Syringe systems and methods for dispensing drug products

Abstract

Syringe systems and methods are provided for delivering injectable drugs. A syringe includes a syringe barrel including a distal end, a proximal end, a bore extending therebetween, a plunger received in the bore, and a plunger rod coupled to move the plunger. A plunger rod retainer is removably coupled to the plunger rod and configured to retain the plunger at a fixed position inside the bore, and a volume is disposed in the bore between the distal end of the syringe barrel and the plunger. When the syringe is at a first configuration, the volume includes a gas having a reduced pressure, and when the syringe is at a second configuration, the volume includes an injectable drug.

Description

SYRINGE SYSTEMS AND METHODS FOR DISPENSING DRUG PRODUCTSFIELD OF THE DISCLOSURE

[0001] The present disclosure relates to syringe systems and methods for dispensing drug products, and in particular, syringe systems having a reduced-pressure volume for delivering injectable drugs to subjects.BACKGROUND OF THE DISCLOSURE

[0002] Injectable drugs are commonly provided in multiple-dose or single-dose vials, and such agents are dispensed from the vials to hypodermic syringes for subsequent delivery to patients. More specifically, this process typically begins by holding the syringe with the needle pointing upwardly. The syringe’s plunger is then retracted to fill the syringe with air, specifically a volume of air equal to the volume of the injectable drug to be administered to a patient. The needle of the syringe is then inserted through a stopper coupled to the opening of a vial, and the plunger is advanced to deliver the air from the syringe to the vial. Next, the vial and the syringe are inverted, and the needle’s tip is held in the injectable drug. The plunger is then retracted to fill the syringe with the injectable drug, and the needle is removed from the vial. The syringe is then ready to deliver the injectable drug to a patient.

[0003] For some individuals, such as diabetics, the above process is relatively difficult or inconvenient. In other settings, such as high-throughput contract pharmacies, the above process is overly time consuming. Accordingly, it would be desirable to provide improved syringe systems.SUMMARY

[0004] The present disclosure relates to syringe systems and methods for dispensing drug products, and in particular, syringe systems having reduced-pressure volumes for delivering injectable drugs to subjects. A plunger rod retainer is removably coupled to a plunger rod of a syringe to retain a plunger inside the bore at a predetermined position, and a volume is disposed in the bore between the distal end of the syringe barrel and the plunger. When the syringe is at a first configuration, the volume includes a reduced pressure volume, which allows for an easy filling of drug products (e.g., an injectable drug) into the syringe. When the syringe is at a second configuration, the volume includes the injectable drug.

[0005] In a first aspect of the disclosure, a syringe system includes a syringe barrel that includes a distal end, a proximal end, and a bore extending between the distal end and the proximal end thereof. A plunger is received in the bore of the syringe barrel. A plunger rod is coupled to the plunger and configured to move the plunger between a first position and a second position. A plunger rod retainer removably coupled to the plunger rod and configured to retain the plunger at a fixed position at the first position. A volume disposed in the bore between the distal end of the syringe barrel and the plunger. When the syringe system is at a first configuration, the volume includes a gas having a reduced pressure, and when the syringe system is at a second configuration, the volume includes an injectable drug.

[0006] In another aspect of the disclosure, a method of making a syringe system is provided. The method includes: providing a syringe barrel including a distal end, a proximal end, and a bore extending between the distal end and the proximal end thereof; positioning a plunger in the bore of the syringe barrel at a predetermined positioned corresponding to an amount a fluid to be received, wherein a plunger rod is coupled to the plunger and configured to move the plunger distally between a first position and a second position; coupling a plunger rod retainer to the plunger rod to retain the plunger at the predetermined position; reducing a pressure in the bore to less than an atmospheric pressure to generate a volume disposed in the bore between the distal end of the syringe barrel and the plunger. The volume includes a gas having a reduced pressure.

[0007] In another aspect of the disclosure, a method of delivering an injectable drug using a syringe system is provided. The syringe system is at a first configuration with a predetermined volume disposed in a bore thereof including a gas at a first pressure. The syringe system further includes a plunger rod retainer removably coupled to a plunger rod and configured to retain a plunger coupled to the plunger rod at a position inside the bore. The method includes coupling a distal end of a syringe barrel to an internal chamber of a vial containing the injectable drug at a second pressure relatively higher than the first pressure; permitting the injectable drug to flow, under a pressure difference between the first pressure and the second pressure, from the internal chamber of the vial into the bore of the syringe barrel to change the syringe system from the first configuration to a second configuration with the predetermined volume at least partially filled with the injectable drug; and removing the plunger rod retainer from the plunger rod to allow the plunger to move inside the bore to deliver the injectable drug from the bore.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] The above-mentioned and other features and advantages of this disclosure, and the manner of attaining them, will become more apparent and will be better understood by reference to the following description of embodiments of the disclosure taken in conjunction with the accompanying drawings, wherein:

[0009] FIG. 1 is a side view of a syringe system before assembling, according to an embodiment of the present disclosure.

[0010] FIG. 2A is a side view of a plunger rod retainer including a disengageable locking mechanism before mounting on a plunger rod, according to an embodiment of the present disclosure.

[0011] FIG. 2B is a side perspective view of a plunger rod retainer including an expandable slit, according to an embodiment of the present disclosure.

[0012] FIG. 2C is a side perspective view of a plunger rod retainer including a scored structure, according to an embodiment of the present disclosure.

[0013] FIG. 2D is a side perspective view of a plunger rod retainer including a distal end configured to engage with a syringe barrel, according to an embodiment of the present disclosure.

[0014] FIG. 3 is a side view of a syringe, according to an embodiment of the present disclosure.

