanism of liposomal delivery into apcs . in order to test the potency of the ubiquisome vaccine , the liposomes of example 1 were used as a vaccine . for vaccination , mice received a single administration of 100 ml of liposomes containing 2 . 5 mg pope and approximately 50 mg peptide antigen . the vaccine was injected bilaterally in mouse tibealis anterior muscle ( 50 ml per muscle ). a single intramuscular injection of the ova ubiquisome vaccine into c57bl / 6 mice induced a strong and specific cd8 + t cell response . for elispot analysis , mice were sacrificed 5 days following vaccination and inguinal and popliteal lymph nodes were harvested . cd8 + t cells from lymph nodes were isolated using the macs magnetic cell separation technique . 1 × 10 5 cd8 + t cells were plated per well in 96 well ip plates . ova ( siinfekl , seq id no . 3 ) or irrelevant peptide - pulsed el4 lymphoma cells were irradiated and plated over cd8 + t cells at density of 10 × 10 4 cells / well . following 20 h incubation and assay development , ifn - g secreting cells were visualized as brown spots on the ip membrane . elispot analysis demonstrates that mice develop a large population of cd8 + t cells recognizing the ova peptide only 5 days following vaccination ( fig4 ). 5 days following vaccination in accordance with example 3 , cells from inguinal and popliteal lymph nodes of vaccinated mice were harvested and incubated with a cd8 + t cell - depleted splenocyte culture , either with or without ova peptide ( siinfekl , seq . id no . 3 ). bfa was added to cultures to prevent golgi - mediated secretion of ifn - g . after 14 hours incubation , cells were stained with anti - cd8 - fitc , then fixed , permeabilized , and stained with anti - ifn - g - pe . two - color flow cytometry analysis was performed to determine the number of ova - specific cd8 + t cells . flow cytometry analysis of intracellular cytokine staining confirms this result , identifying a population of ova - specific t cells equivalent to 0 . 42 % of the total cd8 + t cell population ( fig5 ). while the elispot and flow cytometry analysis determined that a local immune response was mounted , tumor challenge of these mice with b 16 melanoma cells expressing ovalbumin suggests a strong systemic response as well . 4 out of 5 mice vaccinated with ubiquisomes rejected mo4 tumor challenge , surviving without tumor for over 70 days ( fig6 ). groups of mice ( 5 mice / group ) were either left untreated or vaccinated with ubiquisomes ( 2 mole % mpl , @ 400 nm size ) as described in example 3 . 5 days later , all mice were challenged with an intradermal inoculum of 1 × 10 5 mo4 cells ( b 16 melanoma cells expressing ovalbumin ). tumor growth was monitored every two days . decreasing the amount of peptide used to make liposomes , even to { fraction ( 1 / 20 )} of the original concentration , does not appear to decrease the effectiveness of the vaccine ( fig4 ). this suggests that the liposomes are a highly efficient vehicle for delivery of antigen . when compared with standard peptide adjuvants titermax gold and qs21 , the mpl - doped liposomal vaccine of the invention elicited 2 - 5 fold higher numbers of cd8 + t cells against the ova antigen ( fig7 ). this response was dependent on the inclusion of monophosphoryl lipid a ( mpl ) as a bilayer - associated immunostimulant , and increasing amounts of mpl elicited proportionally stronger cd8 + t cell responses ( fig8 ). the ph - sensitivity of the liposome enhanced the immune response , however ph stable liposomes also elicited strong cd8 + t cell responses ( fig7 ). importantly , it was shown that generation of cd8 + t cell immunity requires the presence of a ubiquitinatable peptide sequence , placed n - terminal to the 18 amino acid ovalbumin sequence ( fig9 ). this evidence supports the model of ubiquisome vaccination involving apc phagocytosis , unloading , and ubiquitin - mediated processing of antigen . liposomes were made with cpg - cholesterol as a bilayer - associated immunostimulant . results show that liposomes containing cpg - cholesterol were highly potent when only a small proportion ( 0 . 01 %) of the molecules in the liposomal bilayer were covalently linked to cpg ( fig1 ). importantly , cpg - cholesterol , used at only 1 / 200 the concentration of mpl , achieved t cell responses comparable to mpl . the oligonucleotide cpg motif used was odn 1826 ( sequence tccatgacgttcctgacgtt ( seq . id no . 4 ), repeated four times , however other motifs will be relevant for human use . a liposomal vaccine in accordance with the invention was prepared by incorporating the ews / atf1 breakpoint having the sequence gggrggmgkilkdlss ( seq . id no . 5 ) into a ubiquitinatable peptide having the sequence rgkeqemataassgkkkggggggrggmgkilkdlss ( seq id no . 6 ). this peptide is incorporated into a liposome as described in example 1 . a liposomal vaccine in accordance with the invention is prepared by incorporating the syt / ssx breakpoint having the sequence qrpygydqimpkkpae ( seq . id no . 7 ) into a ubiquinatable peptide having the sequence rgkeqemataassgkkkgggqrpygydqimpkkpae ( seq id no . 8 ). this peptide is incorporated into a liposome as described in example 1 . a liposomal vaccine in accordance with the invention is prepared by incorporating the tls / chop breakpoint having the sequence rggfnkfgvfkkevyl ( seq . id no . 9 ) into a ubiquinatable peptide ( rgkeqemataassgkkkgggrggfnkfgvfkkevyl ( seq . id no . 10 )) which is incorporated into a liposomal system using the procedure of example 1 . a liposomal system in accordance with the invention is prepared by incorporating the aspl / tfe3 breakpoint having the sequence qqeqererlpvsgnll ( seq . id no . 11 ) into a ubiquinatable peptide ( rgkeqemataassgkkkgggqqeqererlpvsgnll ( seq . id no . 12 ) which is incorporated into a liposomal system using the procedure of example 1 . a liposomal system in accordance with the invention is prepared by incorporating the bcr / abl breakpoint having the sequence ivhsatgfqsskalqrpvasdfep ( seq . id no . 13 ) into a ubiquinatable peptide ( rgkeqemataassgkkkgggivhsatgfqsskalqrpvasdfep ( seq . id no . 13 ) which is incorporated into a liposomal system using the procedure of example 1 . gln arg pro tyr gly tyr asp gln ile met pro lys lys pro ala glu ile val his ser ala thr gly phe gln ser ser lys ala leu gln arg | liposomal system formed from a peptide having a ubiquitinatable region and an antigenic region , a ph - sensitive liposomal carrier ; and a bilayer - associated adjuvant , such as mpl are useful as vaccine compositions . these compositions are surprisingly effective in inducing an in vivo immune response to the antigen corresponding to the antigenic region . |
an exemplary drop dispensing attachment 10 constructed in accordance with the principles of the present invention is illustrated in fig1 - 3 . the attachment 10 includes an axial member 12 having an inlet lumen 14 aligned generally along a longitudinal axis 16 of the device . a cross member 18 is attached to the axial member 12 and includes at least one laterally extending leg 20 and usually a second laterally extending leg 22 . preferably , the legs 20 and 22 are arranged in an arcuate geometry to define a nose bridge rest region 24 therebetween . the laterally extending leg 20 includes an outlet lumen 30 which preferably terminates in a nozzle 32 found within a recess 34 in the end of the leg 20 . preferably , the recess 34 terminates in a very thin circumferential segment or “ lip ” 36 at its lower end which will be positioned at the medial canthus or inner corner of the eye during the dispensing procedure , as described in more detail below . the thin lip 36 is desirable since it puts the drop in contact with the skin , thereby drawing it away from the device by capillary action and reducing the possibility of back contamination of the device and the bottle &# 39 ; s content . the axial member 12 will be adapted to be removably ( or in some cases permanently ) attached to a squeeze bottle or other droplet dispenser . although not illustrated in detail , the axial member may be threaded , provided with an interference fit , or otherwise specially adapted to removably receive the squeeze bottle . alternatively , of course , the attachment 10 could be formed as an integral part of the squeeze bottle or other droplet dispenser . the attachment 10 may be formed from a variety of materials , typically being cast or molded from a suitable polymer such as polycarbonate , or silicone . the dimensions are chosen to fit a typical patient , with the lumens having diameters from 0 . 25 mm to 1 mm , the nozzle diameter being from 0 . 25 mm to 1 mm , and the distance from the axis 16 to the lip 36 being 15 mm to 25 mm . the materials are preferably malleable and conform to a variety of nasal bridge contours . referring now to fig4 and 5 , use of the attachment 10 attached to a dispensing bottle 40 for delivering drops to an eye e of a patient will be described . initially , the patient attaches the attachment 10 to the bottle 40 , if it has not already been done . after that , the patient may hold the bottle , or in some cases less desirably the attachment 10 , in order to engage the nose bridge region 24 of the attachment against the nose bridge nb of the patient . the assembly of the attachment 10 and squeeze bottle 40 will be held so that the lip 36 of the leg 20 is positioned over the inner corner ic of the eye e . proper positioning of the assembly will generally be as shown in fig4 , where the assembly is generally between the eyes rather than over either eye . by squeezing the bottle 40 , droplets are dispensed through the attachment 10 and out of the nozzle 32 , as illustrated in fig5 . the droplets will fall onto the inner wall of the recess 34 and then from the lip 36 and slide into the eye . conveniently , if the patient wishes to dispense drops into the other eye , the assembly of the bottle 40 and attachment 10 may simply be turned 180 ° about the axis 16 so that the dispensing leg 20 now lies over the other eye . the bottle may then be squeezed to deliver lubricant , medication , and / or irrigant to the other eye as just described with respect to the first eye . a drop dispensing system 100 constructed in accordance with the principles of the present invention and comprising a dropper bottle 102 , a compression ring 104 , and an attachment 106 for laterally deflecting the eye drop is illustrated in fig6 - 8 . the dropper bottle 102 can be any conventional eye dropper having a tip 108 intended to dispense a drop in a conventional manner . the attachment 106 is a modified version of the attachments described earlier , as will be described in more detail below . the compression ring 104 is adapted to permit removable placement of the attachment 106 on the tip 108 . thus , it will be appreciated that an axial member 110 and the compression ring 104 can be modified and constructed as appropriate to allow removable attachment to any type of eye dropper bottle available to be modified . the materials and general dimensions of the attachment 106 may be similar or identical to those described earlier for attachment 10 . the principal differences between attachment 106 and the prior attachment 110 is that the laterally extending leg 112 which carries the outlet lumen 114 and nozzle 116 extends over a greater arc length than that of the prior embodiment . as will be described in more detail with respect to fig9 below , this modified configuration allows the nozzle 116 to dispense a drop directly into the eye without the drop first landing on any portion of the peripheral wall of recess 118 . the attachment 106 will typically comprise a second leg 120 to complete the cross - member . the attachment 106 further differentiates the earlier attachment in that a pair of cut - outs 122 are formed in the peripheral wall about recess 118 , as best seen in fig8 . these cut - outs help assure that the drop will not contact the peripheral wall and further provide venting of the recessed region when the device is in use dispensing a drop into the eye . referring now to fig9 , the dropper bottle system 100 is used by placing the middle of the cross - member against the patient &# 39 ; s nose bridge so that the lateral arm 116 is generally over the inner corner of the patient &# 39 ; s eye e . the axis of axial member 110 will be held vertically and the nozzle 116 will be able to dispense a drop d directly into the corner of the eye , while the cut - out and remaining peripheral wall around the recess 118 contacts the inner portion of the eye or tissue surrounding the eye . cut - out 122 helps prevent pooling of the droplet and helps vent the region within the recess , although presence of the cut - out is not essential for proper operation of the device . fig1 illustrates an attachment 200 which has a geometry very similar to that of attachment 10 ( fig1 and 2 ), except that a large cut - out 202 is formed in the lower lip 36 of the attachment . all other numbering in fig1 will be the same as in fig1 and 2 . a still further embodiment of a nozzle 300 oriented vertically over an opening or aperture 302 in a cross - member 318 is illustrated in fig1 . the opening 302 of the nozzle 300 is defined by inwardly flared walls 304 . the nozzle 300 will release a drop d directly over the eye with little risk of contacting an edge of the cross - member , thus significantly reducing any opportunity for contamination of the device or bottle contents , as illustrated in fig1 a where the patient has fully tilted his or her head . the inwardly flared side walls 304 will act to redirect the drop d to the medial canthal or inner corner of the eye even when the head is not inclined fully back , as illustrated in fig1 b . while the invention has been described with reference to specific embodiments , the description is illustrative of the invention and is not to be construed as limiting the invention . various modifications and applications may occur to those skilled in the art without departing from the true spirit and scope of the invention as defined by the appended claims . | apparatus for attaching to a squeeze bottle or other dispenser for delivering drops to an eye comprises an axial member and a laterally extending leg . the axial member is attached to the bottle and receives drops or liquid therefrom . the leg is rested against the patient &# 39 ; s nose bridge so that it releases drops into the eye , preferably a corner of the eye . |
fig1 shows a top view of a load - bearing element in the form of a plate 1 with a row of attachment bores 2 arranged along the longitudinal direction of plate 1 according to a first embodiment of the invention . bores 2 are through - bores that exhibit an oval central opening 3 . at opening 3 there are two side walls 5 on opposite sides of axis 4 which extend parallel to the direction of longitudinal axis 4 of plate 1 and extend at right angles to the surfaces of the plate . these parallel side walls 5 are connected on both ends by semicircular walls 6 , each forming a semi - cylindrical boundary so that together the aforementioned oval opening 3 results . in other forms of the invention , oval bores 2 can also be provided . bores 2 can also be elliptical or of a common elongated form . what is essential is the multiplicity of functions for the selection of attachment elements or fasteners made possible by insert 10 shown in fig5 . through the mostly elongated form of plate 1 , elongated bores 2 are preferred over circular bores in order to maintain flexibility with the insertion of screws with larger diameters . in one embodiment not shown in the drawings , the bore may be essentially cylindrical with the disadvantage that the insert has less material for providing inclined holes in the insert . the elongated form that is asymmetrical with respect to axis 13 ( fig4 ) but rather is symmetrical only with respect to one of the long axes 4 and the flat surfaces enclosing axis 13 actually provides the opportunity , through suitable inserts ( see fig1 and 11 ), of firmly fixing defined angles in inclined axes 43 and 53 . arranged around the not necessarily circular or cylindrical walls 5 , 6 forming opening 3 is chamfered surface area 7 , extending and tapering inwardly from the upper surface 8 of plate 1 that faces away from the bone during implantation . the form of this area 7 can be more easily seen in the cross - section of fig2 and is preferably part - spherical . fig2 shows a sectional side view of the load bearing element or bone plate 1 according to fig1 . similar characteristics appear in all figures with the same reference numerals . from fig2 , one can clearly see in a preferred embodiment , tapered area 7 in the longitudinal direction of axis 4 , forms an angle of 37 . 5 degrees with surface 8 . this results in an angle of 142 . 5 degrees to side walls 5 , 6 . naturally , other angles are also possible , particularly it would be possible to have a bore 2 that has no chamfered area 7 , which would thus exhibit a purely cylindrical or oval - cylindrical inner boundary surface . the top surface 8 of load - bearing element 1 is formed somewhat deeper in the side area 18 near bores 2 . the same is true for upper edge 15 of side wall 5 , which are shown to be lower ( closer to the plate bottom surface ) in a direction opposite the bore ends in longitudinal direction 4 . bottom surface 9 , which is closest to the bone in insertion during surgery is here locally flat . normally , plates 1 can exhibit continuous surfaces 8 and undersurfaces 9 which at each point , for the function of positioning on the bone can always be considered to be flat . but here too , positioning on curved or bent surfaces can be provided . fig3 shows a top view of the load - bearing element or plate 1 according to fig1 with insert 10 located in bore 2 . each insert 10 is designed to be shaped complementary to bore 2 for locking therein with respect to areas 7 and side walls 5 . insert 10 has a central bore 11 with an internal threading 12 . fig4 shows a sectional side view of the load - bearing element 1 with insert 10 according to fig3 therein . for this , a first embodiment for insert 10 was selected in which main axis 13 of central bore 11 runs perpendicular to surface 8 . in the preferred embodiment , insert 10 has an area 19 that extends beyond lower surface 9 that is adjacent the bone . in particular , insert 10 has locking mechanisms that are better shown in fig5 and are not visible in fig4 because they are along its edges . in particular , the locking mechanism can be two projecting rims that engage the underside of plate 1 after the insertion of insert 10 . this will be explained in more detail in connection with fig5 to 11 . in any event , insert 10 , when it is inserted into plate 1 , with its extension area 19 , forms a distance spacer with regard to the bone material into which a screw that has been inserted into bore 11 is turned . fig5 shows a perspective view of an insert 10 to be used with a load - bearing element 1 according to fig1 . the reference numeral 21 refers to the surface of insert 10 having a circumference 22 that meets with the edge of area 18 of plate 1 . in the preferred embodiment , a spherical surface 23 extends downwardly from surface 21 and is shaped so as to have complementary surface contact with surface 7 . in cutting this recess by means of spherical cutting spherical areas are formed in surface 23 . semicircular extension 24 extends downwardly from surface 23 and is in conforming contact , without any significant play , with area 6 of bore 2 . the area lying opposite the longitudinal surface 5 consists of a resilient extension 25 on each side , in which , in the preferred embodiment shown , each extension 25 is provided with slots 26 . each extension 25 has , on its lower edge , a projecting rim 27 facing outward from the point of view of the insert with an upward - facing shoulder 28 with an outer edge 29 . preferably , projecting rim 27 is only slightly rounded in going toward shoulder 28 . the surface of rim 27 that is facing toward the bone is then preferably inclined . extension 25 is also to a certain extent , flexible . in inserting insert 10 , extension 25 then slides into bore 2 and is deflected inwardly by the projecting rim 27 . once insert 10 is completely inserted , shoulder 28 slides against underside 9 of plate 1 and locks insert 10 in plate 1 . this locking is additionally ensured by the subsequent insertion of a bone screw ( not shown ). through the pressure of the screw on the internal thread of extension 25 inward deflection of extension 25 is prevented so that projecting rim 27 is secured under plate 1 . it should be noted that extension 25 and with it projecting rim 27 need not necessarily be arranged as two extensions 25 on the opposing longer sides of insert 10 . the design can also include resilient extensions on the narrow sides of an insert , i . e . corresponding to the location of the semicircular cylindrical extensions 24 . extensions 25 can also be arranged in an alternating manner . there can also be only one or two more extensions . extensions 25 can act as spacers . this can be even further accentuated , as shown in fig1 . fig6 shows a side view of insert 10 according to fig5 . extension section 19 is provided in side areas 7 . the projecting rim 27 is formed on an end area of extension 25 . slots 26 extend to the area of spherical surface 23 . of course slots 26 can also be designed to be shorter or longer . fig7 shows a side view of the narrow side of insert 10 according to fig5 . fig8 shows a cross - sectional view of a load - bearing element 31 according to a second embodiment of the invention and fig9 shows a top view of the load - bearing element 31 according to fig8 with insert 30 inserted according to the second embodiment . the difference between the first and second embodiments is that in the second embodiment at least along the length of the longitudinal axis 4 of the load - bearing element 31 is that recess 33 is provided on the bottom surface 9 around opening 2 . this recess can also be provided on the narrow side , as shown in fig8 . in addition , insert 30 is provided with a projecting rim 27 that is arranged in such a way that the bottom of insert 30 does not project beyond lower surface 9 . the underside 29 of insert 30 is thus at least flush with the aforementioned surface 9 of the load - bearing element 1 . otherwise , the resilient engagement of insert 30 in recess 2 is designed in the same way as the engagement of the first embodiment . but here , if desired , the underside 29 of insert 30 can extend beyond the aforementioned surface 9 of the load - bearing element . fig9 shows a sectional side view of load - bearing element or bone plate 31 according to fig8 with insert 30 according to the second sample embodiment inserted therein . fig1 shows a sectional side view of a long side of another insert 40 to be used with a load - bearing element 1 according to fig1 or fig8 . insert 40 preferably has a flush underside 29 , but could also be configured similarly to underside 19 and extend beyond plate surface 9 . the main difference between insert 40 and the insert shown in fig5 lies in its internal bore 11 . axis 43 of bore 11 is slanted preferably at about 15 degrees in the direction of the longitudinal axis 4 . preferably , in a kit provided for surgery , there would be a series of different inserts with various angles , of , for example 5 , 10 , 15 and 20 degrees , to name a few possible values . as bores 2 are symmetrical with respect to axis 13 , and relatively symmetrical with respect to the perpendicular to the longitudinal axis 4 , inserts 40 can be inserted turned 180 degrees . thus , each insert with a specified angle of , for example , 15 degrees , can be inserted at a plus 15 degree or a minus 15 degree angle . fig1 shows a sectional side view of a narrow side of yet another insert 50 to be used with a load - bearing element 1 according to fig1 or fig8 . the preferred insert 50 has an underside 19 extending beyond the bottom plate surface 9 but could also be configured similarly to underside 29 and be flush with the bottom plate surface . the main difference between alternate insert 50 and the insert shown in fig5 lies in its internal bore 11 . axis 53 of bore 11 is shown to be inclined in the direction toward longitudinal axis 4 for example at an incline of 5 degrees , i . e . in a plane perpendicular to the offset shown in fig1 . preferably , in a set provided for surgery , there would be a series of different inserts with various angles , of , for example , 2 . 5 , 5 , 7 . 5 and 10 degrees , to name a few possible values . as bores 2 are symmetrical with respect to axis 13 , and relatively so with respect to the longitudinal axis 4 , inserts 50 can be inserted turned 180 degrees , so that having each insert with a specified angle , the corresponding “ negative ” angle is also covered . the angles provided for the embodiments of insert 50 according to fig1 are significantly smaller , since the bore width is less than the length . the angle is about half the size than in the sample embodiments of insert 40 according to fig1 . this is because axis 53 is angled perpendicular to the elongated portion of load - bearing element 1 and bore 2 , such that there is less room in the insert for the bore to be angled . generally , steep angles are not necessary , as fixation elements such as screws are generally arranged in essentially the same and / or similar angles to load - bearing element 1 . it is also possible to provide inserts inclined in both the aforementioned directions ( i . e . with inclines corresponding to axis 43 and axis 53 ) of fig1 , 11 , respectively . fig1 shows a perspective view of an insert 60 which is modified from insert 10 according to fig5 . insert 60 may to be used with a load - bearing element 1 according to fig1 or fig8 . reference 61 refers to a groove that is set into extension 25 to increase resilience . groove 61 runs between two slots 26 . as discussed above , surface 23 , forming a spherical base with respect to upper surface 21 , is built in so as to have complementary surface contact to surface 7 . in the embodiment according to fig1 , groove 61 is set at the upper end area of slit 26 , in order to allow the maximum spring action . this produces an area 62 from which extends spherical area 23 . although the described drawings already show a whole series of possible configurations of the invention , the invention is and should be limited only by the parameters of the attached claims . the advantage of the invention is that it offers the surgeon , with a plate 1 with conventional standard bores 2 , the possibility of forming a plurality of angularly - stable mono - axial bore by means of an inset , and furthermore , that this is made possible intra - operatively . although the invention herein has been described with reference to particular embodiments , it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention . it is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims . | an implantable orthopedic device having a load - bearing element , such as a bone plate , with at least one opening for a fixation element and one insert which can be inserted in an inclined opening in a receptacle in the bore . this insert has an external form that is at least partially complementary to the internal form of the receptacle and a central through - bore for receiving the body of the fixation element such as a bone screw . the insert also provides a locking system for holding the insert in the receptacle , in which the insert exhibits at least one locking mechanism with which conformal locking with the load - bearing element may be achieved . |
fig1 a through 1h show delivery of a heart valve support . fig2 a through 2d are perspective view of a heart valve support . fig3 is a section side view of a heart valve support . fig4 a through 4c are side and detailed views of a delivery tool and heart valve support . fig6 a and 6b are sectional side views of a catheter delivery tool . fig7 a through 8i show delivery of a heart valve support . as shown in the examples of fig1 a through 1g distortion of an annulus 18 of a heart valve 16 can be corrected simply and quickly by the following steps : a . push 201 ( fig1 a ) a conical head end basket 220 of a delivery tool 200 into the valve to force the distorted annulus ( 203 , fig1 f ) to conform to a desired configuration ( e . g ., a circle 205 , fig1 g ) and to a size that is larger ( e . g ., in diameter 207 ) than a desired final diameter 209 of the annulus ( fig1 h ). ( the tool and basket are shown in side view and the valve and annulus are shown in sectional side view .) b . continue to push 201 the delivery tool to drive an expander heart valve support 100 ( which has the desired configuration and the larger size and is temporarily held in its expanded configuration on the tool ) towards the annulus to seat multiple recurved hooks 120 located along the periphery of the support simultaneously into the valve tissue at multiple locations along the periphery 121 of the annulus ( fig1 b ). c . after the hooks are seated , pull 209 ( fig1 c ) on and evert the tip 230 of the head end basket from the inside to cause the support to roll so that the tips 122 of the hooks rotate 211 and embed themselves more securely into the annulus tissue ( fig1 c ). d . after the hooks are further embedded , continue to pull 209 ( fig1 d ) on the inside 213 of the tip of the head end basket to break the tool away from the support ( fig1 e ), allowing the support to contract to its final size and shape 215 ( fig1 h ) and leaving the support permanently in place to maintain the annulus in the desired final configuration and size . the entire procedure can be performed in less than a minute in many cases . by temporarily forcing the annulus of the valve to expand to the desired circular shape , it is possible to attach the support quickly , easily , and somewhat automatically by forcing multiple hooks into the tissue at one time . the physician avoids having to attach individual sutures or clips one at a time along the periphery of a distorted annulus and then cinch them together to reform the supported annulus to a desired shape and size . thus , the physician does not even need to be able to see the annulus clearly ( or at all ). once attached , when the tool is removed , the support automatically springs back to its final shape and size . as shown in fig2 a and 2d , in some implementations , the support includes a circular ring body 110 that bears the hooks 120 . the body 110 can be expanded from ( a ) a minimal - diameter long - term configuration ( fig2 a ) to which it conforms after it has been attached to the annulus to ( b ) an expanded delivery configuration ( fig2 d ) to which it conforms when it is held on the head end basket of the tool and while it is being attached in the steps shown in fig1 a , 1 b , and 1 c . the long - term configuration is normally circular and has the diameter of a healthy annulus for a particular patient . when attached , the support maintains the health configuration of the annulus so that the valve will work properly . in some examples , the body 110 has the same shape ( e . g ., circular ) but different diameters in the delivery configuration and the long - term configuration . the body is constructed of a material or in a manner that biases the body to contract to the long - term configuration . for example , all or portions of the body 110 may be formed as a helical spring 110 a such as a continuous helical spring connected at opposite ends to form a circular body or one or more interconnected helical spring segments ( fig2 b ). in some examples , the support body 110 b may be a band of shape memory material such as nitinol or a biologically compatible elastomer that will return to the long - term configuration after being expanded to the delivery configuration ( fig2 c ). the hooks 120 may number as few as three or as many as ten or twenty or more and may be arranged at equal intervals along the body or at unequal intervals as needed to make the body easy and quick to delivery , permanent in its placement , and effective in correcting distortion of the valve annulus . the hooks are configured and together mounted along the circular outer periphery so that they can be inserted simultaneously into the tissue along the periphery of the annulus and then firmly embedded when the tool is pulled away and the basket is everted . for this reason , as shown in fig2 e each of the hooks has two pointed features . one pointed feature is a sharp free end 122 pointing away from the valve leaflets during delivery . the other pointed feature is a barb 128 formed at a bend between the sharp free end 122 and an opposite connection end 124 where the hook is attached , e . g ., welded or glued , to the body 110 . the barb points toward the valve leaflets during delivery . each hook 120 can be formed of biologically compatible materials such as platinum , gold , palladium , rhenium , tantalum , tungsten , molybdenum , nickel , cobalt , stainless steel , nitinol , and alloys , polymers , or other materials . during delivery the barbs of the hooks are together forced into the tissue at a series of locations around the outer periphery of the temporarily expanded annulus . in a later step , the sharp free ends are forced to rotate somewhat away from the leaflets for permanent attachment . to cause the hooks to rotate during delivery , the hooks 120 are attached permanently to the support body 110 and the support body can be rolled 123 ( fig3 ) about an axis 112 of the support body , as indicated . one way to cause the rolling of the support body and the associated rotation of the hooks is to enable the body to change its configuration by rotation of the entire body about an axis represented by the central circular axis 153 , much as a rubber o - ring can be rolled about its central circular axis . the reconfiguration of the body to cause the rotation of the hooks can be achieved in other ways . in some examples , applying an axial force ( arrows 113 ) to the inner peripheral edge of the ring ( we sometimes refer to the support broadly as a ring ) will cause the ring to tend to roll and the hooks to embed themselves in the annulus as intended . by properly mounting the inner periphery of the ring on the outer periphery of the delivery tool , the axial force 113 can be applied by pulling the tool away from the leaflets of the valve , as explained earlier . for delivery to the valve annulus , the valve support 100 is expanded to its delivery configuration and temporarily mounted on a delivery head 220 of the tool 200 ( fig4 a ). the support must be expanded enough in its temporary mounting on the tool so that when the head - end basket of the tool is pushed against the annulus to force it to expand to the size and shape of the expanded support , the annulus has reached a circular , non - distorted shape . the tapered profile of the head end basket of the delivery tool allows the tool to accommodate supports of various sizes . the heart valve support 100 is held in place on the delivery head 220 using one or more releasable connections 246 . the connections 246 are arranged to translate forces from the tool 200 to the support 100 in either of two opposite directions , 248 and 250 toward or away from the leaflets of the valve . when the support has been embedded in the annulus and the tool is pulled in the direction 250 to release it from the support , the force on the connections 246 exceeds a predetermined threshold , the connections break , releasing the tool from the support at the end of the delivery process . the connections 246 may be , in some examples , breakable sutures 252 ( fig4 a ). in some examples , the connections 246 include retainers that can take , e . g ., the configurations shown as 254 a or 254 b ( fig4 b & amp ; 4c , respectively ). in the example shown in fig4 b , the retaining element 254 a has one rigid finger 256 to translate forces from the tool 200 to the support 100 when the tool is moved in direction 248 while the support is attached to the tool and being pushed into the heart tissue . a second deformable finger 258 aids in maintaining the connection between the support 100 and the tool 200 when the tool is moved in direction 250 and is deformable ( dashed lines ) to release the valve support 100 from the tool 200 when the force in direction 250 relative to the embedded support exceeds a predetermined threshold . in the example shown in fig4 c , the retaining element 254 b includes a finger 260 having a crook 262 to receive the support 100 and to translate forces from the tool 200 to the support 100 when the tool is moved in direction 248 . the finger has a resiliently deformable tip 264 that is biased towards the tapered body 222 and helps to maintain the connection between the support 100 and the tool 200 and is deformable ( shown in hidden lines ) to release the valve support 100 from the tool 200 when the tool is moved in the second axial direction 250 against an embedded support and the force exceeds a predetermined threshold . as shown in fig5 , in an example of a tool 200 that can be used for delivery of the support during open heart surgery , a basket 220 is connected at its broad end to a set of stiff wires or other rigid projections 216 from a long shaft 210 having a handle 212 at the operator &# 39 ; s end 214 . thus the projections 216 connect the shaft 210 to the basket 220 and transfer pulling or pushing force between the shaft and the basket ( and in turn to the support ). the example of the basket shown in fig5 includes a tapered body 222 having a network of interconnected struts 224 defining an array of openings 226 together forming a tapered semi - rigid net . the basket ( which we also sometimes refer to as a delivery head ) 220 has a rounded tip 228 . the head 222 tapers radially outwardly with distance along a longitudinal axis 234 of the head 220 from the tip 228 towards the operator . the broad end 232 of the tapered body 222 is firmly attached to the projections 216 , which taper in the opposite direction from the taper of the basket . in some implementations , the shaft 210 defines a lumen 236 extending between the heart valve end 218 of the shaft 210 and the handle 212 . a wire 238 is arranged to move freely back and forth within the lumen 236 . the wire 238 has one end 240 that extends from the handle 212 and an opposite end 242 that is connected to the inside of tip 228 . the wire 238 can be pulled ( arrow 244 ) to cause the delivery head 220 to collapse ( hidden lines ) and evert radially inwardly starting at the tip 228 . returning to a more detailed discussion of fig1 a through 1e , the operator begins the delivery of the support by pushing the tapered end 230 of the head basket 220 into the valve 16 ( e . g ., the tricuspid valve ) to cause the valve leaflets 14 to spread apart . because the head - end basket is tapered , by continuing to push , the operator can cause the annulus 18 of the tricuspid valve 16 to conform to a desired shape , typically circular . during insertion , because of its taper , the head - end basket is self - centering . the taper of the basket 220 translates the insertion force in direction 248 in a radial force that causes the annulus 18 to expand and temporarily assume a desired shape ( and a larger than final diameter ). as the operator continues to push on the tool , the ring of barbs of the hooks touch and then enter the heart tissue along a ring defined by the outer periphery of the annulus and the sharp free ends of the hooks enter and seat themselves within the tissue , much like fish hooks . once the hooks are embedded in the tissue , the operator pulls on the near end 240 of wire 238 to cause the basket 220 to collapse , evert , and be drawn out of the valve 16 . eventually , the everted portion of the basket reaches the valve support 100 . by further tugging , the operator causes the body 110 of the support 100 to roll about its central axis ( as in the o - ring example mentioned early ) which causes the hooks 120 to embed firmly in the tissue of the annulus 18 of the valve 16 . using a final tug , the operator breaks the connection between the tool 200 and the valve support 100 and removes the tool 200 , leaving the valve support 100 in place . as the basket 220 passes the points of connection 246 , the forces exerted by the embedded hooks 120 on the support body 110 , acting in direction 248 , exceed the forces exerted by the withdrawing basket 220 on the support body 110 ( through the connections 246 ), acting in direction 250 , thereby causing the connections 246 to release the support 100 . the tool 200 is then withdrawn , allowing the valve support 100 , along with the annulus 18 , to contract to the long - run configuration . in implementations useful for delivery of the support percutaneously , as shown in fig6 a , the delivery head 220 a can be made , for example , from a shape memory alloy , such as nitinol , which will allow the body 222 a to be collapsed radially toward the longitudinal axis 234 a during delivery of the head from a percutaneous entry point into the heart . the delivery head 220 a is biased towards the expanded , tapered orientation shown in fig6 a . thus , the delivery head 220 a , in the form of a tapered semi - rigid net , is connected to a catheter shaft 210 a through projections 216 a that extend radially outwardly from the catheter shaft 210 a and taper in a direction opposite the taper of the delivery head 220 a . the projections 216 a are resiliently mounted to the catheter shaft 210 a and are biased towards the tapered orientation shown , for example , by spring biased projections 216 b shown in fig6 b . the projections 216 a include springs 278 , e . g ., torsion springs ( as shown ), mounted to the catheter shaft 210 a and forming a resilient connection . a wire 238 a slides within a lumen 236 a of the shaft 210 a in a manner similar to the one described earlier . the tool 200 a also includes a sheath 280 in which the catheter shaft 210 a can slide during placement of the support . the sheath 280 , the catheter shaft 210 a , and the wire 238 a are all flexible along their lengths to allow the tool 200 a to be deflected and articulated along a blood vessel to reach the heart . to delivery the support percutaneously , as shown in fig7 a , when the delivery head is prepared for use , the sheath 280 is retracted beyond the projections 216 a , allowing the delivery head 220 a to expand . the valve support 100 is then expanded to the delivery configuration and mounted on the tapered body 222 a . the valve support 100 is connected to the delivery head 220 a using releasable connections , e . g ., breakable sutures and / or retaining elements ( as described earlier ). the sheath 280 is then moved along the catheter shaft 210 a towards the delivery head 220 , causing the projections 216 a and the delivery head 220 a to contract radially inwardly to fit within the sheath 280 , as shown in fig7 b . in the contracted configuration , the tip 228 a of the delivery head 220 a fits against the end 282 of the sheath 280 . the rounded tip 228 a may provide easier delivery and maneuverability in navigating the blood vessels to reach the heart . to deliver the support to the valve annulus , the end 230 of the tool 200 a is fed percutaneously through blood vessels and into the right atrium 24 ( fig8 a ). the sheath 280 is then retracted , exposing the valve support 100 and allowing the projections 216 a , the delivery head 220 a , and the support 100 to expand , as shown in fig8 a . the catheter shaft 210 a is then advanced , e . g ., under image guidance , in direction 248 a along an axis 30 of the annulus 18 . the operator forces the distal end 230 a of the self - centering delivery head 220 a into the valve 16 ( fig8 b ) using feel or image guidance , without actually seeing the valve 16 . once the tip is in the valve 16 , the operator pushes on the end 214 a of the catheter shaft 210 a to force the tool further into the valve 16 . this causes the tapered body 222 a of the delivery head 220 a to restore the shape of the annulus 18 to a circle or other desired shape ( such as the distinctive “ d ” shape of a healthy mitral valve ). the tool 200 a is self - centering because of its shape . the net - like construction of the delivery head 220 a ( and the head used in open heart surgery , also ) allows blood to flow through the valve even while the delivery head 220 a is inserted . as tool 200 a reaches the point at which the support hooks touch the annulus , by giving an additional push , the operator drives the hooks 120 of the valve support 100 together into all of the annular locations at which it is to be attached , as shown in fig8 c . the configuration of the valve support 100 and the tool 200 a and the manner of temporary attachment of the support 100 to the tool 200 a assure that the hooks 120 will penetrate the valve 16 exactly at the correct positions , just along the outer edge of the annulus 18 . once the valve support 100 has been attached to the valve 16 , the operator pulls on the proximal end 240 a causing the delivery head 220 a to evert ( hidden dashed lines ) and be drawn out of the valve 16 ( shown in fig8 d ). eventually the everted portion of the tool 200 a reaches the valve support 100 . by further tugging , the operator causes the torus of the support 100 to roll all around its periphery which jams the hooks 120 securely into the annulus 18 of the valve 16 , as illustrated in fig8 e , seating the support permanently and permitting later growth of tissue around the support 100 . the depth and radial extent of each of the placed hooks 120 is essentially the same as a conventional suture so that their placement is likely to be as effective and familiar to the operator and others as conventional sutures . using a final tug , the operator breaks the connections 246 between the tool 200 a and the valve support 100 and retracts the catheter shaft 210 , leaving the support 100 in place . the catheter shaft 210 is retracted to a position beyond the valve annulus 18 and the wire is advanced in the first direction allowing the delivery head 220 a to assume its original tapered shape ( fig8 f ). the catheter shaft 210 a is then retracted into the sheath 280 ( fig8 g ), and the tool 200 a is withdrawn . in other examples , as shown in fig8 h and 8i , the tip 228 a of the tool 200 a has a compressed dimension that is smaller than an internal diameter 284 of the sheath 280 , permitting the catheter shaft 210 a to be retracted directly into the sheath 280 after deployment , as shown in fig8 i . with the tool 200 a withdrawn , the valve support 100 contracts reshaping the annulus 18 such that the valve leaflets 14 coapt to prevent a backflow of blood during systole . for example , distortion of either the tricuspid valve or mitral valve can be corrected . for tricuspid valve repair , the hooks can be arranged around only about three - quarters of the support and therefore the annulus . for mitral valve repair , the hooks can cover the entire periphery of the annulus . for mitral valve repair , a back - up valve can be provided as part of the delivery tool to maintain heart function during the delivery procedure . materials other than shape memory materials may be used as the material for the support body , and other ways can be used to force the support back to a desired size following expansion , including , for example , cross - bars that span the opening of the support . in addition , the left atrial appendage of the heart can be closed . for example , the tool can be pushed into an opening of an atrial appendage causing the opening to assume a predetermined shape . the tool can be continued to be pushed in order to embed the hooks of the expanded support into the periphery of the opening of the appendage . the tool can then be withdrawn , releasing the support , and allowing the support to contract . the support can have a relatively small contracted diameter such that , when the tool is withdrawn , releasing the support , the support can contract to a relatively small size , effectively closing off the appendage . in addition to the open heart and percutaneous deployment procedures , the valve support can also be deployed through the chest . the head of the tool need not be a basket , but can take any form and strength that enables the valve annulus to be forced open to a shape that corresponds to the shape of the support . the basket can be made of a wide variety of materials . the basket can be held and pushed using a wide variety of structural mechanisms that permit both pushing and pulling on the support both to seat and embed the support in the annulus tissue and disconnect the support from the tool . the support could take a wide variety of configurations , sizes , and shapes , and be made of a wide variety of materials . the hooks could be replaced by other devices to seat and embed the support using the pushing force of the tool . the hooks of the support need not be embedded directly in the annulus but might be embedded in adjacent tissue , for example . | in general , in an aspect , an annulus of a heart valve is caused to dilate to a predetermined configuration . while the annulus is dilated , a valve support is attached to tissue at locations along the annulus . after attachment , the support is caused to contract . |
while this invention is susceptible of embodiment in many different forms , there is shown in the drawings , and will be described in detail , several specific embodiments with the understanding that the present disclosure is to be considered as an exemplification of the principles of the invention and is not intended to limit the invention to the embodiments illustrated . autonomous patch 10 is shown in fig1 as comprising housing 20 , power source 22 , transmitting means 24 , and storage device 27 . patch 10 is configured for removable placement upon the skin or other tissue of a patient , generally in proximate relationship with an already - implanted medical device 29 ( fig3 ). once operatively placed upon a patient , patch 10 allows for transcutaneous programming and / or power transfer to the implanted device 29 , wherein the programming / power transfer is dictated by a pre - programmed control program contained within storage device 27 of patch 10 . patch 10 may be used with any number of conventional implanted devices . for example , defibrillators , pacemakers , neurostimulators , cochlear implants and implantable pumping devices are all devices that could be coupled with patch 10 . the implantable pumping devices are an especially important category , as the alteration of the operational parameters of implantable pumps can be frequent . such pumps may include positive displacement pumps , dynamic pumps , lift pumps , electromagnetic pumps , and osmotic pumps , among others . further , patch 10 may be used with a device or devices intended to be used in conjunction with one of the above devices . for example , patch 10 could alter the operating parameters of an electrically powered valve mechanism associated with an implanted pump . generally , each of the above devices may comprise an electrically or electrochemically powered device capable of providing medical treatment . the operational control of which may be alterable via a conventional rf receiver ( or other similar type ) in association with an external / remote operational control altering means . such an alteration could include changing the stimulation voltage of a neurostimulator , or the drug delivery flow rate of an implantable pump , for example . other alterations could include modifying the delivery rate of a valve associated with an implantable pump , or altering a control mechanism for an osmotic pump so as to cause changes in its osmotic delivery rate . in any case , patch 10 allows for at least one of programming and power to be transmitted transcutaneously to the implanted medical device . housing 20 of patch 10 is shown in fig1 as encompassing transmitting means 22 , power supply 24 and storage device 27 within sealed compartment 28 . housing 20 additionally includes on / off switch 21 , for beginning and halting the operation of patch 10 . housing 20 can have any geometrical shape , including , but not limited to hemispherical , cylindrical , cubic , and the like , as may be needed for particular medical applications . as can be seen , housing 20 is associated with attachment means 30 , which can include an adhesive bandage ( as shown ), an adhesive backing on sealed compartment 28 , or any number of other means for securing the device , allowing the device to be adhered to and then removed from a particular patient , as needed . for example , attachment means could comprise a bracelet having a hook and eye latch , or velcro ® latch , or an elastic band , as well as other conventional means for attachment . housing 20 preferably includes a display device ( not shown ) associated with the external portion of housing 20 . display device can include any number of conventional displays , including an lcd screen or the like . display device is associated with the components of patch 10 , so that , after activation of the patch 10 , any number of operational parameters can be displayed to the user . such parameters could include the power level of the device , the amount of medicament remaining within the implanted device , the time course of treatment to that time , or any other necessary or desired operating parameter . power source 22 is shown in fig1 within compartment 28 as comprising a conventional button cell lithium ion battery which is in electrical communication with all components of patch 10 , including transmitting means 24 . as will be understood by those having ordinary skill in the art , any type of power source , including other types of batteries , can be used as the power source provided it has the appropriate capacity and energy density to enable operative transmission by transmitting means 24 to implanted device 29 for a desired period of time . it is contemplated that the power source 22 may be replaced as needed by replacing the battery , or by recharging the power source 22 in any conventional means . it is preferred , however , that the patch 10 comprises a single - use power source 22 that is replaced with an additional patch 10 having a fresh power source 22 , when needed , as will be discussed below . additionally , it is contemplated , though not shown in the drawings , that the compartment 28 additionally includes a releasable plastic strip between power source 22 and the electrical leads for delivering power to patch 10 . the strip creates an open circuit state within patch 10 so that , in a storage environment , power source 22 can be inserted and left within compartment 28 without activating patch 10 or draining power source 22 . thereafter , the plastic strip can be removed , placing power source 22 in operative electrical contact with the components of patch 10 . other structures and devices that operate similarly to the plastic strip could alternatively be used . transmitting means 24 can comprise any of a number of devices capable of transmitting a signal and / or projecting a field as required by the function of the particular implanted device . for example , transmitting means can comprise rf transmitter 25 for transmitting radio frequency signals . on the other hand , and as shown in fig2 transmitting means 24 could comprise coil 26 ′, which is capable of producing an electric field upon application of a current . coil 26 ′ may be paired with another coil , coil 26 ″, to create a current in coil 26 ″ via mutual inductance . an example of mutual inductance is shown in fig3 in which an electric field is projected from coil 26 ′, and coil 26 ″ is placed within the field . once within the field , a current is produced within coil 26 ″ via inductance , and the current is proportional to the flux of the electric field produced by coil 26 ′ through coil 26 ″. storage device 27 comprises any number of types of memory - storage apparatuses , including programmable dram and sdram . importantly , storage device 27 of the present invention includes one or more pre - programmed control programs that , as will be explained further below , direct the signal sent by transmitting means 24 so as to alter the operation of implanted device as desired . actual programming can readily be accomplished by those with ordinary skill in the art using conventional microprocessor programming techniques . the pre - programmed control program of patch 10 comprises a fixed program . that is to say , once patch 10 has been assembled , and storage device 27 has been programmed with the control program , the patch 10 is in final condition . the control program that is associated with the patch 10 will not be changed or altered during the operation of the device . instead , it will remain fixed , providing the same control signals to the implanted device throughout its operation . in operation , patch 10 is placed onto the skin of a patient using attachment means 30 at or near the proximate location of an implanted medical device . patch 10 includes at least enough power in power source 22 to operate transmitting means 24 and storage device 27 throughout its operative life . once in place , patch 10 can be used to transmit at least one of power or programming to the implanted device . in one embodiment of the present invention , patch 10 transmits solely power to the implanted device . in this embodiment , the power is transmitted via transmission means 24 , described above . for example , in the embodiment of the present invention shown in fig1 transmission comprises an rf transmitter 25 for transmitting power via a radio frequency to implanted device . alternatively , transmission means 24 could also comprise another transmission method , such as is shown in fig2 with coil 26 ′ creating an electric field that creates an electric flux in coil 26 ″, transmitting power from one coil to the other . when power is transmitted from patch 10 to the implanted device , the power can be used in a number of ways . the implanted device could simply use the transmitted power to operate under standard operating conditions . in this case , patch 10 transmits power using , for example , rf transmitter 25 , to the implanted device . implanted device 10 receives the power , and continues to operate as normal . the characteristics of the power signal transmitted from patch 10 do not effect operation of the implanted device at all , but instead simply act as a remote power source . advantageously , when patch 10 depletes the installed power source 22 , a new patch can be placed on the patient , without lengthy interruption of the operation of the device or requiring time - consuming recharging . alternatively , the characteristics of the signal transmitted from transmission means 24 could be used to direct the operation of the implanted device . for example , storage device 27 of patch 10 can contain a specific program for altering the frequency and / or amplitude of an rf signal sent from rf transmitter 25 , or for altering the electric field produced by coil 26 ′. the alterations in the power signal can be used to directly manipulate the implanted device , providing additional power or removing power as needed . for example , an implanted pharmaceutical pump can be manipulated to increase the delivery rate of fluid by increasing the power to the pump . thus , the simple manipulation of transmitted power can allow a user to control an implanted device . in another embodiment , patch 10 can be used to only transmit a fixed control signal to an implanted device that is operating under its own power . in this embodiment , transmitting means 24 ( preferably an rf transmitter 25 ) sends a signal to the implanted device , the characteristics of which are regulated by the storage device 27 . the implanted device receives the signal , and uses that signal to reprogram the implanted device as desired . such a signal can be used to modify voltages of the device , fluid delivery rates , sensitivities of sensors , etc . essentially , any programmable commands may be transmitted via transmitting means 24 , as would be known by one of ordinary skill in the art . preferably , patch 10 is capable of combining both of the functions discussed above . that is , patch 10 is preferably capable of transmitting both power and fixed control signals to the implanted device . in one preferred embodiment of the present invention the patch device disclosed above is used with one or more additional patch devices in a medical treatment kit , shown in fig4 . in this embodiment , storage device 26 of each patch is preprogrammed with a specific program for transfer of instructions or power to the implanted medical device . for example , in the embodiment discussed above wherein the implanted medical device comprises a pharmaceutical pump , the individual patches may contain specific and different reprogramming information for delivery of a drug at varying delivery rates . further , the individual patches may additionally transfer a lesser or greater magnitude of power to the implanted device , thereby facilitating the varying delivery rates . each patch , however , corresponds to discrete sets of programming signals and / or power transfer patterns so that the placement of a particular patch in operable position on a patient facilitates the particular treatment regimen or regimens associated with that particular patch . preferably , within this system , each patch is marked on its external side with indicia 32 , as can be seen in fig4 . indicia 32 may include numbers , letters , roman numerals , colors , shapes , and the like , with each indicia corresponding to the particular control program , or power level , of the particular patches in the patch kit . as will be explained further below , the relationship of the indicia 32 with the particular delivery / power program associated with each patch helps to facilitate easy and reliable reprogramming ( or continued operation ) of the implanted devices , as needed . the present system would be advantageous , for example , in an outpatient pain treatment regimen . after implanting a pharmaceutical pump containing a pain medication such as morphine , a physician could issue one or more patches containing delivery instructions and / or power for the implanted device . the doctor could then issue specific patches to the patient , with each patch corresponding with a specific drug delivery rate . included with these patches would be instructions for their use , such as , for example , that patch “ a ” can be used for light pain , patch “ b ” for increased pain , and patch “ c ” for severe pain . the patient could , on their own initiative , or at the direction of a medical caregiver , alter the delivery rates of the implanted pharmaceutical pump simply by removing one patch , and replacing it with another . in this way , the physician may allow a patient the ability to modify the dose delivered from a pump within limits specified by the physician . the control programs contained within the patches given to the patient determine the limits of the treatment regimen . the present medical treatment kit could similarly be used with numerous other applications , as would be known by one of ordinary skill in the art . for example , the patches could be used to adjust the frequency within a neurostimulator for treatment of pain and / or tremors , or for adjusting the frequency / cadence of a pacemaker . of course , numerous other applications could also be envisioned for the teachings of the present invention . the foregoing description merely explains and illustrates the invention and the invention is not limited thereto except insofar as the appended claims are so limited , as those skilled in the art who have the disclosure before them will be able to make modifications without departing from the scope of the invention . | the present invention is directed to a self contained control patch for an implanted medical device , comprising a housing capable of being removably associated with an external surface of a patient , a transmitter for transmitting at least one of a transcutaneous power signal and a transcutaneous control signal to an implanted device ; and a pre - programmed storage device containing at least one control program , wherein the control program dictates the nature of the signal from the transmitting means . additionally , the present invention is directed to a system of such patches comprising two or more patches , with each patch being pre - programmed with a discrete set of instructions . methods for using the patches are additionally disclosed . |
descriptive terminology used in this application . for purposes of further identifying and describing the various preferred embodiments of the present invention , the following terms and phrases shall have the meaning set forth below . “ undesirable biological response ” is defined as any event in which normal bodily function is impaired due to a reaction to a single chemical or a compound of chemicals , in rapid or prolonged progression , in mild or severe manifestation . “ internalization ” is defined as the movement of any external agent ( natural or synthetic ) into the internal body . this includes primary pathways of internalization through the skin as well as secondary pathways of internalization such as consumption / ingestion and inhalation . the “ internal body ” shall include every structure , system and organ involved in the biological responses that make possible normal bodily function , and includes ( but is not limited to ) the skin , vascular system , respiratory system , and digestive track . with regards to the skin , an agent will not be considered in the internal body until it has passed through the stratum corneum , which , due to its relatively inert and non - living composition , is not directly involved in normal bodily function . “ reduce the risk ” shall mean a reduction in the magnitude and severity of potential risks associated with the internalization of a non - pharmaceutical or food - grade compound . reduction of risk is an important concept , given that almost any agent available to biological organisms can be potentially harmful or toxic , depending on its usage , duration of exposure , and amount of exposure . additionally , reduction of risk is not confined to a specific class or classification of agents , whether or not completely natural or synthetic , as virtually all agents have a limit to their safety , either immediately or associated with intermittent , short - term , or with prolonged exposure . organic vs . non - organic ingredients . the most preferred embodiments of the present invention also incorporate organic ingredients , to the extent practicable . the united states department of agriculture ( usda ) defines “ organic ” to mean foods whose ingredients cannot have been made by using most synthetic fertilizers and pesticides , genetic engineering , growth hormones , irradiation or antibiotics . it is estimated that by using a normal complement of body and skin care products , the average woman applies more than 200 chemicals to her skin each day . furthermore , recent research has shown that as much 60 % of these chemical ingredients are absorbed into the bloodstream . it has also been found that the number of people with eczema , allergies and skin complaints is on the rise , with these conditions most likely being aggravated by the chemicals in basic cosmetic and skincare products . many skin care products contain known or suspected carcinogens , neurotoxins and hormone disruptors . additionally , as known by those skilled in the art , synthetic as well as natural fragrances are frequently allergenic to a certain segment of the populace . further , some ingredients , like lanolin , which comes from sheep &# 39 ; s wool , can be contaminated with pesticides . other chemicals used in formulating skin care products can interact with nitrites to form carcinogens called nitrosamines . the best way to prevent potentially harmful synthetic and natural chemicals from entering the body is to use only organic materials . regulations governing organically grown compounds also prohibit the use of genetically modified ingredients . if a product claims it &# 39 ; s organic , it must contain at least 95 percent of organically grown produce . for a product to claim that it has been ‘ made with organic ingredients ’, it must contain over 70 percent of organically grown ingredients . the skin is the largest organ in your body . it is responsible for maintaining the correct body temperature and it regulates your body &# 39 ; s fluid balance . each day through many hundreds of thousands of skin pores , the average human secretes over 850 ml of fluid . the same glands are also an essential route for the elimination of toxins collected via the blood and lymphatic system . blocking the skin could force the waste back inside the system . the skin functions as a nutritional factory , producing vitamin d , necessary in the formation of bone , and participates in the metabolism of carbohydrates and amino acids . it is important to remember , that the skin is a living part of your body — often referred to as the ‘ third kidney ’— with several well - developed and interrelated circulation systems ; blood , sweat , sebum , nerve and lymph , any of which can be damaged by absorption of chemicals or enhanced by a good skin care system . two major leading causes of allergy and irritation in skin care products are fragrances and preservatives . other commonly reported symptoms include nausea , mood changes , depression , lethargy , restlessness , irritability , memory lapses and inability to concentrate . many chemicals found in fragrances are commonly designated as hazardous components in other products . manufactures are not required to list on product labels the ingredients used in formulating their fragrances , scents or perfumes and it is estimated that 95 % of the ingredients in most fragrances are made from synthetic chemicals . while fragrances made with all natural ingredients can also cause skin irritation , it is less likely to occur . cosmetic products require preservatives or bactericides to prevent them from being contaminated . some of the most allergenic and irritating preservatives release small amounts of formaldehyde , which is an irritant as well as a carcinogen and neurotoxin . many skin care products , both natural and from mainstream companies , contain either diethanolamine or triethanolamine ( wetting agents ), abbreviated on labels as dea and tea , and sometimes shown bound to other compounds as in cocamide dea , tea or sodium lauryl sulfate . neither dea nor tea is carcinogenic . however , if these products also contain nitrites — often present as contaminants and not disclosed on cosmetic labels , their presence in cosmetics can cause a chemical reaction leading to the formation of nitrosamines , with many nitrosamines viewed as carcinogenic or potentially carcinogenic compounds . a group of preservatives called parabens are also causing concern due to their oestrogen - mimicking properties . there are four main types of parabens , these being butyl - paraben , ethyl - paraben , methyl - paraben and propyl - paraben . when consumed orally , the human body seems capable of disarming these agents and preventing them from significantly altering the natural hormone levels . however , when these same ingredients are absorbed through the skin , they appear to be far more active . a recent study found higher than normal concentrations of parabens in human breast tumor tissue . elevated oestrogen levels are thought to be a primary factor for increasing the risk of breast cancer , and the discovery of oestrogen - mimicking compounds in cancer tissue . the researchers have suggested that the use of parabens in underarm deodorants may , particularly when used after shaving , be a contributory factor in the increasing number of breast cancer cases . in addition to the above risk , exposure to propyl - paraben has been shown to reduce daily sperm production in men . although the reason for this action is unknown , it would seem prudent for both men and women to avoid unnecessary contact with parabens until their safety is confirmed . natural vs . synthetic ingredients . there is much debate about where “ natural ” stops and “ synthetic ” begins with regards to cosmetic and personal care ingredients . unfortunately , there is no universally accepted definition for either class of ingredients . for the purpose of this patent application and the various preferred embodiments of the present invention , “ natural ” and “ synthetic ” will be defined as set forth below . a ) any material derived from a natural living or non - living source that remains chemically unchanged from its naturally existing state . extraction of such material by means of mechanical manipulation ( such as grinding , powderizing , physical filtration , etc ) or naturally derived solvents ( such as carbon dioxide , water , oils , etc ) is acceptable as long as the original chemical structure is preserved . b ) an extract of a compound existing in nature that is either chemically or mechanically processed , but whose natural chemical structure is preserved ( i . e . tetrahydrocurcuminoids is a specific example of a natural chemical constituent extracted from turmeric root ). c ) a compound derived by mechanically mixing two or more inert compounds existing in nature together , by which no chemical reaction occurs . d ) a compound derived by mechanically mixing two or more compounds existing in nature together , by which a chemical reaction naturally occurs with no introduction of non - natural compounds . e ) any material , synthesized or not , whose exact chemical structure exists in nature . it is important to accept ingredients that are synthesized to identically mirror natural compounds as “ natural ” because : i ) it is not always possible to obtain raw materials right from nature at reasonable prices and with commercially reliable availability ; and ii ) if the ingredients are chemically identical to the ingredient in its natural state , then there is no practical difference . a ) any chemical or compound chemically synthesized and manufactured “ from scratch ” in a laboratory or industrial setting whose chemical structure does not and cannot match anything found in nature . b ) any chemical or compound that has been created by the chemical manipulation of one or more natural materials in a laboratory or industrial setting whose final chemical structure does not and cannot match anything found in nature . c ) a chemical or compound that has been chemically synthesized and manufactured to “ copy ” a natural material , but is left in its racemic form ( i . e . it is not put through a chiral separation process to isolate the appropriate when it should be ). several examples of the use of racemic compounds will offer additional background as to the practical implications of the current practices in the cosmetics and skin care industries . for example , 1 - alpha bisabolol , also known as levomenol , is a colorless viscous oil that is the primary constituent of the essential oil derived from german chamomile ( matricaria recutita ). it is almost insoluble in water and glycerin , but well soluble in ethanol . bisabolol is also known to have various anti - irritant , anti - inflammatory and anti - microbial properties . bisabolol also has a weak sweet floral aroma and is used in various fragrances . it has also been used for hundreds of years in cosmetics because of its perceived skin healing properties . in laboratory synthesis , the molecule that matches the natural form of bisabolol is the left - handed molecule but the synthetic version of bisabolol , typically used in cosmetics , is a racemic mixture . similarly , the natural form of vitamin e is the d - alpha tocopherol molecule . the laboratory - synthesized molecule that matches the naturally occurring form is also the right - handed ( d ) version . with many cosmetic and skin care products advertised as containing vitamin e , the inclusion of the non - natural , “ racemic ” molecule is common . this version is the dl tocopherol version and has been known to cause allergic reactions in some people . only the split “ d ” molecule mirrors the natural version but it is common to see the racemic version used in various formulations for products designed for use by humans . panthenol , also known as vitamin b5 , comes in two enantiomers , the d and l versions . while only d - panthenol ( dexpantheno is considered biologically active , both forms are known to have moisturizing properties . for cosmetic use , panthenol comes either in the d form , or as a racemic mixture containing both the d and l enantiomers ( dl - panthenol ). the racemic version is commonly used in the cosmetic and skin care industry for a variety of topically applied products . given the broad scope of the present invention , it would be useful to present several examples of specific formulations and methods of manufacture that may be considered illustrative but not limiting in the explanation of certain preferred embodiments of the present invention . the examples shown below are only two of the many products that could be formulated using the concepts and methods of the present invention . facial cleanser formulation . this is a formula and manufacturing process for a facial cleanser in accordance with a preferred embodiment of the present invention . part a — in a glass beaker , bring 3220 gm . of treated water to a temperature of 80 ° centigrade . add 0 . 1 gm . biotin and 2 gm . of aloe powder and 1 gm . of potassium sorbate and 40 gm . structure xl and 10 gm . of methocel 10 - 101 powder . place part a into a standard mixer on low speed . part b — mix together 511 gm . ricinoleamidopropyl betaine with 439 gm . ritafactant 138 an ( deecyl glucoside , sodium lauroyl lactylate ) and 5 gm . d - panthenol and 11 gm . l - bisabolol and 10 . 8 gm . d - alpha tocopherol . add part b into part a while the mixer is on low speed . part c — mix together 135 . 6 gm . sorbitol with 1 . 2 gm . octaquest e - 30 and 30 gm . % stail ( phenethyl alcohol 58 % and caprylyl glycol 42 % conc .). mix part c into previously combined part a and part b . skin lotion formulation . this is a formula and manufacturing process for a skin lotion cleanser in accordance with a preferred embodiment of the present invention . part a — heat 3 , 250 ml of treated water to 85 ° degree centigrade and add 4 gm . l - sodium hyaluronate . after the hyaluronate has dissolved , add 2 gm . potassium sorbate and mix well . then , in a glass bowl add 80 ml glycerin with 16 gm . xanthan gum to make a paste and combine with liquid ingredients . part b — combine 320 gm . oliven 1000 ( b & amp ; t ) with 371 . 6 gm . myristol 318 ( caprylic / capric triglyceride ) and 81 gm . jojoba oil . heat combined ingredients to 85 ° centigrade . use a 4 - inch dispersion blade and combine a with part b and mix together for 25 minutes . follow this with a regular cool bath process and add the following ingredients at 40 degree centigrade 40 ml d - vitamin e ( d - tocopherol )( covitol ik00069 ) and 40 gm d - panthenol and 20 gm l - alpha bisabolol and 0 . 2 gm biotin and 50 ml treated water and 48 gm stabil and 2 ml octaquest e - 30 ( edds ). referring now to fig1 , a flow chart for formulating compounds in accordance with the preferred embodiments of the present invention is depicted . as shown in fig1 , typically , a base for the formulation is created ( step 110 ). this base may be a liquid , such as purified or treated water , and may include other ingredients such as oil . next , one or more chirally correct ingredients can be added ( step 120 ), if desired . next , one or more natural ingredients can be added ( step 130 ), if desired . finally , one or more organic ingredients can be added ( step 140 ), if desired . those skilled in the art will also recognize that the process set forth in fig1 is intended to create product formulations that are less likely to cause undesirable biological responses , allergic reactions , etc . as shown in fig1 , it is possible to include any and / or all of the various components , in any order , as may be required for the specific product formulation . those skilled in the art will also recognize that , in at least some cases , the exact order of adding the various ingredients may be altered without materially affecting the outcome of the manufacturing process . accordingly , those skilled in the art will recognize that the unique combinations of ingredients set forth herein are selected so as to be the healthiest and chemically benign components possible for use in cosmetic and skin care applications . it should also be noted that the various preferred embodiments of the present invention are not directed towards preventing or eliminating all potential risks associated with internalization of racemic compounds . rather , the methods of the present invention are directed towards reducing and minimizing toxicity or harmfulness , particularly with regards to long - term exposure due to inadvertent or accidental exposure to racemic compounds and agents that may produce undesired biological responses , as well as non - natural and non - organic compounds with unknown effect on the biological system of humans and animals . lastly , it should be appreciated that these embodiments are preferred exemplary embodiments only , and are not intended to limit the scope , applicability , or configuration of the invention in any way . rather , the foregoing detailed description provides those skilled in the art with a convenient road map for implementing a preferred exemplary embodiment of the invention , it being understood that various changes may be made in the function and arrangement of elements described in the exemplary preferred embodiment without departing from the spirit and scope of the invention as set forth in the appended claims . | as disclosed herein , a series of compounds that are not generally intended for internalization such as cosmetic and skin care products are formulated using chirally correct components , organic ingredients , and natural or naturally derived ingredients . in this fashion , any deleterious biological effects due to inadvertent or incidental internalization may be reduced or minimized to a greater extent . the chirally correct formulations may be used in various types of skin creams , cleansers , lotions , etc . that are formulated for application to the external surfaces of a biological entity , including humans and animals . in addition to the use of chirally correct ingredients , other formulations include additional natural and / or organic ingredients . |
