The present invention relates to an injection device capable of delivering multiple doses of a liquid medicament contained therein without the need to refill the device between doses.
Various types of drug treatments, including hormone therapy and the like, require administration of the drug-containing liquid medicament at regular intervals over an extended period of time. For example, a specific hormone treatment can require daily administration of the drug for a period of thirty days. In such a situation, it is advantageous to provide a device that allows the patient to self-administer the injection to avoid repeated trips to a doctor's office or the like.
Various injection devices have been developed that allow self-administration of multiple doses of medication. For example, U.S. Pat. No. 4,592,745 provides an injection device that includes a unidirectional transmission mechanism that advances a piston rod in successive axial steps based on advancing axial movement of a pressure device. Similarly, U.S. Pat. No. 3,790,048 discloses an injection device that uses a cam barrel and a ratchet to translate actuation of a trigger to cause advancement of a plunger and to cause the plunger to remain stationary during repositioning of the trigger. In both of these devices, the reciprocal motion of the trigger is such that the return stroke follows the same path as the dosing stroke, but in an opposite direction.
U.S. Pat. No. 6,562,006 discloses a device that uses rotation of the trigger to reset the device for successive dosing. The device described in U.S. Patent Application Pub. No. 2004/0097783 is also adjustable between a priming dose and an injection dose. The dosing of these devices is selectable by the user, which can allow errors in selecting the dose, potentially reducing the efficacy of the medication or leading to harmful side effects.
U.S. Patent Application Pub. No. 2007/0088288 describes a device that allows a user to administer a fixed dose of the liquid medicament contained therein. The device does not use a reduction mechanism, but rather has a trigger that disengages from the piston rod when depressed to give the user a feeling of a longer trigger motion.
A device is needed that allows for repeated administration of a dose of medicament that is easy to use correctly in self-administration.
An aspect of the present invention relates to a medicament dispensing mechanism configured to eject successive doses of the medicament from a medicament chamber. An embodiment of the dispensing mechanism includes a housing and a plunger rod configured for ejecting the doses of medicament from the chamber. The dispensing mechanism further includes an actuation mechanism that comprises a trigger associated with the housing and having a ready and a fired position with respect thereto. The trigger is configured for manipulation by a user for successive movement in a dosing motion from the ready position to the fired position generally in axial translation in which the trigger is associated with the plunger rod to cause the plunger rod to eject one of the doses of a predetermined volume and a resetting motion from the fired position to the ready position that comprises axial rotation, wherein the trigger is uncoupled from the plunger rod during the resetting motion. In a preferred embodiment, the volume of the doses is preset and fixed.
In a preferred embodiment, the trigger comprises a plurality of ready positions and fired positions disposed in sequence with each other, the ready positions preferably being circumferentially spaced about the housing.
A further embodiment of the device preferably includes an anti-retrograde mechanism associated with the actuation mechanism for preventing rearward movement thereof against the direction of operation of the actuation mechanism through at least a portion of the dosing and resetting motions. The anti-retrograde mechanism can be associated with the trigger for preventing rearward movement thereof from the ready position against the direction of the resetting motion. Additionally or alternatively, the anti-retrograde mechanism can be associated with the trigger for preventing rearward movement thereof from the fired position against the direction of the dosing motion.
The actuation mechanism can comprise a driver rotatably associated with the housing and driven to rotate in a driving direction by the trigger during the dosing motion. In an embodiment, the driving direction is in an opposite rotational direction than the rotational spacing between the fired position and adjacent ready position of the trigger, the driver being associated with the plunger rod for causing the plunger rod to eject said one of the doses.
The dispensing mechanism can be included in an injector that further comprises a cartridge associated with the housing and defining the chamber, a plunger disposed in the chamber to seal the medicament therein, wherein the plunger rod is associated with the plunger for forcing the plunger in a distal direction for ejecting the doses, and a needle in fluid communication with the chamber for injecting the doses into a patient.
Another aspect of the present invention relates to medicament dispensing mechanism configured to eject successive doses of the medicament from a medicament chamber. The dispensing mechanism includes a housing, and a plunger rod configured for ejecting the doses of medicament from the chamber. The dispensing mechanism further includes an actuation mechanism that comprises a trigger associated with the housing and having a ready and a fired position with respect thereto. The trigger is configured for manipulation by a user for successive movement in a dosing motion from the ready position to the fired position, during the dosing motion the trigger being associated with the plunger rod to cause the plunger rod to eject one of the doses and a resetting motion from the fired position to the ready position, wherein the trigger is uncoupled from the plunger rod during the resetting motion. The dispensing mechanism further includes an anti-retrograde mechanism associated with the actuation mechanism for preventing rearward movement thereof against the direction of operation of the actuation mechanism through at least a portion of the dosing and resetting motions.
In an embodiment of the dispensing mechanism, the actuation mechanism comprises a driver rotatably associated with the housing and driven to rotate by the trigger during the dosing motion. The driver is associated with the plunger rod for causing the plunger rod to eject said one of the doses, and the anti-retrograde mechanism is configured for preventing rearward movement of the driver with respect to the trigger against the dosing motion.
A further aspect relates to medicament administering device including a housing, a container portion associated with the housing and defining an medicament chamber containing a medicament and including a plunger moveably disposed within an end thereof. A needle is in fluid communication with the interior cavity and configured for injecting the medicament. The device further includes a reduction mechanism including a plunger rod in threaded association with the housing and configured to move the plunger in a proximal direction upon rotation thereof, a trigger moveable in a generally axial direction, and a driver associated with the trigger and plunger rod for rotating upon movement of the trigger in the axial direction and thereby causing the plunger rod to rotate relative to the housing for ejecting the medicament through the needle, wherein the driver includes a projection, and the trigger includes a stepped surface facing the projection for engaging the projection upon movement of the trigger in a direction opposite the axial direction to prevent rearward movement thereof.