[0015] FIG. 4 is a side view of a first syringe and a second syringe including the respective plunger rod retainers having different lengths, according to an embodiment of the present disclosure.

[0016] FIG. 5 is a side view of a syringe system to transfer an injectable drug from a vial.

[0017] FIG. 6 is a side view of a plunger rod retainer including securement structures in contact with a syringe barrel and the plunger rod, according to an embodiment of the present disclosure.

[0018] FIG. 7 is a flow diagram, illustrating a method of making a syringe system.

[0019] FIG. 8 is a flow diagram, illustrating a method of delivering an injectable drug using a syringe.

[0020] Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set out herein illustrate exemplary embodiments of the disclosure and such exemplifications are not to be construed as limiting the scope of the disclosure in any manner.DETAILED DESCRIPTION

[0021] For the purpose of promoting an understanding of the principles of the disclosure, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the disclosure is thereby intended. Any alterations and further modifications in the described embodiments, and any further applications of the principles of the disclosure as described herein are contemplated as would normally occur to one skilled in the art to which the disclosure relates. One or more embodiments are shown in great detail, although it will be apparent to those skilled in the relevant art that some features that are not relevant to the present disclosure may not be shown for the sake of clarity.

[0022] The terms “couples”, “coupled”, “coupler” and variations thereof are used to include both arrangements wherein the two or more components are in direct physical contact and arrangements wherein the two or more components are not in direct contact with each other (e.g., the components are “coupled” via at least a third component), but yet still cooperate or interact with each other.

[0023] In some instances throughout this disclosure and in the claims, numeric terminology, such as first, second, third, fourth, etc., is used in reference to various components of features. Such use is not intended to denote an ordering of the components or features. Rather, numeric terminology is used to assist the reader in identifying the components or features being referenced and should not be narrowly interpreted as providing a specific order of components or features.

[0024] Syringe systems and methods according to the present disclosure can dispense one or more injectable drugs, which may also be referred to as medications or therapeutic agents. Such injectable drugs may include, for example, epinephrine, anaesthetics, analgesics,steroids, insulins, insulin analogs such as insulin lispro or insulin glargine, insulin derivatives, GLP-1 receptor agonists such as dulaglutide or liraglutide, glucagon, glucagon analogs, glucagon derivatives, gastric inhibitory polypeptide (GIP), GIP analogs, GIP derivatives, combined GIP / GLP-1 agonists such as tirzepatide or retatrutide, basal insulins, such insulin efsitora alfa, oxyntomodulin analogs, oxyntomodulin derivatives, and other treatments for diabetes and / or obesity, such as with lepodisiran (LPA siRNA), volenrelaxin, amylin agonist long acting, PNPLA3 siRNA, AP0C3 siRNA, DACRA qw II, GIPR agonist long acting, glucose sensing insulin receptor agonist, nisotirostide, bimagrunab, NRG4 agonist, SCAP siRNA, mazdutide, therapeutic antibodies including but not limited to IL-23 antibody analogs or derivatives, such as mirikizumab that can be used for treatment of Crohn’s disease or ulcerative colitis, IL-17 antibody analogs or derivatives, such as ixekizumab that can be used for treatment of plaque psoriasis, IL- 13 antibody analogs or derivatives, such as lebrikizumab that can be used for treatment of atopic dermatitis, therapeutic agents for pain-related and / or migraine treatments, such as galcanezumab or lasmiditan, or for treatment of atopic dermatitis, such as with lebrikizumab ucenprubart, for treatment of Alzheimer’s and / or dementia, such as with donanemab, remternetug, or GRN gene therapy, for treatment of Parkinson’ s disease and / or Gaucher’s disease, such as with GBA1 gene therapy, for treatment of Hidradenitis Suppurativa, such as with eltrekibart, for treatment of rheumatoid arthritis, such as with peresolimab, and any therapeutic agent, such as with CD 19, that is capable of delivery by the devices described herein. Such injectable drugs may also include imaging / contrast agents, radiopharmaceutical agents, or any other drug that is capable of delivery by systems and methods according to the present disclosure. Suitable drug products may include one or more active ingredients dissolved in a liquid solvent (e.g., water for injection). Syringe systems and methods according to the present disclosure can be operated in a manner generally as described herein by a user (for example, a healthcare professional, a caregiver, or another person) to deliver one or more injectable drugs to a subject (for example, a patient, the user himself or herself, another person, or an animal).

[0025] FIG. 1 is a side view of a syringe system 100 prior to assembling, according to an embodiment of the present disclosure. The syringe system 100 includes a syringe barrel 10 having a distal end 12, a proximal end 14, and a bore 16 extending between the distal end 12 and the proximal end 14 thereof. The distal end 12 and the proximal end 14 may each includean opening to couple to the bore 16. The proximal end 14 may be associated with a syringe flange 17, while the distal end 12 may be associated with a fluid coupling of the syringe. The syringe barrel 10 may include, for example, a cylindrical body made of glass or plastic. Markings or scales may be provided on the outside wall of the syringe barrel 10 to indicate the volume or amount of the injectable drug inside the bore 16. Syringes described herein can be a lubricated syringe (or three-piece syringe), a non- lubricated syringe (or two-piece syringe).

[0026] A plunger 22 can be received in the bore 16 of the syringe barrel 10. The plunger 22 can be movably carried within the bore 16 by a plunger rod 20, which is coupled to the plunger 22 and configured to move the plunger 22 between a first position adjacent the distal end 12 of the syringe barrel 10 and a second position adjacent the proximal end 14 of the syringe barrel 10. The plunger 22 may form a sealing mechanism with an inner wall of the syringe barrel 10. The plunger rod 20 extends between a distal end 21 and a proximal end 23 opposite the distal end 21 thereof. The distal end 21 of the plunger rod 20 can be coupled to the plunger 22 via, for example, a traded post (not shown) carried by the plunger 22. The plunger rod 20 includes a thumb tab 26 (shown as a radial flange) disposed at the proximal end 23 of the plunger rod 20 opposite the plunger 22.

