Syringe plunger stopper for high dosage accuracy drug delivery

Abstract

To provide a stopper for drug delivery with high dosage accuracy. [Solution] A stopper for attachment to a plunger rod and use in a syringe barrel to accurately dispense fluid, the stopper having a first portion formed from a first material and a second portion formed from a second material, the second material being more rigid than the first material, the insert being encapsulated by the first material, and the second portion being configured to be attached to the plunger rod.

Description

[Technical field]

[0001] The present invention relates generally to stoppers for high dosage accuracy drug delivery, such as for use in syringes, injectors, pens, and other types of auto-injectors, and more particularly to stoppers that exhibit a reduced amount of distortion, reduce fill-to-fill variation in bubble size, and maintain a seal with the inner wall of a syringe barrel with lower contact pressures at rest. The stoppers also reduce the amount of hysteresis, i.e., the phenomenon where a physical property lags behind the change in the effect that causes the change. [Background technology]

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 62 / 671,618, entitled "Syringe Plunger Stopper for High Dosage Accuracy Drug Delivery," filed May 15, 2018, the entire disclosure of which is incorporated herein by reference in its entirety.

[0003] Efforts have been made to improve the accuracy of doses administered using injection pens, auto-injectors, and other types of injectors. While these efforts have met with some success, in many cases this success is offset by increased device cost, device complexity, and / or unsustainable tolerances applied to parts of the injector drive unit, such as dial ratchets, gear rack settings, etc. Even after these efforts, dose variability still occurred due to the performance of the stopper in the flow path not meeting certain compliance standards. These failures typically occur due to distortion of the elastomeric vial closure (if equipped) and plunger stopper and its hysteresis, i.e., residual air bubbles in the liquid after the stopper is placed and / or the delayed response the body exhibits in response to changes in the forces affecting it once the load is removed.

[0004] Auto-injectors are typically used by non-medical personnel to inject themselves with certain medications that require regular injections of a drug or product, i.e., on a daily basis. Since self-injectors are typically not well educated in the operation of medical injection products, there is a need for a self-injection device that is easy to use and very safe. In particular, needle insertion must be at the correct depth, the correct dose of product must be injected, and the syringe must be deactivated and discarded after use to prevent accidental needle stick injuries. The assembly and operation of a typical auto-injector is described in commonly assigned U.S. Patent No. 5,399,433, which is incorporated herein by reference in its entirety.

[0005] Drug delivery pens are used to self-inject precisely measured doses of medication. Drug delivery pens are widely used by diabetics to self-inject, i.e., insulin. A typical drug delivery pen includes a cartridge containing a sufficient amount of liquid medication for several doses. A pen needle attached to the pen device is used to inject the dose into a tissue area, such as an intramuscular, subcutaneous, or intradermal tissue layer. The assembly and operation of a typical pen injection device is described in commonly assigned U.S. Patent No. 5,399,933, the entirety of which is incorporated herein by reference. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] U.S. Pat. No. 8,568,359 [Patent Document 2] U.S. Patent No. 7,645,264 Summary of the Invention [Means for solving the problem]

[0007] According to one aspect, the invention comprises a stopper adapted for attachment to a plunger rod for use in a syringe barrel to accurately dispense fluids. The stopper includes a first portion formed from a first material and a second portion formed from a second material, the second material having a higher rigidity than the first material. The second portion is configured to be attached to the plunger rod. According to one embodiment, the second portion comprises an insert. The insert can be formed from a semi-rigid or rigid material. According to one example, the insert can be manufactured from a metal such as aluminum, zinc, extruded, stamped, or cast steel. According to another example, the insert can be formed from a non-metallic material having rigid or semi-rigid properties, i.e., polyetheretherketone (PEEK), or epoxy resin, or a similar but less expensive polyetherimide that has a higher glass transition temperature than that required for molded rubber.

[0008] The insert can be formed by injection molding, or by an extrusion / cutting process, or by a sintering process. The female threads can be disposed within the second portion for mating with the plunger rod. It can be appreciated that the insert can be secured to the plunger rod by other well known techniques, such as a friction fit, or the like.