These and other objects, features and advantages of the invention will be apparent from a consideration of the following non-limiting detailed description considered in conjunction with the drawing figures, in which:
Referring to
Injector 10 is constructed to be suitable for administering repeated, successive doses of a liquid medicament. Preferably, the medicament is delivered in successive repeated fixed doses, although in some embodiments, the dosage can be controlled and adjusted. Some medicaments that can be used with the injector of the preferred embodiment include parathyroid hormone (“PTH”) and various other medications such as exenatide and the like. Because of the repeated nature of the dosing of these types of medicaments, it is beneficial to use a device that aides a patient in self-administration of the doses. Further, many such medicaments should be delivered in a precise amount to ensure efficacy and to reduce side-effects.
To reliably provide repeated small doses of a liquid medicament, cartridge 24 is constructed to hold a predetermined number of doses, preferably corresponding to a predetermined period of medicament administration. For example, one embodiment of injector 10 can be intended for use with a PTH solution that is to be administered once daily for thirty successive days at a dose of 0.08 mL administered through movement of a plunger 25 through a distance of about 1.1 mm. Accordingly, cartridge 24 can be configured to contain about 3 mL of PTH. In an embodiment, cartridge has a diameter of about 12 mm and a height of approximately 64 mm to contain 3 mL of medicament, although other dimensions can be used to achieve the desired accuracy. Cartridges containing more or less medicament can be provided and can vary in diameter, height or both. For example a cartridge can be configured to hold between about 1 mL and 10 mL of liquid medicament, and more preferably between about 2 mL and 5 mL of liquid medicament. Similarly, the device can be configured to dispense different amounts of the liquid medicament per dose. For example, a dose of liquid medicament can be between about 0.05 mL and 0.2 mL. Preferably a dose of liquid medicament is between about 0.07 mL and 0.1 mL. Further, the overall volume can be increased to include a predetermined amount of additional volume that remains in the cartridge when the intended dosing is complete. This reduces the likelihood of an incomplete final dose or the presence of air in an injection.
In an embodiment, a given lower housing 24 can be used to hold a number of differently-sized cartridges, such as by providing a cartridge sleeve that is sized to act as a shim between the lower housing 22 and a cartridge that is smaller than the interior of lower housing 22. A number of differently-sized cartridge sleeves can be provided, as necessary for differently-sized cartridges. Additionally, larger and smaller variations of a cartridge can be formed having the same diameter but with different heights and correspondingly-sized lower housing units, all of which can be used with a single sized proximal section 30.
Cartridge 24 has a dispensing end 26 that is configured for providing an outlet for the administered dose of the liquid medicament. Suitable dispensing ends are known and are preferably in the form of a needle of a length and configuration to deliver the medicament to the desired depth and injection site. Alternatively, the dispensing end can be configured to be attached to an intravenous line or the like. In the embodiment of
Proximal section 30 contains a dosing mechanism that is contained within upper housing 32 and configured to cause movement of plunger 25 through the predetermined dosing distance in a number of successive increments that corresponds to the number of doses to be administered. The dosing mechanism includes a user-manipulable trigger that allows the user to actuate the mechanism. In the embodiment shown in
As shown in
In the embodiment of
The pattern of linked dispensing and resetting portions 44,46 preferably restricts the movement of the push button 34 to a dispensing motion and a resetting motion. The dispensing motion involves movement of the push button 34 in a distal direction from a ready position to an end position. In the ready position, the plunger is located preferably such that the projections 40 are positioned at the proximal end of the dispensing portions 44. In the end position the projections 40 are positioned at the distal end of the dispensing portions 44. It is noted that the number of projections 40 located on push button 34 can vary. In the embodiment shown, wherein the housing has a upper track 42 including four sets of linked dispensing 44 and resetting 46 portions, push button 34 can have between 1 and 4 projections, most preferably having one projection per the number of repetitions of the linked dispensing 44 and resetting 46 portions of upper track 42. Multiple projections can be used to provide a more robust structure with more accurate movement. In an embodiment having multiple projections, the projections are preferably located along a common radial plane and are spaced apart at intervals equal to the interval of the dispensing and resetting portions 44,46. For example, in the embodiment, shown in
The resetting motion of push button 34 includes a combination of rotation of push button 34 and translational movement of push button 34. The specific movement includes rotational movement such that the projections 40 first move generally circumferentially or horizontally from the distal ends of dispensing portions 44 through the lower horizontal portions 48 thereof and translational movement in the proximal direction such that projections 40 move through generally axial or vertical sections 52 thereof and, finally, rotational movement such that projections 40 move through upper generally circumferential or horizontal sections 50 thereof to the proximal ends of the dispensing portions 44. After movement through the resetting portion has been completed, push button will have been rotated through an angle equal to the phase of the dispensing and resetting sections 44,46. In the embodiment shown, such an angle will be approximately 90°. Other arrangements resulting in different angles are possible. After such rotation, the projections 40 will be positioned within a dispensing section 44 that is adjacent to the one in which they were located prior to the resetting motion. It is noted that when the projections 40 move through the curved sections 54,56, the motion will include both rotational and vertical movement.
To aid a user of injector 10 in carrying out the resetting motion, spring 58 is included within upper push button 34. As shown in
Upper track 42 preferably includes anti-retrograde features that help to restrict the motion of push button to a forward direction, and to prevent retrograde movement thereof along upper track 42. In the present embodiment, the desired directions are translation in the distal direction for dispensing, and rotation in the clockwise direction and translation in the proximal direction during resetting. Further the anti-retrograde features are configured such that at the end of the dispensing motion, push button 34 can only be moved in the resetting direction, and such that at the end of the resetting motion, push button 34 can only be moved in the dispensing projection.
