Barrel-coated sequential stoppers for multi-chamber syringes

Abstract

A stopper for a multi-chamber syringe includes a body having a first end surface, a second end surface, a peripheral surface extending between the first and second end surfaces, and at least one slit extending through the body for allowing fluid to flow through the body of the stopper. The stopper includes a first barrier film attached to the first end surface of the body and a second barrier film attached to the second end surface of the body. The first barrier film and / or the second barrier film include a slit or opening that coincides with the slit extending through the body to allow fluid to flow through the stopper. Provided herein are a multi-chamber syringe including this stopper, as well as a method for making this stopper.

Description

[Technical Field]

[0001] Cross-references to related literature This application claims priority to U.S. patent application Ser. No. 17 / 972,620, filed Oct. 25, 2022, and entitled "Barrel-Coated Sequential Stopper for Multi-Chamber Syringe," the entire disclosure of which is incorporated herein by reference.

[0002] The present application relates generally to stoppers configured for use with syringes containing multiple fluid doses, and particularly to stoppers for syringes that provide for the release of a first or initial fluid, such as a first type of medical fluid, followed by the release of a second fluid, such as a different type of medicinal fluid or a flush solution. [Background technology]

[0003] Multi-chamber syringes can be used for sequential delivery of a second medical fluid following administration of a first medical fluid. Conventional multi-chamber syringes generally include a syringe barrel having a proximal chamber and a distal chamber separated by a stopper, seal, valve, or film to separate the first fluid from the second fluid. Conventional multi-chamber syringes also include a plunger mechanism for sequentially ejecting the first and second fluids from the syringe barrel. Specific examples of conventional syringe barrels and multi-chamber syringes with plunger mechanisms for sequentially ejecting the first and second fluids from the syringe barrel are described in U.S. Patent No. 5,623,999, entitled "Dual-Chamber Syringe and Associated Linking System," and U.S. Patent No. 5,623,999, entitled "Modular Dual-Chamber Syringe System."

[0004] The multi-chamber syringe may include or be connected to a needle cannula, such as a pen syringe with a sharp tip, for injecting a second medical fluid, subsequent to a first medical fluid, directly into a patient's blood vessel. Alternatively, the multi-chamber syringe may be configured to be connected to a vascular access device (VAD), such as an intravenous (IV) catheter (e.g., a peripheral catheter or a central venous catheter), or another fluid delivery device for sequential delivery of a second medical fluid, subsequent to a first medical fluid, through the VAD.

[0005] In some cases, a multi-chamber syringe is used to deliver a second type of therapeutic agent or drug following a first type of therapeutic agent or drug. The multi-chamber syringe can be used to provide a flushing solution through the VAD before and / or after the administration of a therapeutic agent. In particular, flushing procedures can be performed before or after the administration of a therapeutic agent to confirm catheter patency, avoid drug incompatibilities, ensure a complete drug dose is administered to the patient, prevent thrombus formation, and / or minimize the risk of bloodstream infections resulting from VAD contamination. Additionally, flushing can prevent the accumulation of blood deposits, blood debris, and IV medications within the catheter or other VAD devices.

[0006] Multi-chamber syringes may be provided as pre-filled syringes, with the syringe chambers filled with a first fluid and / or a second fluid during manufacture and prior to shipment to the medical facility for use. In such cases, it is important that the fluids in contact with the surfaces of the multi-chamber syringe are sealed and / or coated with a biocompatible protective coating or layer to prevent degradation or contamination of the medical fluid contained in the syringe prior to use.

[0007] A problem with conventional multi-chamber syringes is the difficulty of coating all surfaces of the syringe, stopper, and other components that may come into contact with the fluid in the pre-filled syringe to prevent contamination. The stoppers, syringes, and assembly methods of the present disclosure are provided to address these problems. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] U.S. Patent No. 9,940,114 [Patent Document 2] U.S. Patent No. 9,833,572 [Patent Document 3] U.S. Patent Application No. 2020 / 0061297 Published [Patent Document 4] WO2022 / 109214A1 publication Summary of the Invention

[0009] In accordance with an embodiment of the present disclosure, a stopper for a multi-chamber syringe includes a body having a first end surface, a second end surface, a peripheral surface extending between the first and second end surfaces, and at least one slit extending through the body for permitting fluid flow through the body of the stopper. The stopper includes a first barrier film attached to the first end surface of the body and a second barrier film attached to the second end surface of the body. The first barrier film and / or the second barrier film include slits or openings that coincide with the slits extending through the body to permit fluid flow through the stopper.