before any embodiments of the present invention are explained in detail , it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the accompanying drawings . the invention is capable of other embodiments and of being practiced or of being carried out in various ways . also , it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting . the use of “ including ,” “ comprising ,” or “ having ” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items . unless specified or limited otherwise , the terms “ mounted ,” “ connected ,” “ supported ,” and “ coupled ” and variations thereof are used broadly and encompass both direct and indirect mountings , connections , supports , and couplings . further , “ connected ” and “ coupled ” are not restricted to physical or mechanical connections or couplings . also , it is to be understood that phraseology and terminology used herein with reference to device or element orientation ( such as , for example , terms like “ central ,” “ upper ,” “ lower ,” “ front ,” “ rear ,” and the like ) are only used to simplify description of the present invention , and do not alone indicate or imply that the device or element referred to must have a particular orientation . in addition , unless otherwise specified , terms such as “ first ,” “ second ,” and “ third ” are used herein for purposes of description and are not intended to indicate or imply relative importance or significance . disclosed herein is a process and apparatus for treating food products with a cleaning substance . although use of the process and apparatus in a number of different applications is contemplated , the use described and illustrated herein by way of example is in an olr ( on - line reprocessing ) environment . in some embodiments , this process and apparatus can employ a design that ensures flood filling and / or drench spraying of animal carcasses with non - recycled acidified chlorine dioxide ( clo 2 ). acidified clo 2 is a dilute solution of clo 2 ( target 25 - 50 ppm solution , in some embodiments ) that is acidified post generation ( target ph 2 . 3 - 2 . 9 , in some embodiments ). both chlorine dioxide and acidified sodium chlorite ( which generates 25 - 50 ppm clo 2 at a recommended use ph of 2 . 2 - 2 . 9 ) have been approved by some regulatory agencies for use in olr . acidification of clo 2 is a way of using the antimicrobial qualities of both agents for olr while providing additional benefits of improved safety , monitoring , and environmental stewardship . in some indirect methods of acid chlorite clo 2 generation ( an example of which is disclosed in u . s . pat . no . 7 , 087 , 208 , the entire contents of which are incorporated herein by reference ), ion exchange provides the acid required to generate the clo 2 intermediate , chlorous acid ; then a platinum catalyst is used to convert the chlorous acid to clo 2 . in such methods , operational safety is improved , since there is no direct mixing of acid and chlorite , which in a mixing failure can result in an explosive concentration of clo 2 . as will be discussed in greater detail below , spray cabinets according to some embodiments of the present invention can be vented , and effluent from the spray cabinet can be contained within a waste stream in order to provide a safe working environment for employees of food processing plants , as per osha air quality requirements . furthermore , by reducing the amount of disinfection by - product sodium chlorite , environmental impact is lessened and food safety is improved . referring now to fig1 to 3 , there is illustrated a cleaning apparatus generally designated by reference number 30 . the cleaning apparatus 30 can define a station incorporated into an automated food processing system . the cleaning apparatus 30 can be installed on an existing or new automated processing line , or in other embodiments , need not necessarily be used in conjunction with an automated processing line . for exemplary purposes , the cleaning apparatus and process will now be described as it relates to processing eviscerated poultry ( e . g ., chickens , ducks , geese , turkeys , and the like ). however , it is noted that the apparatus and process can also be employed as a station for automated processing of such food in other stages of a food processing system ( e . g ., prior to evisceration ), and for other animal carcasses , fish , and other foods , such as vegetables and fruit , as would be apparent to those skilled in the art in view of this disclosure . in any case , the cleaning apparatus 30 can be used for treating various types of food with an anti - microbial agent to remove pathogens and / or retard spoilage caused by microbes . as illustrated in fig1 and 2 , the cleaning apparatus 30 can include a housing 36 having an entrance 32 and an exit 34 that allows eviscerated poultry carcasses 20 to enter and exit the housing 36 by means of a conveyor 10 ( see fig2 ). also with reference to fig2 , water curtains 60 adjacent the housing entrance 32 and / or exit 34 can be used in order to help contain cleaning substances and byproducts of the cleaning process within the housing 36 . the housing structure 36 can be fabricated from a corrosion resistant material or a combination of such materials , such as stainless steel , or usda approved thermoplastics . it is not necessary that the invention be constrained to a design having only one such housing structure 36 along a processing system , as shown in the illustrated embodiment . other possible configurations will be explained in the description that follows . the conveyor 10 ( if used ) can comprise a track 12 that extends along each station of the processing system . the track 12 can be located anywhere with respect to the housing 36 facilitating the movement of carcasses through the housing 36 , such as at an overhead location , a side location , or a floor location . with reference to fig2 , each poultry carcass 20 can be hung from a yoke 16 secured to a track follower 14 that can be moved along the track 12 of the automated processing system . the poultry carcasses 20 can be hung so that the vent 18 of each carcass 20 is oriented upward to permit spraying of a cleaning substance into the cavities as well as onto the exterior surfaces of the carcass 20 during cleaning operations . many cleaning substances in various forms ( gas , liquid , powder ) can be used in conjunction with the cleaning apparatus 30 without departing from the scope of the present invention . these substances can be detergents , disinfectants , brine solutions , anti - microbial agents , and any other sterilizing , sanitizing , or cleaning substances acceptable for use in cleaning food product . for example , appropriate anti - microbial agents include phosphates , sodium chlorite , hydrogen peroxide , ozone , periacetic acid , hypochlorous acid , citric acid , lactic acid , sodium hypochlorite , ozonated water , combinations of substances comprising at least one of the foregoing antimicrobials , and the like . for the purposes of this description however , chlorine dioxide gas in solution is used . in some embodiments , a mixing chamber 94 is used to prepare cleaning fluid for use in the cleaning apparatus 30 . operation of the mixing chamber 94 can be an integral part of an automated processing system for control and operation of the cleaning apparatus and connected equipment supplying cleaning fluid thereto . in some embodiments , a batch tank ( not shown ) can be connected between the mixing chamber 94 and any or all of the supply pipes 40 in order to collect and store mixed cleaning fluid prior to use . such collection and storage can take place following dilution of one or more concentrated cleaning substances in the mixing chamber 94 . sensors can be located in the batch tank or suitable conduit ( s ) connecting the batch tank to the mixing chamber in order to measure and / or monitor ph , concentration , temperature , flow , and volume , among other things . in this manner , any desired property or properties of the resulting solutions used in the cleaning apparatus 30 can be controlled to ensure they meet regulatory standards . in other embodiments , the mixing chamber 94 can be connected directly to one or more of the supply pipes 40 of the cleaning system . an example of a mixing chamber 94 is shown in fig7 , which illustrates a device that can be used to mix concentrated cleaning fluid with diluent ( e . g ., water , in some embodiments ) for later delivery to the cleaning apparatus 30 . as shown in fig7 , the mixing chamber can be defined in a “ y ”- shaped fitting 90 having a first inlet 64 , a second inlet 74 , and an outlet 84 . the second inlet 74 of the “ y ”- shaped fitting 90 can be positioned at an angle 80 with respect to the first inlet 64 . in some embodiments , more than two inlets and / or more than one outlet can be provided for the mixing chamber 94 , such as to introduce concentrated cleaning fluid into the fitting through more than one inlet and / or to introduce diluent into the fitting 90 through more than one inlet . these alternative fittings can be particularly useful in applications where more than one type of diluent and / or more than one type of concentrated cleaning fluid is to be mixed . in some embodiments , sensors can be provided in either or both inlet 64 , 74 , and / or conduits 66 , 76 to monitor properties of the component substances entering the mixing chamber 94 . although the angle 80 illustrated in fig7 is desirable in many applications , in other embodiments other acute angles between a vertical orientation of the fitting 90 and the second inlet 74 can be utilized . it should also be noted that the outlet 84 of the fitting 90 can be at any angle with respect to the inlets 64 , 74 , and can be in the same or a different plane from that formed by the angle between the inlets 64 , 74 . fig7 illustrates a first supply tube 66 and a second supply tube 76 that can be connected to the first inlet 64 and the second inlet 74 of the fitting 90 , respectively . the first supply tube 66 and the second supply tube 76 provide conduits for a first element of the mixture ( the general movement of which can be represented by arrow 68 ) and a second element of the mixture ( the general movement of which can be represented by arrow 78 ) to the inlets 64 , 74 of the mixing chamber 94 . an outlet tube 86 can be connected to the outlet 84 of the mixing chamber to provide a conduit for the mixed fluid ( the general movement of which can be represented by arrow 88 ) from the mixing chamber 94 . in other embodiments , the mixing chamber 94 can be defined in at least one fitting of another shape , a container , a combination of fittings and / or containers , and the like . however , an acute angle between one of the inlets 74 and another vertically - oriented or substantially vertically oriented inlet 64 can produce good performance results in many applications . alternatively , an acute angle formed between each of the inlets 64 , 74 and a substantially horizontal orientation can also produce good performance results . the inlets 64 , 74 can both define a “ y ”- shaped fitting 90 in these manners , and can be used to introduce one element into the flow of another for mixing purposes . as noted above , in other embodiments , the fitting 90 can be adapted to introduce more than one other element into another , such as through the use of three or more inlets ( which can permit simultaneous introduction of such elements , in some embodiments ). alternatively , such mixing can be accomplished by introducing different elements into the mixing chamber 94 through the same inlet 64 , 74 in consecutive steps . in addition , the fitting 90 can be provided with any number of mechanical implements ( not shown ) to assist in the mixing process . the mechanical implements can be actively powered or can make use of the power generated by the flowing fluid ( s ). in some embodiments , the “ y ”- shaped fitting 90 can be adapted from a “ y ” strainer , in which case the strainer can be removed or modified to make room for the second supply tube 76 ( if necessary ). also if necessary , the second supply tube 76 can be connected to the second inlet 74 of the “ y ”- shaped fitting 90 with a cap 72 having a tapped hole or modified to have a tapped hole for accommodating the supply tube 76 . in some embodiments , one or more connectors 70 can be used to form a sealed connection between the second supply tube 76 and the cap 72 and / or the second inlet 74 . such connectors include , without limitation , any type of compression fittings , threaded fittings , and the like . such connection types can be provided at any of the inlets or outlets of the “ y ”- shaped fitting 90 . the connectors , tubing , and mixing chamber can be made of polyflo or other materials suitable for the types of fluid being supplied through the “ y ”- shaped fitting 90 , including many types of metal , alloys , composites , plastics , and combinations of these , among others . additionally , any of these materials can be treated with a coating to prevent corrosion . both direct and indirect connections between the tubes and the inlets / outlets can be made by welding , soldering , threaded connections , adhesive , or by other means known to those of skill in the art . the shape and orientation of the mixing chamber 94 , the inlets 64 , 74 , and the outlets 84 can be designed to facilitate the mixing process . in the embodiment of fig7 , the mixing chamber 94 can be oriented such that the flow 68 of the first element is in a substantially downward direction . for the purposes of this description , the arrow 68 represents the flow of diluent ( e . g ., water , in the illustrated embodiment ). the second element of the mixture can flow in a partially downward direction due to the angle 80 . for the purposes of this description , arrow 78 represents the flow of the concentrated cleaning chemical ( e . g ., chlorine dioxide , in the illustrated embodiment ). in some embodiments , the second supply tube 76 can extend beyond the second inlet 74 into the flow path 68 of the first element ( water , in this case ), creating a blending zone 92 where the flows 68 , 78 meet . one or more metering valves ( not shown ) can be located at or upstream of at least one inlet or supply tube of the “ y ”- shaped fitting 90 to measure , monitor , and / or control the flow of any or all of the elements . similarly , flow meters and / or other sensors can be located at or downstream of the outlet 84 or outlet tube 86 to measure , monitor , and / or control the flow 88 of the mixed solution from the mixing chamber 94 . providing the second flow path 78 at an acute angle 80 to the first flow path 68 can minimize back pressure on the supply tube 76 , which can help ensure sufficient blending of the elements . it should be noted that in other embodiments of the present invention , the supply of diluent and the supply of concentrate to the mixing chamber 94 in the illustrated embodiment can be reversed while still performing the desired mixing function . in such cases , the supply tube 76 can be provided in the first inlet 64 and / or the supply tube 66 can be provided in the second inlet 74 . also , in other embodiments , the diluent and concentrate can both be supplied to the mixing chamber via respective supply tubes 76 ( or 66 ). in some embodiments , the cleaning apparatus 30 has one or more zones 22 , 24 , 26 in which carcasses 20 are exposed to one or more types of cleaning substances . the zones 22 , 24 , 26 can be completely or partially open to one another within the housing 36 . for example , the cleaning apparatus illustrated in fig2 has two dividing walls 33 partially separating zone one 22 from zone two 24 , and zone two 24 from zone three 26 . these dividing walls 33 can separate the zones 22 , 24 , 26 from each other to any degree , and in some embodiments ( see fig5 ) do so substantially completely with the exception of openings sufficiently large to permit the passage of carcasses 20 between the zones 22 , 24 , 26 . the cleaning substances can extend through any number of different supply pipes 40 to the cleaning apparatus , such as one or more supply pipes per zone 22 , 24 , 26 , one or more supply pipes common to two or more zones , and the like . in the illustrated embodiment of fig2 , for example , each zone 22 , 24 , 26 has a dedicated supply pipe 40 supplying cleaning fluid to the respective zone . the supply pipe ( s ) 40 can extend from a mixing apparatus ( e . g ., mixing chamber , vessel , conduit , and the like , not shown ) in which the cleaning fluid is prepared and / or stored . with reference to fig3 , in some embodiments , the supply pipes 40 for one or more zones 22 , 24 , 26 are connected to and supply cleaning fluid to at least one header pipe 42 in each zone 22 , 24 , 26 . the header pipes 42 provide conduits for cleaning fluid between the supply pipe 40 and at least one outlet . in some embodiments , the outlet can be a nozzle of a desired type ( e . g ., first type of spray nozzle 44 or a second type of nozzle 46 ). the header pipe 42 can have multiple branches ( not shown ) oriented in any direction within the housing 36 . additionally , each of the nozzles 44 , 46 connected to the header pipe 42 can be oriented in any direction within the housing . in some embodiments , the spray nozzle 44 dispenses a relatively low volume of cleaning substance , and can do so at a relatively high pressure . in some embodiments , flat jet spray nozzles are used for spray nozzle 44 . also in some embodiments , the second type of nozzle 46 dispenses a relatively high volume of the cleaning substance , and can do so at a relatively low pressure . this second type of nozzle can comprise a variety of nozzles , such as a flood nozzle , a full cone nozzle , and the like . the apparatus 30 can incorporate valves 52 ( see fig4 - 6 ) and / or pumps ( not shown ) to control the flow rate of the cleaning substance dispensed from each nozzle 44 , 46 . some embodiments can also include sensors 56 that can be coupled to or incorporated integrally within the pipes 40 , 42 , valves 52 , tanks ( not shown ), and / or nozzles 44 , 46 , or positioned in any suitable manner within ( each zone 22 , 24 , 26 ) or outside of the housing 36 for process control and / or safety purposes . these sensors 56 can be used to monitor one or more properties of the cleaning substance supplied within the apparatus 30 , such as the ph level of a cleaning fluid , the concentration of cleaning agent in the cleaning fluid , and the like . these sensors 56 can be connected to processing equipment ( not shown ) in any desired manner for sensing and controlling such properties of the cleaning substance supplied within the apparatus 30 , such as for sensing and controlling the chemical concentration or acidity level ( dosing ) in any zone in the apparatus 30 , or the rate of delivery of the cleaning substance in each zone 22 , 24 , 26 . in this regard , feedback loops can enable constant or periodic adjustment of such properties based upon signals received from the sensors . in some embodiments , data from the sensors is collected , processed , displayed , and recorded in a central location , such as a control panel viewable by a user . the control panel can provide for manual or automatic adjustment of dosing equipment as well as integrated ventilation , drainage , and safety / alarm systems . some examples of possible properties that the sensors 56 can monitor include : pressure , chemical concentration , temperature , ph , humidity , liquid level , and flow rate , among others . any type and number of sensors can be used for detecting one or more properties of the cleaning substance supplied within the apparatus 30 , the effluent drained from the apparatus 30 , or the air quality surrounding the apparatus 30 . in some embodiments , different types of sensors can be utilized for different zones 22 , 24 , 26 of the apparatus 30 , depending upon various factors in each zone ( e . g ., in light of the environmental conditions to which the sensors will be exposed in a given zone , the need to monitor one or more chemical properties with more precision in a given zone , and the like ). for example , in some embodiments , zones 1 and 3 can be provided with amperometric sensors such as those from walchem inc . in order to measure and / or monitor the concentration of chlorine dioxide in these zones , and in some embodiments for recording this concentration over a period of time . as another example , zone 2 can be provided with one or more on - line spectrophotometric probes such as those from optek inc . in order to measure and / or monitor the relatively high level of chlorine dioxide in zone 2 . such sensors can also be provided as part of a control feedback loop to regulate the concentration of the cleaning fluid ( e . g . by controlling the flow of elements into the mixing chamber 94 ). also , any of the zones 22 , 24 , 26 can be provided with ph sensors for monitoring and / or controlling the ph of the fluid in such zones . for example , in the illustrated embodiment , zones 2 and 3 are provided with ph sensors in order to measure and / or monitor the acidity of the cleaning fluid in these zones . these sensors can also be provided as part of a feedback loop in order to control the acidity of the cleaning fluid in any of the zones 22 , 24 , 26 . for example , an acid pump can be tied to the flow meter , such that additional acid can be fed to the zone 2 antimicrobial solution as determined by the ph probe or the flow meter that is measuring the dilution water volume delivery rate . one or more flow sensors can also be used in any of the zones 22 , 24 , 26 to monitor and possibly record the flow rate of chemical solution in such zones 22 , 24 , 26 . for example , burkert paddle wheel flow sensors can be provided in any or all of the first , second , and third zones 22 , 24 , 26 of the illustrated embodiment for such purposes , and can provide a control feedback loop to regulate the flow rate of the cleaning solution in these zones 22 , 24 , 26 or to perform other functions ( e . g ., ph control of one or more zones 22 , 24 , 26 such as to zone 3 in some embodiments , flow rate history recording in any of the zones 22 , 24 , 26 , and the like ). other types of sensors in other zones and combinations of zones are possible , and fall within the spirit and scope of the present invention . additionally , electrochemical or other types of air monitors ( not shown ) can be included in the system . for example , an air monitor can be located near the mixing chamber and batch tank ( which can be located in a separate chemical room , in some embodiments ), and another air monitor can be located on the processing floor near the operators , inspectors , and spray cabinet . alarms can be tied to these sensors to alert personnel and / or shut down the system if certain levels are exceeded . in some embodiments , the alarm can be a flashing light , a siren , or an automatically generated email message regarding the specifics of the situation , among others . in an embodiment using acidified clo 2 as the cleaning substance , electrochemical clo 2 gas detectors ( such as those manufactured by industrial scientific corp . with a minimum detection limit of 0 . 01 ppm ) can be placed within a reasonable distance ( e . g ., approximately 5 feet ) of the apparatus to ensure operator safety and to add redundancy to other sensors within the system . with reference now to fig2 - 6 of the illustrated embodiment , the floor of the housing 36 can have at least one drainage section 50 , and can connect to one or more drain pipes 48 removing the cleaning substance ( s ) from the housing 36 . in the illustrated embodiment of fig2 , the cleaning substance collected in each of three drainage sections 50 is comingled in a common drain pipe 48 and passed to a recovery or disposal tank ( not shown ). in other embodiments , drainage sections 50 can also have dedicated drain pipes 48 that pass their contents separately to recovery or disposal tanks . the cleaning fluids passing through the drain pipe ( s ) 48 can be recovered and recycled in some embodiments , such as by recycling cleaning fluid in the illustrated embodiment of fig2 into the chlorine dioxide supplied to the apparatus 30 . in other embodiments , the cleaning fluids exiting through the drain pipe ( s ) 48 are not recycled to the apparatus 30 . in some embodiments , the apparatus 30 can use exhaust vents 54 to evacuate airborne toxins and / or other chemicals from the housing 36 ( e . g . gas that comes out of solution , powder , vapors , etc .). as described above , some embodiments can also include a monitoring system with sensors 56 that can be mounted inside and / or outside the housing 36 for process control and / or safety purposes . the function of the illustrated apparatus 30 is most easily described by distinguishing the steps of a cleaning process . in the illustrated embodiment of fig2 , each step takes place in a separate spatial zone 22 , 23 , 24 within the housing 36 . in some embodiments , one or more of these spatial zones can be combined . as shown in fig1 , the first zone 22 is located within the housing 36 closest to the entrance 32 . in the first zone 22 , a pre - rinse can be used to remove gross soils ( primarily fecal contamination ) from eviscerated poultry carcasses 20 in some applications . zone one 22 of the illustrated embodiment is shown in fig4 . in some embodiments , at least one set of two header pipes 42 can extend upward adjacent side walls of the housing 36 . any number of spray nozzles 44 can extend from each of the header pipes 42 . each spray nozzle 44 can be directed to dispense the cleaning substance toward the carcasses 20 on the conveyor 10 . the spray nozzles can be positioned and directed to drench spray the carcasses ( i . e ., contact all external surfaces with the solution being sprayed ). the ends of the header pipes 42 can be shaped to extend toward the conveyor line and in a generally downward direction to direct the cleaning substance dispensed from nozzles 46 at the ends of the header pipes 42 toward the carcasses 20 on the conveyor 10 . these nozzles 46 can be used to flood ( i . e ., fill or substantially fill ) the interior cavities of the carcasses 20 with the cleaning substance . in some embodiments , the pre - rinse provided by zone one 22 , provides category 1 ( hedonic scale ) carcasses , such that there is no visible contamination of the carcass . in some embodiments , a chlorine dioxide solution at a concentration of no less than about 0 . 1 ppm is dispensed from nozzles 44 , 46 in zone one 22 . alternatively , a chlorine dioxide solution at a concentration of no less than about 1 . 0 ppm dispensed from nozzles 44 , 46 in zone one 22 can be used to provide desired results . also , in some embodiments , a chlorine dioxide solution at a concentration of no greater than about 5 . 0 ppm is dispensed from nozzles 44 , 46 in zone one 22 . alternatively , a chlorine dioxide solution at a concentration of no greater than about 3 . 0 ppm dispensed from nozzles 44 , 46 in zone one 22 can be used to provide desired results . the acidity level of the chlorine dioxide solution dispensed in this section ( zone one 22 ) is not adjusted in the illustrated embodiment of fig2 - 6 , but can be in other embodiments . in some embodiments , the above - described chlorine dioxide solution is dispensed from the collective nozzles 44 , 46 in zone one 22 at a flow rate of no less than about 2 gpm . alternatively , this chlorine dioxide solution can be dispensed from the collective nozzles 44 , 46 in zone one 22 at a flow rate of no less than about 12 gpm . in other embodiments , the above - described chlorine dioxide solution is dispensed from the collective nozzles 44 , 46 in zone one 22 at a flow rate of no greater than about 10 gpm . in still other embodiments , the above - described chlorine dioxide solution is dispensed from the collective nozzles 44 , 46 in zone one 22 at a flow rate of no greater than about 20 gpm . alternatively , this chlorine dioxide solution can be dispensed from the collective nozzles 44 , 46 in zone one 22 at a flow rate of no greater than about 16 gpm . in the illustrated embodiment of fig2 - 6 , the second zone 24 of the apparatus 30 is located within the housing 36 downstream of the conveyor 10 from the first zone 22 . in the second zone 24 , efficacious quantities of the cleaning substance ( at a generally higher chemical concentration than zones one and three 22 , 26 , and possibly at a generally lower flow rate than zone one 22 ) can be applied in order to significantly reduce the pathogen levels on the inner and outer surfaces of the poultry carcasses 20 . zone two 24 of the illustrated embodiment of fig2 - 6 is shown in fig5 . in some embodiments , at least one set of two header pipes 42 can extend upward adjacent side walls of the housing 36 . any number of spray nozzles 44 can be connected to the header pipes 42 and can be directed to dispense the cleaning substance toward the carcasses 20 on the conveyor 10 . in the illustrated embodiment of fig2 - 6 , the ends of the header pipes 42 are shaped to extend toward the conveyor line and in a generally downward direction to direct the cleaning substance dispensed from spray nozzles 44 at the ends of the header pipes 42 toward the carcasses 20 on the conveyor 10 . in some embodiments , nozzles are positioned and directed to contact all internal and external surfaces of the carcass ( or other item ), by film spraying . in some embodiments , a chlorine dioxide solution at a concentration of no less than about 10 ppm is dispensed from the spray nozzles 44 in zone two 24 . alternatively , a chlorine dioxide solution at a concentration of no less than about 25 ppm dispensed from the spray nozzles 44 in zone two 24 can provide desired results . also , in some embodiments , a chlorine dioxide solution at a concentration of no greater than about 100 ppm is dispensed from the spray nozzles 44 in zone two 24 . alternatively , a chlorine dioxide solution at a concentration of no greater than about 50 ppm is dispensed from the spray nozzles 44 in zone two 24 . the acidity level of the chlorine dioxide solution can be adjusted to a ph of 2 - 4 in some embodiments , and can be adjusted to other levels in other embodiments , as desired . in one particular embodiment , an acidified chlorine dioxide solution , such as described in co - pending pct patent application no . pct / us2007 / 085211 , is used in zone two 24 . the entire contents of co - pending pct patent application no . pct / us2007 / 085211 is hereby incorporated by reference . in some embodiments , the above - described chlorine dioxide solution is dispensed from the collective spray nozzles 44 in zone two 24 at a flow rate of no less than about 1 gpm . alternatively , this chlorine dioxide solution can be dispensed from the collective spray nozzles 44 in zone two 24 at a flow rate of no less than about 4 gpm . in some embodiments , the above - described chlorine dioxide solution is dispensed from the collective spray nozzles 44 in zone two 24 at a flow rate of no greater than about 10 gpm . alternatively , this chlorine dioxide solution can be dispensed from the collective spray nozzles 44 in zone two 24 at a flow rate of no greater than about 8 gpm . as shown in fig2 , a third zone 26 is located within the housing 36 downstream of the conveyor 10 from the first and second zones 22 , 24 . in the third zone 26 , a post - rinse can be used to remove excess amounts of the cleaning agent from the poultry carcasses 20 . this post - rinse can be provided by supplying a cleaning substance having a lower concentration of cleaning agent than provided in zone two 24 . in some embodiments , this lower concentration flow can be used to lower the concentration of cleaning agent on the carcasses 20 in zone three 26 to a level meeting national or local health and / or safety regulations prior to exit of the carcasses 20 from the housing 36 . for example , in some embodiments , the concentration of residual chlorine dioxide on the carcasses 20 can be reduced to no greater than 3 ppm upon exiting zone three 26 . by utilizing such a cleaning agent flow in zone three 26 , a higher and more effective cleaning fluid flow in zone two 24 can be used while still quickly bringing the food product within health and / or safety regulations upon completion of the cleaning process . zone three 26 of the illustrated embodiment is shown in fig6 . in some embodiments , at least one set of two header pipes 42 can extend upward adjacent the side walls of the housing 36 . any number of spray nozzles 44 can extend from each of the header pipes 42 . each spray nozzle 44 can be directed to dispense the cleaning substance toward carcasses 20 on the conveyor 10 . in the illustrated embodiment of fig2 - 6 , the ends of the header pipes 42 are shaped to extend toward the conveyor line and in a generally downward direction to direct the cleaning substance dispensed from spray nozzles 44 at the ends of the header pipes 42 toward the carcasses 20 on the conveyor 10 . the nozzles 44 in this zone 26 can be used to film spray the inside and outside of the carcasses 20 . in some embodiments , a chlorine dioxide solution at a concentration of greater than 0 ppm is dispensed from the spray nozzles 44 in zone three 26 . alternatively , a chlorine dioxide solution at a concentration of no less than about 1 ppm dispensed from the spray nozzles 44 in zone three 26 can be used to provide desired results . also , in some embodiments , a chlorine dioxide solution at a concentration of no greater than about 5 ppm is dispensed from the spray nozzles 44 in zone three 26 . alternatively , a chlorine dioxide solution at a concentration of no greater than about 3 ppm dispensed from the spray nozzles 44 in zone three 26 can be used to provide desired results . the acidity level of the chlorine dioxide solution can be adjusted to a ph of 2 - 4 in some embodiments , and can be adjusted to other levels in other embodiments , as desired . in some embodiments , the above - described chlorine dioxide solution is dispensed from the collective spray nozzles 44 in zone three 26 at a flow rate of no less than about 0 . 5 gpm . alternatively , this chlorine dioxide solution can be dispensed from the collective spray nozzles 44 in zone three 26 at a flow rate of no less than about 1 gpm . in some embodiments , the above - described chlorine dioxide solution is dispensed from the collective spray nozzles 44 in zone three 26 at a flow rate of no greater than about 5 gpm . alternatively , this chlorine dioxide solution can be dispensed from the collective spray nozzles 44 in zone three 26 at a flow rate of no greater than about 4 gpm . as illustrated in fig1 , the housing 36 can also include an automated cleaning header 58 that provides at least one conduit for a cleaning substance to be dispensed within the housing 36 to clean the apparatus 30 . although the various embodiments of the apparatus 30 described above have a single housing , it should be noted that separate housings 36 can exist along the processing line in which at least one step of the treatment process can be performed . additionally , the invention can incorporate other treatment processes along with those disclosed herein , including the use of brushes or other cleaning devices that can mechanically assist in the cleaning process . furthermore , although chlorine dioxide solution is the cleaning substance used in each step of the illustrated embodiments described above , in other embodiments , different substances can be used in one or more of the steps . other modifications , changes , and substitutions are intended in the foregoing description and in the accompanying drawings , and in some instances , some features of the invention will be employed without a corresponding use of other features . for example , in some embodiments , the pre - rinse step need not necessarily be used if there is a minimal amount of particulate matter on the food items being processed . also , although entrance and / or exit water curtains 60 can be used , in other embodiments such water curtains 60 may not be necessary . the embodiments described above and illustrated in the figures are presented by way of example only and are not intended as a limitation upon the concepts and principles of the present invention . as such , it will be appreciated by one having ordinary skill in the art that various changes in the elements and their configuration and arrangement are possible without departing from the spirit and scope of the present invention . | an apparatus and method for cleaning carcasses is described and illustrated , as is a device for mixing a cleaning substance that can be used in such applications . in some embodiments , the apparatus and method utilize a multi - phase cleaning substance spraying procedure in which the cleaning substance has desired levels of chlorine dioxide and is delivered to the carcasses at desired flow rates , both of which can vary between phases of the procedure and / or at different locations of the carcasses being cleaned . |
the novel complexes may be produced by reacting the acid , e . g . 2 , 6 - pyridinedicarboxylic acid , with a tetraalkoxygermanium , preferably tetramethoxygermanium or tetraethoxygermanium . the tetraalkoxygermanium may be formed directly in the reaction mixture , for instance , from a germanium tetrahalide and an alkali metal alcoholate , e . g . germanium tetrachloride and sodium ( m ) ethanolate ( obtained by dissolving metallic sodium in ( m ) ethanol ). the reaction may be performed in an organic solvent medium such as hexane , heptane , methanol or ethanol ; the reaction temperature is usually within the range of 60 ° to 90 ° c . the reaction is preferably performed under an inert gas atmosphere such as argon or nitrogen , the reaction time being about 3 - 5 hours . the target product is recovered by conventional methods , for instance , filtration and drying in vacuum , for example , at 1 torr at 40 ° c . the invention also provides a pharmaceutical composition containing as the active ingredient an effective amount of the germanium complex with a pharmaceutically acceptable carrier , excipient , or diluent . the pharmaceutical composition may be administered by different routes such as oral , parenteral , intranasal , etc . for oral application , the composition may be used in the form of tablets , aqueous suspensions , dispersed powders or granules , as well as syrups or elixirs . the compositions intended for oral administration may be obtained by any method known in the art used for preparation of pharmaceutical compositions . such compositions may contain one or more agents selected from sweeteners , aromatizers , dyeing agents and preservatives used for pharmaceutical preparations possessing good aesthetic and taste qualities . the tablets may contain the active ingredient in a mixture with non - toxic pharmaceutically - acceptable excipients which are commonly used for preparation of tablets . said excipients may be inert diluents such as calcium carbonate , sodium carbonate , lactose , calcium phosphate , granulating and disintegrating agents , for example , maize starch , cellulose derivates or alginic acid . the tablets may have no coating or be coated by known methods , e . g . with a membrane delaying the process of decomposition thereof in the gastrointestinal tract , exerting thereby a prolonged effect . aqueous suspensions may contain the active ingredient in a mixture with excipients suitable for the preparation of aqueous suspensions . pharmaceutical compositions for parenteral administration , for instance , subcutaneous or intramuscular , may comprise sterile injection solutions in water or physiological saline . for intranasal administration , the pharmaceutical composition may comprise a solution of the germanium complex in water or physiological saline solution . as will be clear to those skilled in the art , the dose of complex to be used will depend upon the desired effect , e . g . immunomodulating , interferon - inducing , anti - infectious , as well as upon the degree of the seriousness of the disease , age and condition of the patient . usually , a single dose is from 0 , 05 mg / kg to 100 mg / kg . the number of administrations may vary from 1 to 4 per day . the novel complex has low toxicity . in investigations of acute toxicity in mice , the ld 50 is 900 mg per kilo body weight . specific examples of obtaining the germanium - organic compound of formula i , the physico - chemical characteristics thereof , examples of pharmaceutical compositions based thereon , as well as the results of biological trials thereof are presented below . the structure of the obtained compound has been confirmed by the data of spectral analysis ( ir , 1 h and 13 c nmr , mass ), the purity was proved by the element analysis data . the ir spectra of germanium bis ( pyridine - 2 , 6 - dicarboxylate ) were obtained on the apparatus “ bruker ifs 113v ”. the 1 h nmr and 13 c nmr were obtained on the spectrometer “ bruker ac - 200 ”. mass - spectra ( eu ) were obtained on the apparatus “ finnigan at incos 50 ” at 70 ev . 6 , 4 g ( 0 , 038 mol ) 2 , 6 - pyridinedicarboxylic acid , 4 , 0 g ( 0 , 02 mol ) tetramethoxygermanium and 25 ml absolute methanol under a nitrogen atmosphere were heated under reflux with vigorous stirring at the boiling point of the solvent ( 64 ° c .) for 3 hours . the sediment was filtered in a shott filter , washed with methanol ( 2 × 10 ml ) and dried at a temperature of 40 ° c . in vacuum ( 1 torr ) for 3 hours . the yield was 6 . 88 g ( 90 %) of the compound based on 2 , 6 - pyridinedicarboxylic acid . the obtained compound comprises colourless crystal needles with a melting temperature of 303 - 305 ° c . ( decomposition ). it is moderately soluble in water , diethylformamide and dimethyl sulphoxide , and insoluble in hydrocarbons , chloroform , ether , ethanol . ir ( ν , cm − , tablets in kbr ): 667 , 768 , 922 , 1095 , 1148 , 1304 , 1368 , 1493 , 1600 , 1732 , 3097 , 2800 - 3100 . 1h nmr ( δ , ppm , 200 , 13 mhz , d 2 o ): 8 , 35 ( m , 6h , h - aromatic ). 13 c nmr ( δ , ppm , 50 , 32 mhz , d 2 o ): 129 , 7 ( β - c ), 143 , 2 ( γ - c ), 147 , 8 ( α - c ), 167 , 4 ( c ═ o ). mass - spectrum ( m / z ), ( 74 ge ): 360 [ m - co 2 ]+, 272 , 228 , 195 , 171 , 154 , 139 , 122 , 112 , 93 , 84 , 77 . elemental analysis for c 14 h 6 gen 2 o 8 : to 1 , 1 g ( 0 , 048 mol ) na and 25 ml of absolute methanol at room temperature under an atmosphere of nitrogen were added 2 , 6 g ( 0 , 012 mol ) tetrachlorogermanium during 5 min . the reaction mass was heated under reflux for 1 , 5 hours , then cooled to 20 ° c . the precipitate ( nacl ) was filtered in a shott filter and washed with methanol ( 3 × 15 ml ). to the resulting filtrate comprising tetraethoxygermanium solution in ethanol , 3 g ( 0 , 18 mol ) of 2 , 6 - pyridinedicarboxylic acid were added . further procedure was as described in example 1 . the yield was 3 , 45 g ( 95 %) based on 2 , 6 - pyridinedicarboxylic acid . the spectral characteristics of the compound obtained in this way are essentially the same as those described above in example 1 . a solution for injection was prepared by dissolving germanium bis ( pyridine - 2 , 6 - dicarboxylate ) in water at room temperature . one ampoule of this solution contains : tablets were prepared by triturating the components in a mortar and forming in the pressing machine . one tablet contains : investigation of induction of α , β , γ interferons in mouse serum in vivo male cba mice weighing 12 - 14 g were inoculated intraperitoneally with the compound i in the form of an aqueous solution in doses of 0 , 005 - 50 mg / kg . the level of interferon synthesis in the blood serum was determined at various intervals ( 5 , 24 , 48 , 72 hours ). interferon titrations were carried out in l - 929 cell cultures . the test virus was mouse encephalomyocarditis virus . the results are presented in table 1 . as will be seen from table 1 , compound i induced serum interferon production , within the first 5 hours postinoculation interferons α and β being detectable , and at later intervals γ interferon . the optimal dose of the compound is 0 , 5 mg / kg . ( a ) human diploid fibroblast cell culture ( m - 19 ) highly sensitive to interferon was seeded into wells of a 96 - well plate in eagle &# 39 ; s medium with 10 % calf embryo serum . on the 3rd day of growth the culture was inoculated with compound i in a concentration of μg / ml . after 24 hours of incubation ( 37 ° c ., 5 % co 2 ), titrations of α - interferon ( reaferon with initial activity 2 × 10 6 iu / ml against 100 tcd of vesicular stomatitis virus ) were carried out . the sensitivity of the cells to interferon was determined by the cytopathic effect of the virus . the results are presented in table 2 . ( b ) cells of the continuous line j - 41 with reduced sensitivity to α - interferon were seeded into 96 - well plates in a concentration of 10 5 cells / ml in medium 199 with 10 % embryo calf serum . next day compound i was added to the cultures in a concentration of 1 μg / ml . interferon titrations and determination of the sensitivity thereto were carried out as described above in ( a ). as will be seen in table 2 , after 24 - hour treatment of m - 19 cells with compound i , the sensitivity of the cells to α - interferon ( reaferon ) increased 8 - fold . after 24 - hour treatment of j - 41 cells with compound i their sensitivity to interferon increased 4 - fold . the above results indicate that compound i may be used in clinical practice for correction of the interferon and enhancement of sensitivity of the patients to interferon preparations . compound i was diluted in physiological saline solution to a concentration of 2 , 5 or 0 , 5 μg / ml . mice of the experimental groups were inoculated with 0 , 2 ml of one of the obtained solutions ( 0 , 5 and 1 μg / mouse respectively ) intraperitoneally . control animals were given injections of physiological saline solutions . at 1 , 2 , 3 , 4 and 7 days after administration of the test compound , the animals were given heparin ( 40 units / mouse ), and then specimens of the peripheral blood , spleen and bone marrow from thighbones . the blood was diluted 1 : 1 with physiological saline solution . bone marrow and spleen suspensions were prepared by the standard method . the content of hemopoietic stem cells ( hsc ) in the blood , bone marrow and spleens of the animals treated with the preparation were tested by the method of exogenous colony formation in the spleen of syngeneic lethally irradiated recipients ; more specifically , diluted peripheral blood ( 0 , 1 ml ), bone marrow cells ( 3 - 5 × 10 4 cells ) or spleen cells ( 5 × 10 5 cells ) were inoculated to lethally irradiated syngeneic recipients which were killed at 8 - 9 days ; their spleens were removed , fixed in bouin &# 39 ; s solution , and the number of visible plaques or colonies developing from hsc was counted . for the determination of the effect of the preparation on proliferation of hsc , suspensions of bone marrow or spleen cells were treated in vitro with oxyurea in a concentration of 1 mg / ml for 2 hours at 37 ° c . before inoculation into irradiated recipients . the number of hsc going into s - phase was determined by the formula a =( a - b )× 100 / a , wherein a is the number of hsc colonies without oxyurea treatment and b is the number of hsc colonies treated with oxyurea . the results are presented in table 3 . as may be seen in table 3 , compound i increases the number of hsc in the blood . no capacity to stimulate hsc release into the s - phase was demonstrated . the preparation was inoculated subcutaneously to cba mice in doses from 0 , 1 to 10 μg per mouse , after which the animals were inoculated with 1 , 25 × 10 6 microbial cells of staphylococcus aureus wood 46 . the survival rate was determined as a percentage of that in the control group of mice which received no compound i . the results were respectively 39 . 8 %, 60 . 0 % and 80 . 7 % at 0 . 1 , 1 . 0 and 10 . 0 μg doses . thus , a dose of 1 μg enhances the resistance of mice to staphylococcus . the model system was an experimental influenza infection in mice caused by the laboratory wsn strain of influenza a virus ( h1n1 ). the virus had been grown in 9 - day - old chick embryos . mice c57b1 / 6 anesthesized with ether were inoculated intranasally each with 50 μl ld50 of the virus diluted 1 : 100 . the preparation was inoculated in a dose of 100 μl ( 20 μg / mouse ) intramuscularly on the day of infection . the control group of the animals received a placebo solution . each group consisted of 10 male mice weighing 14 - 16 g . the deaths of the animals were recorded every day for 14 days , and at the end of the experiment the average survival time and lethality were determined . the data are presented in table 4 . dogs with an established diagnosis of distemper ( duration of the disease from 10 to 30 days ; in 3 animals — the intestinal form of the disease , in 2 - pulmonary form , and in 3 animals — the neuro - paralytic stage ) were inoculated intramuscularly with 2 - 4 ml ( depending on the animal &# 39 ; s weight ) of 0 , 5 % solution of the test compound i in distilled water twice daily for 3 - 10 days . after this course of treatment all the animals became clinically normal . | a germanium complex of germanium and an aromatic or nono - aromatic , carbocyclic or heterocyclic dicarboxylic acid , e . g . germanium bis has anti - infectious , interferon - inducing , and immunomodulating activity . |
while the invention is susceptible of various modifications and alternative constructions , certain illustrated embodiments thereof have been shown in the drawings and will be described below in detail . it should be understood , however , that there is no intention to limit the invention to the specific form disclosed , but , on the contrary , the invention is to cover all modifications , alternative constructions , and equivalents falling within the spirit and scope of the invention as defined in the claims . in the following description and in the figure , like elements are identified with like reference numerals . the use of “ or ” indicates a non - exclusive alternative without limitation unless otherwise noted . the use of “ including ” means “ including , but not limited to ,” unless otherwise noted . fig1 shows a preferred embodiment of the oral appliance of the invention , referred to as 10 , which includes an appliance body 12 . the appliance body 12 may be generally configured like a prior art orthodontic retainer , and can be made of hard or soft plastic or other suitable materials . embedded in the appliance body 12 are one or more tongue parameter sensors 14 . tongue parameter sensors 14 are configured to measure one or all of several tongue parameters , including force , pressure , and touch . to detect the position of the tongue , parameter sensors 14 are primarily configured to detect touch or a light force or light pressure . the appliance body can be formed from a dental impression and cast , or may be made in a range of different sizes for different size mouths . it may also be provided to a patient in a form that enables him to fit the device to his teeth in a forming step , such as with heat formable material . technology which is suitable for the tongue parameter sensors 14 includes strain gauges , piezoresistors , air pressure sensors , and capacitance touch switches . these and other standard and readily available electronic technologies can serve as a basis for the tongue parameters sensors 14 . electrical connections between the tongue parameter sensors 14 and the electronic processor 16 are provided by conductive pathways which may be copper wires embedded in the matrix of the appliance body 12 , or which can also be painted or etched or otherwise affixed to the outside surfaces of the appliance body 12 . for instance , a conductive paint can form a link between the tongue parameter sensors 14 and the electronic processor 16 . also , conductive pathways can be applied using an adhesive to either surface of the appliance body 12 . the electronic processor 16 receives signals from the tongue parameter sensors 14 , interprets them and responds with a response appropriate to the condition being treated . if a response was needed it would typically be an electronic stimulus produced by a stimulus generator 20 , and would require energy from a power source 22 . the electronic processor 16 would send a signal to one or more stimulus electrodes 18 , positioned on the ventral side 30 of the appliance body 12 . in this particular configuration the electronic components are connected by a tether 26 , and the electronic processor 16 , stimulus generator 20 , and power source 22 are located exterior to the patient &# 39 ; s mouth . the power source could be in the form of a battery for instance . these components could also be made in a wireless mode , and in the wireless mode these components could be located anywhere near the patient and the appliance body 12 . for instance , these components would be attached to the patient &# 39 ; s pillow or clothing , worn on a wrist strap , or attached to the patient &# 39 ; s bed or any other furniture . in miniature format , the electronics components could also be located on the appliance body 12 . feedback can also be in the form of a visual cue , or an audible cue , or as a vibration or other tactile cue . parameters that the tongue parameter sensors 14 would be configured to detect would include the time of contact , or the lack of contact of the tongue to the palate , or the lack of contact of the tongue from one tooth to another . in response to information such as this , a stimulus generator 20 would send the pre - selected stimulus to electrodes 18 . examples of tongue position detection would include the normal tongue - up and forward position , and abnormal tongue - down position , or tongue - back position , and abnormal tongue - forward position . other conditions the device could be used with include tongue thrust swallow , mouth breathing , low tongue posture , posterior pharyngeal constriction , speech impediment , clenching and bruxism . the electronic processor 16 , or a version of the processor which is programmable , is shown in fig3 as programmable processor 24 , would be configured to interpret data to evaluate such patient activities as “ tongue up ” posture , “ tongue back ” posture , too much clenching of the jaw , too little clenching of the jaw , etc . other abnormal jaw position conditions which would be sensed include the normal teeth apart position , and abnormal teeth together positions , and the normal swallow teeth - together position . the tongue parameter 14 sensors would be located in different positions and the type of sensors would be modified for the specific problem for which the patient was being treated . a different electronic processor 16 or appliance body 12 might be supplied for each of the different kinds of tongue and jaw related problems that the device could handle . it is also possible that one appliance body 12 and one electronic processor 16 or programmable processor 24 could be utilized to detect and treat some or all of these tongue and jaw position situations . the tongue parameter sensors 14 are located on the oral side 30 , and the stimulus electrodes are on the tissue side 28 . included in fig1 is a palate portion 34 . although the preferred embodiment , the palate portion 34 is optional . in addition to the palate portion 34 , the device includes a semi - circular tooth area portion 36 of the appliance body 12 . this portion of the appliance body of this embodiment is basically equivalent to a soft mouth guard and would typically be fit to a person &# 39 ; s teeth so that a comfortable fit is achieved . a jaw position sensor 32 may be present . the jaw position sensor 32 senses when the patient &# 39 ; s jaw is in a closed or open position , by sensing contact with a tooth in the lower jaw adjacent to the jaw position sensor . the programmable processor 24 has pre - selected interpretation instructions for interpreting the signals from the tongue parameter sensors 14 and the jaw position sensors 32 . based on information received from each of these types of sensors , and the condition being treated , the programmable processor 24 would send a stimulus to the stimulus electrodes 18 . the stimulus sent to the stimulus electrodes 18 would typically be a very light electric shock , which would typically but not necessarily be calibrated to be insufficient to wake a patient up . however it would at least raise the patent &# 39 ; s level of consciousness to a level to cause correction of the contraindicated behavior related to jaw or tongue position . in this manner a bio feedback loop would be established to train the patient to not perform the contraindicated behaviors , including certain tongue positions and jaw positions . this conditioning would follow the strategy of classical conditioning and over a period of time would teach the patient to develop new habits of tongue posture and jaw position . 1 . a removable plastic retainer - like oral appliance , custom made from an upper or lower dental cast of the patient &# 39 ; s teeth . 2 . one or more electronic pressure sensors located on the palate , lower lingual , and occlusal surfaces of the plastic appliance . the sensor may be a strain gage , load cell , contact switch or other piezoelectric sensor . the sensors connect to extra - oral electronics through electric wires exiting the mouth between the lips , or wireless radio frequency transmission . 3 . stimulus electrodes are embedded in the appliance , contacting the oral mucosa and the palate . 4 . electronic circuitry in a compact box is tethered to the retainer and worn on the head or torso . a version in which the electronics circuitry is entirely contained in the retainer is envisioned . 5 . sensor powering and detection circuit . 6 . programmable microprocessor records forces of the tongue against the palate and teeth , or lower teeth against the upper teeth . the processor evaluates sensor data . data is evaluated for contact force , contact duration , and the interval between contacts . if the sensor detects undesirable tongue and tooth contacts , it activates the “ prod ” circuit . 7 . stimulus generator delivers a non painful , but annoying electric shock ( prod ) to the palate . 1 . ebot - tp ( electric biofeedback oral trainer - tongue in palate ) the sensor is in the anterior palate to train the tongue to rest against the anterior palate . treatment for tongue thrust , snoring and sleep apnea . 2 . ebot - b ( electric biofeedback oral trainer - bruxer ) the sensor is on the occlusal surface of the teeth to train the lower jaw to adopt a rest position with the teeth slightly apart . treatment for bruxism , temporomandibular symptoms . 3 . ebot - ob ( electric biofeedback oral trainer - open bite ) the sensor is on the occlusal surface of the posterior teeth to increase the frequency , duration , and magnitude of clenching behavior . 4 . ebot - s ( electric biofeedback oral trainer - speech ) the sensors are located on the palate to encourage site - specific contact from the tongue against the palate . treatment for correction of speech articulation errors , and conditions the tongue for improved strength and coordination . while there is shown and described the present preferred embodiment of the invention , it is to be distinctly understood that this invention is not limited thereto , but may be variously embodied to practice within the scope of the following claims . from the foregoing description , it will be apparent that various changes may be made without departing from the spirit and scope of the invention as defined by the following claims . | the invention is a removable plastic oral appliance which includes sensors for detecting the position of a patient &# 39 ; s tongue and mandible . pressure sensors in the appliance itself detect tongue contact and pressure against the palate or the lower teeth against the upper teeth . the sensors are connected electronically to an electronic processor which interprets the information against one or more contra - indicated tongue or jaw positions or activities , and selects an appropriate response from a pre - selected range of responses . the electronic processor sends a signal to a stimulus electrode to cause the patient to stop the contraindicated tongue position , jaw position , or activity . |
the following description is of the best mode presently contemplated for carrying out at least one embodiment of the invention . this description is not to be taken in a limiting sense , but is made merely for the purpose of describing the general principles of the invention . the scope of the invention should be determined with reference to the claims . fig1 shows a heart stimulation or heart monitoring system including an imd 10 , such as a heart stimulator or heart monitor , that is connected to a cardiac lead 20 , according to one or more embodiments of the invention . in at least one embodiment , the distal end of the cardiac lead 20 may include one or more electrodes 31 and 32 that pick up electrical signals of the heart 40 . in one or more embodiments , sensing of electrical activity of the heart in the imd 10 may be performed in different ways . as shown in fig1 , in at least one embodiment of the invention , electrical cardiac signals may be sensed between two electrodes 31 and 32 at the distal end of the cardiac lead 20 , as bipolar sensing . in one or more embodiments , electrical cardiac signals may be sensed between one electrode 31 or 32 at the distal end of the cardiac lead 20 and the electrically conductive housing of the imd 10 , as unipolar sensing . in at least one embodiment of the invention , the imd may be connected to multiple leads each having at least one electrode that extend to different tissue locations of the heart . fig2 shows parts of the further structure of the imd 10 , according to one or more embodiments of the invention . by way of at least one embodiment , the imd 10 may include at least one electrode connection 110 that is coupled by a capacitor 120 to the input of a sensing unit 130 and optionally to the output of a stimulation unit ( not illustrated in fig2 ). in at least one embodiment , the capacitor 120 and input resistors of the sensing unit may form a first filter . in at least one embodiment , the first filter may be a high - pass filter . in one or more embodiments , the capacitor 120 may be replaced by an analogue filter . in at least one embodiment , the sensing unit 130 may output different signals to a signal processing unit 140 and to a lead failure detection unit 150 , as will be described in detail hereafter . in one or more embodiments , a control unit ( not illustrated in fig2 ) may be connected to one or more of the sensing unit 130 , the optional stimulation unit , the signal processing unit 140 and to the lead failure detection unit 150 to control their operation . in at least one embodiment , the control unit may include or may be connected to a memory to store one or more of operation parameters , operation commands and signals received from the other units of the imd 10 . in one or more embodiments , the signal processing unit 140 and the lead failure detection unit 150 may be in direct connection . in at least one embodiment , the cardiac stimulator may include a clock generator ( not illustrated in fig2 ), which provides clock signals . according to one or more embodiments , the imd 10 may include an electric energy source ( not illustrated in fig2 ), for example in the form of a battery or an accumulator , which supplies energy to the components of the imd 10 . in at least one embodiment of the invention , the electric signal received by the electrode may run through capacitor 120 to an analogue pre - amplifier 131 and an optional analogue filter 132 , and may then be converted using an a / d converter 133 into a digital signal . in at least one embodiment , the electric signal received by the electrode may first run through the analogue filter and may then be fed via the pre - amplifier to the a / d converter . in one or more embodiments , the analogue pre - amplifier 131 and the analogue filter 132 may be omitted . in at least one embodiment , the digital signal at the output of the a / d converter 133 may be a wideband filtered time - discrete and amplitude - discrete representation of the analogue input signal of the a / d converter 133 and may then be forwarded to the lead failure detection unit 150 and to a second filter 134 . in one or more embodiments , the output signal of the second filter 134 may form a second filtered signal that is fed to a signal processing unit 140 to detect physiological events . for example , in at least one embodiment , electric signals from an electrode placed in the ventricle that are above a specific amplitude threshold value may be identified as natural contraction of the ventricle and are forwarded to the control unit . in one or more embodiments , the imd may include one or more of multiple sensing units , processing units and lead detection units if multiple leads are connected , for example separate units for a right atrial lead and for a right ventricular lead . by way of at least one embodiment , the lead failure detection unit 150 may receive the wideband filtered output signal of the a / d converter 133 and analyzes the signal to detect lead failures . fig3 shows a right atrial ( upper trace ) and a right ventricular ( lower trace ) electrocardiogram of atrial and ventricular signals over time during ventricular pacing at the output of the second filter 134 , according to one or more embodiments of the invention . fig4 shows the same right atrial ( upper trace ) and right ventricular ( lower trace ) electrocardiogram , but wideband filtered at the output of the a / d converter 133 , according to one or more embodiments of the invention . in fig3 and fig4 , by way of at least one embodiment , a s indicates a sensed atrial event and a s - ff indicates a far - field sensing of the ventricular depolarization . in one or more embodiments , failure indicates the point of time where the atrial electrode was in contact to the housing for a short time . in the filtered signal shown in fig3 , by way of at least one embodiment , the short appears as a peak similar to a sensed atrial event , having an amplitude significantly higher than the far field signal and may therefore be misinterpreted as sensed atrial event . fig4 shows , according to one or more embodiments , that in the wideband filtered signal the short is represented by an abrupt drop of the atrial signal amplitude followed by an exponential return to the previous mean signal amplitude . fig5 shows a right atrial ( upper trace ) and a right ventricular ( lower trace ) electrocardiogram of atrial and ventricular signals over time without pacing at the output of the second filter 134 , according to one or more embodiments of the invention . fig6 shows the same right atrial ( upper trace ) and right ventricular ( lower trace ) electrocardiogram , but wideband filtered at the output of the a / d converter 133 , according to one or more embodiments of the invention . in fig5 and fig6 , in at least one embodiment , a s indicates a sensed atrial event and a s - ff indicates a far - field sensing of the ventricular intrinsic event . in one or more embodiments , failure indicates the point of time where the atrial electrode was in contact to another electrode for a short time . in the filtered signal shown in fig5 , by way of at least one embodiment , the short again appears as a peak similar to a sensed atrial event , having a amplitude significantly higher than the far field signal and may therefore be misinterpreted as sensed atrial event . fig6 shows , according to one or more embodiments , that in the wideband filtered signal the short is represented by an abrupt drop of the atrial signal amplitude followed by an exponential return to the previous signal amplitude . as shown in fig3 , 5 and 6 , by way of at least one embodiment of the invention , lead failures may cause significant signal morphologies in the wideband filtered analog - digital converted signal . in one or more embodiments , lead failures such as shorts or interruptions , may cause impulses at the input connector 110 . in at least one embodiment , the first filter formed by the capacitor 120 and input resistors may form a high - pass filter . in one or more embodiments , the step response may be detected at the output of the a / d converter 133 . in at least one embodiment , the characteristic signal features of a lead failure condition may be an abrupt change of the signal amplitude followed by an exponential return to the previous mean signal amplitude . in one or more embodiments , the lead failure detection unit 150 may continuously analyze the output signal of the a / d converter 133 for the occurrence of such characteristic signal features . in at least one embodiment , an abrupt change of the signal amplitude may be detected by analyzing the slew rate of the signal amplitude . in at least one embodiment , a minimum slew rate may be detected . in one or more embodiments , the signal amplitude may be compared to one or more predetermined thresholds or amplitude ranges at one or more pre - determined times or during pre - determined time windows . by way of at least one embodiment , the thresholds may be adaptive , for example a percentage of the mean or maximal or averaged signal amplitude . in at least one embodiment , the times or time - windows may also be adaptive , for example depending of the heart rate . according to one or more embodiments , the return to the previous signal level may be slower than any intrinsic cardiac signal and may be detected by comparing the signal amplitude to the determined step response of the first filter for the respective amplitude step . in at least one embodiment of the invention , a simplified method to detect the exponential return may include the determination of time between the abrupt change of the signal amplitude and the return to a previous mean signal amplitude . in one or more embodiments , if signal features characteristic for a lead failure condition are detected , lead failure detection unit 150 indicates a lead failure condition . in at least one embodiment , signal processing unit ( spu ) 140 may continuously analyze the output signal of filter 134 to detect body signals in the second filtered signal . in at least one embodiment , signal processing unit 140 may detect cardiac signals or cardiac events like p - waves , qrs - complexes or t - waves . if a body signal is detected and lead failure detection unit ( lfdu ) 150 indicates at the same time a failure condition , according to one or more embodiments , the detected body signal , such as the detected cardiac signals , may be marked as invalid . as such , in at least one embodiment , a wrong diagnosis or wrong therapy decision may be avoided . it will be apparent to those skilled in the art that numerous modifications and variations of the described examples and embodiments are possible in light of the above teaching . the disclosed examples and embodiments are presented for purposes of illustration only . other alternate embodiments may include some or all of the features disclosed herein . therefore , it is the intent to cover all such modifications and alternate embodiments as may come within the true scope of this invention . | a device and method that detects a lead failure condition for a lead having at least one electrode in contact with body tissue , wherein the lead is connected to the device . the device includes a first filter that filters an electric signal sensed by the at least one electrode to a first filtered signal , and a lead failure detection unit that detects signal characteristics of the first filtered signal . the lead failure detection unit indicates a lead failure condition when the detected signal characteristics correspond to a step response of the first filter . |
referring now to the drawings , fig3 shows a simplified schematic diagram of a patient defibrillation device of the present invention . capacitor c 1 is the main energy storage element or voltage source . it is to be understood that capacitor c 1 may be comprised of a plurality of individual capacitors so connected so as to provide the desired output voltage ( see , e . g ., fig4 ). a voltage source , such as battery b 1 , can provide the charging current for the capacitors . switches s 1 and s 2 connect the patient to the defibrillator circuitry such as by patient electrodes e 1 and e 2 . the secondary , switch controlled , voltage source is comprised of capacitor c 2 , inductor l 1 , semiconductor switch q 1 , diode d 1 , and the control circuitry cc . in the present invention capacitor c 1 is charged to a voltage v 1 and capacitor c 2 is charged to a lower voltage v 2 . switches s 1 and s 2 are closed which thereby connects the patient between the two voltages by means of the electrodes e 1 and e 2 . current thus begins to flow through the patient , particularly to the patient &# 39 ; s heart . the current level i is determined by ohm &# 39 ; s law as ( v 1 − v 2 )/ r patient . this current thus flows to and charges c 2 causing its voltage to increase . the boost configured switching circuitry comprised of l 1 , q 1 , d 1 and the control circuit extract energy from c 2 and “ pump ” or deliver it back into c 1 . as c 1 discharges , the control circuit also adjusts the switching action to maintain the voltage difference v 1 − v 2 substantially constant and thus the current or electrotherapy pulse delivered to the patient is generally maintained at the desired level . [ 0034 ] fig4 is a diagram of another preferred embodiment of the invention . as before capacitor c 1 is the main energy storage element now comprised of four aluminum electrolytic capacitors c 1 a , c 1 b , c 1 c , c 1 d connected in series . typical preferred values would be about 800 uf for each capacitor and would each be charged to approximately 400 volts for a total voltage of 1600 . switches s 1 and s 2 connect the patient to the defibrillator circuitry through electrodes e 1 and e 2 . for purposes of illustration only , it will be assumed that the patient impedance is 75 ohms . also , as before , the secondary switched voltage source is comprised of capacitor c 2 , inductor l 1 , semiconductor switch q 1 , diode d 1 and the control circuitry , as well as resistors r 1 and r 2 . the main storage capacitor c 1 is charged to 1600 volts by a high voltage charger hv through isolating diode d 4 . capacitor c 2 is preferably a small high frequency aluminum electrolytic capacitor with a value of about preferably 10 uf . resistors r 1 and r 2 form a voltage divider to charge c 2 via high voltage charger hv to an initial voltage of about 400 volts . closing switches s 1 and s 2 connects the patient between the two voltages and provides the electrotherapy pulse to the patient through electrodes e 1 and e 2 . the voltage across the patient is 1600 − 400 = 1200 . current thus begins to flow through the patient , and particularly to the patient &# 39 ; s heart , to provide the defibrillator electrotherapy pulse . the patient current level is therefore determined by ohm &# 39 ; s law to be ( 1600 − 400 )/ 75 = 16 amps . after passing through the patient , this current then passes on to and charges c 2 , causing its voltage to increase . the boost configured switching circuitry comprised of l 1 , q 1 , d 1 , and the control circuit extract energy from c 2 and deliver it back into charging capacitors c 1 a and c 1 b . capacitors c 3 a and c 3 b are preferably small value low impedance ceramic capacitors to absorb the high frequency current pulses from the inductor &# 39 ; s discharge . as c 1 discharges , it delivers less voltage to the patient . the control circuit automatically adjusts the switching action to maintain the voltage difference between c 1 and c 2 at 1200 volts , and thus the patient electrotherapy pulse current is maintained at the desired level of 16 amps . since c 1 a and c 1 b have their charge partially replaced by the switching action , their voltage decays slower than c 1 c and c 1 d . at some point c 1 c and c 1 d have no charge remaining and diodes d 2 and d 3 prevent them from becoming reverse biased . an advantage of the present invention is that it can automatically and substantially constantly deliver the desired electrotherapy pulse of 16 amps to a patient of unknown impedance . for example , the initial voltage on c 2 can be set for the lowest expected patient impedance such as 25 ohms ( i . e ., c 2 is 1200 volts , since ( c1600 − 1200 / 25 )= 16 ). once the pulse is initiated the voltage delivered by c 2 can be ramped down quickly by the control circuitry which automatically detects the resistance of the patient via the sensor inputs until the patient current reaches the desired level . in addition to the embodiments discussed above , the present invention can incorporate other switch circuitry components to provide added advantages . for example , a transformer , in the form of a coupled flyback inductor , can be used in place of the inductor . such a coupled flyback inductor is shown in fig5 . this component will also operate to transfer the voltage from the second voltage source to the first voltage source as the electrotherapy pulse is being delivered through the patient . the present invention can also be configured to provide a biphasic waveform having a positive going segment and a negative going segment in a second pulse . an integral h - bridge circuit as shown in fig6 can provide this function . in this embodiment diode d 1 is replaced by an insulated gate bipolar transistor ( igbt ) or mosfet q 2 with either an internal or external anti - parallel diode d 5 and a further semiconductor switch s 3 . during the forward ( positive ) first phase switch s 3 is open , while during the reverse ( negative ) second phase switch s 1 is opened and switch s 3 is closed and igbt / mosfet q 2 is turned on . as a further refinement to the present invention , a negative voltage may be induced on the second voltage source c 2 in order to completely drain the voltage from the main voltage source c 1 . if the regulator components are reconfigured to allow the voltage on second voltage source c 2 to go negative , the current through the patient can be controlled until the entire charge is drawn from main voltage source c 1 instead of dropping out of regulation when the voltage on c 2 reaches zero . this makes the defibrillator additionally energy efficient as a typical tew defibrillator still has approximately 12 % of the stored energy remaining at the end of the pulse . alternatively , this technique could also be used to produce a regulated second phase for a biphasic pulse wherein switch s 1 is opened and switch s 3 is closed ( see fig6 ). alternatively , generation of the second ( negative ) phase pulse can be accomplished by using an external h - bridge . this uses the basic circuit as shown in fig3 but switches s 1 and s 2 are replaced with an h - bridge comprises switches s 4 a , s 4 b , s 4 c and s 4 d as shown in fig7 . this allows biphasic pulse generation and regulation of the second ( reverse ) phase if desired . during the positive pulse , switches s 4 a and s 4 b are closed , while during the negative pulse , switches s 4 c and s 4 d are closed . in the embodiment shown in fig8 an integral charger can be used which uses a single inductor l 1 as both the charging inductor and the regulating inductor . generally , magnetic components are relatively physically large and may in turn result in a larger than desired defibrillator device . this circuit configuration eliminates the need for a separate charging inductor or transformer , thereby eliminating components so as to reduce the overall size and weight of a defibrillator . while switch s 5 has been added , they are still small relative to the eliminated components . in another embodiment of the present invention , the individual capacitors comprising the main voltage source can be connected in parallel rather than in series in order to optimize the circuit for various patient impedances . if the impedance of the patient is known or can be estimated before the application of electrotherapy pulse , the individual elements of c 1 can be arranged to optimize the pulse delivery . series arrangements of the individual capacitors would be more desirable for higher patient impedances , while a parallel arrangement would be preferred for lower impedances . in a further extension of the present invention , an exponential conclusion to the first phase can be created . if at some point during the discharge cycle the switching action to semiconductor switch q 1 is disabled and it is turned on continuously , the electrotherapy pulse will go to a conventional exponential discharge . this configuration could be utilized to generate a waveform as shown in fig9 that eliminates the high peak currents usually associated with exponential waveforms . a falling current waveform could be produced by reducing the charge removal from main voltage source c 1 for a time and then permitting this voltage to increase . if the switching action to q 1 is disabled for a period of time , the voltage on second voltage source c 2 will increase as charge flows into it . this reduces the voltage difference ( v 1 − v 2 ) across the patient and therefore reduces the patient current . this technique can be used to produce waveforms where the current falls in a predetermined manner . a unique advantage of the present invention is that , within certain limits , any arbitrary waveform can be generated to provide defibrillation to a patient . in this embodiment , it is not a requirement that the difference value v 1 − v 2 remain constant . therefore , the present invention can be easily re - configured to produce any waveform determined by medical science to be most advantageous for a patient , in terms of delivering the desired energy level while minimizing adverse affects to the patient and / or the patient &# 39 ; s heart . the invention disclosed herein enables the use of high voltage capacitors having relatively low capacitance . for example , it is estimated that 2000 volt 85 or 15 mfd thin film ( polyvinilidine fluoride ) capacitor could provide delivered energy of 150 and 25 joules respectively for an external or implantable defibrillator . the waveform could have a desirable duration of 10 to 12 milliseconds instead of the less desirable 2 or 3 millisecond duration that would occur with a typical rc time constant . utilizing a flattop modified btew , these energies are expected to be highly effective and the energy density for this type of capacitor is expected to be as high 5 . 5 joules per cubic centimeter which enables size reduction due both to improved energy effectiveness and to improved capacitor energy density . while specific embodiments of practicing the invention have been described in detail , it will be appreciated by those skilled in the art that various modifications and alternatives to those details could be developed in light of the overall teachings of the disclosure . accordingly , the particular arrangements disclosed are meant to be illustrative only and not limiting to the scope of the invention which is to be given the full breadth of the following claims , and any and all embodiments thereof . | a circuit for producing an arbitrary defibrillator waveform using switching techniques which reduce the usual high current or high voltage stress on the switching element . this allows existing semiconductor devices to be used in an application previously closed to them . the result is a defibrillator able to produce desirable rectangular waveforms without the waste of energy found in existing approaches . this allows the use of a smaller energy storage capacitor for a given delivered energy . the application discussed here is a cardiac defibrillator but the techniques presented could be applied to other power conversion situations . |