[0009] The first material can be comprised of an elastomeric material, such as a material typically used for stoppers. The first material can be molded around the second material / insert. Alternatively, the insert can be embedded in the first material of the first part. According to one design, the second part or insert can include a tubular member having barbs extending radially around its outer surface configured to embed the second part or insert within the first material of the first part. The insert can be a "C" shaped member that provides some flexibility to the insert. According to one embodiment, the tubular member / insert can have a closed front surface for directly supporting the first material at the front surface of the stopper.

[0010] According to another embodiment, the stopper can include a third portion forming the distal end of the stopper, the third portion being formed from a third material consisting of an elastomeric material having barrier properties. Alternatively, the distal end of the stopper can be coated with a barrier film such as ethylene tetrafluoroethylene (ETFE) or a microporous membrane such as PTFE, expanded PTFE (ePTFE), polypropylene (PP), polyethylene (PE), etc., to minimize drug contact with the base rubber, thereby preventing leaching of the rubber product into the formulation.

[0011] According to another aspect, the invention includes a stopper adapted for attachment to a plunger rod for use in an auto-injector for precisely dispensing a fluid, the stopper including a first portion formed from a first material and a second portion formed from a second material, the second material having a higher rigidity than the first material. The second portion is configured for attachment to a piston rod. The piston rod can be a spring-loaded piston rod. The first material of the first portion of the stopper is comprised of an elastomeric material and the second portion includes an insert formed from a semi-rigid or rigid material. The insert can be embedded within the elastomeric material of the first portion.

[0012] According to yet another aspect, the invention comprises a stopper adapted to mount a lead screw for use with an injection drug delivery pen having a dose knob for accurately dispensing fluid, the stopper comprising a first portion formed from a first material and a second portion formed from a second material, the second material being more rigid than the first material, the second portion configured to be mounted to the lead screw. The dose knob and lead screw are configured to set a dose of fluid to be injected and to inject the administered fluid through the lead screw and the stopper from a drug cartridge mounted to the drug delivery pen. The first material of the first portion of the stopper is made of an elastomeric material and the second portion comprises an insert formed from a semi-rigid or rigid material. The insert can be embedded within the elastomeric material of the first portion. [Brief description of the drawings]

[0013] The above and other features and advantages of the present disclosure, as well as the manner in which they are achieved, will become more apparent, and the disclosure itself will be better understood, by referring to the following description of embodiments of the present disclosure in conjunction with the accompanying drawings.

[0014] [Figure 1] FIG. 1 is a cross-sectional view of a syringe assembly including a stopper for high dosage accuracy drug delivery according to an embodiment of the present invention. [Diagram 2] 2 is a top perspective view of the stopper of FIG. 1 according to an embodiment of the present invention. [Diagram 3] 3 is a cross-sectional view of the syringe assembly of FIG. 1 and the stopper of FIG. 2 in accordance with an embodiment of the present invention. [Figure 4A] 3 is a bottom left perspective view of the stopper of FIG. 2 in accordance with an embodiment of the present invention. FIG. [Figure 4B] 3 is a bottom right perspective view of the stopper of FIG. 2 in accordance with an embodiment of the present invention. FIG. [Diagram 5] 3 is a top perspective view of an insert of the stopper of FIG. 2 according to an embodiment of the present invention. [Figure 6]3 is a bottom perspective view showing the insert and top portion of the stopper of FIG. 2 in accordance with an embodiment of the present invention. FIG. [Figure 7] FIG. 3 is a bottom view of the stopper of FIG. 2 with an insert embedded therein, according to an embodiment of the present invention. [Figure 8A] FIG. 1 is an exploded perspective view of a prior art auto-injector that may utilize the stoppers for high dosage accuracy drug delivery of the present invention. [Figure 8B] FIG. 8B is a cross-sectional view of the prior art auto-injector of FIG. 8A in a ready-to-use position that can utilize the stoppers for high dosage accuracy drug delivery of the present invention. [Figure 8C] FIG. 8B is a cross-sectional view of the device of FIG. 8A after removal of a prior art needle shield that can utilize the stoppers for high dosage accuracy drug delivery of the present invention. [Figure 9A] 1 is an exploded perspective view of the components of a prior art medication delivery pen injection device that may utilize the stoppers for high dosage accuracy medication delivery of the present invention; FIG. [Figure 9B] FIG. 1 is a partial cross-sectional view of a prior art drug delivery pen injection device in a dosed and loaded state that can utilize the stopper for high dosage accuracy drug delivery of the present invention.