[0027] A plunger rod retainer 30 is removably coupled to the plunger rod 20 and configured to retain the plunger 22 at a position between the first position and the second position. FIGS. 2A-D illustrate various plunger rod retainers 30A, 30B, 30C and 30D, according to some embodiments. The plunger rod retainers 30A, 30B, 30C and 30D each include a sheath structure 32 wrapping around at least a portion of the plunger rod 20. The sheath structure 32 extends between a distal end 31 and a proximal end 33 thereof along an axis direction 35, and has a predetermined axial length L (FIG. 1) between the ends 31 , 33. The plunger rod retainer 30 may have a hollowed cylinder shape having dimensions (e.g., diameter) suitable for slipping over the plunger rod 20. The plunger rod retainer 30 may be made of any suitable materials which can provide a relative flexibility to wrap around the plunger rod 20 and a relative rigidity to prevent the axial movement of the plunger 22.

[0028] In the embodiment depicted in FIG. 1 or 3, the distal end 31 of the plunger rod retainer 30 is positioned at a location with an axial distance d with respect to the distal end 21 of the plunger rod 20, to which the plunger 22 is attached. The portion 20-1 of the plunger rod 20 adjacent to the distal end 21 thereof is not covered by the sheath structure 32 and canbe inserted into the bore 16 along with the plunger 22. The proximal end 33 of the plunger rod retainer 30 may be in abutting contact with the thumb tab 26.

[0029] In an embodiment, the plunger rod retainer 30 may include a disengageable locking mechanism 34 (FIG. 6) to allow the plunger rod retainer 30 to be secured on the plunger rod 20 and removed from the plunger rod 20 thereafter. FIG. 2A is a side view of the plunger rod retainer 30A including a pair of locking members 34A extending along opposite edges of the sheath structure 32 in the axis direction 35. The pair of locking members 34A can be engaged with each other to mount and secure the sheath structure 32 on the plunger rod 20. In an embodiment, the pair of locking members 34A may form a zipper structure including, e.g., a pair of flexible strips of metal or plastic with interlocking projections closed or opened by pulling a slide along them, used to fasten the sheath structure 32 on the plunger rod. In an embodiment, the pair of locking members 34A may form a hook-and-loop fastener structure including, e.g., a pair of fabric strips having hooks and loops which can be temporarily fastened together. An aspect of locking members 34A can be combined with the other embodiments described herein.

[0030] In an embodiment, the plunger rod retainer 30 may include an expandable portion to allow the sheath structure to be removed from the plunger rod. FIG. 2B is a side perspective view of the plunger rod retainer 30B including an expandable portion 34B extending in the axis direction 35 from the distal end 31 to the proximal end 33. The expandable portion 34B may include any flexible material (e.g., flexible fabric) and dimensions (e.g., a width of a slit) to allow the sheath structure 32 to slide off from the plunger rod 20. It is to be understood that the sheath structure 32 may include two or more expandable structures (e.g., slits) to allow the removal of the sheath structure 32 from the plunger rod 20. An aspect of expandable portion 34B can be combined with the other embodiments described herein.

[0031] In an embodiment, the plunger rod retainer 30 may have an adjustable length along the axis direction 35 between the distal end 31 and the proximal end 33 thereof. FIG. 2C is a side perspective view of the plunger rod retainer 30C including a scored structure 34C positioned adjacent to the distal end 31. The scored structure 34C may include a series of discrete notches to facilitate the removal of the respective sections 32-1, 32-2 and 32-3 from the sheath structure 32. Each notch may extend in a direction substantially parallel to the distal end 31. The sections 32-1, 32-2 and 32-3 have respective lengths of 11, 12 and 13. Oneor more peel tabs may be provided to facilitate peeling off the respective sections 32-1, 32-2 and 32-3. After the removal of section 32-1 having the length 11, the sheath structure 32 has a reduced length L1=L-11, and the bottom edge of section 32-2 acts as the new distal end 31. After the removal of section 32-2 having the length 12, the sheath structure 32 has a further reduced length L2=L1-12, and the bottom edge of section 32-3 acts as the new distal end 31. After the removal of section 32-3 having the length 13, the sheath structure 32 has a further reduced length L3=L2-13, and the bottom edge of the remaining section of the sheath structure acts as the new distal end 31 . An aspect of scored structure 34C can be combined with the other embodiments described herein. For example, the sheath structure may include scored structure 34C, expandable portion 34B, or a combination thereof.

[0032] In an embodiment, the plunger rod retainer 30 may include a connection mechanism at the distal end 31 thereof. FIG. 2D is a side perspective view of the plunger rod retainer 30D including a connection mechanism 34D configured to engage with a syringe barrel. The connection mechanism 34D at the distal end 31 of the sheath structure 32 is configured to engage with the proximal end 14 of the syringe barrel 10 to prevent the plunger 22 from moving inside the bore 16. The connection mechanism 34D may include any suitable snug and secure connections such as, e.g., a bayonet mount. In an embodiment, the distal end 31 of the sheath structure 32 may have a tapered proximal end (not shown) which has a wedge or interference fit into an opening at the proximal end 14 of the syringe barrel 10, in which the plunger is slidably disposed. An aspect of connection mechanism 34D can be combined with the other embodiments described herein.

