Medical delivery devices with oxygen permeation inhibition

Abstract

This invention relates to a medical delivery device comprising: a lubricant-free syringe having a proximal end, a distal end, and an inner surface, the inner surface defining a fluid chamber for receiving at least one therapeutic agent; an elastomeric stop having an outer surface forming a fluid-impermeable seal with the inner surface of the syringe, wherein the elastomeric stop includes a plurality of ribs, each pair of ribs having a valley between them; and at least one ring member located within at least one valley, wherein the at least one ring member comprises an oxygen-absorbing material, an oxygen-adsorbing material, or a combination of both.

Description

[0001] This application is a divisional application of Chinese patent application No. 201880094904.1 entitled "Medical Delivery Device with Oxygen Inhibition" (the invention patent application No. 201880094904.1 is an international patent application PCT / US2018 / 029019 that entered the Chinese national phase). Technical Field

[0002] This disclosure relates to medical delivery devices, and more particularly to syringes, autoinjectors, and pens configured to inhibit oxygen permeation into fluids or substances contained within the medical delivery device. Background Technology

[0003] Medical delivery devices such as syringes, autoinjectors, and pens typically include a syringe, a stop positioned within the syringe, and a plunger or actuation mechanism that moves the stop. As the pharmaceutical industry seeks new and more convenient methods of drug delivery, pre-filled syringes, autoinjectors, and pens have become preferred options for unit-dose drug delivery. Pre-filled syringes minimize drug waste and extend product lifespan while enabling patients to self-administer injectable medications. Specifically, pre-filled syringes, autoinjectors, and pens eliminate dosing errors and prevent overfilling. Drug instability over extended periods remains a concern with pre-filled syringes. Drug instability can be due to, for example, the interaction between the syringe and the fluid composition contained therein.

[0004] Therefore, the design and quality of pre-filled syringes help ensure that the fluid composition contained therein remains uncontaminated. Contamination can occur, for example, due to contact between the fluid composition and several different components of a syringe, autoinjector, or pen. For instance, syringes, autoinjectors, and pens may include a syringe barrel and may have a plunger rod for actuating the syringe and delivering the drug, with the syringe barrel having a stop slidably fitted within it. The stop is typically made of an elastomer. Conventionally, silicone oil is applied to the stop and / or the syringe barrel to reduce sliding friction between the stop and the syringe barrel and improve the seal between them. When medication is administered, the silicone oil allows the stop to slide easily within the syringe barrel, thereby ensuring complete drug delivery.

[0005] The use of silicone in pre-filled syringes, auto-injectors, or pens is a concern in the industry because oils can degrade drugs and / or may inject a certain amount of silicone into them. The use of silicone in pre-filled syringes, auto-injectors, and pens may be of particular concern to biopharmaceutical companies because it may cause certain proteins to aggregate.

[0006] Furthermore, some fluid compositions in pre-filled syringes, autoinjectors, and pens are oxygen-sensitive and may be oxidized or adversely affected by contact with oxygen. This oxygen sensitivity can be problematic for pre-filled syringes, autoinjectors, and pens, as they typically allow small amounts of air to seep into the syringe during storage. Consequently, oxygen-sensitive drugs or pharmaceutical formulations may require additional excipients, packaging, and / or manufacturing steps to enhance stability and prevent degradation. However, these approaches increase the overall complexity of the device or pharmaceutical formulation's construction.

[0007] Therefore, there is a need for silicone-free pre-filled syringes, autoinjectors, and pens that are configured to inhibit or prevent oxygen from permeating into the syringe, autoinjector, or pen syringe. Summary of the Invention

[0008] This disclosure relates to medical delivery devices (e.g., syringes, autoinjectors, and pens) comprising a silicone-free syringe having a proximal end and a distal end, and an inner surface defining a fluid chamber for receiving at least one therapeutic agent; an elastomeric stop whose outer surface forms a fluid-impermeable seal with the inner surface of the syringe; and a plunger rod or actuation mechanism that displaces the stop within the syringe. The syringe has a diameter-reducing region located at the proximal end to enhance the interference fit between the elastomeric stop and the inner surface of the syringe. The stop includes at least one rib that abuts against the diameter-reducing region when the stop is in an unpressed (unpressed) state. The diameter of the diameter-reducing region is smaller than the diameter of the remainder of the syringe. The syringe may include a transition section (e.g., a truncated cone or tapered transition section) positioned between the diameter-reducing region at the proximal end and a diameter-larger region at the distal end to provide a gradual transition between them.

[0009] A coating material may be provided on a portion of the inner surface of the syringe to form a region with a reduced diameter. At least one rib of the stop member contacts the coating material in the unpressed state. In some embodiments, the coating material may comprise an oxygen-absorbing material and / or an oxygen-adsorbing material, or a combination of both. In another embodiment, the coating comprises a material with low oxygen permeability. In yet another embodiment, the coating is formed of a suitable material with a low coefficient of friction to improve sealing at the proximal end of the medical device while also reducing breakage and slippage forces. In an exemplary embodiment, the coating material extends no more than half the length of the syringe.

[0010] In another embodiment, at least one insert contacts the inner surface of the syringe to form a region with a reduced diameter. The insert is formed of or includes a gas barrier to prevent oxygen from permeating into the syringe. The insert may be fixed to the inner surface of the syringe (e.g., via an adhesive), or it may be integrally formed on the inner surface of the syringe. In one embodiment, the insert is a solid polymer tube bonded (adheded) to the inner surface of the syringe.

[0011] In another embodiment, the region with reduced diameter includes a laminate having one or more fluoropolymer films attached to the inner surface of the syringe. The laminate may be formed from a single high-strength film (e.g., PTFE) or multiple high-strength films. The film thickness may range from about 0.5 μm to about 100 μm. In some embodiments, the laminate may be bonded (adhesive) or otherwise attached to the inner surface of the syringe. In an alternative embodiment, the laminate may be thermoformed on the inner surface of the syringe.

[0012] In another embodiment, this disclosure relates to a medical device (e.g., a syringe, autoinjector, and pen) comprising a silicone-free syringe having a proximal end and a distal end, and an inner surface defining a fluid chamber for receiving at least one therapeutic agent; an elastomeric stop having an outer surface that forms a fluid-impermeable seal with the inner surface of the syringe; and a plunger rod or actuation mechanism that displaces the stop within the syringe. The stop includes a plurality of ribs and valleys between each pair of ribs. At least one ring member is disposed within one or more valleys of the stop. The ring member may include an oxygen-absorbing material and / or an oxygen-adsorbing material that binds to and / or otherwise removes any oxygen that may permeate into the valley. In some embodiments, each valley of the elastomeric stop includes at least one ring member. The medical device may also include a coating on the inner surface of the syringe, on a portion adjacent to the proximal end of the syringe, to form a coated area that forms a region with a reduced diameter, the diameter of which is smaller than the diameter of the uncoated area of ​​the syringe.

[0013] In another embodiment, this disclosure relates to a medical device (e.g., a syringe, an autoinjector, and a pen) comprising a silicone-free syringe having a proximal end and a distal end, and an inner surface defining a fluid chamber for containing at least one therapeutic agent; an elastomeric stop having an outer surface that forms a fluid-impermeable seal with the inner surface of the syringe; a plunger rod attached to the stop and mounted within the syringe syringe for distally moving the stop within the syringe; and a barrier coating on a portion of the stop. The barrier coating may comprise an oxygen-barrier material. The barrier coating may surround a portion of the stop not exposed to the fluid chamber. In some embodiments, the barrier coating may surround the entire stop, provided that it is inert to the therapeutic agent contained within the syringe syringe. The stop may comprise an elastomeric body having a plurality of ribs and valleys between each pair of ribs. Coatings may be provided on the ribs and in the valleys between each pair of ribs. In some aspects, the plunger rod also includes a coating.

[0014] The above and other embodiments, along with their many advantages and features, are described in more detail below in conjunction with the non-limiting drawings. Attached Figure Description

[0015] The accompanying drawings are provided to give a further understanding of the present disclosure and are included in and form part of this specification, illustrating embodiments and, together with the description, serving to explain the principles of the present disclosure.

[0016] Figure 1a A cross-sectional view of a syringe syringe having a region with a reduced diameter is shown according to some embodiments.

[0017] Figure 1b An exploded view of a syringe syringe having a region with a reduced diameter according to some embodiments is shown;

[0018] Figure 2a -c illustrates the process steps for coating the inner surface of a syringe syringe according to some embodiments;

[0019] Figure 3 A cross-sectional view of a syringe syringe having a coating on its inner surface according to some embodiments is shown;

[0020] Figure 4 The diagram illustrates the relationship between [various embodiments] and [other embodiments]. Figure 3 An exploded view of the stop rib that contacts the inner surface of the syringe barrel;

[0021] Figure 5 A cross-sectional view of a stop member pressed into a syringe syringe according to some embodiments is shown;

[0022] Figure 6A perspective view of a syringe having a ring member surrounding the valley of a stop member according to some embodiments is shown;

[0023] Figure 7 Illustrations are shown according to some embodiments Figure 6 A cross-sectional view of the syringe;

[0024] Figure 8 A cross-sectional view of a syringe with a coated stop is shown according to some embodiments;

[0025] Figure 9 A cross-sectional view of a syringe with a coated stop and a plunger rod according to some embodiments is shown.

[0026] Figure 10-17 These are schematic cross-sectional side views of a stop member according to some embodiments, depicting different types of laminates applied to the stop member; and

[0027] Figure 18 This is a schematic cross-sectional view of an autoinjector according to some embodiments. Detailed Implementation

[0028] Those skilled in the art will readily understand that various aspects of this disclosure can be implemented by any number of methods and constructions for devices to perform the intended functions. It should also be noted that the accompanying drawings referenced herein are not necessarily drawn to scale and may be enlarged to illustrate various aspects of this disclosure, and in this regard, the drawings should not be construed as limiting. The terms "silicone" and "silicone oil" are used interchangeably herein.

[0029] This disclosure relates to medical delivery devices (e.g., syringes, autoinjectors, and pens) that are silicone-free or substantially silicone-free for storing and delivering medical fluids. As used herein, the term "substantially silicone-free" means that the syringe barrel and / or stop has an unquantifiable or trace amount of silicone or other liquid lubricant. Medical delivery devices are configured to inhibit or prevent oxygen from permeating into the syringe barrel of the medical delivery device. This disclosure provides stoppers suitable for use in syringes that are silicone-free or substantially silicone-free or otherwise lubricant-free (without or substantially no silicone or other liquid lubricant), inhibiting or preventing oxygen from entering the syringe barrel and contacting the therapeutic fluid in the medical delivery device. For ease of description, the following disclosure refers to syringes, but the description is equally applicable to autoinjectors or pens. Furthermore, in alternative embodiments, the syringe barrel may include silicone (or another lubricant), and such embodiments are considered to be within the scope of this disclosure.

[0030] Figure 1aA syringe 10 (e.g., a pre-filled syringe) according to one or more embodiments is shown. The syringe 10 includes a silicone-free or substantially silicone-free syringe 15 having opposing distal ends 20 and proximal ends 25, and a fluid chamber 30 positioned between the distal ends 20 and proximal ends 25. In some embodiments, the syringe 15 has a hydrophilic inner surface. The distal end 20 of the syringe 15 may include an injection port 35 extending through it and communicating with the fluid chamber 30. In some embodiments, the syringe is formed of a silicone-free or other lubricant-free glass material, such as, for example, borosilicate glass.

[0031] In some embodiments, a cap 40 is disposed at the distal end 20 of the syringe 15. The cap 40 includes a proximal end 45 that mates with the distal end 20 or injection port 35 and a closed distal end 50. The cap 40 inhibits or prevents ambient air from communicating with the fluid chamber 30 through the distal end 20 or injection port 35. Optionally, a puncture element 55 is also disposed at the distal end 20 of the syringe 15. The puncture element 55, such as a needle, includes a distal end 65 and a proximal end 60 that mates with the distal end 20 or injection port 35. As those skilled in the art will appreciate, within the scope of the invention, in some embodiments, the injection port 35 may include a sharp needle sheath or a blunt-tipped cannula, such as those used with so-called needle-free systems. For illustrative and not limiting purposes, as shown herein, the puncture element 55 is formed as a sharp, elongated needle sheath including a proximal end 60, a sharp distal end 65, and an inner lumen 70 extending between the proximal end 60 and the distal end 65. The proximal end 60 of the needle cannula can be securely attached to the injection port 35 of the syringe 15.

[0032] In some embodiments, the cap 40 is mounted on the injection port 35 and releasably engages the injection port 35 of the syringe 15. The cap 40, which may be formed of a rigid material such as plastic or a flexible material such as rubber, or similar materials or combinations known to those skilled in the art, may be configured with a sealing element or the like of appropriate size. Thus, the cap 40 inhibits or prevents ambient air from communicating with the fluid chamber 30 through the injection port 35.

[0033] The proximal end 25 of the syringe 15 may include a flange 80 that serves as a finger retainer for pressing and pulling the plunger rod 85 within the syringe 15. The plunger rod 85 has opposing distal ends 90 and proximal ends 95, with a stop 100 attached at the distal end 90. The stop 100 includes opposing proximal ends 105 and distal ends 110. As those skilled in the art will understand, the stop 100 may include one or more circumferentially extending annular ribs that form a liquid-tight seal with the syringe 15. In at least one embodiment, the stop 100 includes two or more ribs 120. In embodiments with multiple ribs, the stop includes a valley 115 between each pair of adjacent ribs 120.

[0034] The syringe may be formed of a substantially rigid or hard material, such as glass (e.g., borosilicate glass), ceramic, one or more polymeric materials (e.g., polypropylene, polyethylene, and copolymers thereof), metallic, or plastic materials (e.g., cyclic olefin polymers (COC) and cyclic olefin copolymers (COP), and combinations thereof). In some embodiments, the syringe is formed of glass (e.g., bare glass without any lubricant), resin, plastic, metal, or similar material, and has an inner wall characterized by the absence of a lubricant, such as, but not limited to, silicone or silicone oil.

[0035] The stop 100 may be formed of an elastomer body 125. The elastomer body 125 may include any elastomer suitable for the application, most particularly rubbers consisting of butyl, bromobutyl, chlorobutyl, silicone, nitrile, styrene-butadiene, polychloroprene, ethylene propylene diene, fluorinated elastomers, or combinations or blends of any of the foregoing. The material of the elastomer body 125 is selected to provide a low coefficient of friction, compliance (flexibility), low extractability and leachability, good barrier properties in relation to extractable and leachable substances from the elastomer body 125, and good air and liquid impermeability.

[0036] In some embodiments, the stop 100 may further include a low-friction barrier membrane surrounding the elastomer body 125. The barrier membrane can inhibit the leaching of material from the elastomer material or the extraction of compounds from a drug through the elastomer. The material of the barrier membrane is selected to provide a low coefficient of friction, flexibility, low extractability and leachability, and good barrier properties, as these are related to the extractability and leachability of the elastomer body 125. For example, the barrier membrane may include one or more fluoropolymer membranes, such as, but not limited to, polytetrafluoroethylene (PTFE) or expanded polytetrafluoroethylene (ePTFE) membranes.

[0037] In some embodiments, the stop 100 may be formed of an elastic body 125 and one or more laminated layers 230. The laminated layer 230 may include a single layer of polymer barrier layer 240. Figure 10 A stop 100 is depicted, which includes an elastomer body 125 and a single layer including a barrier layer 240.