[0010] In accordance with another embodiment of the present disclosure, a multi-chamber syringe for sequential release of at least a first fluid followed by a second fluid comprises a first end, a second end comprising fluid ports for release of the first and second fluids from the barrel, and a sidewall extending between the first and second ends of the barrel. The syringe also comprises a first stopper and a second stopper slidably disposed in the barrel. The second stopper may comprise any of the stopper features described above for a multi-chamber syringe. The first and second stoppers define a first chamber of the syringe barrel between the first and second stoppers configured to contain the second fluid, and a second chamber between the second stopper and the second end of the syringe barrel configured to contain the first fluid.

[0011] In accordance with another embodiment of the present disclosure, a pre-filled syringe comprises the multi-chamber syringe described above and a predetermined volume of a second fluid disposed in a first chamber of the pre-filled syringe, the pre-filled syringe being provided with the first chamber fluidly separated from the second chamber, thereby containing the predetermined volume of the second fluid within the pre-filled syringe.

[0012] In accordance with another embodiment of the present disclosure, a method for sequentially expelling fluids from the previously described pre-filled syringe includes moving a plunger rod fixedly connected to a first stopper of the syringe in a proximal direction, which moves a second stopper of the syringe in a proximal direction to aspirate a first fluid into a second chamber of the syringe barrel, and once the first fluid is in the second chamber, moving the plunger rod in a distal direction in one continuous motion, thereby expelling a second fluid, subsequent to the first fluid, from a fluid port of the syringe barrel.

[0013] According to another embodiment of the present disclosure, a molding method for the aforementioned stopper for a multi-chamber syringe includes molding a first part and a second part of the body of the stopper into a partially molded state. The method includes joining a first barrier film to a first end of the partially molded first part and joining a second barrier film to a second end of the partially molded second part. The method also includes bonding the first part to the second part in a final molding, thereby forming a stopper comprising a body having the first and second barrier films laminated to the body. Finally, the method includes forming a slit through the body and through the first barrier film and / or the second barrier film.

[0014] Non-limiting illustrative examples of embodiments of the present disclosure will be described in the following paragraphs.

[0015] (Clause 1) A stopper for a multi-chamber syringe, the stopper comprising: a body having a first end surface, a second end surface, a peripheral surface extending between the first and second end surfaces, and at least one slit extending through the body for permitting fluid flow through the body of the stopper; a first barrier film adhered to the first end surface of the body; and a second barrier film adhered to the second end surface of the body, the first barrier film and / or the second barrier film having a slit or opening that coincides with the slit extending through the body to permit fluid flow through the stopper.

[0016] (Clause 2) The stopper of clause 1, further comprising at least one protruding portion extending axially from the proximal end of the body for separating the stopper from another stopper of a multi-chamber syringe.

[0017] (Clause 3) The stopper of clause 1 or clause 2, wherein the peripheral surface of the body includes at least one rib configured to contact the inner surface of the sidewall of the syringe barrel and at least one recessed portion configured to be spaced apart from the inner surface of the sidewall of the syringe barrel.

[0018] (Clause 4) The stopper of any one of clauses 1 to 3, wherein the first stopper and / or the second stopper comprises a thermoplastic elastomer such as silicone, polypropylene, polyethylene, or synthetic or natural rubber (e.g., isoprene).

[0019] (Clause 5) The stopper of any one of clauses 1 to 4, wherein the body further comprises a bore extending axially through a portion of the body from the first end toward the second end of the body.

[0020] (Clause 6) The stopper of clause 5, wherein the hole has an open first end, a closed second end having a substantially flat second surface, and an annular side surface between the first end and the second end, the annular side surface having a recessed portion and a protruding portion.

[0021] (Clause 7) The stopper of clause 6, wherein the slit extending through the body extends between the flat second surface of the bore and the second end surface of the body.

[0022] (Clause 8) The stopper of any one of clauses 1 to 7, wherein at least one slit extends substantially transverse to the central longitudinal axis.

[0023] (Clause 9) The stopper of any one of clauses 1 to 8, wherein the body is made by joining two separately molded parts together by a continuous molding process.

[0024] (Clause 10) The stopper of clause 9, wherein the two separately molded parts of the body are each formed by one-shot injection molding.