[0033] With reference to FIG. 6, in an embodiment, one or more securement structures 37A, such as clips or ties, (shown in dashed lines as an optional feature in FIG. 6) may be provided to removably secure the distal end 31 of the sheath structure 32 to the proximal end 14 of the syringe barrel 10, such as to the syringe flange 17. The securement structure 37A may further inhibit axially distal movement of the plunger rod. In another embodiment, one or more securement structures 37B, such as clips or ties, may be provided to removably secure the proximal end 33 of the sheath structure 32, such as to the thumb tab 26 of the plunger. The securement structure 37A may further inhibit axially proximal movement of the plunger rod. The securement structures 37A, 37B may be attached or integrally formed with the plunge rod retainer 30. As shown in FIG. 6, the securement structures 37A, 37B are shown extending radially outward from the axis and include a recess sized and shaped toreceive the corresponding syringe component, the thumb tab 26 and the syringe flange 17. The plunger retainer rod 30 may include either one or both of the securement structures 37A, 37B. An aspect of securement structures 37A, 37B can be combined with the other embodiments described herein. For example, the sheath structure may include scored structure 34C, expandable portion 34B, securement structures 37A, 37B, or any combination thereof

[0034] The syringe system 100 includes a valve 44 coupled to the distal end 12 of the syringe barrel 10. The valve can have a proximal port for fluidly coupling to the distal end 12 of the syringe barrel 10 and a distal port for fluidly coupling to a needle 52, with a valve member disposed between the ports that can be moved to place the valve 44 in an open configuration and a closed configuration. The valve 44 can be, for example, a two-way valve. The distal port may be configured as a needle hub 42 configured to receive a needle 52. The needle 52 may have a protective cap to prevent contamination. When the valve 44 is closed, a volume 15 is enclosed inside the bore 16 between the distal end 12 of the syringe barrel 10 and the plunger 22. The plunger 22 is retained in position by the plunger rod retainer 30 to maintain the volume 15.

[0035] A syringe system described herein can be made or manufactured by any suitable methods. In an embodiment, a syringe barrel can be provided, including a distal end, a distal end, and a bore extending between the distal end and the proximal end thereof. A plunger can be positioned in the bore of the syringe barrel. A plunger rod can be coupled to the plunger and configured to move the plunger between a first position adjacent the distal end of the syringe barrel and a second position adjacent the proximal end of the syringe barrel.

[0036] A plunger rod retainer of any one or combination of embodiments described herein can be removably coupled to the plunger rod to retain the plunger at a third position between the first position and the second position to determine a volume disposed in the bore between the distal end of the syringe barrel and the plunger. In an embodiment, a sheath structure can be removably wrapped around at least a portion of the plunger rod.

[0037] FIG. 3 illustrates a syringe 100-3 of the syringe system 100 of FIG. 1 after assembling. The plunger rod retainer 30 removably coupled to the plunger rod 20 can retain the plunger 22 at a predetermined position inside the bore 16. The predetermined position can correspond to a desired volume amount of fluid to be received in the syringe barrel. A volume 15 of gas is enclosed in the bore 16 between the distal end 12 of the syringe barrel 10and the plunger 22 when the valve 44 is closed. In the depicted embodiment, the plunger rod retainer 30 is removably wrapped around a portion of the plunger rod 20. The distal end 31 of the plunger rod retainer 30 engages with the proximal end 14 of the syringe barrel 10 to prevent the plunger 22 from moving inside the bore 16.

[0038] In an embodiment, a location of the distal end 31 of the plunger rod retainer 30 between opposite ends 21 , 23 of the plunger rod 20 can be determined to determine the volume 15 disposed in the bore 16 between the distal end 12 of the syringe barrel 10 and the plunger 22. For example, as illustrated in FIG. 1, the distal end 31 of the plunger rod retainer 30 is positioned at a location with the distance d with respect to the distal end 21 of the plunger rod 20, to which the plunger 22 is attached. When the portion 20-1 of the plunger rod 20 and the plunger 22 are inserted into the bore 16, the distal end 31 of the plunger rod retainer 30 engages with the proximal end 14 of the syringe barrel 10 to retain the plunger 22 in position, e.g., at a location inside the bore 16 about the depth d from the proximal end 14 of the syringe barrel 10.

[0039] As shown in Fig. 3, the predetermined volume 15 is disposed in the bore 16 between the distal end 12 of the syringe barrel 10 and the plunger 22. The volume 15 can be determined based on the depth d of the plunger 22. For example, the volume 15 may have a first volume vl corresponding to a first depth dl, a second volume v2 corresponding to a second depth d2, etc. For a given syringe barrel 10, when the depth d increases, the volume 15 decreases.

[0040] In an embodiment, the depth d can be adjusted by adjusting the length L of the plunger rod retainer 30. When the length L of the plunger rod retainer 30 decreases, the depth d increases. For example, the depth d can be increased by removing one or more of the respective sections 32-1, 32-2 and 32-3 of the plunger rod retainer 30C as shown in FIG. 2C.

[0041] FIG. 4 illustrate a side view of a first syringe 100-1 and a second syringe 100-2 including the respective plunger rod retainers 30-1 and 30-2 having different lengths 11 and 12. The plunger rod retainers 30-1 and 30-2 can retain the respective plunger 22 at different positions inside the bore 16, e.g., at a first depth dl and at a second depth d2, respectively, which correspond to a first volume VI and a second volume V2 of the volume 15.