[0038] Examples of elastomers that can be used to form the elastomer body 125 include any elastomer suitable for this application, most particularly composed of butyl, bromobutyl, chlorobutyl, silicone (silicone resin), nitrile, styrene-butadiene, polychloroprene, ethylene-propylene-diene, fluorinated elastomers, thermoplastic elastomers (TPE), thermoplastic vulcanizates (TPV), and those marketed under the trade name VITON. ®Rubber composed of materials sold, as well as combinations and blends thereof. Exemplary elastomer materials include, but are not limited to: butyl rubber, bromobutyl rubber, chlorobutyl rubber, silicone rubber, nitrile rubber, styrene-butadiene rubber, polychloroprene rubber, ethylene propylene diene rubber, fluorinated elastomers, and combinations thereof.

[0039] Examples of fluoropolymers that can be used to form barrier layer 240 include any fluoropolymer suitable for this application, most particularly densified expanded fluoropolymers such as densified expanded polytetrafluoroethylene (ePTFE). Other suitable fluoropolymers include, but are not limited to, expanded polytetrafluoroethylene (ePTFE), fluorinated ethylene propylene (FEP), polyvinylidene fluoride, polyvinyl fluoride, perfluoropropyl vinyl ether, perfluoroalkoxy polymers, tetrafluoroethylene (TFE), parylene AF-4, parylene VT-4, and copolymers and combinations thereof. Non-fluoropolymers such as, but not limited to, polyethylene, polypropylene, parylene C, and parylene N can be used to form barrier layer 240.

[0040] In one or more embodiments, the barrier layer 240 may comprise or be formed of one or more of the following materials: ultra-high molecular weight polyethylene as taught in U.S. Patent No. 9,732,184 to Sbriglia; parylene as taught in U.S. Patent Publication No. 2016 / 0032069 to Sbriglia; polylactic acid as taught in U.S. Patent No. 9,732,184 to Sbriglia et al.; and / or VDF-co-(TFE or TrFE) polymers as taught in U.S. Patent No. 9,441,088 to Sbriglia.

[0041] In some embodiments, the barrier layer 240 may comprise, or be made of, an expanded fluoropolymer or a densified expanded fluoropolymer, preferably expanded polytetrafluoroethylene (ePTFE) or densified expanded polytetrafluoroethylene. The dense ePTFE film may be prepared according to the methods described in U.S. Patent No. 7,521,010 to Kennedy et al., U.S. Patent No. 6,030,694 to Dolan et al., U.S. Patent No. 5,792,525 to Fuhr et al., or U.S. Patent No. 5,374,473 to Knox et al. Expanded copolymers of PTFE, such as those described in U.S. Patent No. 5,708,044 to Branca, U.S. Patent No. 6,541,589 to Baillie, U.S. Patent No. 7,531,611 to Sabol et al., U.S. Patent Application No. 8,637,144 to Ford, and U.S. Patent No. 9,139,669 to Xu et al., may be used.

[0042] Barrier layer 240 may also include an expandable polymer material comprising a functional tetrafluoroethylene (TFE) copolymer material having a microstructure characterized by nodes interconnected by fibrils, wherein the functional TFE copolymer material includes a functional copolymer of TFE and PSVE (perfluorosulfonyl vinyl ether), or a functional copolymer of TFE and another suitable functional monomer, such as, but not limited to, vinylidene fluoride (VDF), vinyl acetate, or vinyl alcohol. The functional TFE copolymer material may be prepared according to methods described, for example, those described in U.S. Patent No. 9,139,669 or U.S. Patent No. 8,658,707 to Xu et al.

[0043] In another embodiment, such as Figure 11 As shown, laminate 230 may include a composite material comprising barrier layer 245 and porous layer 250. Barrier layer 245 may include fluoropolymers such as densified expanded fluoropolymers (e.g., densified expanded polytetrafluoroethylene), polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), fluorinated ethylene propylene (FEP), polyvinylidene fluoride, polyvinyl fluoride, perfluoropropyl vinyl ether, perfluoroalkoxy polymers, tetrafluoroethylene (TFE), parylene AF-4, parylene VT-4, and copolymers and combinations thereof. Non-fluoropolymers such as polyethylene, polypropylene, parylene C, and parylene N may also be used to form barrier layer 245. It should be understood that any materials described above with respect to barrier layer 240 may be used in barrier layer 245 or used as barrier layer 145. The porous layer 250 may comprise ePTFE (e.g., the ePTFE taught in U.S. Patent No. 6,541,589 to Baille) or other porous, expandable (and often fibrous) fluoropolymers. The laminate 230 having the barrier layer 245 and the porous layer 250 can be constructed by coating or otherwise depositing a barrier polymer (e.g., a fluoropolymer) onto the porous layer 250 to form a composite material. One such example is depositing a granular or powdered fluoropolymer, such as powdered PTFE, onto the surface of the porous ePTFE layer during a coating process. The ePTFE layer should be configured to have sufficient thermal stability to allow heat treatment of the deposited granular or powdered fluoropolymer to form the barrier layer, or to bond the deposited barrier layer to the porous ePTFE layer. It should be noted that the porous (e.g., ePTFE) layer may be filled with organic or inorganic materials to provide color, lubricity, or other functional properties.

[0044] According to some embodiments, the elastomeric material of the elastomer body 125 may at least partially permeate the porous layer 250. Figure 12 A cross-sectional view of the stop is shown, depicting a barrier layer 245, a porous layer 250, and an elastomer body 125. Specifically, Figure 12This illustrates a partial permeation region 260 where the elastomeric material of the elastomer body 125 partially permeates into the porous layer 250. This permeation of the elastomeric material of the elastomer body 125 into the porous layer 250 improves the bond (adhesion) between the elastomer body 125 and the laminate 230.

[0045] Depending on other aspects, the material of the barrier layer 245 may at least partially permeate the porous layer 250. Figure 13 A cross-sectional view of the stop is shown, depicting a barrier layer 245, a porous layer 250, and an elastomer body 125. Specifically, Figure 13 A partially permeated region 265 is shown where the material of barrier layer 245 partially permeates into porous layer 250. This permeation improves the bond (adhesion) between barrier layer 245 and porous layer 250. The partially permeated region 265 also provides support to barrier layer 245, imparting strength, toughness, compliance, and stability, which can be beneficial in the molding process and applications.

[0046] In some embodiments, the barrier layer 245 may substantially fill the porous layer 250. In another embodiment, the porous layer 250 may be filled to a degree substantially similar to that of the barrier layer 245 and the elastomer, thereby leaving few openings in the porous structure. In yet another embodiment, both the barrier layer 245 and the elastomer partially fill the porous layer 250, while leaving some openings between them. Other variations in the permeation of the elastomer and / or barrier layer 245 will be apparent to those skilled in the art. Each can offer advantages, such as reduced friction, improved barrier performance, and improved sealing, depending on the specific application, when the various desired characteristics of the finished device are properly considered. Known methods for controlling the degree of permeation of the barrier polymer or elastomer also include variations in time, temperature, pressure, and the porosity of the porous material. In one aspect, the porous material may, for example, have a porosity that varies with depth.

[0047] In another embodiment, the barrier layer 245 may be formed of a composite fluoropolymer or non-fluoropolymer material having a barrier layer and a binding layer, such as that described in Gunzel's U.S. Patent Publication No. 2016 / 0022918. It should be noted that, as used herein, the term "binding layer" may include fluoropolymer and / or non-fluoropolymer materials. The binding layer may include or be formed of ePTFE or other porous expandable fluoropolymers (e.g., ePTFE as taught in Baille's US 6541589). Alternatively, the binding layer may be formed of or comprise non-fluoropolymer materials. Non-limiting examples of suitable non-fluoropolymer materials for or used as binding layers include non-fluoropolymer membranes, non-fluoropolymer microporous membranes, nonwoven materials (e.g., spunbond, meltblown fiber materials, electrospun nanofibers), polyvinylidene fluoride (PVDF), nanofibers, polysulfone, polyethersulfone, polyarylsulfone, polyetheretherketone (PEEK), polyethylene, polypropylene, and polyimide.

[0048] In another embodiment, the barrier layer 245 can be made by forming a thin, dense composite material comprising a porous ePTFE layer and a thermoplastic barrier layer. In this regard, a thermoplastic with a low coefficient of friction is preferred. Therefore, thermoplastics based on fluoropolymers such as FEP, PFA, and THV are suitable. The barrier element according to this aspect can be an FEP / ePTFE laminate obtained by following the methods taught in Bacino's WO 94 / 13469. The barrier layer can be formed in a female mold at a process temperature above the softening temperature or even above the melt (melt) temperature of the FEP film.

[0049] The composite materials described herein, formed from expanded fluoropolymers (e.g., ePTFE) and fluoropolymer-based thermoplastics (e.g., FEP), allow for the formation of surprisingly thin yet robust barrier films. In one embodiment, the ePTFE layer can act as a support during molding to allow for a thin barrier film. The porous ePTFE layer can also act as a reinforcing agent for the thermoplastic layer to maintain film strength and barrier layer integrity as described above, and the porous ePTFE layer can also serve as a bonding layer when portions of the ePTFE are allowed to remain porous and oriented inward toward the mold interior.

[0050] In another embodiment, the barrier layer 245 may comprise a composite of a dense ePTFE membrane and a porous ePTFE thin layer bonded (adhered) to the barrier membrane. The dense ePTFE membrane can be obtained as described in U.S. Patent No. 7,521,010 to Kennedy et al. The ePTFE / dense ePTFE composite material can be combined in a manner described in U.S. Patent No. 6,030,694 to Dolan et al. In this embodiment, the composite material comprises a dense ePTFE membrane layer and a porous ePTFE layer. The porous ePTFE layer is configured such that most of the porosity is retained during thermoforming. It is also flexible enough to improve the seal against the syringe barrel wall. To achieve this, at least a portion of the porous layer remains sufficiently open after thermoforming and post-compression molding with an elastomer. This open (open-pore) porosity allows for a degree of compressibility, which can contribute to the fit (compliance) and seal of the stop against the surface.

[0051] In another embodiment, such as Figure 14 As shown, laminate 230 comprises a composite material having at least three layers: a densified expanded fluoropolymer layer 270, a molten fluoropolymer barrier layer 275, and a porous layer 280. The densified expanded fluoropolymer layer 270 may include or be formed from densified ePTFE. The molten fluoropolymer barrier layer 275 may include fluoropolymers, such as densified expanded fluoropolymers, PTFE, ePTFE, densified ePTFE, or fluorinated ethylene propylene (FEP), polyvinylidene fluoride, polyvinyl fluoride, perfluoropropyl vinyl ether, perfluoroalkoxy polymers, and copolymers and combinations thereof. Non-limiting examples of non-fluoropolymers that may be used in the barrier melt layer 275 include polyethylene and polypropylene. The porous layer 280 may include or be formed from ePTFE or other porous expanded fluoropolymers. The laminate 230, having a dense expanded fluoropolymer layer 270, a molten fluoropolymer barrier layer 275, and a porous layer 280, can be constructed by coating or otherwise depositing the dense expanded fluoropolymer onto the porous layer to form a composite material. The dense ePTFE membrane, fluoropolymer, and porous layer can be thermoformed to prepare a preform, which can then be bonded to the elastomer body 125 by injection molding, compression molding, priming, and post-lamination, or by other suitable methods known to those skilled in the art. In a non-limiting embodiment, the laminate 230 is formed from a dense fluoropolymer (e.g., dense ePTFE), a thermoplastic adhesive (e.g., FEP), and a porous fluoropolymer (e.g., ePTFE).

[0052] According to some aspects, such as Figure 15As shown, the elastomeric material of the elastomer body 125 can at least partially permeate the porous layer 280. According to other embodiments, such as... Figure 16 As shown, the material of the molten fluoropolymer barrier layer 275 can at least partially permeate the porous layer 180. In other embodiments, such as Figure 17 As shown, the material of the molten fluoropolymer barrier layer 275 can at least partially permeate the densified expanded fluoropolymer layer 270.

[0053] It should be understood that, as described in U.S. Patent Nos. 8,722,178, 2012 / 0251748, and 2016 / 0022918 to Ashmead et al., the stop 100 may comprise an elastomeric material or a barrier polymer to permeate to varying degrees into a porous material or a densified, expandable fluoropolymer layer. It should also be understood that many variations of the methods described herein may be used to form the stop 100 without departing from the scope and / or spirit of the invention.

[0054] In one embodiment, the elastomer 125 of the stop may have an ePTFE membrane or a dense ePTFE membrane thereon. The high strength of the expandable membrane allows for the formation of an extremely thin barrier membrane. Barrier membranes with thicknesses ranging from 0.5 micrometers to 20 micrometers can be prepared. The membrane is preferably less than 30 micrometers. The membrane can be optionally pretreated or post-treated using methods known to those skilled in the art, such as chemical etching, plasma treatment, corona treatment, roughening, or other methods, to improve its adhesion to the elastomer body. In some embodiments, the membrane, such as an ePTFE membrane or a dense ePTFE membrane, surrounds the elastomer body 125 integrally. In other embodiments, the membrane partially surrounds the elastomer body 125. For example, the membrane may surround only the portion of the stop that does not come into contact with fluid or drug within the syringe.

[0055] In other embodiments, the barrier film may also comprise a composite fluoropolymer film having a barrier layer and a porous layer. The barrier layer may be formed from dense expanded polytetrafluoroethylene (ePTFE), expanded polytetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP), polyethylene, polypropylene, polyvinylidene fluoride (PVDF), polyvinyl fluoride (PVC), perfluoropropyl vinyl ether (PFLE), perfluoroalkoxy polymers, etc. The porous layer may be formed from ePTFE or other porous expanded and advantageously fibrillated fluoropolymers (e.g., ePTFE taught in U.S. Patent No. 3,953,566 to Gore). The ePTFE layer may advantageously be filled with organic or inorganic materials to provide color, lubricity, or other functions. In a non-limiting embodiment, the barrier layer is a three-layer composite material comprising a dense fluoropolymer (e.g., dense ePTFE), a thermoplastic binder (e.g., FEP), and a porous fluoropolymer (e.g., ePTFE).

[0056] The stop described herein can be used in syringes for storing and delivering fluids typically used for medical purposes. In some embodiments, the syringe is pre-filled with fluid (e.g., a pre-filled syringe). In at least one embodiment, the syringe contains a fluid for treating a disease, such as, but not limited to, eye diseases (e.g., macular degeneration and glaucoma) and diabetes. Advantageously, the syringe does not contain lubricants such as silicone or other liquid lubricants. Therefore, the syringe barrel in the syringes described herein contains no or substantially no silicone or other liquid lubricants.

[0057] In at least one embodiment, the syringe of this disclosure includes a syringe barrel comprising a diameter-reduced region located at the proximal end of the syringe barrel to enhance the interference fit between the stop and the inner surface of the syringe barrel, thereby preventing or inhibiting oxygen permeation into the syringe barrel. Figure 1a and 1b As shown, the syringe 15 has a reduced-diameter region 16 to enhance the interference fit between the stop 100 and the inner surface of the body at the reduced-diameter region 16. With the increased interference fit, resistance to oxygen permeation also increases. To provide the increased interference fit while ensuring sufficient minimum pressing force for ease of operation, the reduced-diameter region 16 is provided only on a portion of the syringe 15, for example, on the portion adjacent to the proximal end 25 of the syringe 15. This allows one or more ribs 120 on the stop 100 to remain within the reduced-diameter region 16 to increase the interference fit and inhibit oxygen permeation before use. Slight movement of the stop 100 during pressing (e.g., distal advancement of the plunger rod 85) allows one or more ribs 120 to move distally within the syringe 15 beyond the reduced-diameter region 16 and easily move through the syringe 15 to expel fluid 135.

[0058] Figure 1aFluid 135 is also shown disposed in the fluid chamber 30 of the syringe 15 of the syringe 10 (e.g., a pre-filled syringe). For illustrative purposes only, fluid 135 is identified herein as a fluid of a predetermined dose, i.e., a therapeutic agent, biological agent, drug, or medicine; however, it should be understood that fluid 135 may be any type of liquid or material that can be expelled from the syringe, or fluid 135 may not be in the receiving chamber (e.g., an unfilled syringe).