As shown in
Post-injection tabs 72 are configured such that the ends thereof abut projections 40 when projections 40 are positioned at the distal end of dispensing sections 44. Post-injection tabs 72 are further oriented such that movement of push button 34 in the dispensing direction is such that projections 40 deflect post-injection tabs 72.
As stated previously, the dosing motion of push button 34 are preferably intended to cause a predetermined, fixed dose of liquid medicament to be dispensed from cartridge 24. Accordingly, the dispensing mechanism is structured to transfer the linear motion of push button 34 through the dispensing movement to rotation of plunger rod 36 through an angle necessary to move plunger 25 through the distance corresponding to one dose. As discussed above, driver 38 is structured such that rotation of driver 38 causes rotation of plunger rod 36 while permitting plunger rod 36 to translate axially with respect thereto. Push button 34 and driver 38 are, accordingly, structured to have interrelating features that cause rotation of driver 38 with response to the dispensing motion of push button 34.
As shown in
As shown in
Preferably, the distance of travel for push button 34 is determined such that, relative to the horizontal length of surface 82, which is influenced by the overall size of injector 10, surface 82 forms an angle 89 (
The dosing mechanism includes an additional anti-retrograde feature between push button 34 and upper housing 32 to prevent movement of push button 34 in the proximal direction once dosing has begun in order to protect the accuracy of the dosing and preventing aspiration into the cartridge 24. As shown in
As shown in
As shown in
Additional arrangements for the dosing mechanism are possible that include a different number of inclined surfaces within the push button and a different number of corresponding pairs of dispensing and resetting sections within the track. As discussed above, the rotation of the driver and the push button in opposite directions means that the number of dosing and resetting cycles carried out in a full rotation of the push button will preferably be the same as the number of dosing and resetting cycles carried out in a full rotation of the driver. Accordingly, the dosing mechanism will include twice as many pairs of dispensing and resetting sections within the track as the number of inclined surfaces within the recess. Therefore, a dosing mechanism can be formed with a single inclined surface and two sets of dosing and resetting sections, in which the driver will rotate through an angle of about 180° for each dosing motion of push button, after which the push button will be rotated through about 180° during resetting. Further, a dosing mechanism can be formed with three inclined surfaces and six sets of dosing and resetting sections, in which the driver will rotate through an angle of about 60° for each dosing motion of the push button, after which the push button will be rotated through about 60° during resetting. Additional inclined portions can be added, reducing the rotation of the driver and increasing the number of dispensing and resetting sections accordingly.
Such a variation in the number of inclined portions can be used to vary the dose size. That is, given a similarly shaped cartridge and plunger rod thread pitch, a decrease in the number of inclined portions will increase the amount of rotation for a single dose, thus increasing the dose size. Similarly, increasing the number of inclined portions will decrease the amount of rotation for a single dose, which will decrease the dose size.
The dose size can also be varied by the geometry of the threads formed on plunger rod 36 and nut 60. That is, by increasing the pitch of the threads, the linear distance traveled by plunger rod, and therefore plunger 25 is increased, leading to a greater dose size. Conversely, by decreasing the pitch of the thread, the dose size is reduced. The dose size can also be varied by changing the diameter of cartridge 24. A higher diameter will increase the dose size, while a smaller diameter will decrease the dose size. These factors can be adjusted to derive an injector that contains a desired amount of liquid medicament and will produce the desired number of doses at a desired, preferably fixed, amount, and will have the desired dosing and resetting motions.
Upper housing 32 can further include a window 100 through which visual indicia relating to the position and intended movement the dosing system are visible. Such indicia are preferably formed on the outside surface of push button 34 and are positioned to be visible at various instances during the dosing and resetting cycle. As shown in
While the dosing mechanism described herein is shown as a part of a needled injection device for a liquid medicament, it is understood that the mechanism can be used in other dispensing devices that include a dispenser that is actuated by linear motion. This includes injection devices that use a mechanism other than a push button as well as other dispensing devices for gels or the like which may or may not contain a medicament.
All of the references specifically identified in the detailed description section of the present application are expressly incorporated herein in their entirety by reference thereto. The term “about,” as used herein, should generally be understood to refer to both the corresponding number and a range of numbers. Moreover, all numerical ranges herein should be understood to include each whole integer within the range.
While illustrative embodiments of the invention are disclosed herein, it will be appreciated that numerous modifications and other embodiments may be devised by those skilled in the art. For example, the features for the various embodiments can be used in other embodiments. In an alternative embodiment, the housing can be fixed to the bracket, and the inner portion, defining at least the bottom of the chutes can slide in and out of the housing. Therefore, it will be understood that the appended claims are intended to cover all such modifications and embodiments that come within the spirit and scope of the present invention.
This application is a continuation of U.S. patent application Ser. No. 12/536,106, filed on Aug. 5, 2009, now U.S. Pat. No. 8,376,993 B2, which in turn claims the benefit of U.S. Provisional Application No. 61/086,363 filed Aug. 5, 2008, the entire contents of each being expressly incorporated herein by reference.