[0025] (Clause 11) The stopper according to any one of clauses 1 to 10, wherein the stopper is A stopper configured to move between (i) a closed position, which prevents fluid from passing through the slit in the body, when the fluid pressure in the syringe barrel is equal to or less than a predetermined opening pressure, and (ii) an open position, which establishes fluid communication between the chambers of the syringe barrel through the stopper, when the fluid pressure in the syringe barrel is at or above the predetermined opening pressure.

[0026] (Clause 12) The stopper of any one of clauses 1 to 11, wherein the slit in the body is biased and is initially provided in a closed position.

[0027] (Clause 13) The stopper of any one of clauses 1 to 12, wherein the first barrier film and / or the second barrier film comprises a disk having a diameter matching the diameter of the first end surface or the second end surface of the body.

[0028] (Clause 14) The stopper of any one of clauses 1 to 13, wherein the first barrier film extends over an annular surface of the body and a surface of the hole defined by the body.

[0029] (Clause 15) The stopper of any one of clauses 1 to 14, wherein the second barrier film extends over a flat or substantial surface of the body.

[0030] (Clause 16) The stopper of any one of clauses 1 to 15, wherein the first barrier film and / or the second barrier film comprises a fluoropolymer such as polyethylene tetrafluoroethylene (PTEE).

[0031] (Clause 17) A stopper according to any one of clauses 1 to 16, wherein the peripheral surface of the main body is free of a barrier film.

[0032] (Clause 18) A stopper according to any one of clauses 1 to 17, wherein the peripheral surface of the main body is not coated.

[0033] (Clause 19) The stopper according to any one of clauses 1 to 18, wherein the first barrier film and / or the second barrier film has a thickness of about 0.013 mm to about 0.25 mm.

[0034] (Clause 20) A multi-chamber syringe for sequentially discharging at least a first fluid followed by a second fluid, the syringe comprising: a barrel having a first end, a second end having fluid ports for discharging the first fluid and the second fluid from the barrel, a sidewall extending between the first and second ends of the barrel; a first stopper slidably positioned in the barrel; and a second stopper having a stopper according to any one of clauses 1 to 19 slidably positioned in the barrel, wherein the first stopper and the second stopper define a first chamber in the syringe barrel between the first and second stoppers configured to contain the second fluid, and a second chamber in the syringe barrel between the second stopper and the second end of the syringe barrel configured to contain the first fluid.

[0035] (Clause 21) A syringe according to Clause 20, wherein the slit in the body is configured to move between (i) a closed position that prevents fluid from passing through the slit in the body when the fluid pressure in the first chamber is equal to or less than a predetermined opening pressure, and (ii) an open position that establishes fluid communication between the first chamber and the second chamber through the second stopper when the fluid pressure in the first chamber is equal to or greater than the predetermined opening pressure.

[0036] (Clause 22) A syringe according to clause 20 or clause 21, wherein movement of the first stopper in a proximal direction through the barrel causes movement of the second stopper in a proximal direction, causing the first fluid to be drawn into the second chamber through the fluid port of the barrel.

[0037] (Clause 23) The syringe of any of Clauses 20 to 22, wherein advancing the first stopper through the barrel moves the second stopper through the barrel and expels the first fluid from the second chamber through the fluid port of the barrel.

[0038] (Clause 24) A syringe according to any one of clauses 20 to 23, wherein movement of the first stopper towards the second stopper, together with the second stopper in its most distal position, increases the fluid pressure in the first chamber in the direction of a predetermined opening pressure for the slit in the body.

[0039] (Clause 25) The syringe of clause 24, wherein when the slit opens, continued distal movement of the first stopper toward the second stopper moves the second fluid from the first chamber, through the slit in the body of the second stopper, to the second chamber and to the fluid port in the barrel, thereby expelling the second fluid from the barrel.

[0040] (Clause 26) The syringe according to any one of Clauses 20 to 25, wherein the barrel contains at least one of polyester, polycarbonate, polypropylene, polyethylene, polyethylene terephthalate, and acrylonitrile butadiene styrene.

[0041] (Clause 27) The syringe of any one of Clauses 20 to 26, wherein the first stopper and / or the second stopper comprises a thermoplastic elastomer such as silicone, polypropylene, polyethylene, or synthetic or natural rubber (e.g., isoprene).