the native micellar casein employed in accordance with the present invention is obtained from animal milk , such as cow &# 39 ; s milk , goat &# 39 ; s milk or ewe &# 39 ; s milk . it is prepared by microfiltration of the milk . the micellar protein is obtained by microfiltration of milk , optionally followed by diafiltration , on a membrane with a porosity of , for example , 0 . 1 to 0 . 2 micrometer . microfiltration selectively concentrates casein without retaining whey proteins , which is thus preferred for reasons of stability to sterilization . aside from its remarkable properties , the native micellar casein thus prepared has proved to be a protein source particularly suitable for enteral compositions . it does not have any of the disadvantages of the above - mentioned proteins : its nutritional qualities are equivalent or superior to those of the proteins traditionally used , it forms a low - viscosity colloidal dispersion in water which enables it to be used in high concentrations ( 5 to 10 %) without any flow problems in the finest tubes , for the same concentration , it gives solutions of lower osmolarity than caseinates , it gives solutions with a whiteness superior to that of caseinates . the invention is illustrated by the following examples in which parts and percentages are by weight ( g per 100 g of liquid composition ) unless otherwise indicated . 300 kg of skimmed cow &# 39 ; s milk , pasteurized for 15 s at 72 ° c ., are treated in a microfiltration installation ( techsep ® module 1s 151 ) equipped with 3 . 4 m 2 of membrane m 14 ( mean pore diameter approximately 0 . 15 micrometer ) at a temperature of 50 ° to 55 ° c . until 200 kg of permeate have been eliminated ( which corresponds to concentration by a volume factor of 3 ). the retentate is then diafiltered with demineralized water by elimination of 500 kg of permeate ( corresponding to a diafiltration volume factor of 5 ). the object of this diafiltration step is to produce the micellar casein with a protein purity of around 85 % with less than 1 % of residual lactose , based on total dry matter . the retentate is then concentrated to a final volume of 50 to 70 l which guarantees a dry matter content of 18 to 20 %. the retentate contains 185 g / kg of total solids with a protein content of 84 %, based on total dry matter . its composition is as follows in g / kg of liquid : fractionation of the proteins in accordance with rowland &# 39 ; s scheme ( rowland , 1938 ; j . dairy res . 9 , 42 - 46 ) shows that , since 96 % of the total protein can be precipitated at ph 4 . 6 , the retentate must be casein . analysis of a dilute dispersion of retentate in a malvern particle sizer shows that the casein is present in the form of particles with a mean diameter of 300 nanometers ( nm ) and that the distribution of the particles is relatively uniform ( one family only ranging from 100 to 400 nm ). this image corresponds exactly to that obtained for skimmed milk which indicates the presence of the micelles characteristic of milk . 2 . 13 kg of the above retentate containing 19 . 5 % total solids and corresponding to 350 g of proteins are transferred to a stirrer - equipped tank thermostatically controlled to 55 ° c . the following ingredients are then added to the dispersion in solid form ( in g ): after the ingredients have dissolved in the retentate , demineralized water is added to a total weight of 4825 g . at this stage , the ph is checked and , if necessary , adjusted to a value of 6 . 8 . the fatty phase , i . e . 175 g of corn oil containing 2 % ( based on the oil ) of soya lecithin as emulsifier , is then added . the mixture is homogenized in a two - stage homogenizer to 20 mpa in the first stage and then to 5 mpa in the second stage . the emulsion is then sterilized by indirect uht treatment ( heat exchanger ) for 20 s at 130 ° c . or by direct uht treatment ( direct injection of steam ) for 5 s at 148 ° c . or even by sterilization in cans or bags for 6 to 8 mins . at 120 ° c . three enteral compositions with the same energy density , i . e ., 4 . 184 kj / ml ( 1 kcal / ml ) are thus prepared as described above : ______________________________________ ingredient (%) composition a 7 native composition b composition c micellar 7 7proteins (% p / v ) casein ca caseinate na / k caseinate______________________________________lipids ( corn 3 . 5 3 . 5 3 . 5oil ) glucides 9 . 5 9 . 5 9 . 5 ( maltodextrins / sucrose ) minerals ca 0 . 21 0 . 2 0 . 07 k 0 . 16 0 . 15 0 . 18 na 0 . 05 0 . 05 0 . 06 mg 0 . 03 0 . 03 0 . 02 p 0 . 12 0 . 12 0 . 07 cl 0 . 1 0 . 1 0 . 03______________________________________ the products obtained after sterilization in cans for 6 minutes at 120 ° c . are compared for their total protein content , their dynamic viscosity ( shear rate 1600 s - 1 , ambient temperature ), osmolarity and organoleptic properties : ______________________________________ presence proteins osmolarity viscosity of foreigncomposition ( total ), % mosm / kgh . sub . 2 o mpa · s tastes______________________________________a 7 . 56 392 6 nob 6 . 81 386 9 yesc 7 . 38 481 30 yes______________________________________ composition a ( native micellar casein ) is clearly distinguished from composition c ( na / k caseinate ) by its reduced viscosity and its low osmolarity . it is distinguished from composition b ( ca caseinate ) by its viscosity and taste . an enteral composition with an energy density of 6 . 276 kj / ml ( 1 . 5 kcal / ml ) and 8 % ( p / v ) of proteins is prepared from &# 34 ; low temperature &# 34 ; skimmed milk powder , i . e ., skimmed milk dried under controlled thermal conditions . 20 kg of low - temperature skimmed milk powder are dispersed in 100 kg of demineralized water at a temperature of 50 ° to 55 ° c . this dispersion , which corresponds to twice - concentrated skimmed milk , is microfiltered in the same installation as in example 1 in the diafiltration mode by passing demineralized water through until 600 kg of permeate have been eliminated . the retentate is then further concentrated to around 60 kg , which represents a dry matter content of 21 % with a protein content , based on dry matter , of 82 %. to prepare the enteral composition , 2 . 323 kg of liquid retentate , representing 400 g of total proteins , are mixed at 55 ° c . with the following ingredients ( g ): after the ingredients have dissolved in the retentate , demineralized water is added to a total weight of the dispersion of 4 . 7 kg . the ph is then adjusted to 6 . 8 , after which 300 g of fatty phase are introduced , the total weight of the dispersion being 5 kg . after homogenization and sterilization as in example 1 , the product has a dynamic viscosity of 112 mpa . s ( shear rate 1600 s - 1 , ambient temperature ) it is white in appearance , has an agreeable sugary taste and is free from foreign tastes . | an enteral composition of protein , glucides , lipids and minerals , which is suitable for tube feeding , employs native micellar casein as the protein . the composition is prepared by obtaining native micellar casein and combining it with the glucides , lipids and minerals . a dispersion of micellar casein may be obtained by microfiltering milk , particularly skim milk , and glucides and minerals are dispersed in the micellar casein retentate obtained , lipids are added to the resulting dispersion and then the mixture is homogenized and sterilized . the microfiltered retentate may be diafiltered for obtaining the dispersion . |
the section of a brewing container ( 3 ) shown in fig1 shows an example of the safety mechanism ( 11 ) according to the invention . fig2 shows an exploded view of the safety mechanism ( 11 ). the brewing container ( 3 ) comprises a bowl - shaped recess ( 55 ) which has its bottom ( 75 ) on the side facing towards the interior of the brewing container ( 78 ) and which is open at the side facing towards the atmosphere ( 77 ). if the thickness of the brewing container wall is not sufficient to take up the entire safety mechanism ( 11 ), there is the possibility to provide enough material for enclosing the bowl - shaped recess ( 55 ) by the use of a substantially cylindrical attachment ( 83 ) at the side of the interior of the brewing container ( 78 ). the bottom ( 75 ) of the recess ( 55 ) comprises at least one hole ( 73 ) which enables the exchange of gases and / or liquids between the interior of the brewing container ( 78 ) and the bowl - shaped recess ( 55 ) such that the pressure in the interior of the brewing container ( 78 ) remains , at the predetermined heating power of the heating device , below the predetermined safety pressure . a pressure - regulating mechanism ( 76 ) is inserted in the recess ( 55 ) which regulates by opening the pressure in the interior of the brewing container ( 78 ) at or below the predetermined heating power of the heating device such that the pressure remains below the predetermined safety pressure . the bowl - shaped recess ( 55 ) is closed by a lock ( 19 ) which locks the pressure - regulating mechanism ( 76 ) in the recess ( 55 ). as also shown in fig3 and 4 , the lock ( 19 ) does not comprise any holes . these holes are usually used for deviating the vapor when opening the pressure - regulating mechanism ( 76 ). one or more vapor deviation channels ( 68 ) are formed instead for deviating the vapor between the brewing container ( 3 ) and the lock ( 19 ), which lead to vapor outlet slits ( 85 ) at the outer side of the brewing container . these vapor deviation channels ( 68 ) are in the examples of the invention shown herein a continuation of the guiding grooves ( 80 ) ( see below ), but they can have any form . the lock ( 19 ) consists of a locking screen ( 82 ) to which a hollow open cylinder ( 79 ) is fixedly attached . this cylinder ( 79 ) clamps the lock ( 19 ) fixedly in the recess ( 55 ) of the brewing container ( 3 ) and contains the pressure - regulating mechanism ( 76 ). other types of fixation of the lock ( 19 ) are possible , for example by soldering of components or by the use of a thread . the locking screen ( 82 ) fits in a recessed trough ( 84 ) in the brewing container , such that the surface ( 50 ) of the brewing container ( 3 ) remains planar , i . e . surface ( 50 ) of the brewing container ( 3 ) and locking screen ( 82 ) form a substantially planar surface . if the design of the brewing container ( 3 ) is different , then the screen ( 82 ) can be adapted accordingly . it is to be noted that the locking screen ( 82 ) can be designed differently compared to the examples shown herein . in particular , is to be noted that the locking screen ( 82 ) is exactly as large as the basis of the cylinder ( 79 ). one or more guiding rails ( 81 ) are attached to the cylinder ( 79 ) which engage in corresponding guiding grooves ( 80 ) within the recess ( 55 ). these guiding rails ( 81 ) are arranged such that the lock ( 19 ) can be inserted in exactly one way into the brewing container ( 3 ) and it orients automatically within certain limits during mounting in order to reduce the error - proneness of the mounting . the latter can be improved by the design of the guiding rails ( 81 ), for example by tapering them towards the lower end . the pressure - regulating mechanism ( 76 ) consists , in the shown examples , of a valve ball ( 15 ) which is pressed against the hole ( 73 ) by a biased spring ( 17 ). an o - ring ( 67 ) is inserted for an improved sealing between hole ( 73 ) and ball ( 15 ) which can also be omitted , depending on the working environments of the safety mechanism ( 11 ). in order to maintain the spring ( 17 ) more precisely at its place , for example because the spring is smaller than the locking cylinder , a spring support ( 18 ) can be optionally used which has for example , the form of a truncated cone and the spring ( 17 ) lies against the side and is centered thereby . in case the pressure in the interior ( 78 ) of the brewing container ( 3 ) is increased , such that the force of the vapor pressure which acts on the ball ( 15 ) is larger than the bias of the spring ( 17 ), the ball ( 15 ) is elevated and gives the way free for the vapor from the interior of the brewing container ( 78 ) via the vapor deviation channels ( 68 ) towards the atmosphere ( 77 ). a non - shown alternative of the pressure - regulating mechanism ( 76 ) is that the lock ( 19 ) is attached in the recess such that the lock ( 19 ) is elevated when the control pressure is exceeded , and the way between the interior of the brewing container ( 78 ) and the atmosphere ( 77 ) is thus opened . here different embodiments are possible , for example that the movement is controlled by a spring , that the mechanism has to be reset manually by a user , or that the lock ( 19 ) is entirely removed from the brewing container ( 3 ). another non - shown example of the invention is extending the above described mechanism by a second safety stage . herein , the bottom ( 75 ) of the bowl - shaped formation has at least a second hole or slit which is normally closed by the inserted lock ( 19 ). in case the pressure in the brewing container increases that strongly that the primary pressure - regulating mechanism ( 76 ) is overcharged , for example by a stronger heating source as predetermined , the lock ( 19 ) is released , as described above , out of its anchoring and opens further openings or slits for the vapor deviation . fig5 shows an example of the invention which is also adapted for the use with electromagnetic radiation . here , the pressure - regulating mechanism ( 76 ) is inserted in a cylinder ( 74 ) that is closed on one side and shields electromagnetic radiation , which is in turn inserted into the lock ( 19 ). by this shielding the use of a spring ( 17 ) of metallic material is possible in connection with electromagnetic radiation . the safety mechanism ( 11 ) shown in fig1 and 5 can be used in beverage makers which are formed by injection molding . thereby no specific manufacturing methods are required for the safety mechanism ( 11 ) and the manufacturing of the safety mechanism ( 11 ) is particularly cost efficient . as a removal from the mold is required in the manufacturing via molding , is in the case that the brewing container wall is inclined with respect to the removal direction as shown , also the mechanism is inclined in relation to the brewing container wall . this has as a consequence that the cylinder ( 79 ) is arranged inclined on the locking screen ( 82 ). the selection of the material of the apparatus is usually arbitrary . the used materials should be food safe in any case and should not change the organoleptic properties of the food product . it is also recommended to select the materials , when using electromagnetic radiation , such that as less as possible unuseful heating occurs . as shown above , in cases in which this is not possible , the heating can be reduced to an acceptable level till an entire prevention by specific shielding . fig6 to 10 show a third example of the safety apparatus ( 11 ) of the invention . the brewing container ( 3 ) of the beverage maker comprises a bowl - shaped recess ( 83 ) with a valve opening ( 73 ) which is closed by a lock ( 103 ) such that a vapor outlet gap ( 109 ) remains free . the lock ( 103 ) consists of a screen ( 123 ), the spring mechanism ( 104 ) and the locking mechanism ( 105 ), which are permanently attached to each other . the spring mechanism ( 104 ) connects the screen ( 123 ) with the elastic locking mechanism ( 105 ) which closes the valve opening ( 73 ). in this way , the final mounting of the safety apparatus ( 11 ) of the beverage maker is particularly simple : it consists only in the insertion of the lock ( 103 ) in the bowl - shaped recess ( 83 ) of the brewing container ( 3 ). the lock ( 103 ) is manufactured in a single manufacturing step . this means that the lock ( 103 ) can be manufactured with one usual , universally applicable injection molding machine in a single operation . these machines can mold around inserted elements as well as use different materials . the spring mechanism ( 104 ) is manufactured from the same material as the screen ( 123 ) and is manufactured together in one single manufacturing operation ( cast ). in order to avoid undercuts , the spring mechanism ( 104 ) consists of a helix with one half - turn . the locking mechanism ( 105 ) is molded from a second material ( so called 2 k - method ) without leaving the machine . in case the screen ( 123 ) with the spring mechanism ( 104 ) is also made from an elastic material , the entire lock ( 103 ) is manufactured in one cast . the lock ( 103 ) contains one wide pin ( 112 ) which engages in the wide recess ( 111 ) of the brewing container ( 3 ) and a narrow pin ( 114 ) which engages in the narrow recess ( 113 ) of the brewing container ( 3 ). this ensures that the lock ( 103 ) is always mounted in the same orientation . a fourth example of the lock ( 103 ) is shown in fig1 . the lock ( 115 ) consists of a screen ( 123 ) with the cylinder ( 116 ) in its center which bounces due to the conical indents ( 118 ). the end ( 117 ) of the cylinder ( 116 ) serves as a locking mechanism . lock ( 115 ) is entirely made from elastic material . the fifth example of the invention is shown in fig1 to 14 . herein , the lock ( 119 ) is entirely formed from an elastic material and is placed together with plugging rips ( 124 ) in the corresponding recesses ( 125 ) in the brewing container ( 3 ). the suspension occurs via the bouncing lamella ( 121 ). their thickness and shape is determined by the precise requirements of the beverage maker . the shown lamella ( 121 ) are slightly bent , their behavior thus has an increased hysteresis . to avoid kinking of the locking mechanism ( 126 ) and a corresponding undesired behavior , it comprises a guiding pin ( 122 ) which protrudes into the valve hole ( 73 ). fig1 shows the third example of the invention when the pressure within the brewing container ( 3 ) is above the activation pressure of the bouncing lamellae ( 121 ). the lamellae ( 121 ) bend and the locking mechanism ( 126 ) elevates . the guiding pin ( 122 ) protrudes still far enough into the valve opening ( 73 ) to provide a guiding for the locking mechanism ( 126 ). if the brewing container ( 3 ) is made from a transparent material , the area in which the pressure - regulating mechanism is located will be provided with a structure on the inner side of the brewing container ( 3 ). this is implemented such that the technical components are not visible for the user . | the invention relates to a safety mechanism for beverage - making devices that extract or dissolve a beverage base material using a hot pressurized liquid . the pressure container of the beverage - making device comprises an inwardly directed crucible - shaped formation , into which the pressure - regulating mechanism is inserted from the outside and which is closed with a closure in a planar manner . the closure does not have any holes , but form intermediate spaces with the pressure container that act as vapor drainage channels . the outlet of the gases on the beverage - making device is located almost invisibly at a transition of two parts . |
the blood treatment device , in particular a hemo ( dia ) filtration device , has a dialyser 1 , which is separated by a membrane 2 into a dialysis liquid chamber 3 , through which dialysis liquid flows , and a blood chamber 4 , through which blood flows . a blood delivery line 5 , into which a blood pump 6 is coupled , leads to the blood chamber 4 , while a blood return line 7 issues from the blood chamber 4 . the blood delivery line 5 and blood discharge line 7 form , together with the blood chamber 4 , the extracorporeal blood circuit i of the blood treatment device . the dialysis liquid system ii of the blood treatment device is described below . the dialysis liquid system ii has a dialysis liquid delivery line 8 , which leads from a dialysis liquid source 9 to the dialysis liquid chamber 3 , and a dialysis liquid return line 10 , which issues from the dialysis liquid chamber 3 and leads to an outflow 11 . the dialysis liquid delivery line 8 has a first section 8 a , which leads from the dialysis liquid source 9 to the first chamber 12 a of a first sterile filter 12 . one chamber 13 a of a balance device 13 is coupled into the first section 8 a of the dialysis liquid delivery line 8 . the second section 8 b of the dialysis liquid delivery line 8 issues from the second chamber 12 b of the first sterile filter 12 and leads to the dialysis liquid chamber 3 . the dialysis liquid return line 10 divides into two sections 10 a and 10 b , which leads to the outlet 11 . a dialysis liquid pump 14 is coupled into the first section 10 a , while an ultrafiltrate pump 26 is coupled into the second section 10 b . the other chamber 13 b of the balance device 13 is also coupled into the first section 10 a . in order to recover a substituate from the dialysis liquid , the hemo ( dia ) filtration device has a second sterile filter 15 , which is divided by a semipermeable membrane 15 c into a first chamber 15 a and a second chamber 15 b . the second sterile filter 15 forms an exchangeable unit , which can be attached to the blood treatment device or removed from the treatment device . to attach and secure the second sterile filter 15 , the blood treatment device has a holder 16 , which has a first attachment piece 16 a , a second attachment piece 16 b , a third attachment piece 16 c and a fourth attachment piece 16 d . the appliance - side attachment pieces 16 a to 16 d can be designed as sockets . the second filter 15 has a first attachment piece 15 d , a second attachment piece 15 e , a third attachment piece 15 f and a fourth attachment piece 15 g . the filter - side attachment pieces 15 d to 15 g can be connected with an exact fit to the appliance - side attachment pieces 16 a to 16 d . the filter - side attachment pieces can be corresponding plugs . the third and fourth appliance - side attachment pieces 16 c , 16 d are connected to each other by a connection line 17 a , to which a bypass line 17 b is attached . two shut - off elements 18 a and 18 b are located on the bypass line 17 b . between the two shut - off elements 18 a and 18 b , a substituate line 17 d , into which a substituate pump 19 is coupled , branches off from a substituate port 17 c . the substituate line 17 d leads to the extracorporeal blood circuit i upstream or downstream of the blood chamber 4 , in order to be able to deliver substituate to the extracorporeal blood circuit i . while the substituate is being delivered , the shut - off element 18 a is opened and the shut - off element 18 b closed . the blood treatment device also has further shut - off elements and bypass lines , and other components too , but these are not shown for sake of clarity . the line sections of the dialysis liquid system ii , through which sterile substituate is delivered from the second chamber 15 b of the second sterile filter 15 to the extracorporeal blood circuit i , represent the substituate segment 17 that has to be kept free of contaminants , in particular from the formation of a biofilm . the substituate segment therefore comprises all the lines or line sections that include the volume lying downstream of the sterile filter , for example the connection line 17 a and the line section of the bypass line 17 b upstream of the substituate port 17 c . the blood treatment devices are tested after assembly . the dialysis liquid system ii is then filled completely with a liquid that contains a cleaning and disinfecting agent . all the line sections of the dialysis liquid system are thus filled . at this time , the substituate line 17 d is not generally attached to the substituate port 17 c . for the subsequent transport and storage of the blood treatment device , the method according to the present invention is carried out using the device according to the present invention . the first and second sterile filters 12 , 15 are removed . the first sterile filter 12 is replaced in a known manner by a known bypass piece . the second sterile filter 15 is replaced by the device according to the present invention , which device is described below with reference to fig2 . the device 20 according to the present invention for carrying out the conservation method has , like the sterile filter 15 , a first attachment piece 20 a , a second attachment piece 20 b , a third attachment piece 20 c and a fourth attachment piece 20 d , which can be connected to the appliance - side attachment pieces 16 a to 16 d . the attachment pieces can once again be designed as plugs that can be inserted with an exact fit into sockets . in a preferred embodiment , the first and third attachment pieces 20 a , 20 c are designed as a common plug , while the second and fourth attachment pieces 20 b , 20 d are designed as a second plug . however , all of the attachment pieces can also be separate from one another . the first and second attachment pieces 20 a , 20 b are connected to each other by a first connection line 21 , and the third and fourth attachment pieces 20 c , 20 d are connected to each other by a second connection line 22 . the first and second connection lines 21 , 22 can be hose lines . a third line 23 , which is closed by a sterile filter 24 , branches off from the second connection line 22 . the sterile filter 24 has a first chamber 24 a and a second chamber 24 b , which are separated by a semipermeable membrane 24 c . the first chamber 24 a of the sterile filter 24 is connected to the third line 22 , in particular a hose line . a hose clamp 25 is provided for clamping off the hose line 23 . the device according to the present invention preferably forms a unit that can be easily and safely secured to the holder 16 in place of the sterile filter 15 . when the device 20 according to the present invention is attached to the blood treatment device , a flow connection is established between the dialysis liquid source 9 and the dialysis liquid chamber 3 , while the substituate segment 17 is separated from the rest of the dialysis liquid system . the liquid located in the substituate segment 17 decoupled from the rest of the dialysis liquid system is now drawn off , such that the substituate segment is free of liquid . for this purpose , the shut - off element 25 on the device according to the present invention is opened , such that air can pass into the substituate segment in order to vent the volume enclosed by the substituate segment 17 . the liquid can be conveyed , for example , to the outflow 11 , for which purpose the pumps 14 and 26 can be operated . the shut - off element 25 is then closed again , and the rest of the dialysis liquid system is filled completely with a liquid that contains an antifreeze agent . the blood treatment device remains in this state until installation at the dialysis centre . when the dialysis device is started up , new sterile filters 12 and 15 are used . the compulsory cleaning and disinfecting cycle then follows . any bacteria are either killed off or flushed out by the direct cleaning and disinfecting . thus , the first use of a filter and all subsequent exchanges can be classed as aseptic procedures , which guarantee that the substituate segment is permanently sterile . it has been found in tests that , in the substituate segment not filled with antifreeze agent , and even after quite a long storage period , a biofilm cannot form that cannot be safely and quickly removed using conventional cleaning and disinfecting measures . an alternative embodiment of the blood treatment device , and of the device according to the present invention for attachment to the blood treatment device , is described below with reference to fig3 and 4 , which embodiment differs from the embodiment described with reference to fig1 and 2 only in that the blood treatment device and the device according to the present invention have only three attachment pieces . the corresponding parts are provided in fig3 and 4 with the same reference signs as in fig1 and 2 . instead of the two filter - side attachment pieces 15 f and 15 g ( fig1 ), the second chamber 15 b of the second sterile filter 15 has only one attachment piece 15 f ′ ( fig3 ), and , instead of the two appliance - side attachment pieces 16 c and 16 d ( fig1 ), the blood treatment device has only one attachment piece 16 c ′ ( fig3 ), wherein the third filter - side attachment piece 15 f ′ is attached to the third appliance - side attachment piece 16 c ′ ( fig3 ). a connection line for the connection of two appliance - side attachment pieces is not required here . the bypass line 17 b of the substituate segment 17 is therefore connected directly to the third appliance - side attachment piece 16 c ′. the first chamber 24 a of the sterile filter 24 is connected directly to the third attachment piece 20 c ′ of the device 20 according to the present invention via the connection line 23 ( fig4 ), such that the substituate segment 17 is closed in a sterile manner ( fig4 ) when the device according to the present invention is attached to the blood treatment device . | the present invention relates to extracorporeal blood treatment devices and methods and devices for conserving extracorporeal blood treatment devices . in accordance with the present invention , an antifreeze agent in introduced only into that part of the dialysis liquid system of the blood treatment device that includes the volume lying upstream of a sterile filter with which sterile substituate is recovered from the dialysis liquid . accordingly , that part of the dialysis liquid system that includes the volume lying downstream of the sterile filter is not filled with an antifreeze agent . the present invention makes it possible , after removal of the sterile filter , to easily and safely separate a substituate segment from the rest of the dialysis liquid system and drain off liquid located in the substituate segment . |
in order to explain the structure and mode of operation of the invention , a generalized model of the invention is shown in the four fig1 sketches . in fig1 the numeral 1 indicates base means , 2 indicates frame means , 3 indicates conveyer belt means , 4 indicates driving means , 5 indicates connecting means , the letter a indicates an object to be moved , and the letter b indicates a supporter to support the object a . also the directions of arrows indicate the moving directions of each part of the conveyer belt means 3 relative to the base means 1 . the dots in fig1 ( a ) and 1 ( d ) indicate that the dotted parts of the conveyer belt means 3 are not moved relative to the base means 1 . fig1 ( a ) shows the first stage of the model in which a part of the upper portion of the conveyer belt means 3 is fixed to the base means 1 by the connecting means 5 , and the frame means 2 is translated to the right by driving the driving means 4 to this right . in the stage , the conveyer belt means 3 is not only translated to the right with the frame means 2 but also is rotated around the frame means 2 . namely , the upper portion of the conveyer belt means 3 is not moved relative to the base means 1 because a part of the upper portion of the conveyer belt means 3 is fixed to the base means 1 . and , the lower portion of the conveyer belt means 3 is moved to the right at the speed of two times faster than that of the frame means 2 . the right end portion of the conveyer belt means 3 is moved upwardly and the left end portion of the conveyer belt 3 is moved downwardly . as exactly shown in fig1 ( a ), when the right end portion of the conveyer belt means 3 enter between the object a and the supporter b , the object a is lifted upwardly by the right end portion of the conveyer belt means 3 and then placed on the upper portion of the conveyer belt means 3 since the frame means 2 is moved to the right at the time . in this stage , the speed of the upper portion of the conveyer belt means 3 relative to the base means 1 is zero . therefore there is not relative motion between the upper portion of the conveyer belt means 3 and the object a . this means that no sliding occurs between them . in other words , the object a is forced just upwardly , but not moved to the right and both of the frame means 2 and conveyer belt means 3 can enter between the object a and supporter b . fig1 ( b ) shows the second state of the model in which the connecting means 5 is open and the frame means 2 is translated to the left by driving the driving means to the left . in this stage , since the conveyer belt means 3 is completely free from the base means 1 , the conveyer belt means is moved to the left together with the frame means 2 without rotating around the frame means 2 . no force except from the frame means 2 is applied to the conveyer belt means 3 so that there is no relative motion between the conveyer belt means 3 and the frame means 2 . therefore , the object a placed on the conveyer belt means 3 is translated to the left together with the conveyer belt means 3 . fig1 ( c ) shows the third stage of the model in which the connecting means 5 is open and the frame means 2 is translated to the right . the third stage of the model is just the inverse of the second stage of the model . in the third stage the object a is translated to the right together with the conveyer belt means 3 . fig1 ( d ) shows the fourth stage of the model in which a part of the upper portion of the conveyer belt means 3 is fixed to the base means 1 and the frame means 2 is translated to the left . the fourth stage of the model is just the inverse of the first stage of the model . in this stage the conveyer belt means 3 is rotated clockwise around the frame means 2 . since the upper portion of the conveyer belt means 3 is not moved but is fixed relative to the base means and the lower portion of the conveyer belt means is sent to the left by the frame means 2 , the conveyer belt means 3 and frame means 2 leave the object a . the object a is naturally placed on the supporter b . as illustrated with the generalized model , the apparatus of the present invention is intended to move an object from one location to another through said four stages . one of the merits of the invention is that it is simple to operate the apparatus . the apparatus requires only to connect or disconnect the connecting means 5 and to drive the driving means 4 forwardly or backwardly . the other merit of the invention is that the apparatus necessitates only one driving means not to drive the conveyer belt means 3 but to drive the frame means 2 . as well known , it is very difficult to drive a conveyer belt because of the slip of the conveyer belt . the apparatus of the present invention overcomes this difficulty by driving the frame means 2 and fixing a part of the upper portion of the conveyer belt means 3 to the base means 1 . hereinafter , a few embodiments of the present invention will be given and the invention will be described in more detail . the first embodiment is shown in fig2 . this embodiment is based on the generalized model shown in fig1 and is formed as an integral part of a wheeled - stretcher for moving a patient . in fig2 parts or portions of the stretcher are indicated with the same numerals as those of the same or similar parts or portions of the model shown in fig1 . the stretcher comprises a well - known flat car 6 , a well - known lift shaft ( not shown ) fixed on said flat car 6 and an apparatus for moving objects placed on said flat car 6 through said lift shaft . the apparatus for moving objects comprises a base 1 which is a shallow rectangular box with an opening on its top , a frame 2 , which is a rectangular board , supported on said base 1 , a conveyer belt 3 rotatably supported on said frame 2 , driving means 4 supported on said base 1 for translate said frame 2 parallel to the short sides of said rectangular box - like base 1 , and a rod like connecting means 5 fixed across on said conveyer belt 3 . the base 1 has a horizontal bottom wall and four vertical wall plates , the first or sidewall plate 11 , the second or end plate 12 , the third or side plate 13 and the fourth or end plate 14 . the four plates are arranged to form a rectanular box - like body open at the top . the first plate 11 corresponds in length to that of the base 1 , and the frame 2 slides on the plate 11 when it moves in or out of the base 1 . the height of the first plate 11 is less than that of the other plate 12 to 14 by the thickness of the frame 2 . the third plate 13 faces the first plate 11 and corresponds to the other long side of the base 1 . the second plate 12 and the fourth plate 14 face each other and correspond to the short sides of the base 1 . two upward projections 15 to be linked with the connecting means 5 are formed at the end portion of each of the second plate 12 and the fourth plate 14 , and beside the first plate 11 . the top surfaces of the second plate 12 and the fourth plate 14 are smooth and the under surfaces of the plates 12 and 14 are provided with teeth 16 . the base 1 is primarily made from stainless steel and aluminum . the frame 2 comprises an upper , horizontal slide plate 21 and a lower , horizontal slide plate 22 , which are like rectangular boards and are disposed one over the other with a certain space between them . two side plates 23 fix the two slide plates 21 and 22 at the both short or end sides thereof . the lower slide plate 22 is provided with a line of openings 221 at the end portion of one of the long side thereof and parallel to the long side . each of fixed belts 222 pass through one of the openings 221 and goes over the other side of the slide plate 22 . the one end of each fixed belt 222 is fixed on the outer side portion of the first plate 11 of the base 1 and the other end of each fixed belt 222 is fixed on the inner side portion of the first plate 11 by suitable fasteners ( not shown in figures ). fastening the ends of the belt 222 causes the belt to roll with respect to plate 22 when the latter moves . further several guide rollers 223 are provided on the upper surface of the lower slide plate 22 . also other guide rollers 211 are provided on the lower surface of the upper slide plate 21 . each of the guide rollers 223 of the lower slide plate 22 faces to one of the guide rollers 211 of the upper slide plate 21 . the frame 2 is placed on the base 1 and is guided by the inner side surfaces of the second plate 12 and the fourth plate 14 of the base 1 . the upper slide plate 21 is made of polyethylene but can be made of another plastic or metal . the lower slide plate 22 is made of a metal plate with smooth surfaces . the metal plate should be treated to lower the frictional coefficient thereof . a conveyer belt 3 is wound on the upper slide plate 21 and envelops almost all the surfaces of the upper slide plate 21 . namely , the under portion of the conveyer belt 3 is held between the guide roller 211 of the upper slide plate 21 and guide roller 223 of the lower slide plate 22 . the both ends of the upper portion of the conveyer belt 3 are bound by the connecting means 5 to form a continuous loop of the conveyer belt 3 . the driving means 4 has a case which is composed of a cover 41 having a shape of a conduit and two supporting board 42 fixed on the end portions of the cover 41 . each of the supporting boards 42 is fixed on each of the side boards 23 of the frame 2 . a driving shaft 43 passes through the both supporting boards 42 and a driving gear 44 is fixed on each end of the driving shaft 43 . each of the driving gears 44 meshes with the teeth 16 of the base 1 . one of the driving gear 44 is in gear with an input gear 45 at the other side of the teeth 16 . the input gear 45 is connected with a driving motor ( not shown in figures ) fixed on one of the supporting boards 42 . also , each of the supporting boards 42 has two guide rollers 46 at the under portion thereof . these guide rollers 46 are in contact with the upper surfaces of the second plate 12 and the fourth plate 14 . the connecting means 5 , which secures the both ends of the conveyer belt 3 , is a tube which lies across the conveyer belt 3 and the both end portions 51 of the connecting means 5 stick out past the both sides of the conveyer belt 3 . each of the end portions 51 is in contact with each of the upper surfaces of the second plate 12 and the fourth plate 14 of the base 1 . also each of the end portions 51 has the hook 52 having a shape of letter j . the two hooks are fixed on a rod shaft 53 which has a handle 54 at one end thereof . therefore , the two hooks 52 are rotated at the same time by rotating the handle 54 . each of the hooks 52 is engageable with one of the projections 15 of the base 1 . the stretcher , or transfer device has the construction mentioned above . next , the functions and effects of the stretcher will be explained . the first step is to connect the hooks 52 of the connecting means 5 with the projections 15 of the base 1 and to install the frame 2 into the base 1 . in order to set the stretcher in the state mentioned above from the state shown in fig2 it is necessary to drive the motor for translating the frame 2 to the right and then to connect the hooks 52 of the connecting means 5 with the projections 15 of the base 1 . next , it is necessary to drive the motor reversely for translating the frame 2 to the left . it may here be remarked incidentally that the relative motions of the upper slide plate 21 and the conveyer belt 3 are the same as explained with regard to fig1 ( a )- 1 ( d ). namely , when the hooks 52 of the connecting means 5 is connected with the projections 15 , the translation of the frame 2 results in rotating the conveyer belt 3 around the frame 2 . in this case , the relative motion of the upper portion of the conveyer belt 3 to the base 1 is zero . on the other hand , when the hooks 52 are not connected with the projections 15 , the conveyer belt 3 is not rotated around the frame 2 by the translation of the frame 2 . the conveyer belt 3 is translated together with the frame 2 to the left or to the right . the relation between the lower slide plate 22 of the flame 2 and the fixed belt 222 is the same as the state where the conveyer belt 3 is connected with the base 1 by the connecting means 5 . namely , since the fixed belt 222 is always connected to the first plate 11 of the base 1 , the fixed belt 222 rotates around the lower slide plate 22 whenever the frame 2 is translated . further , as the fixed belt 222 is fixed to the first plate 11 under the lower slide plate 22 , the relative speed between the under portion of the fixed belts 222 and the base 1 is zero in the normal condition . the two kinds of guide rollers provided respectively on the lower side of the upper slide plate 21 and on the upper side of the lower slide plate 22 work not only to prevent the conveyer belt 3 from contacting with the fixed belt 222 but also to convey the load applyed on the upper slide plate 21 to the lower slide plate 22 . the moving direction of the lower portion of the conveyer belt 3 is perpendicular to the applying direction of the load and the guide rollers will be rotated by very small force . therefore , the resistance which is applied to the belt 3 by the load applied to the upper slide plate 21 does not increase very much . the stretcher which is in the state mentioned above is moved close to the bed on which a patient lies . then , the height of the apparatus for moving objects is adjusted according to that of the bed so that the lower surface of the lower slide plate 22 of the frame 2 may become equal in height to the top surface of the bed . then , after the connection of the hooks 52 of the connecting means 5 and the projections 15 of the base 1 , the driving means 4 is driven to pull the frame 2 out of the base 1 onto the bed . the positioning of the outermost end portion of the lower slide plate 22 of the frame 2 prevents the lower portion of the conveyer belt 3 from contacting with the surface of the bed . also since the lower portion of the fixed belt 222 of the lower slide plate 22 does not move relatively to the surface of the bed , the fixed belt 222 works to push down the bed . especially , the fixed belt 222 is helpful where the bed is covered with a sheet . however , the lower slide plate 22 and the fixed belt 222 do not act directly on the patient . even if the lower slide plate 22 and the fixed belt 222 are removed from the frame and parts 2 , the remaining frame can move a patient without special difficulties or pain given to the patient , but may cause damage to the upper surface of the bed or tuck up the sheet on the bed . according to the advance of the frame 2 , the edge of the frame 2 enters between the patient and the bed and the patient is lifted slightly and ridden on the conveyer belt 3 . when the patient is placed on the middle of the upper portion of the conveyer belt 3 , the driving means 4 is stopped . then , the hooks 52 of the connecting means 5 are released from the projections 15 of the base 1 and the driving means 4 is driven reversely to translate the frame 2 carrying the patient into the base 1 . in this case , no outer force is applied to the conveyer belt 3 except the force applied by the upper slide plate 21 , therefore the conveyer belt 3 does not rotate around the upper slide plate 21 of the frame 2 and the patient remains placed on the middle of the upper portion of the conveyer belt 3 . in this state , the patient can be carried to any place , for example , to an operating room and moved onto an operating table by the stretcher . the steps for moving the patient from the stretcher to the operating table are just the reverse of the steps for moving the patient from the bed to the stretcher . also the steps are the same as the steps explained with regard to fig1 ( c ) and fig1 ( d ). therefore , further explanation of the steps of the present case will be omitted . next , the second embodiment of the apparatus for moving objects , which has multiple frames and multiple conveyer belt 3 , will be explained . the apparatus is shown in fig3 and fig4 and is different from the first embodiment in frames and conveyer belts . namely , the base , the driving means and the connecting means of the second embodiment are the same as those of the first embodiment . here , the frame ( a perspective view thereof is shown in fig5 ) and the conveyer belts of the second embodiment will be mainly explained . in fig3 and fig5 same parts or portions of the second embodiment as those of the first embodiment are marked with the same numerals as those of the first embodiment shown in fig2 . the apparatus for moving objects is characterized by that eight frames 20 , each of which has a rectangular box like shape and is provided with one conveyer belt 30 , are arranged parallel to each other and are pivoted with one shaft at one of the end portions thereof . the frame 20 , which is shown in fig5 is like a slender vacant box , and the leading end is thinner , or of less height than the trailing end , and has an opening 201a which opens upwardly . another rectangular opening 201b , which opens upwardly , is provided near the trailing end portion of the frame 20 . further opening 201c , which opens downwardly , is provided near said leading portion and another broad opening 201d , which opens downwardly , is provided near said trailing end portion . at each of the openings 201a to 201d is pivotedly provided one of four rollers 202a to 202d . further , additional two rollers 202e and 202f are provided between the two rollers 202a and 202b . the conveyer belt 30 comes in the opening 201a , turns around the outer side of the roller 202a , goes over the rollers 202e , 202f , turns around the outer side of the roller 202b and comes out of the opening 201b . the both ends of the conveyer belt 30 are fixed together with the connecting means 5 over the upper side of the frame 20 . a fixed belt 203 comes in the opening 201c , turns around the outer sides of the rollers 202c and 202d , and comes out of the opening 201d . the both ends of the fixed belt 203 are fixed to the first plate 11 of the base 1 . at the trailing end of the frame 20 is provided a through hole 203a through which a shaft 204 made of a pipe passes . the shaft 204 passes through the through holes 203a of the eight frames 20 and arranges the eight frames 20 in parallel with each other . the eight frames 20 are driven through the shaft 204 by the driving means 4 . in this embodiment , a driving shaft 43 is rotatably provided within the pipe like shaft 204 . the driving force is transmitted from the driving means 4 to the frame 20 through the driving shaft 43 and the pipe like shaft 204 . all the eight conveyer belts 30 are fixed to a pole like member 51 of the connecting means 5 . the apparatus of the second embodiment having the construction mentioned above not only operate in the same manner as the apparatus of the first embodiment but also changes the leading edge line of the frames 20 according to the shape of a patient to be moved . namely , as each of the frames 20 can be rotated around the shaft 204 with respect to the other frames 20 , the edge portion of each of the frames 20 moves upwardly or downwardly . therefore , the edge line formed of the end portions of the frames 20 is changed in parts upwardly or downwardly by the shape of the patient and the frames are able to move between the patient and the bed . also , the driving force for driving the frames 20 can be substantially decreased . each of the apparatuses embodied above is applied to a wheeled stretcher . however , the apparatuses can be applied to a litter or a non - wheeled stretcher or to some other machinery such as hospital equipments . further in the embodiments , the driving means 4 includes a motor , but the driving means 4 can be driven by man power . | a variety of objects , including an invalid or a non - ambulatory hospital patient may be moved from one location to another . the transfer device includes a conveyer belt , a frame for supporting said conveyer belt , a base for holding said frame , driving means for translating said frame relative to said base , and connecting means for connecting or releasing a part of the upper portion of said conveyer belt with said base . when the connecting means connects a part of the upper portion of said conveyer belt with the base , the conveyer belt is not only carried with the frame , but also is rotated around the frame by driving the frame relative to the base . on the other hand , when the connecting means releases the belt from the base , the conveyer belt is also carried with the frame but is not rotated around the frame by driving the frame relative to the base . a patient is moved by placing the device adjacent to him . at first the connecting means is operated to connect a part of the upper portion of the conveyer belt and the base , and then the frame is driven toward the patient . when the frame together with the conveyer belt contact with the body of the patient , the leading edge of the conveyer belt which is rotating in an upwardly - oriented direction , gently and uniformly lifts the patient up onto the frame . then , the connecting means is operated to release the conveyer belt and the base , and the frame is driven reversely . the patient on the frame is carried with the frame to just above the base . the transfer device may include the second belt which is placed just below the first conveyer belt and is fixed always to the base . further the transfer device may form an integral part of an apparatus such as a wheeled stretcher , or it may be used independently . upon arrival the patient is off loaded by operating the transfer device adversely . |
recent development of a wide variety of nano - powders has resulted in the improvement of many products and development of other products for new applications . similar improvements are gained by applying this nano - powder technology to cermets . this is especially beneficial in the molten metal processing of cermets since lower temperatures and shorter times at temperature allow consolidation of the present cermets . these processing advantages prevent coarsing of the microstructure during processing and provide a finer grain structure in the cermets , which increases performance over previous cermets . this finer microstructure is enhanced further by the additions of lighter weight and / or harder ceramic powders in the nano - powder state . the partial or complete substitution of boron carbide powder with these ceramic nano - powders before molten metal infiltration gives lighter weight and / or harder cermets , which results in a direct improvement in ballistic performance for armor applications . these new ceramic additions include borides , nitrides , and / or carbides of the lighter elements , e . g ., al , b , c , mg , be , ca , si , li , ti and v . these new ceramic substitutions also allow the additional options of using lighter weight alloys that wet the compacted ceramic bodies used in the molten metal infiltration process . a wider variety of alloys can now be used for molten metal infiltration due to improved wetting between these blended ceramics and the molten alloys . these alloys include , but are not limited to , combinations of the light elements of al , mg , be , li , ti , v , etc . the general properties of desired alloys usable in the present invention are low density alloys ( less than 2 . 8 gm / cc ) that wet the ceramics at a reasonable temperature (& lt ; 1150 c ) during a relatively short infiltration period (& lt ; 3 hours ). the new ceramic powders can be formed from the elements or from the pre - reacted compounds of borides , nitrides and / or carbides . blending of the compounds is preferred in most cases due the reactive nature and / or toxicity of some elements . blends of these nano - powder ceramics can be prepared by several methods ( flame spray , milling , and / or sol - gel processes ). nano - powders of b4c can be mixed with various amounts of other nano - powders to make up the final powder blend needed to form the powder compact for molten metal infiltration . the powders should be pressed to greater than 55 % of theoretical density for armor applications . other applications may require less ceramic and more metal content for higher tensile strength and toughness but less hardness . the metal alloys used in the molten metal infiltration process are selected for their wetability with the specific ceramic composite at a low infiltration temperature (& lt ; 1150 c ). the better the wetting of the molten alloy to the cermaic , the shorter the time at temperature for nearly complete infiltration (& gt ; 98 %). similarly , the lower the infiltration temperature required , the shorter the time needed to complete the infiltration . less time at the infiltration temperature results in a finer microstructure and better performance of the cermet . a typical example of forming these new cermets is the selection of the nano - powder blend of boron carbide aluminum boride and magnesium boride . this powder blend would be cold pressed to greater than 55 % density and heat treated in a protective environment ( vacuum , argon , etc .) to form a porous component that would have a density lower than b4c if pressed alone . a metal alloy ( with good wetting characteristics for this component ) would be melted in contact with the ceramic component at a low temperature in a protective atmosphere ( vacuum , argon , etc .) to achieve nearly complete infiltration in a short time (& lt ; 1 hour ). subsequent heat treatments of the infiltrated component could be made to adjust the properties of the cermet for a specific application . use of the toxic element , be , is possible if the compositions selected for the ceramic compound and / or metal alloy does not exceed toxicity limits set for this element for the specific application . the foregoing description of the invention has been presented for purposes of illustration and description and is not intended to be exhaustive or to limit the invention to the precise form disclosed . many modifications and variations are possible in light of the above teaching . the embodiments disclosed were meant only to explain the principles of the invention and its practical application to thereby enable others skilled in the art to best use the invention in various embodiments and with various modifications suited to the particular use contemplated . the scope of the invention is to be defined by the following claims . | new cermets with improved properties and applications are provided . these new cermets have lower density and / or higher hardness than b4c cermet . by incorporating other new ceramics into b4c powders or as a substitute for b4c , lower densities and / or higher hardness cermets result . the ceramic powders have much finer particle size than those previously used which significantly reduces grain size of the cermet microstructure and improves the cermet properties . |
a test system according to an embodiment of the present disclosure is a self - contained total microbe test referring to fig1 a , a test system 100 includes an ampoule barrel 101 , an ampoule 102 and a cap 103 . the ampoule 102 may be removed from the ampoule barrel 101 . referring to fig1 b , the ampoule 102 includes a frangible tip 104 . the frangible tip 104 may be offset from a center of a main body 105 of the ampoule 102 . the ampoule 102 is a sealed container , which is opened open breaking the frangible tip 104 . the interior of the ampoule 102 is a vacuum - sealed environment . upon , breaking the tip 104 , the ampoule 102 is adapted to draw a predetermined volume of liquid according to an internal pressure of the ampoule 102 . referring to fig1 c , the ampoule barrel 101 includes an opening 106 for receiving an ampoule . the ampoule barrel 101 includes a tip 107 for allowing a liquid into the ampoule barrel 101 . the barrel tip 107 includes one or more ports for drawing the liquid into the ampoule barrel 101 under the vacuum of an ampoule . the tip 107 of the ampoule barrel may be off center relative to a longitudinal center of the ampoule barrel 101 . an off center tip 107 may be inserted into a sampling cup , wherein the sampling cup may be held on edge to pool a sample , increasing a depth of the sample . the off center tip 107 may be immersed in the pooled sample . fig2 is a cross - section view of a test system 100 . an ampoule barrel 101 receives an ampoule 102 . a seal 201 , formed of for example , a rubber substance secures the ampoule 102 . a tip 104 of the ampoule 102 projects through the seal 201 and into a sample chamber . upon placing the barrel tip 107 in a liquid , the seal 201 prevents the liquid from passing into an upper portion of the ampoule barrel 101 . the cap 103 is removable . the cap 103 prevents contaminants from entering the ampoule barrel 101 or contacting the barrel tip 107 prior to a test . referring to fig3 , the ampoule barrel 101 includes ports , e . g ., 301 and 302 , for allowing a liquid to pass into a lower portion or sample chamber 303 of the ampoule barrel 101 . the ports may be located on an end , e . g ., 301 , of the ampoule barrel 101 and / or on a side of the ampoule barrel , e . g ., 302 . the seal 201 prevents the liquid form passing into an upper portion of the ampoule barrel 101 . the ampoule 102 includes a frangible tip 104 . the tip 104 includes a terminus 305 . the terminus 305 has a rounded structure . above the terminus 305 , a score 306 is provided on a portion of the tip 104 . the score 306 is located to control the height at which the tip 104 breaks . the score 306 may be located on a portion , e . g ., about 90 degrees or about 180 degrees , of the circumference of the tip 104 . for example , as shown in fig3 , the score 306 is located on a portion of the tip 104 away from the direction of the intended breakage . the ampoule 102 may be depressed into the ampoule barrel 101 , wherein the terminus 305 meets an angled face 304 of the ampoule barrel 101 . a pressure applied to the ampoule 102 causes the ampoule to descend into the ampoule barrel 101 with the seal 201 . the angled face 304 converts the pressure into a lateral pressure on the terminus 305 of the tip 104 . the tip 104 breaks at about the height of the score 306 under the lateral pressure . the terminus 305 breaks away from the tip 104 allowing the liquid in the lower portion 303 of the ampoule barrel 101 into the ampoule 102 . a flow rate at which the ampoule 102 draws liquid may be slower than a flow rate of the ports of the ampoule barrel 101 . the tip 104 may be sheathed , such that upon breaking the terminus 305 , a lower portion of the tip drop away into the ampoule barrel 101 and a remaining portion of the tip 104 is guarded within the sheath . referring to fig4 a - c , upon drawing a sample into the ampoule 102 a sampling cap 401 may be placed over a broken tip of the ampoule 102 . a sheath 402 guards any sharps . the sampling cap 401 includes a nipple 403 . the nipple 403 fits within the sheath 402 . the cap 401 reduces a potential for contact with the liquid in the ampoule 102 . the nipple 403 cooperates with the sheath 402 , securing the sampling cap 401 to the ampoule 102 . the nipple 403 may be a tube through which a syringe 404 or other device may gain access to the contents of the ampoule 102 . referring to fig5 - 7 , various ampoule barrels are depicted . it should be noted that modifications and variations of the ampoule barrels are contemplated herein . referring to fig5 a - d , ampoule barrels 101 having a bottom port 501 with no offset relative to a centerline of the ampoule barrel 101 are shown . referring to fig5 a , a lead in angle 502 of the face 304 is about 60 degrees . the ampoule 102 includes an offset tip 104 . the tip 104 is guarded by a sheath 402 . the offset tip 104 is aligned to meet the face 304 as the ampoule 102 descends into the ampoule barrel 101 . fig5 b illustrates an ampoule barrel 101 having a face 304 with a lead in angle of about 30 degrees . fig5 c and 5d illustrate ampoule barrels 101 having a face 304 . the face 304 has a radius . for example , the radius of the face 304 in fig5 c is about 0 . 500 inches and the radius of the face 304 in fig5 d is about 0 . 110 inches . the radius of the face 304 converts the descent of the ampoule 102 into a lateral force that breaks the tip 104 . referring to fig6 a - d , a bottom port 501 of the ampoule barrel 101 is offset , for example , by 0 . 065 inches from a centerline of the ampoule barrel 101 . referring to fig6 a , a lead in angle 502 of the face 304 is about 30 degrees . a height of the face is not uniform around the ampoule barrel 101 . the rotation of the ampoule 102 within the ampoule barrel 101 ensures that the tip 104 contacts the face 304 upon descending into the ampoule barrel 101 . the rotation may be adjusted manually . a mechanism , such as a cooperating shape of the ampoule barrel 101 and ampoule 102 , may secure an alignment a sheath 402 may be implemented as a guard over the tip 104 . referring to fig6 b , a lead in angle of the face 304 is about 60 degrees . referring to fig6 c and 6d a face 304 has a radius of about 0 . 500 inches and 0 . 250 inches , respectively . referring to fig7 a - d , a bottom port 501 of the ampoule barrel 101 is offset , for example , by 0 . 130 inches from a centerline of the ampoule barrel 101 . referring to fig7 a , a lead in angle 502 of the face 304 is about 30 degrees . the angle of the face varies around the circumference of the ampoule barrel 101 between about 90 degrees and about 75 degrees . a height of the face is not uniform around the ampoule barrel 101 . the rotation of the ampoule 102 within the ampoule barrel 101 ensures that the tip 104 contacts the face 304 upon descending into the ampoule barrel 101 . referring to fig7 b , a lead in angle of the face 304 is about 60 degrees . referring to fig7 c and 7d a face 304 has a radius of about 0 . 500 inches and 0 . 250 inches , respectively . a sheath 402 may be implemented as a guard over the tip 104 . referring to fig8 a - c , a test system 100 may be loaded into a carrier 801 . the carrier 801 may be capped by a top 802 . the carrier comprises one or more trenches 804 for receiving a portion of an ampoule 102 . the trench 804 has a depth adapted to support an unused system 100 such that the ampoule 102 is not pressed into the ampoule barrel 101 ; a distance between a bottom of the trench and the upper surface 805 prevents the descent of the ampoule into the ampoule barrel . a flange 803 of the ampoule barrel 101 rests on an upper surface of the carrier 801 . an ampoule 102 according to an embodiment of the present disclosure is a sterile vacuum packaging ampoule containing a dry , non - hazardous , test reagent system . the ampoule 102 prevents user contamination or hazard , has about a 4 - year product shelf life , does not trigger transportation restrictions and does not need climate - controlled storage . a test of a liquid may be performed using a test system 100 according to an embodiment of the present disclosure . a sample module or ampoule barrel 101 secures a test ampoule 102 for extracting a liquid sample . the ampoule barrel 101 limits a sample taker &# 39 ; s exposure to the liquid . when used with a pre - dosed test ampoule 102 , the ampoule barrel 101 and test ampoule 102 automatically start a test of the sampled liquid under the pressure of the vacuum . referring to fig9 a , the sample chamber 303 houses an ampoule tip breaker assembly 900 . the ports or inlets , e . g ., 301 and 302 , may be formed on the walls of the ampoule barrel 101 and at a tip of the ampoule barrel 101 . any number of inlets may be used . the inlets allow the sample to freely enter the sample chamber at a rate at least as great as the sample enters the ampoule 102 . thus , the sample may enter the ampoule 102 in a predetermined dose , substantially unaffected by suction or fluid resistance . the ampoule tip breaker assembly 900 is stabilized in the sample chamber 303 to receive a tip 104 of the ampoule 102 . referring to fig9 b and 9c , the ampoule tip breaker assembly 900 is formed such that the sample may flow around the assembly and enter the ampoule 102 . the ampoule tip breaker assembly 900 includes a surface disposed at an angle for breaking the frangible portion of the test ampoule . the surface may be a hollow tube 901 for receiving a tip 104 of an ampoule 102 and for breaking the tip 104 . the hollow tube 901 is disposed at an angle to apply a substantially lateral force against the tip to facilitate the breaking of the tip . 104 for example , the hollow tube may be disposed at about 45 degrees from the walls of the sample chamber . the assembly 900 includes a stabilizer support 902 disposed at an angle for supporting the hollow tube 901 , e . g ., at about 90 degrees from the angle of the hollow tube 901 . the stabilizer support 302 and the hollow tube 901 may be formed as one piece . the hollow tube 901 may collect a broken portion of the tip of the ampoule 102 upon breaking away from the ampoule 102 . the stabilized ampoule tip breaker 900 breaks the tip of the ampoule 102 upon the application of pressure to the ampoule 102 , forcing the test ampoule tip 104 to engage a surface disposed at an angle . the tip 104 of the ampoule 102 is submerged in liquid as to avoid suction entrained air and creating an unacceptable ampoule fill . the test ampoule may be a hard - surfaced , self - filling container . the test ampoule includes mixed test indicators / media in predetermined quantities for performing a complete microbiological test . the test ampoules may be sealed , having a vacuum of about 20 - 30 inches of mercury or more . the test ampoule and contents may be insensitivity to storage conditions and may have a shelf life of about 4 years or more . the test ampoule includes a frangible area that can be broken , allowing a predetermined amount of sample to enter the test ampoule and be exposed to the test indicators / media . the test ampoule may be an ampoule as described in u . s . pat . nos . 5 , 159 , 799 entitled vial with powdered reagent , 5 , 550 , 032 entitled biological assay for microbial contamination , and 5 , 935 , 799 entitled biological assay for microbial contamination , each patent being incorporated herein by reference in the entirety . a test ampoule may be a pre - dosed , hermetically sealed , vacuum ampoule . the vacuum packaging of test ampoule preserves the reagent / media for years and needs no special storage conditions such as refrigeration . when the test is started , a aqueous sample of a predetermined volume , e . g ., 7 . 5 ml , is automatically drawn into the test ampoule . the volume of sample drawn can be any predetermined amount , depending on , for example , the size of the test ampoule and the strength of the vacuum . the test may be concluded when the test ampoule turns a predetermined color , e . g ., orange or red . the elapsed time from test start to test end determines the level of microbial contamination . test results may come as fast as one ( 1 ) hour for concentrations of 201 or twelve ( 12 ) hours for 10 1 microbial concentrations . the test ampoule may be used as presence / absence test at 24 hours . a triphenyltetrazoliumchloride ( ttc ) indicator may react to aerobic microbial activity in the sample to include facultative species . fungi may also be detected . the presence of fungi may be indicated by floating red particles after 24 hours . time / concentration calibrations are based upon mixed microbial populations typically found in industrial and natural waters . waters dominated by a particular species may use a one - time calibration adjustment . each test ampoule comes complete with a sample / ampoule , snapping cup , dechlorinating solution , sample identification labels , waste - water instructions and a results / instruction chart test incubation temperature can be controlled , and may be set to , for example , 95 ° f . or room temperature . test incubation can be performed manually by purchasing a reusable carry incubation tube or using a standard laboratory heat block or oven . automatic incubation and end of test detection can accomplished using an incubator / auto - analyzer . factory - prepared test calibrations / formulations and / or private labeling may also to used . an insulated chamber , such as an autoincubation chamber , suitable to hold a plurality of test ampoules at a controlled temperature and for specific time initiates and maintains an incubation temperature for a period of time and may return to refrigeration . this chamber may be transportable for all operational phases of the test ( refrigeration to incubation back to refrigeration ). the test ampoule , sample module , and insulated chamber may be pre - assembled into a clean or sterilized product that is operated by the sample technician or test initiator . referring to fig1 , an ampoule for a desired test is selected 1000 . the ampoule is placed in an ampoule barrel . the ampoule barrel is at least partially immersed in a liquid sample , and the tip of the ampoule is broken to begin a test 1001 . the ampoule containing a sample is extracted from the sample module 1002 . a cap may be placed over the broken tip of the test ampoule . the cap may include , for example , a bar code for tracking and / or a color chart for determining results . the test ampoule may be placed in an autoincubation testing chamber 1003 . the autoincubation testing chamber may be designed for shipping to a laboratory or other location , wherein the autoincubation testing chamber may be coupled to a power source . a control device of the autoincubation testing chamber controls a temperature profile ( e . g ., heating or cooling of samples under test ). the control device may include a processor for outputting control signals to a heater or chiller , and memory device for storing , for example , temperature and time settings . the results may be checked at a predetermined end time 1004 . the timing shown in fig1 are provide as examples , actual times may differ depending on the test and procedures . referring to fig1 a - b , the ampoule barrel 101 includes an offset tip 201 . a sheath 402 is fitted over a tip 104 of the ampoule 102 . the sheath 402 is formed of a rubberized polyvinyl chloride , a silicon compound or the like . the sheath 402 is press fit on the tip 104 of the ampoule 102 . the sheath 402 extends from the tip 104 through the offset tip 101 of the ampoule barrel 101 . the sheath 402 couples the ampoule 102 to the ampoule barrel 101 through the adhesion of the sheath 402 to the ampoule 102 and ampoule barrel 101 . the ampoule 102 and ampoule barrel 101 shown in fig1 a may be implemented with a cap 103 , wherein the cap 103 substantially prevents the ampoule 102 from descending into the ampoule barrel 101 . the cap 103 blocks the sheath 402 and the ampoule 102 from being descending into the ampoule barrel 101 . the ampoule 102 may be depressed into the ampoule barrel 101 , wherein a terminus 305 meets an angled face 304 of the ampoule barrel 101 . a pressure applied to the ampoule 102 causes the ampoule to descend into the ampoule barrel 101 . the angled face 304 converts the pressure into a lateral pressure on the terminus 305 of the tip 104 . the tip 104 breaks under the lateral pressure . the terminus 305 breaks away from the tip 104 allowing a liquid in which the offset tip 201 is submerged . the terminus 305 is held within the sheath 402 while allowing the liquid to pass . further , the sheath 402 guards a remaining portion of the tip 104 within the sheath 402 . having described embodiments for apparatus and method for sampling a liquid , it is noted that modifications and variations can be made by persons skilled in the art in light of the above teachings . it is therefore to be understood that changes may be made in the particular embodiments of the invention disclosed . | a sampling apparatus including an ampoule , an ampoule barrel for receiving the ampoule through a first opening , and a sheath fitted over a tip of the ampoule and extending from the ampoule and through a second opening of the ampoule barrel . |