[0042] The gas pressure in the volume 15 can be reduced to generate a reduced pressure volume. The reduced pressure can be less than an atmospheric pressure (one atm, or 101.325kPa). For example, the reduced pressure may be at about 0.9 atm (91.193 kPa) or lower, at about 0.8 atm (81.060 kPa) or lower, at about 0.7 atm (70.928 kPa) or lower, at about 0.6 atm (60.795 kPa) or lower, at about 0.5 atm (50.663 kPa) or lower, at about 0.4 atm (40.530 kPa) or lower, at about 0.3 atm (30.398 kPa) or lower, at about 0.2 atm (20.265 kPa) or lower, or at about 0.1 atm (10.133 kPa) or lower.

[0043] In an embodiment, the reduced-pressure volume 15 can be generated by removing at least a portion of the gas (e.g., air), via the valve 44 coupled to the distal end 12 of the syringe barrel 10, out of the bore 16. In an embodiment, a vacuum pump (not shown) can be coupled to the valve 44 and used to remove the gas from the bore 16 to generate the reduced-pressure volume 15. When the pressure is reduced to a predetermined value, the valve 44 can be closed to enclose and seal the reduced-pressure volume 15 between the distal end 12 of the syringe barrel 10 and the plunger 22. During the process of reducing the gas pressure inside the bore 16, the plunger rod retainer 30 can secure the plunger rod 20 and the plunger 22 in position to prevent the plunger 22 from moving inside the bore 16, e.g., preventing the plunger 22 from moving toward or away from the distal end 12 of the syringe barrel 10.

[0044] In an embodiment, the distal end 12 of the syringe barrel 10 can be in a fluid communication with a pressure reduction space to remove the gas from the bore 16 to the pressure reduction space. For example, the syringe 100-3 as shown in FIG. 3 can be positioned inside a pressure reduction chamber (not shown) having a predetermined gas pressure lower than atmospheric pressure. The valve 44 can be open to allow the gas inside the bore 16 to flow into the pressure reduction chamber due to the pressure difference. When the pressure in the volume 15 is reduced to a predetermined value, the valve 44 can be closed to enclose and seal the reduced-pressure volume 15 between the distal end 12 of the syringe barrel 10 and the plunger 22. During the process of removing the gas out of the bore 16 to reduce the gas pressure, the plunger rod retainer 30 can retain the plunger rod 20 and the plunger 22 in position to prevent the plunger 22 from moving inside the bore 16, e.g., preventing the plunger 22 from moving toward or away from the distal end 12 of the syringe barrel 10.

[0045] In an embodiment, a medication delivery device package can be provided to a user prior to delivering an injectable drug to a subject. The medication delivery device package may include a syringe at a first configuration, such as, for example, the syringe 100-3 of FIG. 3 including a reduced-pressure volume 15. The reduced-pressure volume 15 is predetermined. In other words, the volume 15 is at a predetermined, reduced pressure, and the plunger rod retainer 30 has a predetermined length or position to secure the plunger 22 at a predetermined position. The valve 44 is closed to enclose and seal the reduced-pressure volume 15. In an embodiment, the amount of an injectable drug, Va, that can be transferred into the syringe may be marked on the syringe barrel 10 of the syringe. It is desirable to have a predictable amount of an injectable drug transferred.

[0046] In an embodiment, a medication delivery device package can be provided to a user prior to delivering an injectable drug to a subject. The medication delivery device package may include a syringe system to be prepared to form the first configuration. For example, the syringe 100-3 of FIG. 3 including the volume 15 at atmospheric pressure can be prepared to generate a reduced-pressure volume. A vacuum pump can be provided with the medication delivery device package to reduce the pressure in the volume 15 to a predetermined, reduced pressure. The valve 44 is then closed to enclose and seal the reduced- pressure volume 15. Based on the predetermined, reduced pressure, the amount of an injectable drug, Va, that can be transferred into the syringe can be determined, which can be marked on the syringe barrel 10 of the syringe.

[0047] hi an embodiment, a medication delivery device package can be provided to a user prior to delivering an injectable drug to a subject. The medication delivery device package may include a syringe system to be assembled and prepared to form the first configuration. The medication delivery device package may include, for example, at least some components of the syringe system 100 of FIG. 1 prior to assembling. A user (e.g., a pharmacist) can assemble the components of the syringe system 100 to form a syringe at the first configuration including the reduced-pressure volume 15. The amount of an injectable drug, Va, that can be transferred into the syringe can be determined, which can be marked on the syringe barrel 10 of the syringe.

[0048] According to an embodiment, a method of delivering an injectable drug to a subject using a syringe described herein is provided. The syringe is at a first configuration with a predetermined volume disposed in a bore thereof including a gas at a first pressure. A plunger rod retainer is removably coupled to a plunger rod of the syringe and configured to retain a plunger of the syringe coupled to the plunger rod at a position inside the bore. A distal end of the syringe can be coupled to an internal chamber of a vial containing theinjectable drug at a second pressure relatively higher than the first pressure. A valve coupled to the distal end of the syringe can be open to permit the injectable drug to flow, under a pressure difference between the first pressure and the second pressure, from the internal chamber of the vial into the bore of the syringe to change the syringe from the first configuration to a second configuration with the predetermined volume at least partially filled with the injectable drug. When the syringe is at the second configuration, the plunger rod retainer can be removed from the plunger rod to allow the plunger to move inside the bore to deliver the injectable drug to a subject.