Number | Name | Date | Kind |
---|---|---|---|
547370 | Chalefou | Oct 1895 | A |
1465793 | Schilling | Aug 1923 | A |
1512294 | Marcy | Oct 1924 | A |
1687323 | Cook | Oct 1928 | A |
2354649 | Bruckner | Aug 1944 | A |
2607344 | Brown | Aug 1952 | A |
2645223 | Lawshe | Jul 1953 | A |
2648334 | Brown | Aug 1953 | A |
2687730 | Hein | Aug 1954 | A |
2688967 | Huber | Sep 1954 | A |
2699166 | Bickinson | Jan 1955 | A |
2717601 | Brown | Sep 1955 | A |
2728341 | Roehr | Dec 1955 | A |
2737946 | Hein, Jr. | Mar 1956 | A |
2813528 | Blackman | Nov 1957 | A |
2866458 | Mesa et al. | Dec 1958 | A |
2888924 | Dunmire | Jun 1959 | A |
2893390 | Lockhart | Jul 1959 | A |
3130724 | Higgins | Apr 1964 | A |
3166069 | Enstrom | Jan 1965 | A |
3375825 | Keller | Apr 1968 | A |
3382865 | Worrall | May 1968 | A |
3526225 | Hayamamachi | Sep 1970 | A |
3557784 | Shields | Jan 1971 | A |
3563098 | Gley | Feb 1971 | A |
3605744 | Dwyer | Sep 1971 | A |
3688765 | Gasaway | Sep 1972 | A |
3702609 | Steiner | Nov 1972 | A |
3742948 | Post et al. | Jul 1973 | A |
3770026 | Isenberg | Nov 1973 | A |
3790048 | Luciano et al. | Feb 1974 | A |
3797489 | Sarnoff | Mar 1974 | A |
3797491 | Hurschman | Mar 1974 | A |
3811441 | Sarnoff | May 1974 | A |
3831814 | Butler | Aug 1974 | A |
3848593 | Baldwin | Nov 1974 | A |
3892237 | Steiner | Jul 1975 | A |
3895633 | Bartner et al. | Jul 1975 | A |
3946732 | Hurscham | Mar 1976 | A |
4031893 | Kaplan et al. | Jun 1977 | A |
4067333 | Reinhardt et al. | Jan 1978 | A |
4127118 | Latorre | Nov 1978 | A |
4171698 | Genese | Oct 1979 | A |
4222392 | Brennan | Sep 1980 | A |
4227528 | Wardlaw | Oct 1980 | A |
4258713 | Wardlaw | Mar 1981 | A |
4282986 | af Ekenstam et al. | Aug 1981 | A |
4316463 | Schmitz et al. | Feb 1982 | A |
4316643 | Burk et al. | Feb 1982 | A |
4328802 | Curley et al. | May 1982 | A |
4333456 | Webb | Jun 1982 | A |
4333458 | Margulies et al. | Jun 1982 | A |
4338980 | Schwebel et al. | Jul 1982 | A |
4373526 | Kling | Feb 1983 | A |
4378015 | Wardlaw | Mar 1983 | A |
4411661 | Kersten | Oct 1983 | A |
4529403 | Kamstra | Jul 1985 | A |
4553962 | Brunet | Nov 1985 | A |
4558690 | Joyce | Dec 1985 | A |
4573971 | Kamstra | Mar 1986 | A |
4592745 | Rex et al. | Jun 1986 | A |
4634027 | Kanarvogel | Jan 1987 | A |
4662878 | Lindmayer | May 1987 | A |
4664655 | Orentreich et al. | May 1987 | A |
4719825 | LaHaye et al. | Jan 1988 | A |
4722728 | Dixon | Feb 1988 | A |
4774772 | Vetter et al. | Oct 1988 | A |
4790824 | Morrow et al. | Dec 1988 | A |
4818517 | Kwee et al. | Apr 1989 | A |
4820286 | van der Wal | Apr 1989 | A |
4830217 | Dufresne et al. | May 1989 | A |
4874381 | Vetter | Oct 1989 | A |
4883472 | Michel | Nov 1989 | A |
4913699 | Parsons | Apr 1990 | A |
4915701 | Halkyard | Apr 1990 | A |
4929238 | Baum | May 1990 | A |
4936833 | Sams | Jun 1990 | A |
4940460 | Casey et al. | Jul 1990 | A |
4966581 | Landau | Oct 1990 | A |
4968302 | Schluter et al. | Nov 1990 | A |
4973318 | Holm et al. | Nov 1990 | A |
4976701 | Ejlersen et al. | Dec 1990 | A |
4982769 | Fournier et al. | Jan 1991 | A |
5062830 | Dunlap | Nov 1991 | A |
5064413 | McKinnon et al. | Nov 1991 | A |
5069670 | Vetter et al. | Dec 1991 | A |
5080648 | D'Antonio | Jan 1992 | A |
5080649 | Vetter | Jan 1992 | A |
5102388 | Richmond | Apr 1992 | A |
5104380 | Holman et al. | Apr 1992 | A |
5137516 | Rand et al. | Aug 1992 | A |
5137528 | Crose | Aug 1992 | A |
5139490 | Vetter et al. | Aug 1992 | A |
5176643 | Kramer et al. | Jan 1993 | A |
5185985 | Vetter et al. | Feb 1993 | A |
5221348 | Masano | Jun 1993 | A |
5226895 | Harris | Jul 1993 | A |
5232459 | Hjertman | Aug 1993 | A |
5256142 | Colavecchio | Oct 1993 | A |
5263934 | Haak | Nov 1993 | A |
5271744 | Kramer et al. | Dec 1993 | A |
5279543 | Glikfeld et al. | Jan 1994 | A |
5279576 | Loo et al. | Jan 1994 | A |
5279585 | Balkwill | Jan 1994 | A |
5279586 | Balkwill | Jan 1994 | A |
5281198 | Haber et al. | Jan 1994 | A |
5290228 | Uemura et al. | Mar 1994 | A |
5295965 | Wilmot | Mar 1994 | A |
5304128 | Haber et al. | Apr 1994 | A |
5304152 | Sams | Apr 1994 | A |
5308341 | Chanoch | May 1994 | A |
5318522 | D'Antonio | Jun 1994 | A |
5320603 | Vetter et al. | Jun 1994 | A |