the following examples set forth preferred materials and procedures in accordance with the present invention . it is to be understood , however , that these examples are provided by way of illustration only , and nothing therein should be deemed a limitation upon the overall scope of the invention . this example compares the relative yields of orf2 using methods of the present invention with methods that are known in the prior art . four 1000 ml spinner flasks were each seeded with approximately 1 . 0 × 10 6 sf + cells / ml in 300 ml of insect serum free media , excell 420 ( jrh biosciences , inc ., lenexa , kans .). the master cell culture is identified as sf + ( spodoptera frugiperda ) master cell stock , passage 19 , lot # n112 - 095w . the cells used to generate the sf + master cell stock were obtained from protein sciences corporation , inc ., meriden , conn . the sf + cell line for this example was confined between passages 19 and 59 . other passages will work for purposes of the present invention , but in order to scale the process up for large scale production , at least 19 passages will probably be necessary and passages beyond 59 may have an effect on expression , although this was not investigated . in more detail , the initial sf + cell cultures from liquid nitrogen storage were grown in excell 420 media in suspension in sterile spinner flasks with constant agitation . the cultures were grown in 100 ml to 250 ml spinner flasks with 25 to 150 ml of excell 420 serum - free media . when the cells had multiplied to a cell density of 1 . 0 - 8 . 0 × 10 6 cells / ml , they were split to new vessels with a planting density of 0 . 5 - 1 . 5 × 10 6 cells / ml . subsequent expansion cultures were grown in spinner flasks up to 36 liters in size or in stainless steel bioreactors of up to 300 liters for a period of 2 - 7 days at 25 - 29 ° c . after seeding , the flasks were incubated at 27 ° c . for four hours . subsequently , each flask was seeded with a recombinant baculovirus containing the pcv2 orf2 gene ( seq id no : 4 ). the recombinant baculovirus containing the pcv2 orf2 gene was generated as follows : the pcv2 orf2 gene from a north american strain of pcv2 was pcr amplified to contain a 5 ′ kozak &# 39 ; s sequence ( seq id no : 1 ) and a 3 ′ ecor1 site ( seq id no : 2 ), cloned into the pgem - t - easy vector ( promega , madison , wis .). then , it was subsequently excised and subcloned into the transfer vector pvl1392 ( bd biosciences pharmingen , san diego , calif .). the subcloned portion is represented herein as seq id no : 7 . the pvl1392 plasmid containing the pcv2 orf2 gene was designated n47 - 064y and then co - transfected with baculogold ® ( bd biosciences pharmingen ) baculovirus dna into sf + insect cells ( protein sciences , meriden , conn .) to generate the recombinant baculovirus containing the pcv2 orf2 gene . the new construct is provided herein as seq id no : 8 . the recombinant baculovirus containing the pcv2 orf2 gene was plaque - purified and master seed virus ( msv ) was propagated on the sf + cell line , aliquotted , and stored at − 70 ° c . the msv was positively identified as pcv2 orf2 baculovirus by pcr - rflp using baculovirus specific primers . insect cells infected with pcv2 orf2 baculovirus to generate msv or working seed virus express pcv2 orf2 antigen as detected by polyclonal serum or monoclonal antibodies in an indirect fluorescent antibody assay . additionally , the identity of the pcv2 orf2 baculovirus was confirmed by n - terminal amino acid sequencing . the pcv2 orf2 baculovirus msv was also tested for purity in accordance with 9 c . f . r . 113 . 27 ( c ), 113 . 28 , and 113 . 55 . each recombinant baculovirus seeded into the spinner flasks had varying multiplicities of infection ( mois ). flask 1 was seeded with 7 . 52 ml of 0 . 088 moi seed ; flask 2 was seeded with 3 . 01 ml of 0 . 36 moi seed ; flask 3 was seeded with 1 . 5 ml of 0 . 18 moi seed ; and flask 4 was seeded with 0 . 75 ml of 0 . 09 moi seed . a schematic flow diagram illustrating the basic steps used to construct a pcv2 orf2 recombinant baculovirus is provided herein as fig1 . after being seeded with the baculovirus , the flasks were then incubated at 27 ± 2 ° c . for 7 days and were also agitated at 100 rpm during that time . the flasks used ventilated caps to allow for air flow . samples from each flask were taken every 24 hours for the next 7 days . after extraction , each sample was centrifuged , and both the pellet and the supernatant were separated and then microfiltered through a 0 . 45 - 1 . 0 μm pore size membrane . the resulting samples then had the amount of orf2 present within them quantified via an elisa assay . the elisa assay was conducted with capture antibody swine anti - pcv2 pab igg prot . g purified ( diluted 1 : 250 in pbs ) diluted to 1 : 6000 in 0 . 05m carbonate buffer ( ph 9 . 6 ). 100 μl of the antibody was then placed in the wells of the mictrotiter plate , sealed , and incubated overnight at 37 ° c . the plate was then washed three times with a wash solution which comprised 0 . 5 ml of tween 20 ( sigma , st . louis , mo . ), 100 ml of 10 × d - pbs ( gibco invitrogen , carlsbad , calif .) and 899 . 5 ml of distilled water . subsequently , 250 μl of a blocking solution ( 5 g carnation non - fat dry milk ( nestle , glendale , calif .) in 10 ml of d - pbs qs to 100 ml with distilled water ) was added to each of the wells . the next step was to wash the test plate and then add pre - diluted antigen . the pre - diluted antigen was produced by adding 200 μl of diluent solution ( 0 . 5 ml tween 20 in 999 . 5 ml d - pbs ) to each of the wells on a dilution plate . the sample was then diluted at a 1 : 240 ratio and a 1 : 480 ratio , and 100 μl of each of these diluted samples was then added to one of the top wells on the dilution plate ( i . e . one top well received 100 μl of the 1 : 240 dilution and the other received 100 μl of the 1 : 480 dilution ). serial dilutions were then done for the remainder of the plate by removing 100 μl form each successive well and transferring it to the next well on the plate . each well was mixed prior to doing the next transfer . the test plate washing included washing the plate three times with the wash buffer . the plate was then sealed and incubated for an hour at 37 ° c . before being washed three more times with the wash buffer . the detection antibody used was monoclonal antibody to pcv orf2 . it was diluted to 1 : 300 in diluent solution , and 100 μl of the diluted detection antibody was then added to the wells . the plate was then sealed and incubated for an hour at 37 ° c . before being washed three times with the wash buffer . conjugate diluent was then prepared by adding normal rabbit serum ( jackson immunoresearch , west grove , pa .) to the diluent solution to 1 % concentration . conjugate antibody goat anti - mouse ( h + 1 )- hrp ( jackson immunoresearch ) was diluted in the conjugate diluent to 1 : 10 , 000 . 100 μl of the diluted conjugate antibody was then added to each of the wells . the plate was then sealed and incubated for 45 minutes at 37 ° c . before being washed three times with the wash buffer . 100 μl of substrate ( tmb peroxidase substrate , kirkgaard and perry laboratories ( kpl ), gaithersburg , md . ), mixed with an equal volume of peroxidase substrate b ( kpl ) was added to each of the wells . the plate was incubated at room temperature for 15 minutes . 100 μl of 1n hcl solution was then added to all of the wells to stop the reaction . the plate was then run through an elisa reader . the results of this assay are provided in table 1 below : these results indicate that when the incubation time is extended , expression of orf2 into the supernatant of the centrifuged cells and media is greater than expression in the pellet of the centrifuged cells and media . accordingly , allowing the orf2 expression to proceed for at least 5 days and recovering it in the supernate rather than allowing expression to proceed for less than 5 days and recovering orf2 from the cells , provides a great increase in orf2 yields , and a significant improvement over prior methods . this example provides data as to the efficacy of the invention claimed herein . a 1000 ml spinner flask was seeded with approximately 1 . 0 × 10 6 sf + cells / ml in 300 ml of excell 420 media . the flask was then incubated at 27 ° c . and agitated at 100 rpm . subsequently , the flask was seeded with 10 ml of pcv2 orf2 / bac p + 6 ( the recombinant baculovirus containing the pcv2 orf2 gene passaged 6 additional times in the sf9 insect cells ) virus seed with a 0 . 1 moi after 24 hours of incubation . the flask was then incubated at 27 ° c . for a total of 6 days . after incubation , the flask was then centrifuged and three samples of the resulting supernatant were harvested and inactivated . the supernatant was inactivated by bringing its temperature to 37 ± 2 ° c . to the first sample , a 0 . 4m solution of 2 - bromoethyleneamine hydrobromide which had been cyclized to 0 . 2m binary ethlylenimine ( bei ) in 0 . 3n naoh is added to the supernatant to give a final concentration of bei of 5 mm . to the second sample , 10 mm bei was added to the supernatant . to the third sample , no bei was added to the supernatant . the samples were then stirred continuously for 48 hrs . a 1 . 0 m sodium thiosulfate solution to give a final minimum concentration of 5 mm was added to neutralize any residual bei . the quantity of orf2 in each sample was then quantified using the same elisa assay procedure as described in example 1 . the results of this may be seen in table 2 below : this example demonstrates that neutralization with bei does not remove or degrade significant amounts of the recombinant pcv2 orf2 protein product . this is evidenced by the fact that there is no large loss of orf2 in the supernatant from the bei or elevated temperatures . those of skill in the art will recognize that the recovered orf2 is a stable protein product . this example demonstrates that the present invention is scalable from small scale production of recombinant pcv2 orf2 to large scale production of recombinant pcv2 orf2 . 5 . 0 × 10 5 cells / ml of sf + cells / ml in 7000 ml of excell 420 media was planted in a 20000 ml applikon bioreactor . the media and cells were then incubated at 27 ° c . and agitated at 100 rpm for the next 68 hours . at the 68 th hour , 41 . 3 ml of pcv2 orf2 baculovirus msv + 3 was added to 700 ml of excell 420 medium . the resultant mixture was then added to the bioreactor . for the next seven days , the mixture was incubated at 27 ° c . and agitated at 100 rpm . samples from the bioreactor were extracted every 24 hours beginning at day 4 , post - infection , and each sample was centrifuged . the supernatant of the samples were preserved and the amount of orf2 was then quantified using sds - page densitometry . the results of this can be seen in table 3 below : this example tests the efficacy of seven pcv2 candidate vaccines and further defines efficacy parameters following exposure to a virulent strain of pcv2 . one hundred and eight ( 108 ) cesarean derived colostrum deprived ( cdcd ) piglets , 9 - 14 days of age , were randomly divided into 9 groups of equal size . table 4 sets forth the general study design for this example . seven of the groups ( groups 1 - 7 ) received doses of pcv2 orf2 polypeptide , one of the groups acted as a challenge control and received no pcv2 orf2 , and another group acted as the strict negative control group and also received no pcv2 orf2 . on day 0 , groups 1 through 7 were treated with assigned vaccines . piglets in group 7 were given a booster treatment on day 14 . piglets were observed for adverse events and injection site reactions following vaccination and on day 19 , piglets were moved to the second study site . at the second study site , groups 1 - 8 were group housed in one building while group 9 was housed in a separate building . all pigs received keyhole limpet hemocyanin ( klh )/ incomplete freund &# 39 ; s adjuvant ( icfa ) on days 21 and 27 and on day 24 , groups 1 - 8 were challenged with a virulent pcv2 . pre - and post - challenge , blood samples were collected for pcv2 serology . post - challenge , body weight data for determination of average daily weight gain ( adwg ), and clinical symptoms , as well as nasal swab samples to determine nasal shedding of pcv2 , were collected . on day 49 , all surviving pigs were necropsied , lungs were scored for lesions , and selected tissues were preserved in formalin for immunohistochemistry ( ihc ) testing at a later date . this was a partially blinded vaccination - challenge feasibility study conducted in cdcd pigs , 9 to 14 days of age on day 0 . to be included in the study , pcv2 ifa titers of sows were ≦ 1 : 1000 . additionally , the serologic status of sows were from a known prrs - negative herd . twenty - eight ( 28 ) sows were tested for pcv2 serological status . fourteen ( 14 ) sows had a pcv2 titer of ≦ 1000 and were transferred to the first study site . one hundred ten ( 110 ) piglets were delivered by cesarean section surgeries and were available for this study on day − 4 . on day − 3 , 108 cdcd pigs at the first study site were weighed , identified with ear tags , blocked by weight and randomly assigned to 1 of 9 groups , as set forth above in table 4 . if any test animal meeting the inclusion criteria was enrolled in the study and was later excluded for any reason , the investigator and monitor consulted in order to determine the use of data collected from the animal in the final analysis . the date of which enrolled piglets were excluded and the reason for exclusion was documented . initially , no sows were excluded . a total of 108 of an available 110 pigs were randomly assigned to one of 9 groups on day − 3 . the two smallest pigs ( no . 17 and 19 ) were not assigned to a group and were available as extras , if needed . during the course of the study , several animals were removed . pig 82 ( group 9 ) on day − 1 , pig no . 56 ( group 6 ) on day 3 , pig no . 53 ( group 9 ) on day 4 , pig no . 28 ( group 8 ) on day 8 , pig no . 69 ( group 8 ) on day 7 , and pig no . 93 ( group 4 ) on day 9 , were each found dead prior to challenge . these six pigs were not included in the final study results . pig no 17 ( one of the extra pigs ) was assigned to group 9 . the remaining extra pig , no . 19 , was excluded from the study . the formulations given to each of the groups were as follows : group 1 was designed to administer 1 ml of viral orf2 ( vorf2 ) containing 16 μg orf2 / ml . this was done by mixing 10 . 24 ml of viral orf2 ( 256 μg / 25 μg / ml = 10 . 24 ml vorf2 ) with 3 . 2 ml of 0 . 5 % carbopol and 2 . 56 ml of phosphate buffered saline at a ph of 7 . 4 . this produced 16 ml of formulation for group 1 . group 2 was designed to administer 1 ml of vorf2 containing 8 μg vorf2 / ml . this was done by mixing 5 . 12 ml of vorf2 ( 128 μg / 25 μg / ml = 5 . 12 ml vorf2 ) with 3 . 2 ml of 0 . 5 % carbopol and 7 . 68 ml of phosphate buffered saline at a ph of 7 . 4 . this produced 16 ml of formulation for group 2 . group 3 was designed to administer 1 ml of vorf2 containing 4 μg vorf2 / ml . this was done by mixing 2 . 56 ml of vorf2 ( 64 μg / 25 μg / ml = 2 . 56 ml vorf2 ) with 3 . 2 ml of 0 . 5 % carbopol and 10 . 24 ml of phosphate buffered saline at a ph of 7 . 4 . this produced 16 ml of formulation for group 3 . group 4 was designed to administer 1 ml of recombinant orf2 ( rorf2 ) containing 16 μg rorf2 / ml . this was done by mixing 2 . 23 ml of rorf2 ( 512 μg / 230 μg / ml = 2 . 23 ml rorf2 ) with 6 . 4 ml of 0 . 5 % carbopol and 23 . 37 ml of phosphate buffered saline at a ph of 7 . 4 . this produced 32 ml of formulation for group 4 . group 5 was designed to administer 1 ml of rorf2 containing 8 μg rorf2 / ml . this was done by mixing 1 . 11 ml of rorf2 ( 256 μg / 230 μg / ml = 1 . 11 ml rorf2 ) with 6 . 4 ml of 0 . 5 % carbopol and 24 . 49 ml of phosphate buffered saline at a ph of 7 . 4 . this produced 32 ml of formulation for group 5 . group 6 was designed to administer 1 ml of rorf2 containing 8 μg rorf2 / ml . this was done by mixing 0 . 56 ml of rorf2 ( 128 μg / 230 μg / ml = 0 . 56 ml rorf2 ) with 6 . 4 ml of 0 . 5 % carbopol and 25 . 04 ml of phosphate buffered saline at a ph of 7 . 4 . this produced 32 ml of formulation for group 6 . group 7 was designed to administer 2 ml of pcv2 whole killed cell vaccine ( pcv2 kv ) containing the max pcv2 kv . this was done by mixing 56 ml of pcv2 kv with 14 ml of 0 . 5 % carbopol . this produced 70 ml of formulation for group 7 . finally group 8 was designed to administer klh at 0 . 5 μg / ml or 1 . 0 μg / ml per 2 ml dose . this was done by mixing 40 . 71 ml klh ( 7 . 0 μg protein / ml at 0 . 5 μg / ml = 570 ml ( 7 . 0 μg / ml )( x )=( 0 . 5 )( 570 ml )), 244 . 29 ml phosphate buffered saline at a ph of 7 . 4 , and 285 ml freunds adjuvant . table 5 describes the time frames for the key activities of this example . following completion of the in - life phase of the study , formalin fixed tissues were examined by immunohistochemistry ( ihc ) for detection of pcv2 antigen by a pathologist , blood samples were evaluated for pcv2 serology , nasal swab samples were evaluated for pcv2 shedding , and average daily weight gain ( adwg ) was determined from day 24 to day 49 . animals were housed at the first study site in individual cages in five rooms from birth to approximately 11 days of age ( approximately day 0 of the study ). each room was identical in layout and consisted of stacked individual stainless steel cages with heated and filtered air supplied separately to each isolation unit . each room had separate heat and ventilation , thereby preventing cross - contamination of air between rooms . animals were housed in two different buildings at the second study site . group 9 ( the strict negative control group ) was housed separately in a converted finisher building and groups 1 - 8 were housed in converted nursery building . each group was housed in a separate pen ( 11 - 12 pigs per pen ) and each pen provided approximately 3 . 0 square feet per pig . each pen was on an elevated deck with plastic slatted floors . a pit below the pens served as a holding tank for excrement and waste . each building had its own separate heating and ventilation systems , with little likelihood of cross - contamination of air between buildings . at the first study site , piglets were fed a specially formulated milk ration from birth to approximately 3 weeks of age . all piglets were consuming solid , special mixed ration by day 19 ( approximately 4½ weeks of age ). at the second study site , all piglets were fed a custom non - medicated commercial mix ration appropriate for their age and weight , ad libitum . water at both study sites was also available ad libitum . all test pigs were treated with vitamin e on day − 2 , with iron injections on day − 1 and with naxcel ® ( 1 . 0 ml , 1m , in alternating hams ) on days 16 , 17 , 18 and 19 . in addition , pig no . 52 ( group 9 ) was treated with an iron injection on day 3 , pig 45 ( group 6 ) was treated with an iron injection on day 11 , pig no . 69 ( group 8 ) was treated with naxcel ® on day 6 , pig no . 74 ( group 3 ) was treated with dexamethazone and penicillin on day 14 , and pig no . 51 ( group 1 ) was treated with dexamethazone and penicillin on day 13 and with naxcel ® on day 14 for various health reasons . while at both study sites , pigs were under veterinary care . animal health examinations were conducted on day 0 and were recorded on the health examination record form . all animals were in good health and nutritional status before vaccination as determined by observation on day 0 . all test animals were observed to be in good health and nutritional status prior to challenge . carcasses and tissues were disposed of by rendering . final disposition of study animals was records on the animal disposition record . on day 0 , pigs assigned to groups 1 - 6 received 1 . 0 ml of pcv2 vaccines 1 - 6 , respectively , im in the left neck region using a sterile 3 . 0 ml luer - lock syringe and a sterile 20 g × ½ ″ needle . pigs assigned to group 7 received 2 . 0 ml of pcv2 vaccine no . 7 im in the left neck region using a sterile 3 . 0 ml luer - lock syringe and a sterile 20 g × ½ ″ needle . on day 14 , pigs assigned to group 7 received 2 . 0 ml of pcv2 vaccine no . 7 im in the right neck region using a sterile 3 . 0 ml luer - lock syringe and a sterile 20 g × ½ ″ needle . on day 21 all test pigs received 2 . 0 ml of klh / icfa im in the right ham region using a sterile 3 . 0 ml luer - lock syringe and a sterile 20 g × 1 ″ needle . on day 27 all test pigs received 2 . 0 ml of klh / icfa in the left ham region using a sterile 3 . 0 ml luer - lock syringe and a sterile 20 g × 1 ″ needle . on day 24 , pigs assigned to groups 1 - 8 received 1 . 0 ml of pcv2 isuvdl challenge material ( 5 . 11 log 10 tcid 50 / ml ) im in the left neck region using a sterile 3 . 0 ml luer - lock syringe and a sterile 20 g × 1 ″ needle . an additional 1 . 0 ml of the same material was administered in to each pig ( 0 . 5 ml per nostril ) using a sterile 3 . 0 ml luer - lock syringe and nasal canula . test pigs were observed daily for overall health and adverse events on day − 4 and from day 0 to day 19 . observations were recorded on the clinical observation record . all test pigs were observed from day 0 to day 7 , and group 7 was further observed from day 14 to 21 , for injection site reactions . average daily weight gain was determined by weighing each pig on a calibrated scale on days − 3 , 24 and 49 , or on the day that a pig was found dead after challenge . body weights were recorded on the body weight form . day − 3 body weights were utilized to block pigs prior to randomization . day 24 and day 49 weight data was utilized to determine the average daily weight gain ( adwg ) for each pig during these time points . for pigs that died after challenge and before day 49 , the adwg was adjusted to represent the adwg from day 24 to the day of death . in order to determine pcv2 serology , venous whole blood was collected from each piglet from the orbital venous sinus on days − 3 and 14 . for each piglet , blood was collected from the orbital venous sinus by inserting a sterile capillary tube into the medial canthus of one of the eyes and draining approximately 3 . 0 ml of whole blood into a 4 . 0 ml serum separator tube ( sst ). on days 24 , 31 , and 49 , venous whole blood from each pig was collected from the anterior vena cava using a sterile 18 g × 1½ ″ vacutainer needle ( becton dickinson and company , franklin lakes , n . j . ), a vacutainer needle holder and a 13 ml sst . blood collections at each time point were recorded on the sample collection record . blood in each sst was allowed to clot , each sst was then spun down and the serum harvested . harvested serum was transferred to a sterile snap tube and stored at − 70 ± 10 ° c . until tested at a later date . serum samples were tested for the presence of pcv2 antibodies by bivi - r & amp ; d personnel . pigs were observed once daily from day 20 to day 49 for clinical symptoms and clinical observations were recorded on the clinical observation record . to test for pcv2 nasal shedding , on days 24 , 25 , and then every other odd numbered study day up to and including day 49 , a sterile dacron swab was inserted intra nasally into either the left or right nostril of each pig ( one swab per pig ) as aseptically as possible , swished around for a few seconds and then removed . each swab was then placed into a single sterile snap - cap tube containing 1 . 0 ml of emem media with 2 % ifbs , 500 units / ml of penicillin , 500 μg / ml of streptomycin and 2 . 5 μg / ml of fungizone . the swab was broken off in the tube , and the snap tube was sealed and appropriately labeled with animal number , study number , date of collection , study day and “ nasal swab .” sealed snap tubes were stored at − 40 ± 10 ° c . until transported overnight on ice to bivi - st . joseph . nasal swab collections were recorded on the nasal swab sample collection form . bivi - r & amp ; d conducted quantitative virus isolation ( vi ) testing for pcv2 on nasal swab samples . the results were expressed in log 10 values . a value of 1 . 3 logs or less was considered negative and any value greater than 1 . 3 logs was considered positive . pigs that died ( nos . 28 , 52 , 56 , 69 , 82 , and 93 ) at the first study site were necropsied to the level necessary to determine a diagnosis . gross lesions were recorded and no tissues were retained from these pigs . at the second study site , pigs that died prior to day 49 ( nos . 45 , 23 , 58 , 35 ), pigs found dead on day 49 prior to euthanasia ( nos . 2 , 43 ) and pigs euthanized on day 49 were necropsied . any gross lesions were noted and the percentages of lung lobes with lesions were recorded on the necropsy report form . from each of the 103 pigs necropsied at the second study site , a tissue sample of tonsil , lung , heart , liver , mesenteric lymph node , kidney and inguinal lymph node was placed into a single container with buffered 10 % formalin ; while another tissue sample from the same aforementioned organs was placed into a whirl - pak ( m - tech diagnostics ltd ., thelwall , uk ) and each whirl - pak was placed on ice . each container was properly labeled . sample collections were recorded on the necropsy report form . afterwards , formalin - fixed tissue samples and a diagnostic request form were submitted for ihc testing . ihc testing was conducted in accordance with standard isu laboratory procedures for receiving samples , sample and slide preparation , and staining techniques . fresh tissues in whirl - paks were shipped with ice packs to the study monitor for storage (− 70 °± 10 ° c .) and possible future use . formalin - fixed tissues were examined by a pathologist for detection of pcv2 by ihc and scored using the following scoring system : 0 = none ; 1 = scant positive staining , few sites ; 2 = moderate positive staining , multiple sites ; and 3 = abundant positive staining , diffuse throughout the tissue . due to the fact that the pathologist could not positively differentiate inguinal ln from mesenteric ln , results for these tissues were simply labeled as lymph node and the score given the highest score for each of the two tissues per animal . results for this example are given below . it is noted that one pig from group 9 died before day 0 , and 5 more pigs died post - vaccination ( 1 pig from group 4 ; 1 pig from group 6 ; 2 pigs from group 8 ; and 1 pig from group 9 ). post - mortem examination indicated all six died due to underlying infections that were not associated with vaccination or pmws . additionally , no adverse events or injection site reactions were noted with any groups . average daily weight gain ( adwg ) results are presented below in table 6 . group 9 , the strict negative control group , had the highest adwg ( 1 . 06 ± 0 . 17 lbs / day ), followed by group 5 ( 0 . 94 ± 0 . 22 lbs / day ), which received one dose of 8 μg of rorf2 . group 3 , which received one dose of 4 μg of vorf2 , had the lowest adwg ( 0 . 49 ± 0 . 21 lbs / day ), followed by group 7 ( 0 . 50 ± 0 . 15 lbs / day ), which received 2 doses of killed vaccine . pcv2 serology results are presented below in table 7 . all nine groups were seronegative for pcv2 on day − 3 . on day 14 , groups receiving vorf2 vaccines had the highest titers , which ranged from 187 . 5 to 529 . 2 . pigs receiving killed viral vaccine had the next highest titers , followed by the groups receiving rorf2 vaccines . groups 8 and 9 remained seronegative at this time . on day 24 and day 31 , pigs receiving vorf2 vaccines continued to demonstrate a strong serological response , followed closely by the group that received two doses of a killed viral vaccine . pigs receiving rorf2 vaccines were slower to respond serologically and groups 8 and 9 continued to remain seronegative . on day 49 , pigs receiving vorf2 vaccine , 2 doses of the killed viral vaccine and the lowest dose of rorf2 demonstrated the strongest serological responses . pigs receiving 16 μg and 8 μg of rorf2 vaccines had slightly higher ifa titers than challenge controls . group 9 on day 49 demonstrated a strong serological response . the results from the post - challenge clinical observations are presented below in table 8 . this summary of results includes observations for abnormal behavior , abnormal respiration , cough and diarrhea . table 9 includes the results from the summary of group overall incidence of clinical symptoms and table 10 includes results from the summary of group mortality rates post - challenge . the most common clinical symptom noted in this study was abnormal behavior , which was scored as mild to severe lethargy . pigs receiving the 2 lower doses of vorf2 , pigs receiving 16 μg of rorf2 and pigs receiving 2 doses of kv vaccine had incidence rates of ≧ 27 . 3 %. pigs receiving 8 μg of rorf2 and the strict negative control group had no abnormal behavior . none of the pigs in this study demonstrated any abnormal respiration . coughing was noted frequently in all groups ( 0 to 25 %), as was diarrhea ( 0 - 20 %). none of the clinical symptoms noted were pathognomic for pmws . the overall incidence of clinical symptoms varied between groups . groups receiving any of the vorf2 vaccines , the group receiving 16 μg of rorf2 , the group receiving 2 doses of kv vaccine and the challenge control group had the highest incidence of overall clinical symptoms (≧ 36 . 4 %). the strict negative control group , the group receiving 8 μg of rorf2 and the group receiving 4 μg of rorf2 had overall incidence rates of clinical symptoms of 0 %, 8 . 3 % and 9 . 1 %, respectively . overall mortality rates between groups varied as well . the group receiving 2 doses of kv vaccine had the highest mortality rate ( 16 . 7 %); while groups that received 4 μg of vorf2 , 16 μg of rorf2 , or 8 μg of rorf2 and the strict negative control group all had 0 % mortality rates . pcv2 nasal shedding results are presented below in table 11 . following challenge on day 24 , 1 pig in group 7 began shedding pcv2 on day 27 . none of the other groups experienced shedding until day 33 . the bulk of nasal shedding was noted from day 35 to day 45 . groups receiving any of the three vorf2 vaccines and groups receiving either 4 or 8 μg of rorf2 had the lowest incidence of nasal shedding of pcv2 (≦ 9 . 1 %). the challenge control group ( group 8 ) had the highest shedding rate ( 80 %), followed by the strict negative control group ( group 9 ), which had an incidence rate of 63 . 6 %. the summary of group incidence of icterus , group incidence of gastric ulcers , group mean lung lesion scores , and group incidence of lung lesions are shown below in table 12 . six pigs died at the first test site during the post - vaccination phase of the study ( group 4 , n = 1 ; group 6 , n = 1 ; group 8 , n = 2 ; group 9 , n = 2 ). four out of six pigs had fibrinous lesions in one or more body cavities , one pig ( group 6 ) had lesions consistent with clostridial disease , and one pig ( group 9 ) had no gross lesions . none of the pigs that died during the post - vaccination phased of the study had lesions consistent with pmws . pigs that died post - challenge and pigs euthanized on day 49 were necropsied . at necropsy , icterus and gastric ulcers were not present in any group . with regard to mean % lung lesions , group 9 had lowest mean % lung lesions ( 0 %), followed by group 1 with 0 . 40 ± 0 . 50 % and group 5 with 0 . 68 ± 1 . 15 %. groups 2 , 3 , 7 and 8 had the highest mean % lung lesions (≧ 7 . 27 %). each of these four groups contained one pig with % lung lesions ≧ 71 . 5 %, which skewed the results higher for these four groups . with the exception of group 9 with 0 % lung lesions noted , the remaining 8 groups had ≦ 36 % lung lesions . almost all lung lesions noted were described as red / purple and consolidated . the summary of group ihc positive incidence results are shown in table 13 . group 1 ( vorf2 — 16 μg ) and group 5 ( rorf2 — 8 μg ) had the lowest rate of ihc positive results ( 16 . 7 %). group 8 ( challenge controls ) and group 9 ( strict negative controls ) had the highest rate of ihc positive results , 90 % and 90 . 9 %, respectively . post - challenge , group 5 , which received one dose of 8 μg of rorf2 antigen , outperformed the other 6 vaccine groups . group 5 had the highest adwg ( 0 . 94 ± 0 . 22 lbs / day ), the lowest incidence of abnormal behavior ( 0 %), the second lowest incidence of cough ( 8 . 3 %), the lowest incidence of overall clinical symptoms ( 8 . 3 %), the lowest mortality rate ( 0 %), the lowest rate of nasal shedding of pcv2 ( 8 . 3 %), the second lowest rate for mean % lung lesions ( 0 . 68 ± 1 . 15 %) and the lowest incidence rate for positive tissues ( 16 . 7 %). groups receiving various levels of rorf2 antigen overall outperformed groups receiving various levels of vorf2 and the group receiving 2 doses of killed whole cell pcv2 vaccine performed the worst . tables 14 and 15 contain summaries of group post - challenge data . results of this study indicate that all further vaccine efforts should focus on a rorf2 vaccine . overall , nasal shedding of pcv2 was detected post - challenge and vaccination with a pcv2 vaccine resulted in a reduction of shedding . immunohistochemistry of selected lymphoid tissues also served as a good parameter for vaccine efficacy , whereas large differences in adwg , clinical symptoms , and gross lesions were not detected between groups . this study was complicated by the fact that extraneous pcv2 was introduced at some point during the study , as evidenced by nasal shedding of pcv2 , pcv2 seroconversion and positive ihc tissues in group 9 , the strict negative control group . seven pcv2 vaccines were evaluated in this study , which included three different dose levels of vorf2 antigen administered once on day 0 , three different dose levels of rorf2 antigen administered once on day 0 and one dose level of killed whole cell pcv2 vaccine administered on day 0 and day 14 . overall , group 5 , which received 1 dose of vaccine containing 8 μg of rorf2 antigen , had the best results . group 5 had the highest adwg , the lowest incidence of abnormal behavior , the lowest incidence of abnormal respiration , the second lowest incidence of cough , the lowest incidence of overall clinical symptoms , the lowest mortality rate , the lowest rate of nasal shedding of pcv2 , the second lowest rate for mean % lung lesions and the lowest incidence rate for positive ihc tissues . interestingly , group 4 , which received a higher dose of rorf2 antigen than group 5 , did not perform as well or better than group 5 . group 4 had a slightly lower adwg , a higher incidence of abnormal behavior , a higher incidence of overall clinical symptoms , a higher rate of nasal shedding of pcv2 , a higher mean % lung lesions , and a higher rate for positive ihc tissues than group 5 . statistical analysis , which may have indicated that the differences between these two groups were not statistically significant , was not conducted on these data , but there was an observed trend that group 4 did not perform as well as group 5 . post - vaccination , 6 pigs died at the first study site . four of the six pigs were from group 8 or group 9 , which received no vaccine . none of the six pigs demonstrated lesions consistent with pmws , no adverse events were reported and overall , all seven vaccines appeared to be safe when administered to pigs approximately 11 days of age . during the post - vaccination phase of the study , pigs receiving either of three dose levels of vorf2 vaccine or killed whole cell vaccine had the highest ifat levels , while group 5 had the lowest ifat levels just prior to challenge , of the vaccine groups . although not formally proven , the predominant route of transmission of pcv2 to young swine shortly after weaning is believed to be by oronasal direct contact and an efficacious vaccine that reduces nasal shedding of pcv2 in a production setting would help control the spread of infection . groups receiving one of three vorf2 antigen levels and the group receiving 8 μg of rorf2 had the lowest incidence rate of nasal shedding of pcv2 ( 8 . 3 %). expectedly , the challenge control group had the highest incidence rate of nasal shedding ( 80 %). gross lesions in pigs with pmws secondary to pcv2 infection typically consist of generalized lymphadenopathy in combination with one or a multiple of the following : ( 1 ) interstitial pneumonia with interlobular edema , ( 2 ) cutaneous pallor or icterus , ( 3 ) mottled atrophic livers , ( 4 ) gastric ulcers and ( 5 ) nephritis . at necropsy , icterus , hepatitis , nephritis , and gastric ulcers were not noted in any groups and lymphadenopathy was not specifically examined for . the mean % lung lesion scores varied between groups . the group receiving 16 μg of vorf2 antigen had the lowest mean % lung lesion score ( 0 . 40 ± 0 . 50 %), followed by the group that received 8 μg of rorf2 ( 0 . 68 ± 1 . 15 %). as expected , the challenge control group had the highest mean % lung lesion score ( 9 . 88 ± 29 . 2 %). in all four groups , the mean % lung lesion scores were elevated due to one pig in each of these groups that had very high lung lesion scores . most of the lung lesions were described as red / purple and consolidated . typically , lung lesions associated with pmws are described as tan and non - collapsible with interlobular edema . the lung lesions noted in this study were either not associated with pcv2 infection or a second pulmonary infectious agent may have been present . within the context of this study , the % lung lesion scores probably do not reflect a true measure of the amount of lung infection due to pcv2 . other researchers have demonstrated a direct correlation between the presence of pcv2 antigen by ihc and histopathology . histopathology on select tissues was not conducted with this study . group 1 ( 16 μg of vorf2 ) and group 5 ( 8 μg of rorf2 ) had the lowest incidence rate of pigs positive for pcv2 antigen ( 8 . 3 %), while group 9 ( the strict negative control group − 90 . 9 %) and group 8 ( the challenge control group − 90 . 0 %) had the highest incidence rates for pigs positive for pcv2 antigen . due to the non - subjective nature of this test , ihc results are probably one of the best parameters to judge vaccine efficacy on . thus , in one aspect of the present invention , the minimum portective dosage ( mpd ) of a 1 ml / 1 dose recombinant product with extracted pcv2 orf2 ( rorf2 ) antigen in the cdcd pig model in the face of a pcv2 challenge was determined . of the three groups that received varying levels of rorf2 antigen , group 5 ( 8 μg of rorf2 antigen ) clearly had the highest level of protection . group 5 either had the best results or was tied for the most favorable results with regard to all of the parameters examined . when group 5 was compared with the other six vaccine groups post - challenge , group 5 had the highest adwg ( 0 . 94 ± 0 . 22 lbs / day ), the lowest incidence of abnormal behavior ( 0 %), the second lowest incidence of cough ( 8 . 3 %), the lowest incidence of overall clinical symptoms ( 8 . 3 %), the lowest mortality rate ( 0 %), the lowest rate of nasal shedding of pcv2 ( 8 . 3 %), the second lowest rate for mean % lung lesions ( 0 . 68 ± 1 . 15 %) and the lowest incidence rate for positive ihc tissues ( 16 . 7 %). in another aspect of the present invention , the mpd of a 1 ml / 1 dose conventional product that is partially purified pcv2 orf2 ( vorf2 ) antigen in the cdcd pig model in the face of a pcv2 challenge was determined . of the three groups that received varying levels of vorf2 antigen , group 1 ( 16 μg of vorf2 ) had the highest level of protection . group 1 outperformed groups 2 and 3 with respect to adwg , mean % lung lesions , and ihc . groups 1 and 2 ( 8 μg of vorf2 antigen ) performed equally with respect to overall incidence of clinical symptoms , group 3 ( 4 μg of vorf2 antigen ) had the lowest mortality rate , and all three groups performed equally with respect to nasal shedding . overall , vorf vaccines did not perform as well as rorf vaccines . in yet another aspect of the present invention , the efficacy of a maximum dose of a 2 ml / 2 dose conventional killed pcv2 vaccine in the cdcd pig model in the face of a pcv2 challenge was determined . of the seven vaccines evaluated in this study , the killed whole cell pcv2 vaccine performed the worst . piglets receiving two doses of killed whole cell pcv2 vaccine had the lowest adwg , the second highest rate of abnormal behavior ( 58 . 3 %), the second highest overall incidence of clinical symptoms ( 58 . 3 %), the highest mortality rate ( 16 . 7 %), the second highest incidence of nasal shedding ( 41 . 7 %), highest mean % lung lesions ( 9 . 88 ± 29 . 2 %), a high incidence of lung lesions noted ( 75 %) and a moderate ihc incidence rate in tissues ( 41 . 7 %). however , it was still effective at invoking an immune response . in still another aspect of the present invention , nasal shedding of pcv2 was assessed as an efficacy parameter and the previous pcv2 efficacy parameters from previous studies were reconfirmed . results from this study indicate that nasal shedding of pcv2 occurs following intra nasal challenge and that pcv2 vaccines reduce nasal shedding of pcv2 post - challenge . furthermore , results from this study and reports in the literature indicate that ihc should continue to be evaluated in future pcv2 vaccine trials as well . some additional conclusions arising from this study are that lymphadenopathy is one of the hallmarks of pmws . another one of the hallmarks of pmws is lymphoid depletion and multinucleated / giant histiocytes . additionally , no adverse events or injection site reactions were noted for any of the 7 pcv2 vaccines and all 7 pcv2 vaccines appeared to be safe when administered to young pigs . this example tests the efficacy of eight pcv2 candidate vaccines and reconfirms pcv2 challenge parameters from earlier challenge studies following exposure to a virulent strain of pcv2 . one hundred and fifty ( 150 ) cesarean derived colostrum deprived ( cdcd ) piglets , 6 - 16 days of age , were blocked by weight and randomly divided into 10 groups of equal size . table 16 sets forth the general study design for this example . the vaccine formulation given to each group were as follows . pcv2 vaccine no . 1 , administered at 1 × 2 ml dose to group 1 , was a high dose ( 16 ug / 2 ml dose ) of inactivated recombinant orf2 antigen adjuvanted with ims 1314 ( 16 ug rorf2 - ims 1314 ). pcv2 vaccine no . 2 , administered at 1 × 2 ml dose to group 2 , was a high dose ( 16 ug / 2 ml dose ) of a partially purified vido r - 1 generated pcv2 orf2 antigen adjuvanted with carbopol ( 16 ug vorf2 - carbopol ). pcv2 vaccine no . 3 , administered at 1 × 2 ml dose to group 3 , was a high dose ( 16 ug / 2 ml dose ) of inactivated recombinant orf2 antigen adjuvanted with carbopol ( 16 ug rorf2 - carbopol ). pcv2 vaccine no . 4 , administered at 1 × 1 ml dose to group 4 , was a high dose ( 16 ug / 1 ml dose ) of a partially purified vido r - 1 generated pcv2 orf2 antigen adjuvanted with carbopol ( 16 ug vorf2 - carbopol ). vaccine no . 5 , administered at 1 × 2 ml dose to group 5 , was a 4 ug / 2 ml dose of an inactivated recombinant orf2 antigen adjuvanted with carbopol ( 4 ug rorf2 - carbopol ). pcv2 vaccine no . 6 , administered at 1 × 2 ml dose to group 6 , was a 1 ug / 2 ml dose of an inactivated recombinant orf2 antigen adjuvanted with carbopol ( 1 ug rorf2 - carbopol ). pcv2 vaccine no . 7 , administered at 1 × 2 ml dose to group 7 , was a low dose ( 0 . 25 ug / 2 ml dose ) of inactivated recombinant orf2 antigen adjuvanted with carbopol ( 0 . 25 ug rorf2 - carbopol ). pcv2 vaccine no . 8 , administered at 1 × 2 ml dose to group 8 , was a high dose ( pre - inactivation titer & gt ; 8 . 0 log / 2 ml dose ) inactivated conventional killed vido r - 1 generated pcv2 struve antigen adjuvanted with carbopol (& gt ; 8 . 0 log kv - carbopol ). on day 0 , groups 1 - 8 were treated with their assigned vaccines . groups 1 - 3 and 5 - 8 received boosters of their respective vaccines again on day 14 . the effectiveness of a single dose of 16 μg of vorf2 - carbopol was tested on group 4 which did not receive a booster on day 14 . piglets were observed for adverse events and injection site reactions following both vaccinations . on day 21 the piglets were moved to a second study site where groups 1 - 9 were group housed in one building and group 10 was housed in a separate building . all pigs received keyhole limpet hemocyanin emulsified with incomplete freund &# 39 ; s adjuvant ( klh / icfa ) on days 22 and 28 . on day 25 , groups 1 - 9 were challenged with approximately 4 logs of virulent pcv2 virus . by day 46 , very few deaths had occurred in the challenge control group . in an attempt to immunostimulate the pigs and increase the virulence of the pcv2 challenge material , all groups were treated with ingelvac ® prrsv mlv ( porcine reproductive and respiratory vaccine , modified live virus ) on day 46 . pre - and post - challenge blood samples were collected for pcv2 serology . post - challenge , body weight data for determination of average daily weight gain ( adwg ) and observations of clinical signs were collected . on day 50 , all surviving pigs were necropsied , gross lesions were recorded , lungs were scored for pathology , and selected tissues were preserved in formalin for examination by immunohistochemistry ( ihc ) for detection of pcv2 antigen at a later date . this was a partially - blind vaccination - challenge feasibility study conducted in cdcd pigs , 6 to 16 days of age on day 0 . to be included in the study , pcv2 ifa titers of sows were ≦ 1 : 1000 . additionally , the serologic status of sows were from a known prrs - negative herd . sixteen ( 16 ) sows were tested for pcv2 serological status and all sixteen ( 16 ) had a pcv2 titer of ≦ 1000 and were transferred to the first study site . one hundred fifty ( 150 ) piglets were delivered by cesarean section surgeries and were available for this study on day − 3 . on day − 3 , 150 cdcd pigs at the first study site were weighed , identified with ear tags , blocked by weight and randomly assigned to 1 of 10 groups , as set forth above in table 16 . blood samples were collected from all pigs . if any test animal meeting the inclusion criteria was enrolled in the study and was later excluded for any reason , the investigator and monitor consulted in order to determine the use of data collected from the animal in the final analysis . the date of which enrolled piglets were excluded and the reason for exclusion was documented . no sows meeting the inclusion criteria , selected for the study and transported to the first study site were excluded . no piglets were excluded from the study , and no test animals were removed from the study prior to termination . table 17 describes the time frames for the key activities of this example . following completion of the in - life phase of the study , formalin fixed tissues were examined by immunohistochemistry ( ihc ) for detection of pcv2 antigen by a pathologist , blood samples were evaluated for pcv2 serology , and average daily weight gain ( adwg ) was determined from day 25 to day 50 . animals were housed at the first study site in individual cages in seven rooms from birth to approximately 11 days of age ( approximately day 0 of the study ). each room was identical in layout and consisted of stacked individual stainless steel cages with heated and filtered air supplied separately to each isolation unit . each room had separate heat and ventilation , thereby preventing cross - contamination of air between rooms . animals were housed in two different buildings at the second study site . group 10 ( the strict negative control group ) was housed separately in a converted nursery building and groups 1 - 9 were housed in a converted farrowing building . each group was housed in a separate pen ( 14 - 15 pigs per pen ) and each pen provided approximately 2 . 3 square feet per pig . groups 2 , 4 and 8 were penned in three adjacent pens on one side of the alleyway and groups 1 , 3 , 5 , 6 , 7 , and 9 were penned in six adjacent pens on the other side of the alleyway . the group separation was due to concern by the study monitor that vaccines administered to groups 2 , 4 , and 8 had not been fully inactivated . each pen was on an elevated deck with plastic slatted floors . a pit below the pens served as a holding tank for excrement and waste . each building had its own separate heating and ventilation systems , with little likelihood of cross - contamination of air between buildings . at the first study site , piglets were fed a specially formulated milk ration from birth to approximately 3 weeks of age . all piglets were consuming solid , special mixed ration by day 21 ( approximately 4½ weeks of age ). at the second study site , all piglets were fed a custom non - medicated commercial mix ration appropriate for their age and weight , ad libitum . water at both study sites was also available ad libitum . all test pigs were treated with 1 . 0 ml of naxcel ®, im , in alternating hams on days 19 , 20 , and 21 . in addition , pig no . 11 ( group 1 ) was treated with 0 . 5 ml of naxcel ® im on day 10 , pig no . 13 ( group 10 ) was treated with 1 ml of penicillin and 1 ml of predef ® 2 × on day 10 , pig no . 4 ( group 9 ) was treated with 1 . 0 ml of naxcel ® im on day 11 , and pigs 1 ( group 1 ), 4 and 11 were each treated with 1 . 0 ml of naxcel ® on day 14 for various health reasons . while at both study sites , pigs were under veterinary care . animal health examinations were conducted on day − 3 and were recorded on the health examination record form . all animals were in good health and nutritional status before vaccination as determined by observation on day 0 . all test animals were observed to be in good health and nutritional status prior to challenge . carcasses and tissues were disposed of by rendering . final disposition of study animals was recorded on the animal disposition record . on days 0 and 14 , pigs assigned to groups 1 - 3 and 5 - 8 received 2 . 0 ml of assigned pcv2 vaccines 1 - 4 , respectively , im in the right and left neck region , respectively , using a sterile 3 . 0 ml luer - lock syringe and a sterile 20 g × ½ ″ needle . pigs assigned to group 4 received 1 . 0 ml of pcv2 vaccine no . 2 , im in the right neck region using a sterile 3 . 0 ml luer - lock syringe and a sterile 20 g × ½ ″ needle on day 0 only . on day 22 all test pigs received 2 . 0 ml of klh / icfa im in the left neck region using a sterile 3 . 0 ml luer - lock syringe and a sterile 20 g × 1 ″ needle . on day 28 all test pigs received 2 . 0 ml of klh / icfa in the right ham region using a sterile 3 . 0 ml luer - lock syringe and a sterile 20 g × 1 ″ needle . on day 25 , pigs assigned to groups 1 - 9 received 1 . 0 ml of pcv2 isuvdl challenge material ( 3 . 98 log 10 tcid 50 / ml ) im in the right neck region using a sterile 3 . 0 ml luer - lock syringe and a sterile 20 g × 1 ″ needle . an additional 1 . 0 ml of the same material was administered in to each pig ( 0 . 5 ml per nostril ) using a sterile 3 . 0 ml luer - lock syringe and nasal canula . on day 46 , all test pigs received 2 . 0 ml ingelvac ® prrs mlv , im , in the right neck region using a sterile 3 . 0 ml luer0lock syringe and a sterile 20 g × 1 ″ needle . the prrsv mlv was administered in an attempt to increase virulence of the pcv2 challenge material . test pigs were observed daily for overall health and adverse events on day − 3 and from day 0 to day 21 . each of the pigs were scored for normal or abnormal behavior , respiration or cough . observations were recorded on the clinical observation record . all test pigs were observed from day 0 to day 7 , and group 7 was further observed from day 14 to 21 , for injection site reactions . average daily weight gain was determined by weighing each pig on a calibrated scale on days − 3 , 25 and 50 , or on the day that a pig was found dead after challenge . body weights were recorded on the body weight form . day − 3 body weights were utilized to block pigs prior to randomization . day 25 and day 50 weight data was utilized to determine the average daily weight gain ( adwg ) for each pig during these time points . for pigs that died after challenge and before day 50 , the adwg was adjusted to represent the adwg from day 25 to the day of death . in order to determine pcv2 serology , venous whole blood was collected from each piglet from the orbital venous sinus on days − 3 and 14 . for each piglet , blood was collected from the orbital venous sinus by inserting a sterile capillary tube into the medial canthus of one of the eyes and draining approximately 3 . 0 ml of whole blood into a 4 . 0 ml serum separator tube ( sst ). on days 25 , 32 , and 50 , venous whole blood from each pig was collected from the anterior vena cava using a sterile 20 g × 1½ ″ vacutainer ® needle ( becton dickinson and company , franklin lakes , n . j . ), a vaccutainer ® needle holder and a 13 ml sst . blood collections at each time point were recorded on the sample collection record . blood in each sst was allowed to clot , each sst was then spun down and the serum harvested . harvested serum was transferred to a sterile snap tube and stored at − 70 ± 10 ° c . until tested at a later date . serum samples were tested for the presence of pcv2 antibodies by bivi - r & amp ; d personnel . pigs were observed once daily from day 22 to day 50 for clinical symptoms and scored for normal or abnormal behavior , respiration or cough . clinical observations were recorded on the clinical observation record . pigs nos . 46 ( group 1 ) and 98 ( groups 9 ) died at the first study site . both of these deaths were categorized as bleeding deaths and necropsies were not conducted on these two pigs . at the second study site , pigs that died after challenge and prior to day 50 , and pigs euthanized on day 50 , were necropsied . any gross lesions were noted and the percentages of lung lobes with lesions were recorded on the necropsy report form . from each of the pigs necropsied at the second study site , a tissue sample of tonsil , lung , heart , and mesenteric lymph node was placed into a single container with buffered 10 % formalin ; while another tissue sample from the same aforementioned organs was placed into a whirl - pak ® ( m - tech diagnostics ltd ., thelwall , uk ) and each whirl - pak ® was placed on ice . each container was properly labeled . sample collections were recorded on the necropsy report form . afterwards , formalin - fixed tissue samples and a diagnostic request form were submitted for ihc testing . ihc testing was conducted in accordance with standard laboratory procedures for receiving samples , sample and slide preparation , and staining techniques . fresh tissues in whirl - paks ® were shipped with ice packs to the study monitor for storage (− 70 °± 10 ° c .) and possible future use . formalin - fixed tissues were examined by a pathologist for detection of pcv2 by ihc and scored using the following scoring system : 0 = none ; 1 = scant positive staining , few sites ; 2 = moderate positive staining , multiple sites ; and 3 = abundant positive staining , diffuse throughout the tissue . for analytical purposes , a score of 0 was considered “ negative ,” and a score of greater than 0 was considered “ positive .” results for this example are given below . it is noted that pigs no . 46 and 98 died on days 14 and 25 respectively . these deaths were categorized as bleeding deaths . pig no . 11 ( group 1 ) was panting with rapid respiration on day 15 . otherwise , all pigs were normal for behavior , respiration and cough during this observation period and no systemic adverse events were noted with any groups . no injection site reactions were noted following vaccination on day 0 . following vaccination on day 14 , seven ( 7 ) out of fourteen ( 14 ) group 1 pigs ( 50 . 0 %) had swelling with a score of “ 2 ” on day 15 . four ( 4 ) out of fourteen ( 14 ) group 1 ( 28 . 6 %) still had a swelling of “ 2 ” on day 16 . none of the other groups experienced injection site reactions following either vaccination . average daily weight gain ( adwg ) results are presented below in table 18 . pigs no . 46 and 98 that died from bleeding were excluded from group results . group 4 , which received one dose of 16 ug vorf2 - carbopol , had the highest adwg ( 1 . 16 ± 0 . 26 lbs / day ), followed by groups 1 , 2 , 3 , 5 , 6 , and 10 which had adwgs that ranged from 1 . 07 ± 0 . 23 lbs / day to 1 . 11 ± 0 . 26 lbs / day . group 9 had the lowest adwg ( 0 . 88 ± 0 . 29 lbs / day ), followed by groups 8 and 7 , which had adwgs of 0 . 93 ± 0 . 33 lbs / day and 0 . 99 ± 0 . 44 lbs / day , respectively . pvc2 serology results are presented below in table 19 . all ten ( 10 ) groups were seronegative for pcv2 on day − 3 . on day 14 , pcv2 titers remained low for all ten ( 10 ) groups ( range of 50 - 113 ). on day 25 , group 8 , which received the whole cell killed virus vaccine , had the highest pcv2 titer ( 4617 ), followed by group 2 , which received 16 ug vorf2 - carbopol , group 4 , which received as single dose of 16 ug vorf2 - carbopol , and group 3 , which received 16 ug rorf2 - carbopol , which had titers of 2507 , 1920 and 1503 respectively . on day 32 ( one week post challenge ), titers for groups 1 - 6 and group 8 ranged from 2360 to 7619 ; while groups 7 ( 0 . 25 ug rorf2 - carbopol ), 9 ( challenge control ), and 10 ( strict negative control ) had titers of 382 , 129 and 78 respectively . on day 50 ( day of necropsy ), all ten ( 10 ) groups demonstrated high pcv2 titers (≧ 1257 ). on days 25 , 32 , and 50 , group 3 , which received two doses of 16 ug rorf2 - carbopol had higher antibody titers than group 1 , which received two doses of 16 ug rorf2 - ims 1314 . on days 25 , 32 and 50 , group 2 , which received two doses of 16 ug vorf2 had higher titers than group 4 , which received only one does of the same vaccine . groups 3 , 5 , 6 , 7 , which received decreasing levels of rorf2 - carbopol , of 16 , 4 , 1 , and 0 . 25 ug respectively , demonstrated correspondingly decreasing antibody titers on days 25 and 32 . the results from the post - challenge clinical observations are presented below . table 20 includes observations for abnormal behavior , abnormal respiration , cough and diarrhea . table 21 includes the results from the summary of group overall incidence of clinical symptoms and table 22 includes results from the summary of group mortality rates post - challenge . the incidence of abnormal behavior , respiration and cough post - challenge were low in pigs receiving 16 ug rorf2 - ims 1314 ( group 1 ), 16 ug rorf2 - carbopol ( group 3 ), 1 ug rorf2 - carbopol ( group 6 ), 0 . 25 ug rorf2 - carbopol ( group 7 ), and in pigs in the challenge control group ( group 9 ). the incidence of abnormal behavior respiration and cough post - challenge was zero in pigs receiving 16 ug vorf2 - carbopol ( group 2 ), a single dose of 16 ug vorf2 - carbopol ( group 4 ), 4 ug rorf2 - carbopol ( group 5 ), & gt ; 8 log kv - carbopol ( group 8 ), and in pigs in the strict negative control group ( group 10 ). the overall incidence of clinical symptoms varied between groups . pigs receiving 16 ug vorf2 - carbopol ( group 2 ), a single dose of 16 ug vorf2 - carbopol ( group 4 ), and pigs in the strict negative control group ( group 10 ) had incidence rates of 0 %; pigs receiving 16 ug rorf2 - carbopol ( group 3 ), and 1 ug rorf2 - carbopol ( group 6 ) had incidence rates of 6 . 7 %; pigs receiving 16 ug rorf2 - ims 1314 ( group 1 ) had an overall incidence rate of 7 . 1 %; pigs receiving 4 ug rorf2 - carbopol ( group 5 ), 0 . 25 ug rorf2 - carbopol ( group 7 ), and & gt ; 8 log kv vaccine had incidence rates of 13 . 3 %; and pigs in the challenge control group ( group 9 ) had an incidence rate of 14 . 3 %. overall mortality rates between groups varied as well . group 8 , which received 2 doses of kv vaccine had the highest mortality rate of 20 . 0 %; followed by group 9 , the challenge control group , and group 7 , which received 0 . 25 ug rorf2 - carbopol and had mortality rates of 14 . 3 % and 13 . 3 % respectively . group 4 , which received one dose of 16 ug vorf2 - carbopol had a 6 . 7 % mortality rate . all of the other groups , 1 , 2 , 3 , 5 , 6 , and 10 had a 0 % mortality rate . the summary of group mean percentage lung lesions and tentative diagnosis is given below in table 23 . group 9 , the challenge control group , had the highest percentage lung lesions with a mean of 10 . 81 ± 23 . 27 %, followed by group 7 , which received 0 . 25 ug rorf2 - carbopol and had a mean of 6 . 57 ± 24 . 74 %, group 5 , which received 4 ug rorf2 - carbopol and had a mean of 2 . 88 ± 8 . 88 %, and group 8 , which received the kv vaccine and had a mean of 2 . 01 ± 4 . 98 %. the remaining six ( 6 ) groups had lower mean percentage lung lesions that ranged from 0 . 11 ± 0 . 38 % to 0 . 90 ± 0 . 15 %. tentative diagnosis of pneumonia varied among the groups . group 3 , which received two doses of 16 ug rorf2 - carbopol , had the lowest tentative diagnosis of pneumonia , with 13 . 3 %. group 9 , the challenge control group , had 50 % of the group tentatively diagnosed with pneumonia , followed by group 10 , the strict negative control group and group 2 , which received two doses of 16 ug vorf2 - carbopol , with 46 . 7 % of 40 % respectively , tentatively diagnosed with pneumonia . groups 1 , 2 , 3 , 5 , 9 , and 10 had 0 % of the group tentatively diagnosed as pcv2 infected ; while group 8 , which received two doses if kv vaccine , had the highest group rate of tentative diagnosis of pcv2 infection , which 20 %. group 7 , which received two doses of 0 . 25 ug rorf2 - carbopol , and group 4 , which received one dose of 16 ug vorf2 - carbopol had tentative group diagnoses of pcv2 infection in 13 . 3 % and 6 . 7 % of each group , respectively . gastric ulcers were only diagnosed in one pig in group 7 ( 6 . 7 %); while the other 9 groups remained free of gastric ulcers . the summary of group ihc positive incidence results are shown below in table 24 . group 1 ( 16 ug rorf2 - ims 1314 ) had the lowest group rate of ihc positive results with 0 % of the pigs positive for pcv2 , followed by group 2 ( 16 ug vorf2 - carbopol ) and group 4 ( single dose 16 ug vorf2 - carbopol ), which had group ihc rates of 6 . 7 % and 13 . 3 % respectively . group 9 , the challenge control group , had the highest ihc positive incidence rate with 100 % of the pigs positive for pcv2 , followed by group 10 , the strict negative control group , and group 8 ( kv vaccine ), with 93 . 3 % and 80 % of the pigs positive for pcv2 , respectively . seven pcv2 vaccines were evaluated in this example , which included a high dose ( 16 μg ) of rorf2 antigen adjuvanted with ims 1314 administered twice , a high dose ( 16 μg ) of vorf2 antigen adjuvanted with carbopol administered once to one group of pigs and twice to a second group of pigs , a high dose ( 16 μg ) of rorf2 antigen adjuvanted with carbopol administered twice , a 4 μg dose of rorf2 antigen adjuvanted with carbopol administered twice , a 1 μg dose of rorf2 antigen adjuvanted with carbopol administered twice , a low dose ( 0 . 25 μg ) of rorf2 antigen adjuvanted with carbopol administered twice , and a high dose (& gt ; 8 log ) of killed whole cell pcv2 vaccine adjuvanted with carbopol . overall , group 1 , which received two doses of 16 μg rorf2 - ims 1314 , performed slightly better than groups 2 through 7 , which received vaccines containing various levels of either vorf2 or rorf2 antigen adjuvanted with carbopol and much better than group 8 , which received two doses of killed whole cell pcv2 vaccine . group 1 had the third highest adwg ( 1 . 80 ± 0 . 30 lbs / day ), the lowest incidence of abnormal behavior ( 0 %), the lowest incidence of abnormal respiration ( 0 %), a low incidence of cough ( 7 . 1 %), a low incidence of overall clinical symptoms ( 7 . 1 %), was tied with three other groups for the lowest mortality rate ( 0 %), the second lowest rate for mean % lung lesions ( 0 . 15 ± 0 . 34 %), the second lowest rate for pneumonia ( 21 . 4 %) and the lowest incidence rate for positive ihc tissues ( 0 %). group 1 was , however , the only group in which injection site reactions were noted , which included 50 % of the vaccinates 1 day after the second vaccination . the other vaccines administered to groups 2 through 7 performed better than the killed vaccine and nearly as well as the vaccine administered to group 1 . group 8 , which received two doses of killed pcv2 vaccine adjuvanted with carbopol , had the worst set of results for any vaccine group . group 8 had the lowest adwg ( 0 . 93 ± 0 . 33 lbs / day ), the second highest rate of abnormal behavior ( 6 . 7 %), the highest rate of abnormal respiration ( 6 . 7 %), was tied with three other groups for the highest overall incidence rate of clinical symptoms ( 13 . 3 %), had the highest mortality rate of all groups ( 20 %), and had the highest positive ihc rate ( 80 %) of any vaccine group . there was concern that the killed whole cell pcv2 vaccine may not have been fully inactivated prior to administration to group 8 , which may explain this group &# 39 ; s poor results . unfortunately , definitive data was not available to confirm this concern . overall , in the context of this example , a conventional killed pcv2 vaccine did not aid in the reduction of pcv2 associated disease . as previously mentioned , no adverse events were associated with the test vaccines with exception of the vaccine adjuvanted with ims 1314 . injection site reactions were noted in 50 . 0 % of the pigs 1 day after the second vaccination with the vaccine formulated with ims 1314 and in 28 . 6 % of the pigs 2 days after the second vaccination . no reactions were noted in any pigs receiving carbopol adjuvanted vaccines . any further studies that include pigs vaccinated with ims 1314 adjuvanted vaccines should continue to closely monitor pigs for injection site reactions . all pigs were sero - negative for pcv2 on day − 3 and only group 2 had a titer above 100 on day 14 . on day 25 ( day of challenge ), group 8 had the highest pcv2 antibody titer ( 4619 ), followed by group 2 ( 2507 ). with the exception of groups 7 , 9 and 10 , all groups demonstrated a strong antibody response by day 32 . by day 50 , all groups including groups 7 , 9 and 10 demonstrated a strong antibody response . one of the hallmarks of late stage pcv2 infection and subsequent pmws development is growth retardation in weaned pigs , and in severe cases , weight loss is noted . average daily weight gain of groups is a quantitative method of demonstrating growth retardation or weight loss . in this example , there was not a large difference in adwg between groups . group 8 had the lowest adwg of 0 . 88 ± 0 . 29 lbs / day , while group 4 had the highest adwg of 1 . 16 ± 0 . 26 lb / day . within the context of this study there was not a sufficient difference between groups to base future vaccine efficacy on adwg . in addition to weight loss — dyspnea , lethargy , pallor of the skin and sometimes icterus are clinical symptoms associated with pmws . in this example , abnormal behavior and abnormal respiration and cough were noted infrequently for each group . as evidenced in this study , this challenge model and challenge strain do not result in overwhelming clinical symptoms and this is not a strong parameter on which to base vaccine efficacy . overall , mortality rates were not high in this example and the lack of a high mortality rate in the challenge control group limits this parameter on which to base vaccine efficacy . prior to day 46 , groups 4 and 7 each had one out of fifteen pigs die , group 9 had two out of fourteen pigs die and group 8 had three out of fifteen pigs die . due to the fact that group 9 , the challenge control group was not demonstrating pcv2 clinical symptoms and only two deaths had occurred in this group by day 46 , porcine respiratory and reproductive syndrome virus ( prrsv ) mlv vaccine was administered to all pigs on day 46 . earlier studies had utilized ingelvac ® prrs mlv as an immunostimulant to exasperate pcv2 - associated pmws disease and mortality rates were higher in these earlier studies . two deaths occurred shortly after administering the prrs vaccine on day 46 — group 4 had one death on day 46 and group 7 had one death on day 47 — which were probably not associated with the administration of the prrs vaccine . by day 50 , group 8 , which received two doses of killed vaccine , had the highest mortality rate ( 20 %), followed by group 9 ( challenge control ) and group 7 ( 0 . 25 ug rorf2 - carbopol ), with mortality rates of 14 . 3 % and 13 . 3 % respectively . overall , administration of the prrs vaccine to the challenge model late in the post - challenge observation phase of this example did not significantly increase mortality rates . gross lesions in pigs with pmws secondary to pcv2 infection typically consist of generalized lymphadenopathy in combination with one or more of the following : ( 1 ) interstitial pneumonia with interlobular edema , ( 2 ) cutaneous pallor or icterus , ( 3 ) mottled atrophic livers , ( 4 ) gastric ulcers and ( 5 ) nephritis . at necropsy ( day 50 ), icterus , hepatitis , and nephritis were not noted in any groups . a gastric ulcer was noted in one group 7 pig , but lymphadenopathy was not specifically examined for . based on the presence of lesions that were consistent with pcv2 infection , three groups had at least one pig tentatively diagnosed with pcv2 ( pmws ). group 8 , which received two doses of killed vaccine , had 20 % tentatively diagnosed with pcv2 , while group 7 and group 4 had 13 . 3 % and 6 . 7 %, respectively , tentatively diagnosed with pcv2 . the mean % lung lesion scores varied between groups at necropsy . groups 1 , 2 , 3 , 4 , 6 and 10 had low % lung lesion scores that ranged from 0 . 11 ± 0 . 38 % to 0 . 90 ± 0 . 15 %. as expected , group 9 , the challenge control group , had the highest mean % lung lesion score ( 10 . 81 ± 23 . 27 %). in four groups , the mean % lung lesion scores were elevated due to one to three pigs in each of these groups having very high lung lesion scores . the lung lesions were red / purple and consolidated . typically , lung lesions associated with pmws are described as tan , non - collapsible with interlobular edema . the lung lesions noted in this study were either not associated with pcv2 infection or a second pulmonary infectious agent may have been present . within the context of this study , the % lung lesion scores probably do no reflect a true measure of the amount of lung infection due to pcv2 . likewise , tentative diagnosis of pneumonia may have been over - utilized as well . any pigs with lung lesions , some as small as 0 . 10 % were listed with a tentative diagnosis of pneumonia . in this example , there was no sufficient difference between groups with respect to gross lesions and % lung lesions on which to base vaccine efficacy . ihc results showed the largest differences between groups . group 1 ( 16 μg rorf2 - ims 1314 ) had the lowest positive ihc results for pcv2 antigen ( 0 %); while groups 9 and 10 had the highest positive ihc results with incidence rates of 100 % and 93 . 3 % respectively . groups 3 , 5 , 6 and 7 , which received 16 , 4 , 1 or 0 . 25 μg of rorf2 antigen , respectively , adjuvanted with carbopol , had ihc positive rates of 20 %, 20 %, 40 % and 46 . 7 %, respectively . group 2 , which received two doses of 16 μg vorf2 adjuvanted with carbopol had an ihc positive rate of 6 . 7 %, while group 4 which received only one dose of the same vaccine , had an ihc positive rate of 13 . 3 %. due to the objective nature of this test and the fact that ihc results correlated with expected results , ihc testing is probably one of the best parameters on which to base vaccine efficacy . thus in one aspect of the present invention , the minimum protective dosage ( mpd ) of pcv2 rorf2 antigen adjuvanted with carbopol in the cdcd pig model in the face of a pcv2 challenge is determined . groups 3 , 5 , 6 and 7 each received two doses of rorf2 antigen adjuvanted with carbopol , but the level of rorf2 antigen varied for each group . groups 3 , 5 , 6 and 7 each received 16 , 4 , 1 or 0 . 25 μg of rorf2 antigen respectively . in general , decreasing the level of rorf2 antigen decreased pcv2 antibody titers , and increased the mortality rate , mean % lung lesions and the incidence of ihc positive tissues . of the four groups receiving varying levels of rorf2 - carbopol , groups 3 and 5 , which received two doses of 16 or 4 μg of rorf2 antigen , respectively , each had an ihc positive rate of only 20 %, and each had similar antibody titers . overall , based on ihc positive results , the minimum protective dosage of rorf2 antigen administered twice is approximately 4 μg . in another aspect of the present invention , the antigenicity of recombinant ( rorf2 ) and vido r - 1 ( vorf2 ) pcv2 antigens were assessed . group 2 received two doses of 16 μg vorf2 and group 3 received two doses of 16 μg rorf2 . both vaccines were adjuvanted with carbopol . both vaccines were found to be safe and both had 0 % mortality rate . group 2 had a pcv2 antibody titer of 2507 on day 25 , while group 3 had a pcv2 antibody titer of 1503 . group 3 had a lower mean % lung lesion score than group 2 ( 0 . 11 ± 0 . 38 % vs . 0 . 90 ± 0 . 15 %), but group 2 had a lower ihc positive incidence rate that group 3 ( 6 . 7 % vs . 20 %). overall , both vaccines had similar antigenicity , but vorf2 was associated with slightly better ihc results . in yet another aspect of the present invention , the suitability of two different adjuvants ( carbopol and ims 1314 ) was determined . groups 1 and 3 both received two doses of vaccine containing 16 ug of rorf2 antigen , but group 1 received the antigen adjuvanted with ims 1314 while group 3 received the antigen adjuvanted with carbopol . both groups had essentially the same adwg , essentially the same incidence of clinical signs post - challenge , the same mortality rate , and essentially the same mean % lung lesions ; but group 1 had an ihc positive rate of 0 % while group 3 had an ihc positive rate of 20 %. however , group 3 , which received the vaccine adjuvanted with carbopol had higher ifat pcv2 titers on days 25 , 32 and 50 than group 1 , which received the vaccine adjuvanted with ims 1314 . overall , although the pcv2 vaccine adjuvanted with ims 1314 did provide better ihc results , it did not provide overwhelmingly better protection from pcv2 infection and did induce injection site reaction . whereas the pcv2 vaccine adjuvanted with carbopol performed nearly as well as the ims 1314 adjuvanted vaccine , but was not associated with any adverse events . in still another aspect of the present invention , the feasibility of pcv2 orf2 as a 1 ml , 1 dose product was determined . groups 2 and 4 both received 16 μg of vorf2 vaccine adjuvanted with carbopol on day 0 , but group 2 received a second dose on day 14 . group 4 had a slightly higher adwg and a lower mean % lung lesions than group 2 , but group 2 had higher ifat pcv2 titers on day 25 , 32 and 50 , and a slightly lower incidence rate of ihc positive tissues . all other results for these two groups were similar . overall , one dose of vorf2 adjuvanted with carbopol performed similar to two doses of the same vaccine . | an improved method for recovering the protein expressed by open reading frame 2 from porcine circovirus type 2 is provided . the method generally involves the steps of transfecting recombinant virus containing open reading frame 2 coding sequences into cells contained in growth media , causing the virus to express open reading frame 2 , and recovering the expressed protein in the supernate . this recovery should take place beginning approximately 5 days after infection of the cells in order to permit sufficient quantities of recombinant protein to be expressed and secreted from the cell into the growth media . such methods avoid costly and time - consuming extraction procedures required to separate and recover the recombinant protein from within the cells . |
fig1 is a perspective view of siphon apparatus 30 of the present invention in its use environment . the use environment comprises a christmas tree 2 which includes a trunk 4 and a plurality of decorated branches 6 . the trunk 4 extends into a christmas tree stand 10 . details of the christmas tree stand 10 and the siphon apparatus 30 are also shown in fig2 which comprises an enlarged view of the apparatus 30 and the trunk 4 and stand 10 which are illustrated in dash dot line . fig3 is a top view of the siphon apparatus 30 , while fig4 is a view in partial section of the apparatus 30 taken generally along line 4 — 4 of fig3 . for the following discussion , reference will primarily be made to fig1 , 3 , and 4 . the stand 10 includes a bottom 12 and a side wall 14 extending upwardly from the bottom 12 . the side wall 14 includes an upper wall portion 16 , and a plurality of screws 18 are shown extending through the upper wall portion 16 . the screws 18 extend to the trunk 4 to hold the trunk 4 , and the tree 2 , generally vertically relative to the stand 10 . the tree 2 includes a bottom 8 of the trunk 4 . the bottom 8 is shown in fig2 . typically , there will be a spike ( not shown ) of some kind on the bottom 12 of the stand 10 , and the bottom 8 will be impaled on the spike or rib to help stabilize the tree 2 in the stand . obviously , there are many different configurations of stands , and the apparatus of the siphon apparatus 30 of the present invention will function appropriately with all of them . the siphon apparatus 30 comprises a pair of receptacle or reservoir elements 32 and 42 which are configured as boots , or “ santa claus boots ,” for purposes of being decorative items , as well as functional items . the boot reservoirs 32 and 42 comprise a container for holding water which flows under siphon principles to the stand 10 . the boot reservoir 32 includes a top lid 34 with a fill aperture 36 extending through the lid 34 . at the bottom of the boot reservoir 32 is a drain aperture 38 . the boot reservoir 42 includes a top lid 44 and a fill aperture 46 extends through the lid 44 . the lids 34 and 44 are concave and thus essentially comprise funnels to facilitate filling the reservoirs with water . the boot reservoir 42 also includes a drain aperture 48 . the two drain apertures for the boot reservoirs 32 and 42 are connected by a conduit 60 . the conduit 60 is best shown in fig5 . fig5 comprises an enlarged view in partial section , with the drain apertures 38 and 48 for the boot reservoirs 32 and 42 , respectively , shown . reference will primarily be made to fig5 for the following discussion . the connecting conduit 60 comprises a tee element which includes an arm 62 extending through the drain aperture 38 . the arm 62 includes a lock element 64 which locks the arm 62 to the reservoir 32 at the drain aperture 38 . a seal element 66 is disposed about the arm 62 on the outer side of the aperture 38 to seal the arm 62 at the aperture 38 to the main body 61 of the connecting conduit 60 . the seal 66 is disposed between a shoulder of the body 61 and the arm 62 . another seal element , not shown , may be disposed in the reservoir 32 about the lock element 64 , if desired . the connecting conduit 60 also includes an arm 72 which is substantially identical to the arm 62 . the arm 62 includes a lock element 74 which extends through the aperture 48 and secures the arm 72 to the reservoir 42 . a seal element 76 is disposed about the arm 72 between the wall of the reservoir 42 at the drain aperture 48 . the seal element 76 is disposed against a shoulder at the main body 61 , substantially identical to the placement of the seal element 66 with respect to the arm 62 and the boot reservoir 32 . again , a seal element ( not shown ) may be placed in the reservoir 42 about the lock element 74 , if desired . the connecting conduit 60 also includes an arm or tee base 80 extending generally perpendicular to the aligned arms 62 and 72 . a conduit 90 is appropriately secured to the arm 80 . the conduit 90 extends to a manual siphon pump assembly 100 . details of the siphon pump 100 are shown in fig6 which comprises a view in partial section of a portion of the siphon pump 100 and its adjacent conduit elements , namely the conduit 90 which extends from the arm 80 of the connecting conduit 60 , and a flexible conduit 140 which extends from the siphon pump 100 to the stand 10 and in fig1 , which is a perspective view in partial section of the elements shown in fig6 . for the following discussion , reference will primarily be made to fig6 and fig1 . the siphon pump assembly 100 includes a tee element 102 which includes a pair of oppositely extending arms 104 and 114 . in the arm 104 there is a valve conduit 106 spaced apart from an i - beam restrictor 110 . the conduit 106 includes a bore 107 . between the valve conduit 106 and i - beam resistor 110 is a ball 108 . the ball 108 has a smaller diameter than the inside diameter and the arm 104 but a larger diameter than the bore 107 of the conduit 106 . the valve conduit 106 is placed upstream in the conduit 90 relative to the flow of water from the water container , namely the boot reservoirs 32 and 42 , and the christmas tree stand 10 . the conduit 90 is appropriately secured to the arm 104 . the arm 114 includes a valve conduit 116 spaced apart from an i - beam restrictor 120 . the conduit 116 includes a bore 117 . a ball 118 is disposed between the conduit 116 and the restrictor 120 . again , the diameter of the ball 118 is less than that of the arm 114 but greater than that of the bore 117 of the conduit 116 . for the arm 114 , the valve conduit 116 is upstream relative to the flow of water between the conduits 90 and 140 . the siphon pump 100 also includes an arm 124 which extends from the tee element 102 generally perpendicular to the arms 104 and 114 . a bulb 126 is appropriately secured to the arm 124 . the purpose of the bulb 126 is , of course , to begin the siphon action to cause water to flow from the container elements 32 and 42 to the christmas tree stand 10 through the respective conduits , as discussed above . it will be understood that the manually squeezing of the bulb 126 will cause the ball 108 to seat against the conduit 106 and will cause the ball 118 to move against the restrictor 120 . thus , no air or water will flow into the conduit 90 , but water will flow from the bulb 126 into the conduit 140 . when the bulb 126 is released and after water is flowing out from the end of the conduit 140 , the lower pressure in the tee element 102 will allow atmospheric pressure in container elements or reservoirs 32 and 42 to begin siphon action , which is well known and understood . hence , water will flow from the container , defined by the two reservoirs 32 and 42 , through the conduits 90 and 140 to the christmas tree stand 10 regardless of the elevation of conduit 140 with respect to reservoirs 32 and 42 . this is best shown in fig2 , 8 , and 9 . fig7 is a view in partial section through the conduit 40 taken generally along line 7 — 7 of fig2 . fig7 shows a conduit 140 open , for conveying water from the container which is comprised of the boot reservoirs 32 and 42 , to the stand 10 . fig8 is a view in partial section through the conduit 40 taken generally along line 8 — 8 of fig2 showing the conduit 140 with a metal rod 150 disposed therein . fig9 is an enlarged view in partial section taken generally from circle 9 of fig2 showing the conduit 140 within the stand 10 . for the following discussion , reference will primarily be made to fig2 and 9 . the rod 150 , which is preferably made of brass or other water non - corrosive material , includes a bottom loop 152 which extends downwardly from the conduit 140 . the conduit 140 includes a distal end 142 , and the bottom loop 152 of the rod 150 extends below the distal end 142 and is typically disposed on the bottom 12 of the stand 10 . the loop 152 extends back to the conduit 140 and is disposed against the conduit 140 to help secure the rod 150 to the conduit 140 , as best shown in fig9 . the rod 150 then extends upwardly within the conduit 140 and includes an upper bend 154 . the bend 154 also defines a loop 144 in the conduit 140 and prevents the conduit from collapsing on itself at the loop 144 , which may otherwise occur . the bend 154 may be made by a user of the apparatus adjacent to the upper wall portion 16 of the stand 10 , or slightly above it . the rod 150 and its upper bend 154 and the loop 144 also serves as a strain relief for the conduit 140 . the bend 154 and loop 144 also helps to prevent the accidental removal of the conduit 140 from the stand 10 . the bottom loop 152 keeps the bottom or distal end 142 of the conduit 140 off the bottom 12 of the stand 10 and accordingly helps to prevent blockage of the conduit 140 , which may otherwise occur . it will be noted that as long as the height of the water in the reservoir 32 , 42 of the apparatus 30 is higher than the water in the stand 10 , water will flow by siphon action through the various conduits 60 , 90 , and 140 , and the check valves , as discussed above . as water is used from the stand 10 , it will be replenished from the container elements or reservoirs 32 , 42 . the remote location of the container elements or reservoirs 32 , 42 allows the water to be replenished easily and conveniently regardless of the height of loop 144 at the upper portion of the wall 16 . thus , the heights of the tree stand wall 16 , with respect to the height of the reservoirs 32 and 42 is relatively unimportant , and siphon action will still occur , providing that there is a difference between the height of the water in the reservoir 32 , 42 and the bottom 142 of the conduit 140 . moreover , it will be noted that the rod 150 may be disposed on the outside or integrated into the conduit 140 and secured thereto . in such case , the “ rod ” may actually be appropriately configured plate , or the like . also , the “ rod ” or plate , or whatever , need not be made of metal , but may be made of any appropriate material which is relatively non - corrosive in water and which provides the desired rigidity . fig1 is a view in partial section of an alternate embodiment of a portion of the apparatus of the present invention . a valve adapter 170 is utilized in place of the lower portion of the conduit 140 , including the distal end 142 and the loop 144 . in the embodiment of fig1 , the adapter 170 , which is preferably made of rigid material , such as plastic , mates with a shut off valve 190 to prevent a flooding situation if the conduit 140 is pulled free , or out of the stand 10 . if the adapter 170 and valve 190 are used , then a brass rod 150 may not be necessary . in such case , the brass rod 150 is simply removed from the conduit 140 , and the conduit is either shortened or the distal end 142 may be connected directly to a tubing connector portion 172 on the adapter 170 . the adapter 170 includes an upper bend portion 174 which then replaces the loop 144 in the conduit 140 . the adapter 170 is simply placed over the top of the tree stand , with the upper bend portion 174 disposed on the wall of the tree stand or in the general area thereof . the adapter 170 includes a straight lower portion 176 and a shoulder 178 adjacent to a bottom end 180 . the shoulder 178 receives the upper portion of the valve 190 . the shut off valve 190 includes a bottom wall 194 remote from the upper end 192 . an orifice 196 extends through the bottom wall 194 . a tapered valve element 200 is disposed in the orifice 196 . a stem 202 extends upwardly from the upper part of the valve element . the tapered valve element 200 is biased within the valve such that the tapered portion closes the orifice 196 . the valve element 200 is biased by a compression spring 204 . the spring 204 extends about the stem 202 and is disposed against the bottom end 180 of the adapter 170 . the spring 204 is a relatively light weight spring such that when the bottom of the valve element 200 contacts the bottom 12 of the stand 10 ( see fig9 ) the element 200 is moved upwardly in the orifice 196 to allow water to flow from the conduit 140 , to the adapter 170 , and through the orifice 196 into the stand 10 . however , if the adapter 170 , secured to the conduit 140 , is removed from the stand 10 , then the spring 204 biases the valve element 200 in the valve 190 against the orifice 196 to prevent the flow of water outwardly . the valve element 200 accordingly comprises a seal to prevent inadvertent flooding , or the like , in case the conduit 140 and the adapter 170 are inadvertently removed from the stand 10 , and also , of course , prevents such flooding or dripping at the conclusion of the christmas season when the conduit 140 and the adapter 170 , with the valve 190 secured thereto , are removed from the christmas tree stand . under some circumstances it may be desirable to simply add the valve 190 to the end of the conduit 140 with the brass rod in place . in such case , an adapter 210 may be used . fig1 comprises a view in partial section of an adapter 210 for mating a valve 190 directly to the end 142 ( see fig9 ) of the conduit 140 . the element 210 may be referred to as an interconnector because it comprises an intermediate element between the valve 190 and the tubing 140 . the interconnector 210 includes a generally cylindrical portion 212 with a top 214 and a connector flange 216 extending outwardly from the top 214 . the connector flange 216 extends into the bottom of the tube 140 at the bottom end 142 . the cylinder 212 includes a bottom 218 and adjacent to the bottom 218 there is a shoulder 220 . the shoulder 220 is comparable to the connector shoulder 178 of the adapter 170 . the valve 190 is disposed on the shoulder 220 . extending through the cylinder 212 is a bore 222 which receives the water flow from the tubing 140 . a second bore 224 extends into the cylinder 212 generally parallel to the bore 222 . however , the bore 224 does not extend all the way through the cylinder 212 , while the bore 222 does extend all the way , longitudinally , through the cylinder 212 . the purpose of the bore 224 is to receive the brass rod 150 . the bottom loop 152 of the brass rod will , of course , be cut off , while the lower portion of the brass rod is thus enabled to extend into the bore 224 . thus , there are various elements to allow the siphon apparatus 30 to be used with virtually any type of tree stand and to enable the apparatus to be used under varying circumstances , depending on the user &# 39 ; s circumstances and desires . while the principles of the invention have been made clear in illustrative embodiments , there will be immediately obvious to those skilled in the art many modifications of structure , arrangement , proportions , the elements , materials , and components used in the practice of the invention , and otherwise , which are particularly adapted to specific environments and operative requirements without departing from those principles . the appended claims are intended to cover and embrace any and all such modifications , within the limits only of the true spirit and scope of the invention . | christmas tree stand watering apparatus includes a water container which may be located somewhat remotely from a christmas tree stand and then a conduit extends from the container into the christmas tree stand . in the embodiment illustrated , the container comprises a pair of reservoir elements , with a connecting conduit connecting the two reservoir elements . a relatively long conduit extends from the connecting conduit to the christmas tree stand . a pump , with appropriate check valves , is disposed in the conduit for starting the siphon action from the container to the christmas tree stand . an element , which may be metallic element , is disposed in the conduit to keep the bottom of the conduit from contacting the bottom of the christmas tree stand and the element extends upwardly within the conduit to provide a stable and secure routing path over the top wall of a stand . a shut off valve may be secured to the end of the conduit in the stand to shut of the flow of water in the event of an accidental removal of the conduit from the stand . |