[0059] Figure 1b An exploded view of a syringe according to some embodiments is shown. The syringe barrel 15, the stop 100, and the plunger rod 85 are three separate and independent components forming the syringe 10. One or more of these components work together to prevent oxygen from permeating into the syringe barrel 15 of the syringe 10 before use.

[0060] As discussed herein, there are various ways to form a region with a reduced diameter to reduce the inner diameter of the syringe 15 over a portion of its length. In one embodiment, as... Figure 1a and 1b As shown, the syringe barrel 15 of the syringe 10 can be manufactured such that a portion of the barrel has a reduced diameter. For example, a glass syringe can be heated and shaped around a mandrel to set its inner diameter. This heat treatment can be applied only to a portion of the syringe barrel 15 to form a region 16 with a reduced diameter. In other embodiments, the syringe barrel 15 may have a first region of constant diameter and a second region of constant diameter, wherein the diameter of the first region is smaller than the diameter of the second region. The two regions may be separated by one or more stages (steps) (not shown), or may transition gradually between the two regions. In another embodiment, the region 16 with a reduced diameter may have a tapered syringe barrel 15 that tapers from a region with a reduced diameter to a region with a larger diameter, for example, having a truncated conical or conical shape. Figure 1a and 1b In the illustrated embodiment, the syringe includes a truncated conical transition section that connects two regions and provides a gradual transition between them. For example, syringe 15 includes a truncated conical taper located between a region with a decreasing diameter and a larger diameter region adjacent to the distal end of the syringe.

[0061] In another embodiment, not shown, the insert contacts the inner surface of the syringe to form a region with a reduced diameter. The insert may be a solid conformable material adhered to or bonded to the inner surface of the syringe 15. Alternatively, the insert may be attached to the inner surface of the syringe 15, for example, via an adhesive, to form a region 16 with a reduced diameter. Alternatively, the insert may be integrally formed on the inner surface of the syringe 15. As used herein, the term "insert" refers to a component formed separately from the syringe, such as a cylindrical component, and which is attached or otherwise secured, for example, bonded (adheded) to the inner surface of the syringe.

[0062] In some embodiments, the syringe 15 may include one or more inserts adhered to the inner surface of the syringe. The inserts may have different diameters and lengths and may be formed of glass, ceramic, metal, or polymer, provided they are compatible with the material forming the syringe 15 and the contents of the syringe 10. For example, the insert may include a polymer tube, such as a fluoropolymer tube, bonded to the inner surface of the syringe 15. The polymer tube may be heated and expanded to bond to the wall of the inner surface of the syringe 15. In some embodiments, the polymer tube bonded to the inner surface of the syringe 15 is a solid material and is preferably a gas barrier to inhibit oxygen permeation. In some embodiments, the polymer tube is heat-deformable to provide a seal on a portion of the inner surface of the syringe 15. In some embodiments, the polymer tube has a low coefficient of friction to allow the stop to slide within the syringe 15.

[0063] In some embodiments, a laminate adhered to or bonded to the inner surface of the syringe 15 may be used to form a region 16 with a reduced diameter. For example, the laminate may be one or more thin film layers bonded (bonded) to the inner surface of the syringe 15. The laminate is bonded (bonded) or otherwise attached to the wall of the inner surface of the syringe. In at least one embodiment, an adhesive is used to attach the laminate to the inner surface of the syringe 15. Alternatively, as described above, the laminate may be thermoformed on the inner surface of the syringe 15.

[0064] In some embodiments, the laminate may be in the form of a single high-strength film or multiple high-strength films formed on the inner surface of the syringe 15. One or more high-strength films may include any material described herein for use as a coating material. The film may have a thickness in the range of about 0.5 micrometers to about 100 micrometers, about 0.5 micrometers to about 20 micrometers, or about 10 micrometers to about 15 micrometers. In some embodiments, the film is less than about 30 micrometers, less than about 20 micrometers, or less than about 10 micrometers. The film may be pretreated or post-treated using chemical etching, plasma treatment, corona treatment, roughening, etc., to improve the interference fit with the stop.

[0065] In other embodiments, a coating material is provided on a portion of the inner surface of the syringe to form a coated area (coated region), which in turn forms a region with a reduced diameter. The coating material 140 may be formed from a liquid coating (coating) material 139 applied to a portion of the inner surface of the syringe 15. Figure 2a -c illustrates a process for coating a syringe 15 according to one aspect of this disclosure. In this process, a portion adjacent to the proximal end 25 of the syringe 15 is coated with a liquid coating material 139 to provide a coating area 145. Figure 2aThe proximal portion of the syringe 15 of the syringe 10 is shown before the coating process. The syringe 15 has a uniform and constant diameter before coating. Suitable materials for the coating material 140 include, but are not limited to, fluorinated ethylene propylene, expanded fluorinated ethylene propylene, expanded polytetrafluoroethylene (ePTFE), epoxy resin, acrylic resin, and combinations thereof.

[0066] As mentioned above, Figure 2a The syringe 15 of the syringe 10 is depicted before immersion in a coating bath (coating bath) 150 containing a liquid coating material 139. Figure 2b In this process, the proximal end 25 of the syringe 15 is immersed in a coating bath 150. The syringe 15 is immersed in the coating bath 150 until the liquid coating material 139 adheres to the inner surface of the syringe 15 to form a coating area 145. Any excess liquid coating material 139 can be removed before it cures on the inner surface of the syringe 15. Depending on the composition of the coating material 139 used, after removal from the coating bath 150, the liquid coating material 139 that has adhered to the interior of the syringe 15 can be dried (e.g., by air or heat), UV cured, thermally cured, or cured in ambient air to form a coating material 140. Alternatively, the liquid coating material 139 can be dried to form the coating material 140. The coating material 140 forms the coating area 145 of the syringe 15, which forms a region with a reduced diameter.

[0067] It should be noted that, Figure 2c The outer surface of the syringe 15 without any liquid coating material 139 is shown. After the syringe 15 is lifted from the coating bath 150, the liquid coating material 139 is removed from the outer surface of the syringe 15 before the liquid coating material can cure or adhere to the outer surface. For example, the liquid coating material 139 can be blown away from the outer surface of the syringe 15 with deionized air. After the liquid coating material is blown away from the outer surface of the syringe 15, only the inner surface of the syringe 15 includes the coating material 140. The coating material 140 on the inner surface of the syringe cures to form a coating area 145.

[0068] In some embodiments, the coating material 140 includes fluorinated ethylene propylene, expanded fluorinated ethylene propylene, epoxy resin, acrylic resin, and combinations thereof. The coating material 140 may also include an oxygen-absorbing material or an oxygen-adsorbing material. In some embodiments, the oxygen-absorbing material may include ascorbic acid, sodium ascorbate, activated carbon, and combinations thereof. The oxygen-adsorbing material may include iron, nickel, tin, copper, zinc, tungsten, cobalt, palladium, platinum, zinc oxide, cerium mixed oxides, zirconium mixed oxides, metal oxides (e.g., zinc oxide and iron oxide), iron hydroxide, iron carbide, ascorbic acid, sodium ascorbate, catechol, phenol, activated carbon, polymeric materials, metal oxides (e.g., titanium oxide), and combinations thereof. The oxygen-absorbing or oxygen-adsorbing material should be compatible with the contents of the syringe. It should be understood that the oxygen-absorbing material and the oxygen-adsorbing material may be used alone or in combination with each other. It should also be understood that the oxygen-adsorbing material is not limited to the materials listed above, but may include any suitable material that captures or retains oxygen on its surface. Similarly, it should be understood that oxygen absorption materials are not limited to those listed above, but may include any suitable material that absorbs, adsorbs, or otherwise consumes oxygen. Additional oxygen absorption or adsorption materials may include low molecular weight organic compounds, such as phenol, and polymeric materials combined with resins and catalysts.

[0069] In some embodiments, the coating material 140 is disposed in a region extending from the flange 80 to no more than half, for example, half, less than half, less than a quarter, or less than an eighth of the length of the syringe 15. On one hand, the coating material 140 does not come into contact with the fluid within the fluid chamber 30 when it may contaminate the fluid. On the other hand, the coating material 140 may come into contact with the fluid within the fluid chamber 30 when it does not contaminate the fluid or is inert.

[0070] In another embodiment, during the coating process, the liquid coating material 139 may include a liquid carrier, optionally a solvent, and a coating precursor dissolved, suspended, or emulsified therein. The coating precursor may optionally be in the form of particles suspended in the liquid carrier. For example, the particle size may be smaller than the thickness of the coating, such that the coating is uniform. After application to the syringe, the liquid carrier is preferably removed, for example, by heating and / or drying, thereby forming a dry coating material on the syringe. During the application process, the temperature range of the liquid coating material can be from about 25ºC to about 350ºC. The temperature, of course, depends on the substrate being coated. Metals, ceramics, and glass can withstand high temperatures, while plastic syringes require lower temperatures. In another embodiment, the liquid coating material contains monomers that can, for example, cure (polymerize) upon application of UV radiation to form a solid coating composition on the syringe.

[0071] The syringe 15 may be immersed in a coating bath 150 and withdrawn at a rate that facilitates the formation of a uniform, defect-free, or substantially defect-free coating of a desired thickness on the syringe 15. For example, the syringe 15 may be coated with a thin film of a thermoplastic resin with a coating material 140, and then dried or cured to form a coated area 145. A pre-molded shape may optionally be pressed against a portion of the inner surface of the syringe 15 against the coating material 140 so that the inner surface substantially conforms to a desired shape or thickness.

[0072] In some embodiments, the syringe 15 may be immersed in the liquid coating material 139 and then subjected to heat treatment, curing, and / or spin drying. In other embodiments, as described above, the coating material may be applied to the syringe by a spraying process or by brushing the liquid coating material 139, and then dried and / or cured as described above to form the coated area 145.

[0073] Figure 2c This shows a portion of the coated syringe that has been removed from the coating bath 150. Figure 2c In the illustrated embodiment, a portion of the proximal end 25 of the syringe 15 is coated to provide a coating region 145. As shown, the syringe 15 of the syringe 10 may have a coating region 145 (formed by a coating material 140) at its proximal end 25, and an uncoated distal end (not shown) adjacent to the coating region 145. The diameter of the coating region 145 (formed by the coating material 140) is smaller than the diameter of the uncoated region. For example, the diameter of the coating region 145 may be at least about 25 micrometers smaller, at least 50 micrometers smaller, or at least 100 micrometers smaller than the diameter of the uncoated region. The smaller diameter caused by the coating region 145 provides a tighter interference fit with the stop 100 to prevent oxygen permeation into the fluid chamber 30 of the syringe. The thickness of the coating region 145 may vary depending on a number of factors, namely, the amount of liquid coating material 139 applied, the viscosity of the coating, and / or the extraction rate during the dip-coating process. The coating material 140 may be ground, machined, or melted to a desired thickness. For example, the thickness of the coating material 140 (and thus the coated area 145) may be in the range of about 0.5 micrometers to about 100 micrometers, about 0.5 micrometers to about 20 micrometers, or about 10 micrometers to about 15 micrometers. In some embodiments, the coating material 140 (and thus the coated area 145) has a thickness of less than about 30 micrometers, less than about 20 micrometers, or less than about 10 micrometers.

[0074] Figure 3A syringe 10 is shown, wherein a portion of the inner surface of the syringe barrel 15 has a coating region 145 formed thereon by a coating material 140 at its proximal end. In one embodiment, at least one or more ribs 120 of a stop member 100 are located within the coating region 145 of the syringe barrel 150 in an unpressed state. For example, at least one rib 120, at least two ribs, or at least three (or more) ribs of the stop member 100 are disposed within the coating region 145 formed by the coating material 140 in an unpressed state. In some embodiments, the entire stop member 100 may be positioned within the coating region 145 in an unpressed state.

[0075] The coating material 140 is located on the portion of the syringe 15 adjacent to the proximal end 25 of the syringe 15. As described above, the diameter of the coated area 145 of the syringe is smaller than the diameter of the uncoated area. As a result, the portion of the stop 100 within the coated area 145 is subjected to greater compression than the portion of the stop 100 within the uncoated area 146.

[0076] In the unpressed state, one or more ribs 120 of the stop member 100 abut against the coating material 140 in the coated area 145. The one or more ribs 120 have a first contact area when abutting against the coating material 140 in the coated area 145 and a second contact area smaller than the first contact area when contacting the uncoated area 146. "Abutting contact" means that the longitudinal edge of the rib contacts the inner wall formed by a region with a decreasing diameter, such as the coated area, thereby compressing the rib.

[0077] Figure 4 It shows Figure 3 An exploded view of one of the ribs 120 of the stop 100 shown. In the unpressed state, the stop 100 includes at least one rib 120 that abuts against the coating material 140 in the coating region 145. The diameter of the coating region 145 of the syringe 15 is smaller than the diameter of the uncoated region 146, which provides an increased interference fit with the rib 120 of the stop 100 in the coating region. The first contact area may be at least 1%, for example at least 5%, or at least 10% larger than the second contact area. Due to the reduced diameter of a portion of the inner surface of the syringe 15, the stop 100 has an increased interference fit with the syringe 15 in the coating region 145. The increased interference fit in the coating region 145 inhibits or prevents oxygen from permeating into the syringe 15 of the syringe 10. In some embodiments, the coating region 145 has an inner diameter that provides a combination of increased interference fit and minimal sliding force.

[0078] Figure 5The syringe is shown in a depressed state, meaning the plunger 95 has been pushed distally so that the stop 100 is no longer in contact with the coating area 145. That is, in the depressed state, all the ribs 120 of the stop 100 are in contact with the uncoated area 146 of the inner surface of the syringe barrel 15. In use, the syringe 10 can administer fluid 135, such as a therapeutic agent, to a patient who requires it. The method of administering fluid can be initiated by loading fluid 135 into the fluid chamber 30. In some embodiments, the syringe 10 is preloaded with fluid 135. In the undepressed state, at least one rib 120 of the stop 100 is in the coating area 145 of the syringe barrel 15. The user can apply force to press the plunger rod 85 to move the stop 100 distally within the syringe barrel 15, and when the plunger rod 85 is pressed, it forces fluid 135 through the injection port 35 at the distal end of the syringe barrel 15. Figure 5 As shown, in the pressed state, the force moves at least one rib 120 from the coated area 145 into the uncoated area 146.

[0079] Due to the enhanced interference fit between one or more ribs 120 and the inner surface of the syringe 15 in the coating region 145, the initial force required to move the stop 100 in the coating region 145 can be greater than the force required to move the stop 100 in the uncoated region 146. However, due to the material used to coat the syringe, the stop 100 moves smoothly in the coating region 145 without the need for a lubricant such as silicone. For example, a greater initial force can be applied to the plunger rod to move the stop within the coating region 145 compared to moving the stop when it is fully within the uncoated region.

[0080] It is also conceivable that, in some embodiments, the composition of the coating material used in the coating area 145 may have a lower coefficient of friction than the material forming the syringe. Thus, in these embodiments, despite the reduction in the diameter of the coating area 145, the initial force may be comparable to the force required to move the stop over the uncoated area, for example, within 5% of that force, or even less.

[0081] In another embodiment, one or more ring members may be provided on the stop to reduce or inhibit oxygen permeation into the syringe barrel. As used herein, the term "ring member" refers to any circumferential member configured to extend laterally around the stop, including but not limited to any annular member, such as an O-ring, ring, or cylindrical member. It should be noted that the shape or overall volume of the ring member can be any shape, as long as it is a container (receptacle) for oxygen absorption and / or adsorption material. Furthermore, the shape of the ring member ultimately depends on the shape of the stop and the syringe barrel. The shape may also depend on the size / depth of the valley of the stop. In this document, for ease of description, the ring member is depicted as circular.