[0049] FIG. 5 is a side view of the syringe system 100 to transfer an injectable drug from a vial 60, typically at atmospheric pressure, into the bore 16. Prior to the transferring, the syringe system 100 is at a first configuration, and the predetermined volume 15 includes a gas having a reduced pressure. The needle 52 is attached to the needle hub 42 adjacent to the distal end 12 of the syringe barrel 10. The needle 52 pierces a septum 61 of the vial 60 to allow the distal end 12 of the syringe barrel 10 to fluidly couple to an internal chamber of the vial 60 containing the injectable drug 62. The injectable drug 62 in the internal chamber of the vial 60 is exposed to a second pressure (e.g., atmospheric pressure) relatively higher than the reduced pressure of the volume 15. The valve 44 is open to allow the injectable drug 62 to flow from the vial 60 to the bore 16 of the syringe barrel 10. Flow of the injectable drug may terminate when any gas in the reduced-pressure volume 15 is sufficiently compressed and reaches atmospheric pressure or, if the reduced-pressure volume 15 is a vacuum, when the volume 15 is filled by the injectable drug 62. During the process of transferring the drug into the bore 16, the plunger rod retainer 30 can secure the plunger rod 20 and the plunger 22 in position to prevent the plunger 22 from moving inside the bore 16, e.g., preventing the plunger 22 from moving toward or away from the distal end 12 of the syringe barrel 10.

[0050] The initial pressure of the reduced-pressure volume 15 may affect the volume of injectable drug that is aspirated from the vial 60 and transferred to the bore 16 of the syringe barrel 10. More specifically, and based on the ideal gas law (if the temperature and amount of any gas in the reduced-pressure volume 15 remain constant), the amount of an injectable drug, Va, transferred into the bore 16 of the of the syringe barrel 10 is as follows:

[0051] Va = V (1 - (Pinitial / Pfmal),

[0052] where V is the initial volume of the reduced-pressure volume 15, Pmitiai is the initial pressure of the reduced-pressure volume 15, and Pfmaiis the final pressure of thereduced-pressure volume 15, which is, after transferring the injectable drug to the bore 15, typically atmospheric pressure. The initial volume V of the reduced-pressure volume 15 can be predetermined by choosing a plunger rod retainer having a desired length and / or positioning the plunger rod retainer at a desired position on the plunger rod, according to some embodiments described herein.

[0053] In an embodiment, the length of the plunger rod retainer 30 can be varied to aspirate different volumes of drug product into the bore of a syringe barrel. For example, the first syringe 100-1 and the second syringe 100-2 of FIG. 4 may each include a 1-mL bore. The plunger rod retainers 30-1 and 30-2 may have a length of, for example, 7.0 cm and 3.5 cm, respectively. The corresponding first volume V 1 and second volume V2 can be, for example, 1.0 mL and 0.5 mL, respectively. At a reduced pressure of 0.5 atm for the first / second volume V1 / V2, the first syringe 100-1 can aspirate 0.5 mL of drug product, and the second syringe 100-2 can aspirate 0.25 mL of drug product. It is to be understood that the plunger rod retainers may have any desired length that is no greater than the length of the corresponding plunger rod, the first / second volume V1 / V2 may have any desired volume that is no greater than the initial volume of the syringe barrel, and the first / second volume V1 / V2 may have any desired value of reduced pressure that is less than one atm, depending on the desired volume of drug product to be aspirated.

[0054] After transferring the pre-determined amount of injectable drug 62 to the bore 15, the syringe system 100 is at a second configuration, and the predetermined volume 15 includes the pre-determined amount of injectable drug. The valve 44 can be closed to enclose and seal the pre-determined amount of injectable drug inside the bore 15, which can be delivered to a subject via the needle 52 attached to the needle hub 42. The pre-determined amount of injectable drug can be delivered by a user inserting the needle 52 into a subject patient (subcutaneous, intramuscular, intravenous, etc.), opening the valve 44, and applying a pressure at the thumb tab 26 to drive the plunger 22 and injectable drug through the needle and into the subject.

[0055] When the syringe is at the second configuration, e.g., containing the predetermined amount of injectable drug in the bore, the plunger rod retainer 30 can be removed from the plunger rod 20. In an embodiment, the plunger rod retainer 30 can be removed by, for example, disengaging a locking mechanism of a sheath structure to allow the sheath structure to be removed from the plunger rod. For example, the plunger rod retainer 30A inFIG. 2A can be removed by disengaging the pair of locking members 34A. In an embodiment, the plunger rod retainer 30 can be removed by, for example, expanding an expandable portion of a sheath structure to allow the sheath structure to be removed from the plunger rod. For example, the plunger rod retainer 30B in FIG. 2B can be removed by expanding the expandable portion 34B of the sheath structure 32. In an embodiment, the plunger rod retainer 30 can be removed by, for example, disengaging the distal end 31 of the plunger rod retainer 30 and the proximal end 14 of the syringe barrel 10. For example, the plunger rod retainer 30D in FIG. 2D can be removed by disengaging the connection mechanism 34D at the distal end 31 of the sheath structure 32 and the proximal end 14 of the syringe barrel 10. After the removal of the plunger rod retainer 30 from the plunger rod 20, the plunger rod 20 can be pushed to move the plunger 22 to expel the drug from the bore 16.

[0056] The syringe systems described herein under a reduced pressure can be manufactured in bulk and distributed to a compounding pharmacy. Alternatively, individual components could be kitted and distributed to a compounding pharmacy, where it is assembled to form the syringe systems described herein and with a vacuum pump to prepare the syringes at a reduced pressure.

[0057] FIG. 7 shows an embodiment of a method of making a syringe system (shown as 200). At step 202, a syringe barrel is provided. The syringe barrel includes a distal end, a proximal end, and a bore extending between the distal end and the proximal end thereof. At step 204, a plunger is positioned in the bore of the syringe barrel. The positioning is at a predetermined positioned corresponding to an amount a fluid to be received. The plunger rod is coupled to the plunger and configured to move the plunger distally between a first position and a second position. At step 206, a plunger rod retainer is coupled to the plunger rod. This is to retain the plunger at the predetermined position. At step 208, a pressure in the bore is reduced to less than an atmospheric pressure. This is to generate a volume disposed in the bore between the distal end of the syringe barrel and the plunger. The volume includes a gas having a reduced pressure. Other method steps can be arrived at with what is disclosed herein.