referring now to the drawings , wherein like reference numerals designate identical or corresponding parts throughout the several views , and more particularly to fig1 - 5 thereof , the disposable grooming drape of the present invention is shown in one embodiment where the drape is installed at a mirror and sink . a drape 9 can be fabricated in a roughly trapezoidal , square or rectangular shape , as shown in an embodiment in fig2 . other shapes are also possible . different drape designs may be fabricated in variable sizes and dimensions to optimally fit specific applications , or a single design may be fabricated to most generally fit multiple applications . in an embodiment , the drape is fabricated from an inexpensive and biodegradable material having pores small enough not to allow pieces of hair readily to pass through . thus , pieces of hair landing on the drape are retained by the drape . in an embodiment , the drape is fabricated from material with a smooth upper surface so as to promote sliding of pieces of hair over that surface . in an embodiment where the drape is positioned with a downward slope along this smooth surface , pieces of hair landing on the drape will tend to slide toward the lower end 7 of the drape . in another embodiment , the drape is fabricated from material with a surface that is sufficiently rough to retard sliding of pieces of hair . such a surface may also tend to arrest and retain pieces of hair , thus minimizing any tendency for them to become airborne again after landing on the drape . in this embodiment , pieces of hair landing on the drape will not tend to slide toward the bottom edge of the drape until those pieces of hair begin to pile up and roll over each other toward the bottom edge of the drape . possible materials to be used in drape fabrication include paper , plastic , foil , and any other material having one or more of the properties presented here , possibly including low cost , ease of disposal , low impact to the environment , ease of storage prior to use , especially storage together with multiple fabrications of the same drape design . in an embodiment , the drape material has the additional property of allowing the drape to be easily folded up and manually compacted for disposal in a small volume . in one embodiment , the drape is mounted by means of one or more temporary attachment points 10 . the edge furthest away from the user is temporarily attached to a vertical surface . in one embodiment , this vertical surface may be a mirror 1 . the drape slants downward and away from this attachment point and toward the user . the lower end 7 , which is then nearest the user , may be attached or free hanging . also , if a sink or other fixture is present in front of the vertical surface , the lower end may extend into or completely over that fixture . if a sink is present , the lower end may extend into the sink bowl , possibly resting near the front of the bowl so as to protect most of the bowl . alternatively , the lower end may extend over the outer front of the sink , completely covering the sink bowl 4 and sink outer rim , not shown . in one embodiment , this near edge 7 is free hanging and extends into the bowl of a sink 4 located in front of the mirror . thus , the drape forms a barrier extending continuously over a downward slope from the vertical surface to the front of the sink bowl , inside the bowl . in one embodiment , the drape may have a sufficient degree of rigidity in the direction from the far end to near end so as to aid in projecting from the vertical surface and laying in an approximately straight line at an angle to both surfaces rather than laying flat on either surface . this rigidity may be inherently due to the structure of the drape material and / or it may be due to folds or other structure in the shape of the drape . in one embodiment of the invention , the vertical positioning of the drape is adjustable . its upper edge may , at the user &# 39 ; s discretion , be positioned higher or lower to account for variability in the distance any horizontal surface projects out from the vertical surface . this may be done so that , as the drape extends down diagonally , it extends out horizontally a distance determined by the user . thus , the drape may be positioned to extend a distance from the vertical surface where that distance is ideally suited to facilitate capture of falling hair . in an embodiment , the drape covers the sink from the back of the sink to the front of the sink bowl 4 , inside the bowl . thus , sink elements at the back of the sink , such as a faucet 3 and faucet handles 2 , are covered from above by the drape . contrary to the designs of conventional devices , as discussed above , in one embodiment of the present invention , there are no cuts or openings in the drape through which any sink elements protrude or through which pieces of hair can fall , in either case allowing pieces of hair to land on sink elements . since , in this embodiment , no water is used , no openings in the drape are required for access to sink elements . in this embodiment , the user would generally position himself or herself facing the sink and mirror and so as to be leaning forward , over the drape , which is then in position to collect pieces of hair falling from the user onto the drape . see fig5 . as pieces of hair land on the drape , they are retained by the drape and tend to migrate downward and forward toward the lower end 7 of the drape , more or less immediately , depending on the texture of the upper front surface 6 of the drape . in one embodiment , the means of temporary attachment comprises an adhesive material applied to the back side of the drape during fabrication of the drape . the downward side of the drape 9 is the side generally facing away from the falling hair . in one embodiment , the adhesive material is applied near the top edge of the downward side of the drape . the adhesive material may be applied to one or more areas of larger or smaller size . in one embodiment , the adhesive material is applied to two small areas 10 , each oblong in shape , with long axis parallel to the top edge of the drape and generally located near the top edge of the drape . in one embodiment , the adhesive applied to the drape during fabrication of the drape is protected after fabrication and prior to use of the drape by temporarily covering the adhesive with one or more pieces of material which protect the adhesive but which can be removed without affecting the adhesive , other than to expose the side of the adhesive away from the drape . in one embodiment , multiple areas of adhesive each with a separate piece of protective material allow the user to selectively remove one or more pieces of protective material while optimizing the location of exposed adhesive relative to points of attachment available on the vertical surface . in one embodiment , there may be other means of temporarily attaching the drape to the vertical surface , not involving adhesive , such as tie strings fabricated out of the same piece of material as the drape . in one embodiment , there may be less variability in the user selection of attachment points . that is , the attachment points may be fabricated into locations of the drape at specific distances from the lateral ( left and right ) sides of the drape . in this embodiment , however , the drape still may be otherwise fabricated to allow the drape to fit across a variable horizontal ( lateral ) distance . this may be accomplished by gathering the drape material horizontally so as to preserve the desired functionality of the drape while allowing the fabricated attachment points of the drape to be variably positioned on the vertical surface . horizontal gathering refers to allowing excess material between the attachment points to be folded “ accordion style ” so as to remain roughly within the same horizontal plane . thus , excess material will not hang out away from the plane of the drape in such a way as to interfere with overall function of the drape . horizontal gathering may be facilitated by fabrication of one or more creases within the drape material , creases extending generally in a direction between the upper rear and lower front edges of the drape . in one embodiment , the lower front edge of the drape is folded along crease 7 forward and upward to create a lip or trap 8 to catch pieces of hair which slide down the drape during use . the width of this lip 8 at the end of the drape as measured from the crease 7 of the fold to the edge 11 of the lip may be , for example , approximately 2 inches . in other embodiments , this fold width may be more or less than 2 inches in order to fit the geometry of a specific application and be capable of retaining somewhat more than the amount of hair anticipated to collect at the bottom of the lower edge of the drape . in one embodiment , the drape is stored , after fabrication and until use , with the lip 8 actually folded over flush with that portion of the drape 6 above the crease 7 . in an alternative embodiment , the drape is stored with the lip 8 open and planar with the rest of the drape 6 . in either embodiment , the crease 7 may be fabricated into the drape . this crease may facilitate folding and may facilitate retaining a desired folded shape during use , as shown in fig4 . fabrication of any of the creases may involve creating a pattern of thickness and density in the drape material along the line of the crease , so that this pattern serves to define the crease and further facilitate retaining a desired shape during use . in one embodiment , adaptability is increased by several means . adaptability is provided by the one or more adhesive attachment points 10 , the design dimensions of the drape , and the ability to fold the drape accordion - style to a user - adjusted effective width . these means combine to allow one drape to fit multiple different configurations of vertical and horizontal surfaces . these multiple configurations may be various sinks , sink elements , countertops , and mirrors or any other combination of vertical and horizontal surface in front of which a person might stand to groom their hair . the ability to fit multiple configurations is further improved in embodiments where the upper rear attachment points 10 may be secured higher or lower on the vertical surface coincident with allowing the lower front edge of the drape to rest at a greater or lesser distance from the vertical surface . in one embodiment , multiple drapes easily may be laid out flat in a stack for compact storage prior to use . in another embodiment , such a stack of disposable drapes may be contained within a storage device which protects the drapes prior to use and which facilitates dispensing one drape at a time for use . one method of using the disposable grooming drapes of the present invention is now described . in one embodiment , drapes are provided for use . a storage container for multiple drapes is located near a combination of vertical and horizontal surfaces . the combination vertical and horizontal surfaces may be a mirror 1 and sink 5 . a user positions him or herself facing the combined surfaces . the user removes one drape from the storage container . the user selects attachment points 10 on the back side of the drape , selecting attachment points spaced at a width roughly equal to the width of the vertical surface . in an embodiment where the attachment points consist of adhesive , the user uncovers the adhesive at the selected attachment points and presses the attachment points onto opposite sides of the vertical surface . the height of attachment to the vertical surface allows the lower end 7 of the drape to extend downward from the attachment points and away from the vertical surface so as to maximally cover the horizontal surface 4 . in an embodiment where the vertical and horizontal surfaces consist of a mirror 1 and sink 5 with faucet 3 and faucet handles 2 , the drape covers and protects the faucet , handles and rear portion of the sink bowl 4 . in this embodiment , the drape extends into and rests on the bottom front portion of the sink bowl 4 . in some embodiments , the lip 8 may have been stored open , and the user next folds the lip 8 at the crease 7 to create the trap 11 . in other embodiments , the drape is stored with the lip 8 already folded to create a trap for falling hair . at this point , the drape is in position and ready to be used . the user then proceeds with hair grooming of any sort as previously described . during grooming , the user leans forward , over the sink , so that any pieces of loose hair fall onto the front surface 6 of the drape and migrate downward and forward along the front surface to collect in the trap 8 . after grooming , the user may clean any tools over the drape so that any pieces of loose hair again fall onto the drape . after clean up , the user may fold the side edges 12 , bottom end 7 , and trap 8 of the drape upward and toward the center of the drape so as to enclose any pieces of hair trapped on the front surface 6 or in the trap 8 . as the user finishes folding up the drape , the user simultaneously detaches the upper , rear edge 10 from the vertical surface and completes folding the drape into a compact form with the previous front surface 6 and trap 8 now enclosed within the interior of the compacted form . this method of folding prevents spilling pieces of hair onto the horizontal surface . the drape now may be easily discarded in a standard or other waste container . in an embodiment , the drape is fabricated from recyclable material , and the waste container may be a waste container for recyclable material . this results in a one - step , no - mess clean - up requiring only seconds to complete . obviously , numerous modifications and variations of the present invention are possible in light of the above teachings . it is therefore to be understood that within the scope of the appended claims , the present invention may be practiced otherwise than as specifically described herein . other features and advantages of the invention will become apparent to those of skill in the art upon reviewing the following detailed description of the preferred embodiments and the accompanying drawings in which like reference numbers indicate identical or functionally similar elements . | a drape for maintaining a sanitary surface . the drape is made of a semi - rigid sheet of material . the semi - rigid sheet includes at least one temporary attachment point . the temporary attachment point is disposed on substantially a first edge of the semi - rigid sheet . additionally , the semi - rigid sheet includes at least one lip . the lip is formed by a portion of the semi - rigid sheet . the lip is disposed at a second edge of the semi - rigid sheet . |
by the term “ coordinating metal ” and “ coordinating metals ” and derivatives thereof , as used herein is meant a metal or a metal containing excipient , suitably a diluent , or metal containing tablet coating material , which forms a complex , such as a chelate complex , in the presence of eltrombopag olamine . examples of such metals include : by the term “ reducing sugar ” as used herein is meant a sugar or sugar containing excipient , suitably a diluent , which reacts with eltrombopag olamine to form a maillard product when admixed together . examples of such reducing sugars include : the term maillard reaction is well known in the art and is utilized herein as to its standard meaning . generally , the term maillard reaction is used herein to mean the reaction of a reducing sugar , as defined herein , in a formulation , suitably granules or solid dosage forms , with eltrombopag olamine that produces a pigment or pigments , suitably a brown pigment . the pigments are referred to herein as maillard products . the production of such maillard products is an indication of chemical instability . as used herein , the term “ improved properties ” and derivatives thereof , contemplates several advantages to the pharmacokinetic profile of the in vivo release of compound b from a formulation , suitably granules or a solid oral pharmaceutical dosage form , that utilizes an aspect of the present invention when compared to a formulation that does not utilize that aspect of the present invention , suitably the formulation is produced on a commercial scale , and will vary depending on the particular aspect of the invention being utilized . examples of improved properties include : increased oral bioavailability , reduced formation of insoluble metal complexes , improved chemical stability , a consistent pharmacokinetic profile and a consistent dissolution rate . as used herein , the term “ drug ” or “ active ingredient ” and derivatives thereof , means compound b or eltrombopag olamine . by the term “ commercial scale ” and derivatives thereof , as used herein is meant , preparation of a batch scale greater than about 20 kg of granulation mix , suitably greater than 50 kg , suitably greater than 75 kg or a batch size suitable to prepare at least about 50 , 000 tablets , suitably at least 75 , 000 tablets , suitably at least 100 , 000 tablets . when indicating that the diluents for use herein and in the claims are substantially free of coordinating metals and / or that are substantially free of reducing sugars , it is contemplated that minor amounts , for example : about 5 % or less , of the diluent component could contain a coordinating metal or metals and / or a reducing sugar or reducing sugars . in this aspect of the invention , it is believed that very minor amounts of coordinating metals and / or reducing sugars can be incorporated into the diluent component without adversely effecting tablet performance . the term “ effective amount ” and derivatives thereof , means that amount of a drug or active ingredient that will elicit the biological or medical response of a tissue , system , animal or human that is being sought , for instance , by a researcher or clinician . furthermore , the term “ therapeutically effective amount ” means any amount which , as compared to a corresponding subject who has not received such amount , results in improved treatment , healing , prevention , or amelioration of a disease , disorder , or side effect , or a decrease in the rate of advancement of a disease or disorder . the term also includes within its scope amounts effective to enhance normal physiological function . as used herein , the term “ formulation ” and derivatives thereof , unless otherwise defined refers to granules and / or solid oral pharmaceutical dosage forms of the invention that contain eltrombopag olamine . by the term “ co - administering ” and derivatives thereof as used herein is meant either simultaneous administration or any manner of separate sequential administration of granules and / or a solid oral pharmaceutical dosage form of the present invention and a further active ingredient or ingredients , known to treat thrombocytopenia , including chemotherapy - induced thrombocytopenia and bone marrow transplantation and other conditions with depressed platelet production . the term further active ingredient or ingredients , as used herein , includes any compound or therapeutic agent known to or that demonstrates advantageous properties when administered with tpo or a tpo mimetic . preferably , if the administration is not simultaneous , the compounds are administered in a close time proximity to each other . furthermore , it does not matter if the compounds are administered in the same dosage form , e . g . one compound may be administered topically and another compound may be administered orally . examples of a further active ingredient or ingredients for use in combination with the presently invented formulations include but are not limited to : chemoprotective or myeloprotective agents such as g - csf , bb10010 ( clemons et al ., breast cancer res . treatment , 1999 , 57 , 127 ), amifostine ( ethyol ) ( fetscher et al ., current opinion in hemat ., 2000 , 7 , 255 - 60 ), scf , il - 11 , mcp - 4 , il - 1 - beta , acsdkp ( gaudron et al ., stem cells , 1999 , 17 , 100 - 6 ), tnf - a , tgf - b , mip - 1a ( egger et al ., bone marrow transpl ., 1998 , 22 ( suppl . 2 ), 34 - 35 ), and other molecules identified as having anti - apoptotic , survival or proliferative properties . by the term “ granules ” and derivatives thereof , as used herein refers to formulated particles that comprise eltrombopag olamine , diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars , and suitably also binders and / or lubricants and / or disintegrants such that the particles are suitable for utilization in preparing solid oral pharmaceutical dosage forms . it is also possible to administer the granules directly to a subject in need thereof as a medicament . however , it is anticipated that the granules are most appropriately utilized in the preparation of solid oral pharmaceutical dosage forms as indicated above . by the term “ solid oral pharmaceutical dosage form ” and “ solid dosage form ” and derivatives thereof , as used herein refers to a final pharmaceutical preparation that comprises eltrombopag olamine , such tablets , capsules , pellets , lozenges and powders ( including coated versions of any of such preparations ) that are suitable for in vivo administration . suitably , the granules and solid oral pharmaceutical dosage forms of the present invention comprise eltrombopag olamine , a diluent ( also known as filler or bulking agent ), and suitably also a binder and / or a lubricant and / or a disintegrant . those skilled in the art will recognize that a given material may provide one or more functions in the tablet formulation , although the material is usually included for a primary function . the percentages of diluent , binder , lubricant and disintegrant provided herein and in the claims are by weight of the tablet . diluents provide bulk , for example , in order to make the tablet a practical size for processing . diluents may also aid processing , for example , by providing improved physical properties such as flow , compressibility , and tablet hardness . because of the relatively high percentage of diluent and the amount of direct contact between the diluent and the active compound in the typical pharmaceutical formulation , the interaction of the diluent with the active compound is of particular concern to the formulator . examples of diluents suitable for general use include : water - soluble fillers and water - insoluble fillers , such as calcium phosphate ( e . g ., di and tri basic , hydrated or anhydrous ), calcium sulfate , calcium carbonate , magnesium carbonate , kaolin , spray dried or anhydrous lactose , cellulose ( e . g ., microcrystalline cellulose , powdered cellulose ), pregelatinized starch , starch , lactitol , mannitol , sorbitol , maltodextrin , powdered sugar , compressible sugar , sucrose , dextrose , and inositol . the diluents that do not contain coordinating metals and diluents that are non - reducing sugars are suitable for tablets of the current invention . suitable diluents for use in this invention include microcrystalline cellulose , powdered cellulose , pregelatinized starch , starch , lactitol , mannitol , sorbitol , and maltodextrin . unsuitable diluents include calcium phosphate ( e . g ., di and tri basic , hydrated or anhydrous ), calcium sulfate , calcium carbonate , magnesium carbonate , kaolin , and spray dried or anhydrous lactose . in one embodiment of the present invention , the diluent is composed of one or both of mannitol and microcrystalline cellulose . the granules and solid oral pharmaceutical dosage forms of the present invention typically comprise from about 25 % to about 89 %, of one or more diluents . one aspect of the present invention comprises granules wherein the granules are formulated using a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars . one aspect of the present invention comprises solid oral pharmaceutical dosage forms wherein the solid dosage forms are formulated using a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars . one aspect of the present invention comprises pharmaceutical tablets , wherein the tablets are formulated using a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars . one aspect of the present invention comprises pharmaceutical capsules , wherein the capsules are formulated using a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars . binders impart cohesive properties to the powdered material . examples of binders suitable for use in the present invention include : starch ( e . g ., paste , pregelatinized , mucilage ), gelatin , sugars ( e . g ., sucrose , glucose , dextrose , molasses , lactose , dextrin , xylitol , sorbitol ), polymethacrylates , natural and synthetic gums ( e . g ., acacia , alginic acids and salts thereof such as sodium alginate , gum tragacanth , irish moss extract , panwar gum , ghatti gum , guar gum , zein ), cellulose derivatives [ such as carboxymethyl cellulose and salts thereof , methyl cellulose ( mc ), hydroxypropyl methyl cellulose ( hpmc ), hydroxypropyl cellulose ( hpc ), hydroxyethyl cellulose ( hec ) and ethyl cellulose ( ec )], polyvinylpyrrolidone , veegum , larch arabogalactan , polyethylene glycol , waxes , water , alcohol , magnesium aluminum silicate , and bentonites . in one embodiment of the present invention , the binder comprises polyvinylpyrrolidone ( pvp ). the granules and solid oral pharmaceutical dosage forms of the present invention typically comprise up to about 8 % binder . the formulations suitably comprise up to about 5 %, suitably up to about 2 % binder . lubricants are generally used to enhance processing , for example , to prevent adhesion of the formulation material to manufacturing equipment , reduce interparticle friction , improve rate of flow of the formulation , and / or assist ejection of the formulations from the manufacturing equipment . examples of lubricants suitable for use in the present invention include : talc , stearates ( e . g ., magnesium stearate , calcium stearate , zinc stearate , palmitostearate ), stearic acid , hydrogenated vegetable oils , glyceryl behanate , polyethylene glycol , ethylene oxide polymers ( e . g ., carbowaxes ), liquid paraffin , sodium lauryl sulfate , magnesium lauryl sulfate , sodium oleate , sodium stearyl fumarate , dl - leucine , and silica derivatives ( e . g ., colloidal silicon dioxide , colloidal silica , pyrogenic silica , and hydrated sodium silicoaluminate ). in one embodiment of the present invention , the lubricant comprises magnesium stearate . the granules and solid oral pharmaceutical dosage forms of the present invention typically comprise up to about 2 % lubricant . the formulations suitably comprise up to about 1 . 5 %, suitably up to about 1 % lubricant . disintegrants are employed to facilitate breakup or disintegration of the formulation after administration . examples of disintegrants suitable for use in the present invention include : starches , celluloses , gums , crosslinked polymers , and effervescent agents , such as corn starch , potato starch , pregelatinized starch , modified corn starch , croscarmellose sodium , crospovidone , sodium starch glycolate , veegum hv , methyl cellulose , microcrystalline cellulose , cellulose , modified cellulose gum ( e . g ., ac - di - sol r ), agar , bentonite , montmorillonite clay , natural sponge , cation exchange resins , ion exchange resins ( e . g ., polyacrin potassium ), alginic acid and alginates , guar gum , citrus pulp , carboxymethylcellulose and salts thereof such as sodium lauryl sulfate , magnesium aluminum silicate , hydrous aluminum silicate , sodium bicarbonate in admixture with an acidulant such as tartaric acid or citric acid . in one embodiment of the present invention , the disintegrant is sodium starch glycolate . the granules and solid oral pharmaceutical dosage forms of the present invention typically comprise an amount from 4 % to about 12 % disintegrant . the formulations suitably comprise from about 6 % to about 10 %, suitably from about 7 % to 9 % disintegrant . the solid oral pharmaceutical dosage forms , suitably tablets , suitably capsules , of the present invention will typically be sized up to 1 gram , e . g ., from about 0 . 01 gram to about 0 . 8 gram . these solid dosage forms typically comprise from about 5 mg to about 900 mg of eltrombopag olamine per dosage form . in suitable embodiments , the solid dosage forms comprise from about 5 to about 200 mg eltrombopag olamine ( e . g ., in an about 100 - 800 mg dosage form ). tablet formulations of the invention may have a variety of shapes , including diamond , modified capsule , modified oval , and hexagonal , and may optionally have a tilt . the choice of particular types and amounts of excipients , and tabletting technique employed depends on the further properties of eltrombopag olamine and the excipients , e . g ., compressibility , flowability , particle size , compatibility , and density . the tablets may be prepared according to methods known in the art , including direct compression , dry granulation , fluid bed granulation , and wet granulation , and the type of excipients used will vary accordingly . it has been found that wet granulation is particularly suitable for providing high strength , low breakage tablets comprising relatively high concentrations of eltrombopag olamine ( e . g ., about 40 % or more ), on a scale suitable for commercial production . suitable wet granulated tablets of the invention comprise granules comprising eltrombopag olamine and one or more of fillers , binders and disintegrants , wherein the granules are mixed with additional filler , binder , disintegrant and / or lubricant to form a compression mixture that is compressed to form tablets . included in the present invention are pharmaceutical compositions in tablet form , suitably prepared on a commercial scale , that comprise eltrombopag olamine , wherein the tablet is made by a wet granulation process using a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars . also included in the present invention are such pharmaceutical compositions that contain a film coat , wherein the film coat contains no coordinating metals , or only an amount of coordinating metal approximately equal to or less than 0 . 025 parts of compound b . also included in the present invention are pharmaceutical compositions that comprise eltrombopag olamine , wherein the tablet is made by a wet granulation process , suitably on a commercial scale , using a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars , and about 90 % of the eltrombopag olamine particles have a particle size greater than 10 micron but less than 90 micron . also included in the present invention are pharmaceutical compositions that comprise eltrombopag olamine , wherein the tablet is made by a wet granulation process , suitably on a commercial scale , using a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars , and about 90 % of the eltrombopag olamine particles have a particle size greater than 10 micron but less than 90 micron , suitably greater than 20 micron but less than 50 micron . also included in the present invention are pharmaceutical compositions that comprise eltrombopag olamine , wherein the tablet is made by a wet granulation process , suitably on a commercial scale , using a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars , and about 50 % of the eltrombopag olamine particles have a particle size greater than 5 micron but less than 50 micron , suitably greater than 5 micron but less than 20 micron . ( i ) from about 2 % to about 65 % eltrombopag olamine ; ( ii ) from about 25 % to about 89 % of diluent ; ( iii ) up to about 8 % binder , suitably up to about 5 %, suitably up to about 4 %; ( iv ) up to about 2 % lubricant , suitably up to about 1 . 5 %, suitably up to about 1 %; and ( v ) from 4 % to about 12 % disintegrant , suitably 6 % to 10 %, suitably from 7 % to 9 %. suitable wet granulated tablets comprise , by weight of the tablet , from about 10 % to about 95 % of eltrombopag olamine active intragranules and from about 5 % to about 90 % of external excipients ; wherein the eltrombopag olamine active intragranules comprise , by weight of the intragranules : ( i ) from about 2 % to about 88 % eltrombopag olamine ; ( ii ) from about 10 % to about 96 % diluent ; ( iii ) from about 2 % to about 5 % binder ; and ( iv ) optionally from 0 % to about 4 % disintegrant ; ( i ) from 0 % to about 70 % diluent ; ( ii ) from about 0 . 25 % to about 2 %, suitably from about 0 . 25 % to about 1 . 25 % lubricant ; and ( iii ) from 4 % to about 10 % disintegrant . in the foregoing embodiments , the diluent is suitably a combination of mannitol and microcrystalline cellulose , the non - reducing sugar is suitably mannitol , the binder is suitably polyvinylpyrolidone , the lubricant is suitably magnesium stearate , and the disintegrant is suitably sodium starch glycolate . suitably , the intragranule filler is a mixture of mannitol and microcrystalline cellulose and the external filler is microcrystalline cellulose . in one embodiment of the current invention , tablets are coated with a film coat formed from an aqueous film coat composition . aqueous film coat compositions suitable for use in the present invention comprise a film - forming polymer , water as a vehicle , and optionally one or more adjuvants such as are known in the film - coating art . when the film coat contains a coordinating metal , as used herein , the amount of coordinating metal is approximately equal to or less than 0 . 025 parts of compound b . the film - forming polymer is selected to form coatings with mechanical properties ( e . g ., mechanical strength , flexibility ) suitable to meet performance requirements , such as those required by the intended use environment ( e . g ., dissolution profile in gastrointestinal fluids ), and / or use ( e . g . solution viscosity ). examples of suitable film - forming polymers include cellulosic polymers ( e . g ., cellulose ethers such as hpmc , hpc , mc , ec , hec , cap , sodium ethyl cellulose sulfate , carboxymethyl cellulose and the like ); polyvinylpyrolidone ; zein ; and acrylic polymers ( e . g ., methacrylic acid / methacrylic acid ester copolymers such as methacrylic acid / methylmethacrylate copolymers and the like ). cellulosic polymers are preferred in the present invention , especially cellulosic ethers and more especially hpmc and hpc . the polymers are typically provided in either aqueous or organic solvent based solutions or aqueous dispersions . however , the polymers may be provided in dry form , alone or in a powdery mixture with other components ( e . g ., a plasticizer and / or colorant ), which is made into a solution or dispersion by the user by admixing with the aqueous vehicle . the aqueous film coat composition further comprises water as a vehicle for the other components , to facilitate their delivery to the tablet surface . the vehicle may optionally further comprise one or more water soluble solvents , e . g ., alcohols ( e . g ., methanol , isopropanol , propanol ) and ketones ( e . g ., acetone ). the skilled artisan can select appropriate vehicle components to provide good interaction between the film - forming polymer and the vehicle to ensure good film properties . in general , polymer - vehicle interaction is designed to yield maximum polymer chain extension to produce films having the greatest cohesive strength and thus mechanical properties . the components are also selected to provide good deposition of the film - forming polymer onto the tablet surface , such that a coherent and adherent film is achieved . the aqueous film coating composition may optionally comprise one or more adjuvants known in the art , such as plasticizers , colorants , detackifiers , secondary film - forming polymers , flow aids , surfactants ( e . g ., to assist spreading ), maltodextrin , and polydextrose . plasticizers provide flexibility to the film , which may reduce film cracking and improve adhesion to the tablet . suitable plasticizers will generally have a high degree of compatibility with the film - forming polymer and sufficient permanence such that the coating properties are generally stable . examples of suitable plasticizers include glycerin , propylene glycol , polyethylene glycols ( e . g ., molecular weight from 200 to 20 , 000 , including union carbide &# 39 ; s peg 400 , 4000 , 6000 , 8000 , and 20 , 000 ), glycerin triacetate ( aka triacetin ), acetylated monoglyceride , citrate esters ( e . g ., triethyl citrate , acetyl triethyl citrate , tributyl citrate , acetyl tributyl citrate ), phthalate esters ( e . g ., diethyl phthalate ), mineral oil and hydrogenated glucose syrup . in one embodiment of the present invention , the plasticizer is chosen from polyethylene glycols , triacetin , propylene glycol , glycerin , and mixtures thereof . the aqueous film coat composition suitably comprises one or more colorants . in addition to enhancing esthetic appeal , the colorant provides product identification . suitable colorants include those approved and certified by the fda , including fd & amp ; c and d & amp ; c approved dyes , lakes , and pigments , and titanium dioxide , provided that the film coat contains no coordinating metals , or only an amount of coordinating metal approximately equal to or less than 0 . 025 parts of compound b . suitably , the colorant comprises one or more coloring agents selected from the group consisting of red iron oxides , red dyes and lakes , yellow iron oxides , yellow dyes and lakes , titanium dioxide , and indigo carmine . for example , the colorant may be selected to provide a light beige shade , for example consisting essentially of a ) red iron oxide , red dye , and / or red lake , b ) yellow iron oxide , yellow dye , and / or yellow lake , and c ) titanium dioxide . alternatively , the colorant may be selected to provide a pink shade ( e . g ., consisting essentially of titanium dioxide and red iron oxide , red dye and / or red lake ); a light green shade ( e . g ., consisting essentially of yellow iron oxide , yellow dye and / or yellow lake , indigo carmine , and titanium dioxide ); a light blue shade ( e . g ., consisting essentially of titanium dioxide and indigo carmine ); or an orange shade ( e . g ., consisting of essentially of titanium dioxide and sunset yellow ). the above mentioned colorants that contain a coordinating metal are acceptable at a level approximately equal to or less than 0 . 025 parts of compound b . in suitable alternative embodiments , the aqueous film coating composition for use in the current invention comprises : suitably , such compositions further comprise a colorant . such compositions may optionally further comprise one or more additional adjuvants such as a detackifier , flow aid , surfactant , and secondary film - forming polymer . examples of optional detackifiers include lecithin , stearic acid , mineral oil , modified derivatized starch , tapioca dextrin , and polyethylene glycol . examples of optional secondary film - forming polymers include sodium alginate , propylene glycol alginate , and polyvinylpyrrolidone . examples of optional surfactants include dioctyl sodium sulfosuccinate and polysorbate 80 . examples of optional flow aids include talc , fumed silica , bentonite , hydrogenated vegetable oils , stearines , and waxes . the aqueous film coat composition will typically comprise from about 5 % to about 25 %, suitably about 5 % to about 20 %, coating solids in the vehicle . in suitable embodiments , the solids typically comprise from about 25 % to about 70 %, suitably about 60 % to about 70 % film - forming polymer , about 5 % to about 10 %, suitably about 6 % to about 8 %, plasticizer , and about 20 % to about 35 % colorant , by weight . a number of suitable aqueous film coating compositions are commercially available . the aqueous film coat composition may be provided in the form of a solution or dispersion . alternatively , the composition may be provided in a dry form that can be combined with the vehicle components according to supplier instructions prior to coating the tablet . suitably , aqueous film coating compositions are those commercially available from colorcon , inc . of west point , pa ., under the trade name opadry and opadry ii ( nonlimiting examples include opadry ys - 1 - 7706 - g white , opadry yellow 03b92357 , opadry blue 03b90842 ). these compositions are available as dry film coating compositions that can be diluted in water shortly before use . opadry and opadry ii formulations comprise a cellulosic film forming polymer ( e . g ., hpmc and / or hpc ), and may contain polydextrose , maltodextrin , a plasticizer ( e . g ., triacetin , polyethylene glycol ), polysorbate 80 , a colorant ( e . g ., titanium dioxide , one or more dyes or lakes ), and / or other suitable film - forming polymers ( e . g ., acrylate - methacrylate copolymers ). suitable opadry or opadry ii formulations may comprise a plasticizer and one or more of maltodextrin , and polydextrose ( including but not limited to a ) triacetin and polydextrose or maltodextrin or lactose , or b ) polyethylene glycol and polydextrose or maltodextrin ). the tablets are also suitably coated to provide a uniform coating without speckling . the tablets are typically coated to provide a dry tablet weight gain of from about 2 to about 5 %, suitably about 3 to 4 %. the uncoated tablet cores are coated with the aqueous film coating composition by methods well known in the art using commercially available equipment ( e . g ., thomas accela - cota , vector hi - coater , compu - lab 36 ). in general , the process usually involves rolling or tumbling the tablets in a pan , or suspending the tablets on a cushion of air ( fluidized bed ), and intermittently or continuously ( preferably continuously ) spraying a fine mist of atomized droplets of the coating composition onto the tablets , the droplets wetting , spreading and coalescing on the surface of the tablets to form an adherent and coherent film coating . the tablets are typically heated to about 40 to 50 ° c ., suitably about 45 to 50 ° c ., e . g ., by air having a temperature of up to about 75 ° c ., suitably about 65 to 70 ° c . pharmaceutical tablets of the invention that are wet - granulated can be prepared by a process comprising the steps of : a ) mixing together the dry materials comprising eltrombopag olamine , a diluent , a binder , and optionally a disintegrant for a time sufficient to homogenize the materials ; b ) adding a granulating fluid to the mixture of dry materials , preferably while mixing ; c ) mixing the granulating fluid with the mixture of dry materials for a granulating time sufficient to generally uniformly wet the dry materials , so as to form wet granules ; a ) mixing the granules prepared in step i ) f ) with external excipients comprising a filler , a lubricant and a disintegrant for a time sufficient to homogenize the granules and external excipients ; and b ) compressing the mixture comprising the granules and external excipients to form a tablet . in preparing wet - granulated granules , the dry materials may be mixed with suitable equipment such as known in the art ( e . g ., niro - fielder blender / granulator , bear varimixer , key high shear mixer / granulator ) for a time sufficient to homogenize the materials , e . g ., for about 3 minutes . the granulating fluid is then added to the dry mixture , preferably while mixing . the granulating fluid is suitably water , although may alternatively be comprised of water in admixture with one or more of binders such as pvp and hpmc , from about 10 v / w % to about 30 v / w % of the granulating fluid , based on the total wet granulation mixture , is suitably used . the granulating fluid and dry materials may be mixed using suitable equipment such as known in the art ( e . g ., niro - fielder blender / granulator , bear varimixer , key high shear mixer / granulator ) for a total time sufficient to generally uniformly wet the dry material so as to form wet granules , suitably for about 3 to about 15 minutes . typically the fluid is added to the dry material with mixing over a period of about 1 to about 15 minutes , then the total batch is mixed for an additional time ( post - granulating fluid - addition time ), of about 0 . 5 minutes to about 6 minutes . in a suitable embodiment , about 10 v / w % to about 30 v / w % granulating fluid and a post - granulating fluid - addition granulating time of about 6 minutes or less is used . suitably , about 24 v / w % granulating fluid and a post - granulating fluid - addition granulating time of less than 3 minutes is used , e . g ., about 2 . 5 minutes . suitably , about 16 v / w % granulating fluid and a post - granulating fluid - addition granulating time of more than 2 . 5 minutes is used , e . g ., about 4 minutes . the wet granules are then wet - milled by methods such as are known in the art for providing a generally uniformly sized wet mass ( such that the granules dry relatively evenly ). suitable wet - milling techniques may involve screening ( e . g ., manual screens ), comminuting mills ( such as a co - mil , including but not limited to a 0 . 375 ″ screen ), or extruders . the wet - milled granules are dried by methods such as are known in the art for providing generally uniform drying , to a low residual amount of granulating fluid ( preferably about 0 . 5 % to about 1 . 0 %). fluid bed dryers are suitable drying equipment . the dried granules are then dry - milled using known methods to provide generally uniformly sized granules ( unimodal distribution ), suitably having a mean particle diameter of less than 240 microns ( found to provide improved content uniformity ). suitable dry - milling equipment includes co - mils , including but not limited to having a 0 . 094 ″ screen . suitably the granules and the dry materials of the compression mix are generally unimodal in size distribution , in order to facilitate formation of a homogeneous mix and to mitigate possible segregation of the mix after blending . if necessary , the dry materials may be pre - screened to provide the desired particle size distribution . screening of the lubricant may be particularly useful to deagglomerate the lubricant . in preparing the compression mixture , the granules , filler , and disintegrant are mixed over a suitable period of time , about 5 to 15 minutes . lubricant is then added and mixed for a suitable period of time , about 1 to 4 minutes . the mixture is then compressed into tablets using presses such as are known in the art ( e . g ., rotary tablet press ). it has been found that the above granulating fluid levels , granulating times , and excipients provide improved processing . the choice of particular types and amounts of excipients , and capsulation technique employed depends on the further properties of eltrombopag olamine and the excipients , e . g ., compressibility , flowability , particle size , compatibility , and density . the capsules may be prepared according to methods known in the art , suitably filling a standard two piece hard gelatin capsule with eltrombopag olamine admixed with excipients , suitably filling a standard two piece hard gelatin capsule with granules prepared according to this invention , suitably on a scale suitable for commercial production . suitable capsules of the invention comprise granules comprising eltrombopag olamine and one or more of fillers , binders and disintegrants , wherein the granules are mixed with additional filler , binder , disintegrant and / or lubricant to form a granular mixture that is filled into capsules . included in the present invention are pharmaceutical compositions in capsule form , suitably prepared on a commercial scale , that comprise eltrombopag olamine , wherein the capsule is made using a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars . also included in the present invention are pharmaceutical compositions that comprise eltrombopag olamine , wherein the capsule is made , suitably on a commercial scale , using a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars , and about 90 % of the eltrombopag olamine particles have a particle size greater than 10 micron but less than 90 micron . also included in the present invention are pharmaceutical compositions that comprise eltrombopag olamine , wherein the capsule is made , suitably on a commercial scale , using a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars , and about 90 % of the eltrombopag olamine particles have a particle size greater than 10 micron but less than 90 micron , suitably greater than 20 micron but less than 50 micron . also included in the present invention are pharmaceutical compositions that comprise eltrombopag olamine , wherein the capsule is made , suitably on a commercial scale , using a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars , and about 50 % of the eltrombopag olamine particles have a particle size greater than 5 micron but less than 50 micron , suitably greater than 5 micron but less than 20 micron . the invented granules and solid oral pharmaceutical dosage forms may be administered in therapeutically effective amounts to treat or prevent a disease state , e . g ., as described in the above referenced international applications nos . pct / us01 / 16863 , pct / us03 / 16255 and pct / us04 / 013468 , the disclosures of which are herein incorporated by reference . it will be recognized by one of skill in the art that the optimal quantity and spacing of individual dosages of eltrombopag olamine formulations of the invention will be determined by the nature and extent of the condition being treated and the particular patient being treated , and that such optimums can be determined by conventional techniques . it will also be appreciated by one of skill in the art that the optimal course of treatment , i . e ., the number of doses of eltrombopag olamine given per day for a defined number of days , can be ascertained by those skilled in the art using conventional course of treatment determination tests . a method of this invention of inducing tpo agonist activity in humans comprises administering to a subject in need of such activity a therapeutically effective amount of a solid oral pharmaceutical dosage form of the present invention . the invention also provides for the use of eltrombopag olamine in the manufacture of a solid oral pharmaceutical dosage form of the present invention . the invention also provides for the use of eltrombopag olamine in the manufacture of a solid oral pharmaceutical dosage form of the present invention for use in enhancing platelet production . the invention also provides for the use of eltrombopag olamine in the manufacture of a solid oral pharmaceutical dosage form of the present invention for use in treating thrombocytopenia . the invention also provides for a solid oral pharmaceutical dosage form for use as a tpo mimetic which comprises eltrombopag olamine and a pharmaceutically acceptable carrier of the present invention . the invention also provides for a solid oral pharmaceutical dosage form for use in the treatment of thrombocytopenia which comprises eltrombopag olamine and a pharmaceutically acceptable carrier of the present invention . the invention also provides for a solid oral pharmaceutical dosage form for use in enhancing platelet production which comprises eltrombopag olamine and a pharmaceutically acceptable carrier of the present invention . the invention also provides a process for preparing solid oral pharmaceutical dosage forms containing a diluent or diluents that are substantially free of coordinating metals and / or that are substantially free of reducing sugars and a therapeutically effective amount of eltrombopag olamine , which process comprises bringing eltrombopag olamine into association with the diluent or diluents . no unacceptable toxicological effects are expected when the compound of the invention is administered in accordance with the present invention . without further elaboration , it is believed that one skilled in the art can , using the preceding description , utilize the present invention to its fullest extent . the following examples , therefore , are to be construed as merely illustrative and not a limitation of the scope of the present invention . all the excipients utilized herein are standard pharmaceutical grade excipients available from numerous manufacturers well known to those in the art . wet granulated , tablets comprising eltrombopag olamine and the ingredients in table 1 were prepared . as a general procedure , the ingredients were blended with the active ingredient and then wet - granulated ( in a high - shear wet - granulator ) with purified water . the wet - granule mass was wet - milled , then dried in a fluid - bed dryer and the dried granules were milled . then extragranular ingredients ( microcrystalline cellulose , if needed , and sodium starch glycolate ) were separately weighed , screened and blended with the granules . magnesium stearate was added and blended with the mixture . the blend was compressed and the tablet cores were then film coated . the tablets were film coated with an aqueous suspension of opadry film coating preparation . eltrombopag olamine tablets containing diluents with the coordinating metal calcium phosphate dibasic anhydrous were manufactured in a similar manner as described above . tablet composition for the tablet coordinating metal diluent is provided in table 2 . in fig1 , the tablet prepared with no coordinating metal diluent ( indicated as “ with non - coordinating metal diluent ”) is a eltrombopag 50 mg tablet generally prepared as described in table 1 above and the tablet prepared with the coordinating metal diluent — calcium phosphate dibasic anhydrous —( indicated as “ with coordinating metal diluent ”) is a eltrombopag 50 mg tablet generally prepared as described in table 2 above . dissolution comparison was performed using usp apparatus ii , 50 rpm , in phosphate buffer ph 6 . 8 containing 0 . 5 % tween 80 . fig2 depicts the effect of api particle size distribution on eltrombopag olamine dissolution . eltrombopag olamine 75 mg tablets were generally prepared in the manner described in example 5 , using different particle sizes . the particle size refers to the particle size of the drug granules used in the formulation . dissolution comparison was performed using usp apparatus ii , 50 rpm , in phosphate buffer ph 6 . 8 containing 0 . 5 % tween 80 . | disclosed are novel pharmaceutical compositions containing 3 ′--- 1 , 5 - dihydro - 3 - methyl - 5 - oxo - 4h - pyrazol - 4 - ylidene ] hydrazino ]- 2 ′- hydroxy -- 3 - carboxylic acid bis - and processes for preparing the same . |
because the typical wound is localized , cell types needed to effect wound repair must be concentrated in and around the injured area . thus it is preferable that the factors necessary to promote the wound healing activity of these cell types be present in the afflicted area . topical delivery of the polypeptide ( s ) is the most efficient way to achieve these goals . the instant invention is based upon the discovery that i1 - 17b can accelerate the wound healing process for all wound types , particularly when administered topically , i . e . to the surface of the wound site . so delivered , all wound types , mechanical or thermal , acute or chronic , infected or sterile , undergo healing more rapidly than similar wounds left to heal naturally or which are treated with currently available methods . however , as mentioned previously , parenteral administration of polypeptides having a role in the wound healing process is also envisioned by the present invention . in accordance with the present invention , the term “ injury ” shall be defined as a wound which extends from the surface of a patient &# 39 ; s skin into the underlying tissue , and in fact the injury may pass completely through the patient , leaving both entrance and exit wounds . “ patient ” refers to a mammal which has suffered an injury as defined above . “ therapeutic agent ” means a compound that produces a therapeutically desirable result , such as accelerated wound healing . in the present invention , the therapeutic agent is il - 17b ( zcyto7 ). additionally , the term “ therapeutic agent ” refers to a combination of il - 17b combined with at least one of the following compounds : a csf , egf , fgf , igf - i , igf - ii , insulin , an interferon , an interleukin , kgf , m - csf , pd - ecgf , pdgf , scf , tgf - α , and tgf - β . here , “ accelerated wound healing ” is defined as the process of wound healing which , as the result of the administration of a therapeutic agent in accordance with the present invention , occurs more rapidly than in a wound not receiving treatment with the therapeutic agent . csfs are hormone - like glycoproteins which regulate hematopoiesis and are required for the clonal growth and maturation of normal hematopoietic precursor cells found in the bone marrow . these factors are produced by a number of tissues . four csfs isolated from human sources have been identified : granulocyte colony stimulating factor ( g - csf ) [ welte et al ., ( 1985 ) proc . nat . acad . sci . usa , vol . 82 : 1526 - 30 ]; granulocyte - macrophage colony stimulating factor ( gm - csf ) [ cantrell et al ., ( 1985 ) proc . nat . acad . sci . usa , vol . 82 : 6250 - 54 ]; macrophage colony stimulating factor ( m - csf ); and multi - colony stimulating factor ( multi - csf , also referred to as interleukin - 3 [ nicola et al ., ( 1984 ) proc . nat . acad . sci . usa , vol . 81 : 3765 - 69 ], each accounting for the differentiation of particular immature progenitor cell types into mature cells . in addition , these factors are required for the maintenance of the mature cell types as well . in vitro , withdrawal of the appropriate csf from culture leads to rapid degeneration of terminally differentiated hematopoietic cells dependent upon that csf . two particular csfs that can be combined with il - 17b are g - csf and gm - csf . egf is a polypeptide growth factor ( the mature , processed form is 53 amino acids in length ( gray et al ., ( 1983 ) nature , vol . 303 : 722 - 25 )). in humans , this protein inhibits gastric acid secretion while murine egf is known to be mitogenic for a number of cell types , including endothelial , epithelial , and fibroblastic cells ( nakagawa et al ., ( 1985 ) differentiation , vol . 29 : 284 - 88 ). fgf comprises a family of single chain proteins 14 - 18kd in size which tightly bind the potent anticoagulant heparin . two fgf types , acidic and basic , have been reported . the 146 amino acid basic form ( bfgf ) is more stable and ten times more potent in stimulating mesodermal cells , such as fibroblasts , endothelial cells , and keratinocytes , than acidic fgf ( afgf ). see esch et al ., ( 1985 ) proc . nat . acad . sci . usa , vol . 85 : 6507 - 11 ). insulin is a protein hormone secreted by the cells of the pancreatic islets . it is secreted in response to elevated blood levels of glucose , amino acids , fatty acids , and ketone bodies , promoting their efficient storage and use as cellular fuel by modulating the transport of metabolites and ions across cell membranes and by regulating various intracellular biosynthetic pathways . insulin promotes the entry of glucose , fatty acids , and amino acids into cells . additionally , it promotes glycogen , protein , and lipid synthesis while inhibiting glucogenesis , glycogen degradation , protein catabolism , and lipolysis . insulin consists of α and β subunits linked by two disulfide bridges . igf - i and igf - ii are members of a growth hormone - dependent family which mediate the effects of growth hormones . these proteins are known to be important in the regulation of skeletal growth . both molecules have close structural homology to insulin and possess similar biological activities . igf - i shares a 43 % amino acid sequence homology with proinsulin , while igf - ii shares 60 % homology with igf - i . the igfs are somewhat unique as compared to the other proteins described herein , in that there is essentially no detectable free igf species present in the blood plasma of mammals . instead , the igfs are bound to specific carrier plasma proteins of higher molecular weight ( ooi et al ., ( 1988 ) j . endocr ., vol . 118 : 7 - 18 ). both igf species stimulate dna , rna , and protein synthesis and are involved in the proliferation , differentiation , and chemotaxis of some cell types . local administration of igf - i is known to stimulate the regeneration of peripheral nerves . in addition , igf - i and pdgf , when administered topically to wounds in pigs , synergize to promote more effective healing than when either factor is administered alone ( skoffner et al ., ( 1988 ) acta . paediatr . scand . ( suppl ), vol . 347 : 110 - 12 ). interferons were first identified as proteins that render cells resistant to infection from a wide range of viruses . three interferon types have been identified , α - ifn , β - ifn , and γ - ifn , which are produced by activated t and nk ( natural killer ) cells . α - ifn is comprised of a family of 15 or so closely related proteins while β - ifn and γ - ifn exist as single species . in addition , a synthetic consensus α - ifn , designed to incorporate regions of commonality among all known α - ifn subtypes , is disclosed in u . s . pat . no . 4 , 897 , 471 , hereby incorporated by reference . all ifns are growth inhibitory molecules playing an important role in the lymphokine cascade . each exerts a wide range of regulatory actions in normal cells , cancer cells , and host immune defense cells . γ - ifn &# 39 ; s activities include macrophage activation for enhanced phagocytosis and tumor killing capacity . at present , these proteins are mainly used in cancer therapy ( balkhill et al ., ( 1987 ) lancet , pg : 317 - 18 ). kgf is an epithelial cell specific mitogen secreted by normal stromal fibroblasts . in vitro , it has been demonstrated to be as potent as egf in stimulating the proliferation of human keratinocytes ( marchese et al ., ( 1990 ) j . cell physiol ., vol . 144 , no . 2 : 326 - 32 ). m - csf , also known as csf - 1 , is a homodimeric colony stimulating factor which acts solely on macrophage progenitors . this macrophage lineage specific protein is produced constitutively in vitro by fibroblasts and stromal cell lines . in vivo , unlike other csfs , m - csf appears early in embryogenesis , suggesting a potential developmental role for this polypeptide ( delamarter , j ., ( 1988 ) biochemical pharmacology , vol . 37 , no . 16 : 3057 - 62 ). pd - ecgf is a platelet derived endothelial cell mitogen having a molecular weight of approximately 45 kd . in contrast to the fgf family of endothelial cell mitogens , pd - ecgf does not bind heparin nor does it induce fibroblast proliferation . however , pd - ecgf does stimulate endothelial cell growth and chemotaxis in vitro and angiogenesis in vivo ( ishikawa et al ., ( 1989 ) nature , vol . 338 : 557 - 61 ). pdgf is a potent stimulator of mesenchymal cell types , like fibroblasts and smooth muscle cells , but it does not stimulate the growth of epithelial or endothelial cells ( ross et al ., ( 1986 ) cell , vol . 45 : 155 - 69 ). at low concentrations , pdgf acts as a chemoattractant for fibroblasts , and also as a chemoattractant and activating signal for monocytes and neutrophils ( deuel et al ., ( 1982 ) j . clin . invest ., vol . 69 : 1046 - 49 ). scf is a novel cellular growth factor that stimulates the growth of early hematopoietic progenitor cells , neural stem cells , and primordial germ stem cells ( pct / us90 / 05548 , filed sep . 28 , 1990 ). scf exhibits potent synergistic activities in conjunction with colony stimulating factors , resulting in increased numbers of colonies and colonies of greater size ( martin et al ., ( 1990 ) cell , vol . 63 : 203 - 11 ). thus , administration of scf to mammals in pharmacologic doses , alone or in combination with other colony stimulating factors or other hematopoietic growth factors , may lead to the improvement of damaged cells in a number of divergent organ systems . tgf - α and tgf - β act synergistically to induce anchorage independent growth in certain cancer cell lines . tgf - β is comprised of a class of disulfide linked homodimeric proteins , each chain being composed of 112 amino acids ( spom et al ., ( 1987 ) j . cell biol ., vol . 105 : 1039 - 45 ). this dimeric protein produces many biological effects , such as mitogenesis , growth inhibition , and differentiation induction depending upon the assay used . tgf - β1 is the most studied tgf - β species in relation to wound healing ( ten dijke , supra ). as a class , tgf - β is a potent monocyte and fibroblast chemoattractant . “ topical administration ” shall be defined as the delivery of the therapeutic agent to the surface of the wound and adjacent epithelium . “ parenteral administration ” is the systemic delivery of the therapeutic agent via injection to the patient . a “ therapeutically effective amount ” of a therapeutic agent within the meaning of the present invention will be determined by a patient &# 39 ; s attending physician or veterinarian . such amounts are readily ascertained by one of ordinary skill in the art and will enable accelerated wound healing when administered in accordance with the present invention . factors which influence what a therapeutically effective amount will be include , the specific activity of the therapeutic agent being used , the wound type ( mechanical or thermal , full or partial thickness , etc . ), the size of the wound , the wound &# 39 ; s depth ( if full thickness ), the absence or presence of infection , time elapsed since the injury &# 39 ; s infliction , and the age , physical condition , existence of other disease states , and nutritional status of the patient . additionally , other medication the patient may be receiving will effect the determination of the therapeutically effective amount of the therapeutic agent to administer . “ pharmaceutically acceptable ” means that the components , in addition to the therapeutic agent , comprising the formulation are suitable for administration to the patient being treated in accordance with the present invention . in accordance with the present invention , “ wound dressings ” are any of a variety of materials utilized for covering and protecting a wound . examples include occlusive dressings , adhesive dressings , antiseptic dressings , and protective dressings . in pharmaceutical preparations , a “ cream ” is a semisolid emulsion of the oil - in - water or water - in - oil type suitable for topical administration . in accordance with the present invention , creams and foams used will also be suitable for use with the therapeutic agents herein described . il - 17b , when administered as taught by the present invention in a therapeutically effective amount , significantly accelerates the wound healing process in all wound types . in natural wound systems , extracellular growth factors such as il - 17b may be present in rate limiting quantities . thus , parenteral and / or topical administration of such factors may promote accelerated wound healing . in vitro il - 17b , is known to stimulate the proliferation of chondrocytes and osteoblasts . it may also induce the expression of other cytokines such as tgf - α and il - 1β . in vivo , administration of exogenous il - 17b is believed to enhance an organism &# 39 ; s ability to respond to injury . any analogs of il - 17b possessing comparable or enhanced in vivo biological activity can be used in accordance with the methods of the present invention . il - 17b is preferably produced by recombinant methods which allows for alteration of the molecule to produce an analog . such analogs may be generated by the deletion , insertion , or substitution of amino acids in the primary structure of the naturally occurring proteins , or by chemical modification , such as by pegylation , of the protein . for example , to enable expression of these polypeptides in procaryotic host microorganisms , an initial methionine codon is required for translation initiation . other analogs may have greater in vitro and / or in vivo biological activity , exhibit greater ph or temperature stability , maintain biological activity over a broader range of environmental conditions , or may have longer half - lives or clearance times in vivo . to manufacture sufficient quantities of il - 17b for commercial pharmaceutical application , these proteins are generally produced as the products of recombinant host cell expression . it is known that biologically active forms of il - 17b can be recovered in large quantities from procaryotic hosts such as e . coli when such hosts , transformed with appropriate expression vectors encoding these polypeptides , are grown under conditions allowing expression of the exogenous gene . it is therefore preferred to utilize il - 17b produced in this manner . the recombinant il - 17b is formulated into a pharmaceutical formulation suitable for patient administration . as will be appreciated by those skilled in the art , such formulations may include pharmaceutically acceptable adjuvants and diluents . when administered systemically , a therapeutically effective amount of the therapeutic agent is delivered by the parenteral route , i . e . by subcutaneous , intravenous , intramuscular , or intraperitoneal injection . wound treatment by parenteral injection may involve either single , multiple , or continuous administration of the therapeutic agent , depending upon various factors , including the injury type , severity , and location . the amount of topical il - 17b to be administered can be determined by one of ordinary skill , but would be expected to range from about 0 . 05 to about 100 μg / cm 2 of il - 17b with the expected most effect range to be about 10 to about 75 μg / cm 2 . in a preferred embodiment , the dosage is 50 μg / cm 2 . other modes of administration , such as parenteral , i . e ., intramuscular or subcutaneous , would expected to be lower and based on pg per kg of patient body weight . in a preferred embodiment of the present invention , recombinant il - 17b should be topically administered to the wound site to promote accelerated wound healing in the patient . this topical administration can be as a single dose or as repeated doses given at multiple designated intervals . it will readily be appreciated by those skilled in the art that the preferred dosage regimen will vary with the type and severity of the injury being treated . for example , surgical incisional wounds cause little damage to surrounding tissues , as little energy is transmitted to the tissues from the object inflicting the injury . it has been found that a single topical administration of the therapeutic agent results in significantly more rapid healing than in identical wounds which go untreated . where the wound is infected and chronically granulating , repeated daily application of the therapeutic agent has been found to produce more rapid wound healing than in similar wounds receiving no treatment . while it is possible to administer the therapeutic agent as a pure or substantially pure compound , i . e . not incorporated into any pharmaceutical formulation , it is preferable instead to present the therapeutic agent in a pharmaceutical formulation or composition . such formulations comprise a therapeutically effective amount of the therapeutic agent with one or more pharmaceutically acceptable carriers and / or adjuvants . the carriers employed must be compatible with the other ingredients in the formulation . preferably , the formulation will not include oxidizing or reducing agents or other substances known to be incompatible with the described polypeptides . all formulation methods include the step of bringing the biologically active ingredient into association with the carrier ( s ) and / or adjuvant ( s ). in general , the therapeutic agent of the instant invention will be formulated by bringing the agent into association with liquid carriers , finely divided solid carriers , or both . formulations suitable for topical administration in accordance with the present invention comprise therapeutically effective amounts of the therapeutic agent with one or more pharmaceutically acceptable carriers and / or adjuvants . an aqueous or collagen - based carrier vehicle is preferred for topical administration of the therapeutic agents described by the present invention . when the formulation is to be administered but one time , a collagen - based carrier vehicle is preferred . an example of such a vehicle is zyderm . rtm . ( collagen corp ., palo alto , calif .). if the wound being treated requires multiple applications of the therapeutic agent at designated intervals , it is preferred to utilize a pharmaceutically acceptable aqueous vehicle for delivery . however , it is also possible to incorporate the therapeutic agent into a variety of materials routinely used in the treatment of wounds . such materials include hyaluronic acid or other glycosaminoglycan - derived preparations , sutures , and wound dressings . when the therapeutic agent used in accordance with the present invention is comprised of more than one protein , the resultant admixture is commonly administered in the same fashion as formulations comprising only one polypeptide as the therapeutic agent . wild type or il - b ( zcyto7 ) homozygous knockout mice were anesthetized with isoflourane and the dorsum shaved and depilated . after 24 hrs mice were anesthetized with isoflourane , and the dorsum cleaned with povidone - iodine and isopropyl alcohol pads . animals received either one or two full thickness wounds of 0 . 5 cm 2 or 1 cm 2 ; these were induced on either flank by the surgical removal of a piece of full thickness dorsal skin . the wound area was then bandaged with a johnson & amp ; johnson bioocclusive dressing and these dressings were removed at three days . animals were examined daily and the size and physical appearance of the wounds assessed . at various time points a 1 cm 2 area of skin surrounding the 0 . 5 cm 2 wound was surgically removed and these samples were processed for histological evaluation by formalin fixation or flash frozen in liquid nitrogen for rna isolation . at various time points , final size and appearance observations were made . the animals were then euthanized and skin surrounding both wounds was collected for histological evaluation and rna isolation as described in example 2 . for histological evaluation , samples were paraffin embedded and stained with hematoxylin and counterstained with eosin by standard techniques . these sections were then scored by light microscopy . in one study , histological evaluation of il - 17b ( zcyto7 ) knockout mice revealed decreased granulation tissue and reduced epithelial migration into the area of the wound bed , consistent with a reduced healing response in knockout animals . visual assessment of wound beds from two separate wound - healing experiments also indicated that il - 17b ( zcyto7 ) knockout mice exhibited increased swelling and redness of the tissue surrounding the wound bed both at early and late time points post wounding , suggesting that inflammatory responses were elevated and sustained in these animals . fig1 graphically represents the observational results of one of these experiments . as indicated in the figure , a much higher percentage of knock - out mice exhibited unusual redness around the wound at both time points when compared to wild - type controls . the observational experiments of example 1 were supported by rna - based expression measurements . using a multiplex approach , the expression of 293 genes in normal and wounded tissue from wild type and knockout mice were examined . multiplex gene expression assays of murine skin tissue samples were performed essentially as described by yang et al . ( yang et al ., “ badge , beadsarray for the detection of gene expression , a high - throughput diagnostic bioassay ”, genomeresearch , 11 : 1888 - 1898 ( 2001 )). total rna was prepared using a standard phenol : chloroform extraction protocol for tissues and converted to antisense rna ( arna ) using ambion messageamp arna amplification kits ( ambion , inc . austin , tex . ), incorporating biotinylated utp and ctp ( perkinelmer life sciences , boston , mass .). arna was quantified by absorbance at 260 nm . gene specific sense oligonucleotides ( 25 - mers ) were synthesized with 5 ′- amino uni - linkers and coupled to luminex xmap carboxylated microspheres according to the manufacturer &# 39 ; s protocol ( luminex corp ., austin , tex .). each gene specific oligonucleotide was coupled to a distinct colored / numbered microsphere ; 1 nmole of oligonucleotide was coupled to 2 . 5 × 10 6 microspheres in a single reaction and suspended in 100 μl of 10 nm tris / 0 . 1 mm edta , ph 8 . 0 . the microspheres were tittered using a hemacytometer . for hybridization of arna to capture probe - coupled microspheres , 5 , 000 microspheres of each gene were pooled , mixed , and suspended in 60 μl of hybridization buffer with 10 μg of arna that had been previously randomly fragmented by heating at 94 ° c . for 35 min . the samples were hybridized at 60 ° c . for 4 - 5 hours with constant mixing . hybridizations were performed in 3m tetramethylammonium chloride ( tmac ) ( sigma , st . louis , mo . ), 50 mm tris ph 8 . 0 , and 4 mm edta , ph 8 . 0 . following washing on a vacuum manifold to remove unbound arna , mixtures were incubated with streptavidin - r - phycoerythrin conjugate for 15 min at room temperature with shaking at 400 rpm , washed , and resuspended in 75 μl of wash buffer ( 1x pbs , 1 mm edta , 0 . 01 % tween 20 ). the microspheres were analyzed on a luminex 100 xmap system ( luminex corp ., austin , tex .) and at least 200 events of each set of individually colored microspheres were counted . many genes failed to show any robust differential expression between wild type and knockout mice during the course of the study . however , the knockout animals did exhibit up - regulation of transcripts for a number of cytokine and chemokine genes in tissues . of 42 cytokine or chemokine transcripts profiled at day 7 post wounding , 36 % showed greater than two fold up - regulation in the knockout when compared to the wild - type . these included tnf - α , il - 6 , il - 1β , il - 20 ( zcyto10 ), il - 22 ( zcyto 18 ), and il - 31 ( zcytor17lig ). a sample data set with up - regulation of these genes at day seven post wounding is shown in fig2 . in contrast to the overexpression of inflammatory cytokines in knockout tissue , there was an under - representation of transcripts associated with fully differentiated epidermis , suggesting that the formation of a fully differentiated epidermis was retarded in the il - 17b ( zcyto7 ) knockout environment . in particular keratin 1 ( krt1 ), keratin 10 ( krt10 ), and involucrin ( ivl ), all of which are associated with differentiated epidermis , were under - represented in knockout when compared to wild - type animals . in addition , there was also decreased expression of cxcl11 , a chemokine previously reported to be required for mobilization of keratinocyes and their migration in a wound environment . a sample data set with down - regulation of transcripts associated with fully differentiated epidermis is shown in fig3 . the mouse model of cutaneous leishmaniasis was performed essentially as described in “ animal models for the analysis of immune responses to leishmaniasis ,” in current protocols in immunology david sacks and peter melby , chapter 19 . 2 . 1 - 19 . 2 . 20 ( 1998 ). this model was used to investigate the role of zcyto7 in wound healing . historically , susceptibility to cutaneous l . major infection has been associated with chronic and progressive swelling at the site of infection , development of th2 responses ( low ifn - g : il - 4 production ratio ; high levels of il - 4 produced ) and production of high levels of il - 10 , elevated levels of serum ige and systemic dissemination of l . major . resistance to cutaneous l . major infection has been associated with acute swelling at the site of infection that ultimately heals , development of th1 responses ( high ifn - g : il - 4 production ratio ), absence of serum ige and containment of l . major to the site of infection . recent publications have shown that cd4 + t cell responses ( th1 vs . th2 ) to l . major are not the only factor that determines resistance vs . susceptibility in the mouse model of cutaneous l . major infection . for example , genetic defects in wound - healing have recently been suggested to explain why some strains of mice are resistant to l . major , including development of th1 responses , but develop more severe and prolonged swelling at the site of infection ( sakthianandeswaren et al ., ( 2005 ) pnas 102 ( 43 ): 15551 - 15556 ). alternatively , defects in neutrophil recruitment to the site of infection may result in a similar l . major disease phenotype in c57b⅙ mice ( ribeiro - gomes et al ., ( 2004 ) j . immunol . 172 : 4454 - 4462 ). all mice were female and age - matched . the c57b⅙ - congenic homozygous zcyto7 wild - type and zcyto7 gene - targeted (“ zcyto7 knockout ”) mice were obtained from in - house stocks . the zcyto7 congenic lines had been derived by in - house backcrossing of heterozygous zcyto7 knockout mice ( ozgene , bentley , australia ) to c57b⅙ mice . c57b1 / 6 and balb / c control mice were purchased from charles river laboratories , wilmington , mass . leishmania major ( l . major , strain whom / ir /-/ 173 ) was cultured in vitro from frozen stocks . infectious l . major promastigotes were prepared by pna - selection performed by incubation of cultured promastigotes ( 4 × 10 8 / ml ) with pna - coated agarose beads ( 1 : 20 dilution ; sigma , st . louis , mo .) followed by differential sedimentation to pellet pna - bound promastigotes . free promastigotes in the supernatant were collected , washed , counted and resuspended in pbs at the appropriate concentration for infection of mice . mice ( n = 5 / group ) were injected subcutaneously in one hind footpad with 1 × 10 6 infectious l . major promastigotes in 30 ul pbs on day 0 of the model . disease progression was followed weekly for 12 weeks by measuring footpad thickness with a metric caliper , measuring body weights with a lab scale and clinical scoring of footpad lesions by eye . clinical scoring : 0 = no lesion , 1 = open lesion of & lt ; 1 mm , 2 = open / necrotic lesion covering part of footpad (˜ 1 - 4 mm ), 3 = open / necrotic lesion covering majority of footpad (& gt ; 4mm ). serum was collected by eye - bleed at day − 2 , week 6 and week 12 of the model . at designated time - points , mice were killed and serum , spleens and draining popliteal lymph - nodes were collected for in vitro analysis . the balb / c mice were killed and serum collected at week 6 post - infection due to the severity of their l . major disease at this time point . spleens and lymph - nodes were not collected for in vitro analysis from balb / c mice . l . major lysate antigen was prepared by repeated freeze - thaw of a sterile , high - density suspension of l . major promastigotes in pbs followed by high - speed centrifugation to remove debris . lysate supernatants were stored in single - use aliquots at − 80 ° c . lack of residual viable l . major was verified by microscopic inspection and by in vitro culture . protein concentration was estimated using a bca kit ( pierce ). optimal dilutions of lysate for t cell stimulation in vitro were identified in preliminary [ 3h ]- incorporation experiments . single - cell suspensions of spleen and lymph - node lymphocytes were prepared in culture medium ( rpmi + 10 % fcs ). spleen and lymph - node cells ( 5 × 10 5 / well ) from each group of mice were pooled and cultured at 37 ° c . in flat - bottom 96 - well plates in triplicate wells with either medium , l . major lysate antigen ( 1 : 100 and 1 : 200 dilutions ) or cona ( 0 . 5 ug / ml ). cell supernatants were collected at 48 hours for analysis of cytokine levels using a luminex kit according to the manufacturer &# 39 ; s instructions . cells were pulsed with 1 uci / well of [ 3h ]- thymidine for an additional 12 hours , and then harvested for analysis of cpm of [ 3h ]- incorporated using a topcount beta counter . data are plotted as the mean cpm for each antigen for each group of mice . relative levels of l . major - specific serum igg1 and igg2a were quantitated by elisa . elisa plates were coated overnight with l . major antigen ( 3 . 4 ug / ml ) in pbs . the plates were blocked with pbs + 1 % bsa , washed , and then incubated for 2 - 3 hours with serum samples serially diluted in pbs + 1 % bsa . the plates were developed by serial 1 hour incubations with biotinylated goat anti - mouse igg1 or igg2a antibody ( southern biotech , brmingham , ala . ), streptavidin - horseradish peroxidase conjugate ( jackson immunoresearch , west grove , pa .) and hrp substrate ( tmb one solution ; promega , madison , wis .). color development was halted by addition of 0 . 1 n hc1 . the absorbance of each well was read at both 450 & amp ; 630 nanometers using a spectra max 190 elisa plate reader ( molecular devices , sunnyvale , calif .). data are plotted as [ a 450 - a 630 ] on the y axis versus 1 / dilution of serum on the x axis . relative levels of total serum ige were quantitated by elisa . elisa plates were coated overnight with ige - specific goat anti - mouse ige antibody ( southern biotech , birmingham , ala .). the plates were blocked with pbs + 1 % bsa , washed , and then incubated for 2 - 3 hours with serum samples serially diluted in pbs + 1 % bsa . the plates were developed by serial 1 - hour incubations with biotinylated goat anti - mouse ige antibody ( southern biotech , birmingham , ala . ), streptavidin - horseradish peroxidase conjugate ( jackson immunoresearch , west grove , pa .) and hrp substrate ( tmb one solution ; promega , madison , wiss .). color development was halted by addition of 0 . 1 n hc1 . the absorbance of each well was read at both 450 & amp ; 630 nanometers using a spectra max 190 elisa plate reader ( molecular devices , sunnyvale , calif .). data are plotted as [ a 450 - a 630 ] on the y axis versus 1 / dilution of serum on the x axis . control balb / c mice were susceptible to l . major and developed severe / progressive l . major disease as would be expected for this strain . signs of progressive disease included progressive swelling of the infected footpads that did not resolve , the development of large open lesions on the infected footpads and the failure to gain weight over time . these mice also had high levels of total ige in their serum . control c57b⅙ mice were resistant to l . major , developed limited footpad swelling that resolved by 8 weeks post - infection , and gained body weight normally as would be expected for this strain . they also developed thl responses , characterized by a high ratio of ifn - gamma : il - 4 production to l . major antigen in vitro and a high ratio of igg2a : igg1 l . major - specific antibody and an absence of ige in their serum . c57b⅙ - congenic zcyto7 wild - type mice had an l . major disease phenotype that was indistinguishable from that of c57b⅙ control mice . they were resistant to l . major and developed moderate footpad swelling that resolved by 8 weeks post - infection . they also developed thl responses , characterized by a high ratio of ifn - gamma : il - 4 production to l . major antigen in vitro and a high ratio of igg2a : igg1 l . major - specific antibody and an absence of ige in their serum . the c57b⅙ - congenic zcyto7 gene - targeted mice were resistant to l . major and gained body weight normally . however they developed significantly larger footpads that took significantly longer (& gt ; 12 weeks ) to resolve than did footpads in c57b1 / 6 and zcyto7 wild - type mice . development of small open lesions also developed on their footpads ; no lesions were observed on the footpads of c57b⅙ and zcyto7 wild - type mice . they had larger spleens and draining lymph - nodes at 12 - weeks , which is consistent with their having more severe symptoms of disease than the control mice at this time - point . they developed th1 responses , characterized by a high ratio of ifn - gamma : il - 4 production to l . major antigen in vitro and a high ratio of igg2a : igg1 l . major - specific antibody and an absence of ige in their serum antibody . this data suggest that zcyto7 is not required for development of th1 responses to l . major , but rather may be important for wound - healing or immune control of l . major infection in vivo . il17b knockout mice exhibit altered disease progression in a dss colitis model to investigate disease susceptibility mice were run through the dextran sulfate sodium ( dss ) model of colitis . this model induces an acute colitis which is manifest by bloody diarrhea , weight loss , shortening of the colon and mucosal ulceration with neutrophil infiltration . dss - induced colitis is characterized histologically by infiltration of inflammatory cells into the lamina propria , with lymphoid hyperplasia , focal crypt damage , and epithelial ulceration . these changes are thought to develop due to a toxic effect of dss on the epithelium and by phagocytosis of lamina propria cells and production of tnf - alpha and ifn - gamma . to induce dss colitis mice were treated with a 2 - 2 . 5 % solution of reagent grade dextran sulfate sodium ( dss , mp biochemicals , solon , oh ), molecular weight 36 , 000 - 50 , 000 administered ad libitum in drinking water . animals received this dss drinking water for 5 days and were then returned to normal water . using this model both onset of colitis in response to dss treatment and subsequent recovery after dss withdrawal can be measured . disease progression can be monitored during the course of the study by loss of weight . in a typical study normal mice will lose 5 - 10 % of bodyweight within 7 - 8 days of initiating dss treatment but will return to a normal weight after 5 days on non - dss drinking water . as indicated in table 1 , in this model il17b knockout mice exhibited an increased weight loss at the peak of disease . in addition il17b knockout mice exhibited a retarded recovery upon transfer to normal water : after 5 days on normal water wild type animals but not il17b knockout mice had regained weight lost during the course of the study . thus the lack ofil17b results in exacerbated disease in the dss colitis model . such a phenotype could be caused by the failure of immune cells or epithelial cells to modulate or repair the damage and inflammation inherent in this model . from the foregoing , it will be appreciated that , although specific embodiments of the invention have been described herein for purposes of illustration , various modifications may be made without deviating from the spirit and scope of the invention . accordingly , the invention is not limited except as by the appended claims . | il - 17b is known to stimulate the proliferation of chondrocytes , bone , and is highly expressed in nervous tissue , resulting in repair of diseased tissue . when il - 17b is absent a marked negative effect on wound healing is noted . the present invention comprises providing il - 17b , by topical , parental , or other administration means , in order to accelerate the wound healing process . the present invention further encompasses a pharmaceutical composition and formulations thereof that utilize il - 17b , either alone or in combination with other cytokines or growth factors known to aid wound healing . the invention also contemplates methods of treating wounds in patients using this pharmaceutical composition . |