[0082] like Figure 6 and 7 As shown, a ring member 160 may be disposed in one or more valleys 115 of the stop member 100. In some embodiments, the ring member 160 contacts the periphery of the valley 115 of the stop member 100 and may be tightly wound around the periphery of the valley 115 of the stop member 100. The ring member 160 may include an oxygen-absorbing material and / or an oxygen-adsorbing material. The oxygen-absorbing or oxygen-adsorbing material binds to and / or otherwise removes oxygen that may enter the valley 115 of the stop member 100 before permeating into the fluid chamber 30, thereby inhibiting contamination of any fluid contained within the syringe, such as oxygen-sensitive drugs or compositions. In some embodiments, the ring member 160 may be adhered to, secured to, or otherwise attached to one or more valleys 115 of the stop member 100. As used herein, the term “oxygen-sensitive” refers to the ability of a substance to be oxidized or adversely affected by contact with oxygen under ambient conditions. In other embodiments, the ring member 160 may include other materials that absorb or adsorb other gaseous substances that may permeate into the syringe.

[0083] Figure 7 Show Figure 6 A cross-sectional view of the syringe. In this embodiment, a ring member 160 is disposed in each valley 115 of the stop member 100. The ring member 160 may be formed of a resilient or rigid circular body. In the event of oxygen permeation into the valley 115 between a pair of ribs 120, the oxygen-absorbing and / or oxygen-adsorbing material in the ring member 160 inhibits or prevents oxygen contamination of the fluid in the fluid chamber 30. Thus, the oxygen-absorbing or oxygen-adsorbing material absorbs, adsorbs, and / or otherwise removes any oxygen from the valleys of the stop member without significantly affecting the sliding force. Suitable materials for the oxygen-absorbing or oxygen-adsorbing material may include, but are not limited to, the materials described above.

[0084] According to some embodiments, ring members comprising or formed of oxygen-absorbing and / or oxygen-adsorbing materials can be manufactured using conventional methods, such as melt extrusion, coating, etc. For example, the ring member can be melt-extruded with a uniformly dispersed amount of oxygen-absorbing and / or oxygen-adsorbing material. In some embodiments, the ring member can be manufactured into the body of a stop member during manufacturing. In some embodiments, the diameter of the ring member is measured and cut to correspond to the circumference of the valleys of the stop member. In other embodiments, an adhesive can be applied to secure the ring member to each valley.

[0085] In some embodiments, to further suppress oxygen permeation, a stop 100 including a ring member may be provided in the syringe barrel including the coated region described above. The coated region is on the inner surface of the syringe barrel, adjacent to the proximal end of the syringe barrel. The coated region forms a region with a reduced diameter, the diameter of which is smaller than the diameter of the uncoated region of the syringe barrel. In this embodiment, the coated region mechanically improves the interference fit between the syringe barrel and the stop member, while the ring member chemically absorbs and / or adsorbs any oxygen that may permeate into the syringe barrel.

[0086] Figure 8 Another embodiment is shown, wherein the stop includes a barrier coating 170 surrounding a portion of the stop 100. In an exemplary embodiment, the barrier coating 170 comprises or is formed of an oxygen-barrier material that inhibits or prevents oxygen from permeating into the syringe without significantly affecting the sliding force of the stop 100 (the force that moves the stop distally) or contaminating the fluid within the fluid chamber 30. In some aspects, the oxygen-barrier material minimizes friction between the stop and the inner surface of the syringe as the plunger rod moves within the syringe while dispensing the fluid composition. For example, the coefficient of friction of the barrier coating 170 may be less than that of the stop material, thereby allowing the stop 100 to move smoothly within the syringe 15. The oxygen-barrier material may be selected from the aforementioned oxygen-barrier materials. Furthermore, the oxygen-barrier material may be selected based on its compatibility with the contents of the syringe.

[0087] In at least one embodiment, the barrier coating 170 surrounds a portion of the stop 100 that is not exposed to the fluid chamber 30. As described herein, the stop 100 includes an elastomeric body having a plurality of ribs 120 and valleys 115 between each pair of adjacent ribs 120. Figure 8 As shown, the barrier coating 170 is disposed on the ribs 120 and the valleys 115 between each pair of ribs 120 that do not contact the fluid chamber 30. Therefore, the barrier coating 170 may not be disposed on the distal fluid contact surface of the stop 100. However, it is conceivable that the barrier coating 170 may also cover the distal surface of the stop 100 (e.g., the entire stop 100) to prevent the fluid composition in the fluid chamber 30 from being adversely affected by contact with the barrier coating 170 (e.g., the barrier coating 170 being inert to the fluid or therapeutic agent in the syringe).

[0088] In some embodiments, the oxygen barrier material is selected from perfluorosulfonic acid, hydrocarbon ionomers, sulfonated polyimide, polyvinyl alcohol, and combinations thereof. Other non-limiting examples of oxygen barrier materials include high-density polyethylene (HDPE), low-density polyethylene (LDPE), ethylene / vinyl alcohol copolymer (EVOH), polypropylene (PP), polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polyamide (PA), polyvinyl alcohol (PVOH), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), polyvinyl trifluoroethylene (PCTFE), vinylidene, chloride / methyl acrylate copolymer, polyamide, polyester, metallized film, aluminum foil, oxide film, and combinations thereof. Metal foil (e.g., aluminum) or SiO2 x The compounds can be used to provide very low oxygen permeability. Metallized films can include other applications such as sputtered coatings or metal layers such as aluminum.

[0089] Various embodiments of the oxygen barrier material can also exist, or alternatively, in the form of a multilayer film. The multilayer film (e.g., 2-layer, 3-layer, 4-layer, 5-layer, or 6-layer film) may include one or more of the oxygen barrier materials previously described, and may also include other non-barrier material layers, such as PET, polyethylene (PE), and / or coated paper (e.g., clay, wax, plastic, etc.) or uncoated paper. Suitable multilayer films include, but are not limited to, PVC / EVOH, PET / EVOH, PET / EVOH / PE, PET / EVOH / PET, PE / EVOH / PE, PVC / PCTFE / EVOH, paper / aluminum (Alu) / PE, PET / aluminum / PE, paper / PE / foil / PE, paper / PET / aluminum, clay-coated paper / PE / foil / LDPE, paper / LDPE / foil / ethylene-ethyl acrylate, and related films. The layers can be bonded together using an adhesive (e.g., a polyolefin blend (a mixture of poly(α-olefin) or polyamide resins)). In some embodiments, the barrier coating 170 comprises an oxygen barrier material as a multilayer film. For example, the barrier coating 170 may include a laminate that is adhered to or bonded to the stop 100.

[0090] In other embodiments, the barrier coating 170 may also include an oxygen-absorbing material or an oxygen-adsorbing material. Suitable materials for use as oxygen-absorbing or oxygen-adsorbing materials may include, but are not limited to, the materials described above.

[0091] Figure 9A cross-sectional view of a syringe according to another embodiment is depicted. In this embodiment, both the plunger rod 85 and the stop 100 include a barrier coating 170 comprising an oxygen-blocking material that inhibits or prevents oxygen from entering the fluid chamber. For example, a portion of the plunger rod 85 attached to the stop 100 may be located within the syringe barrel 15. In one embodiment, the portion of the plunger rod 85 located within the syringe barrel 15 may also include the barrier coating 170 to assist in preventing oxygen from entering the syringe. The barrier coating 170 on the plunger rod 85 can serve as an initial barrier to inhibit oxygen permeation before reaching the stop 100.

[0092] In some embodiments, the syringe may include any combination of the embodiments described above. For example, it is conceivable that the syringe barrel may include a coating on a portion of its inner surface to form a region with a reduced diameter; the stop may include one or more ring members comprising an oxygen-absorbing or oxygen-adsorbing material; and the stop may include an oxygen-barrier material. In this way, the coating mechanically improves the interference fit between the syringe barrel and the stop, while the ring members chemically absorb and / or adsorb any oxygen that may permeate into the syringe barrel, and the oxygen-barrier material on the surface of the stop prevents any oxygen from entering.

[0093] The process of coating a stop with an oxygen barrier material may include immersing a portion of the stop in a suitable solution containing the aforementioned oxygen barrier material and / or an oxygen absorbing or adsorbing material. In some embodiments, the portion of the stop that will come into contact with the fluid in the syringe is not immersed in the solution, i.e., it remains inert. The stop may be removed from the solution and allowed to dry or cure completely. For example, in one embodiment, a clean stop may be partially immersed in the solution until the solution adheres to the stop, then removed from the solution, and excess solution on the stop may be blown off with deionized air. The stop may then be dried in an atmosphere at approximately 25°C for approximately one hour.

[0094] In some embodiments, the syringe may include any combination of the embodiments described above. For example, it is conceivable that the syringe barrel may include a coating on a portion of its inner surface to form a region with a reduced diameter; the stop may include one or more ring members comprising oxygen-absorbing or oxygen-adsorbing material; and the stop may include an oxygen-barrier material. In this way, the coating mechanically improves the interference fit between the syringe barrel and the stop, while the ring members chemically absorb and / or adsorb any oxygen that may permeate into the syringe barrel, and the oxygen-barrier material on the surface of the stop prevents any oxygen from entering.

[0095] Figure 18An autoinjector 400 according to some embodiments is shown. The autoinjector 300 includes a syringe 301, an injection member 303 for injecting a drug solution, and a stop 304. The stop 304 may be integral with or attached to a plunger rod 305. The inner surface 303 of the body 301 may be unlubricated. Within the scope of the invention, the stop 304 may include ribs and / or as per [reference to...]. Figure 10-17 The stop described and illustrated may be a stop without ribs. The autoinjector 300 may be combined with a variable actuating force applied to the stop 304.

[0096] On the other hand, the syringes and auto-injectors or pens described in detail herein can be used in combination with various therapeutic compounds such as pharmaceuticals and biologics, including but not limited to: antibodies, antisenses, RNA interference, gene therapy, primary and embryonic stem cells, vaccines, and combinations thereof. For example, the embodiments described herein can be used in combination with any or all of the following:

[0097] Cell therapies utilizing cells primarily derived from the following types of cells: endoderm, such as exocrine secretory epithelial cells and hormone-secreting cells; ectoderm, such as keratinized epithelial cells, moist barrier epithelial cells, sensory transduction cells, autonomic nerve cells, supporting cells of sensory organs and peripheral neurons, neurons and glial cells of the central nervous system, and lens cells; mesoderm, such as metabolic and storage cells, barrier function cells (lung, intestine, exocrine glands, and urogenital tract), extracellular matrix cells, contractile cells, blood and immune system cells, germ cells, trophoblasts, mesenchymal cells, or combinations thereof. Other cells that are genetically, chemically, or physically modified or altered are considered to be within the scope of this invention.

[0098] Examples of exocrine epithelial cells include, but are not limited to: salivary gland mucin cells, salivary gland 1, von Eybner gland cells in the tongue, mammary gland cells, lacrimal gland cells, ceruminous gland cells in the ear, dark cells of exocrine sweat glands, light cells of exocrine sweat glands, apocrine sweat gland cells, Merskeletal gland cells of the eyelids, sebaceous gland cells, Bowman's gland cells of the nose, Brunner's gland cells of the duodenum, seminal vesicle cells, prostate cells, bulbourethral gland cells, Bardolyn's gland cells, urethral gland cells, endometrial cells, solitary goblet cells of the respiratory and digestive tracts, gastric mucin cells, gastric gland enzyme-producing cells, gastric gland acid-secreting cells, pancreatic acinar cells, Panette's cells of the small intestine, type II lung cells, and pulmonary Clara cells; hormone-secreting cells include, but are not limited to: anterior pituitary cells Cells, including: pituitary middle lobe cells, large-celled neurosecreting cells, intestinal and respiratory tract cells, thyroid cells, parathyroid cells, adrenal cells, testicular interstitial cells secreting testosterone, theca interna cells secreting estrogen, luteal cells of ruptured follicles secreting progesterone, glomerular cells, renal macula dense cells, renal peripolar cells, renal glomerular mesangial cells, and pancreatic islet cells; keratinized epithelial cells, including but not limited to: epidermal keratinocytes, epidermal basal cells, keratinocytes of nails and toenails, nail bed basal cells, medullary hair stem cells, cortical hair stem cells, epidermal hair stem cells, epidermal root sheath cells, root sheath cells of Huxley's stratum, root sheath cells of Henle's stratum, outer root sheath cells, and hair matrix cells; on the moist stratification barrier. Skin cells include, but are not limited to: the lamellar squamous epithelial surface epithelial cells and basal epithelial cells of the cornea, tongue, oral cavity, esophagus, anal canal, distal urethra, and vagina; urothelial cells; sensory transduction cells include, but are not limited to: auditory inner hair cells of the organ of Corti, auditory outer hair cells of the organ of Corti, basal cells of the olfactory epithelium, cold-sensitive first-order sensory neurons, heat-sensitive first-order sensory neurons, Merkel cells of the epidermis, olfactory receptor neurons, pain-sensitive first-order sensory neurons, retinal photoreceptor cells in the eye: proprioceptive first-order sensory neurons, tactile first-order sensory neurons, type I carotid somatic cells, type II carotid somatic cells, type I hair cells of the vestibular system, type II hair cells of the vestibular system, and type I taste bud cells; autonomic nerve cells include, but are not limited to: cholinergic... Nerve cells, adrenergic nerve cells, polypeptide nerve cells; supporting cells of sensory organs and peripheral neurons, including but not limited to: inner column cells of the organ of spirals, outer column cells of the organ of spirals, inner finger cells of the organ of spirals, outer finger cells of the organ of spirals, marginal cells of the organ of spirals, Hansen cells of the organ of spirals, supporting cells of the vestibular organ, supporting cells of taste buds, supporting cells of olfactory epithelium, Schwann cells, satellite glial cells, and enteric glial cells; neurons and glial cells of the central nervous system, including but not limited to: astrocytes, neurons, oligodendrocytes, and spindle neurons; lens cells, including but not limited to: anterior lens epithelial cells and lens fiber cells containing lens proteins; metabolic and storage cells, including but not limited to: adipocytes: liver adipocytes;Barrier function cells include, but are not limited to: renal parietal cells, glomerular podocytes, proximal renal tubule brush border cells, Henry's thin segment cells, distal renal tubule cells, renal collecting duct cells, principal cells, intercalated cells, type I lung cells, pancreatic duct cells, non-striatal cells, principal cells, intercalated cells, ductal cells, intestinal brush border cells, exocrine gland striatal cells, gallbladder epithelial cells, efferent tubule nonciliated cells, epididymal principal cells, and epididymal basal cells; extracellular matrix cells include, but are not limited to: ameloblast epithelial cells. Cells including: auricular vestibular system epithelial cells, interdental epithelial cells of the organ of Corti, loose connective tissue fibroblasts, corneal fibroblasts, tendon fibroblasts, bone marrow reticular tissue fibroblasts, other non-epithelial fibroblasts, outer membrane cells, intervertebral disc nucleus pulposus cells, cementoblasts / cementocytes, odontocytes / periodontal cells, hyaline chondrocytes, fibrochondrocytes, elastic chondrocytes, osteoblasts / osteoblasts, osteoprogenitor cells, vitreous cells of the vitreous body, stellate cells of the auricular perilymphatic space, hepatic stellate cells, pancreatic stellate cells; contractile cells including but not limited to: skeletal muscle cells, satellite cells, cardiomyocytes, smooth muscle cells, myoepithelial cells of the iris, myoepithelial cells of exocrine glands; blood and immune cells. Systemic cells include, but are not limited to: erythrocytes, megakaryocytes, monocytes, connective tissue macrophages, epidermal Langerhans cells, osteoclasts, dendritic cells, microglia, neutrophils, eosinophils, basophils, hybridoma cells, mast cells, helper T cells, suppressor T cells, cytotoxic T cells, natural killer T cells, B cells, natural killer cells, reticular cells, stem cells of the blood and immune system, and progenitor cells for targeted therapy; germ cells include, but are not limited to: oogonia / oocytes, spermatids, spermatogonia, spermatocytes, spermatocytes; trophoblasts include, but are not limited to: ovarian follicle cells, testicular Sertoli cells, thymic epithelial cells; interstitial cells include, but are not limited to: interstitial tissue kidney cells, and combinations thereof.