[0058] FIG. 8 shows an embodiment of a method of delivering an injectable drug using a syringe system (shown as 300). The syringe system is at a first configuration with a predetermined volume disposed in a bore thereof including a gas at a first pressure. The syringe system further includes a plunger rod retainer of any one or combination ofembodiments described herein removably coupled to a plunger rod and configured to retain a plunger coupled to the plunger rod at a position inside the bore. At step 302, a distal end of a syringe barrel is coupled to an internal chamber of a vial. The vial contains the injectable drug at a second pressure relatively higher than the first pressure. At step 304, the injectable drug is permitted to flow, under a pressure difference. The pressure difference is between the first pressure and the second pressure. The flow is from the internal chamber of the vial into the bore of the syringe barrel to change the syringe system from the first configuration to a second configuration with the predetermined volume at least partially filled with the injectable drug. At step 306, the plunger rod retainer is removed from the plunger rod. This is to allow the plunger to move inside the bore to deliver the injectable drug from the bore. Other method steps can be arrived at with what is disclosed herein.

[0059] While the embodiments herein have been described as having exemplary designs, the present disclosure can be further modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the disclosure using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this disclosure pertains.

[0060] Various aspects are described in this disclosure, which include, but are not limited to, the following aspects:

[0061] Aspect 1. A syringe system comprising: a syringe barrel including a distal end, a distal end, and a bore extending between the distal end and the proximal end thereof; a plunger received in the bore of the syringe barrel; a plunger rod coupled to the plunger and configured to move the plunger between a first position and a second position; a plunger rod retainer removably coupled to the plunger rod and configured to retain the plunger at a fixed position at the first position; and a volume disposed in the bore between the distal end of the syringe barrel and the plunger, wherein when the syringe system is at a first configuration, the volume includes a gas having a reduced pressure, and when the syringe system is at a second configuration, the volume includes an injectable drug.

[0062] Aspect 2. The syringe system of Aspect 1 , wherein the plunger rod retainer comprises a sheath structure wrapping around at least a portion of the plunger rod.

[0063] Aspect 3. The syringe system of Aspect 2, wherein the sheath structure has at least one of a distal end configured to engage with the proximal end of the syringe barrel toprevent the plunger from moving distally inside the bore and a proximal end configured to abut against a radial flange of the plunger to prevent the plunger from moving proximally from inside the bore.

[0064] Aspect 4. The syringe system of Aspect 2, wherein the sheath structure includes at least one of an expandable portion to allow the sheath structure to be removed from the plunger rod or a scored structure configured to facilitate removal of a section from the sheath structure.

[0065] Aspect 5. The syringe system of Aspect 2, wherein the sheath structure includes a disengageable locking mechanism to allow the sheath structure to be removed from the plunger rod.

[0066] Aspect 6. The syringe system of any one of Aspects 1-5, further comprising a valve coupled to the distal end of the syringe barrel.

[0067] Aspect 7. The syringe system of any on one Aspects 1-6, further comprising a needle hub at the distal end of the syringe barrel and configured to receive a needle.

[0068] Aspect 8. A method of making a syringe system, the method comprising: providing a syringe barrel including a distal end, a distal end, and a bore extending between the distal end and the proximal end thereof; positioning a plunger in the bore of the syringe barrel at a predetermined positioned corresponding to an amount a fluid to be received, wherein a plunger rod is coupled to the plunger and configured to move the plunger distally between a first position and a second position; coupling a plunger rod retainer to the plunger rod to retain the plunger at the predetermined position; and reducing a pressure in the bore to less than an atmospheric pressure to generate a volume disposed in the bore between the distal end of the syringe barrel and the plunger, the volume including a gas having a reduced pressure.

[0069] Aspect 9. The method of Aspect 8, wherein the plunger rod retainer comprises a sheath structure wrapping around at least a portion of the plunger rod.

[0070] Aspect 10. The method of Aspect 9, wherein the sheath structure has at least one of a distal end configured to engage with the proximal end of the syringe barrel and a proximal end configured to abut against a radial flange of the plunger to prevent the plunger from moving inside the bore.

[0071] Aspect 11. The method of Aspect 9, wherein the sheath structure includes an expandable portion to allow the sheath structure to be removed from the plunger rod.

[0072] Aspect 12. The method of Aspect 9, wherein the sheath structure includes a disengageable locking mechanism to allow the sheath structure to be removed from the plunger rod.

[0073] Aspect 13. The method of any one of Aspects 8-12, wherein reducing the pressure in the bore further comprises drawings at least a portion of the gas, via a valve coupled to the distal end of the syringe barrel, out of the bore.

[0074] Aspect 14. The method of Aspect 13, further comprising closing the valve to seal the volume including the gas having the reduced pressure inside the bore.

[0075] Aspect 15. A method of delivering an injectable drug using a syringe, the syringe being at a first configuration with a volume disposed in a bore thereof including a gas at a first pressure, the method comprising: coupling a distal end of a syringe barrel to an internal chamber of a vial containing the injectable drug at a second pressure relatively higher than the first pressure; permitting the injectable drug to flow, under a pressure difference between the first pressure and the second pressure, from the internal chamber of the vial into the bore of the syringe barrel to change the syringe from the first configuration to a second configuration with the volume including the injectable drug; and removing a plunger rod retainer from a plunger rod to allow a plunger coupled to the plunger rod to move inside the bore to deliver the injectable drug from the bore.