5330431 | Herskowitz | Jul 1994 | A |
5332399 | Grabenkort et al. | Jul 1994 | A |
5334144 | Alchas et al. | Aug 1994 | A |
5342308 | Boschetti | Aug 1994 | A |
5350367 | Stiehl et al. | Sep 1994 | A |
RE34845 | Vetter et al. | Jan 1995 | E |
5391151 | Wilmot | Feb 1995 | A |
5405362 | Kramer et al. | Apr 1995 | A |
5415648 | Malay et al. | May 1995 | A |
5451210 | Kramer et al. | Sep 1995 | A |
5505694 | Hubbard et al. | Apr 1996 | A |
5514107 | Haber et al. | May 1996 | A |
5542760 | Chanoch et al. | Aug 1996 | A |
5544234 | Terajima et al. | Aug 1996 | A |
5549561 | Hjertman | Aug 1996 | A |
5554134 | Bonnichsen | Sep 1996 | A |
5562625 | Stefancin, Jr. | Oct 1996 | A |
5569190 | D'Antonio | Oct 1996 | A |
5569236 | Kriesel | Oct 1996 | A |
5573042 | De Haen | Nov 1996 | A |
5599302 | Lilley et al. | Feb 1997 | A |
5599309 | Marshall et al. | Feb 1997 | A |
5605542 | Tanaka et al. | Feb 1997 | A |
5637094 | Stewart, Jr. et al. | Jun 1997 | A |
5637100 | Sudo | Jun 1997 | A |
5649912 | Peterson | Jul 1997 | A |
5658259 | Pearson et al. | Aug 1997 | A |
5665071 | Wyrick | Sep 1997 | A |
5688251 | Chanoch | Nov 1997 | A |
5704911 | Parsons | Jan 1998 | A |
5725508 | Chanoch et al. | Mar 1998 | A |
5730723 | Castellano et al. | Mar 1998 | A |
5743889 | Sams | Apr 1998 | A |
5769138 | Sadowski et al. | Jun 1998 | A |
5785691 | Vetter et al. | Jul 1998 | A |
5788670 | Reinhard et al. | Aug 1998 | A |
5801057 | Smart et al. | Sep 1998 | A |
5807309 | Lundquist et al. | Sep 1998 | A |
5820622 | Gross et al. | Oct 1998 | A |
5827232 | Chanoch et al. | Oct 1998 | A |
5846233 | Lilley et al. | Dec 1998 | A |
5851198 | Castellano et al. | Dec 1998 | A |
5860456 | Bydlon et al. | Jan 1999 | A |
5865795 | Schiff et al. | Feb 1999 | A |
5865799 | Tanaka et al. | Feb 1999 | A |
5868711 | Kramer et al. | Feb 1999 | A |
5873857 | Kriesel | Feb 1999 | A |
5875976 | Nelson et al. | Mar 1999 | A |
5879327 | Moreau DeFarges et al. | Mar 1999 | A |
5891085 | Lilley et al. | Apr 1999 | A |
5893842 | Imbert | Apr 1999 | A |
5919159 | Lilley et al. | Jul 1999 | A |
5921966 | Bendek et al. | Jul 1999 | A |
5925017 | Kriesel et al. | Jul 1999 | A |
5928205 | Marshall | Jul 1999 | A |
5951528 | Parkin | Sep 1999 | A |
5957897 | Jeffrey | Sep 1999 | A |
5960797 | Kramer et al. | Oct 1999 | A |
5989227 | Vetter et al. | Nov 1999 | A |
6004297 | Steenfeldt-Jensen et al. | Dec 1999 | A |
6056716 | D'Antonio et al. | May 2000 | A |
6077247 | Marshall et al. | Jun 2000 | A |
6083201 | Skinkle | Jul 2000 | A |
6099504 | Gross et al. | Aug 2000 | A |
6123684 | Deboer et al. | Sep 2000 | A |
6132395 | Landau et al. | Oct 2000 | A |
6159181 | Crossman et al. | Dec 2000 | A |
6171276 | Lippe et al. | Jan 2001 | B1 |
6203529 | Gabriel et al. | Mar 2001 | B1 |
6221046 | Burroughs et al. | Apr 2001 | B1 |
6221053 | Walters et al. | Apr 2001 | B1 |
6223408 | Vetter et al. | May 2001 | B1 |
6231540 | Smedegaard | May 2001 | B1 |
6258078 | Thilly | Jul 2001 | B1 |
6264629 | Landau | Jul 2001 | B1 |
6309371 | Deboer et al. | Oct 2001 | B1 |
6319224 | Stout et al. | Nov 2001 | B1 |
6383168 | Landau et al. | May 2002 | B1 |
6391003 | Lesch, Jr. | May 2002 | B1 |
6406456 | Slate et al. | Jun 2002 | B1 |
6471669 | Landau | Oct 2002 | B2 |
6494865 | Alchas | Dec 2002 | B1 |
6544234 | Gabriel | Apr 2003 | B1 |
6562006 | Hjertman et al. | May 2003 | B1 |
6568259 | Saheki et al. | May 2003 | B2 |
6569123 | Alchas et al. | May 2003 | B2 |
6569143 | Alchas et al. | May 2003 | B2 |
6584910 | Plass | Jul 2003 | B1 |
6589210 | Rolfe | Jul 2003 | B1 |
6620137 | Kirchhofer et al. | Sep 2003 | B2 |
6641561 | Hill et al. | Nov 2003 | B1 |
6645170 | Landau | Nov 2003 | B2 |
6673035 | Rice et al. | Jan 2004 | B1 |
6689092 | Zierenberg et al. | Feb 2004 | B2 |
6706000 | Perez et al. | Mar 2004 | B2 |
6746429 | Sadowski et al. | Jun 2004 | B2 |
6767336 | Kaplan | Jul 2004 | B1 |
6805686 | Fathallah et al. | Oct 2004 | B1 |
6899698 | Sams | May 2005 | B2 |
6932793 | Marshall et al. | Aug 2005 | B1 |
6936032 | Bush, Jr. et al. | Aug 2005 | B1 |
7018364 | Giambattista et al. | Mar 2006 | B2 |
7066907 | Crossman et al. | Jun 2006 | B2 |
7112187 | Karlsson | Sep 2006 | B2 |
7118552 | Shaw et al. | Oct 2006 | B2 |