[0099] Examples of antibodies, antisenses, RNA interference, or gene therapies targeting protein targets or genes include: capillary dilatational ataxia mutations, tumor protein p53, checkpoint kinase 2, breast cancer susceptibility proteins, double-strand break repair proteins, DNA repair protein RAD50, Nibrin (NBN protein), p53-binding proteins, DNA damage checkpoint protein-mediated, H2A histone family member X, microcephalin, C-terminal binding protein 1, and the structural maintenance of chromosome protein 1A; esterases; phosphatases; examples of ion channels include, but are not limited to, ligand-gated ion channels and voltage-gated ion channels; examples of growth factors include, but are not limited to, nerve growth factor (NGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), C-fos-induced growth factor (FIGF), platelet activating factor (PAF), transforming growth factor β (TGF-β), b, a morphogenetic protein (BMP), activin, inhibin, fibroblast growth factor (FGF), and granulocyte colony-stimulating factor (G-CSF). Examples of G protein-coupled receptors (GPCRs) include: granulocyte-macrophage colony-stimulating factor (GM-CSF), glial cell-derived neurotrophic factor (GDNF), growth differentiation factor 9 (GDF9), epidermal growth factor (EGF), transforming growth factor-α (TGF-α), growth factor (KGF), migration-stimulating factor (MSF), hepatocyte growth factor-like protein (HGFLP), hepatocyte growth factor (HGF), hepatocellular carcinoma-derived growth factor (HDGF), and insulin-like growth factor; examples of G protein-coupled receptors (GPCRs) include, but are not limited to, adenosine receptors. The receptor family includes: adrenergic receptor family, angiotensin II receptor, apelin receptor, angiotensin receptor family, brain-specific angiogenesis inhibitor family, bradykinin receptor family, bufotenoid receptor family, complement component 3a receptor 1, complement component 5a receptor 1, calcitonin receptor family, calcitonin receptor-like family, calcium-sensitive receptor, cholecystokinin A receptor (CCK1), cholecystokinin B receptor (CCK2), chemokine (CC motif) receptor family, sphingosine 1-phosphate receptor family, succinate receptor, and cholinergic receptor family. Chemokine-like receptor family, cannabinoid receptor family, corticotropin-releasing hormone receptor family, prostaglandin D2 receptor, chemokine C-X3-C receptor family, chemokine (CXC motif) receptor family, Burkitt lymphoma receptor, chemokine (CXC motif) receptor family, cysteine ​​leukotriene receptor 2 (CYSLT2), chemokine receptor (FY), dopamine receptor family, G protein-coupled receptor 183 (GPR183), lysophosphatidylcholine receptor family, endothelin receptor family, coagulation factor II (thrombin) receptor family, free fatty acid receptor family, formylpeptide receptor family, follicle-stimulating hormone receptor (FSHR)GABA-B receptor, glycopyridine receptor family, glucagon receptor, growth hormone-releasing hormone receptor (GHRH), gastric growth hormone secretagogue receptor (GHR1b), growth hormone secretagogue receptor 1b (GHSR1b), gastric inhibitory peptide receptor (GIP), glucagon-like peptide receptor family, gonadotropin-releasing hormone receptor (GnRH), pyroglutamyl transferase (PGT) receptor, glucagon-like peptide receptor family, gonadotropin-releasing hormone receptor (GnRH), pyroglutamyl transferase (PGT) receptor, glucagon-like peptide receptor (GIP) receptor, glucagon-like peptide receptor (GIP) receptor, glucagon-releasing hormone receptor (GnRH), glucagon-like peptide receptor (GRP) receptor, ...releasing hormone receptor (GHRH), glucagon-like peptide receptor (GRP) receptor, glucagon-like peptide receptor (GRP) receptor, glucagon-like peptide receptor (GRP) receptor, glucagon-releasing hormone receptor (GRP) receptor, gluc (mylated) RF amide peptide receptor (QRFPR), G protein-coupled bile acid receptor 1 (GPBA), hydroxycarboxylic acid receptor family, lysophosphatidylcholine receptor 4 (LPA4), lysophosphatidylcholine receptor 5 (GPR92), G protein-coupled receptor 79 pseudogene (GPR79), hydroxycarboxylic acid receptor 1 (HCA1), G protein-coupled receptors (C5L2, FFA4, FFA4, FFA4, GPER, GPR1, GPR101, GPR107, GPR119, GPR12, GPR123, GPR132, GPR135, GPR139, GP R141, GPR142, GPR143, GPR146, GPR148, GPR149, GPR15, GPR150, GPR151, GPR152, GPR157, GPR161, GPR162, GPR17, GPR171, GPR1 73. GPR176, GPR18, GPR182, GPR20, GPR22, GPR25, GPR26, GPR27, GPR3, GPR31, GPR32, GPR35, GPR37L1, GPR39, GPR4, GPR45, GPR5 0, GPR52, GPR55, GPR6, GPR61, GPR65, GPR75, GPR78, GPR83, GPR84, GPR85, GPR88, GPR97, TM7SF1), metabotropic glutamate receptor family, gastrin-releasing peptide receptor (BB2), orexin receptor family, histamine receptor family, serotonin receptor family, KISS1-derived peptide receptor (kissing agonist), leucine repeat-containing G protein-coupled receptor family, horizontal gonadotropin receptor (LH), leukotriene B4 receptor (BLT1), adenosine monophosphate Cycloyl-activated peptide receptor 1 (mPAC1), motilin receptor, melanocortin receptor family, melanin condensing hormone receptor 1 (MCH1), neuropeptide Y1 receptor (Y1), neuropeptide Y2 receptor (NPY2R), opioid receptor family, oxytocin receptor (OT), P2Y purine receptor 12 (mP2Y12), P2Y purine receptor 6 (P2Y6), pancreatic peptide receptor family, platelet-activating factor receptor family, prostaglandin E receptor family, prostaglandin IP1 receptor (IP1), MAS-associated GPR, member families, rhodopsin, relaxin family peptide receptor familySomatostatin receptor family, tachykinin receptor family, melatonin receptor family, vasopressin receptor family, vasoactive intestinal peptide receptor 1 (mVPAC1), neuroregulatory peptide B receptor (BB1), neuroregulatory peptide U receptor 1 (NMU1), neuropeptide B / W receptor family, neuropeptide FF receptor 1 (NPFF1), neuropeptide S receptor 1 (NPS receptor), neuropeptide Y receptor family, neurotensin receptor 1 (NTS1), opsin 5 (OPN5), opioid receptor-like receptor (NOP), oxoanthocyanin (OXE) receptor 1 (OXE), oxoglutarate (α-ketoglutarate) receptor 1 (OXGR1), purinergic receptor family, pyrimidine receptor family, prolactin-releasing hormone receptor (PRRP), prodylinin receptor family, platelet-activating receptor (PAF), prostaglandin F receptor family Prostaglandin I2 (prostacyclin) receptor family, parathyroid hormone receptor family, muscarinic 4 (rM4), prostaglandin DP2 receptor (rGPR44), prodylin receptor family, relaxin family peptide receptor family, secretin receptor (secretin), smoothed receptors, coiled receptors (smoothienokinase receptors), microamine-associated receptor family, tachykinin family, thromboxane A2 receptor (TP), thyrotropin-releasing hormone receptor (TRH1), thyroid-stimulating hormone receptor (TSH); examples of protein kinases include, but are not limited to: AP2-associated kinases, Homo sapiens ABL proto-oncogene 1-non-receptor tyrosine protein kinase family, c-abl oncogene 1 receptor tyrosine kinase family, v-abl Abelson mouse leukemia virus oncogene homolog 2, activin A receptor family, chaperone proteins- The ABC1 activity (ADCK3) of the bc1 complex homolog (S. pombe), kinase 4 containing the aarF domain (ADCK4), v-akt murine thymoma virus oncogene homolog family, anaplastic lymphoma receptor tyrosine kinase family, protein kinase A family, protein kinase B family, kinase 1 containing an ankyrin repeat and kinase domain (ANKK1), NUAK family-SNF1-like kinase, mitogen-activated protein kinase kinase family aurora kinase (Aurora kinase) kinase A (AURKA), Aurora kinase B (AURKB), Aurora kinase C (AURKC), AXL receptor tyrosine kinase (AXL), BMP2 inducible kinase (BIKE), B lymphotyrosine kinase (BLK), bone morphogenetic protein receptor family, BMX non-receptor tyrosine kinase (BMX), v-raf murine sarcoma virus oncogene homolog B1 (BRAF), protein tyrosine kinase 6 (BRK), BR serine / threonine kinase family, Bruton's gamma globulinemia tyrosine kinase (BTK), calcium / calmodulin-dependent protein kinase family, cyclin-dependent kinase family, cyclin-dependent kinase-like family, CHK1 checkpoint homolog (S. pombe) (CHEK1).CHK2 checkpoint homolog (S. pombe) (CHEK2), insulin receptor, isotype A (INSR), insulin receptor, isotype B (INSR), rho-interacting serine / threonine kinase (CIT), v-kit Hady-Zuckerman 4 feline sarcoma virus oncogene homolog (KIT), CDC-like kinase family - Hepatocyte growth factor receptor (MET), proto-oncogene tyrosine protein kinase receptor, colony-stimulating factor family receptor, c-src tyrosine kinase (CSK), casein kinase family, megakaryocyte-associated tyrosine kinase (CTK), death-associated protein kinase family, bicorticosteroid family, discoidin domain receptor tyrosine kinase, dystrophic myotonic protein kinase (DMPK), bispecific tyrosine-(Y)-phosphorylation regulated kinase family, epidermal growth factor receptor family, eukaryotic translation initiation factor 2-α kinase 1 (EIF2AK1), EPH receptor family, hepatocyte ligand A receptor family, hepatocyte ligand B receptor family, v-erb-b2 erythroblast leukemia virus oncogene homolog family, mitogen-activated protein kinase family, endoplasmic reticulum to nucleus signal transduction 1 (ERN1), PTK2 protein tyrosine kinase 2 (FAK), fer (fps / fes-related) tyrosine kinase (FER). Feline sarcoma gene (FES), fibroblast growth factor receptor family, Gardner-Rasheed feline sarcoma virus (v-fgr) oncogene homolog (FGR), fms-associated tyrosine kinase family, Fms-associated tyrosine kinase family, fyn-associated kinase (FRK), SRC-associated FYN oncogene, cyclin G-associated kinase (GAK), eukaryotic translation initiation factor 2α kinase, growth hormone receptor, G protein-coupled receptor kinase 1 (GRK1), G protein-coupled receptor kinase family, glycogen synthase kinase family, germ cell-associated 2 (monokinase) (HASPIN), hematopoietic cell kinase (HCK), homeodomain interacting protein kinase family, mitogen-activated protein kinase kinase kinase kinase family, hormone-upregulated Neu-associated kinase (HUNK), intestinal cell (MAK-like) kinase (ICK), insulin-like growth factor 1 receptor (IGF1R), conserved helical-loop-helical ubiquitous kinase (IKK-α), B cell κ light chain polypeptide gene enhancement. Inhibitors of various kinases include: kinase β family, insulin receptor (INSR), insulin receptor-associated receptor (INSRR), interleukin-1 receptor-associated kinase family, IL2-inducible T-cell kinase (ITK), Janus kinase family, kinase insertion domain receptors, v-kit Hady-Zuckerman 4 feline sarcoma virus oncogene homolog, lymphocyte-specific protein tyrosine kinase (LCK), LIM domain kinase family, serine / threonine kinase family, leucine-rich repeat kinase family, and v-yes-1 Yamaguchi sarcoma virus-associated oncogene homolog (LYN).Male germline-associated kinase (MAK), MAP / microtubule affinity-regulated kinase family, microtubule-associated serine / threonine kinase family, maternal embryonic leucine zipper kinase, c-mer proto-oncogene tyrosine kinase (MERTK), proto-oncogene (hepatocyte growth factor receptor), MAP kinase-interacting serine / threonine kinase family, myosin light chain kinase family, mixed lineage kinase domain protein isotypes, CDC42-binding protein kinase family, serine / threonine kinase family, macrophage stimulation 1 receptor (c-met-associated tyrosine kinase) (MST1R), rapamycin (serine / threonine kinase) (mTOR), muscle-skeleton-receptor tyrosine Kinases (MUSK), myosin light chain mechanism target kinase family, NIMA (never in mitotic gene a) related kinase family, serine / threonine protein kinase NIM1 (NIM1), nemo-like kinase (NLK), oxidative stress response 1 (OSR1), p21 protein (Cdc42 / Rac) activated kinase family, serine / threonine kinases containing PAS domain, platelet-derived growth factor receptor family, 3-phosphoinositol-dependent protein kinase-1 (PDPK1), calcium-dependent protein kinase 1, phosphorylase kinase γ family, phosphatidylinositol 4,5-bisphosphate 3-kinase, phosphatidylinositol-3-kinase family, phosphatidylinositol 4-kinase family. Phosphoinositol kinase, containing FYVE index, Pim-1 oncogene (PIM1), Pim-2 oncogene (PIM2), Pim-3 oncogene (PIM3), phosphatidylinositol-4-phosphate 5-kinase family, phosphatidylinositol-5-phosphate 4-kinase family protein kinases, membrane-associated tyrosine / threonine 1 (PKMYT1), protein kinase N family, polo-like kinase family, protein kinase C family, protein kinase D family, cGMP-dependent protein kinase family, eukaryotic translation initiation factor 2-α kinase 2 (PRKR), X-linked protein kinase (PRKX), prolactin receptor (PRLR), PRP4 pre-mRNA processing factor 4 homolog B (yeast) (PRP4), PTK2B protein tyrosine kinase 2β (PTK2B), SIK family kinase 3 (QSK), v-raf-1 murine leukemia virus oncogene homolog 1 (RAF1), neurotrophic tyrosine kinase receptor type family, receptor (TNFRSF)-interacting serine-threonine kinase family, diserine / threonine and tyrosine protein kinase (RIPK5), Rho-related, coiled-coil protein kinase family, c-ros oncogene 1, receptor t-tyrosine kinase (ROS1), ribosomal protein S6 kinase family, SH3-binding domain kinase 1 (SBK1), serum / glucocorticoid-regulated kinase family, putative noncharacteristic serine / threonine protein kinase (Sugen kinase 110) (SgK110), salt-inducible kinase family,SNF-associated kinase (SNRK), src-associated kinase, SFRS protein kinase family, spleen tyrosine kinase (SYK), TAO kinase family, TANK-binding kinase 1 (TBK1), TEC protein tyrosine kinase (TEC), testis-specific kinase 1 (TESK1), transforming growth factor, β-receptor family, tyrosine kinase with immunoglobulin-like and EGF-like domain 1 (TIE1), TEK tyrosine kinase, endothelial cell (TIE2), angiopoietin-1 receptor (Tie2), disorganized kinase family, TRAF2 and NCK interacting kinase (TNIK), non-receptor tyrosine kinase family, TNNI3 interacting kinase (TNNI3K), transient receptor potential cation channel Testis-specific serine kinase family, TTK protein kinase (TTK), TXK tyrosine kinase (TXK), tyrosine kinase 2 (TYK2), TYRO3 protein tyrosine sinusoidal kinase (TYRO3), unc-51-like kinase family, phosphatidylinositol 3-kinase, vaccinia-associated kinase 2 (VRK2), WEE1 homologue family, WNK lysine-deficient protein kinase family, v-yes-1 Yamaguchi sarcoma virus oncogene homologue 1 (YES), kinase SZK (ZAK) containing a sterile α motif and leucine zipper, ζ-chain (TCR)-associated protein kinase 70 kDa (ZAP70); examples of nuclear hormone receptors include, but are not limited to, androgen receptor (AR), estrogen-associated receptor α (... ESRRA), estrogen receptor 1 (ESR1), nuclear receptor subfamily 1-H-member 4 (NR1H4), nuclear receptor subfamily 3-C-member 1 (glucocorticoid receptor) (NR3C1), nuclear receptor subfamily 1-H-member 3 (hepatic X receptor α) (NR1H3), nuclear receptor subfamily 1-H-member 2 (hepatic X receptor β) (NR1H2), nuclear receptor subfamily 1-H-member 2 (hepatic X receptor β) (NR1H2), nuclear receptor subfamily 3-C-member 2 (mineralocorticoid receptor) (NR3C2), peroxisome proliferator-activated receptor α (PPARA), peroxisome proliferator-activated receptor γ (PPARG), peroxisome proliferator-activated receptor δ (PPARD) The epigenetic targets include, but are not limited to, progesterone receptor α (PGR), progesterone receptor β (PGR), retinoic acid receptor-α (RARA), retinoic acid receptor-β (RARB), retinoid X receptor-α (RXRA), retinoid X receptor-γ (RXRG), thyroid hormone receptor-α (THRA), thyroid hormone receptor-β (THRB), retinoic acid-associated orphan receptor, liver X receptor, farnesol X receptor, vitamin D receptor, pregnane X receptor, constitutive androstenedione receptor, hepatocyte nuclear factor 4, estrogen receptor, estrogen-associated receptor, glucocorticoid receptor, nerve growth factor-induced B, and germ cell nuclear factor. Examples of epigenetic targets include, but are not limited to, ATPase family AAA domain protein 2 (ATAD2A).ATPase family - AAA (ATAD2B) containing the 2B domain, AAA-2B (ATAD2B) containing the ATPase family domain, Bromo domain-1A (BAZ1A) adjacent to the zinc finger domain, Bromo domain-1B (BAZ1B) adjacent to the zinc finger domain, Bromo domain-2A (BAZ2A) adjacent to the zinc finger domain, Bromo domain-2B (BAZ2B) adjacent to the zinc finger domain, Protein 1 (BRD1) containing the Bromo domain, Protein 2 (BRD2) containing the Bromo domain - first bromobromo domain, Protein 2 (BRD2) containing the first and second bromobromo domains. Bromomer domain (BRD2), Bromomer domain-containing protein 2 isoform 1-Brommer domain 2 (BRD2(2)), Bromomer domain-containing protein 3-Brommer domain 1 (BRD3(1)), Bromomer domain-containing protein 3-first Bromomer domain (BRD3), Bromomer domain-containing protein 3-first and second Bromomer domains (BRD3), Bromomer domain-containing protein 3-Brommer domain 2 (BRD3(2)), Bromomer domain-containing protein 4-first Bromomer domain (BRD4), Bromomer domain-containing protein 4 isoform long-Brommer domain 1 and 2 (BRD4(1-2)), Bromomer domain-containing protein 4 isoform long-Brommer domain 2 ( BRD4(2)), protein 4 isoform short containing bromo domain (BRD4(full-length-short-iso.)), protein 7 containing bromo domain (BRD7), protein 8-bromo domain 1 containing bromo domain (BRD8(1)), protein 8-bromo domain 2 containing bromo domain (BRD8(2)), protein 9 isoform 1 containing bromo domain (BRD9)), testis-specific first bromo domain containing bromo domain (BRDT), testis-specific first and second bromo domains containing bromo domain (BRDT), bromo domain testis-specific protein isoform β-bromo domain 2 (B RDT(2)), Bromo domain and PHD finger-1 (BRPF1), Bromo domain and PHD finger-3 (BRPF3), Bromo domain and PHD finger-3 (BRPF3), Bromo domain and WD repeat-3-second Bromo domain (BRWD3(2)), Cat's Eye Syndrome Key Region Protein 2 (CECR2), CREB-binding protein (CREBBP), E1A-binding protein p300 (EP300), EP300 (EP300), Nucleosome remodeling factor subunit BPTF isotype 1 (FALZ), Nucleosome remodeling factor subunit BPT (FALZ), Euchromatin histone-lysine N-methyltransferase 2 (EHMT2).Histone acetyltransferase-KAT2A (GCN5L2), euchromatin histone-lysine N-methyltransferase 1 (EHMT1), histone-lysine N-methyltransferase MLL (MLL), polybromo 1-Bromo domain 1 (PB1(1)), polybromo 1-Bromo domain 2 (PB1(2)), polybromo 1-Bromo domain 2 (PBRM1(2)), polybromo 1-Bromo domain 5 (PBRM1(5)), histone acetyltransferase KAT2B (PCAF), pH-interacting protein-1 Bromo domain (PHIP(1)), pH-interacting protein-2 Bromo domain (PHIP(2)), protein kinase C-binding protein 1 (PRKCBP1), protein arginine N-methyltransferase 3 (PRMT3), SWI / SNF-associated matrix-associated chromatin actin-dependent regulators - subfamily a-member 2 (SMARCA2), SWI / SNF-associated matrix-associated chromatin actin-dependent regulators - subfamily a-member 4 (SMARCA4), nucleosomal protein SP110 (SP110), nucleosomal protein SP140 (SP140), transcription initiation factor TFIID subunit 1 (TAF1(1-2)), TAF1 RNA polymerase II-TATA box-binding protein (TBP) related factor-250kDa-Bromo domain 2 (TAF1 (2)), TFIID subunit 1-1 Bromo domain (TAF1L(1)), TFIID subunit 1-2 Bromo domain (TAF1L(2)), 24 containing a triplet motif (TRIM24(Bromo)), 24 containing a triplet motif (TRIM24(PHD-Bromo)), E3 ubiquitin-protein ligase TRIM33 (TRIM33), 33 containing a triplet motif (TRIM33(PHD-Bromo)), WD repeat 9-1 Bromo domain (WDR9(1)), WD repeat 9-2 Bromo domain (WDR9(2)); membrane transport proteins including but not limited to: ATP-binding cassette (ABC) super Family, solute carrier (SLC) superfamily, multidrug resistance protein 1 (P-glycoprotein), organic anion transporter 1 and proteins such as EAAT3, EAAC1, EAAT1, GLUT1, GLUT2, GLUT9, GLUT10, rBAT, AE1, NBC1, KNBC, CHED2, BTR1, NABC1, CDPD, SGLT1, SGLT2, NIS, CHT1, NET, DAT, GLYT2, CRTR, B0AT1, SIT1, XT3, y+LAT1, BAT1, NHERF1, NHE6, ASBT, DMT1, DCT1, NRAMP2, NKCC2, NCC, KCC3, NACT,MCT1, MCT8, MCT12, SLD, VGLUT3, THTR1, THTR2, PIT2, GLVR2, OCTN2, URAT1, NCKX1, NCKX5, CIC, PiC, ANT1, ORNT1, AGC1, ARALAR, Citrin, STLN2, aralar2, TPC, MUP1, MCPHA, CACT, GC1, PHC, DTD, CLD, DRA, PDS, Prestin, TAT1, FATP4, ENT3, ZnT2, ZnT10, AT1, NPT2A, NPT2B, HHRH, CST, CDG2F, UGAT, UGTL, UGALT, UGT1, UGT2, FUCT1, CDG2C, NST PAT2, G6PT1, SPX4, ZIP4, LIV4, ZIP13, LZT-Hs9, FPN1, MTP1, IREG1, RHAG, AIM1, PCFT, FLVCR1, FLVCR2, RFT1, RFT2, RFT3, OATP1B1, OATP1B3, OATP2A1; structural proteins including but not limited to: tubulin, heat shock proteins, microtubule stabilizers, oncoprotein 18, stathmin, kinin-8 and kinin-14 families, Kip3, Kif18A; proteases including but not limited to: ADAM (integrin and metalloproteinase) family; other molecular targets in signal transduction including but not limited to: cell cycle 25 homolog A (CDC25A), forkhead O3. Box O3), nuclear factor α (NFKBIA), nuclear factor (erythrocyte-derived 2)-like 2 (NFE2L2), natriuretic peptide receptor A (NPR1), tumor necrosis factor receptor superfamily member 11a (TNFRSF11A), v-rel reticuloendothelial virus oncogene homolog A (avian) (RELA), sterol regulatory element binding transcription factor 2 (SREBF2), CREB-regulated transcriptional coactivator 1 (CRTC1), CREB-regulated transcriptional coactivator 2 (CRTC2), X-box binding protein 1 (XBP1), catalin (cadherin-associated protein), β1 (CTNNB1), and combinations thereof.