referring to fig1 , it will there be seen that the reference numeral 10 denotes an illustrative embodiment of the present invention as a whole . the first embodiment of novel system 10 includes a working base or quadrant 12 and an opposing top member or opposing quadrant 14 having essentially the same structure as working quadrant 12 . more particularly , working quadrant 12 and opposing quadrant 14 share a generally straight , parallelepiped configuration having a predetermined length , width , and height . working quadrant 12 has a flat upper surface 12 a and opposing quadrant 14 has a flat lower surface 14 a . flat upper surface 12 a is disposed in confronting relation to lower flat surface 14 a . in a first embodiment , a pair of upstanding guideposts , collectively denoted 16 , interconnects working quadrant 12 and opposing quadrant 14 . the respective lowermost ends of guideposts 16 are secured to working quadrant 12 by any suitable means , near opposite ends thereof . two longitudinally spaced apart throughbores 18 are formed in opposing quadrant 14 to slidingly receive said posts so that opposing quadrant 14 may be easily moved toward or away from working quadrant 12 as indicated by double - headed directional arrow 20 . posts 16 , 16 are snugly received within their respective bores 18 , 18 so that friction maintains opposing quadrant 14 in any position of functional adjustment along the length of posts 16 , 16 . moving opposing quadrant 14 therefore requires the application of manual force to said opposing quadrant . a first row of bores , where each bore is denoted 22 , is formed in working quadrant 12 in closely spaced apart relation to longitudinally - extending leading edge 13 of working quadrant 12 . a second row of bores , where each bore is denoted 23 , is formed in parallel relation to the first row of bores . the first row of bores is positioned between the second row of bores and said longitudinally - extending edge . fig1 further depicts a plurality of metal pins , collectively denoted 24 a , 24 b and a plurality of cast teeth and gums , collectively denoted 26 . each bore 22 is adapted to snugly receive a metal pin 24 a and each bore 23 is adapted to snugly receive a metal pin 24 b . the provision of two pins prevents each cast tooth and gum or set of cast teeth and gum from rotating . upper surface 12 a of working quadrant 12 is perfectly flat . it is therefore easy to see if each cast tooth 26 is perfectly seated , i . e ., with its pins 24 a , 24 b fully seated within its associated bores 22 , 23 , respectively . working quadrant 12 is hollow except in the region below bores 22 and 23 . as indicated in the more realistic bottom plan view of fig2 b , a solid material 27 is provided within which bores 22 , 23 are formed . in a preferred embodiment , all parts of the working quadrant , including the material within which the bores are formed , are formed of a high impact plastic . the use of metallic or other materials is also within the scope of this invention . as depicted in fig2 a , apertures 22 are positioned in offset relation to longitudinally - extending edge 13 of working quadrant 12 as mentioned above so that the forward edge 26 a of each cast tooth 26 is substantially flush with said longitudinally - extending edge . this minimizes the amount of trimming that must be performed . in the example of fig2 a , the only areas of working quadrant 12 that needs to be trimmed of excess cast material on the labial side of teeth 26 are collectively denoted 28 . as further indicated in fig2 a , most of working quadrant 12 is removed . the removed area in this particular example is denoted 30 . however , a relatively large area , denoted 32 , may be left in place because area 32 is hidden from view behind teeth 26 and therefore need not be removed . this saves time and also reduces abrasion to cast teeth 26 . when the excess cast material has been removed , opposing quadrant 14 is simply lowered until cast teeth 26 carried thereby engage cast teeth 26 mounted on working quadrant 12 . if the bite is optimal , the upper and lower cast teeth are detached from opposing quadrant 14 and working quadrant 12 , respectively , and hinged together using any one of the above - listed commercially available hinge articulators . a thin metallic film or foil 25 , depicted in the more realistic views of fig2 c , 2 d , and 4 , overlies flat upper surface 12 a and covers bores 22 , 23 . the foil is punctured by pins 24 a , 24 b when the novel structure is used as perhaps best understood from fig2 c and 2d . foil 25 prevents dental stone from entering the bores 22 , 23 that are not used , i . e ., the bores that do not receive pins 24 a , 24 b remain covered by said foil 25 and thus flat upper surface 12 a remains flat . in the absence of foil 25 , some of the dental stone could enter into the unused bores and cause bumps or other uneven spots on surface 12 a , thus preventing teeth 26 from seating cleanly thereagainst . there is no corresponding plurality of pin - receiving bores 22 , 23 formed in opposing quadrant 14 . fig3 – 8c also provide a more realistic view of the novel two - piece model and die system . in those figures , guideposts 16 , 16 of the first embodiment are eliminated and working quadrant 12 is interconnected to opposing quadrant 14 by an articulation hinge 34 ( fig3 and 4 ) having a first part 34 a connected to working quadrant 12 and a second part 34 b connected to opposing quadrant 14 as best depicted in fig4 . this hinged embodiment is the second embodiment of the invention . adjustment rod 35 ( fig3 and 4 ) is slideably and snugly received within a throughbore formed in opposing quadrant 14 . its flat lowermost end 35 a abuts flat upper surface 12 a of working quadrant 12 and thus serves as a stop means for hinge 34 when working quadrant 12 and opposing quadrant 14 are disposed in optimal juxtaposition with one another as depicted ion fig3 . it should be understood that quadrants 12 and 14 , depicted diagrammatically in fig1 and 2a in connection with the guidepost embodiment of the invention , actually have the structure as depicted in fig2 b , 2 c , 2 d , and 3 – 7 . accordingly , the more detailed description of said quadrants as made hereinafter also applies to the quadrants of fig1 and 2a . as best understood in connection with fig3 , opposing quadrant 14 is an essentially hollow structure , including the aforesaid flat lower surface 14 a and sidewalls 36 projecting upwardly from a periphery thereof . a plurality of sets of apertures is formed in flat lower surface 14 a and the sets of apertures are arranged in a row as best depicted in fig5 . each set of apertures is denoted 38 in said fig5 . an enlarged view of one set of apertures 38 is provided in fig7 . more particularly , as best depicted in said fig7 , four apertures 38 a , 38 b , 38 c , and 38 d arranged in circumferentially spaced relation to one another collectively form one set of apertures . in a commercial embodiment of the invention , there are ten ( 10 ) sets of said apertures . a mounting post 40 , depicted in fig4 and 6 , is associated with each set of apertures so that in said commercial embodiment there are ten ( 10 ) of said mounting posts . each mounting post 40 is centered with respect to its associated set of apertures , each mounting post is fluted , and each mounting post depends from lower flat surface 14 a of working quadrant 14 as best understood from fig4 . more particularly , each mounting post 40 has four semicircular flutes , collectively denoted 42 in fig7 , each of which is in registration with an associated aperture and the depth of each flute is substantially equal to the radius of its associated aperture . in this way , no part of a mounting post 40 occludes any of its four associated apertures as clearly depicted in said fig7 . flutes 42 extend from flat lower surface 14 a to a point about two - thirds of the extent of each mounting post . accordingly , about the lower third of each mounting post is not fluted , thereby forming a disc - shaped head 44 at the bottom of each mounting post . thus , there is an undercut 46 formed in each mounting post 40 where a flute 42 meets head 44 . in the commercial embodiment where each set of apertures 38 has four apertures 38 a , 38 b , 38 c , and 38 d , and where each mounting post 40 has four flutes 42 , the number of undercuts 46 in each mounting post is four . the number of apertures and hence the number of flutes and hence the number of undercuts may be increased or decreased . four ( 4 ) is merely considered to be an optimal number but other numbers of apertures per set of apertures and hence other numbers of flutes and undercuts are within the scope of this invention . this arrangement of sets of apertures 38 where each set of apertures has a mounting post 40 associated with it and where each mounting post is fluted as described and surmounted by an unfluted , disc - shaped head 44 to create a plurality of undercuts 46 is provided to hold the cast teeth 26 and associated gums that depend from lower flat surface 14 a of opposing quadrant 14 . the dental stone used to make the gums and teeth fills the apertures and the flutes . the respective heads 44 of the mounting posts 40 support the dental stone because the mounting posts depend from said flat lower surface . fig8 a , 8 b , and 8 c depict a third embodiment where a working base 50 has the same structure as working quadrant 12 but is semicircular in configuration . as such , it represents a full lower set of teeth and not just a quadrant as in the first two embodiments . opposing top member 52 also has the same structure as opposing quadrant 14 in all respects except that said opposing top member is semicircular and represents a full set of upper teeth and not just a quadrant as in the first two embodiments . the same reference numerals are used in view of the common structure of the three embodiments . the novel structure thus removes much of the guesswork associated with prior art techniques . thus , the level of skill required to make a good set of model teeth is substantially reduced . much less time is required as well . a lab equipped with the novel system will also become known for its consistency and reliability . moreover , patient complaints about ill - fitting crowns and dentures will diminish . it will thus be seen that the objects set forth above , and those made apparent from the foregoing description , are efficiently attained . since certain changes may be made in the above construction without departing from the scope of the invention , it is intended that all matters contained in the foregoing description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense . it is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described , and all statements of the scope of the invention that , as a matter of language , might be said to fall therebetween . | a model and die system has a working quadrant of parallelepiped construction and a opposing quadrant of the same construction . the working quadrant has an upper flat surface disposed in confronting relation to a lower flat surface of the opposing quadrant . pin - receiving bores are formed in the working quadrant and mounting members depend from the opposing quadrant . each cast tooth supported by the working quadrant has a pin depending from it and is fully seatable against the upper flat surface . each cast tooth mounted on the upper flat surface is secured to a mounting post that depends from the upper flat surface . in a first embodiment , the quadrants are held in spaced apart , adjustable vertical relation to one another by a pair of parallel guideposts . in a second embodiment , an articulated hinge performs that function . in a third embodiment , a semicircular base opposes a semicircular top member . |
the present invention relates in a first aspect to a small wearable ultrasound device for signalling changes according to claim 1 . in an example the present device is positioned between the umbilicus and the pubic bone . when the bladder fills with urine , the bladder size will increase and it will come in the range of the ultrasound beam . when the ultrasound wave passes through the bladder , the front wall and back wall of the bladder will be the two main barriers . these barriers will both create an echo signal that will be received by the sensor . it has been found that each wall of the bladder produces two signals , namely from the outside and the inside of the wall , which signals can be resolved as separate echo &# 39 ; s , in order to determine a wall thickness . in order to improve resolution such is typically taken into account . in children below the age of 10 years , the bladder is an abdominal organ and is situated between the pubic bone and the navel . in these young children the probe may be positioned perpendicularly to the abdominal wall . however , when the child gets older , the bladder will move towards the pelvic region and in children above 10 years and adults , the ultrasound probe will be positioned in an angle of 5 to 45 degrees to ensure that the bladder is in sight . it is noted that e . g . using amplitude mode measuring also information obtained with respect to a ( relative ) thickness of a wall may be used for monitoring and signalling purpose , in a similar fashion as e . g . above . in an example the present device will be semi - permanently attached to the skin using e . g . a belt , an adhesive gel , or adhesive bandage . this makes it possible to measure ( semi -) continuously . to limit the use of energy the device may be set to measure only a few times per minute or even once every 1 - 5 minutes or during certain times of the day or night . it may also use an algorithm to calculate the best moments for measuring based on earlier measurements . the present device may have a compact pcb or chip with a high voltage driver and / or integrated or separate sensor readout circuit in a single package , and further comprising a battery with a battery management circuit . therewith a bundle of high voltage cables between transducers in the scanner and high voltage circuits for driving the transducers is replaced . another problem of bladder scanners currently on the market is that the driving power of the high voltage drive circuit is dimensioned on driving the charge for the cable mainly . since in the present invention the cable is omitted , far less driving power is needed , a smaller power source suffices , and the circuits on the chip can become much smaller , which facilitates a small footprint of the high voltage chip . the present optimized design may overcome at least some of these problems . the present device also saves considerable electrical driving power , which offers the advantage of less heating of the high voltage driver chip . the present device may be ( in combination with ) an app on a mobile phone - like ( or tablet ) device for wireless readout , in order to display the estimated filling degree of the bladder with urine . the wearable device comprises a means for providing electrical energy , such as an electrical energy source , and an energy converter . examples of an electrical energy source are a battery , and a capacitor . likewise an energy converter may be used , such as a converter that converts body warmth into electricity , movement into electricity , pressure into electricity , etc . it also may include supporting electronics which comprise at least a battery management circuit enabling several days or weeks or longer of battery life . such can be achieved by management of a stand - by function with a low power consumption , a high voltage circuit for the transmit pulse on the piezoelectric transducers , a receive / sense circuit for detection of the echo and time between the echo &# 39 ; s , and possibly in the same package , a data processing and communication circuit , a display circuit or wireless rf , or a wired transmission . the wearable device comprises a detector for detecting reflected ultrasound . at least one of the detectors and at least one of the ultrasound generators of the device are preferably one and the same ; this combination is also referred to as a transducer ; more preferably most or all detectors ( or detecting elements ) and generators ( or generating elements ) are one and the same , i . e . the at least one first and second elements are each individually capable of generating and detecting . in an example of the direct above at least one mems is used . in an example of the present device the at least one first transducer is capable of generating an ultrasound frequency pulse , and the device further comprises at least one second transducer , wherein the second transducer is capable of detecting a reflected ultrasound frequency pulse of a few milliseconds to microseconds duration , at frequencies of 20 khz - 10 mhz . so a first series of transducers is used as signal generator , and a second series as detector . in an example the present device comprises at least one array of first transducers . as an alternative or in addition it may comprise at least one array of second transducers . each array individually may comprise 2 - 10 6 transducers , preferably 3 - 10 4 transducers , such as 4 - 6 transducers . the arrays may be substantially rectangular , hexagonal , t - shaped , +- shaped , round , ellipsoidal , etc ., and combinations thereof . there with a large variation in power ( s ) and / or frequencies can be provided . in addition or as an alternative the transducers may be placed either at different locations on the skin , or all at the location described above but with different angles to the skin . also a series of transducers provides an ultrasound ( combined ) signal , which signal provides more accurate information , e . g . on an amount of liquid . this allows e . g . for broad resonance mode actuation , build from the adjacent resonant frequencies . it requires less damping for a broad frequency spectrum compared to prior art systems as the broadening per peak can be less if several peaks of adjacent frequencies are excited simultaneously . this allows for better energy efficiency and it saves power in the scan head , which will as a result have a more or less constant temperature . in an example the present device may function as a multichannel device . in an example the present wearable device comprises a series of transducers , each transducer individually providing an ultrasound having a frequency and a power , the series providing a multi - frequency spectrum of ultrasounds and / or powers . therewith an adaptable signal can be provided , for obtaining reliable and adequate results . high end applications , such as for 3d - imaging , may have a large number of transducers , such as 2 14 . applications such as a bladder monitor may have a relative small number of transducers . medium end applications , wherein for instance some image formation is required , may have 10 - 1000 transducers . in an example of the present invention the transducers are capable of operating separately , sequentially , in phase - shift mode , in parallel mode , in frequency scan mode , in spatial scan mode , in intensity mode , in pulsed mode , variations thereof , and combinations thereof . in addition it is also possible to use at least one frequency , such as harmonic frequencies . in an example operating is switched from one mode to another , and / or from one ( series of ) frequency to another ( series ). as such it has been found that determination of the liquid volume is improved in accuracy , error rate , etc . in an example of the present invention the device is wireless , and comprising a transceiver for ( wireless ) communication between the device and an external supporting device . the transceiver preferably is capable of operating using one or more of blue - tooth , 1g , 2g , 3g , 4g , zigbee , wifi , peer - to - peer communication , optical communication , infrared communication , near field communication , rf - communication , and ultrasound communication . the device may connect to a read out system , wired or wireless powered , for measuring and calculation of the bladder / urine volume , and communication of this value like by a display or alarm function . in an example the present invention the device comprises stored on the device and / or stored on the external supporting device software . the software is for one or more of processing data , filtering a signal , calculating a liquid volume , calculating a fill threshold , calculating a fill speed , operating the device , controlling the at least one transducers , performing statistics , such as removing outliers , determining an average , determining a standard deviation , calculating a filling level , calculating a relative filling grade , predicting parameters , such as fill rate and fill level . the device may comprise at least one apodization filter , which optionally is a software apodization filter . the filter may correct for signals provided by the present system and reflections obtained , e . g . the position sensor . in an example the software is one or more of self - learning , adaptable , and neural network based . as such for any given individual user the present device can be optimized during use , providing optimised settings . when a user makes use of subsequent or sequential use of the present device , i . e . using a first device , then using a second device , and so on , the optimized use settings of a first device can be transferred to a subsequent or sequential device , thereby maintaining and optionally further improving a use . likewise data can be transferred . the software and settings may be stored on the device itself , on an external supporting device ( being in ( wireless ) contact with the ultrasound device ), or both . in an example of the present device the contacting means comprises an acoustical matcher between the skin and the transducer / device . an example thereof is a gel for establishing contact between the device and the skin . it is preferred to use a polyisocyanopeptide based thermo gel . the thermogel stiffens upon temperature increase , contrary to ordinary gels . an improved contact is established therewith . in an example in view of prolonged use a gel having wetting ability and curing / hardening upon temperature increase is used . the polyisocyanopeptide based thermo gel has such properties . on top of that the polyisocyanopeptide based thermo gel can be used in minute amounts ( mgr ./ litre ), it is biocompatible , safe ( non - toxic ) in use , can be applied as a spray , etc . in an example a package for containing the gel may be used . in view of the above further properties it preferably is a semi - permeable package , such as a gel pad . in an example the present device comprises two or more posture sensors , typically three or more . included in the sensor or in the device maybe software for interpretation of data obtained and for further use of said data . in a further example a ( further ) posture sensor may be provided at a more remote place such as on a leg , a thigh or a side of the belly . the present at least one posture sensor is preferably a tilt sensor . an advantage of such a sensor is that it consumes much less energy compared to other sensors , partly due to an absence of a need to measure continuously and to interpret data continuously . it is noted that a single measurement to determine posture is often sufficient for the present purpose . in between measurements the sensor may be in idle mode ; the period of the idle mode can be from seconds to 30 minutes . no integration of a signal is required , nor further manipulation of the signal . such also limits generation of noise , either directly on the signal or as a by - effect . the tilt sensor may relate to a ( partly ) free standing membrane , a mass spring system , a magnetic field detector , and combinations thereof . the present sensor is also much more accurate and reliable than other comparable sensors . in an example the present device comprises a movement sensor , such as an accelerometer , gyroscope , and a magnetic sensor . the sensor may be a 1d , 2d and 3d sensor . when a gyroscope is added a limit use thereof is preferred , e . g . in view of energy consumption . it has been found that movement of a user disturbs a determination . false signals , biased signals , erroneous signals , etc . may be generated . by providing a movement sensor a determination can be postponed , rejected , repeated , etc . based on the information retrieved from the sensor . an example of an accelerometer is an adxl362 ( of analog devices , see datasheet 2012 - 2014 , rev . c ). as such reliability and practical use of the device can be enhanced . in general by making use of a position of a user , movement of a user , and so on , unnecessary measurements can be prevented , a quality of monitoring can be improved , energy consumption can be reduced , etc . such information can also be considered as an indication of a user &# 39 ; s health ; this information can be used to optimize a use of the present device . in an example the present device comprises one or more of an alarm generator , a false signal detector , a false contact detector , a touch sensor , a pressure sensor , a clock , a timer , a multiplexer , an activator , an electric stimuli generator , a vibrator , an adc , an amplifier , a led for signaling , a sound generator , a gps - sensor , and an on - off button . the alarm generator provides an alarm if e . g . a preset value of liquid volume is exceeded . the false signal detector identifies false signals and may generate e . g . a repetition of the determination . if contact between the device and skin is insufficient or failing the false contact sensor may generate a signal . the touch sensor provides information of contact as well . the pressure sensor can be used e . g . during delivery of a baby . the clock and timer can be used to generate pulses at a given time and time interval , such as a predetermined time and time interval , respectively . the multiplexer addresses the individual transducers in a pre - determined manner . the activator may provide a signal to a user in order to activate the user , such as to visit the toilet , such as by providing an electric stimulus , by a vibrator , by a sound , such as a beep , etc . in an example of the present device the contacting means are removable from the device . as such the same device may be re - used , such as be replacing an improper contact . in an example of the present device the positioner is an adhesive , a strap , a belt , a blister , and combinations thereof . the positioner is preferably as small as possible , such as an adhesive , in order to improve wearability . in an example of the present device the device is one or more of an ic , an asic , a mems , a printed circuit board ( pcb ), and combinations thereof . it is preferred to have a very small device , in view of costs , manufacturability , ease of wear , replaceability , etc . in an example the present device comprises one or more of transceiver , for communicating with an outside world , an rfid , a unique identification code and at least one threshold , the threshold for determining a pre - set unique minimum amount of liquid . with the rfid and / or unique code information on a user and the device can be linked to one and another , and passed on . also in view of caretaking signals received from the present device can be linked directly to a user ( patient or client ) wearing the device and appropriate action can be taken , if necessary . in view of action a unique threshold can be used . in an example of the present device the device is integrated , such as in a disposable . the disposable may be a blister . the integration may also be in a handheld device , such as a scanner , which may be used in a hospital or the like . in an example of the present device the voltage source and the at least one transducer are in electrical contact , optionally with an intermediate multiplexer , preferably a low capacitance contact , such as by a bond wire , bond ball , and interconnect . in an example of the present device it consists of one integrated package . in an example of the present device the positioning means and contacting means are one and the same , such as in a blister , a piece of tape , adhesive plaster , and elastoplast . in a second aspect the present invention relates to a use of the present device for monitoring a liquid volume , such as in a body part , such as in a bladder , in a joint , in a gut , in a prostate , in the thorax , in the pericardial sac , in the meninges or cerebrospinal area , and in a blood vessel , for detecting aneurism , for detecting infection , such as in a bladder , for detecting dehydration , for measuring the amniotic fluid in the uterus , for detecting urine influx rate from at least one kidney , for determining a liquid volume in a lung , for pleural effusion , for cardiac tamponade , for hydrocephalus , for training , for ultrasound image forming , such as in an endoscope , and in a catheter , for warning , for continuous monitoring over longer periods of time , for monitoring during normal life , and for monitoring in and outside a hospital or caretaking environment . in other words the present device has found a wide range of applications , which have been detailed partly throughout the description . in a further aspect of said the present device is used in combination with a further device , such as an emg , optical transmitter , near infrared transmitter , electromagnetic wave transmitter , temperature sensor , and microphone for additional signaling or for gathering additional information on the patient . the present device may be used for continuous or semi - continuous monitoring of ballooning of arteries , aneurysm of the aorta , and blood vanes , possibly located close to the bladder . for such applications a higher resolution than needed to detect the volume of the bladder may be required . such a resolution can for instance be provided by using mems transducers ; an image of blood vanes is possible . using an image it can be observed if ballooning occurs . bursting blood vessels can lead to death by internal bleeding if no medical surgery is applied within minutes . another use relates to a flow meter or sensor , such as for urine flow and blood flow . a differences in volume per unit of time can be monitored during e . g . urination . in a third aspect the present invention relates to a method of operating the present device comprising the steps of determining an amount of liquid in a bladder , based on the amount determined , performing a further act , such as changing a diaper , visiting a toilet , catheterizing , or refraining from further action . with the amount determined for each individual user , e . g . based on historical data , a filling level or the relative filling grade may be determined . these latter may be regarded as an indication of when a user needs to visit a toilet . in the present method preferably at least one calibration curve is ( first ) established and used . the curve may also be established during use . in an example of the present method the ultrasound device provides a signal if a pre - set unique minimum amount of liquid is exceeded , such as by a sound , an optical signal , vibration , electric stimulus , wireless communication to an observer , to a smartphone , to a mobile phone , to a tablet , to an app , to a computer , to a server , wherein the signal preferably comprises a unique code identifying a person and / or ultrasound device , and a location of said person or device . such further measures support proper operation of the present device . in an example of the present method the at least one first transducer provides at least one pulse at one or more of a given time - interval , a given time , a pre - determined time , upon error - detection for generating a warning . herewith a time interval , and / or a time where upon a measurement may take place can be controlled . also if an error is detected appropriate response can take place , such as a repetition of a measurement . in an example of the present method the at least one first transducer has a center frequency of 20 khz - 50 mhz , an active area of 4 * 10 − 4 - 2000 mm 2 , such as 100 - 500 mm 2 , a near field length of 0 . 1 - 50 mm , such as 1 - 20 mm , is positioned at an angle of 5 - 15 degrees relative to the skin , and wherein the at least one second transducer is positioned at an angle of 0 - 50 degrees relative to the skin , preferably 5 - 45 degrees , such as 10 - 30 . when a mems is used an active area may be 4 * 10 − 4 - 10 2 mm 2 . these settings and dimensions have found to give the best results . in an example of the present method the ultra sound signal is combined with a further signal , such as temperature , or tilt . in a further example information such as from anamnesis of patient such as age , family background , behavior , etc . may be combined . in an example such and other signals are analyzed with statistical methods , such as bayesian statistics , neural networks , and self - learning algorithms , to derive quantitative information on e . g . status or degree of filling ( excess ) of the bladder or other organs ; such information may be used as a basis for an alarm for intervention . the invention is further detailed by the accompanying figures and examples , which are exemplary and explanatory of nature and are not limiting the scope of the invention . fig1 is a schematic set - up of part of the present device . fig2 is a schematic set - up of the present device . fig3 - 4 show a schematic set - up of the present device . in fig1 a schematic set - up of part of the present device is given . therein a number of ( 6 ) transducers ( n ) is attached to the device comprising electronics ( p ). the transducers ( n ) are connected to the electronics ( p ) via a cable . in the electronics a multiplexer ( f ) selects one of the transducers ( n ). a high - voltage driver ( d ) generates a pulse that excites the transducer such that it generates an ultrasound wave . the transducer converts the reflected ultrasound wave into an electrical signal which is amplified by a low noise amplifier ( m ). a signal dependent attenuation is compensated for by an optional time gain amplifier ( l ) which can be configured digitally by using a digital - to - analogue converter ( h ). after digitization of the signal by the analogue - to - digital - converter ( k ), the data can be stored in a volatile memory ( a ) and non - volatile memory ( g ), such as an sd card . signal processing can be performed on the device using the digital configurable logic , such as an fpga ( j ), possibly combined with information from a posture sensor ( b ). the information obtained can be send wirelessly to a computer , phone or tablet by a wireless transceiver ( c ). further a power supply ( i ) and a t / r switch ( e ) are shown . in fig2 a schematical set - up of the present device is given . therein a positioner 1 in the form of a ribbon is shown . the device is connected to electronics by a wire 4 . the present ultrasound transducer ( s ) and optional further components are in a casing 2 . the positioner 1 comprises a recess which fits an optional positioning knob 3 for further precisely positioning the device . measured ultrasound signals are processed using specifically made software . before interpretation of the data , the received signals will first be pre - processed by filtering and / or amplifying the signal . this step reduces the influences of high and / or low frequency noise in the signal . a time - gain amplifier and / or a band pass frequency filter may be used . furthermore , the signals will be analysed by a custom - made algorithm , which will determines the time between the echo pulses , which is used to calculate a distance between the front wall and back wall of the bladder ( bladder depth ) by multiplication of this time lapse with the speed of ultrasound in the body . using a bench - top setting several measurements were made in healthy adults proofing that the distance between an anterior wall and posterior wall can be measured and that the distance measured varies based on the degree of filling of the bladder . an algorithm is used to make the above visible and enable the setting of an alarm , if relevant . a technical design ( attached ) has been made for a clinical prototype which encompasses all elements currently thought to be necessary to be effective . this clinical prototype may be worn semi - permanently . using the transducer to be used in the clinical prototype in combination with a time - gain amplifier and the bench - top set used earlier , measurements have been made in healthy adults and these have been compared to measurements made by an expert using standard ultrasound . the bladder depth measured is compared with earlier measurements and possibly with the predicted course of the increase of the bladder depth , and the algorithm determines if the measurement is in line with expectations . unexpected outliers are discarded and new measurements may be made . repeated unexpected results may cause an alarm being set off to warn the wearer and / or his caretaker ( s ) that the device may not be working properly . the present algorithm also determines if the alarm should be activated by using one or more of the rules set out below : 1 . if the measured bladder depth exceeds a predetermined limit , the alarm is set off . this limit may be based on : age , and / or length , and / weigh , and / or gender / sex of the wearer ; or maybe be determined individually ( see below ) 2 . by comparing the new measured bladder depth with the previous measurements , the algorithm determines the increase in bladder depth . when the bladder becomes completely full the increase in bladder depth will slow down , or even stop completely , and an alarm is set off . 3 . if the time since a last urination exceeds a predetermined time the alarm is set of . this predetermined time limit may be set individually or be based on age , weight , length and or gender / sex of the wearer . parameters used by the algorithm to determine the moment that the alarm is set off may be tuned individually to adjust for the individual situation . this may be done manually and / or automatically : the algorithm may be self - learning , in a way all the relevant data of a user are saved and by using a built - in algorithm the system will calculate the best individual limit for setting off the alarm . relevant parameters and indicators may be status of a pregnancy , age , weight , sex , medical history , post - operative situation , medication , and anaesthetic . the algorithms used for determining bladder depth , the moment for setting of the alarm and regulating individual limits , may also use data on posture and movement as generated by a accelerometer of other movement and / or posture sensor either as part of the device or separate . an algorithm is used to determine an optimal position of the device , such as by searching an echo of a signal . the amplitude and characteristics are required to fall within pre - set boundary conditions . an algorithm is used to establish a quality of a signal ; if required a measurement can be repeated , improved , such as by phase - shift , etc . algorithms may be present for detecting aneurism , amount of rest urine , dehydration , etc . additional transducers may be present for said purpose . an algorithm may be present for providing bio - feedback , e . g . in order to train a user , such as a child . an algorithm may be present to minimize energy consumption , e . g . by taking into account a learning curve . an algorithm may be present to set an alarm when the bladder is 80 % filled , and when it is fully filled . an algorithm is used to measure a thickness of the belly wall and of belly fat . this measurement is used to further optimise functioning of the present device . an error detection algorithm is present , e . g . for detecting “ absence ” of a bladder . initially a first transducer is excited with a voltage pulse and an echo is detected by a second transducer if an echo signal is sensed within a pre - set time interval for the echoes from the front and back of the cavity with liquid . for instance in case of a bladder a pre - set time is close to the time interval of 20 microseconds and 200 microseconds , for a front and back wall respectively . the echo signals are recorded by the second transducer . after repeating this for several first and second transducers and recording the strength of the echo signals , those transducers are selected having a suitably strong echo signal for further use . in an alternative the first and second transducer are one and the same . using these selected transducers a measurement is executed as a sequence of , for instance , 5 pulses and detection of the echo after each pulse . the time difference between de first and second echo &# 39 ; s within the interval is used to calculate the distance between front and back wall of the cavity , in this example the bladder . with an algorithm , depending on the angular viewing angles of the transducers along all directions , the size of the cavity is calculated . the use of the present device may involve an initiation procedure when the device is positioned , such as on the body of a human being for detection of a liquid filled cavity , such as a bladder . during the initiation voltage pulses are applied at a set of one or more first transducers , and after detection of echo signals on second transducers during a pre - set time window , an algorithm determines which transducers give a favourable signal , which leads to a selection of a set of transducers for an optimized operation with more ( further ) pulse excitations . at installation of the present device on a person , the tuning may be done with the help of a doctor or professional help for optimized viewing angles and time intervals for having a good signal . in an example of an application , the present device can be used to determine the rest urine after letting out urine naturally , as rest urine is considered a main cause for infections . an advantage over existing rest urine equipment is that with the present device the patient is free to move around while waiting to urinate without a required presence of a health care professional who will use a handheld non - wearable device for measurement of the rest urine . by adding a self - adhesive tape or pad , the present bladder monitor can be properly positioned against a patient &# 39 ; s abdomen without irritation to the skin . the material of the tape or pad is preferably water based , for example a silicone gel . examples of current clinical applications using these kind of materials are wound dressings , bandages , and scar management . another clear example of using medical - grade , self - adhesive silicone is the nubra ®, a strapless , backless adhesive bra . an advantage of using self - adhesive silicone is that it can be used multiple times and also allows proper acoustic coupling for ultrasound applications . e . g . without a use of an ultrasound gel . an important aspect in ultrasound imaging is found to be the ultrasound coupling . currently , liquid ultrasound gel is used to minimize the acoustic interference of air . however , by using this method , the ultrasound will eventually dry out . in this respect a patch is considered consisting of a chamber which holds an ultrasound transducer . the transducer faces outward towards the opening of the chamber . inside the chamber , a quantity of ultrasound conductive medium is placed to keep contact with the surface . to minimize a loss of ultrasound medium , it is possible to introduce a semi - permeable membrane . such may include a semi - permeable membrane that is configured to be “ leaky ”, thereby allowing the contact surface to become slight wet , and allowing efficient ultrasound transmission . the semi - permeable membrane can be thin for efficient ultrasound energy transfer , and to allow liquid to wet the contact surface of the body of ultrasound transmission ( e . g . a human ). the prototype comprises an non - slip strap fixed on the inside of an elastic belt , to increase stability and reduce movement ; a self - adhesive silicone tape 21 to position the bladder monitor assembly against the abdomen of a patient ; optionally the bladder monitor can be integrated into a special developed undergarment / pant ; in addition a silicone barrier ( ring ) 22 may be provided . considering the conductive ultrasound medium , experiments are performed to determine if the self - adhesive silicone tape 21 resulted in accurate enough measurements of the bladder diameter ( by ultrasound ). if the transmission of ultrasound is reduced , a liquid coupling may be used . the liquid coupling gel 23 may be in the middle in front of the transducer . the self - adhesive tape will secure the position of the sensor against the abdomen . when an elastic band ( or pants ) is used to position the present device , a non - slip strap can be made on the inside of a belt . the non - slip strap is found to increase the friction with the skin , keeping the belt ( properly ) more in place . another possibility is an integration of the present bladder monitor into the undergarment of the patient . in 2008 , phillips published a patent application ( wo 2008 / 004159 a2 ) for an integrated wireless module into the undergarment of the patient . the patent points out that “ it is particularly suitable for implementation in a continuously wearable undergarment with integrated measuring sensors or electrodes , so as to be directly in contact with the subject &# 39 ; s skin .” a pants prohibits the upwards movement of the present bladder monitor , as result of the strap between the legs . however , without a direct / airless connection to the skin , the bladder monitor will not be able to measure accurate data . for this reason , an undergarments is only useful , when the transducer assembly is in addition stuck to the skin ( for example by a silicone adhesive tape ). an example of a suitable tilt sensor is an adafruit learning system tilt sensor . the sensor has a sensitivity in a range of ± 15 degrees , requires a power supply of 24 v and 5 ma . the tilt sensor can be integrated with microcontroller , such as a texas instrument msp430f2012 . in addition further integration is possible , such as into a circuit board layout or ic . see for example document slaa309 of june 2006 in this respect . the invention although described in detailed explanatory context may be best understood in conjunction with the accompanying examples and figures . | a wearable ultrasound device for signalling changes in human or animal body , and use of such a wearable device for signalling over a prolonged period of time . in an example the changes occur in a bladder . such is especially relevant for elderly persons , women after delivery of a baby , lesion patients , demented people , children , and others , have a difficulty to control functioning of the bladder , and to be at the toilet on time to urinate . |
exemplary embodiments are described in greater detail below with reference to the accompanying drawings . in the following description , like drawing reference numerals are used for like elements , even in different drawings . the matters defined in the description , such as detailed construction and elements , are provided to assist in a comprehensive understanding of the exemplary embodiments . however , it is apparent that the exemplary embodiments can be practiced without those specifically defined matters . also , well - known functions or constructions are not described in detail since they would obscure the description with unnecessary detail . in describing layer structures , when an element or layer is referred to as being “ on ” another element or layer , the element or layer may be directly on another element or layer or intervening elements or layers . fig1 illustrates a biometric analysis system 100 according to an exemplary embodiment . referring to fig1 , the biometric analysis system 100 may include a biometric sensor 11 and a control unit ( e . g ., controller ) 14 . the biometric sensor 11 may emit light l 11 onto a region a 1 of interest of an object 10 under examination and acquire diffused light l 12 that is reflected from the region a 1 of interest . the control unit 14 may analyze biometric information of the object 10 by using the diffused light l 12 obtained from the biometric sensor 11 . the biometric sensor 11 may include a light source unit ( e . g ., light source ) 12 that emits the light l 11 to the object 10 and a spectrometer 13 that measures the diffused light l 12 generated from the region a 1 of interest . the control unit 14 may include a signal processing unit ( e . g ., signal processor ) 15 and a user interface 16 . also , the biometric analysis system 100 may further include a storage unit ( e . g ., storage or memory ) 18 that stores the biometric information of the object 10 that is processed in the signal processing unit 15 . the biometric sensor 11 used in the biometric analysis system 100 according to an exemplary embodiment is a non - invasive biometric sensor and may include the light source unit 12 and the spectrometer 13 , which will be described in detail below . the light l 11 may be emitted from the light source unit 12 of the biometric sensor 11 onto the region a 1 of interest of the object 10 . the type of the light l 11 may be selected in connection with biometric information to be obtained from the object 10 under examination . for example , the light source unit 12 may emit light of near infrared region having a wavelength in a range from about 0 . 7 μm to about 2 . 5 μm . a light source used in the light source unit 12 may include a light emitted diode ( led ) or a laser diode . the light l 11 may collide with a surface and internal molecular structure of the object 10 under examination , and may become a diffused light l 12 , a wavelength of which is changed when the diffused light l 12 is re - emitted after being absorbed in the molecular structure . the diffused light l 12 may include various spectrums due to different degrees of wavelength transformation according to the state of molecules that constitute the region a 1 of interest of the object 10 . accordingly , the diffused light l 12 emitted from the region a 1 of interest may include biometric information of the region a 1 of interest , and thus , biometric information ( e . g ., blood glucose contents ) may be obtained by analyzing the diffused light l 12 . the light l 12 may be diffused in all directions , and thus , in order to correctly detect the biometric information of the object 10 , the diffused light l 12 may be required to be transmitted to the spectrometer 13 with minimum loss . accordingly , a collimator may be included in the biometric sensor 11 to collimate the direction of the diffused light l 12 reflected from the object 10 in a constant direction towards the spectrometer 13 . an optical reflection material layer to reflect the diffused light l 12 towards the spectrometer 13 may be formed in the collimator , and the optical reflection material layer may have a compound parabolic concentrator ( cpc ) shape . the biometric sensor 11 according to an exemplary embodiment employs an optical system structure by which the light l 11 is emitted onto the region a 1 of interest and the diffused light l 12 reflected from the region a 1 of interest may be input to the spectrometer 13 . fig2 is schematic view of the biometric sensor 11 of a biometric analysis system according to an exemplary embodiment . referring to fig2 , the biometric sensor 11 may include a light source 22 that emits light l 21 onto a region a 2 of interest of the object 20 under examination and a collimator 26 that causes a travel direction of diffused light l 22 to be aligned in a certain direction . the light source 22 may emit light in a near infrared region having a wavelength in a range from about 0 . 7 μm to about 2 . 5 μm , and may include an led or a laser diode . the travel direction of the diffused light l 22 may be collimated in a constant direction by the collimator 26 . an opening for exposing the region a 2 of interest of the object 20 may be formed on a region of the collimator 26 . a focusing element 24 may be disposed on an optical path via which the light l 21 emitted from the light source 22 is emitted onto the region a 2 of interest of the object 20 under examination that is exposed through the region of the collimator 26 . the focusing element 24 may be , for example , a focus lens . the light l 21 emitted from the light source 22 may be incident onto the region a 2 of interest through an appropriate focal distance control by the focusing element 24 . a window ( e . g ., through - hole ) 28 may be formed on a side of the collimator 26 on the optical path of the light l 21 so that the light l 21 reaches the region a 2 of interest . the light l 21 emitted from the light source 22 may be focused on the window 28 of the collimator 26 by the focusing element 24 . in this manner , since the focusing element 24 and the window 28 are formed on the optical path , the light l 21 emitted from the light source 22 may be incident onto the entire region a 2 of interest , and thus , a maximum irradiation region may be ensured . also , an excessive exposure of the region a 2 of interest to the light l 21 may be prevented by adjusting the light l 21 emitted to the region a 2 of interest . accordingly , an optical loss may be prevented , high efficiency spectrums may be ensured , and a signal - to - noise ratio may be improved during a biometric information analysis . the light l 21 emitted onto the region a 2 of interest may collide with a surface and internal molecular structure , and may be emitted as a diffused light l 22 , a wavelength of which is changed when the diffused light l 22 is re - emitted after being absorbed in the molecular structure . the emitted diffused light l 22 may be collimated in a constant direction , for example , towards the spectrometer 13 of fig1 by the collimator 26 . fig3 is a schematic view of a biometric sensor according to another exemplary embodiment . referring to fig3 , a light source of the biometric sensor according to the current exemplary embodiment may include a light source 32 that emits light l 31 onto a region a 3 of interest of an object 30 under examination and a focusing element 34 that is formed on an optical path between the region a 3 of interest and the light source 32 . the biometric sensor may include a collimator 36 that adjust a travel direction of diffused light l 32 reflected from the object 30 to be aligned with a spectrometer . for example , the collimator 36 may cause the travel direction of the diffused light l 32 to be parallel to a lengthwise direction of the collimator 36 . a region of the collimator 36 may be opened to expose the region a 3 of interest to the outside . a window 38 may be formed on a side of the collimator 36 on the optical path via which the light l 31 emitted from the light source 32 is incident onto the region a 3 of interest . the light l 31 emitted from the light source 32 may be focused on the window 38 of the collimator 36 by the focusing element 34 . the window 38 may be an opening or a through - hole placed on a side of the collimator 36 , and may be a region on which the light l 31 emitted from the light source 32 is focused . a width of the window 38 may be appropriately controlled and is not specifically limited . in comparison to the optical sensor of fig2 , in the optical sensor of fig3 , an incidence angle of the light l 31 is almost 90 ° with respect to the region a 3 of interest . in this manner , the optical sensor according to the current exemplary embodiment may emit the light l 31 with various incidence angles to the region a 3 of interest , and an optical irradiation region and optical density with respect to the object 30 may be controlled . fig4 is a schematic view of a biometric sensor according to another exemplary embodiment . referring to fig4 , a biometric sensor according to the current exemplary embodiment may include a light source unit that includes a light source 42 that emits light l 41 onto an region a 4 of interest of the object 40 under examination and a focusing element 44 formed on an optical path between the light source 42 and the region a 4 of interest . the optical path between the light source 42 and the region a 4 of interest may be variously controlled . in order to control the optical path , the biometric sensor according to the current exemplary embodiment may further include an optical path converter 45 . in fig4 , as an example , the optical path converter 45 has a prism type . however , the optical path converter 45 may be a mirror having a flat panel type or a beam splitter . the biometric sensor may include a collimator 46 that induces the travel direction of diffused light l 42 towards a spectrometer 400 . a region of the collimator 46 may be opened to expose the region a 4 of interest . a window 48 may be formed on a side of the collimator 46 via which light , an optical path of which is changed by the optical path converter 45 after being emitted from the light source 42 , is incident onto the region a 4 of interest passing through the collimator 46 . the window 48 may be a region on which the light l 41 emitted from the light source 42 is focused . a width of the window 48 may be appropriately controlled , and is not specifically limited . an angle θ between the collimator 46 and a surface may be appropriately controlled to readily collimate the diffused light l 42 emitted from the region a 4 of interest to the spectrometer 400 , and the angle θ is not specifically limited . as described above , in the optical sensor according to the current exemplary embodiment , the optical path of the light l 41 emitted from the light source 42 may be converted by the optical path converter 45 to have various optical paths . also , the light l 41 may be emitted onto the region a 4 of interest with various angles , and the control of an optical irradiation region and an optical density with respect to the object 40 under examination may be possible . fig5 is a cross - sectional view of a structure that includes an optical sensor according to an exemplary embodiment . the structure of fig5 includes the biometric sensor of fig4 . referring to fig5 , the structure may include a housing 500 and a light source 52 that emits light and a focusing element 54 located on an optical path of the light emitted from the light source 52 that are located within the housing 500 . the housing 500 may also include an optical path converter 55 that may change an optical path of the light emitted from the light source 52 . here , a light source unit may include the light source 52 , the focusing element 54 , and the optical path converter 55 . a collimator 56 may be formed on a region of the housing 500 . an opening 51 may be formed on a region of the collimator 56 and the housing 500 . the opening 51 may be located on a region of interest of an object under examination . a window 58 may be formed on a side of the collimator 56 via which light emitted from the light source 52 enters the opening 51 . a spectrometer 59 at which diffused light emitted from the collimator 56 is collimated and focused may be formed on an edge of the collimator 56 . the housing 500 that surrounds the biometric sensor may be formed of various materials , for example , flexible materials . also , the housing 500 may be formed of a material that blocks external light . the biometric sensor may be a wearable device to be worn on the object 10 under examination , for example , may be a bracelet type device that can be worn on a wrist . at this point , all of the constituent elements of the biometric analysis system 100 as depicted in fig1 may be included in the wearable device . also , optionally , only the structure of the light source unit 12 may be mounted in the wearable device and a signal of the diffused light l 12 measured by the spectrometer 13 may be transmitted to an external device . also , the light source unit 12 may be implemented as a wearable device and the control unit 14 may be embodied separately from the wearable device . fig6 is a flow chart illustrating a method of biometric analysis by using a biometric analysis system according to an exemplary embodiment . referring to fig1 and 6 , the region a 2 of interest of the object 20 under examination may be determined to obtain biometric information from the region a 2 ( operation s 1 ). for example , in order to measure a blood glucose content of a human body , a wrist portion may be designated as a region of interest . the light l 21 is emitted onto the region a 2 of interest from a light source of the light source unit 12 ( operation s 2 ). while the region a 2 of interest is in contact with a boundary of an opening of a collimator , a laser light in a region of near infrared having a wavelength in a range from about 0 . 7 μm to about 2 . 5 μm may be emitted onto the region a 2 of interest from the light source unit 12 . when the light l 21 is incident onto the region a 2 of interest , diffused light l 12 that includes biometric information of the region a 2 of interest may be emitted from the region a 2 of interest . the diffused light l 12 is collimated by a collimator and is detected by the spectrometer 13 ( operation s 3 ). the diffused light l 12 detected by the spectrometer 13 is transmitted to the control unit 14 where biometric information or biometric signal of the region a 2 of interest is analyzed ( operation s 4 ). the control unit 14 may include a signal processing unit 15 that analyzes the biometric information of the object 10 under examination from the signal that is generated from the diffused light l 12 and is measured by the spectrometer 13 . the signal processing unit 15 may be driven by a microprocessor . the signal processing unit 15 may analyze properties of the object 10 under examination by using the raman spectroscopy or a method of analyzing a near infrared ray absorption spectrum . when the light l 21 is emitted into the object 10 under examination , the light l 21 is diffused in various directions after colliding with atoms or molecules in the object 10 under examination . the raman spectroscopy uses the diffusion , in particular , inelastic scattering of the light l 21 in various directions . here , inelastic scattering denotes the emission of light after being absorbed by the atoms or molecules as opposed to merely a simple reflection at surfaces of atoms or molecules . the diffused light l 12 emitted from the object 10 under examination may have a relatively longer wavelength than that of the incident light l 21 , and a wavelength difference between the light l 21 and the diffused light l 12 may be approximately below 200 nm . various properties , such as vibration of molecules and a structure of molecules in the object 10 under examination may be detected by analyzing a spectrum of the diffused light l 12 . the control unit 14 may further include the user interface 16 , and the user interface 16 may further include an input unit through which various commands are inputted in a process of analyzing biometric information and a display unit on which a biometric analyzing process and the result are visually displayed . next , the analysis result of the biometric information of the object 10 under examination may be stored in the storage unit 18 by the control unit 14 . optionally , after analyzing the biometric information of the object 10 under examination by the control unit 14 , a process for comparing the measured biometric information with biometric information of the object 10 under examination stored in advance may be performed . the results of the comparison and evaluation may be restored in the storage unit 18 . the biometric sensor according to an exemplary embodiment may prevent an optical loss of diffused light that is emitted from an object under examination after emitting the light from a light source onto a region of interest of the object under examination . since a focusing element and a window are formed on an optical path of light that is emitted from a light source onto an object under examination , a required irradiation region may be ensured and an excessive exposure to light may be prevented . also , a high efficiency spectrum may be ensured and a signal - to - noise ratio may be improved . the foregoing exemplary embodiments are merely exemplary and are not to be construed as limiting . the present teaching can be readily applied to other types of apparatuses . also , the description of the exemplary embodiments is intended to be illustrative , and not to limit the scope of the claims , and many alternatives , modifications , and variations will be apparent to those skilled in the art . | a biometric sensor that measures biometric information and a biometric analysis system including the biometric sensor are provided . the biometric sensor may include : a light source configured to emit light toward a region of interest of an object under examination , the light being diffused at the region of interest ; a collimator that includes a though - hole and is configured to collimate the diffused light received from the region of interest ; and a spectrometer configure to analyze the diffused light transmitted by the collimator . |
fig1 depicts a sump assembly of the present invention indicated generally by reference numeral 10 . sump assembly 10 includes distal suction means or drain 12 , a front elevational view of which is shown in fig2 fluidly connected to an elongated , tubular body or suction tube 13 . the drain 12 allows for suctioning or irrigation at the distal end of the sump assembly . the drain 12 has one or more ports 14 for entry of the secretions and fluids , and the number of ports employed , and formed into the distal end of the suction means , depends upon the degree of suction of vacuum means required in order to remove secretions of a select viscosity from its accumulation at the vicinity of the inward end of the previously employed and inserted endotracheal tube . the ports 14 in the drain permit entry of unwanted secretions into the drain 12 whereupon the secretions are removed via vacuum to a disposal receptacle . in addition , the drain 12 has a radiopaque mark 16 to indicate its inserted location . the radiopaque mark 16 allows for positioning the distal suction means appropriately with respect to the endotracheal tube 30 ( fig5 ) already installed . the drain 12 is generally in the form of a ring open at the bottom to permit fitting around the endotracheal tube ( see fig2 and 3 ). the drain 12 , may undertake any related shape , such as that as shown in fig1 , 6 or may even comprised openings 15 ( see , fig8 and 12 ) formed in the distal end of the tubular body 13 . thus , the shape of drain 12 is not necessarily critical to its functionality , but has to have sufficient structure . however , if the drain 12 also functions as a guide ring , as shown in fig1 and 5 , for example , it must be configured so as to allow for its slide along the endotracheal tube 30 tube , during its insertion , or removal , and to locate proximate the lower end of the endotracheal tube , and just above its inflated cuff 32 , so as to provide means for removal of the secretions accumulated at that location , and to minimize the risk of generating complications or infections , as previously explained . as a guide ring , the drain 12 generally is configured as a clip , as shown in fig2 . the assembly may include one or more additional guide rings 20 , also configured like clips , positioned along the length of the tube 13 in a spaced apart relationship , to facilitate insertion and removal as will be explained below . the relationship of the drain 12 of the present invention and the endotracheal tube 30 is depicted in fig5 where the drain 12 approaches the position of the cuff 32 of the endotracheal tube . when the endotracheal tube 30 is installed in the patient , the cuff 32 is inflated to provide a snug , secure fit . the cuff 32 is inflated by injecting air into the cuff by bulb 34 which retains the injected air by means of a valve 35 so as to cause the inflation of said cuff , and to prevent the secretions generated above the cuff 32 from permeating downwardly , and into the trachea , and to prevent its localizing therebelow and causing the type of infection as previously described . the bulb 34 may be formed as a pump , having resiliency to it , and by squeezing of the same , sucking air into the bulb and forcing it downwardly through the tubing 36 , to inflate the associated cuff 32 . obviously , the valve also allows for deflation of the cuff , when operated to achieve this result . but , because the cuff , when inflated , acts as a barrier against downward migration of such secretions , they accumulate above the cuff , and the purpose of this current invention is to provide means for evacuating those secretions before they cause deleterious problems to the patient , because of their presence . at the proximal end of the tube 13 is a connecting fitting 28 . the connecting fitting 28 can be connected to a vacuum source , such as a powered vacuum pump , a syringe or the like , or other suitable attachments . furthermore , the suction can be discontinued and materials , such as antibiotics or other medications , can be introduced into the fitting with a syringe , flow through the tube 13 to be instilled in the patient through the ports 14 in the drain 12 . the subject matter of this invention is to provide for a clamping of the sump assembly 10 onto the endotracheal tube 30 , as shown , and then sliding it by means of its guides whether the guides be a drain 12 , or only guide rings 20 , downwardly upon the previously implanted endotracheal tube , until it locates at the position desired . furthermore , in order to facilitate such manipulation , it is likely that lubricating means may be provided internally of the drain 12 , and the guide ring 20 , either in the form of some type of lubrication , which may be manually placed thereon , in order to reduce any friction generated between these components and the endotracheal tube . or , the tube 13 may be a compound tube , and have a separate channel that extends downwardly through the guide ring 20 , and into the drain 12 to dispense a small amount of lubricant thereon , during insertion and withdrawal of the assembly , in order to facilitate its application . or , even a separate tube , such as that similar to what is shown at 13 , may be applied to the guide ring 20 , and the drain 12 , to add lubrication in the manner as previously described . this device may also be utilized for delivery other materials , as stated above , such as irrigants , antibiotics , or other solutions into the vicinity of the lower end of the inserted endotracheal tube . additionally , diagnostic sampling of secretions may be performed , in order to provide for their testing , to determine the extent of any bacterial or other contamination , and the type of infection that may be generated at the vicinity of the cuff 32 , so that proper treatment may be prescribed . as can be seen in fig6 and 7 of the drawings , the endotracheal tube 30 , with its previously located cuff 32 , and having its air tube 36 attached thereto , will have been emplaced into the trachea and downwardly into the vicinity of its final location . in an alternative embodiment the tubular body or tube 13 , is preformed into a spiraling configuration , as can be noted , and can be applied to the endotracheal tube 30 , by turning or rotating , in a manner of threading to provide for its shifting downwardly upon the endotracheal tube 30 , as it is turned , in a spiral fashion , to attain a locating of drain 12 just proximately above the cuff 32 , and once it achieves this location , its intake ports 14 will allow for evacuation of secretions accumulated at that location , just above the cuff , to attain the results as explained for this invention . this is just an alternative or modification to the concept of this invention , which is to use a tubing , which may be turned in a screwlike motion , to thread it onto the tubing 30 , until such as it achieves a locating as disclosed in fig7 . thus , the spirally configured tube 13 will function as a guide , for the sump assembly , to provide for its subsequent locating downwardly within the trachea , in order to provide for the evacuation of the accumulation of fluids at that location , and hopefully a minimization of the generation of any infections , at that location . fig8 illustrates another embodiment of the sump assembly of the present invention , particularly the guides 40 . as can be seen , the embodiment of the invention shown in fig8 does not have a separate drain structure but includes drain openings 15 formed in the distal end of tube 13 . since there is no separate drain structure to function as a guide , this sump assembly includes a guide 40 at the distal end , proximate the openings 15 . furthermore , additional guides 40 are spaced toward the proximal end . the guides 40 are shown in greater detail in fig1 a - 10d and include a semicircular clip section 42 and a circular tube channel 44 formed like a boss at the tip of the clip . the tube 13 is positioned in the tube channel 44 and can be secured there in by ultrasonic welding or other appropriate means . the sump assembly illustrated in fig8 is installed on the endotracheal tube in the same manner as other embodiments . fig9 illustrates a representative embodiment of a sump assembly 10 of the present invention placed in a patient along with an endotracheal tube . for reference , the physiological structures of the patient will be referenced as landmarks and include the epiglottis e , the vocal cords v and the accumulated secretions s above the cuff 32 of the endotracheal tube 30 . as will be appreciated , the sump assembly 10 of the present invention is optimally placed adjacent the endotracheal tube 30 with a drain opening 15 accessible by the secretions s when suction is applied through the tube 13 . fig1 and 12 better illustrate the installation of a sump assembly 10 of the present invention adjacent an endotracheal tube 30 . as shown , the distally positioned guide 20 is placed over the proximal end of the endotracheal tube 30 . the assembly is urged down the endotracheal tube with the guide 20 keeping it adjacent the tube . as the sump assembly moves down the length of the endotracheal tube , subsequent guides 20 are attached to the endotracheal tube , as shown in fig1 . the endotracheal tube 30 illustrated in fig1 includes indexing marks 46 which can be aligned with indexing marks 48 on the sump tube 13 . alignment of the appropriate indexing marks aid in the proper positioning of the drain opening 15 with respect to the cuff 32 . fig1 a and 13b illustrate another alternative embodiment of guide . it will be noted that guide 50 includes a clip 54 and a tubing cradle 56 . the guide 50 is constructed from a resilient material , such as plastic . by applying pressure such as squeezing the legs 58 of the clip 54 , the cradle 56 opens for the insertion of the tubing 13 . release of the legs 58 of the clip allows the cradle to close and secure the tube 13 therein . variations or modifications to the subject matter of this invention may occur to those skilled in the art upon review of the summary herein , and upon undertaking a study of the description of its preferred embodiment . such variations may be within the scope of this invention . | a sump assembly having a tubular body with a drain at the distal end for use with an endotracheal tube which provides for the removal of the secretions around and near the endotracheal tube cuff , while the endotracheal tube remains in the nasal or throat passages of the patient . |