[0042] (Clause 28) The syringe of any one of clauses 20 to 27, wherein the slit in the body of the second stopper is biased and is initially provided in a closed position.

[0043] (Clause 29) The syringe of any one of clauses 20 to 28, further comprising a plunger rod coupled to the first stopper for moving the first stopper through the barrel.

[0044] (Clause 30) The syringe of clause 29, wherein the second fluid, following the first fluid, is expelled from the syringe barrel by one continuous movement of the plunger rod distally into the syringe barrel.

[0045] (Clause 31) The syringe of clause 29 or clause 30, wherein the syringe is configured such that, following the first fluid, the second fluid is expelled from the syringe barrel by a single manual actuation of the plunger rod.

[0046] (Clause 32) The syringe of any of clauses 29 to 31, wherein the plunger rod has a proximal end with a press plate, a distal end with a thread connector, and a body extending between the proximal and distal ends.

[0047] (Clause 33) The syringe of clause 32, wherein the first stopper has a threaded hole that engages with the threaded connector of the plunger rod, thereby securing the plunger rod to the second stopper.

[0048] (Clause 34) A syringe according to any one of clauses 29 to 33, wherein the stopper is configured such that movement of the plunger rod in the proximal or distal direction moves both the first stopper and the second stopper.

[0049] (Clause 35) A syringe according to any one of clauses 29 to 34, wherein the plunger rod is fixedly connected to the first stopper, and the plunger rod and / or the first stopper is not connected to the second stopper.

[0050] (Clause 36) The syringe of any of clauses 29 to 35, further comprising a removable plunger cap engaged between the plunger rod and the barrel to prevent movement of the plunger rod until the removable plunger cap is removed from the syringe.

[0051] (Clause 37) A pre-filled syringe comprising the syringe of any one of clauses 20 to 36 and a predetermined volume of a second fluid disposed in a first chamber in the pre-filled syringe, the pre-filled syringe being provided with the first chamber fluidly separated from the second chamber, thereby containing the predetermined volume of the second fluid within the pre-filled syringe.

[0052] (Clause 38) A pre-filled syringe according to clause 37, wherein the second fluid comprises saline and / or heparin flush solution.

[0053] (Clause 39) A pre-filled syringe according to Clause 37, wherein the syringe further comprises a plunger rod connected to the first stopper for moving the first stopper and / or the second stopper through the barrel.

[0054] (Clause 40) The pre-filled syringe of clause 39, further comprising a removable plunger cap engaged between the plunger rod and the barrel to prevent movement of the plunger rod until the removable plunger cap is removed from the syringe, thereby: A prefilled syringe that maintains fluid separation between the first and second chambers until the removable plunger cap is removed.

[0055] (Clause 41) A method for sequentially expelling fluids from a prefilled syringe according to any one of clauses 37 to 40, said method comprising: moving a plunger fixedly connected to a first stopper of the syringe in a proximal direction, which moves a second stopper of the syringe in a proximal direction to aspirate a first fluid into a second chamber of the syringe barrel; and, upon dispensing the first fluid into the second chamber, moving a plunger rod in a distal direction in one continuous motion, thereby expelling a second fluid, following the first fluid, from a fluid port of the syringe barrel.

[0056] (Clause 42) The method of clause 41, wherein one continuous movement of the plunger rod is performed by one manual operation.

[0057] (Clause 43) The method of clause 41 or clause 42, wherein drawing the first fluid into the second chamber includes attaching a needle to a fluid port of a syringe, inserting the needle into a fluid container, and drawing the first fluid from the fluid container into the second chamber of the syringe.

[0058] (Clause 44) Any of the methods of clauses 41 to 43, further comprising connecting at least one patient to a fluid port of the syringe barrel before moving the plunger rod distally, and fluid expelled from the syringe is passed to the patient through at least one patient line.

[0059] (Clause 45) The method of any one of clauses 41 to 44, wherein the first fluid comprises a therapeutic agent.

[0060] (Clause 46) A molding method for a stopper of any of clauses 1 to 19, the method comprising the steps of: molding a first part and a second part of a body of the stopper into a partially molded state; connecting a first barrier film to a first end of the partially molded first part; connecting a second barrier film to a first end of the partially molded second part; adhering the first part to the second part in a final molding, thereby forming a stopper comprising a body having the first and second barrier films laminated to the body; and forming slits through the body and through the first barrier film and / or the second barrier film.