7218962 | Freyman | May 2007 | B2 |
7220247 | Shaw et al. | May 2007 | B2 |
7292885 | Scott et al. | Nov 2007 | B2 |
7442185 | Amark et al. | Oct 2008 | B2 |
7449012 | Young et al. | Nov 2008 | B2 |
7488313 | Segal et al. | Feb 2009 | B2 |
7488314 | Segal et al. | Feb 2009 | B2 |
7500964 | Shaw et al. | Mar 2009 | B2 |
7517342 | Scott et al. | Apr 2009 | B2 |
7519418 | Scott et al. | Apr 2009 | B2 |
7635348 | Raven et al. | Dec 2009 | B2 |
7635350 | Scherer | Dec 2009 | B2 |
7717877 | Lavi et al. | May 2010 | B2 |
7762996 | Palasis | Jul 2010 | B2 |
7794432 | Young et al. | Sep 2010 | B2 |
7862543 | Potter et al. | Jan 2011 | B2 |
8021335 | Lesch, Jr. | Sep 2011 | B2 |
8048035 | Mesa et al. | Nov 2011 | B2 |
8066659 | Joshi et al. | Nov 2011 | B2 |
8162873 | Muto et al. | Apr 2012 | B2 |
20010049496 | Kirchhofer et al. | Dec 2001 | A1 |
20020007149 | Nelson et al. | Jan 2002 | A1 |
20020010428 | Vedrine et al. | Jan 2002 | A1 |
20020045866 | Sadowski et al. | Apr 2002 | A1 |
20020183690 | Arnisolle | Dec 2002 | A1 |
20020188251 | Staylor et al. | Dec 2002 | A1 |
20030083621 | Shaw et al. | May 2003 | A1 |
20030105430 | Lavi et al. | Jun 2003 | A1 |
20030130619 | Safabash et al. | Jul 2003 | A1 |
20030158523 | Hjertman et al. | Aug 2003 | A1 |
20030229330 | Hickle | Dec 2003 | A1 |
20030236502 | De La Serna et al. | Dec 2003 | A1 |
20040039336 | Amark et al. | Feb 2004 | A1 |
20040097783 | Peters et al. | May 2004 | A1 |
20040097883 | Roe | May 2004 | A1 |
20040097993 | Whayne | May 2004 | A1 |
20040143213 | Hunter et al. | Jul 2004 | A1 |
20040220524 | Sadowski et al. | Nov 2004 | A1 |
20040267207 | Veasey et al. | Dec 2004 | A1 |
20040267355 | Scott et al. | Dec 2004 | A1 |
20050020979 | Westbye et al. | Jan 2005 | A1 |
20050033234 | Sadowski et al. | Feb 2005 | A1 |
20050080377 | Sadowski et al. | Apr 2005 | A1 |
20050101919 | Brunnberg | May 2005 | A1 |
20050165360 | Stamp | Jul 2005 | A1 |
20050177115 | Broennimann et al. | Aug 2005 | A1 |
20050240145 | Scott et al. | Oct 2005 | A1 |
20050256499 | Pettis et al. | Nov 2005 | A1 |
20050261634 | Karlsson | Nov 2005 | A1 |
20060025747 | Sullivan et al. | Feb 2006 | A1 |
20060224124 | Scherer | Oct 2006 | A1 |
20060258990 | Weber | Nov 2006 | A1 |
20070025890 | Joshi et al. | Feb 2007 | A1 |
20070088288 | Barron et al. | Apr 2007 | A1 |
20070093775 | Daly | Apr 2007 | A1 |
20070123829 | Atterbury et al. | May 2007 | A1 |
20070129686 | Daily et al. | Jun 2007 | A1 |
20070185432 | Etheredge et al. | Aug 2007 | A1 |
20080154200 | Lesch | Jun 2008 | A1 |
20080185069 | Clark | Aug 2008 | A1 |
20090204062 | Muto et al. | Aug 2009 | A1 |
20090254027 | Moller | Oct 2009 | A1 |
20090254035 | Kohlbrenner et al. | Oct 2009 | A1 |
20090292240 | Kramer et al. | Nov 2009 | A1 |
20090299278 | Lesch et al. | Dec 2009 | A1 |
20090304812 | Staniforth et al. | Dec 2009 | A1 |
20090312705 | Grunhut | Dec 2009 | A1 |
20100016326 | Will | Jan 2010 | A1 |
20100036318 | Raday et al. | Feb 2010 | A1 |
20100114058 | Weitzel et al. | May 2010 | A1 |
20100121272 | Marshall et al. | May 2010 | A1 |
20100137798 | Streit et al. | Jun 2010 | A1 |
20100152702 | Vigil et al. | Jun 2010 | A1 |
20100160894 | Julian et al. | Jun 2010 | A1 |
20100191217 | Hommann et al. | Jul 2010 | A1 |
20100262083 | Grunhut et al. | Oct 2010 | A1 |
20100268170 | Carrel et al. | Oct 2010 | A1 |
20100292653 | Maritan | Nov 2010 | A1 |
20100318035 | Edwards et al. | Dec 2010 | A1 |
20100318037 | Young et al. | Dec 2010 | A1 |
20110034879 | Crow | Feb 2011 | A1 |
20110087192 | Uhland et al. | Apr 2011 | A1 |
20110098656 | Burnell et al. | Apr 2011 | A1 |
20110125076 | Kraft et al. | May 2011 | A1 |
20110137247 | Mesa et al. | Jun 2011 | A1 |
20110144594 | Sund et al. | Jun 2011 | A1 |
20110238003 | Bruno-Raimondi et al. | Sep 2011 | A1 |
20120004608 | Lesch, Jr. | Jan 2012 | A1 |
20120046609 | Mesa et al. | Feb 2012 | A1 |
20120095443 | Ferrari et al. | Apr 2012 | A1 |
20120172885 | Drapeau et al. | Jul 2012 | A1 |
20120203184 | Selz et al. | Aug 2012 | A1 |
20120302989 | Kramer et al. | Nov 2012 | A1 |
Number | Date | Country |
---|---|---|
0072057 | Feb 1983 | EP |
0103664 | Mar 1984 | EP |
1752174 | Mar 1986 | EP |
0518416 | Dec 1992 | EP |