[0015] Like reference characters indicate corresponding parts in the several views. The illustrations described herein illustrate exemplary embodiments of the present disclosure, and such illustrations should not be construed as limiting the scope of the present disclosure in any way. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] The following description is provided to enable a person skilled in the art to make and use the described embodiments contemplated for practicing the invention. However, various modifications, equivalents, variations, and alternatives will be readily apparent to those skilled in the art. Any and all such modifications, variations, equivalents, and alternatives are intended to be within the spirit and scope of the invention.

[0017] Hereinafter, for purposes of explanation, the terms "upper", "lower", "right", "left", "vertical", "horizontal", "top", "bottom", "lateral", "longitudinal", and their derivatives shall refer to the present invention as oriented in the drawings. However, it will be understood that the present invention may be subject to various alternative modifications unless expressly specified to the contrary. It should also be understood that the specific devices illustrated in the accompanying drawings and described in the following specification are merely exemplary embodiments of the present invention. As such, specific dimensions and other physical characteristics relating to the embodiments disclosed herein are not to be considered as limiting.

[0018] 1, which illustrates a cross-sectional view of a syringe assembly, generally designated 10, including a stopper 12 for high dosage accuracy drug delivery. The syringe assembly includes a plunger rod 14. The stopper 12 and plunger rod 14 are adapted for use within a syringe barrel 16. The syringe barrel 16 has a generally elongated body including a distal or front end 18 that includes an exit opening and / or a mechanism for attaching a separate medical device, such as a luer 20, and an open proximal or rear end 22 having a finger grip 24 for receiving the stopper 12 and plunger rod 14.

[0019] The plunger rod 14 includes an elongated body portion 26, a proximal end 28 having a flange 30, and a distal end 32. A base or connector portion 34 extends axially from the distal end 32 of the plunger rod 14 and has a diameter smaller than that of the stopper 12. This connector portion 34 is configured to mate with a cavity 36 located at a proximal end 37 of the stopper 12 (as shown in FIGS. 3 and 4A). This mating engagement between the connector portion 34 and the stopper cavity 36 can be by friction fit, threaded engagement, or any other well-known configuration. Typically, the connector portion 34 of the plunger rod 14 supports the stopper 12 at its center.

[0020] Reference is now made to Figures 2-4B, which show a stopper 12 according to the present invention. The stopper 12 comprises a first portion 40 formed from a first material and a second portion 42 formed from a second material. The stopper 12 comprises a plurality of ribs 43 on its outer diameter. The first material of the first portion 40 of the stopper 12 can be made of any material suitable for providing sealing properties while under compression.

[0021] The second portion 42 formed from the second material has a higher rigidity than the first portion 40 formed from the first material. The second portion 42 is configured to be attached to the base or connector portion 34 of the plunger rod 14. According to one embodiment, the second portion comprises an insert. The insert can be formed from a semi-rigid or rigid material. According to one example, the insert 44 can be a metal, such as aluminum, zinc, steel, or another other metal. According to another example, the insert 44 can be formed from a non-metallic material having rigid or semi-rigid properties, such as a high temperature plastic or other material known in the art. The insert 44 can be disposed within the cavity 36 of the stopper 12 and / or the stopper 12 can be molded around the insert 44 to form the cavity 36.