[0076] Aspect 16. The method of Aspect 15, wherein the plunger rod retainer comprises a sheath structure wrapping around at least a portion of the plunger rod.

[0077] Aspect 17. The method of Aspect 16, wherein removing the plunger rod retainer further comprises expanding an expandable portion of the sheath structure to allow the sheath structure to be removed from the plunger rod.

[0078] Aspect 18. The method of Aspect 16, wherein removing the plunger rod retainer further comprises disengaging a locking mechanism of the sheath structure to allow the sheath structure to be removed from the plunger rod.

[0079] Aspect 19. The method of any one of Aspects 15-18, wherein permitting the injectable drug to flow from the internal chamber of the vial into the bore of the syringe barrel further comprises opening a valve coupled to the distal end of the syringe barrel.

[0080] Aspect 20. The method of Aspect 19, further comprising closing the valve to seal the volume including the injectable drug inside the bore before removing the plunger rod retainer.

Claims

WHAT IS CLAIMED IS1. A syringe system comprising: a syringe barrel including a distal end, a proximal end, and a bore extending between the distal end and the proximal end thereof; a plunger received in the bore of the syringe barrel; a plunger rod coupled to the plunger and configured to move the plunger between a first position and a second position; a plunger rod retainer removably coupled to the plunger rod and configured to retain the plunger at a fixed position at the first position; and a volume disposed in the bore between the distal end of the syringe barrel and the plunger, wherein when the syringe system is at a first configuration, the volume includes a gas having a reduced pressure, and when the syringe system is at a second configuration, the volume includes an injectable drug.

2. The syringe system of claim 1, wherein the plunger rod retainer comprises a sheath structure wrapping around at least a portion of the plunger rod.

3. The syringe system of claim 2, wherein the sheath structure has at least one of a distal end configured to engage with the proximal end of the syringe barrel to prevent the plunger from moving distally inside the bore and a proximal end configured to abut against a radial flange of the plunger to prevent the plunger from moving proximally from inside the bore.

4. The syringe system of claim 2, wherein the sheath structure includes at least one of an expandable portion to allow the sheath structure to be removed from the plunger rod or a scored structure configured to facilitate removal of a section from the sheath structure.

5. The syringe system of claim 2, wherein the sheath structure includes a disengageable locking mechanism to allow the sheath structure to be removed from the plunger rod.

6. The syringe system of any one of claims 1-5, further comprising a valve coupled to the distal end of the syringe barrel.

7. The syringe system of any one of claims 1-6, further comprising a needle hub at the distal end of the syringe barrel and configured to receive a needle.

8. A method of making a syringe system, the method comprising: providing a syringe barrel including a distal end, a distal end, and a bore extending between the distal end and the proximal end thereof; positioning a plunger in the bore of the syringe barrel at a predetermined positioned corresponding to an amount a fluid to be received, wherein a plunger rod is coupled to the plunger and configured to move the plunger distally between a first position and a second position; coupling a plunger rod retainer to the plunger rod to retain the plunger at the predetermined position; and reducing a pressure in the bore to less than an atmospheric pressure to generate a volume disposed in the bore between the distal end of the syringe barrel and the plunger, the volume including a gas having a reduced pressure.

9. The method of claim 8, wherein the plunger rod retainer comprises a sheath structure wrapping around at least a portion of the plunger rod.

10. The method of claim 9, wherein the sheath structure has at least one of a distal end configured to engage with the proximal end of the syringe barrel and a proximal end configured to abut against a radial flange of the plunger to prevent the plunger from moving inside the bore.1 1. The method of claim 9, wherein the sheath structure includes an expandable portion to allow the sheath structure to be removed from the plunger rod.

12. The method of claim 9, wherein the sheath structure includes a disengageable locking mechanism to allow the sheath structure to be removed from the plunger rod.

13. The method of any one of claims 8-12, wherein reducing the pressure in the bore further comprises drawings at least a portion of the gas, via a valve coupled to the distal end of the syringe barrel, out of the bore.

14. The method of claim 13, further comprising closing the valve to seal the volume including the gas having the reduced pressure inside the bore.

15. A method of delivering an injectable drug using a syringe, the syringe being at a first configuration with a volume disposed in a bore thereof including a gas at a first pressure, the method comprising: coupling a distal end of a syringe barrel to an internal chamber of a vial containing the injectable drug at a second pressure relatively higher than the first pressure; permitting the injectable drug to flow, under a pressure difference between the first pressure and the second pressure, from the internal chamber of the vial into the bore of the syringe barrel to change the syringe from the first configuration to a second configuration with the volume including the injectable drug; and removing a plunger rod retainer from a plunger rod to allow a plunger coupled to the plunger rod to move inside the bore to deliver the injectable drug from the bore.

16. The method of claim 15, wherein the plunger rod retainer comprises a sheath structure wrapping around at least a portion of the plunger rod.

17. The method of claim 16, wherein removing the plunger rod retainer further comprises expanding an expandable portion of the sheath structure to allow the sheath structure to be removed from the plunger rod.

18. The method of claim 16, wherein removing the plunger rod retainer further comprises disengaging a locking mechanism of the sheath structure to allow the sheath structure to be removed from the plunger rod.

19. The method of any one of claims 15-18, wherein permitting the injectable drug to flow from the internal chamber of the vial into the bore of the syringe barrel further comprises opening a valve coupled to the distal end of the syringe barrel.

20. The method of claim 19, further comprising closing the valve to seal the volume including the injectable drug inside the bore before removing the plunger rod retainer, and opening the valve after the removing step, and applying a pressure to the plunger rod to deliver the injectable drug.

Images