1161961 | Dec 2001 | EP |
1518575 | Mar 2005 | EP |
2506161 | Nov 1982 | FR |
2635009 | Feb 1990 | FR |
6677523 | Aug 1952 | GB |
1181037 | Feb 1970 | GB |
1216813 | Dec 1970 | GB |
10-507935 | Aug 1998 | JP |
11-347121 | Dec 1999 | JP |
2000-245839 | Sep 2000 | JP |
2001-523485 | Nov 2001 | JP |
WO 9219296 | Nov 1992 | WO |
WO 9409839 | May 1994 | WO |
WO 9411041 | May 1994 | WO |
WO 9529720 | Nov 1995 | WO |
WO 9529730 | Nov 1995 | WO |
WO 9621482 | Jul 1996 | WO |
WO 9714455 | Apr 1997 | WO |
WO 9721457 | Jun 1997 | WO |
WO 9741907 | Nov 1997 | WO |
WO 9748430 | Dec 1997 | WO |
WO 9831369 | Jul 1998 | WO |
WO 9832451 | Jul 1998 | WO |
WO 9903521 | Jan 1999 | WO |
WO 9910030 | Mar 1999 | WO |
WO 9922790 | May 1999 | WO |
WO 9962525 | Dec 1999 | WO |
WO 0024441 | May 2000 | WO |
WO 0029050 | May 2000 | WO |
WO 0193926 | Dec 2001 | WO |
WO 02089805 | Nov 2002 | WO |
WO 03070296 | Aug 2003 | WO |
WO 03097133 | Nov 2003 | WO |
WO 2004028598 | Apr 2004 | WO |
WO 2004108194 | Dec 2004 | WO |
WO 2005002653 | Jan 2005 | WO |
WO 2006079064 | Jul 2006 | WO |
WO 2006086899 | Aug 2006 | WO |
WO 2007047200 | Apr 2007 | WO |
WO 2007063342 | Jun 2007 | WO |
WO 2007131013 | Nov 2007 | WO |
WO 2007131025 | Nov 2007 | WO |
WO 2008005315 | Jan 2008 | WO |
WO 2008009476 | Jan 2008 | WO |
WO 2008089886 | Jul 2008 | WO |
WO 2008112472 | Sep 2008 | WO |
WO 2010108116 | Sep 2010 | WO |
Entry |
---|
“Skin”, American Medical Association (AMA) Current Procedural Terminology , 1998, http://www.ama-assn.org/ama/pub/category/print/7176.html, 1 page. |
Becks et al., “Comparison of Conventional Twice-Daily Subcutaneous Needle Injections to Multiple Jet Injections of Insulin in Insulin-Dependent Diabetes”, Clinical and Investigative Medicine, 1981, p. 33B. |
Binder, “Absorption of Injected Insulin”, ACTA Pharmacological ET Toxicologica, 1969, 27(Supp 2), 3 pages. |
Bonetti et al., “An Extended-Release formulation of Methotrexate for Subcutaneous Administration”, Cancer Chemotherapy Pharmacology, 1994, 33, 303-306. |
Braun et al., “Comparison of the Clinical Efficacy and Safety of Subcutaneous Versus Oral Administration of Methotrexate in Patients with Active Rheumatoid Arthritis”, Arthritis and Rheumatism, Jan. 2008, 58(1), pp. 73-81. |
Chen et al., “Blood Lipid Profiles and Peripheral Blood Mononuclear Cell Cholesterol Metabolism Gene Expression in Patients with and Without Methotrexate” BMC Medicine, 2011, 9(4), 9 pages. |
Chiasson et al., “Continuous Subcutaneous Insulin Infusion (Mill-Hill Infuser) Versus Multiple Injections (Medi-Jector) in the Treatment of Insulin-Dependent Diabetes Mellitus and the Effects of Metabolic Control on Microangiopathy” Diabetes Care, Jul.-Aug. 1984, 7(4), pp. 331-337. |
Cohn et al., “Clincal Experience with Jet Insulin Injection in Diabetes Mellitus Therapy: A Clue to the Pathogenesis of Lipodystrophy”, Ala. J. Med. Sci., 1974, 11(3), pp. 265-272. |
Cowie et al., “Physical and Metabolic Characteristics of Persons with Diabetes”, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, 1995, 95(1468), pp. 117-120. |
European Patent Application No. 03707823.5, Supplementary European Search Report, dated Mar. 30, 2005 with Communication dated Apr. 25, 2005 regarding Proceeding Further with the European Patent Application Pursuant to Article 96(1), and Rule 51(1) EPC, 3 pages. |
European Patent Application No. 00976612.2, Communication Pursuant to Article 96(2) EPC, dated May 10, 2004, 5 pages. |
Hingson et al., “A Survey of the Development of Jet Injection in Parenteral Therapy”, Nov./Dec. 1952, 31 (6), pp. 361-366. |
Hoekstra et al., Bioavailability of Higher Dose Methotrexate Comparing Oral and Subcutaneous Administration i n Patients with Rheumatoid Arthritis, The Journal of Rheumatology, 2004, 31(4), pp. 645-648. |
International Patent Application No. PCT/US2012/46742, International Search Report and Written Opinion dated Nov. 16, 2012, 11 pages. |
International Patent Application No. PCT/US2009/052835, International Search Report dated Mar. 15, 2010, 5 pages. |
International Patent Application No. PCT/US2013/029085, International Search Report dated May 13, 2013, 2 pages. |
International Patent Application No. PCT/US2010/028011, International Search Report, dated Jun. 29, 2010, 5 pages. |