[0022] With continued reference to FIGS. 4A and 4B, and with reference to FIGS. 5-7, the insert 44 can have a tubular shape. An opening 46 can be formed between the ends 48 of the insert forming a "C" shaped member, which provides some flexibility to the insert 44. As shown in FIGS. 5-7, according to one design, the insert 44 can have a plurality of radially extending barbs 50 extending around its outer surface 52. These barbs 50 can be configured to embed the second portion or insert 42, 44 within the first material of the first portion 40. According to one embodiment, the barbs 50 can have a triangular shape. The second portion or insert 42, 44 can have an inner surface 54 that defines the cavity 36 of the stopper 12. The inner surface 54 can be smooth or can include internal threads (not shown) configured to mate with the base / connector portion 34 of the plunger rod 14.

[0023] The insert 44 may be formed by injection molding or by an extrusion / cutting process or any other known process. Internal threads (not shown) may be formed in the insert 44 during the molding or extrusion process for securing the stopper 12 to the plunger rod 14. It is understood that the stopper 12 with the insert 44 may be secured to the plunger rod 14 by other known techniques, such as a friction fit or the like.

[0024] The first material used to form the first portion 40 of the stopper 12 can be comprised of an elastomeric material, such as materials typically used for stoppers, including, but not limited to, natural rubber, synthetic rubber, thermoplastic elastomers, or combinations thereof. The first material can be molded around the second portion / insert 42, 44. Alternatively, the insert 44 can be embedded in the first material of the first portion 40. In yet another design, the second portion / insert 44 can be fully encapsulated by the elastomeric material of the first portion 40 of the stopper 12. According to one embodiment, and with particular reference to FIG. 6, the second portion / insert 44 is first molded into the inner surface 62 of the front surface 64 or "cap" located at the distal end of the stopper 12, and then a second mold shot of elastomeric material forming the first portion 40 can fully encapsulate the insert 44. In this particular configuration, the material of the first portion 40 directly engages the connector portion 34 of the stopper 12. According to one embodiment, the insert 44 can have a closed front surface (not shown) formed from a second material for abutting the inner surface 62 of the first material of the first portion and directly supporting a front surface 64 located at a distal end 66 of the stopper 12.

[0025] According to another embodiment, the stopper can include a third portion 70 that forms the front surface 64 of the stopper 12. The third portion 70 can be formed from a third material that is an elastomeric material having suitable barrier properties for contact with the contents in the syringe barrel 16. According to one embodiment, the first portion 40 and the third portion 70 can be formed from different materials and can be formed in a two-shot molding process. Alternatively, the first portion 40 and the third portion 70 can be formed from the same material and a barrier film can be laminated separately onto the front surface 64 of the stopper. Suitable barrier films include, but are not limited to, microporous membranes such as ethylene tetrafluoroethylene (ETFE), ePTFE, polypropylene (PP), polyethylene (PE), and the like, that can minimize drug contact with the base rubber, thereby preventing leaching of the rubber product into the formulation.

[0026] 8A-8C, there is shown an example of an auto-injector, generally designated 110, according to the prior art that may utilize the stoppers for high dosage accuracy drug delivery of the present invention. The auto-injector 110 includes a housing, designated 120a and 120 in FIG. 8A and generally designated 120 in FIG. 8B and 8C, enclosing a container 122 having a fluid or medication disposed therein. The container 122 has an open proximal end and a substantially closed distal end having a needle 116 associated therewith. The container 122 is movable relative to the housing 120. A stopper 162 is disposed within the container 122 and cooperates with a distal end portion 161 of a piston rod 160. The piston rod 160 may be a spring loaded piston rod via a spring 182. A push button 170 may be provided to function as a trigger for the auto-injector 110. The device also includes a spring 184 between the container 122 and the safety shield 130. With the deshielder 180 and needle shield 123 removed, the device is ready for activation. The user then applies the distal end of the safety shield 130 to the injection site and applies a distal force to the housing 120, which causes the safety shield 130 to move proximally, compressing the spring 184 and placing the reservoir 122 in an active state. The injection step can now be triggered by applying a distally directed push force to the push button 170.