[0061] (Clause 47) The method of clause 46, wherein the first part and the second part are molded by one-shot injection molding.

[0062] (Clause 48) The method of clause 46 or clause 47, wherein the step of connecting the first barrier film to the first molded part includes adhering a flat sheet of barrier material to a first end of the first part and trimming the flat sheet to match the shape of the first end of the first part.

[0063] (Clause 49) The method of clause 48, wherein the step of connecting the second barrier film to the second molded part includes adhering a flat sheet of barrier material to the second end of the second part and trimming the flat sheet to match the shape of the second end of the second part.

[0064] (Clause 50) The method of any of clauses 46 to 49, wherein the step of bonding the parts together includes curing the parts at a temperature of about 50°C to about 70°C.

[0065] (Clause 51) The method of any of clauses 46 to 50, wherein the first barrier film and / or the second barrier film comprises a fluoropolymer.

[0066] (Clause 52) The method of any of clauses 46 to 51, wherein the first part and the second part are molded together along an uncoated surface of each part.

[0067] (Clause 53) The method of any of clauses 46 to 52, wherein the step of adhering the first part to the second part includes placing the first part in a front half of a mold and placing the second part in a rear half of the mold, and closing the mold to attach the parts together along their uncoated surfaces.

[0068] (Clause 54) The method of clause 53, wherein the separation lines between the components are relaxed to about 0.05 mm to about 0.2 mm.

[0069] (Clause 55) The method of clause 53 or clause 54, wherein the step of bonding the parts together includes applying sufficient temperature and pressure to mold and form a unitary body from the first part and the second part. [Brief explanation of the drawings]

[0070] [Figure 1A] FIG. 1A is a perspective view of a multi-chamber syringe according to an embodiment of the present disclosure. [Figure 1B] FIG. 1B is an enlarged perspective view of the multi-chamber syringe of FIG. 1A. [Figure 2A] 2A is a perspective view of a stopper of the multi-chamber syringe of FIG. 1A according to an embodiment of the present disclosure. [Figure 2B] FIG. 2B is a top plan view of the stopper of FIG. 2A. [Figure 2C] FIG. 2C is a cross-sectional view of the stopper of FIG. 2A. [Figure 3A] FIG. 3A is a side view of the multi-chamber syringe of FIG. 1A in an initial or partially filled position. [Figure 3B] FIG. 3B is a side view of the multi-chamber syringe of FIG. 1A in the filled position. [Figure 3C]FIG. 3C is a cross-sectional view of the multi-chamber syringe of FIG. 1A with a filled proximal chamber and an empty distal chamber. [Figure 3D] FIG. 3D is a side view of the multi-chamber syringe of FIG. 1A in a final position after ejection of the first and second fluids from the syringe. [Figure 4] FIG. 4 is a flow chart illustrating a method of expelling a medication fluid from the multi-chamber syringe of FIG. 1A. [Figure 5] FIG. 5 is a flow chart illustrating a method of forming a stopper having a barrier coating according to an embodiment of the present disclosure. [Figure 6A] FIG. 6A is a schematic diagram illustrating method steps for making a stopper having a barrier film that can be used in a multi-chamber syringe according to an embodiment of the present disclosure. [Figure 6B] FIG. 6B is a schematic diagram illustrating method steps for making a stopper having a barrier film that can be used in a multi-chamber syringe according to an embodiment of the present disclosure. [Figure 6C] FIG. 6C is a schematic diagram illustrating method steps for making a stopper having a barrier film that can be used in a multi-chamber syringe according to an embodiment of the present disclosure. [Figure 6D] FIG. 6D is a schematic diagram illustrating method steps for making a stopper having a barrier film that can be used in a multi-chamber syringe according to an embodiment of the present disclosure. [Figure 6E] FIG. 6E is a schematic diagram illustrating method steps for making a stopper having a barrier film that can be used in a multi-chamber syringe according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0071] The following description is presented to enable one of ordinary skill in the art to make and use the described embodiments contemplated for practicing the invention. Various modifications, equivalents, substitutions, and alternatives will be apparent to those skilled in the art. All such modifications, equivalents, substitutions, and alternatives are intended to be within the spirit and scope of the invention.