[0100] Examples of known biologics include, but are not limited to: Abbosynagis, Abegrin, Actemra, AFP-Cide, Antova, Arzerra, Aurexis, Avastin, Benlysta, Bexxar, Blontress, Bosatria, Camppath (alemumab), CEA-Cide, CEA-Scan, Cimzia, Cyramza, Ektomab, Erbitux. itux), FibriScint, Gazyva, Herceptin, hPAM4-Cide, HumaSPECT, HuMax-CD4, HuMax-EGFr, Humira, HuZAF, Hybri-ceaker, Ilaris, Indimacis-125, Kadcyla, Lemtrada, LeukArrest, LeukoScan, Lucentis, Lymphomun LymphoScan, LymphoStat-B, MabThera, Mycograb, Mylotarg, Myoscint, NeutroSpec, Numax, Nuvion, Omnitarg, Opdivo, Orthoclone OKT3, OvaRex, Panorex, Prolia, Prostascint, Remycare, Remycare Remicade, Removab, Rencarex, ReoPro, Rexomun, Rituxan, RoActemra, Scintimun, Simponi, Simulect, Soliris, Stelara, Synagis, Tactress, Theracim, Theragyn, Theraloc, TysabriVectibix, Verluma, Xolair, Yervoy, Zenapax, and Zevalin, or combinations thereof.

[0101] Examples of known monoclonal antibodies include, but are not limited to: 3F8, 8H9, abamoxicillin, abcixicillin, abituzumab, abrilumab, actoxumab, adalimumab, adenomyumab, aducanumab, afasevikumab, afemoxicillin, afutumumab, peazacillin, ALD518, ALD403, alenzacillin, alirocumab, atomoxicillin pentiate, amatuximab, AMG 334, Anatumomab mafenatox, and anetumab. ravtansine), Anifrolumab, Anifrolumab, Apocizumab, Asimozizumab, Astragalusumab, Atezolizumab, Atinumab, Avelumab, Bavituximab, Bavituximab, Betumomab (Bectumomab), Begelomab, Benralizumab, Bertilimumab, Besilesomab, Bevacizumab, Bezlotoxumab, Biciromab, Bimekizumab, Bivatuzumab Mertansine, Bleeselumab, Bosozumab, Blococizumab, Brazikumab, Butuximab, Blagizumab, Brolucizumab, Brontictuzumab, Burosumab, Cabiralizumab, Canakinumab, Cantuzumab mertansine, Cantuzumab ravtansine, Caplacizumab, Carbomerizumab capromabPendetide, Carlumab, Carotuximab, Caputoxumab, cBR96-Doxorubicin Immunoconjugate, Cedelizumab, Cergutuzumab Amunaleukin, Sertolizumab, Cetuximab, Citatuzumab Bogatox, Cetuximab, Clazakizumab, Clenoliximab, Tistansoc Rituximab, Codrituzumab, Coltuximab ravtansine, Conatumumab, Concizumab, CR6261, Crenzumab, Crotedumab, Dacizumab, Dalotuzumab, Dapirolizumab pegol, Datumumab, Dectrekumab, Demcizumab, Denintuzumab mafodotin, Denosumab, Depatuxizumab mafodotin, deroximab, detumomab, dinutuximab, diridavumab, domagrozumab, atorlimomab aritox, Drozitumab, Duligotumab, Dupilumab, Durvalumab, Dusigitumab, Ecromeximab, Edobacomab, Ejuzal, Efazal, Efengumab, Eldelumab, Elgemtumab, Elotuzumab, Elsilimomab, Emactuzumab, Emibetuzumab, Emicizumab, Enavatuzumab, Enfortumabvedotin), PEGylated enlimomabpegol, enoblituzumab, enokizumab, enticumab, ensituximab, epitomomab cituxetan, epazolizumab, errenumab, erlizumab, ertumaxomab, etaracizumab, estradiol, evinacumab, evolocumab, exbivirumab, fasolesomab, faralimomab, farletuzumab, fasumab, FBTA05, felvizumab, fezakinumab, fibatuzumab, ficlatuzumab, figitumumab ab), Firivumab, Flanvotumab, Fletikumab, Fontolizumab, Foralumab, Foravirumab, Fresolimumab, Fulranumab, Futuximab, Galcanezumab, Galiximab, Ganitumab, Gantenerumab, Gavilimomab, Ozomicin, Gevokizumab, Girentuximab, Glembatumumab vedotin, golimumab, gomilumab, guselukumab, ibalizumab, imimolumabtiuxetan), Icrucumab, Idarucizumab, Igovomab, IMA-638, IMAB362, Imalumab, imciromab, Imgatuzumab, Inclacumab, Indatuximab ravtansine, Indusatumab vedotin, Inebilizumab, infliximab, inoxiliximab, inoliximab, inomumab, Inotuzumab ozogamicin, Intetumumab, Ipilimumab, Iratumumab, Isatuximab, Itolizumab, Ixekizumab, Krishnamurat, Labetuzumab, Lambolizumab, Lampalizumab, Lanadelumab, Landogrozumab, Laprituximab emtansine), LBR-101 / PF0442g7429, Roche's monoclonal antibody, Lemalesomab, Lendalizumab, Lenzilumab, Lerdelimumab, Lesamumab, Rivirumab, Lifastuzumab vedotin, Ligelizumab, Lilotomabsatetraxetan, Lintozumab, Lirilumab, Lodelcizumab, Lokivetmab, Lorvotuzumab mertansin, Lucatumumab, Lulizumabpegol), Lumretuzumab, LY2951742, Mapamoumab, Margetuximab, Maslimomab, Maslimuzumab, Maveruzumab, Metelimumab, Milatuzumab, Minretumomab, Mirvetuximabsoravtansine, Mitumab, Mojamuzumab, Monalizumab, Morolimumab, Moveruzumab, Moxetumomab pasudotox, Moroumab-CD3, Nacolomab Namilumab, Naaptumomabestafenatox, Naratuximab emtansine, Narnatumab, Nataduzumab, Navicixizumab NaNavivumab, Nembakumab, Nemolizumab, Nerelimomab, Nesvacumab, Nivolumab, Nofetumomab merpentan, Obiltoxaximab, Atorizumab, Ocrelizumab, Odulimomab, Olaratumab, Olokizumab, Onartuzumab, Ontuxizumab, Opicinumab, Oportuzumab Monatox, Ogovomumab, Orticumab, Otelixizumab, Otlertuzumab, Oxelumab, Ozanezumab, Ozoralizumab, Pargexizumab, Pallizumab, Pamrevlumab, Panitumab, Pankomab, Panobacumab, Parsatuzumab, Pacozumab, Pasotuxizumab, Patelizumab (Pateclizumab), Patritumab, Pembrolizumab, Pemtumomab, Perakizumab, Pertuzumab, Pidilizumab, Pinatuzumab vedotin, Pintumomab, Placulumab, Plozalizumab, Pogalizumab, Polatuzumab vedotin, Ponezumab, Prezalizumab, Priliximab, Pritoxaximab, Pritumumab, PRO140. Quilizumab, Racotumomab, Radretumab, Rafivirumab, Ralpancizumab, Ramucirumab, Ranibizumab, Raxibacumab, Refanezumab, Regavirumab, Reslizumab, Rinucumab, Risankizumab, Rituximab, Rivabazumab pegol, Robatumumab, Roledumab, Romosozumab, Rontalizumab, Rovalpituzumab tesirine, Rovelizumab, Ruplizumab, Sacituzumab govitecan, Samalizumab, Sapelizumab, Sarilumab, Satumomab pendetide, seribantumab, setoxaximab, sevirumab, SGN-CD19A, SGN-CD33A, sibrotuzumab, sifamumab, siltuximab, simtuzumab, siplizumab, sirukumab, sofituzumab vedotin, Solanezumab, Solitomab, Sonepizumab, Sontuzumab, Stamulumab, Sulesomab, Suvizumab, Tabalumab, Tacatuzumabtetraxetan, tadocizumab, talizumab, tamtuvetmab, tanezumab, taplitumomab paptox, tarextumab, tefibazumab, telimomab aritox, Tenatumomab, Teneliximab, Teprotumumab, Tesidolumab, Tetulomab, Tezepelumab, TGN1412, Ticilimumab, Tigatuzumab, Tildrakizumab, Timolumab, Tisotumab vedotin), TNX-650, tocilizumab, toralizumab, tosatoxumab, tositumomab, tovetumab, tralokinumab, trastuzumab, trastuzumab emtansine, TRBS07, tregalizumab, tremelimumab, trevogrumab, tucotuzumab celmoleukin, tuvirumab, ublituximab, ullocuplumab, urelumab, urtozazumab, utekinumab, utomilumab, vadastuximab talirine, vandortuzumabvedotin, vantictumab, vanucizumab, vapaliximab, varlilumab, veterizumab, vedotin, vetozumab, vepalimomab, vesencumab, visilizumab, vobarilizumab, volociximab, vosetuzumab Mafodotin, Votumumab, Xentuzumab, Zanomimumab, Zalutumumab, Zamumab, Zatuximab, Ziralimumab, and Zolimomab aritox, or combinations thereof.