[0027] According to the present invention, the stopper 162 shown in Figures 8B and 8C can be replaced with the stopper 12 of the present invention, as shown in Figures 2-4B and described in detail above. Replacing the stopper 162 with the high dose accuracy stopper 12 of the present invention increases the accuracy of the fluid or medication dispensed by the auto-injector. As described above, the stopper 12 includes a first portion 40 formed from a first material and a second portion 42 formed from a second material. The first material of the first portion 40 of the stopper 12 can be made of any material suitable for providing sealing properties while under compression. The second portion 42 formed from the second material has a higher rigidity than the first portion 40 formed from the first material. The second portion 42 can be attached to the distal end portion 161 of the piston rod 160 of Figures 8B and 8C. The second portion 42 can include an insert 44 formed from a semi-rigid or rigid material. The insert 44 can be placed into the cavity 36 of the stopper 12 and / or the stopper 12 can be molded around the insert 44 to form the cavity 36. The auto-injector can then be operated in the same manner as the auto-injector of Figures 8A-8B. Use of the stopper 12 of the present invention can improve drug dosage accuracy because of its reduced amount of distortion during advancement, its lower contact pressure at rest, and because it reduced amount of hysteresis.

[0028] 9A and 9B, there is shown an injectable drug delivery pen, generally designated 210, according to the prior art that can utilize the stopper for high dose accuracy drug delivery of the present invention. The injectable pen injection device 210 includes a dose knob / button 212, an outer sleeve 214, and a cap 216. The dose knob / button 212 allows a user to set the dose of drug to be injected. The outer sleeve 214 is gripped by the user when injecting the drug. The cap 216 is used by the user to hold the pen injector 210 securely in a shirt pocket, purse, or other suitable location. The dose knob / button 212 has a dual purpose and is used to set the dose of drug to be injected and to inject the drug administered via a lead screw 218 and stopper 220 from a drug cartridge 224 that is attached to the pen that delivers the drug via a reservoir housing 232. The drug cartridge 224 is typically attached to a standard pen injector housing via known attachment means. The medication cartridge 224 may comprise a tube sealed at one end 228 with a septum 230 and at the other end with a stopper 220. In a standard drug delivery pen, all of the dosing and delivery mechanisms are within the outer sleeve 214. These mechanisms are understood by those skilled in the art and will not be described in detail herein. The pen needle assembly 210 includes a patient needle 234 retained by a sliding seal 235 and extending from the pen needle assembly 237 on the patient side, and a septum piercing needle cannula 236 located within a housing reservoir 232 on the non-patient side of the patient. The septum piercing needle cannula 236 is in fluid communication with the patient needle 234 via a check valve 240 and a secondary reservoir 242. The pen needle assembly 237 can be coupled to the reservoir housing 232 via the pen needle connection portion 250 and the wall portion 252 of the secondary reservoir 242 by a threaded configuration such as threads on the reservoir housing 232, although other attachment means such as direct attachment to the drug cartridge 224 via threads 226 can also be used.When the reservoir housing 232 is attached to the drug cartridge 224, the septum piercing cannula 236 pierces the septum 230, but the septum 230 does not move relative to the drug cartridge 224. However, the stopper 220 is axially displaceable within the drug cartridge 224 while maintaining a fluid-tight seal. Distal movement of the stopper 220 within the drug cartridge 224 (by advancement of the lead screw 218) forces the drug into the patient needle 234 of the needle assembly 237.

[0029] According to the present invention, the stopper 220 of the injection pen 210, as shown in Figures 2-4B and described in detail above, can be replaced with the stopper 12 of the present invention. The stopper 12 can be fixed on the lead screw 218 shown in Figures 9A and 9B. As described above, the stopper 12 includes a first portion 40 formed from a first material and a second portion 42 formed from a second material. The first material of the first portion 40 of the stopper 12 can be made of any material suitable for providing sealing properties while under compression. The second portion 42 formed from the second material has a higher rigidity than the first portion 40 formed from the first material. The second portion 42 can be attached to the lead screw 218 of the plunger rod 14. The second portion 42 can include an insert 44 formed from a semi-rigid or rigid material. The insert 44 can be placed in the cavity 36 of the stopper 12 and / or the stopper 12 can be molded around the insert 44 to form the cavity 36. The dose knob / button 212 can be used to set the dose of drug to be injected and inject the dosed drug from a drug cartridge 224 via the lead screw 218 and stopper 12 of the present invention. The use of the stopper 12 of the present invention can improve drug dose accuracy due to its reduced amount of distortion during advancement, its lower contact pressure at rest, and it reduced amount of hysteresis.