with reference to the figures , a feminine sanitary device 10 is described , shown , and otherwise disclosed herein in accordance with one or more preferred embodiments of the present invention . the device 10 of the present invention provides substantially improved protection over the prior art , particularly when the user assumes non - vertical positions , such as , for example , when reclining or laying in a prone , supine , or side position . preferably , the device 10 broadly comprises an elongated body including a central portion 12 , a back extension 14 , a front extension 16 , one or more raised areas 18 , and one or more wings 20 . referring particularly to fig3 a and 3 b , the body includes a substantially fluid - absorbent core 24 interposed between a substantially fluid - impermeable backing 26 and a substantially fluid permeable cover 28 for absorbing and retaining fluid . this cross - sectional construction is generally substantially consistent over the entire body , including the central portion and the extensions . the central portion 12 is substantially elongated and rectangular in shape and adapted for placement against the female genital area in much the same manner as a prior art pad . the back extension 14 is connected to or otherwise extends substantially continuously from a rearward end of the central portion 12 , presents additional surface area , and is adapted for placement against the user &# 39 ; s lower buttock area to absorb at least some of any fluid that may avoid absorption by the central portion 12 and flow rearward along bodily contours into this lower buttock area such as when the user is in a substantially supine position . the back extension 14 may have substantially any suitable simple shape , ( as shown in fig1 ) such as round or triangular , or complex shape ( as shown in fig2 ), such as round or triangular with appropriately shaped scallops , cut - outs , or other relief features 29 to more closely accommodate the user &# 39 ; s legs or other body parts . the front extension 16 is connected to or otherwise extends substantially continuously from a forward end of the central portion 12 , also presents additional surface area , and is adapted for placement against the user &# 39 ; s pelvic or lower abdominal area to absorb at least some of any fluid that may avoid absorption by the central portion 12 and flow forwardly along bodily contours when the user is in a substantially prone position . the front extension 16 may be given substantially any suitable simple shape , such as round or triangular , or complex shape , such as round or triangular with appropriately shaped scallops , cut - outs , or other relief features similar to those shown in fig2 to more closely accommodate the user &# 39 ; s legs or other body parts . referring particularly to fig4 , securement mechanisms 30 may be provided for one or more of the central portion 12 , back extension 14 , or front extension 16 in order to aid in maintaining the portion or area in its proper operating position . such securement mechanisms 30 may take the form of adhesive or hook - and - loop tape associated with a backside of the device 10 for removably securing it to an undergarment worn by the user . such securement mechanisms 30 may supplement or replace the one or more wings 20 which are discussed below . referring particularly to fig3 a and 3 b , the one or more raised areas 18 are located on the body in areas where fluid flow is likely to occur . while the fluid - absorbent core 24 extends substantially throughout the entire body , the areas 18 provide even greater absorbing ability or capacity . this enhanced ability or capacity of the areas 18 may be achieved either by use of a different and even more absorbent material than the super - absorbent core material , by use of additional thicknesses of the core or other material , or by any combination thereof to achieve the desired characteristic . such additional thicknesses of material provide a raised shape , such as a rounded swelling or even , as appropriate , a wedge , that results in more certain and sustained contact with the user &# 39 ; s body and therefore better protection . as shown in fig3 a and 3 b , the height of the raised areas 18 , 118 may vary from approximately between 0 . 25 inch to 1 . 0 inch based on a variety of factors , including , for example , desired absorbing capacity . the raised area 118 of fig3 b is substantially higher than the raised area 18 of fig3 a , potentially allowing the raised area 118 of fig3 b to both maintain closer contact with the user &# 39 ; s body and provide greater absorbing capacity due to its greater amount of absorbent core material 124 . it is contemplated that there may be any one or more of three such areas 18 : a vaginal area 32 , a rear area 34 , and a front area 36 . the vaginal area 32 may be provided with an appropriate shape , such as an elongated elliptical shape , and positioned in a center area of the central portion 12 . the rear area 34 may be provided with an appropriate shape , such as a triangular shape , and positioned rearwardly of the vaginal area 32 , such as near the intersection of the central portion 12 and the back extension 14 where the human body forms a natural crevice and intersection for fluid flowing rearwardly along bodily contours . the front area 36 may be provided with an appropriate shape , such as a triangular shape , and positioned forwardly of the vaginal area 32 , such as near the intersection of the central portion 12 and the front extension 16 to intercept fluid flowing forwardly along bodily contours . it is contemplated that the areas may be of equal , differing , or even varying height depending on the desired performance characteristics at that location . the raised areas 18 are preferably constructed of a material or materials and in such a manner that fluid absorbed by the raised areas 18 is able or even encouraged to migrate into adjacent areas of the device 10 so as to slow or avoid substantial or complete saturation of the raised areas 18 which might diminish or preclude further absorption and thereby diminish or preclude further performance or operation of the device 10 . the one or more wings 20 project outwardly perpendicularly from the central portion 12 of the body and function both to provide protection against fluid flowing sidewardly and to facilitate maintaining the device 10 in its proper operating position . preferably , one wing projects outwardly from each side of the central portion 12 , has some absorbent ability , and includes a securement mechanism , such as described above , to allow for securing the body to the undergarment worn by the user in an otherwise substantially conventional manner . from the preceding description , it will be appreciated that the feminine sanitary device of the present invention provides a number of substantial advantages over the prior art , including , for example , providing significantly improved protection , particularly when the user assumes non - vertical positions , such as , for example , when reclining or laying in a prone , supine , or side position . in particular , the oversized and appropriately shaped back and front extensions provide greater protection against fluid not absorbed by the central portion , and the appropriately located raised areas further improve protection . although the invention has been described with reference to the preferred embodiments illustrated in the attached drawings , it is noted that equivalents may be employed and substitutions made herein without departing from the scope of the invention as recited in the claims | a contoured and shaped feminine sanitary device comprising a substantially fluid - impermeable bottom layer , a substantially fluid - absorbent core , and a substantially fluid - permeable top layer , with at least one raised area and at least one of back or front extensions for facilitating and enhancing fluid absorption in certain areas and during certain activities . |
the hand - held power tool illustrated in fig1 is embodied as a trimmer 1 that has a drive unit in the form of an electric drive motor 2 . the electric drive motor 2 drives a tool 5 by means of a drive shaft 4 , guided and supported e . g . in a guide tube 3 . in the illustrated embodiment , the tool 5 is a cutting head 6 with a cutting string 7 . for protecting the operator who holds and uses the trimmer 1 , a safety shield 8 is arranged at the lower end of the guide tube 3 . by means of electric cable 9 the electric drive motor 2 can be connected to a stationary electrical power net ; alternatively , the drive motor 2 can be supplied by means of a battery , preferably a rechargeable battery 12 that is advantageously arranged in the housing of the power tool and enables cordless working . in the illustrated embodiment , a curved guide tube 3 is provided . straight guide tubes are of course also possible . the length of the drive shaft 4 is variable . it can be expedient to arrange the tool head 6 directly on the motor shaft of the drive motor 2 which then also has the function of a drive shaft 4 . in the illustrated embodiment , a handle 10 is provided on the guide tube 3 for holding and guiding the trimmer 1 . a second handle 11 can be provided expediently in the housing area of the drive motor 2 . as shown in fig2 , the electric drive motor 2 drives the tool head 5 by means of drive shaft 4 . the speed of the drive shaft 4 is detected by speed sensor 21 and supplied by means of signal line 22 to the control device 20 . moreover , a measuring arrangement 23 is provided for measuring current and voltage in the electric cord 9 and the detected values are supplied to the control device 20 by means of signal line 24 . based on the supplied data , the control device 20 can determine the power draw as well as the speed of the electric motor 2 and compare this to a first operating curve which is saved in a characteristic field . such an operating curve is illustrated , for example , in fig3 and provides information in regard to power p as a function of the speed n . in a first embodiment of the invention during operation of the electric drive motor 2 the power draw p and the speed n are permanently monitored and compared with this first operating curve i . this first operating curve i corresponds advantageously to an idle curve but can also be a different operating curve . the operating curve ii corresponds to a load curve . the first operating curve i covers a low power range at low speed while the second operating curve ii covers a large power range at higher speed . when during monitoring of the detected operating parameters of the electrical drive motor 2 it is determined that the resulting monitoring point 30 deviates from the operating point 31 of the operating curve i , expediently the magnitude of the deviation from the operating curve i is determined in the control unit 20 and , depending on the output signal , switching to a different operating curve ii is triggered . in a simple way , the output signal can be compared with a predetermined threshold value . when the threshold value that specifies the permissible deviation is surpassed , switching to the second operating curve ii is realized . by switching to the second operating curve ii not only greater power p is enabled but also a higher speed n . switching from the operating curve i ( idle curve ) to the operating curve ii ( load ) is realized expediently without substantial delay . switching of the operating curve ii ( load ) to operating curve i ( idle ), on the other hand , is expediently done with delay . the switching process itself has thus a hysteresis . for example , switching can be done when the detected deviation of the point 30 from the operating curve i exists over an extended period of time , i . e ., the deviation surpasses a threshold value for time . this hysteresis can be set particularly easily by means of a timing member 25 . only after the set time of the timing member 25 has elapsed , switching to the operating curve i ( idle ) takes place inasmuch as at the point in time when the set time of the timing member has elapsed the switching criteria are still fulfilled . in this way , it is achieved that in case of a short - term drop of the power draw in operation of the trimmer 1 , the electric motor 2 is not immediately switched to the idle curve ; this could impede efficient working . advantageously , the on / off switch of the electrical power tool can be designed such that for complete depression of the switch like a “ kick down ”, there is an immediate switching to the operating curve ii . the configuration can be such that switching to the operating curve i ( idle curve ) is done automatically by means of the control device 20 and returning to operating curve ii ( load ) is accomplished by completely depressing the on / off switch . expediently , the on / off switch can actuate a contact ( push button ) in the completely depressed position so that immediately a switching signal for switching to the operating curve ii is triggered . by means of the power - adjusted speed control according to the invention it is achieved that for a drive motor operating free of load the speed n is lowered to a low speed of , for example , 6000 / min by means of limiting the power draw ; at the time of applying a load , the changed operating state is detected as a result of the deviation from the first operating curve i in order to switch immediately to a corresponding operating point 32 of the second operating curve ii that enables a higher power uptake and thus higher speed . in load operation , the maximum electrical power p is drawn and thus higher power output by the electric drive motor is made available . when the load is no longer existing , the drawn electric power p drops while simultaneously the speed increases . this is detected by the control device 20 and , advantageously with delay , switching back to the first operating curve i as an idle curve is carried out . the speed drops to a lower idle speed . switching between the operating curves can be done alternatively or additionally in accordance with other criteria . according to a further embodiment , an acoustic pick - up 28 is provided which is connected by means of a signal line 29 to the control device 20 . the output signal of the acoustic pick - up 28 is monitored by the control device 20 and switching between the operating curves is done as a function of the output signal . advantageously , the output signal of the acoustic pick - up 28 is compared to a threshold value . when the threshold value is surpassed , which is the case when the motor is operated free of load according to operating curve ii at high speed in idle , switching to the operating curve i ( the idle curve ) takes place . the noise level drops . the output signal of the acoustic pick - up drops . in order not to cause immediate switching to the operating curve ii ( load curve ), the switching to the operating curve ii can be made dependent on other criteria , for example , on the power draw of the drive motor 2 . another simple possibility resides in that a second threshold value is provided , wherein switching back to the operating curve ii is carried out when surpassing or dropping below this threshold value . for example , dropping below the second threshold value and switching could be triggered when the power tool is loaded — by starting work with the power tool — in idle situation on the operating curve i so that a further drop in speed is caused and thus a reduction of the output signal is effected . a microphone 26 is advantageously suitable as an acoustic pick - up 28 ; it receives the acoustic sounds of the tool or of the drive motor . expediently , the microphone is arranged near the acoustic noise source , i . e ., near the tool or the tool head . an advantageous configuration of the acoustic pick - up 28 can be provided in the form of pick - up 27 for structure - borne sound ; the pick - up 27 is arranged directly on the tool head 6 , on the guide tube 3 or the drive motor 2 or the drive motor housing . the pick - up 27 for structure - borne sound is substantially immune with regard to any foreign acoustic sounds . the specification incorporates by reference the entire disclosure of german priority document 10 2006 018 678 . 8 having a filing date of apr . 21 , 2006 . while specific embodiments of the invention have been shown and described in detail to illustrate the inventive principles , it will be understood that the invention may be embodied otherwise without departing from such principles . | a hand - held power tool has an electric drive motor having a drive shaft and a tool connected to the drive shaft and rotatably driven by the drive shaft . the drive motor has a control device that has correlated therewith at least a first operating curve and a second operating curve . the control device operates the electric drive motor in idle according to the first operating curve and operates the electric drive motor under load according to the second operating curve . the first operating curve covers the low power range at low speed and the second operating curve covers a large power range at high speed . |
an illustrative embodiment of a decorative spa enclosure is shown in fig1 and 2 . the enclosure 11 includes four side panels 13 , 15 , 17 , 19 . three of the side panels 15 , 17 , 19 may be identically constructed while side panel 13 is provided with an opening 29 for purposes of installing a spa equipment control panel . at each of the four corners of the enclosure 11 , respective side panels interface with corner pieces 21 , 23 , 25 , 27 . each of the corner pieces 21 , 23 , 25 , 27 is preferably a molded plastic part , each having an elongated scallop or depression 31 , 34 , 33 , 32 formed therein . a downlight 36 is located above each scallop or depression 31 , 34 , 33 , 32 so as to illuminate it to provide an aesthetically pleasing appearance at night . each of the side panels 13 , 15 , 17 , 19 are preferably formed from a thin , e . g ., 0 . 350 inches thick , plastic sheet , and are supported by respective backing frame structures 57 . the frame structures 57 are shown as comprising a rectangular lattice work in fig1 and 2 . however , they could be variously configured , as those skilled in the art will appreciate . the panels 13 , 15 , 17 , 19 and corner pieces 21 , 23 , 25 , 27 are attached to and supported by an internal cabinet structure . the cabinet structure includes lower horizontal frame members 43 , 44 and vertical support members 41 , as well as upper horizontal frame members 45 . the lower horizontal frame support member 44 is fixedly attached to the adjacent horizontal frame member 43 ′ the vertical frame members 41 are fixedly attached to the lower horizontal frame member 44 and to the upper horizontal frame member 45 . base frame members 56 , 58 are further provided to enhance the rigidity of the structure . the frame and cabinet structures shown may be fabricated from wood , composite , or other suitable materials . additionally , bullnoses e . g ., 47 , 49 are disposed around the upper periphery of the frame structure . these bullnoses 47 , 49 are provided to support an outer lip of a cooperating spa shell , which preferably conceals them to form a complete spa unit , for example , as illustrated in fig7 . the construction of one of the corner pieces 25 is illustrated in further detail in fig3 to 6 . the corner piece 25 is preferably thermo formed from a single abs plastic sheet using an appropriate mold . the corner piece 25 includes a curved , contoured body portion 75 and a scallop or depression 33 , which includes a smaller depression 73 that provides for installation of a cover buckle 37 provided to facilitate tie - down of a spa cover . the scallop or depression 33 has a generally linear upper edge 78 with respective sides 91 , 93 curving symmetrically toward an end point 95 to create a shield - like shape . in fig6 , numeral “ 74 ” indicates the arcuate cross - section of the depression 33 . at the lower end of the corner piece 25 is formed a horizontally extending bottom web 79 . the horizontally extending bottom web 79 may include screw recesses 81 , 83 for facilitating attachment to the cabinet structure . in fig3 - 6 , dimension w 1 may be , for example , 19 . 377 inches , while dimension w 2 may be 17 . 738 inches according to one illustrative embodiment . each of the respective side panels 13 , 15 , 17 , 19 includes first and second horizontal grooves 61 , with use of a single groove as illustrated in fig7 being an optional alternative . the side panels are preferably formed of abs plastic with an acrylic film applied to the front surface thereof . preferably the plastic and film are extruded together at the same time (“ co - extruded ”). this process may enable , for example , a decorative wood - grain effect to be obtained . with such a wood grain appearance , the flat plastic panel gives the appearance of wood siding , as illustrated in fig7 . fig8 illustrates a buckle 37 used for connection of a spa cover , according to embodiments . the buckle may be equipped with a locking mechanism as a safety feature to prevent the spa cover from being removed without the use of a key or combination . while the apparatus and method have been described in terms of what are presently considered to be the most practical and preferred embodiments , it is to be understood that the disclosure need not be limited to the disclosed embodiments . it is intended to cover various modifications and similar arrangements included within the spirit and scope of the claims , the scope of which should be accorded the broadest interpretation so as to encompass all such modifications and similar structures . the present disclosure includes any and all embodiments of the following claims . | a portable spa enclosure provides an aesthetically pleasing cover for pre - manufactured spas . additionally , spa hardware is concealed by the spa enclosure , while lighting is recessed to provide a “ soft ” light solution . |
an artificial intervertebral disk 1 according to a first embodiment of the invention will be now described with reference to fig1 to 6 . the artificial intervertebral disk 1 comprises , as show in fig1 ( a ) and 1 ( b ), a pair of upper and lower first and second connecting bodies 2 and 3 . as shown in fig4 when the artificial intervertebral disk 1 is mounted on an ailed part , the opposing inner surfaces 4 and 5 of the first and second connecting bodies 2 and 3 are connected to each other at the contacting surfaces thereof ( see fig5 and 6 ), and upper and lower outer surfaces 6 and 7 of the first and second connecting bodies 2 and 3 are connected to upper and lower vertebral bodies m1 and m2 of the cut artificial intervertebral disk 1 in a surface contacting state . the first connecting body 2 is positioned at the upper side and the second connecting body 3 is positioned at the lower side in the fig1 to 4 , but they may be turned upside down . as shown in fig1 ( a ) and 1 ( b ) and fig3 ( a ) and 3 ( b ), a hemispherical movable protrusion 11 having an arc shape at the tip end lower portion in cross section is formed integrally with a flat - shaped base body 10 at the lower side . on the other hand , the second connecting body 3 has a flat shaped base body 12 which is depressed to form a movable receiver part 13 , and the movable protrusion 11 of the first connecting body 2 is movably engaged with the receiving part 13 at the upper surface thereof . more in detail , a bank 14 is formed integrally with the base body 12 at the upper peripheral side thereof to protrude therefrom , and a receiving surface 15 having an arc surface 17 which is low at the central portion thereof is formed on the inner bottom surface of the bank 14 , wherein a recessed part of the upper opening formed by the bank 14 and receiving surface 15 forms the movable receiver part 13 . in the state where the movable protrusion 11 provided on the first connecting body 2 and the movable receiver part 13 provided on the second connecting body 3 are engaged and connected with each other , a vertical gap t1 having a given interval is defined between the lower surface of the base body 10 of the first connecting body 2 and the upper end of the bank 14 of the second connecting body 3 , and a horizontal gap t2 having a given interval is defined between the outer periphery of the movable protrusion 11 of the first connecting body 2 and the inner periphery of the bank 14 of the second connecting body 3 . next , as shown in fig1 ( a ) and 1 ( b ), fig2 and fig3 ( a ) and 3 ( b ), a plurality of triangular pyramidal fixed protrusions 20 , 20a , . . . are integrally formed on the outer surfaces 6 and 7 of the first and second connecting bodies 2 and 3 . although the fixed protrusions 20 , 20a , . . . have triangular pyramidal shapes , they may be selected arbitrarily from any shapes such as conical , square , or triangular shape in cross section , or a shape having a long ridge line , etc . as shown in fig4 the first and second connecting bodies 2 and 3 of the artificial intervertebral disk 1 which are inserted into the normal vertebral bodies m1 and m2 in a surface contacting state during the surgical operation are pressed by the upper and lower vertebral bodies m1 and m2 , so that the fixed protrusions 20 , 20a , . . . and the vertebral bodies m1 and m2 are firmly connected with one another as time passes after the surgical operation . a part to be grasped or a notch or the like , not shown , may be formed on the outer portion , etc . of the artificial intervertebral disk 1 when the artificial intervertebral disk 1 is inserted into the ailed part for the surgical operation , and for the convenience of the handling of surgical jig . the operation of the artificial intervertebral disk 1 will be now described as follows . in the artificial intervertebral disk 1 inserted into the ailed part , the vertebral column is inclined forward physiologically like a bow as shown in fig4 although it depends on the ailed part where the artificial intervertebral disk 1 is inserted into the lumber vertebra or cervical vertebral so that the first connecting body 2 is inclined relative to the second connecting body 3 . the insertion inclination angle a of the upper vertebral body m1 ( first connecting body 2 ) is about 4 . 5 ° relative to the lower vertebral body m2 ( second connecting body 3 ) in fig4 . in such an inserting state , various motion modes occur depending on the change of the posture of the human body in everyday life , so that the first connecting body 2 is inclined and displaced relative to the second connecting body 3 . for example , as shown in fig5 the contacting surface of the movable protrusion 11 of the first connecting body 2 relative to the receiving surface 15 of the second connecting body 3 slides back and forth so that the second connecting body 3 is turnable . alternately , as shown in fig6 ( a ) and 6 ( b ), the movable protrusion 11 turns on the receiving surface 15 of the second connecting body 3 so that the horizontal position of the second connecting body 3 relative to the first connecting body 2 moves . as a motion mode of the artificial intervertebral disk 1 , two examples are explained but these two examples may occur at the same time , and hence the artificial intervertebral disk 1 has the movability or motion property considering the above . although the inclination angles of the first and second connecting bodies 2 and 3 are determined at the time of the insertion of the artificial intervertebral disk 1 and the motion thereof , the vertical gap t1 and horizontal gap t2 between the artificial intervertebral disk 1 and the first connecting body 2 expand or contract owing to the change , i . e . the increase or decrease of the inclination angles depending on the inserting state of the artificial intervertebral disk 1 into the ailed part . in the case of the artificial intervertebral disk 1 shown in fig5 and fig6 ( a ) and 6 ( b ), it is preferable to set the intervals of the vertical gap t1 and horizontal gap t2 so that the forward inclination angle b when the vertebral column flexes forward may be about 14 to 15 ° and the backward inclination angle c when it flexes backward may be about 6 to 8 °. although the forward and backward inclination angles b and c when the vertebral column flexes forward and backward are determined by the condition of an able - bodied , the artificial intervertebral disk 1 can be inserted into the ailed part with a given angle and the sufficient motion property is secured even if the base bodies 10 and 12 of the first and second connecting bodies 2 and 3 may be set to be in parallel with each other when manufacturing the first and second connecting bodies 2 and 3 . the widths of the vertical gap t1 and horizontal gap t2 may be determined to secure the inserting condition of the artificial intervertebral disk and the motion property of the artificial intervertebral disk 1 after the surgical operation . the motion property of the vertebral column when it flexes back and forth will be now described . the normal intervertebral disk is differentiated in the height at the front portion ( belly side ) and the back portion ( back side ), that is , since the intervertebral disk at the front portion is slightly higher than that at the back portion so that the lumber vertebra and cervical vertebral have curved portions at the front portion so that they flex forward ( lean backward ) physiologically . the motion of the lumber vertebra , etc . is not a simple three - dimensional movement about a specific point but includes a slight horizontal movement in the back and forth directions . the first embodiment has the motion mode similar to such a complex motion mode . the second to fifth embodiments which are modified examples of the first embodiment of the invention will be now described as follows . in the artificial intervertebral disk 1 of the second embodiment shown in fig7 ( a ) and 7 ( b ), the receiving surface 15 is formed of a horizontal surface 16 which is low at the central portion and an arc surface 17 which is high at the periphery thereof compared with the receiving surface 15 of the first embodiment having the arc surface 17 which is low at the central portion . in the artificial intervertebral disk 1 of the third embodiment shown in fig8 ( a ) and 8 ( b ), the receiving surface 15 is formed of the horizontal surface 16 . in the artificial intervertebral disk 1 of the forth and fifth embodiments shown in fig9 ( a ) and 9 ( b ), and fig1 ( a ) and 10 ( b ), the material of an inner surface layer 18 of the movable receiver part 13 is different from that of the movable receiver part 13 , wherein the material of the inner surface layer 18 of the receiving surface 15 alone is different in fig9 ( a ) and 9 ( b ) while the materials of the inner surface layer 18 of the bank 14 and a top end layer 19 as well as the receiving surface 15 are different in fig1 ( a ) and 10 ( b ). although the shapes shown in fig9 ( a ) and 9 ( b ) and fig1 ( a ) and 10 ( b ) correspond to those of the first embodiment , they may apply to those of the second and third embodiments . the materials of the first and second connecting bodies 2 and 3 in the first , second and third embodiments , and the materials of the first and second connecting bodies 2 and 3 and those of the inner surface layer 18 and the top end layer 19 in the fourth and fifth embodiments are respectively formed of a material having stability inside the living body such as adaptability for a human body ( affinity ), mechanical strength , and corrosion resistance . for example , the material of the first and second connecting bodies 2 and 3 comprises stainless steel , titanium , tantalum , platinum , and alloys thereof and it is worked in a given size and shape , and particularly , the outer surfaces 6 and 7 , the fixed protrusions 20 , 20a , . . . which are connected with the vertebral bodies m1 and m2 are coated with hydroxyapatite or other affinity material having excellent affinity with a living body . the first and second connecting bodies 2 and 3 may be formed of aluminum , zirconia and a ceramic material such as appetite instead of a metallic material , and these materials may be appropriately changed and replaced by those having affinity with a living body and those which are subjected to a surface treatment . further , employed as a material for the inner surface layer 18 and the top end layer 19 is that having excellency in wear which is caused by contact and friction between the first and second connecting bodies 2 and 3 when they move , for example , high polymer resin such as polyethylene or the like which has such hardness that the material is not compressed and deformed when the artificial intervertebral disk 1 is inserted into the human body . in other words , since the artificial intervertebral disk 1 comprises a pair of upper and lower first connecting bodies 2 and 3 , the artificial intervertebral disk 1 is composed of two pieces , and the artificial intervertebral disk 1 can be simply manufactured . accordingly , it is possible to easily set the first and second connecting bodies 2 and 3 serving as two pieces of the artificial intervertebral disk 1 . further , since the movable protrusion 11 is formed integrally with the base body 10 of the first connecting body 2 at the opposing inner surface 4 wherein the movable protrusion 11 has the arc shape at the tip end thereof in cross section , while the movable receiver part 13 is formed by depressing the base body 12 of the second connecting body 3 at the opposing inner surface 5 , so that the movable protrusion 11 of the first connecting body 2 has movability , namely , the movable protrusion 11 is turned and slidably moved on the receiving surface 15 of the second connecting body 3 . as a result , motion property is given to the vertebral column on which the artificial intervertebral disk 1 is mounted so that the function of the human body at the normal time is recovered so that the everyday life is not impeded , and no unnatural force is applied between the normal vertebral bodies and the intervertebral disks , thereby preventing the recurrence of the treated part . still further , since the movable receiver part 13 comprises the receiving surface 15 which contacts the tip end of the movable protrusion 11 and the bank 14 protruding from the periphery of the receiving surface 15 , the movable protrusion 11 is changed in position and posture thereof inside the movable receiver part 13 so that the movable protrusion 11 is not removed from the movable receiver part 13 , namely , the first connecting body 2 is not separated from the second connecting body 3 , thereby improving the stability . still further , since the vertical gap t1 is defined between the opposing inner surface 4 of the base body 10 of the first connecting body 2 and the top end of the base body 10 , and the horizontal gap t2 is defined between the outer periphery of the movable protrusion 11 and the inner periphery of the bank 14 , the amount of motion is secured by appropriately setting the vertical gap t1 and horizontal gap t2 . as a result , the excessive motion of the movable protrusion 11 on the receiving surface 15 in all directions can be restricted by the bank 14 , etc ., thereby securing the safety . still more further , since the receiving surface 15 is formed of the arc surface 17 which is low at the central portion , or the central portion of the receiving surface 15 has the horizontal surface 16 , and the horizontal surface 16 is formed of the arc surface 17 at the periphery thereof which is high at the outer side thereof , the movable protrusion 11 is liable to move on the central portion of the receiving surface 15 , and it is possible to easily align the center of the vertebral column , and the receiving surface 15 is formed of the horizontal surface 16 so that the movable protrusion 11 can perform the motion including the back and forth movements . more still further , the inner surface layer 18 of the receiving surface 15 in the movable receiver part 13 or the inner surface layer 18 of the bank 14 and the top end layer 19 are respectively made of a material having low wear , the receiving surface 15 is hardly worn even by the motion between the movable protrusion 11 and receiving surface 15 , thereby maintaining the life and function of the artificial intervertebral disk 1 or the shock caused by the contact of the bank 14 against the top end layer 19 can be absorbed . since the first connecting body 2 is inclined relative to the second connecting body 3 when the artificial intervertebral disk 1 is mounted on an 5 ailed part , and the first connecting body 2 can be inclined relative to the second connecting body 3 by 14 ° to 15 ° forward and 6 ° to 8 ° backward when it is in a state of movement , it is possible to carry out the motion like at the normal condition , thereby giving a natural motion to the artificial intervertebral disk 1 . since a plurality of fixed protrusions 20 , 20a . . . are provided at the outer surfaces 6 and 7 of the two connecting bodies 2 and 3 , it is possible to fix the artificial intervertebral disk 1 between the vertebral bodies m1 and m2 , thereby achieving a very excellent practical effect . | an operation for fixing a vertebral column by an autogenetic or a spacer has no movability or motion property , leading to an impedance of everyday life functions and recurrence of damage at the treated part . an artificial intervertebral disk comprising a movable protrusion which is formed integrally with a base body of a first connecting body and which has an arc shape in cross section at the tip end thereof , a movable receiver part formed by depressing a base body of a second connecting body at an opposing inner surface thereof , and wherein the movable receiver part comprises a receiving surface which contacts the tip end of the movable protrusion and a bank protruding from the periphery of the receiving surface , and a vertical gap is defined between the first and second connecting bodies and a horizontal gap is defined between the outer periphery of the movable protrusion and the inner periphery of the bank , whereby the first and second connecting bodies of the artificial intervertebral disk mounted on the ailed part have movability such as turning and sliding to thereby give a motion property to the vertebral column so that the aforementioned problem is solved . |
it was unexpectedly discovered that , in addition to the well - documented d2 - receptor group antagonistic activity , molindone has specific antagonist activity at the d5 dopaminergic receptor . a heterologous competition assay was designed for a receptor affinity screening of molindone . recombinant d5 receptors were expressed in a gh4 cell line and specific binding was characterized by displacement of another molecule with affinity for the d5 receptor ( the “ ligand ”). “ specific binding ” refers here to the difference in the binding of the ligand to the receptors in the presence and absence of an excess of the active agent . an initial screen was performed with 10 − 5 μm molindone . the conditions and results of the assay are summarized in the tables 1 and 2 . the affinity of molindone for the d5 receptor was further characterized by determining the 1050 , or concentration that inhibits 50 % of control specific binding . for this experiment , a range of molindone concentrations was selected for the ligand blocking assay . the 1050 was determined using non - linear regression analysis of the competition curves using hill equation curve fitting . the inhibition constants ki , wherein ki is defined as the concentration of the competing ligand ( molindone ) that will bind to half the binding sites at equilibrium in the absence of radioligand or other competitors , were calculated using cheng prusoff equation . the results of the affinity assay are summarized in tables 3 and 4 , and in fig1 . the final step of the assay was to characterize whether the binding is of an agonist or antagonist nature . for the d5 receptor , this was accomplished through an assay that examined the agonist effect on the d5 receptor , i . e ., the generation of camp or the blockade of this effect when stimulated by a d5 agonist , dopamine . this was also done with a range of concentrations to determine the relative agonist vs antagonist binding ki . the ec 50 values ( concentration producing a half - maximal specific response ) and ic 50 values ( a concentration causing a half - maximal inhibition of the control - specific agonist response ) were determined by non - linear regression analysis of the concentration - response curves generated with mean replicate values using hill equation curve fitting . the apparent dissociation constants for antagonists k b were calculated using the modified cheng prusoff equation . the conditions of the screening are presented in table 5 . it was found that molindone ( 10 − 5 μm ) exhibited 59 % inhibition of the sch23390 binding at the d5 receptor . the ki was determined to be 2 . 4 × 10 − 6 . the binding was determined to be that of an antagonist . the full results of the screening are summarized in tables 6 - 8 and in fig2 - 3 . based on the receptor findings , it was suggested that molindone may be effective for the treatment of aggression in humans , in particular , in children with adhd , in smaller doses than is currently customary . a lower daily dose of the drug results in a diminishing frequency and severity of the adverse effects of the treatment to a level of tolerability , thus resulting in improvement in patient compliance . in one embodiment , the invention is directed to a method of treatment of aggression in humans , in particular children , diagnosed with adhd , bipolar disorder , autism , and post traumatic stress disorder by administering molindone in a total daily dose that is at least 10 % lower than the current dose for its use as an antipsychotic agent . in other embodiments , the dose is 15 % lower , 25 % lower , 35 % lower , and 50 % lower than the current dose . in one embodiment of the invention , molindone is administered in a dose range of from 10 mg / day to 200 mg / day . in other embodiments , molindone is administered in dose ranges of from 3 mg / day to 200 mg / day ; 15 mg / day to 120 mg / day ; 15 mg / day to 90 mg / day ; 30 mg / day to 90 mg / day ; or 36 mg / day to 72 mg / day . the success of the treatment is evident in the marked decrease in the number instances of undesirable behavior exhibiting aggression , irritability and impulsivity . such behavior may be exemplified , without limitation , by disobedience ; negativism ; provocative opposition to authority figures ; violations of minor rules ; temper tantrums ; argumentativeness ; provocative behavior ; stubbornness ; blaming others for his or her own mistakes ; being touchy , easily annoyed , angry , resentful , spiteful or vindictive ; and swearing . in another embodiment , the invention encompasses a method of treatment of aggression in children with adhd with molindone that is characterized by an improved adverse effect profile . the adverse effects that are diminished by the method of the present invention may be , but are not limited to , drowsiness , depression , hyperactivity and euphoria , extrapyramidal reactions , akathisia , akinesia , dystonic syndrome , tardive dyskinesia , tachycardia , nausea , dry mouth , urinary retention , and constipation . the efficacy and the adverse effect profile of the lower dose treatment of the current invention were evaluated in a randomized , multicenter , parallel group , dose ranging study to evaluate the safety and tolerability of molindone in children with attention - deficit - hyperactivity disorder ( adhd ) and persistent serious conduct problems , where the subjects are administered molindone hydrochloride given 3 times daily in a dose range of 5 to 20 mg / day in children & lt ; 30 kg , and 10 to 40 mg / day in children ≧ 30 kg ( example 1 and fig4 ). effectiveness , safety and tolerability of molindone was evaluated in a randomized , multicenter , parallel group dose - ranging study in children with adhd and persistent serious conduct problems . subjects were randomized based on weight at baseline to 1 of 4 treatment groups . the dosing for subjects with weight of less than 30 kg was initiated at 1 . 67 mg / day and 3 . 34 mg / day for subjects weighing 30 kg or more . a titration schedule was followed until the target dose ( treatment group 1 , 2 , 3 or 4 ) was reached . subjects remained at target dose for 6 weeks ( table 9 ). side effects from the administration of molindone in all four treatment groups were mild , self - limiting and within the limits of tolerability , i . e . no subjects discontinued the study because of the side effects ( fig5 ). | the invention comprises a method of treatment of aggression and similar behavioral syndromes , such as impulsivity and irritability , by a pharmaceutical agent exhibiting combined d2 and d5 antagonistic activity . |
a remote controller for animal training includes a user hand - held transmitter for transmitting coded command signals . the command signals are transmitted via a microprocessor amplified through a rf system and outputted through an antenna . the remote controller further includes a training device worn by the animal to be trained . an rf receiver receives command signals with individual output levels of three different styles of stimuli to the sensory system of the animal in order to allow the animal to properly react or respond to these levels of stimuli . a hand - held transmitter uses a voltage frequency converter ( vfc ) for converting input from a three - terminal potentiometer voltage to a frequency proportional thereto . the frequency signal is input to a microprocessor . the microprocessor has a security code function to limit control of the training device to that of the remote controller . five function switches allow for the selection of one of five types of stimulation , 1 ) brief electrical impulse stimulation , 2 ) continuous electrical impulse stimulation , 3 ) boost continuous electrical impulse stimulation , at a preset level above the continuous stimulation setting , 4 ) magnetic buzzer stimulation , and 5 ) light stimulation . the switches are connected to the rf circuitry to produce and amplify signals denoting the selected stimulation then delivered to an antenna driver and in turn to a tuned broadcast antenna . an animal collar receiver receives the rf transmitted coded signals from the transmitter . a detector circuit detects the coded signals and send them to an on - board microprocessor . the microprocessor converts the coded signals and activates one of five driver circuits for then outputting the selected stimuli and the appropriate level to the animal . the same rf circuitry on both the remote controller and the training device can function as paired transceivers to broadcast intelligent data back to the hand - held transmitter . a stimulator adjustment control includes a voltage divider network with a three - terminal potentiometer . the potentiometer is coupled to a voltage to frequency converter circuit ( vfc ) which converts the voltage level into individual separate frequencies . these separate frequencies allow the microprocessor to send the appropriate signal to the individual stimuli drivers for the five different outputs at the animal collar to articulate many different gradual levels of output from each of the five individually selectable stimuli . both the transmitter and receiver employee a dc battery pack for operating each system through an on - board regulator and power switch . in one embodiment , rechargeable batteries and their charging circuits are installed . on / off power switches are provided in each the transmitter and the receiver to activate and deactivate each system independently . in one embodiment , an lcd screen is employed in the transmitter and offers the user the capability to observe in a visual display the level setting , the state of the transmitter battery and which one of the five select function buttons is powered up when that particular button is pressed , preferably by icon . with the capability to adjust gradual levels upward and downward while also providing different styles of stimulation , the control offers the animal opportunities to be successful while allowing the user to build a more meaningful relationship with the animal . to allow greater potential for successful training results , these sensory detectors and their drive circuitry would include utilizing optical , photo , infrared , air flow , vibration , tilt , pressure , reflective , magnetic , temperature , voltage , current , frequency , and percussion transducer / sensors of all sorts and kinds . such electronic control activations would include utilizing the following signal types as cues : sound — audible , ultrasonic , and subsonic created by mechanical speaker / microphone , relay buzzer , solid - state , piezoelectric , ceramic , ferrite , magnetic , condenser , and percussion ( utilizing all frequencies , pulse rates , duty cycles , pulse widths , amplitudes , duration , repetition rates and such .) light — all spectrum colors , brilliances , and such ( utilizing all frequencies , pulse rates , duty cycles , pulse widths , amplitudes , duration , repetition rates and such .) taste — sweet to poison . smell — pungent to flowery . electrical impulse — transformer control of low current ( 50 micro - amps to 100 milliamps ) with high - voltage ( 50 vac to 10 , 000 vac ) ( utilizing all frequencies , pulse rates , duty cycles , pulse widths , amplitudes , duration , repetition rates and such .) vibration — motor - drive , mechanical offset fulcrum , pancake , ceramic , percussion and transducer ( utilizing all frequencies , pulse rates , duty cycles , pulse widths , amplitudes , duration , repetition rates and such .) looking more specifically to the figures , fig2 and 4 depict a hand - held remote controller 100 . if any one of first to fifth function buttons ( switches ) of the remote controller is pressed , corresponding data and id codes set by an id code setting means are provided to an oscillator / modulator 151 . then , rf signals generated in the oscillator / modulator 151 are amplified at an rf amplifier 152 and an rf output terminal 153 , filtered at a low - pass filter 154 to remove harmonics , and then emitted through an antenna 155 as radio waves . a stimulation adjustment control 130 uses a potentiometer as a “ volume ” ( magnitude ) control which allows precise control or gradual change of the stimulation level suitably for an animal , differently from the prior art . a conventional stimulation adjustment means uses a mechanical selector switch , and such a selector switch cannot subdivide a stimulation level precisely . fig3 and 5 depict a training device 200 . the training device 200 receives the rf signals emitted in the transmission of the remote controller 100 of fig2 and 4 respectively through an antenna 221 included therein . then , a high - frequency amplifier 222 amplifies weak radio waves , and a mixer 224 makes a secondary intermediate frequency such that a detector 227 extracts the data sent from the transmitter via a filter 226 . the extracted data is input to a low - frequency amplifier included in a microprocessor 210 . the microprocessor 210 outputs a signal to a selected one of an electrical impulse stimulation generator if the id code contained in itself is identical to the id code sent from the transmitter . hereinafter , each component of the remote controller ( transmitter ) 100 and the training device ( receiver ) 200 shown in fig2 to 5 will be described in detail based on the first and second embodiments . in the following description , if “ the second embodiment ” is mentioned , the corresponding description will apply only to the second embodiment . however , the following description will apply to both the first and second embodiments unless otherwise specifically stated . 121 : brief stimulation button ( first function button ) brief low - frequency electrical impulse stimulation ( 3 to 5 pulses ) is generated at the training device regardless of the time during which the button of the remote controller is pressed . continuous low - frequency electrical impulse stimulation is generated at the training device during the time that the button of the remote controller is pressed ( 12 seconds at the maximum ). 123 : + 20 level boost continuous stimulation button ( third function button ) boost low - frequency electrical impulse stimulation is preset at 20 levels higher than the continuous impulse level and is generated at the training device during the time that the button of the remote controller is pressed ( 5 to 7 seconds at the maximum ). a brief buzz sound is generated at the training device ( 3 to 5 pulses ) regardless of the time during which the button of the remote controller is pressed . an led light at the training device is turned on at the first press and turned off at the second press regardless of the time between when the button of the remote controller is pressed . the volume control is used for adjusting the stimulation level of the training device . a low - frequency electrical impulse stimulation corresponding to the level set by the volume control is generated at the training device by means of the first , second and third function buttons . an analog voltage according to the level output from the volume control 130 is converted into frequency , which is a digital value recognizable by a microprocessor in the remote controller , and then transmitted to the microprocessor in the training device . for example , 20 hz signal is provided to the microprocessor in case a volume output voltage is 0 . 1 v ( i . e . level 1 ), and 100 hz signal is provided to the microprocessor in case a volume output voltage is 0 . 5v ( i . e . level 5 ). the microprocessor controls all functions input from the function buttons 120 and outputs an id code signal . the microprocessor also has a power on / off function . the microprocessor recognizes and processes the frequency signal supplied according to a stimulation level operates a display 140 and operates a rf control 156 , which controls an rf oscillator 151 and an rf amplifier 152 when a function is operated . in the two - way system ( in the second embodiment ), the microprocessor processes the data received from the training device 200 . for instance , the microprocessor computes a distance between a user and an animal based on position data of the user and the animal . the level set by the volume control 130 , and a residual battery capacity of the remote controller is displayed . in the two - way system ( in the second embodiment ), a residual battery capacity of the training device , a direction and distance of an animal from the user , a moving speed of the animal , and so on are displayed on the display 142 . the remote controller uses fm ( frequency modulation ), and a modulation - allowable vcxo is applied to give rf oscillation and modulation at the same time . rf output from the oscillator and modulator 151 is low , so the rf amplifier amplifies the output rf such that a following output terminal can be operated . the rf output is for amplifying rf such that the remote controller and the training device are within a reachable distance . the low - pass filter blocks high frequencies in the rf signal other than fundamental waves . the antenna transmits rf composed of fundamental waves , which has passed through the low - pass filter 154 . in the two - way system ( in the second embodiment ), the antenna receives rf signal transmitted from the training device . when any one of the first to fifth button 121 ˜ 125 of the remote controller is pressed , the rf control supplies power to the oscillator / modulator 151 and the rf amplifier 152 such that the oscillator / modulator 151 and the rf amplifier 152 are operated . the regulator & amp ; power switch has a constant - voltage ic function that is operated in association with the microprocessor 110 . if the power switch of the remote controller is pressed over 0 . 5 second , the power is turned on . if the power switch is pressed for over 1 second again after the power is turned on , the power is turned off . the battery 162 is a rechargeable battery and thus the charging device is used . the gps module 170 receives signals from the gps of the training device 200 to provide the microprocessor 110 with position data of the trainer . the two - way receiver 180 is used for receiving the information of the training device , and the two - way receiver 180 gives data to the microprocessor 110 . the antenna receives rf signal transmitted from the remote controller 100 . in the two - way system ( in the second embodiment ), the antenna transmits rf signal to the remote controller 100 . it is preferable that the antenna 221 is an internal ( built - in ) antenna and a detachable external antenna 221 ′ ( see fig1 ) is further provided to extend a reachable distance . the high - frequency amplifier amplifies weak rf signals induced to the receiving antenna 221 . osc is an oscillator that oscillates in itself to give a secondary intermediate frequency . rf signal supplied from the high - frequency amplifier 222 is mixed with the signal supplied from the osc 223 to make an intermediate frequency that is a secondary frequency . the intermediate - frequency amplifier amplifies the intermediate frequencies made at the mixer 224 . the filter filters the intermediate frequencies made at the mixer 224 to remove noise . the detector detects function signals and id signals sent from the remote controller . a low - frequency amplifier included in the microprocessor amplifies analog signals detected by the detector 227 ; and , in case the received signal is identical to id code already stored , a signal of any one selected from the first to fifth button 121 ˜ 125 of the remote controller is output . in the two - way system ( in the second embodiment ), the microprocessor processes the information of the training device and gives the information to a two - way transmitter 280 . the d / a converter is used for outputting a stimulation level , set by the volume control of the remote controller , as analog signals . the electrical impulse stimulation generator generates high - voltage stimulations to give low - frequency electrical impulse stimulations to an animal utilizing a transformer output . the stimulation terminals are electrodes for supplying electrical impulse stimulation to an animal . when the first , second and third function button 121 ˜ 123 of the remote controller are pressed , the stimulation generating circuit control 234 supplies power to the electrical impulse stimulation generator 232 to operate the electrical impulse stimulation generator 232 . the buzzer driver is used for operating a magnetic buzzer when the fourth function button 124 of the remote controller is pressed . the magnetic buzzer 242 is used for converting electric signals into sound signals . the light driver 251 is used for operating at least one led light when the fifth function button 125 of the remote controller is pressed . two high - brightness led &# 39 ; s 252 are applied to convert electric signals into light signals . the regulator & amp ; power switch 261 has a constant - voltage ic function that is operated in association with the microprocessor 210 . if the magnet is contacted with the lead switch of the training device over 0 . 5 second , the power is turned on . if the magnet is contacted over 0 . 5 second again after the power is turned on , the power is turned off . the battery 262 is a rechargeable battery and thus the charging means 263 is used . the gps ( global positioning system ) 270 obtains reference signals from at least three satellites to provide the microprocessor 210 with position data of the animal . the two - way transmitter 280 is used for transmitting the information of the training device , and the two - way transmitting 280 emits data as radio waves . meanwhile , in the former embodiments , the training device 200 includes the d / a converter 231 for converting the set stimulation level to an analog signal capable of being processed by the electrical impulse stimulation generator 232 and then outputting the analog signal . the d / a converter may be implemented in various ways , but generally the d / a converter is connected to the number of output pins of the microprocessor 210 which corresponds to the number of the stimulation level . in other words , though it is depicted in fig3 and 5 that the d / a converter 231 is connected to the microprocessor 210 by one line , for example in the case where the number of the stimulation level is 256 (= 2 8 ), the d / a converter 231 is connected to eight output pins of the microprocessor 210 . therefore , there is a disadvantage in that the capacity and size of the microprocessor generally configured with asic increases . in order to solve this disadvantage , u . s . pat . no . 5 , 666 , 908 and u . s . pat . no . 6 , 637 , 376 teach or suggest a configuration not using a d / a converter . in other words , in u . s . pat . no . 5 , 666 , 908 and u . s . pat . no . 6 , 637 , 376 , a microprocessor outputting a digital value outputs a pulse train corresponding to a stimulation level ( intensity ), and the pulse train is intactly applied ( strictly , through a buffer ) to a transistor which controls a primary current of a transformer serving as an electrical impulse stimulation generator . in detail , in u . s . pat . no . 5 , 666 , 908 , the microprocessor generates a pulse train in which a pulse width is changed in proportion to the stimulation level while a pulse period , a pulse magnitude and a pulse train duration are fixed . in addition , in u . s . pat . no . 6 , 637 , 376 , a pulse train in which a pulse amplitude and a pulse train duration are fixed but the number of pulses included in a certain pulse train duration is changed in proportion to the stimulation intensity or in which the number of pulses is fixed but the separation between pulses is changed is generated ( as a result , the duty cycle is changed in proportion to the stimulation intensity ). the pulse train generated as above is applied to a transistor which controls a primary current of a transformer , and current flows to the primary side of the transformer during the pulse on period ( duty cycle ) to generate electrical impulse stimulation to the secondary side . u . s . pat . no . 5 , 666 , 908 and u . s . pat . no . 6 , 637 , 376 allow the circuit in the training device to simplify and the number of output pins of the microprocessor to reduce since a d / a converter is not used separately . however , since the configuration for generating a pulse train corresponding to the stimulation level must be provided in the microprocessor , the microprocessor becomes complicated and has a large capacity . in addition , since the intensity ( level ) of the electric impulse , a stimulus , is not controlled by the magnitude of pulses in the pulse train but controlled by only the pulse on period , only the time during which the electric impulse of the same intensity continues may be controlled . however , in the third embodiment of the present invention , the level ( intensity ) of stimulation is controlled in the true sense of the word without using a d / a converter and without increasing the complexity of the microprocessor . for this purpose , in the third embodiment , as shown in fig6 , a digitally controllable volume control ( hereinafter , referred to as a “ digital volume ”) 330 is used instead of the d / a converter . the digital volume 330 may be implemented with several resistance elements and cmos switches and may be configured as an integrated circuit chip . the digital volume 330 receives the digital signal representing a stimulation level from the microprocessor 210 and outputs a voltage proportional thereto . in other words , in the words of u . s . pat . no . 5 , 666 , 908 and u . s . pat . no . 6 , 637 , 376 , the digital volume 330 outputs a pulse in which the width or number of voltage pulses or the duty cycle is fixed but the pulse amplitude or magnitude is variable . the voltage with a variable magnitude which is an output of the digital volume 330 is intactly applied to a transistor which controls a primary current of a transformer of the electrical impulse stimulation generator to allow the current proportional to the voltage value to flow to the primary side so that the electrical impulse stimulation with a voltage proportional thereto is generated at the secondary side . the digital volume 330 of this embodiment may be considered as a d / a converter in a broad sense since the input , output and functions of the digital volume 330 are identical to those of the d / a converter 231 of the former embodiments . however , the d / a converter 231 of the former embodiments occupies a plurality of output pins of the microprocessor 210 , while the digital volume 330 of this embodiment occupies only a small number of output pins regardless of the number of stimulation levels . therefore , in this embodiment , it is possible to reduce the capacity and size of the microprocessor which allows the training device 200 worn by an animal to become lighter . for example , in the case where the number of stimulation levels is 256 , the d / a converter 231 of the former embodiments occupies eight output pins , while the digital volume 330 of this embodiment occupies only three output pins regardless of the number of stimulation levels . hereinafter , the third embodiment of the present invention will be described with reference to fig6 and 7 , based on only the components of the training device ( receiver ) 200 , different from those of the former embodiments . in fig6 , the component designated by the same reference symbol as in fig3 and 5 is identical to that of the former embodiment . meanwhile , only the input and output pins of the microprocessor 210 associated with the digital volume 330 are shown in fig7 , and the input and output pins not associated with the digital volume 330 are not shown therein . a power is applied from the battery 262 to the power pin vcc , and the power pin vcc supplies the power to a circuit in the digital volume . the data pin da exchanges commands and data ( including stimulation level data ) with the microprocessor 210 in a serial communication . the commands and data input to or output from the data pin da include fields for command codes ( id codes ) such as writing and reading , address fields designating a register which is a target of each command , and data fields representing a data value ( a stimulation level value ) to be written in the designated register by the address field . the length ( bits ) of each field is suitably determined according to the number of command types , the number of registers , and the number of stimulation levels . for example , in the case where the number of stimulation levels is 256 , the length of the data field becomes 8 bits . the clock pin cl provides a basic clock regulating the operation timing of each circuit in the digital volume . writing is allowed in each register of the digital volume only when the write protection pin wp is activated . the high output pin vh outputs a highest voltage value ( a voltage value of the power received from the power pin vcc ) corresponding to the highest stimulation level . the low output pin vl outputs a lowest voltage value ( typically , 0 v ) corresponding to the lowest stimulation level . the wiper output pin vw outputs a voltage value corresponding to the stimulation level stored in a wiper register 332 . the wiper output pin vw is connected to a base of a transistor 232 b which controls a primary current of a transformer 232 a of the electrical impulse stimulation generator 232 , and current proportional to the output voltage ( stimulation level ) of the wiper output pin flows to the primary side of the transformer 232 a so that a high voltage proportional to the stimulation level is induced to the secondary side of the transformer 232 a and is applied to the stimulation terminal 233 . the wiper register 332 stores the stimulation level value input through the data pin da or stored in a non - volatile register 333 , and may be implemented as a volatile memory element . the length ( bits ) of the wiper register is identical to the length of data fields of the commands and data input or output through the data pin da . the voltage proportional to the stimulation level stored in the wiper register 332 is output from the wiper output pin vw . for example , in the case where the number of stimulation levels is 256 ( the length of the wiper register is 8 bits ) and the value presently stored in the wiper register is 25 , the highest voltage ( the voltage of the high output pin vh ) is divided by 256 and then the voltage corresponding to the twenty fifth is output through the wiper output pin vw . the non - volatile register 333 stores a value stored last in the wiper register 332 when the digital volume 330 or the training device 200 turns off , or stores an initial value ( an initial stimulation level value ) that needs to load to the wiper register 332 when the digital volume 330 or the training device 200 turns on . in the case where the initial stimulation level value is not specially set or the last value of the wiper register 332 is not stored , or if the wiper register 332 is configured with a non - volatile memory element , the non - volatile register 333 may not be provided . the control logic 331 is a logic circuit controlling each component of the digital volume 330 . the control logic 331 interprets commands and data input through the data pin da and reads or writes values of the wiper register 332 or the non - volatile register 333 according to logic values of the clock pin cl and the write protection pin wp . meanwhile , though it has been illustrated in the above third embodiment that the training device 200 communicates with the remote controller 100 and applies an electrical impulse stimulation to an animal according to the stimulation level set in the remote controller 100 , the training device 200 of the third embodiment may also be used solely without the remote controller 100 . in other words , the training device 200 has a sensor for sensing a specific behavior of an animal , which requires correction , for example barking or moving out of a set area , and when such a specific behavior of the animal is sensed by the sensor , the training device 200 may automatically apply a stimulation of a level defined by applying the number or degree of such specific behaviors to a predetermined algorithm . this algorithm may increase the stimulation level as the number or degree of specific behaviors increases , and may decrease or initialize the stimulation level if the specific behavior is not sensed for a predetermined time , in a traditional way . in this case , the remote controller and an antenna and circuits associated for communication with the remote controller are not needed . instead , a sensor for sensing a specific behavior of an animal is required . in addition , there is a need to program and store the predetermined algorithm in the microprocessor 210 of the training device . meanwhile , the animal training system of the present invention may also be configured to train two or more animals simultaneously by using a single remote controller . in other words , the animal training system may include a single remote controller , and two or more training devices capable of communicating with the single remote controller by rf communication , each respectively worn by the animals to be trained . the fourth embodiment is directed to such a system including a single remote controller and a plurality of training devices . hereinafter , the fourth embodiment of the present invention will be described in detail with reference to fig8 to 10 , based on points that are different from the former embodiments . in fig8 to 10 , the component designated by the same reference symbol as in fig1 and 2 is identical to that of the former embodiment . the animal training system of the fourth embodiment includes a single remote controller 100 ′ and two training devices 200 - 1 and 200 - 2 , as shown in fig8 . even though fig8 is depicted as if two remote controllers 100 ′ are used , only one remote controller 100 ′ is depicted as being observed from different positions . in addition , even though the remote controller 100 ′ of fig8 has a different appearance from the remote controller 100 shown in fig1 , the remote controller 100 ′ of fig8 has the same basic functions as the remote controller 100 of fig1 except for some components required for controlling the two training devices 200 - 1 and 200 - 2 separately . in addition , each of the two training devices 200 - 1 and 200 - 2 is substantially identical to the training device 200 of the former embodiments . moreover , the above two training devices have the same basic configuration except that they have some different detailed configurations required for selectively responding to the remote controller . additionally , the above two training devices may be differently marked to be distinguished from each other . the remote controller 100 ′ of this embodiment includes an animal selection switch 126 for selecting a training device 200 - 1 and 200 - 2 ( or , an animal ) to be controlled ( to be trained ), which is a big difference from the former embodiments . in other words , a user may select an animal 1 ( e . g ., dog 1 ) or an animal 2 ( e . g ., dog 2 ) by using the animal selection switch 126 in the form of a toggle switch , and apply a stimulation such as an electric impulse stimulation , a sound stimulation and a light stimulation to the selected animal by the manipulation as in the examples described above . at this time , the remote controller 100 ′ may be set to use different communication frequencies or different id codes for the training devices 200 - 1 and 200 - 2 in order to control only a selected training device 200 - 1 or 200 - 2 ( in other words , in order that only a selected training device responds to the control of the remote controller ). accordingly , the training devices 200 - 1 and 200 - 2 are configured to communicate with the remote controller 100 ′ by using different corresponding communication frequencies or are endowed with different id codes . if the animal training system of this embodiment as described above is used , a plurality of animals may be controlled ( trained ) by using only one remote controller 100 ′. however , the plurality of animals controlled ( trained ) by one remote controller 100 ′ may have different sensitivities against stimulation . for this reason , whenever an animal to be trained changes , the stimulation level applied to the animal should be appropriately adjusted . however , adjusting the stimulation level whenever a selected animal changes is very cumbersome , and in a case where an urgent control is necessary , a user may fluster and not be able to easily adjust the stimulation level suitably . in this consideration , the animal training system of this embodiment finds and memorizes an appropriate stimulation level of each animal through trial and error , and then , when an animal is selected by the animal selection switch 126 , the animal training system automatically sets the stored appropriate stimulation level for the animal . further , in this embodiment , a locking function and an unlocking function are provided so that the stored appropriate stimulation level for each animal does not change even though a volume control 130 ′ is manipulated . in detail , the remote controller 100 ′ of this embodiment includes a locking unit for locking the level of presently set electric impulse stimulation so that the level does not change even though the volume control 130 ′ is manipulated . the locking unit includes a storage unit for storing the level of electric impulse stimulation set by the volume control 130 ′, and a locking button configured to be pressed by the user so that the level of electric impulse stimulation set for the training device 200 - 1 or 200 - 2 selected by the animal selection switch 126 is stored in the storage unit . the storage unit may be a memory element 111 provided in the microprocessor 110 , as shown in fig9 . the memory element 111 may be implemented into a register , and the memory element 111 is preferably a non - volatile memory whose contents do not erase even when the power is off . in this embodiment , the locking button is not a separate button , and the volume control 130 ′ also functions as the locking button . in other words , the volume control 130 ′ is configured to turn , and the volume control 130 ′ adjusts the level of electric impulse stimulation in proportion to its turning amount and a locking function which is performed when the volume control 130 ′ is pressed along its turning axis ( see the arrow in fig1 ). if the volume control 130 ′ is pressed in its axial direction as described above , the microprocessor 110 stores the level of electric impulse stimulation , presently set by the turning operation of the volume control 130 ′ and displayed at the center of the display 140 , in the storage unit 111 as a level of stimulation for the animal presently selected by the animal selection switch 126 . after that , even though the volume control 130 ′ is turned , the turning operation is ignored , and the stimulation level does not change . at this time , the display 400 displays the animal whose stimulation level is presently selected , stored and locked ( for example , in a case where the stimulation level is locked for dog 1 , an symbol “ 1d ” is displayed , and in a case where the stimulation level is locked for dog 2 , a symbol “ 2d ” is displayed , as shown in fig1 ) to inform the user of the animal whose stimulation level is locked . in a state where the appropriate stimulation level for each animal is stored and locked , if an animal selected by the animal selection switch 126 changes , the stimulation level stored for the selected animal is automatically displayed on the display 140 . in this state , if the user instantly pushes the stimulation button ( for example , the brief stimulation button 121 or the continuous stimulation button 122 ) without adjusting the stimulation level , the present stimulation level is sent to the selected training device 200 - 1 or 200 - 2 and is applied to the selected animal . meanwhile , when the level of electric impulse stimulation for a specific animal is in a locked state , if the locking button ( or , the volume control 130 ′) is pushed again , the locked state is released . in other words , the microprocessor 110 turns off the symbol (“ 1d ” or “ 2d ” in fig1 ) showing the selected animal whose stimulation level is stored and locked , and allows the level of electric impulse stimulation to be changed by the turning operation of the volume control 130 ′. as described above , the animal training system of this embodiment stores and locks appropriate stimulation levels for a plurality of animals , and therefore it is not necessary to separately adjust the stimulation level even though a selected animal is changed , which allows the user to rapidly and conveniently cope with the change of the selected animal . meanwhile , even though it has been described in the fourth embodiment that a user may select one of two animals ( in other words , the user may select one of two training devices ), the user may select one of three or more animals , not limited to the above . in addition , even though it has been described in the fourth embodiment that the volume control 130 ′ has a function of the locking button together , the locking button may be provided independently of the volume control 130 ′, not limited to the above . further , the first to fourth embodiments may be combined as desired . for example , the stimulation level storing and locking function of the fourth embodiment may be applied to an animal training system having a single remote controller and a single training device . in addition , the 2 - way function of the second embodiment may be applied to the third or fourth embodiment , and the digital volume of the third embodiment may be applied to the first , second or fourth embodiment . meanwhile , in the embodiments described above , by pressing the + 20 level boost continuous stimulation button ( third function button ) 123 , the electric impulse stimulation applied to the animal to be trained may be boosted by 20 levels during the time when the + 20 level boost continuous stimulation button ( third function button ) 123 is pressed ( for example , 5 to 7 seconds ) so that low - frequency electric impulse stimulation at 20 levels higher than the present level is applied . this boost stimulation mode may be effectively used when the animal to be trained repeats behaviors which should be corrected . however , the levels (+ 20 levels ) increased in the boost stimulation mode may be inappropriate depending on the sensitiviy of the animal to be trained . therefore , in a fifth embodiment of the present invention , the number of levels increasing in the boost stimulation mode ( or , a level increment ) may be set by the user as desired . for this , the remote controller of this embodiment further includes a level increment setting means for setting a level increment in the boost stimulation mode , compared with the remote controller 100 , 100 ′ of the former embodiments . in detail , the level increment setting means includes a mode start and end button for starting a level increment setting mode when being pressed over a predetermined time ( for example , 5 seconds ) and quitting the level increment setting mode when being pressed again over a predetermined time ( for example , 5 seconds ) after the level increment is set , a volume control manipulated by the user to set the level increment , a display for displaying the set level increment to be recognized by the user , and a storage unit for storing the set level increment if the level increment setting mode ends . here , the mode start and end button may be separately provided to the remote controller 100 , 100 ′ of the former embodiments or may also be implemented by using the existing buttons 120 . in other words , for example , the brief stimulation button 121 may operate as the mode start and end button when being pressed over a predetermined time . in addition , the volume control manipulated to set a level increment in the level increment setting mode may employ the volume control 130 , 130 ′ of the former embodiments , and the display for displaying a level increment may employ the display 140 of the former embodiments . in addition , the storage unit may be a memory element 111 provided in the microprocessor 110 of the fourth embodiment , which has been illustrated with reference to fig9 . the memory element 111 may be implemented in the form of register and is preferably a non - volatile memory whose contents are not erased even though power is off . a method for setting a level increment in the boost stimulation mode by using the level increment setting means configured as above will be described below . first , the mode start and end button , namely the brief stimulation button 121 in the above example , is pressed over a predetermined time ( for example , 5 seconds ). however , since the brief stimulation button 121 is originally configured to generate short low - frequency electric impulse stimulation ( three to five pulses ) in the training device regardless of the time during which the button is pressed in the remote controller , the level increment setting mode starts and simultaneously a stimulation level currently set by the volume control 130 , 130 ′ is applied to an animal to be trained . therefore , in order to prevent this problem , before the brief stimulation button ( mode start and end button ) 121 is pressed , the volume control 130 , 130 ′ is manipulated to set the stimulation level to 0 . the brief stimulation button 121 is pressed after the stimulation level is set to 0 . by doing so , if the level increment setting mode starts , the display 140 displays a level increment in the boost stimulation mode which is set to be 0 ( or , 20 as a default value ) to blink . since the level increment blinks , the user may recognize that the level increment setting mode starts . in this state , the user manipulates ( or turns ) the volume control 130 , 130 ′ to set the number of levels increasing in the boost stimulation mode ( or , a level increment ) as desired ( here , the level increment may be set within a certain range ). then , the display 140 displays the level increment value to blink according to the manipulation of the volume control 130 , 130 ′ by the user . if the set level increment is displayed by the display 140 in a blinking state , the user presses the brief stimulation button ( mode start and end button ) 121 again over a predetermined time ( for example , 5 seconds ). then , the blinking state of the level increment displayed by the display 140 is released ( namely , coming to a lighting state ) so that the level increment is displayed without blinking . in addition , the set level increment is stored in the memory 111 , and the level increment setting mode ends . meanwhile , in the above example where the existing brief stimulation button 121 is used as the mode start button , before the mode start button 121 is pressed , the volume control 130 , 130 ′ is manipulated to adjust the stimulation level to 0 . for this reason , even though the brief stimulation button 121 pressed to apply electric impulse stimulation to an animal to be trained after the level increment setting mode ends , the stimulation may not actually be applied to the animal to be trained . therefore , in this case , it is needed to set the level of electric impulse stimulation applied to the animal to be trained by manipulating the volume control 130 , 130 ′ after the level increment setting mode ends . as an alternative , the stimulation level storing and locking functions of the fourth embodiment above may be applied to this embodiment , so that the electric impulse stimulation level stored and locked may be maintained after and before the level increment setting mode . however , in this case , since the volume control 130 ′ is in a locked state , even though the volume control 130 ′ is manipulated after the mode start and end button 121 is pressed , the stimulation level is not set to be 0 , and so the level increment setting mode may not start . to solve this problem , the volume control 130 ′ which is also used as a locking button may be configured to exhibit its original locking / releasing function in case of being pressed along its turning axis over a predetermined time ( for example , 5 seconds ) and to allow the stimulation level to be temporarily set to 0 in order to start the level increment setting mode in case of being pressed for a shorter time ( or , vice versa ). each step of the level increment setting mode described above may be programmed and preferably implemented as software or firmware in the microprocessor 110 . by doing so , this embodiment may be implemented by changing only the software without greatly changing the hardware . as described above , the animal training system of this embodiment may allow more appropriate and convenient training since a user may set the number of levels increasing in the boost stimulation mode ( or , a level increment ) as desired according to the sensitivity of the animal to be trained . meanwhile , even though the fifth embodiment has been illustrated based on electric impulse stimulation as an example , the boost stimulation mode and the level increment setting mode may also be identically applied to other kinds of stimulations such as sound , vibration , light and smell , in addition to the electric impulse stimulation . in addition , even though the fifth embodiment has been illustrated based on the case where a single animal is trained ( or controlled ) by using a single remote controller , this embodiment may be identically applied to a system having a plurality of training devices as in the fourth embodiment . further , the first to fifth embodiments may be combined as desired . thus , an improved animal training system has been disclosed . while embodiments and applications of this invention have been shown and described , it would be apparent to those skilled in the art that many more modifications are possible without departing from the inventive concepts herein . therefore , the invention is not to be restricted except in the spirit of the appended claims . | an animal training device and system which uses a voltage to frequency conversion technology providing the capability to adjust in gradual incremental levels upward and downward for consistent and individual electronic control of separate output to an animal undergoing training to learn new behaviors which are desired by its owner / handler / trainer . the device is contained in a housing which is worn around the neck of an animal by means of a collar strap or attached to a harness that properly fits onto an animal . the primary use is with dogs , but all kinds of domestic animals may be trained using this device . this vfc technology is offered in a variety of electronic platforms . whether one - way or two - way remote controller with manual activation by the user , automatic activation by remote sensor detectors , or automatically activated by an on - board microprocessor circuitry sensing the animals own actions , either or all device outputs allow the animal &# 39 ; s caretaker the unique capability to select an appropriate level of one of a variety of cue signals at a given moment allowing the animal not to be overwhelmed or to cause any over - reactions . |