International Patent Application No. PCT/US2009/036682, International Search Report, dated Jul. 7, 2009, 5 pages. |
International Patent Application No. PCT/US2007/068010, International Search Report, dated Sep. 24, 2007, 3 pages. |
International Patent Application No. PCT/US03/03917, International Search Report, dated Nov. 26, 2003, 1 page. |
Katoulis et al., Efficacy of a New Needleless Insulin Delivery System Monitoring of Blood Glucose Fluctuations and Free Insulin Levels, The International Journal of Artificial Organs, 1989, 12(5), 333-339. |
Kurnik et al., “Bioavailability of Oral vs. Subcutaneous low-dose Methotrexate in Patients with Crohn's Disease”, Aliment Pharmacol Ther., Apr. 2003, 18, pp. 57-63. |
Malone et al., “Comparison of Insulin Levels After Injection by Jet Stream and Disposable Insulin Syringe”, Diabetes Care, Nov.-Dec. 1986, 9(6), 637-640. |
“The Historical Development of Jet Injection and Envisioned Uses in Mass Immunization and Mass Therapy Based Upon Two Decades' Experience”, Military Medicine, Jun. 1963, 128, pp. 516-524. |
Pehling et al, “Comparison of Plasma Insulin Profiles After Subcutaneous Administration of Insulin by Jet Spray and Conventional Needle Injection in Patients with Insulin-Dependent Diabetes Mellitus”, Mayo Clin. Proc., Nov. 1984, 59, pp. 751-754. |
Reiss et al., “Atheroprotective Effects of Methotrexate on Reverse Cholesterol Transport Proteins and Foam Cell Transformation in Human THP-1 Monocyte/Macrophages”, Arthritis and Rheumatism, Dec. 2008, 58(12), pp. 3675-3683. |
Taylor et al., “Plasma Free Insulin Profiles After Administration of Insulin by Jet and Conventional Syringe Injection”, Diabetes Care, May-Jun. 1981, 4(3), 337-339. |
Weller et al., “Jet Injection of Insulin vs the Syringe-and-Needle Method”, JAMA, Mar. 1966, 195(10), pp. 844-847. |
Westlake et al., “The Effect of Methotrexate on Cardiovascular Disease in Patients with Rheumatoid Arthritis: A Systematic Literature Review”, Rheumatology, Nov. 2009, 49, pp. 295-307. |
Worth, “Jet Injection of Insulin: Comparison with Conventional Injection by Syringe and Needle”, British Medical Journal, Sep. 1980, 281, pp. 713-714. |
International Patent Application No. PCT/US2013/029085, Written Opinion, dated May 13, 2013, 5 pages. |
International Patent Application No. PCT/US2010/028011, Written Opinion, dated Jun. 29, 2010, 5 pages. |
Zachheim et al., “Subcutaneous Administration of Methotrexate”, Journal of the American Academy of Dermatology, 1992, 26(6), p. 1008. |
Halle et al., “Twice-Daily Mixed Regular and NPH Insulin Injections with New Jet Injector Versus Conventional Syringes: Pharmacokinetics of Insulin Absorption”, Diabetes Care, May-Jun. 1986 9(3), pp. 279-282. |
International Patent Application No. PCT/US2012/046639, International Search Report and Written Opinion dated Apr. 22, 2013, 8 pages. |
Glynn-Barnhart et al., “Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy”, 1992, 12(5), abstract only, 2 pages. |
Hamilton et al., “Why Intramuscular Methotrexate May be More Efficacious Than Oral Dosing in Patients with Rheumatoid Arthritis”, British Journal of Rheumatology, 1997, 36(1), pp. 86-90. |
Stamp et al., “Effects of Changing from Oral to Subcutaneous Methotrexate on Red Blood Cell Methotrexate Polyglutamate Concentrations and Disease Activity in Patients with Rheumatoid Arthritis”, The Journal of Rheumatology, 2011, 38(12), 2540-2547. |
Tukova et al., “Methotrexate Bioavailability after Oral and Subcutaneous Administration in Children with Juvenile Idiopathic Arthritis”, Clinical and Experimental Rheumatology, 2009, 27, 1047-1053. |
Wright et al., “Stability of Methotrexate Injection in Prefilled Plastic Disposable Syringes”, International Journal of Pharmaceutics, Aug. 1988, 45(3), 237-244. |
Lunenfeld, “Stable Testosterone Levels Achieved with Subcutaneous Testosterone Injections”, The aging Male, Mar. 2006, 9(1), 70 pages. |
Number | Date | Country | |
---|---|---|---|
20130158508 A1 | Jun 2013 | US |
Number | Date | Country | |
---|---|---|---|
61086363 | Aug 2008 | US |
Number | Date | Country | |
---|---|---|---|
Parent | 12536106 | Aug 2009 | US |
Child | 13754092 | US |