[0102] Examples of vaccines developed for viral diseases include, but are not limited to: Hepatitis A vaccine, Hepatitis B vaccine, Hepatitis E vaccine, HPV vaccine, Influenza vaccine, Japanese encephalitis vaccine, MMR vaccine, MMRV vaccine, Polio vaccine, Rabies vaccine, Rotavirus vaccine, Chickenpox vaccine, Shingles vaccine, Smallpox vaccine, Yellow fever vaccine, Adenovirus vaccine, Coxsackie B virus vaccine, Cytomegalovirus vaccine, Human dengue fever vaccine, Human eastern equine encephalitis virus vaccine, Ebola vaccine, Enterovirus 71 vaccine, Epstein-Barr vaccine, Hepatitis C vaccine, HIV vaccine, and Human HTLV-1. T-cell lymphoblastic leukemia vaccine, Marburg virus vaccine, norovirus vaccine, human respiratory syncytial virus vaccine, severe acute respiratory syndrome (SARS) vaccine, human West Nile virus vaccine; examples of bacterial diseases include, but are not limited to: anthrax vaccine, DPT vaccine, Q fever vaccine, Hib vaccine, tuberculosis (BCG) vaccine, meningococcal vaccine, typhoid vaccine, pneumococcal conjugate vaccine, pneumococcal polysaccharide vaccine, cholera vaccine, dental caries vaccine, ehrlichiosis vaccine, leprosy vaccine, Lyme disease vaccine, Staphylococcus aureus vaccine, Streptococcus pyogenes vaccine, syphilis vaccine, tularemia vaccine, plague. Yersinia germaphobia vaccine; examples of parasitic diseases include, but are not limited to: malaria vaccine, schistosomiasis vaccine, chagashi vaccine, hookworm vaccine, human onchocerciasis and river blindness vaccine, trypanosomiasis vaccine, and visceral leishmaniasis vaccine; examples of non-infectious diseases include, but are not limited to: Alzheimer's amyloid vaccine, breast cancer vaccine, ovarian cancer vaccine, prostate cancer vaccine, and oncolytic virus agents (T-VEC); vaccines also include, but are not limited to, the following trade names: ACAM2000, ActHIB, Adacel, Afluria, and quadrivalent Afluria. QUADRIVALENT, Agriflu, BCG vaccine, BEXSERO, Biothrax, Boosterx, Cervarix, Comvax, DAPTACEL, DECAVAC, Engerix-B, FLUAD, Fluarix, Fluarix Quadrivalent, Flublok, Flucelvax, Flucelvax Quadrivalent, FluLaval, FluMist, FluMist Quadrivalent, Fluvirin, FluzoneQuadrivalent, Fluzone, High-Dose Fluzone and Intradermal Fluzone, Gardasil, Gardasil 9, Havrix, Hiberix, Imovax, Infanrix, IPOL, Ixiaro, JE-Vax, KINRIX, Menactra, MenHibrix, Mennomune-A / C / Y / W-135, Menveo, MMR II, MM-Vax, Pediarix, PedvaxHIB, Pentacel, Pneumovax 23. Poliovax, Prevnar, Prevnar 13, ProQuad, Quadracel, Quadrivalent, RabAvert, Recombivax HB, ROTARIX, RotaTeq, TENIVAC, TICEBCG, Tripedia, TRUMENBA, Twinrix, TYPHIM Vi, VAQTA, Varivax, Vaxchora, Vivotif, YF-Vax, Zostavax, and combinations thereof.

[0103] Examples of injectable drugs include, but are not limited to: Ablavar (gadofosveset trisodium injection), Abarelix Depot, Abobotulinumtoxin A injection (Dysport), ABT-263, ABT-869, ABX-EFG, Accretropin (somatropin injection), Acetadote (acetylcysteine ​​injection), Acetazolamide Injection, Acetadote, Tocilizumab Injection, and Actrelin Ovine Trifluoroacetate for Injection. Triflutate), Actummune, Alteplase, Acyclovir for injection (Zovirax injection),