[0072] For purposes of the following description, the terms "upper," "lower," "right," "left," "vertical," "horizontal," "top," "bottom," "lateral," "longitudinal," and derivatives thereof, will refer to the present invention as they are oriented in the drawings. As used herein, the term "proximal" refers to the portion or end of a device, such as a syringe or catheter, that is grasped, manipulated, or used by a practitioner or another user. The term "distal" refers to the end or portion of a device that is furthest from the portion of the device that is grasped, manipulated, or used by a practitioner. For example, the "proximal end" of a syringe refers to the portion that a practitioner presses to advance a stopper through the syringe barrel. The "distal end" of a syringe refers to the end that is attached to a vascular access device or that includes a needle cannula configured to be inserted through a patient's skin. However, it should be understood that the present invention contemplates various alternative modifications unless expressly specified to the contrary. It should also be understood that the specific devices illustrated in the accompanying drawings and described in the following specification are merely exemplary embodiments of the present invention. Hence, specific dimensions and other physical characteristics related to the embodiments disclosed herein are not to be considered as limiting.

[0073] Referring to the drawings, the present disclosure relates to pistons, plungers, or stoppers 110, 112 for use with a multi-chamber syringe 10. One of the stoppers, referred to herein as the distal stopper 112, can be configured to separate a medication container, such as a syringe barrel, into a distal chamber containing a first or initial fluid to be injected into a patient and a proximal chamber containing a subsequent or second fluid to be delivered to the patient after the initial fluid. In some embodiments, the distal stopper 112 includes a built-in check valve that allows a second fluid contained in the proximal chamber of the syringe 10 to pass through the distal stopper 112 only after the first fluid has been expelled from the distal chamber of the syringe 10. Thus, the multi-chamber syringe 10 of the present disclosure can be used for fluid delivery of multiple medication fluids sequentially into a patient's blood vessel through a needle cannula inserted into the patient's blood vessel with only a single needle stick to be performed by the practitioner and without additional fluid delivery steps. In another embodiment, the multi-chamber syringe 10 of the present disclosure allows for the delivery of multiple medicinal fluids to a patient sequentially through a VAD without the need to attach multiple syringes or fluid containers to the VAD.

[0074] As described in more detail herein, the distal stopper 112 can also include a leachable / extractable barrier layer, coating, or film over the fluid in contact with the surface of the distal stopper 112. In particular, a first or proximal barrier coating or film can be disposed on the distal stopper 112 and in contact with the fluid contained in the proximal chamber, and a second or distal barrier coating or film can be disposed to contact the fluid contained in the distal chamber of the syringe 10. Having barrier layers, coatings, or films over both fluids in contact with the surface of the distal stopper 112 means that the syringe 10 can be used with sensitive drug fluids, such as drugs that are prone to degradation when placed in prolonged contact with another plastic material.

[0075] The present disclosure also relates to the function of a pre-filled or partially-filled multi-chamber syringe 10 that includes a proximal stopper 110 and a distal stopper 112. In particular, the multi-chamber syringe 10 can be configured to expel a second fluid from the syringe through a fluid port or nozzle of the syringe 10, following a first fluid. As previously mentioned, the first fluid, as used herein, can be a medicinal fluid, which refers to a drug, total parenteral nutrition (TPN) fluid, or another therapeutic agent used for a chronic or acute condition, as known in the art. Exemplary therapeutic agents can include, for example, pharmaceuticals, chemicals, biological agents, or biochemicals that, when delivered to a patient in a therapeutically effective amount, achieve a desired therapeutic effect. The second fluid can be another type of therapeutic agent or another medical fluid, such as a medication. The second fluid can also be a flushing fluid, such as saline and / or a heparin lock flushing fluid. An example of a saline flushing fluid is 0.9% sodium chloride USP for injection. An example of a heparin lock flush solution is 0.9% sodium chloride with 100 USP heparin per mL or 10 USP heparin per mL. Alternative flush solutions are known in the art and may be used with the syringe 10 of the present disclosure.

[0076] The syringe 10 of the present disclosure allows a practitioner, such as a medical technician, nurse, physician's assistant, physician, or other trained or untrained clinician, healthcare caregiver, to administer a first fluid followed by a second fluid without having to change syringes or fluid containers between the delivery of the first and second fluids. Furthermore, the syringe 10 of the present disclosure allows a practitioner to provide sequential delivery of a second fluid followed by a first fluid through a single sequential advancement of the plunger rod of the syringe 10.