[0030] While the present disclosure has been described as having an exemplary design, the present disclosure may be further modified within the spirit and scope of the present disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the disclosure using its general principles. Further, this application is intended to cover departures from the present disclosure such as custom or practice in the art to which this disclosure pertains and which fall within the scope of the appended claims.

Claims

1. 1. A stopper for attachment to a plunger rod for use in a syringe barrel to accurately dispense a fluid, the stopper comprising a first portion formed from a first material and a second portion formed from a second material, the first material being an elastomeric material, the second material including an insert having greater rigidity than the first material, the insert being encapsulated by the first material such that the first material completely surrounds the insert, and a portion of the first portion is configured to be attached to the plunger rod such that the first material of the first portion directly engages the plunger rod and such that the insert does not directly contact the plunger rod.

2. The stopper of claim 1 , wherein the insert is formed from a semi-rigid or rigid material.

3. The stopper of claim 1 , wherein the insert is configured to be molded onto a front inner surface at a distal end of the stopper and then the first portion is molded around the insert.

4. The stopper of claim 3 , wherein the insert is formed by injection molding or by an extrusion / cutting process.

5. The stopper of claim 3 , wherein the insert and the first portion are formed in a two-shot molding process.

6. The stopper of claim 1 , wherein the first portion includes internal threads for mating with the plunger rod.

7. 2. The stopper of claim 1, wherein the second portion comprises a tubular member having barbs extending radially about an outer surface thereof configured to embed the second portion within the first material of the first portion.

8. 2. The stopper of claim 1, wherein the insert comprises a tubular member having opposed ends defining an opening between the ends.

9. The stopper of claim 8 , wherein the tubular member comprises a C-shaped portion.

10. The stopper of claim 1 , wherein the insert comprises a tubular member having a closed front surface for directly supporting an inner surface of the first material at a distal end of the stopper.

11. 10. The stopper of claim 1, wherein the stopper comprises a third portion forming a distal end of the stopper, the third portion being formed from a third material comprising an elastomeric material having barrier properties or coated with a barrier film.

12. 1. A stopper adapted for attachment to a plunger rod for use in an automatic injector for accurately dispensing a fluid, the stopper comprising a first portion formed from a first material and a second portion formed from a second material, the first material being an elastomeric material, the second material including an insert having greater rigidity than the first material, the insert being encapsulated by the first material such that the first material completely surrounds the insert, and a portion of the first portion configured to be attached to a plunger rod such that the first material of the first portion directly engages the plunger rod and such that the insert does not directly contact the plunger rod.

13. A stopper as described in claim 12, wherein the second portion comprises an insert formed from a semi-rigid or rigid material, the insert being encapsulated by the elastomeric material of the first portion by a two-shot molding process.

14. 1. A stopper adapted to attach to a lead screw for use with an injection pen having a dose knob for accurately dispensing fluids, the stopper comprising a first portion formed from a first material and a second portion formed from a second material, the first material being an elastomeric material, the second material including an insert having a greater rigidity than the first material, the insert being encapsulated by the first material such that the first material completely surrounds the insert, and a portion of the first portion configured to be attached to the lead screw such that the first material of the first portion directly engages the lead screw and such that the insert does not directly contact the lead screw.

15. 15. The stopper of claim 14, wherein the dose knob and lead screw set a dose of fluid to be injected and injects the administered fluid through the lead screw and stopper from a drug cartridge attached to a drug delivery pen.

16. The stopper of claim 14, wherein the second portion comprises an insert formed from a semi-rigid or rigid material, and the insert is encapsulated by the elastomeric material of the first portion by a two-shot molding process.

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