[0137] , Adacel, Adalimumab, Adenoscan (adenosine injection), Adenoscan, Adrenaclick, AdreView (lobenguanidine for intravenous use) 1123) Injection), Afluria, Ak-Fluor (fluorescein injection), Aldurazyme (laronidase), Ceredase (alegonase injection), Alkeran (melphalan hydrochloride injection), Aloprim (sodium allopurine for injection), Alprostadil, Sumatriptan (sumatriptan injection), ALTU-238, Amino acid injection, Aminosyn, Apidra, Apremilast, Caverject Impulse (dual-lumen system for alprostadil injection), AMG 009, AMG076, AMG 102, AMG 108, AMG 114, AMG 162, AMG 220, AMG 221, AMG 222, AMG 223, AMG 317, AMG 379, AMG 386, AMG 403, AMG 477, AMG 479, AMG517, AMG 531, AMG 557, AMG 623, AMG655, AMG706, AMG 714, AMG 745, AMG 785, AMG 811, AMG 827, AMG 837, AMG 853, AMG 951, Amiodarone Hydrochloride Injection, Amobarbital Sodium Injection, Amobarbital Sodium, Anakinra, Anti-Abeta A<β> Antibody, Anti-Beta7 β7 Antibody, Anti-Beta20 β20 Antibody, Anti-CD4 CD4 CD40 Antibody, Anti-CD20 CD20 CD40 Antibody, Anti-IFNα Antibody, Anti-IL13 IL13 OX40L Antibody 40L), oxLDS antibody (Anti-oxLDS), NGF antibody (Anti-NGF), NRP1 antibody (Anti-NRP1), Arixtra (sodium pentosan), Amphadase (hyaluronidase injection), Ammonul (sodium phenylacetate and sodium benzoate injection), Anaprox, Anzemet injection (dolasetron mesylate injection), Apizon (lysine insulin [rDNA source] injection), Apomab, Aranesp (alfadabetin), Argatroban (argatroban injection), arginine hydrochloride injection (R-Gene) 10. Triamcinolone (Aristocort), Aristospan, Arsenic Trioxide Injection (Trisenox), Articane Hydrochloride (Articane HCl), Septocaine Injection, Arzerra (Olfamumab Injection), Asclera (Policocalol Injection), Ataluren, Ataluren-DMD, Atenolol Injection (Tenormin I.V. Injection), Atracurium Besylate Injection (Atracurium Besylate Injection), Avastin, Azactam Injection (Aztreonam Injection), Azithromycin (Zithromax Injection), Azactam Injection (Azactam Injection), Baclofen Injection (and Intrathecal Injection (LIORESAL)). Intrathecal water, antibacterial water (for injection), baclofen injection (also available as intrathecal injection), and balin in oil ampoules.OilAmpules (Dimercarprol injection), BayHepB, BayTet, Benadryl, Bendamustine Hydrochloride Injection (Treanda), Benzatropine Mesylate Injection (Cogentin), Betamethasone Injectable Suspension (Celestone Soluspan), Bicillin CR 900 / 300 (Penicillin G Benzathine Penicillin and Penicillin G Procaine Injection), Blenoxane (Blenoxane Sulfate Injection), Blenoxane Sulfate Injection, Boniva Injection (Ibandronate Sodium). Sodium injection), cosmetic Botox (Onabotulinumtoxin A for injection), BR3-FC, Bravelle (follicle-stimulating hormone injection), Bretylium (brevital), and sodium methylhexyphenidate barbiturate. Sodium (sodium methobital for injection), Brethine, Briobacept, BTT-1023, Bupivacaine hydrochloride, Exenatide (Byetta), Ca-DTPA (calcium pentetate sodium injection), Cabazitaxel injection (Jevtana), Caffeine Alkaloid (caffeine and sodium benzoate injection), Calcitriol injection (Calcitrol), Calcitriol injection (calcitrol injection), Calcium chloride (10% calcium chloride injection), Calcium edetate sodium (calcium disodium EDTA injection), Camppath (alemtuzumab), Camptosar injection (irinotecan hydrochloride), Cananumumab injection (Ilaris), Capastatin sulfate. Sulfate (Capreomycin for Injection), Capreomycin Sulfate for Injection, Cardiolite (Technetium Tc99 for Injection), and Capreomycin Sulfate Prep Kit for Technetium Tc99.Sestamibi), Carticel, Cathflo, Cefazolin for injection and dextran (Cefazolin injection), Cefepime hydrochloride, Cefotaxime, Ceftriaxone, Cerezoyme, Carnitor injection, Caverrject, Betamethasone sodium phosphate, Celsior, Cerebyx (Fosphenytoin sodium) Sodium injection), Ceredase (exametazime injection), Ceretec (exametazime injection), Cetuzumab, CF-101, chloramphenicol sodium succinate (chloramphenicol sodium succinate injection), chloramphenicol sodium succinate injection (chloramphenicol sodium succinate), Cholestagel (cholesvelam hydrochloride), chorionic gonadotropin alpha injection (Ovidrel), Cimzia, Cisplatin (cisplatin injection), Clolar (clofarabine injection), Clomiphene citrate, Duraclon (clonidine injection), Cogentin (benzyltropine mesylate injection), Colistimethate injection (Coly-Mycin M), Coly-Mycin M (colistin injection), Compath, Vaprisol (conjugated equine estrogen for injection), Premarin (conjugated equine estrogen for injection), Copaxone, Actrelin (trifluoroacetic acid for injection), Corvert (ibutilide fumarate).Fumarate injection, Cubicin (dapoxetine injection), CF-101, Cyanokit (hydroxycobalamin for injection), Cytarabine Liposome injection (DepoCyt), Cycobalamin, Cytovene (guanosine propionate), DHE45, Dacizumab, Dacogen (decitabine injection), Dalteparin, Dantrolin IV (dalteparin sodium for injection), Dantrolin sodium for injection (dalteparin IV), Dapoxetine injection (Cubicin), Darbepoietin α, DDAVP injection (desmopressin acetate injection), Decavax, Decitabine injection (dapoxetine), Anhydrous ethanol (anhydrous ethanol injection), Prolia injection, Testosterone enanthate (Delatestryl), Estradiol valerate (Delestrogen), Dalteparin sodium (Delteparin) Sodium, Depacon (sodium valproate injection), Depomedal (methylprednisolone acetate injection suspension), DepoCyt (cytarabine liposome injection), DepoDur (morphine sulfate XR liposome injection), Desmopressin acetate injection (DDAVP injection), Depo-estradiol, Depo-Provera 104mg / ml, Depo-Provera 150mg / ml, Depo-Testosterone, Dilazopiclone for injection, Intravenous infusion only (Totect), Glucose / electrolytes, Glucose and sodium chloride injection (5% glucose in 0.9% sodium chloride), Glucose, Diazepam injection (Valium injection), Digoxin injection (Lanoxin injection), Dilaudid-HP (dihydromorphone hydrochloride) Injectable drugs, dimercaprol injection (Barr in oil ampoules), diphenhydramine injection (Benadryl injection), dipyridamole injection (Persantine injection), DMOAD, docetaxel for injection (Taxotere), dolasetron mesylate injection (Anzemet injection), Doribax (doribenem for injection), doribax for injection, doxercalciferol injection (Hectorol injection), Doxil (doxorubicin hydrochloride liposomes).Liposome injection, Doxil (liposome doxorubicin hydrochloride injection), Duraclon (colatin injection), Duramorph (morphine injection), Dysport (Abo botulinum toxin A injection), Kalbitor (caratate injection), EC-naproxen (methoxynaprotic acid), calcium disodium EDTA injection (calcium disodium edetate), Edex (prostaglandin for injection), Engerix, Enlon (enlon chloride injection), Eliglustat tartrate, oxaliplatin injection, Emend injection (fosaprepitant). Dimeglumine injection, enalapril injection, edrophonium injection, enoxaparin sodium. Sodium injection (Lovenox), Eovist (Gadoxetate Disodium injection), Enbrel (etanercept), Enoxaparin, Epicel, Epinepherine, Epipen, Epipen Jr., Eprazitumab, Erbitux, Ertapenem injection (Invanz), Erythropoietin, Nephramine, Estradiol Cypionate, Estradiol Valerate Valerate, etanercept, exenatide injection (Byetta), Evlotra, facalcidylase (Adalsidase β), famotidine injection, FDG (fluorodeoxyglucose F18 injection), feraheme (Ferumoxytol nano-iron oxide injection), Feridex 4th generationIV (Ferumoxide nanoparticles injectable solution), Fertinex, Ferumoxide nanoparticles injectable solution (Ferumex IV), Nano-iron oxide injection (Furamo), Flagyl injection (Metronidazole injection), Fluarix, Fludara (fludarabine phosphate), Fludeoxyglucose F18 injection (FDG), fluorescein injection (Ak-Fluor), Follistim AQ Cartridge (follicle-stimulating hormone beta injection), Follicle-stimulating hormone alpha injection (Gonal-f) RFF), follicle-stimulating hormone beta injection (Frostine AQ cartridge), Folotyn (pralatrexate solution for intravenous injection), Fondaparinux sodium, Forteo (teriparatide (rDNA-derived) injection), Fostamatinib, Fosaprepitant dimethylglucamine Dimeglumine injection (Emend injection), Foscavir sodium phosphonoformate injection, Cerebyx sodium phosphonoformate injection, Lusedra sodium phosphonopropofol injection, Fragmin, Fuzeon (enfuvirtide), GA101, Multihance gadobenzamide injection, Ablavar gadofenoxetate trisodium injection, ProHance gadoteridol injection, OptiMARK gadoversetamide injection, Eovist gadoxetate disodium injection, Ganirelix (ganirelix acetate injection), Gardasil, GC1008, GDFD, Gemtuzumab for injection Ozogamicin (Mylotarg), recombinant human growth hormone (Genotropin), gentamicin injection, GENZ-112638, golimumab injection (Simponi injection), Gonal-fRFF (Follicle-Stimulating Hormone Alpha Injection), Granisetron Hydrochloride (Kytril Injection), Gentamicin Sulfate, Granitiralate Acetate, Glucagon, HAE1, Haldol (Haloperidol Injection), Havrix, Hectorol Injection (Doxercalciferol Injection), Hedgehog Pathway Inhibitor Inhibitor, Heparin, Herceptin, hG-CSF, Humalog, Human Growth Hormone, Humatrope, HuMax, Humegon, Humira, Humulin, Boniva Ibandronate Sodium Injection, NeoProfen Ibuprofen Lysine Salt Injection, Corvert Idamycin PFS (Idarubicin Hydrochloride Injection), Idarubicin Hydrochloride Injection (Idamycin PFS), Ilaris (Cananumumab Injection), Primaxin Imipenem and Cilastatin Injection IV), Imitrex, Incobotulinumtoxin A (Xeomin), Increlex (Mecasermin [rDNA source] injection), Indocin IV (Indomethacin injection), Indomethacin IV injection, Infanrix, Innohep, Insulin, NovoLog (insulin aspart [rDNA source] injection), Lantus (insulin glargine [rDNA source] injection), Apizon (insulin lisgludec [rDNA source] injection), Intron A (insulin α-2b recombinant for injection), Intron A (insulin α-2b recombinant for injection), Invanz (ertapenem injection), Invega Sustenna (paliperidone palmitate extended-release formulation).Palmitate Extended-Release (injectable suspension), Invirase (saquinavir mesylate), Iobenzylguanidine 1123 injection for intravenous infusion (AdreView), Iopromide injection (Ultravist), Ioflucan injection (Optiray), Iplex (mecaserinelinfepe [rDNA source] injection), Iprivask, Irinotecan hydrochloride (Camptosar injection) Injectables, sucrose iron injection (Venofer), Istodax (romidesin for injection), itraconazole injection (Sporanox injection), Jevtana (cabatasoxetine injection), Jonesa, Kalbitor (icaralotide injection), KCl in D5NS (potassium chloride injection in 5% glucose and sodium chloride), KCl in D5W, KCl in NS, oral ointment (Kenalog 10 injection) (triamcinolone acetate) Acetonide (injectable suspension), Kepivance (palivmin), Keppra (levetiracetam) injection, keratinocytes, KFG, kinase inhibitors, Kinret (anaspirin), Kinlytic (urokinase injection), Kinrix, Clonazepam (clonazepine), Kytril (granisetron hydrochloride injection), Lacosamide tablets and injections (Vimpat), Lactated Ringer's solution, Lanosin injection (digoxin injection), Lansoprazole for injection (Putopyrin IV), Lantus, Leucovorin (leucovorin injection), Lente (L), Leptin, Levemir, LeukineSargramostim), Leuprorelin Acetate, Levothyroxine, Levetiracetam (Keplan injection), Enoxaparin (Lovenox), Levocarnitine Injection (Carnitine Injection), Lexiscan (Regadenoson Injection), Baclofen Injection, Liraglutide [rDNA] Injection (NovoRapid), Enoxaparin (Lovenox) (Enoxaparin Sodium Injection), Ranibizumab (Lucentis) (Ranibizumab Injection), Lumizyme, Lupron (Leuprorelin Acetate Injection), Lusedra (Propofol Sodium Injection), Maci, Magnesium Sulfate (Magnesium Sulfate) Injectable drugs), mannitol injection (mannitol IV), ephedrine (bupivacaine hydrochloride and epinephrine injection), Maxipime (cefepime hydrochloride for injection), MDP multi-dose kit for technetium injection (technetium Tc99m ethametime injection), mecaserine [rDNA source] injection (Increlex), mecaserine linfepe [rDNA source] injection (Iplex), melphalan hydrochloride injection (Alkeran injection), methotrexate, menactra, Menopur (fertility stimulant injection), fertility stimulant for injection (Repronex), mesobarbital sodium for injection (Brevital)Sodium, Methyldopa ethyl hydrochloride injection solution (Methyldopa ethyl hydrochloride), Methylene blue (Methylene blue injection), Methylprednisolone acetate injection suspension (DepoMedrol), MetMab, Metoclopramide injection (Reglan injection), Mifepristone (Follicle-stimulating hormone for injection), Metronidazole injection (Flagyl injection), Midazolam, Midazolam injection, Mimpara (Cinacalet), Minocycline injection (Dimethylaminotetracycline injection), Mipomersen, Mitoxantrone concentrate for injection (Novantlon), Morphine injection (Morphine sulfate) Morphine Sulfate XR Liposome Injection (DepoDur), Sodium Morphine (Sodium Morphine Injection), Motesanib, Mozobil (Plerixa for Injection), Multihance (Gadobemycin Injection), Multiple Electrolytes and Glucose Injection, Multiple Electrolytes Injection, Mylotarg (Genuine Tadalafil and Ozolmicin for Injection), Myozyme (Alglucosidase Alfa), Nafcillin Injection (Nafcillin Sodium), Nafcillin Sodium (Nafcillin Injection), Naltrexone XR Injection (Vivitrol), Naproxen (Methoxynaprotic Acid), NeoProfen (Ibuprofen Lysine Salt Injection), Nandrol Caprate (Nandrol) Decanoate, Neostigmine methylsulfate (neostigmine methylsulfate injection), NEO-GAA, NeoTect (technetium Tc99m diprotide injection), Nephramine (essential amino acid injection), Neulasta (pefragil), Neupogen (filgrastim), NovoMix, NovoRapid, NeoRecormon, Neutrexin (trimethoprim glucuronide injection), NPH(N), Nexterone (amiodarone hydrochloride injection), N Orditropin (somatropin injection for growth hormone), normal saline (sodium chloride injection), Novartis (mitoxantrone concentrate for injection), NovoMix 70 / 30 Innolet (70% NPH-neutral protamine human insulin suspension and 30% regular human insulin injection), NovoRapid (insulin aspart [rDNA-derived] injection), Nplate (romistastatin), Nutropin (nutropin for injection (rDNA-derived growth hormone)), Nutropin AQ, NutropinDepot (growth hormone for injection (rDNA source)), Octreotide acetate injection (Sanderdin LAR), Octreizumab, Olfamumab injection (Arzerra), Olanzapine sustained-release injectable suspension (Zyprexa Relprevv), Omnitrope (growth hormone [rDNA source] injection), Ondansetron hydrochloride injection (Syconazole injection), OptiMARK (gadofol injection), Amsali injection (iodophorol injection), Orencia, Osmitrol injection in Aviva (mannitol injection in Aviva plastic container 250), Osmitrol injection in Viaflex (mannitol injection in Viaflex plastic container 250), Bone Protection Osteoprotegrin, Ovidrel (human chorionic gonadotropin alpha injection), oxacillin (oxacillin for injection), oxaliplatin injection (Lexadine), oxytocin injection (pyridoxine), paliperidone palmitate sustained-release injectable suspension (Saistada), pamidronate disodium injection (pamidophosphate sodium injection), panitumumab injection for intravenous infusion (Vectibix), papaverine hydrochloride injection (paaverine injection), papaverine injection (paaverine hydrochloride injection), parathyroid hormone, paricalcitol injection trigger bottle (Fliptop)Vial (Zemplar injection), PARP inhibitors, Pediarix, PEGlntron, Peginterferon, Pegfilgrastim, Benzathine penicillin G and procaine penicillin G, Pentetate calcium sodium injection (Ca-DTPA), Pentetate zinc sodium injection (Zn-DTPA), Pepcid injection (Famotidine injection), Pergonal, Pertuzumab, Phentolamine mesylate (Phentolamine injection), Phentolamine salicylate (Phenylate injection), Phentolamine salicylate (Phenylate injection), Piperacillin and Tazobactam injection (Zosy) n), Pyridoxine (oxytocin injection), Plasma-Lyte 148 (multi-electrolyte injection), Plasma-Lyte 56 and glucose (multi-electrolyte and glucose injection in Vivaldi plastic container 50), PlasmaLyte, Plexa for injection, Asclera, potassium chloride, Folotyxal solution for intravenous injection, Symlin acetate injection, Premarin injection (conjugated estrogen for injection), Cardiolite Tc-99 statabi preparation kit for injection, Primaxin IV (lansoprazole for injection). IV (Imipenem and Cilastatin for Injection), Prochymal, Procrit, Progesterone, ProHance (Gadoterol Injection), Prolia (Denizumab Injection), Promirtine Hydrochloride Injection (Promethazine Hydrochloride Injection), Propranolol Hydrochloride Injection (Propranolol Hydrochloride Injection), Quinidine Gluconate Injection (Quinidine Injection), Quinidine Injection (Quinidine Gluconate Injection), R-Gene10 (arginine hydrochloride injection), ranibizumab injection (ranibizumab (Lucentis)), ranitidine hydrochloride injection (Zantac injection), Raptiva, Reclast (zoledronic acid injection), Recombivarix HB, Regardson injection (Lexicon), Metoclopramide injection, Remicade, Renagel, Renvela (sevelamer carbonate), Repronex (fertility stimulant for injection), Retrovir IV (zidovudine injection), rhApo2L / TRAIL, Ringer's and 5% glucose injection Ringer's Injection (Ringer's Glucose), Ringer's Injection, Rituxan, Rituximab, Rocephin (Ceftriaxone), Rocuron (Zemuron), Interferon-A (Interferon α-2a), Romazicon (Flumazenil), Istodax (Romidix for Injection), Saizen (Growth Hormone Injection), Sclerostin (Actreotide Acetate Injection), Sensipar (Cinacalcet), Sensorcaine (Bupivacaine Hydrochloride Injection), Septocaine (Articaine Hydrochloride and Epinephrine Injection), Serostim LQ (growth hormone (rDNA-derived) injection), Simponi injection (golimumab injection), Sodium acetate (sodium acetate injection), Sodium bicarbonate (5% sodium bicarbonate injection), Sodium lactate (sodium lactate injection in AVIVA), Sodium phenylacetate and sodium benzoate injection (Ammonul), Growth hormone (rDNA-derived) for injection (Nutropin), Sporanox injection (itaranzol injection), Stelara injection (Utecgen), Stemgen, Sufentanil (sufentanil citrate injection), Sufentanil citrate injection (sufentanil), Sumavel, Sumatriptan injection (Alsuma), Semeline, Semeline pen, Systemic Hedgehog Antagonist, Synvisc-One (Heliotropin GF) 20 single-dose intra-articular injections), Erlotinib (Tarceva), Taxotere (docetaxel for injection), Technetium Tc99m, Vibativ (for injection), Temsirolimus (for injection), Torisel (for injection), Atenolol IV (for injection), Teriparatide (rDNA-derived) (for injection), Testosterone Cyclopentapropionate, Testosterone Heptanate, Testosterone Heptanate, Tev-Tropin (growth hormone, rDNA-derived, for injection), tgAAC94, Thallium Chloride, Theophylline, Thiotepa (Thiotepa injection), Thymoglobulin (anti-thymocyte globulin (rabbit), Thyroid Stimulating Hormone Alpha for Injection), Ticarcillin Sodium and Clavulanate Potassium (Galex). (Galaxy) (Tymplocin Injection), Digen Injection (Trimethoprim Hydrochloride Injectable), Tymplocin Injection (Ticarcillin Sodium and Clavulanate Potassium Galexis), Tenecteplase (TNKase), Tobramycin Injection (Topycin Injection), Tocilizumab Injection (Antenex), Torisel (Tesirolimus Injection), Totect (Dextromethorphan for Injection, Intravenous Infusion Only), Trastuzumab-DM1, Travasol (Amino Acid (Injectable)), Treanda (Bendamustine Hydrochloride Injection), Trelstar (Triptorelin Hydrochloride Injectable Suspension). Pamoate for Injectable Suspension), Triamcinolone Acetonide Acetate, Triamcinolone Diacetate, Aristospan Injection 20mg, Triesence (Triamcinolone Acetonide Injectable Suspension), Trimethoprim Hydrochloride Injectable (Tigan Injection), Trimethoprim Glucuronide Injection (Neutrexin), Triptorelin Naphthyl ...Vi), Iopromide Injection, Urokinase Injection, Kinlytic, Stelara Injection, Ultralente (U), Diazepam (Valium), Sodium Valproate Injection (Pakine), Valtropin (Growth Hormone Injection), Vancomycin Hydrochloride Injection, Vaprisol (Conivar Hydrochloride) Panitumumab injection, VAQTA, Vasovist (gadolinium fosetyl-tetrate injection for intravenous infusion), Vectibix (panitumumab injection for intravenous infusion), Venofer (iron sucrose injection), Visudyne (verteporfen injection), Vibativ (tervavancin injection), Victoza (liraglutide [rDNA] injection), Vimpat (lacosamide tablets and injection), vincaline sulfate (vincaline sulfate injection), Vincasar PFS (Vincristine Sulfate Injection), NovoMix, Vincristine Sulfate (Vincristine Sulfate Injection), Visudyne (Verteporfin Injection), Vitamin B-12, Vivitrol (Naltrexone XR Injection), Voluven (Hydroxyethyl Starch in Sodium Chloride Injection), Xeloda, Xenical (Orlistat), Xeomin (Botulinum Toxin A Injection), Xolair, Zantac Injection (Ranitidine Hydrochloride Injection), Zemplar Injection (Paricalcitol Injection Trigger Bottle), Zemuron (Rocuronium Bromide) Injectable formulations, Zenapax (dalizumab), Zevalin, Zidovudine injection (Litovial IV), Zithromax injection (azithromycin), Zn-DTPA (zinc sodium pentimate injection), Ondansetron hydrochloride injection, Zingo, Zoledronic acid for injection (Zometa), Zoledronic acid injection (Reclast), Zoledronic acid for injection, Zosyn (piperacillin and tazobactam injection), ZyprexaRelprevv (olanzapine sustained-release injectable suspension), and combinations thereof.

[0104] Although the invention has been described in detail, modifications within the spirit and scope of the invention will be apparent to those skilled in the art. It should be understood that various aspects and embodiments of the invention, as well as various features, as set forth in the foregoing and / or appended claims, can be combined or interchanged, in whole or in part. In the foregoing description of the various embodiments, those implementations relating to another embodiment can be suitably combined with other embodiments, as will be understood by those skilled in the art.

Claims

1. A medical delivery device, the medical delivery device comprising: A lubricant-free syringe having a proximal end, a distal end, and an inner surface, the inner surface defining a fluid chamber for receiving at least one therapeutic agent; An elastomeric stop member having an outer surface that forms a fluid-impermeable seal with the inner surface of the syringe, wherein the elastomeric stop member includes a plurality of ribs, with a valley between each pair of ribs; and At least one ring member, said at least one ring member being located within at least one valley; The coating material is positioned on the inner surface of the syringe adjacent to the proximal end of the syringe to form a region with a reduced diameter, thereby enhancing the interference fit between the elastomeric stop and the inner surface of the syringe. The at least one ring component includes an oxygen-absorbing material, an oxygen-adsorbing material, or a combination of both.

2. The medical delivery device as claimed in claim 1, characterized in that, Two or more of the valleys include at least one annular member.

3. The medical delivery device as described in claim 1, characterized in that, The at least one therapeutic agent is selected from antibodies, antisense molecules, RNA interference, primary cells, embryonic stem cells, vaccines, and combinations thereof.

4. The medical delivery device as claimed in claim 1, characterized in that... Suitable for treating eye diseases.

5. The medical delivery device as claimed in claim 1, characterized in that, The medical delivery device is a syringe.

6. The medical delivery device as claimed in claim 1, characterized in that, The medical delivery device is an automated injector.

7. The medical delivery device as claimed in claim 1, characterized in that, The medical delivery device is a pen.

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