[0077] As used herein, "single continuous advancement of the plunger rod" means that a practitioner can push the plunger rod distally through the barrel of the syringe 10 in one continuous motion to expel a first fluid followed by a second fluid from the syringe barrel. For example, a practitioner does not need to perform multiple needle sticks or disconnect the syringe or another device from the VAD between the first and second fluid deliveries. Furthermore, by using the syringe 10 of the present disclosure, a practitioner does not need to twist, rotate, pull the plunger rod, or take any other action such as pushing another part or mechanism of the syringe 10 to deliver the first and second fluids sequentially. Thus, fluids can be expelled sequentially from the syringe 10 in response to a single continuous distal movement of the plunger rod by the practitioner (which may be performed as a single "manual" actuation or movement, i.e., the practitioner holds the syringe 10 and pushes the plunger rod through the barrel with one hand). Thus, the syringe 10 of the present disclosure simplifies the method of administering a second fluid to a VAD and / or patient, following a first fluid, as compared to conventional fluid delivery practices.

[0078] In some embodiments, syringe 10 is provided as a partially filled syringe, with the syringe chamber filled with flushing fluid or another medical fluid during manufacture. The partially filled syringe may include a cap, clip, fastener, and / or other packaging that holds the plunger rod in place and ensures that flushing fluid does not leak from the partially filled syringe unexpectedly, such as during shipping.

[0079] In some embodiments, the syringe 10 of the present disclosure can be configured to allow a practitioner to aspirate a medical fluid into the syringe 10 before delivering the fluid to a patient. For example, a practitioner can insert the nozzle or needle of the syringe 10 into a vial containing a first fluid (e.g., a medical fluid) and then aspirate the medical fluid into the chamber of the syringe 10 by moving the plunger rod of the syringe 10 proximally. After the first fluid has been aspirated into the chamber of the syringe 10, a sequential delivery of the first fluid followed by the second fluid can occur by connecting a pen syringe cannula to the syringe 10 or connecting the syringe 10 to a fluid port of a VAD and then moving the plunger rod of the syringe 10 distally, thereby expelling the second fluid from the syringe and then the first fluid into the VAD.

[0080] By eliminating the need to use different syringes for the delivery of the first and second fluids, the multi-chamber syringe 10 of the present disclosure simplifies the fluid administration procedure and provides substantial time savings compared to conventional fluid administration procedures. The syringe 10 of the present disclosure may reduce the risk of infection and may allow administration of medical fluids immediately after flushing the VAD, preventing drug blockage in the VAD.

[0081] The present disclosure also relates to a molding method for creating the distal stopper 112 with a barrier coating or film. As described in more detail herein, this molding method can be a one-shot injection molding process in which separate parts are formed. The injection molded parts are then molded together in the final mold, producing a stopper with one integral body having a barrier coating or film adhered to both the proximal and distal surfaces of the body. (Multi-chamber syringe for continuous drug delivery)

[0082] 1A and 1B illustrate an embodiment of a multi-chamber syringe 10 for sequential release of at least one first fluid F1 (shown in FIG. 3B) contained in a second or distal fluid chamber 14 followed by a second fluid F2 (FIGS. 1A and 3A-3C) contained in a first or proximal fluid chamber 12. As previously mentioned, the first fluid F1 can be a medical fluid, such as a drug or another therapeutic agent, delivered to a patient through a needle cannula or through a VAD, such as a catheter or IV line. The second fluid F2 can be another type of therapeutic agent or a flushing fluid, such as saline solution, and / or an anticoagulant, such as heparin. The type and amount of solution contained in the proximal fluid chamber 12 and / or the distal fluid chamber 14 may vary depending, for example, on the particular type of needle cannula, catheter, or IV line used to infuse and / or achieve a therapeutic effect. In some embodiments, the syringe 10 contains or is configured to contain between about 1 mL and 20 mL of the first fluid F1 and / or the second fluid F2, or preferably between about 5 mL and about 10 mL of the first fluid F1 and / or the second fluid F2.