with reference to fig1 - 11 , the preferred embodiments of the present invention may be described . the dermatome 10 is comprised of a handle 12 , a battery unit 14 , and a head unit 16 . the handle 12 is attached to the battery unit 14 at one end and the head unit 16 at the other end . as shown in fig1 a from a top view , the head unit 16 is substantially an irregular hexagon shape . the back end 18 of the head unit 16 , which is the end attached to the handle 12 , is parallel to the front end 20 of the head unit 16 , which is at the opposite end of the head unit 16 . the back end 18 of the head unit 20 is shorter in length than the front end 20 of the head unit 16 . as shown in fig1 b , the head unit 16 slopes from the back end 18 of the head unit 16 to the front end 20 of the head unit 16 . as shown in fig2 and fig1 , the front end 20 of head unit 16 comprises a blade 22 , an axle 24 , and two blade guard units 26 . the axle 24 extends across the length of the front end 20 of the head unit 16 , thus between the left side wall 28 and right side wall 28 of the head unit 16 . the axle 24 is preferably cylindrical in shape . two blade guard units 26 are received by the axle 24 . each blade guard unit 26 is comprised of a top section 30 , middle section 32 , and bottom section 34 . the middle section 32 is substantially vertical and comprises a circular hole in the middle where the blade guard unit 26 is received by the axle 24 . attached to the middle section 32 at one end is top section 30 , which is arc - shaped . attached to the middle section 32 at the opposite end is bottom section 34 . the bottom section 34 extends perpendicularly to the middle section 32 . the bottom sections 34 of the two blade guard units 26 extend away from each other towards the left and right ends 28 of the head unit 16 . the blade 22 abuts the bottom sections 34 of the blade guard units 26 . thus , the blade edge is only exposed on the portion of the blade between the two blade guard units 26 . because bottom sections 34 of the blade guard units 26 may contact the skin of the patient when the distance between the blade guard units 26 is maximized for wide cuts , in an alternative embodiment , bottom sections 34 of blade guard units 26 may be curved at their ends to avoid contact with the skin . as shown in fig8 , the arc - shaped top section 30 allows the medical professional operating the dermatome 10 to easily grab the blade guard unit 26 and move it left or right along the axle 24 . in this regard , the width of the cut can be controlled in real time . for example , as the physician is moving the dermatome across the surface of the patient &# 39 ; s skin , the physician can manually move the blade guard units to increase or decrease the width of the cut of skin or skin tissue being removed from the patient . in addition to moving side - to - side along the axle 24 , in one embodiment , the blade guard units may be rotated on the axle 24 from the front end 20 of the head unit 16 to the back end 18 , and vice versa . while the blade guard units 26 can be manually moved along the axle 24 , in an alternative embodiment , the blade guard units 26 can be moved relative to one another by electronic means . as shown in fig1 , blade 22 is secured between a blade plate 42 and the bottom surface of head unit 16 . the blade plate 42 and the bottom surface of the head unit 16 are preferably attached via two screws . in the preferred embodiments , however , the blade 22 is not permanently attached to either the head unit 16 or the blade plate 42 . the blade 22 has a sharp blade edge facing outward from the front end 20 of the head unit 16 of the dermatome 10 , which generally defines a plane p that is generally parallel to longitudinal axis l as shown in fig8 . the axis l is generally defined by the dermatome 10 such that the handle 12 also generally extends along axis l . as shown in fig7 , a blade driver 44 is in communication with the blade 22 , which allows the blade 22 to oscillate and cut the skin tissue when the sharp blade edge makes contact with the skin tissue . the blade driver is preferably a rotational motor and is of the type well - known to those skilled in the art . the blade 22 can preferably move laterally approximately five millimeters . the dermatome 10 also comprises a depth adjuster system . the depth adjuster allows the surgeon to adjust the depth of the blade 22 that is exposed to the patient &# 39 ; s skin and thus control the depth of the skin harvested or tissue excised during the surgery . as shown in fig7 , the depth adjuster system is comprised of two stepper motor actuators 36 in communication with means for activating the actuators , preferably a button panel 48 . two actuators are preferable for safety and stability of the dermatome 10 . by pushing button 50 , the actuator 36 extends the blade 22 in increments ( e . g . 2 / 1000 inch ) towards the front end 20 of the head unit 16 . by protracting the blade , the portion of the blade 22 that is exposed is increased . in one embodiment , in addition to moving the blade forward , the blade is also tilted downwardly . button 50 can subsequently be pushed to further adjust the blade exposure as necessary for the particular medical procedure . in contrast , by pushing button 52 , the blade 22 is retracted away from the front end 20 of the head unit 16 and the exposed blade is decreased by an increment , such as 2 / 1000 inch . button 52 can also be pushed again to adjust the blade exposure as necessary for the particular medical procedure . in an alternative embodiment , the blade 22 can be controlled by buttons 50 , 52 allowing the user of the dermatome to also change the blade angle on the fly ( i . e . in real time ). the depth adjuster system and blade 22 are configured to cut as small as 30 / 1 , 000 inch of skin tissue . in an alternative embodiment , the depth adjuster system can be controlled electronically through use of one or more lasers and one or more sensors in the dermatome 10 . as the dermatome 10 contacts the skin of the patient , the laser ( not shown ) emits light through the skin . the reflected light is then received by a sensor ( not shown ). the amount of light received by the sensor will differ depending on the depth of the damaged tissue . the laser and sensor are integrated into a feedback system in which the blade guard units 26 and depth adjuster system can be electronically altered to ensure that only damaged tissue is cut . as an alternative to a laser , a low powered ultrasound ( not shown ) could also be used in this feedback system . the blade 22 comprises a low friction coating , preferably teflon ® coating or carbon - like diamond coating which allows multiple harvests and / or excisions without the need to lubricate or change the blade . the battery 14 alleviates the need for heavy tubing and an air connection , thus making the dermatome 10 lighter and easier to operate . the dermatome is preferably made of aluminum , magnesium alloys , or other composite materials . these materials are significantly lighter than steel . as shown in fig3 - 4 , the head unit 16 and the handle 12 are attached via complementary connectors found on the back end 18 of head unit 16 and the front end 38 of the handle 12 . by holding the lever 40 on the back end 20 of the head unit 16 , power is supplied from the battery 14 to allow movement of the blade 22 . the lever 40 is in communication with the other portions of the dermatome 10 via a circuit board or processor of the type that is well - known to those skilled in the art . in one embodiment , the dermatome 10 is also comprised of a safety button 54 located on the button panel 48 . in this embodiment , the lever 40 must be held and the safety button 54 pushed before power is supplied from the battery 14 . to stop the motion of the blade 22 , the lever 40 can be released . fig5 and 9 show the inner mechanical workings of the power system of the dermatome 10 , including the battery 14 and the power switch 46 , which is in communication with the lever 40 . the battery 14 is preferably a standard non - sterile ortho pack which is well - known to those skilled in the art . the present invention has been described with reference to certain preferred and alternative embodiments that are intended to be exemplary only and not limiting to the full scope of the present invention . | a dermatome including a battery unit , a handle , and a head portion . the head portion includes guards capable of being adjusted to control the width and the depth of the cut without an interruption in the medical procedure . |
referring first to fig1 of the drawings , a schematic representation of the globe of the eye 10 is shown , which resembles a sphere with an anterior bulged spherical portion 12 that represents the cornea . the eye 10 is made up of three concentric coverings that enclose the various transparent media through which light must pass before reaching the light sensitive retina 14 . the outer - most covering is a fibrous protective portion that includes a posterior layer which is white and opaque , called the sclera 16 , which is sometimes referred to as the white of the eye where it is visible from the front . the anterior ⅙th of this outer layer is the transparent cornea 12 . a middle covering is mainly vascular and nutritive in function and is made up of the choroid 18 , the ciliary 20 and the iris 22 . the choroid generally functions to maintain the retina . the ciliary muscle 21 is involved in suspending the lens 24 and accommodating the lens . the iris 22 is the most anterior portion of the middle covering of the eye and is arranged in a frontal plane . the iris is a thin circular disc corresponding to the diaphragm of a camera , and is perforated near its center by a circular aperture called the pupil 26 . the size of the pupil varies to regulate the amount of light that reaches the retina 14 . it contracts also to accommodate , which serves to sharpen the focus by diminishing spherical aberrations . the iris 22 divides the space between the cornea 12 and the lens 24 into an anterior chamber 28 and posterior chamber 30 . the inner - most covering is the retina 14 , consisting of nerve elements which form the true receptive portion for visual impressions that are transmitted to the brain . the vitreous 32 is a transparent gelatinous mass which fills the posterior ⅘ths the globe 10 . the vitreous supports the ciliary body 20 and the retina 14 . referring to fig2 of the drawings , the globe of an eye 10 is shown as having a cornea 12 with a normal curvature represented by a solid line 34 . for people with normal vision , when parallel rays of light 36 pass through the corneal surface 34 , they are refracted by the corneal surfaces to converge eventually near the retina 14 ( fig1 ). the diagram of fig2 discounts , for the purposes of this discussion , the refractive effect of the lens or other portions of the eye . however , as depicted in fig2 when the eye is hyperopic the rays of light 36 are refracted to converge at a point 38 behind the retina . if the outer surface of the cornea 12 is caused to steepen , as shown by dotted lines 40 , such as through the implantation of a corneal implant of an appropriate shape as discussed below , the rays of light 36 are refracted from the steeper surface at a greater angle as shown by dotted lines 42 , causing the light to focus at a shorter distance , such as directly on the retina 14 . fig3 shows a similar eye system to that of fig2 except that the normal corneal curvature causes the light rays 36 to focus at a point 44 in the vitreous which is short of the retinal surface . this is typical of a myopic eye . if the cornea is flattened as shown by dotted lines 46 through the use of a properly - shaped corneal implant , light rays 36 will be refracted at a smaller angle and converge at a more distant point such as directly on the retina 14 as shown by dotted lines 48 . a hyperopic eye of the type shown in fig2 can be corrected by implanting an implant 50 having a shape as shown in fig4 a , 4 b . the implant 50 is in the shape of a meniscus lens with an outer surface 52 that has a radius of curvature that is smaller than the radius of curvature of the inner surface 54 . when a lens of this type is implanted using the method discussed below , it will cause the outer surface of the cornea to become steeper in shape as shown by reference numeral 40 in fig2 correcting the patient &# 39 ; s vision so that light entering the eye will converge on the retina as shown by the dotted lines 42 in fig2 . the lens 50 shown in fig4 a and 4 b is formed with a bi - meniscus shape , with the anterior and posterior surfaces having different radii of curvature . the anterior surface has a greater radius than the posterior surface . the lens 50 preferably has a nominal diameter of about 4 . 5 mm . the center of the lens is preferably no greater than 50 micrometers thick to enhance the diffusion characteristics of the material from which the lens is formed , which allows for more effective transmission of nutrients through the lens material and promotes better health of the anterior corneal tissue . the outer edge of the lens 50 has a thickness that is less than the dimensions of two keratocytes ( i . e ., about 15 micrometers ) juxtaposed side - by - side , which are the fixed flattened connective tissue cells between the lamellae of the cornea . an edge thickness as specified prevents stacking and recruitment of keratocytes in the lens material so that keratocyte stacking and recruitment does not take place . this in turn eliminates unorganized collagen that forms undesirable scar tissue and infiltrates the lens , which tends to compromise the efficacy of the lens . on the other hand , in order to cure myopia , an implant 56 having the shape shown in fig5 a , 5 b , can be used where an outer surface 58 is flatter or formed with a larger radius than that of the inner surface 60 which is formed with a radius of curvature substantially identical to that of the corneal stroma bed generated by the lamellar dissection described below . the implant 56 has a transition zone 62 formed between the outer and inner surfaces 58 , 60 , which is outside of the optical zone . in this way , the curvature of the outer surface of the cornea , as shown in fig3 is flattened to an extent appropriate to achieve the proper refractive correction desired so that light entering the eye will converge on the retina as shown in fig3 . alternatively , instead of using a solid implant as shown in fig5 a , 5 b , for correcting myopia , a ring 64 of the type shown in fig6 a , 6 b could be used . this ring has substantially the same effect as the implant shown in fig5 a , 5 b , by flattening the outer surface of the cornea shown in fig3 . the ring 64 has a center opening 66 that is preferably larger than the optical zone so as not to cause spherical aberrations in light entering the eye . implants of the type shown in fig4 and 6 can be implanted in the cornea using a lamellar dissectomy shown schematically in fig7 a , 7 b . in this procedure , a keratome ( not shown ) is used in a known way to cut a portion of the outer surface of the cornea 12 along dotted lines 68 as shown in fig7 a . this type of cut is used to form a corneal flap 70 shown in fig7 b , which remains attached to the cornea 12 through what is called a hinge 72 . the hinge 72 is useful for allowing the flap 70 to be replaced with the same orientation as before the cut . as is also known in the art , the flap is cut deeply enough to dissect the bowman &# 39 ; s membrane portion of the cornea , such as in keratome surgery or for subsequent removal of the tissue by laser or surgical removal . a corneal flap of 100 to 200 microns , typically 160 to 180 microns , will be made to eliminate the bowman &# 39 ; s membrane tension . this reduces the possibility of extrusion of the implants due to pressure generated within the cornea caused by the addition of the implant . implants of the type shown in fig4 and 6 are shown implanted in corneas in fig8 and 10 , respectively , after the flap has been replaced in its normal position . these figures show the corrected shape for the outer surface of the cornea as a result of implants of the shapes described . implants can also be formed with a cylindrical addition in one axis of the lens in order to correct for astigmatism , as shown in the implants in fig1 - 16 . such implants can be oval or elliptical in shape , which the longer axis either in the direction of cylindrical power addition or perpendicular to it . for example , the implant can be circular as shown in fig1 a where the implant 72 has axes identified as x , y . in the case of a circular implant 72 , the axes of the implant have different diopter powers as shown in fig1 b and 11 bc , which are cross - sectional views of the implant 72 along the x and y axes , respectively . the different thicknesses of the lenses in fig1 b and 11 c illustrate the different diopter powers along these axes . alternatively , as shown in fig5 a , an astigmatic implant 74 can be oval or elliptical in shape . the implant 74 also has axes x , y . as shown in the cross - sectional views of the implant 74 in fig1 b , 12 c , along those two axes , respectively , the implant has different diopter powers as shown by the different thicknesses in the figures . because implants of the type identified by reference numeral 72 , 74 are relatively small and transparent , it is difficult for the surgeon to maintain proper orientation along the x and y axes . in order to assist the surgeon , tabs 76 a , 76 b or indentations 78 a , 78 b are used to identify one or the other of the axis of the implant to maintain proper alignment during implantation . this is shown in fig1 , 16 where , for example , indentations 76 a , 76 b , are aligned with axis x which has been determined as the proper axis for alignment in order to effect the astigmatic correction . alternatively , other types of markers could be used such as visual indicators such as markings on or in the implants outside of the optical zone . referring to fig1 - 21 , implants with presbyopic corrections are shown . in fig1 , an compound implant 80 is shown , which is appropriate for hyperopic correction , which has an additional power section 82 in the center . as shown , the implant 82 has anterior and posterior curvatures similar to those in fig4 a , 4 b , in order to correct for hyperopia . in fig1 , a central power add 84 is formed on another compound implant 86 , which has a base shape similar to the one shown in fig5 a , 5 b , and is appropriate for a myopic correction . in fig1 , a central power portion 88 is added to an simple planal implant 90 which has outer and inner surfaces of equal radii , which does not add any correction other than the central power . the central power add portions 82 , 84 , and 88 are preferably within the range of 1 . 5 - 3 mm in diameter , most preferably 2 mm , and which provide a multi - focal outer corneal surface where the central portion of the cornea achieves an added plus power for close - up work . in addition to the based device having no correction , or corrections for hyperopia or myopia , the base device can have a simple spherical correction for astigmatism as shown in fig2 a , where a central power add 92 is added to an implant 94 similar to the one shown in fig1 a , which also includes tabs 76 a , 76 b . as shown in fig2 b in order to enhance the acuity of a presbyopic implant , a transition zone 96 can be formed around the central power add 98 for implant 100 . this transition zone 96 is a sharp zone change in power from central added power to peripheral base power and is anchored over a radial distance 0 . 5 to 0 . 2 mm start to from the end of the central zone . implantation of the device shown in fig2 b , is illustrated in fig2 a , 21 b , where a flap 102 formed through a lamellar dissectomy is shown pulled back in fig2 a so that the implant 100 can be positioned , and then replaced as shown in fig2 b for the presbyopic correction . as shown , the formation of a sharp transition 96 on the implant 100 provides a well defined central power after implantation is complete . fig2 and 23 illustrate lenses 166 , 168 , respectively , which are useful for correcting myopia with astigmatism . as shown , these lenses are ring - shaped , similar to the one in fig6 a , 6 b . however , the lenses 166 , 168 include rib sections 166 a , 168 a , respectively , which extend across the center of each lens and define voids between the ribs and the outer periphery of the lenses . these solid rib sections shape the astigmatic component by providing solid portions under the flatter meridian of the astigmatic myopic eye , when these flatter portions are located above the ribs . the ribs 166 a , 168 a can be formed in any suitable shape such as , by way of example , the rib 166 a being squared off as shown in fig2 or the rib 168 a being rounded s shown in fig2 , where they contact their respective rings . another example of a design for correcting myopia with astigmatism is a lens 170 as shown in fig2 , which is also ring - shaped but has one its quadrants 170 a filled in . this lens can be used where the flatter portion of an astigmatic eye is located in a position where the quadrant can be located beneath the flatter portion . the solid portion of the lens will tend to raise the flattened portion so that a smooth rounded outer surface is formed . as can readily be appreciated , lenses can be formed with solid portions located in any number of places where they can positioned under the flattened portion of an astigmatic eye to achieve the same end . the implants described above are preferably formed of a microporous hydrogel material in order to provide for the efficacious transmission of nutrients from the inner to the outer surface of the implants . the hydrogels also preferably have micropores in the form of irregular passageways , which are small enough to screen against tissue ingrowth , but large enough to allow for nutrients to be transmitted . these microporous hydrogels are different from non - microporous hydrogels because they allow fluid containing nutrients to be transmitted between the cells that make up the material , not from cell - to - cell such as in normal hydrogel materials . hydrogels of this type can be formed from at least one , and preferably more , hydrophillic monomer which is polymerized and cross - linked with at least one multi - or di - olefinic cross - linking agent . an important aspect of the materials of the present invention is that the microporous hydrogel have micropores in the hydrogel . such micropores should in general have a diameter ranging from 50 angstroms to 10 microns , more particularly ranging from 50 angstroms to 1 micron . a microporous hydrogel in accordance with the present invention can be made from any of the following methods . hydrogels can be synthesized as a zero gel by ultraviolet or thermal curing of hydrophillic monomers and low levels of cross - linking agents such as diacrylates and other uv or thermal initiators . these lightly cross - linked hydrogels are then machined into appropriate physical dimensions and hydrated in water at elevated temperatures . upon complete hydration , hydrogel prosthesis are flash - frozen to temperatures below negative 40 degree c ., and then gradually warmed to a temperature of negative 20 degree c . to negative 10 degree c . and maintained at the same temperature for some time , typically 12 to 48 hours , in order to grow ice crystals to larger dimensions to generate the porous structure via expanding ice crystals . the frozen and annealed hydrogel is then quickly thawed to yield the microporous hydrogel device . alternatively , the hydrated hydrogel device can be lyophilized and rehydrated to yield a microporous hydrogel . still further , the microporous hydrogel can also be made by starting with a known formulation of monomers which can yield a desired cross - linked hydrogel , dissolving in said monomer mixture a low molecular weight polymer as a filler which is soluble in said mixture and then polymerizing the mixture . resulted polymer is converted into the required device shape and then extracted with an appropriate solvent to extract out the filled polymer and the result in a matrix hydrated to yield a microporous device . still further and alternatively , microporous hydrogels can also be made by any of the above methods with the modification of adding an adequate amount of solvent or water to give a pre - swollen finished hydrogel , which can then be purified by extraction . such formulation can be directly cast molded in a desired configuration and do not require subsequent machining processes for converting . | prosthetic implants designed to be implanted in the cornea for modifying the cornea curvature and altering the corneal refractive power for correcting myopia , and myopia with astigmatism , such implants formed of a micro - porous hydrogel material . |
referring now to the drawings , and more particularly to fig1 , there is shown an agricultural work system 10 that includes an agricultural work vehicle , such as tractor 12 that tows an agricultural implement 14 , which is depicted as a multi - row pivot transport seeder . seeder 14 can include a toolbar 16 with left and right marker assemblies 18 , 20 that are attached to left and right ends 22 , 24 of toolbar 16 , respectively . supports 25 can support marker assemblies 18 , 20 when in a folded position . seeder 14 can include other elements such as drawbar 26 for connection to tractor 12 , large seed hoppers 28 , 29 which provide seeds to row or seed units 30 , and platform and gate assembly 32 for accessing and filling large seed hoppers 28 , 29 . row or planting units 30 can include a variety of elements for dispensing seed , fertilizer , pesticide , herbicide and other agricultural materials . such elements can include , but are not limited to , a furrow opening apparatus ; gage wheels ; a pair of lateral spaced , or staggered , furrow opener discs , or alternatively , and without detracting or departing from the spirit and scope of the present invention , a runner opener type for providing a furrow in the ground ; a pair of furrow closer discs , a seed meter , a press wheel arranged in fore - and - aft relationship relative to each other ; and a agricultural chemical hopper . additionally , seeder 14 can have planting units 30 with individual seed boxes in addition to the large seed hoppers 28 , 29 . as noted above , the seeder 14 has a pair of bulk fill hoppers 28 , 29 . bulk fill hopper 28 holds seed for the seed units 30 mounted to the left wing of frame 16 and bulk fill hopper 29 holds seed for the seed units 30 mounted to the right wing of frame 16 . as shown in fig2 , the seed units 30 are flow coupled to its bulk fill hopper by supply hoses 34 . seed is metered from the bulk fill hopper 28 to the hoses by a seed metering assembly 36 , as known in the art . each seed unit 30 has a seed box 38 and the seed is delivered from the bulk fill hopper to the individual seed boxes 38 . in contrast to a conventional seeder , and in accordance with one embodiment of the invention , supply hoses 34 from the seed metering assembly 36 are flow - coupled to alternating seed boxes 38 . jumper hoses 40 and splitters 42 are used to deliver seed to those seed boxes 38 not directly connected to a supply hose 34 flow - coupled to the seed metering assembly 36 . as will be described more fully below , a seed box that is directly flow - coupled to the seed metering assembly 36 is filled in a first fill stage and thus will be designated as seed box 38 ( a ). a seed box that is indirectly flow - coupled to the seed metering assembly 36 via a jumper hose 40 and splitter 42 is filled in a second fill stage and thus will be designated as seed box 38 ( b ). in the illustrated embodiment , there are equal number first fill stage seed boxes 38 ( a ) and second fill stage seed boxes 38 ( b ). in this regard , for each pair of seed boxes 38 , one is a first fill stage seed box and the other one is a second fill stage seed box . it is understood however that multiple seed boxes may be daisy - chained together such that one seed box 38 ( a ) is directly coupled to the seed metering assembly 36 and a series of jumper hoses 40 and splitters 42 are successive used to flow - couple the downstream seed boxes to the seed metering assembly . with additional reference to fig3 - 4 , splitter 42 has a splitter inlet 44 adapted to engage a quick - connect coupler 46 of a feeder hose 48 . it will be appreciated that the feeder hose 48 may be supply hose 34 or jumper hose 40 depending upon the seed distribution arrangement being used . in the arrangement shown in fig2 , the splitter inlet 44 is flow - coupled to a supply hose 34 . the splitter 42 also has a primary splitter outlet 50 and a secondary splitter outlet 52 . the primary splitter outlet 50 , which is at lower position than the secondary splitter outlet 52 , is adapted to engage a quick - connect coupler 54 of a seed box 38 ( a ) and the secondary splitter outlet 52 is adapted to engage a quick - connect coupler 56 of a jumper hose 40 . while the preferred embodiment is described and shown as having two splitter outlets , it is understood that the splitter 42 may have more than two outlets . the splitter 42 is oriented such that the splitter inlet 44 receives an air / seed mixture along a downwardly and angled flow path , as represented by the velocity flow vector 58 . the air / seed mixture passes from the splitter inlet 44 and is forced under air and gravity to the primary splitter outlet 50 , which passes the air / seed mixture along a vertical downward flow path , generally represented by the velocity flow vector 60 . the secondary splitter outlet 52 extends from the splitter body 62 at angle such that the air / seed mixture generally bypasses the secondary splitter outlet 52 . that is , the secondary splitter outlet 52 is configured to pass air and seed along an angled and upward direction , generally represented by velocity flow vector 64 . the inlet or splitter body 62 includes an outer perimeter 70 and an inner perimeter 72 formed by an opening therethrough . a secondary splitter body 68 also includes an outer perimeter 74 and an inner perimeter 76 formed by an opening therethrough . the secondary splitter body 68 , as discussed in greater detail below , has a first portion 78 of its outer perimeter 74 which is positioned nearest or next to the seedbox 38 ( a ). the secondary splitter body 68 also has a second portion 80 of its outer perimeter 74 which is positioned opposite the first portion 76 . a junction between the first portion 78 and the outer perimeter 70 of the splitter body 62 forms an acute angle , as shown in fig4 by arrow a . a junction on the opposite side , namely , between the second portion 80 and the outer perimeter 70 of the splitter body 62 forms an obtuse angle , shown in fig4 by arrow o . referring now to fig4 a , air / seed mixture is fed to the splitter inlet 44 along the splitter body 62 and passed through primary splitter outlet 50 to load seed into the seed box 38 ( a ) during a primary fill stage . the air / seed mixture will continue to be fed from the inlet 44 to the primary splitter outlet 50 until the seed box 38 ( a ) fills and seed begin to backfill up through the primary splitter outlet 50 . when seed has backed up past the primary outlet 50 into the splitter body 62 to a level generally adjacent the secondary splitter outlet 52 , as shown in fig4 b , seed , entrained in air , that is passed through the splitter inlet 44 will be directed toward the secondary splitter outlet 52 and passed through the secondary splitter outlet 56 along the secondary velocity flow vector 64 . in this regard , the backed up seed closes off the primary splitter outlet 50 to force any incoming air / seed mixture to the secondary splitter outlet 52 during a secondary fill stage . it will be appreciated that negligible quantities of seed may be passed through the secondary splitter outlet 52 during the primary fill stage , but the angled upward orientation of the secondary splitter outlet 52 prevents large amounts of seed from being presented to the secondary splitter outlet 52 until seed has closed off the primary splitter outlet 50 . it will also be appreciated that the use of the terms “ primary ” and “ secondary ” connotes only the fill order and does not suggest any difference in function or importance . referring now to fig5 , the velocity flow vectors representative of the flow of an air / seed mixture is shown . in one preferred embodiment , the angle α formed between the inlet velocity flow vector 58 and the secondary outlet velocity flow vector 64 is a non - obtuse angle , and is preferably an acute angle , such as 85 degrees . the angle β formed between the inlet velocity flow vector 58 and the primary outlet velocity flow vector 60 is an acute angle , and is preferably 80 degrees . the angle γ formed between primary outlet velocity flow vector 60 and the secondary outlet velocity flow vector 64 is an obtuse angle , and is preferably 145 degrees . referring now to fig6 , as noted above , in one embodiment , a jumper hose 40 and a splitter 42 is used to connect a single second fill stage seed box 38 ( b ) to a supply hose 34 that supplies seed to a first fill stage seed box 38 ( a ). in another embodiment , as illustrated in fig7 for example , multiple jumper hoses 40 and multiple splitters 42 may be used “ daisy - chain ” multiple seed boxes . in the arrangement illustrated in fig7 , the arrangement of seed boxes results in the aforedescribed first and second fill stage seed boxes 38 ( a ) and 38 ( b ), respectively , but also includes third fill stage seed boxes 38 ( c ). a third fill stage second seed box 38 ( c ) is filled after its associated second fill stage seed box 38 ( b ) is filled . in this regard , a supply hose 34 is flow - coupled to the inlet 44 of a splitter 42 , a seed box 38 ( a ) is flow - coupled to the primary splitter outlet 50 , and a jumper hose 40 is flow - coupled to the secondary splitter outlet 52 . instead of the other end of the jumper hose 40 being flow - coupled to a seed box 38 ( b ), the jumper hose 40 is flow - coupled to the splitter inlet 44 of another splitter 42 . the primary splitter outlet 50 is flow - coupled to a seed box 38 ( b ) and the jumper hose 40 is flow - coupled at one end to the secondary splitter outlet 52 and an opposite end to a seed box 38 ( c ). the configuration of the splitter 42 interconnected between the second fill stage seed box 38 ( b ) and the third fill stage seed box 38 ( c ) is similar in function to the splitter interconnected between the second fill stage seed box 38 ( b ) and the first fill stage seed box 38 ( a ). as such , the third fill stage seed box 38 ( c ) is not filled with seed until after the second fill stage seed box 38 ( b ) has been filled . thus , in this embodiment , a single supply hose 34 may be used to deliver seed to three ( 3 ) seed boxes . it is understood that additional jumper hoses and splitters may be used to link more than three ( 3 ) seed boxes to one another to further reduce the number of hoses flow - coupled directly to the seed metering assembly 36 . the invention has been described with respect to delivering seed to a series of seed units . it is understood however that the invention may also be used to deliver other particulate matter , such as granular herbicide , granular fertilizer , or other granular chemicals to a series of dispensing units . many changes and modifications could be made to the invention without departing from the spirit thereof . the scope of these changes will become apparent from the appended claims . | a splitter divides an air / product mixture flow , delivered thereto in an air - powered distribution line , between a primary and a secondary distribution channel , which may be flow - coupled to a product hopper or a hose flow - coupled to another product hopper or another splitter . the air / product mixture enters the inlet of the splitter along an angled downward flow path and exits a primary outlet , flow - coupled to the primary distribution channel , along a vertical downward flow path . air / product flow is exhausted by a secondary outlet , which is flow - coupled to the secondary distribution channel , at an angled upward flow path . the velocity flow vector along which the air / product mixture is exhausted from the secondary outlet is at an acute angle relative to the velocity flow vector along which the air / product mixture is received by the inlet of the splitter . |
[ 0020 ] fig1 illustrates a pad 10 having a first sealable bag 12 , a first hypothermia and / or hyperthermia device 14 , and a pad cover 16 . the bag 12 contains at least a first conformable material 18 , and a thermally conductive medium 20 . the thermal conductive medium 20 is any liquid or viscous gel that transfers energy generated by the device 14 to a patient ( not shown ). examples of this liquid include water , water - based solutions , oil - based solutions , oils , alcohols , mixtures thereof , and viscous gels . the conformable material 18 is any material having apertures that do not easily kink , preferably , a gelatinous elastomeric material . examples of types of gelatinous materials , which are heat formable and heat reversible , are fully described in u . s . pat . nos . 4 , 369 , 284 , 4 , 618 , 213 , 5 , 262 , 468 , 5 , 336 , 708 , and 5 , 508 , 334 , which are hereby incorporated by reference herein , and those made by pittsburgh plastic . the gelatinous materials manufactured by pittsburgh plastic are allegedly distinct from the patented types . this conformable material can be of any shape or design , so long as it has a three - dimensional shape that supports a patient or object on the pad 10 . the hypothermia and / or hyperthermia device 14 is any conventional hypo / hyperthermia blanket — an example of this blanket is the mul - t - pad ® or the thermacare ® blanket by gaymar industries , inc . of orchard park , n . y .— and its corresponding pump — the medi - therm ii ® temperature regulator by gaymar industries , inc . of orchard park , n . y .—, an electric blanket , a cold compress , and a convective device . the convective device pumps or blows air or other gaseous medium ( collectively “ air ”) having a predetermined temperature . the air obtains the desired temperature in a conventional air temperature regulator ( for example , an air conditioner , a heat pump , a thermacare ® blower unit , or the medi - therm ii ® temperature regulator ) and then circulates through a mesh screen like the air queen by teijin , inc . or a nonwoven polymeric device having a plurality , of tubes with numerous apertures therein . the air is then distributed throughout the entire pad 10 . in any embodiment of device 14 , the device 14 affects the temperature that a patient ( not shown ) or object ( not shown ) is exposed to , and , in some embodiments , the medium 20 that encompasses the conformable material 18 . the bag 12 is any sealable instrument that contains at least the thermally conductive medium 20 and conformable material 18 in place . preferably , the bag 12 is plastic , and it can be sealed thermally , acoustically , by a zipper , zip locked , or even by velcro ®. the pad cover 16 is any conventional material used to cover a pad 10 . the pad cover 16 can encompass the entire pad 10 , the preferred embodiment as shown , or cover the pad 10 like a conventional mattress sheet . in either embodiment the pad cover 16 can be cloth , leather , plastic or conventional cover material . the materials of the pad cover 16 allow the patient or object , on the pad 10 , to feel the desired temperature of the pad 10 ( air or medium 20 ). the pad cover 16 can also allow moisture to pass through it . thereby , it helps control the patient &# 39 ; s temperature and prevents overcooling or overheating . turning to fig2 a patient 22 disperses a portion of the thermal conductive medium 20 in the bag 12 and contacts at least a portion of the conformable material 18 when the patient 22 lies on the pad 10 . the conformable material 18 provides support to the patient 22 , increases the effective surface contact of the pad 10 to the patient 22 to ensure greater desired thermal conductivity to the patient 22 , maintains the stability of the bag 12 , and reduces the pressure to the patient 22 . by maintaining the stability of the bag 12 , the conformable material 18 ensures the patient ( or object ) 22 , on the pad 10 , from directly contacting the hypothermia and / or hyperthermia device 14 . in other words , the patient 22 does not “ bottom out ” to or directly contact the device 14 . in a preferred embodiment , the conformable material 18 has apertures 24 . the apertures 24 , in this embodiment , go from the bottom to the top of the material 18 and ensure the thermal conductive medium 20 is between the patient 22 and the hypothermia and / or hyperthermia device 14 . however , in order to decrease , and essentially avoid , kinking — which is discussed above and , as a reminder , inhibits the medium 20 or the air from contacting the patient — and which is common in many mattress materials , the preferred embodiment of the conformable material 18 is a gelantinous elastomer material . the gelantinous elastomer material has a structure design that admittedly bends and indents , as shown in fig9 when a patient lies thereon , but does not kink . thereby , the air or medium can go through the apertures 24 . the hypothermia and / or hyperthermia device 14 heats or cools the thermal conductive material 20 and the patient 22 to a predetermined temperature . since the thermal conductive material 20 contacts most , if not all , portions of the contacting side 23 of the patient 22 , the material 20 ensures a uniform , or nearly uniform application of the predetermined temperature to the contacting side 23 . turning to fig3 the pad 10 contains at least a second bag 12 a . the second bag 12 a has at least a second conformable material 18 a and a second thermal conductive material 20 a . the second thermal conductive material 20 a , the second bag 12 a , and the second conformable material 18 a can be the same or different materials as the previously listed corresponding elements 12 , 18 , 20 . turning to fig4 an alternative embodiment of fig3 is shown . a second hypothermia and / or hyperthermia device 14 a is positioned under the second bag 12 a . the second hypothermia and / or hyperthermia device 14 a can be set at the same or different temperature as the hypothermia and / or hyperthermia device 14 . thereby , the first thermally conductive material 20 can apply one temperature to one portion of the contacting side 23 b of the patient 22 and the second thermally conductive material 20 a can apply the same or a different predetermined temperature to another portion contacting side 23 c . turning to fig5 an alternative embodiment of fig4 is shown . a third conformable material 18 b underlies the hypothermia and / or hyperthermia devices 14 , 14 a . this material 18 b offers further support to the patient 22 , maintains the stability of the bags 12 , 12 a , and further reduces the pressure to the patient 22 . obviously , this third material 18 b can underlie , or alternatively be over ( not shown ), the hypothermia and / or hyperthermia device ( s ) 14 , 14 a of fig1 - 4 . turning to fig6 an alternative embodiment of fig1 is shown . the hyperthermia and / or hypothermia device 14 is within the bag 12 under , or alternatively be over ( not shown ), the conformable material 18 and surrounded by the thermal conductive medium 20 . in this embodiment , the conventional inlet - outlet 77 of the device 14 , i . e ., the pump hoses of the medi - therm ii ® system , protrudes from the sealed bag 12 . obviously this embodiment can be used in the other embodiments illustrated in fig3 and 4 . [ 0032 ] fig7 illustrates an alternative embodiment of fig1 wherein the conformable material is not inserted in a bag 12 or surrounded by a medium 20 . in this embodiment , the hypothermia and / or hyperthermia device 14 is a convective unit and the air goes through the apertures 24 of the gelatinous elastomer material 18 . [ 0033 ] fig1 and 12 a illustrate an alternative embodiment of fig7 . along with the apertures 24 , the conformable material 18 has a plurality of side apertures 24 a interspaced between the upper wall 560 and a lower wall 562 of the material 18 . side apertures 24 a receive air and then distribute the air throughout the conformable material 18 . in one embodiment ( like that shown in fig7 ) the device 14 is positioned below the conformable material 18 . in yet another embodiment , as shown in fig1 , the device 14 is positioned at an end 563 of the conformable material 14 . thereby the air goes into the side apertures 24 a and is distributed throughout the conformable material 18 and apertures 24 , to effect the patient &# 39 ; s 22 temperature . turning to fig1 , another embodiment of the present invention relates to the positioning of the hypothermia and / or hyperthermia device 14 . the device 14 can also be positioned above the conformable material 18 . the device 14 adjusts the temperature of the air within the pad 10 , and that air cools or heats or maintains the temperature of the patient 22 . the air also circulates through the pad 10 within the apertures 24 ( and maybe 24 a ). turning to fig1 and 11 , the air of fig7 circulates under the cover 16 , and escapes from , preferably predetermined , a gap 345 in the cover . extending from gap 345 is a tube 347 , flexible or not , that directs the air under a conventional blanket 348 , as shown in fig1 , or into an aperture 349 of a convective blanket 350 , like the thermacare ® blanket by gaymar industries , inc ., as shown in fig1 . alternatively , the pad cover 16 has a material that transfers the temperature to the patient but influences the air to a predetermined gap ( s ) 345 in the pad 10 . the predetermined gap ( s ) 345 can be located anywhere within the pad , i . e . at the bottom of the pad , a side of the pad as shown in fig1 and 11 , if necessary , under the patient 22 , or under the blanket 348 directly . turning to the method of the invention the preferred embodiment of the present invention is as an operating table pad and / or any other structure or object used in an operating room or hospital - like mattress system , such as bed systems or seat cushions . an operating technician inserts at least one pad 10 , having a hypothermia and / or hyperthermia device 14 , and a conformable material 18 , under a predetermined area of a patient 22 . the technician then adjusts the device 14 to a predetermined temperature , in some instances the device 14 can only obtain one temperature . in either case , the device 14 adjusts the pad 10 to the predetermined temperature . at any time before or after the device 14 is initially adjusted to the predetermined temperature , the patient 22 lies on the pad 10 and the contacting side 23 of the patient 22 will be or is exposed to the predetermined temperature . although a particular preferred embodiment of the invention has been illustrated and described in detail for illustrative purposes , it will be recognized that variations or modifications of the disclosed apparatus , including the rearrangement of parts , lie within the scope of the invention defined by the claims . the embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows : | the present invention relates to a first conformable material having a three - dimensional shape and a first hypothermia and / or hyperthermia device . this invention is used as a pad for sleeping , lying down , or sitting , to maintain a desired temperature to the contacting surface of a body to the pad . |
fig1 shows a complete longitudinal section of an injection apparatus . it is a gear rack pen for self - administering , for example , insulin or growth hormones . a first , front casing section 1 and a second , rear casing section 3 form a casing of the pen . the casing sections 1 and 3 are sleeve bodies . to form the casing , they are plugged into each other along a common central longitudinal axis l , in a non - releasable connection . furthermore , the connection is such that the casing sections 1 and 3 cannot be moved relative to each other , either axially or rotationally about the longitudinal axis l . an ampoule 2 accommodated in the front casing section 1 forms a reservoir for a product which is administered by way of injection using the pen . an outlet of the ampoule 2 is sealed by a membrane . an injection needle n is however guided through the membrane and protrudes via a rear end into the ampoule 2 . a piston k is accommodated at a rear end of the ampoule 2 facing away from the outlet . an axial movement of the piston k along the longitudinal axis l in an advancing direction pointing towards the ampoule outlet delivers product from the ampoule 2 and through the injection needle n , thus administering it . in the state shown , the front casing section 1 is covered by an outer protective cap p and the injection needle n , still separate , is covered by an inner protective cap which of course has to be removed before administering . the rear casing section 3 forms a mechanism holder by mounting a piston rod 8 acting on the piston k in the advancing direction and the other components of the pen , which participate in selecting a product dosage to be delivered and delivering the product dosage selected . these other components are a drive member 10 and an operating element 18 which together form a drive device 37 for the piston rod 8 , and furthermore a dosing member 35 which in cooperation with the rear casing section 3 serves to select the product dosage to be delivered from the ampoule 2 . in fig2 , these components and their couplings are shown enlarged . reference may also always be additionally made to the cross - sectional representation in fig3 . on the outer surface of the piston rod 8 , four rows of teeth 9 formed from serrated teeth extend in the longitudinal direction , each offset by 90 ° with respect to each other . the rows of teeth 9 each exhibit the same separation . each of the rows of teeth 9 is offset by a quarter pitch with respect to each of the other rows of teeth 9 , in order to improve the dosing precision in a way known in its own right . the rear casing section 3 forms blocking elements 4 which engage with the rows of teeth 9 . the piston rod 8 is blocked by the engagement of the blocking elements 4 , such that it is not possible to move the piston rod 8 counter to the advancing direction of the piston k . movement of the piston rod 8 in the advancing direction , however , is permitted . in order to advance the piston rod 8 , the drive device 37 engages with the rows of teeth 9 of the piston rod 8 via slaving means 11 , behind the blocking elements 4 . the drive device 37 is formed by the sleeve - shaped drive member 10 and the sleeved - shaped operating element 18 . the operating element 18 is pushed from behind onto the drive member 10 . the connection between the drive member 10 and the operating element 18 is such that the operating element 18 cannot be axially moved relative to the drive member 10 , but can be rotated about the longitudinal axis l relative to the drive member 10 . the longitudinal axis l forms a translational axis of the drive device 37 and the driven device k , 8 consisting of the piston k and the piston rod 8 , and furthermore , a rotational axis of the operating element 8 . the drive device 37 viewed as a whole protrudes through the dosing member 35 . the slaving means 11 of the drive member 10 can be bent free , in particular free from the dosing member 35 , elastically outwards from the mesh , in the radial direction , in order to enable the drive device 37 to move relative to the piston rod 8 counter to the advancing direction . the slaving means 11 are formed in a section of the drive device 37 protruding forwards out of the dosing member 35 ; in the example embodiment , they form the front end of the drive device 37 . the engagement of the slaving means 11 and the shape of the rows of teeth 9 are such that the piston rod 8 is necessarily slaved by a movement of the drive device 37 in a drive direction directed towards the piston k , said drive direction being identical to the advancing direction . in the depicts exemplary embodiment , the rows of teeth 9 are pointed in the advancing direction in a shape of serrated teeth . in modified embodiments , however , the piston rod 8 could comprise , instead of one or more rows of teeth 9 , recesses or other engaging means for slaving means of a drive device , if it is only ensured that piston rod 8 is necessarily slaved in the advancing direction but is prevented from being slaved counter to the advancing direction . the dosing member 35 is formed by a sleeve - shaped inner dosing body 13 and a sleeve - shaped outer dosing body 14 , which are produced as separate parts and immovably connected to each other . in particular , it is not possible for the two dosing bodies 13 and 14 to either axially move or rotate about the longitudinal axis l relative to each other . the outer dosing body 14 concentrically surrounds the inner dosing body 13 . a slight annular gap , into which the likewise sleeve - shaped rear casing section 3 protrudes , remains circumferential between the two dosing bodies 13 and 14 . the rear casing section 3 , together with the dosing body 35 , forms a swivel joint , more precisely a screw joint , which causes a rotational movement of the dosing member 35 about the longitudinal axis l to result in a translational movement of the dosing member 35 in or counter to the advancing direction , i . e ., a axial translational movement relative to the rear casing section 3 , depending on the direction of rotation . the longitudinal axis l forms a rotational axis and a translational axis of the dosing member 35 . to form the swivel joint , the rear casing section 3 and the dosing member 35 are in threaded engagement . the threaded engagement is between an inner thread 6 formed on an inner surface area of the rear casing section 3 and an outer thread 16 formed on an outer surface area of the inner dosing body 13 . although less preferred , the threaded engagement could instead also be formed between an outer thread of the rear casing section 3 and an engaging inner thread of the outer dosing body 13 . by rotating the dosing body 35 , the user selects the product dosage to be administered . since , through the threaded engagement , the dosing member 35 also simultaneously performs an axial translational movement , a delivery stroke of the length ah is set for the drive device 37 , which corresponds to the product dosage selected . the inner dosing body 13 forms a dosing stopper 15 which limits the movement of the drive device 37 counter to the advancing direction . more precisely , a facing area of the dosing stopper 15 pointing in the advancing direction forms the dosing stopper 15 at its front end . the dosing stopper 15 is formed by an annular collar running around the longitudinal axis l , said collar protruding radially inwards towards the drive member 10 via an inner surface area of the inner dosing body 13 . the dosing stopper 15 , more precisely its front stopper area , runs around the longitudinal axis l at an axially constant height , i . e . a linear dosing stopper 15 is formed at a single height . opposite the dosing stopper 15 in the advancing direction , the rear casing section 3 forms a delivery stopper 5 which limits the movement of the drive device 37 in the advancing direction . the drive device 37 can thus be moved in and counter to the advancing direction between the delivery stopper 5 , which is fixed to the casing and even formed by the rear casing section 3 itself , and the translationally adjustable dosing stopper 15 . the drive device 37 in turn forms a counter stopper , namely the delivery and dosing stopper 12 , on an outer surface area of the drive member 10 . the delivery and dosing stopper 12 is formed by an annular collar via a front stopper area facing the delivery stopper 5 and a rear stopper area facing the dosing stopper 15 . the delivery and dosing stopper 12 protrudes radially outwards from an outer surface area of the drive member 10 towards a facing inner surface area of the rear casing section 3 . the rear casing section 3 is completely transparent or at least transparent in the section which overlaps a maximum delivery stroke of the drive device 37 . the transparency serves to verify the axial position of the drive device 37 , in particular the position of the drive member 10 which engages directly with the piston rod 8 and is rigidly connected to it via the engagement in the advancing direction . for the purpose of a particularly precise optical verification , the drive member 10 is provided with a thin marking line , preferably a circumferential marking line , which is clearly visible through the rear casing section 3 and forms an indicator 32 ( fig9 to 11 ). advantageously , the delivery and dosing stopper 12 itself can form the marking line by forming a thin tip , radially outwards . the delivery and dosing stopper 12 is suitable as an indicator for verifying , alone because it radially protrudes almost directly up to the rear casing section 3 or even contacts it with sliding contact . the radially outer surface area of the delivery and dosing stopper 12 or the entire , radially outer tip is preferably additionally provided with a thin marking line which is attached on the surface or in a recess on the surface or is formed in the material , and can advantageously be fluorescent . as may be seen in connection with fig9 to 12 , and in particular in fig1 , the rear casing section 3 comprises a dosage scale 30 over the length of a maximum delivery stroke ahmax . the dosage scale 30 can be attached to the inner surface area or more preferably to the outer surface area of the rear casing section 3 or let into the transparent surface of the rear casing section 3 . in the example embodiment , it is attached to the outer surface area . the dosage scale 30 is formed by dosage numbers which indicate dosage units and by dosage marks 31 . each of the dosage numbers is each assigned to one of the dosage marks 31 . the dosage marks 31 are formed by short , thin lines which each extend in the circumferential direction of the rear casing section 3 . the dosage numbers are arranged over the circumference of the casing section 3 , ascending towards the rear , in the form of spiral around the rotational axis l of the dosing member 35 . correspondingly , the dosage marks 31 are spirally arranged , such that each of the dosage marks 31 exhibits a different axial height to each of the other dosage marks 31 . the dosage marks 31 thus represent , in a fine axial grading , every product dosage which can be selected and delivered in whole dosage units . due to the transparency of the rear casing section 3 , the axial position of the drive device 37 can be read , namely as the axial position which the indicator 32 of the drive device 37 assumes relative to the dosage marks 31 . in the example embodiment , the cited marking line running around the longitudinal axis l on the radially outer tip of the delivery and dosing stopper 12 forms the indicator 32 of the drive device 37 . in order to make it easier to read the dosage scale 30 , in particular for people with low visual acuity , the outer dosing body 14 comprises a viewing window 34 in a surface section which overlaps the dosage scale 30 , said viewing window being developed into a magnifier 34 a . the viewing window 34 is sufficiently large and of such a shape that precisely one of the dosage numbers of the dosage scale 30 can be identified as the dosage selected , through the viewing window 34 . in the example embodiment , it is only ever possible to read exactly one dosage number through the viewing window . in order that the dosage can be selected in discrete steps corresponding to the dosage numbers of the dosage scale 30 , the dosing member 35 and the rear casing section 3 are each in releasable latching engagement in discrete rotational angular positions which the dosing member 35 can assume relative to the rear casing section 3 . the latching engagement is formed between axially extending grooves 7 and engaging members 17 which engage with the grooves 7 . in the example embodiment , the axial grooves 7 are let into the rear casing section 3 on the outer surface area . the engaging members 17 are correspondingly formed as short latching cams on the inner facing surface area of the outer dosing body 14 . the engaging members 17 are linearly guided axially in the axial grooves 7 in each of the discrete rotational angular positions of the dosing member 35 . a rear end position of the dosing member 35 is defined by the engaging members 17 abutting a rear facing limiting area of the axial grooves 7 . a front end position of the dosing member 35 is defined by a rear connecting stay , which the dosing bodies 13 and 14 form between themselves , abutting against a rear facing area of the rear casing section 3 . the dosing member 35 can be adjusted back and forth , from rotational angular latching position to rotational angular latching position , between these two extreme dosing positions , in order to axially adjust the dosing stopper 15 . the maximum delivery stroke ahmax of the drive device 37 is as large as the axial distance which the dosing stopper 15 exhibits from the delivery stopper 5 in the rear end position of the dosing member 35 minus the axial thickness of the delivery and dosing stopper 12 . although the user can at any time freely alter the product dosage set between the two extreme dosing positions , it is advantageous for most applications if a dosage , once set , no longer has to be altered . the injection apparatus can therefore be flexibly set to the needs of different users on the one hand , and used with an optimal setting for a particular user for repeatedly administering the same product dosage . in this sense , a dosage memory is also simultaneously obtained through the dosing member 35 which can be rotationally and translationally moved and therefore adjusted in combination , relative to the rear casing section 3 . one advantage which should by no means be neglected is that the dimensional accuracy and simply regulation of the dimensional accuracy and the stable design of the components which are decisive for dosing and delivery are realized using very few components . this contributes to the fact that the apparatus has a simply design and not least is therefore cheap , but nonetheless operates with precision and ensures exact dosing . the nested arrangement of the dosing bodies 13 and 14 is also advantageous , providing multi - functionality of the dosing member 35 despite its simple construction . for the dosing member 35 directly forms the dosing engagement with the casing of the injection apparatus , the dosing stopper 15 for the drive device 37 , a gripping part for the user and a part of a duplex dosage display , namely the display for the dosage selected on the one hand and the display for the dosage delivered on the other . as a further advantage , the injection apparatus enables simple and reliable priming , i . e ., bleeding the product - guiding parts between the piston k and the exit opening of the injection needle n . to illustrate the priming function , reference is made to fig1 and 2 and in particular also to fig3 , 4 and 5 . in order to fulfill the priming function , the inner dosing body 13 and the operating element 18 are engaged . the engagement consists of a guiding curve and an engaging member which engages with the guiding curve . the engaging member can be moved in a defined manner in the guiding curve between axial stoppers on the one hand and radial stoppers on the other . the guiding curve on the one hand and the engaging member on the other are formed on the mutually facing surface areas of the inner dosing body 13 and the operating element 18 . as shown in fig3 and 4 , the engaging member indicated as 19 is formed on an outer surface area of the operating element 18 , while the guiding curve indicated as 20 is let into the facing inner surface area of the inner dosing body 13 . the guiding curve 20 comprises a long axial section 21 and a contrastively short axial section 22 and a connecting section 24 which extends in the circumferential direction and connects the two axial sections 21 and 22 to each other , at their rear ends . the two side walls of the axial sections 21 and 22 , which oppose each other in the circumferential direction in the area of the connecting section 24 , form rotational stoppers 25 and 26 for the engaging member 19 . the long axial section 21 extends in the advancing direction up to the dosing stopper 15 , more precisely up to the rear facing area of the annular collar forming the dosing stopper 15 . the shorter axial section 22 runs parallel to the axial section 21 and is formed as a short blind groove . a front facing area of the axial section 22 forms a priming stopper 23 . the axial sections 21 and 22 feed onto the rear facing end of the inner dosing body 13 . the connecting section 24 is correspondingly open at the rear facing end . the engaging member 19 is formed by an axial rib formed on the outer surface of the operating element 18 . this axial rib forms the priming stopper on its free front facing area . because the engaging member 19 engages with the guiding curve 20 formed in this way , the operating element 18 can perform the shape of the movement corresponding to the guiding curve 20 , relative to the inner dosing body 13 , namely any selected delivery stroke ah up to the maximum delivery stroke ah max , the contrastively smaller priming stroke ph and the rotational selecting movement . since the operating element 18 is connected to the drive member 10 such that it cannot move axially but can rotate about the longitudinal axis l , the operating element 18 can be rotated back and forth between the rotational stoppers 25 and 26 without acting on the drive member 10 . axial translational movement in either the long axial section 21 or the short axial section 22 is then only possible , however , together with the drive member 10 . because the connecting section 24 is arranged on the rear ends of the axial sections 21 and 22 , the rotational movement of the operating element 18 between the two rotational stoppers 25 and 26 , i . e ., from the delivery position to the priming position and vice versa , is only possible when the drive member 10 is abutting the dosing stopper 15 via its delivery and dosing stopper 12 . in this “ loaded ” position , the engaging member 19 can be moved by rotating the operating element 18 relative to the inner dosing body 13 against the rotational stopper 25 and thus into axial flush with the priming stopper 23 . in this rotational angular position of the operating element 18 , the priming position , the drive device 37 can be moved in the advancing direction by axially pressing onto the operating element 18 up to the priming stopper 23 . the axial length ph of this priming stroke is only a few dosing units , for example two , three or four dosing units . the axial distance between the priming stopper 23 and the priming counter stopper which forms the engaging member 19 is correspondingly short . it is advantageous if the operating element 18 is in releasable latching engagement with the inner dosing body 13 flush with the axial sections 21 and 22 , i . e ., on the rotational stoppers 25 and 26 , respectively . in order to obtain the latching engagement with the inner dosing body 13 in each of the delivery position and the priming position , the engaging member 19 is again provided with a thin , axial latching cam on its narrow outer surface area , said cam coming to rest in the two rotational stopper positions of the operating element 18 in each of two axial latching grooves formed correspondingly in the guiding curve 20 . in the exemplary embodiment , two identical guiding curves 20 and engaging members 19 are provided which diametrically oppose each other . in the variant of fig4 , the connecting section 24 runs , simply linearly , at a single axial height . fig5 shows a guiding curve 20 with a connecting section 24 ′ whose front guiding wall leads from the priming stopper 23 obliquely backwards into the long axial section 21 . due to the oblique trajectory of the connecting section 24 ′, a translational movement of the operating element 18 — and together with it of the drive member 10 — counter to the advancing direction and relative to the piston rod 8 is caused by a reverse rotational movement of the operating element 18 from the rotational stopper 25 towards the rotational stopper 26 . in accordance with the embodiment of a priming process , the user therefore does not have to specially retract the drive device 37 again relative to the piston rod 8 , i . e . load it . rather , the winding or loading movement is forced by the reverse rotational movement . the guiding curve 20 in fig5 otherwise corresponds to the guiding curve 20 in fig4 . the functionality of an embodiment of an injection apparatus in accordance with the present invention will now be described . fig6 and 9 show the rear part of the injection apparatus in a longitudinal section , and each in a view in a state from which the dosage can be selected . correspondingly , the drive device 37 abuts the delivery stopper 5 , and the dosing member 35 assumes its axially front end position . a slight distance remains between the delivery and dosing stopper 12 of the drive device 37 and the dosing stopper 15 of the dosing member 35 , said distance corresponding to two dosing units . accordingly , the dosage of two dosage units can be read in the viewing window 34 . furthermore , the dosage mark 31 assigned to this dosage can also clearly be seen . since the drive device 37 abuts the delivery stopper 5 via its delivery and dosing stopper 12 , the marking line of the drive device 37 forming the indicator runs parallel to the dosage mark 31 , with an axial distance . the distance corresponds to two dosage units . this situation can be seen in fig9 . the injection apparatus is “ loaded ” by retracting the drive device 37 , relative to the piston rod 8 , up to the dosing stopper 15 . when this loading movement has been performed , two dosing units can be delivered by then advancing the drive device 37 and the thereby slaved piston rod 8 . fig1 shows this state , in which the drive device 37 abuts the dosing stopper 15 via its delivery and dosing stopper 12 . the dosing mark 31 assigned to the dosage number “ 2 ” and the indicator overlap each other exactly . from the state shown in fig6 and 9 , the user selects the dosage . to select the dosage , the dosing member 35 has merely to be rotated about the longitudinal axis l relative to the rear casing section 3 . here , the outer dosing body 14 forms a gripping part and the inner dosing body 13 forms a dosing screw whose rotational movement is directly converted into the axial adjusting movement by the threaded engagement , for the purpose of selecting the dosage . the dosing is in discrete rotational angular positions which the dosing member 35 successively assumes relative to the rear casing section 3 . fig7 and 11 show the injection apparatus directly after the dosage has been selected . a dosage of 42 dosage units has been set , as can be read in the viewing window in fig1 . in the state shown in fig7 , selecting the dosage has been concluded but the injection apparatus is not yet “ loaded ”, for the drive device 37 is still abutting the dosing stopper 5 . this is indicated on the dosage scale 30 by the indicator 32 , as can be seen in fig1 . fig8 shows maximum dosing . fig1 shows the injection apparatus in a state in which selecting the dosage has been concluded but the drive device 37 has not been retracted by the thus defined delivery stroke of length ah , but rather only by a part of this stroke . in the state shown by way of example in fig1 , the drive device 37 has been retracted by a stroke corresponding to a product dosage of eight dosage units . this is indicated in fig1 by the axial position of the indicator 32 on the dosage scale 30 . as illustrated in fig1 , a simple but reliable display of the remaining amount is obtained through the transparency of the rear casing section 3 , the form of the indicator 32 and the arrangement of the dosage scale 30 . if , namely , the ampoule no longer contains the full product dosage of , for example , 42 dosage units before the drive device 37 is retracted , then the drive device 37 can only be retracted counter to the advancing direction until the length of its next delivery stroke in the advancing direction corresponds to the product dosage still available in the ampoule 2 for a final delivery . in the exemplary embodiment , this remaining amount is eight dosage units . the indicator 32 and the dosage mark 31 assigned to the dosage of eight dosage units correspondingly overlap each other . the remaining amount which can be delivered is defined by a stopper acting between the piston rod 8 and the drive device 37 . this stopper limits the effective length of the piston rod 8 , i . e . the length by which the piston rod 8 can be moved as a whole in the advancing direction , from its position before a first delivery up until the ampoule 2 is evacuated . in the exemplary embodiment , the piston rod 8 forms this stopper for the slaving means 11 in its rear part , i . e ., the slaving means 11 cannot elastically evade this stopper . in the foregoing description , embodiments of the invention , including preferred embodiments , have been presented for the purpose of illustration and description . they are not intended to be exhaustive or to limit the invention to the precise form disclosed . obvious modifications or variations are possible in light of the above teachings . the embodiments were chosen and described to provide the best illustration of the principals of the invention and its practical application , and to enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated . all such modifications and variations are within the scope of the invention as determined by the appended claims when interpreted in accordance with the breadth they are fairly , legally , and equitably entitled . | an administering apparatus with a dosage display , including a casing , a reservoir for a fluid product , a driven device which acts on the product , a dosing means for selecting a product dosage to be delivered which includes a dosage scale including a number of dosage marks axially spaced from each other , and a drive device coupled to the driven device for driving the driven device , the drive device performing a delivery stroke from an initial position , in a drive direction , to a delivery stopper , the length of the delivery stroke counter to the drive direction being limited by selecting the product dosage using the dosing means , wherein the casing is transparent at least in an area overlapping the dosage scale , and wherein the drive device forms an indicator to the dosage scale in order to indicate the initial position of the drive device . |