[0083] In some embodiments, the syringe 10 includes a barrel 16 having an open proximal end 18, a distal end 20 with a nozzle or fluid port 22 for the discharge of a first fluid F1 and a second fluid F2 from the barrel 16, and a sidewall 24 extending between the proximal end 18 and the distal end 20. The fluid port 22 of the barrel 16 can be a connector, such as a luer connector, a thread connector, or a snap connector, configured to be coupled to a needle cannula for accessing the interior of a medical vial containing a medical fluid. The fluid port 22 of the syringe 10 can also be a needleless connector configured to be coupled directly or indirectly to a fluid port, valve, or another distal access port of a VAD. For example, a typical VAD fluid port is a pierceable or pre-slit septum made of rubber or another elastomeric material that allows insertion of a sharp or blunt needle cannula for injecting or withdrawing fluid from the VAD's catheter. Another typical VAD fluid port is a valve that does not require a needle to access the VAD. Alternatively, the valve may be activated by the frustoconical tip of the syringe barrel 16 to provide fluid communication between the interior of the barrel 16 and the VAD.

[0084] In some embodiments, the barrel 16 of the syringe 10 may be substantially similar in shape, size, and configuration to the barrel of a syringe used to administer flushing fluid to a VAD, as known in the art. For example, the barrel 16 may be a cylindrical structure molded from a rigid thermoplastic material such as polyester, polycarbonate, polypropylene, polyethylene, polyethylene terephthalate, acrylonitrile butadiene styrene, or another injection-moldable or moldable resin material known in the art. An exemplary syringe barrel is described, for example, in U.S. Patent No. 6,233,999, entitled "Flush Syringe Assembly with Controlled Pulse-Tiled Flushing," which is incorporated herein by reference.

[0085] Syringe 10 further includes a first or proximal stopper 110 and a second or distal stopper 112 slidably disposed within barrel 16 of syringe 10. Stoppers 110, 112 divide barrel 16 into a proximal chamber 12 and a distal chamber 14. In particular, as shown in FIG. 1A, proximal chamber 12 is located between the distal end of proximal stopper 110 and the proximal end of distal stopper 112. Distal chamber 14 (shown in FIG. 3C) is located between the distal end 112 of distal stopper 112 and distal end 20 of barrel 16.

[0086] As described in more detail herein, stoppers 110, 112 may include many of the features of syringe stoppers or plungers conventionally known in the art. For example, stoppers 110, 112 may include a substantially cylindrical body formed from a flexible and / or deformable material, such as a thermoplastic elastomer material. Examples of thermoplastic elastomers include, but are not limited to, silicone, polypropylene, polyethylene, or synthetic or natural rubber (e.g., isoprene), or mixtures thereof. Stoppers 110, 112 may include axially extending ribs 114, 132 or rings that seal against the interior surface of syringe barrel 16 so that stoppers 110, 112 can pass fluid through syringe barrel 16 toward distal end 20 of barrel 16.

[0087] 1A and 1B, more specifically, proximal stopper 110 may include a proximal end surface 116, a distal end surface 118, and an outer peripheral surface 120 extending between proximal end surface 116 and distal end surface 118. Proximal stopper 110 may further include one or more annular ribs 114 protruding from outer peripheral surface 120. Annular ribs 114 are configured to seal with the inner surface of sidewall 24 of syringe barrel 16 to allow predictable fluid flow through syringe barrel 16. In some embodiments, proximal stopper 110 includes multiple annular ribs 114 to improve stability and prevent proximal stopper 110 from tilting, shifting, or deforming as proximal stopper 110 moves through syringe barrel 16. For example, as shown in FIGS. 1A and 1B, proximal stopper 110 includes three ribs 114. In other embodiments, the proximal stop 110 may include fewer than three ribs 114 or more than three ribs 114 .

[0088] As shown in FIG. 1A , distal end surface 118 of proximal stopper 110 is in fluid contact with a surface that contacts second fluid F2 contained in proximal chamber 112 of syringe barrel 16. Proximal end surface 116 of proximal stopper 110 does not contact fluid during normal and / or anticipated use of syringe 10. To protect the fluid contained in proximal chamber 112, the first stopper may include a barrier coating, layer, or film covering, referred to herein as a distal barrier film 122, on the liquid-contacting portion of distal end surface 118 of proximal stopper 110. Exemplary stoppers including those with a barrier layer, which can be used as proximal stoppers 110 for the multi-chamber syringes 10 disclosed herein, are described in detail in U.S. Patent Application Publication No. 2009 / 0129999, entitled "Barrier-Coated Stoppers and Methods of Manufacturing," which is incorporated herein by reference.

[0089] As described in U.S. Patent Application Publication No. 2007 / 012999, barrier film 112 may optionally be formed from a fluoropolymer, such as a polymer formed from polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), expanded polytetrafluoroethylene (ePTFE), or similar fluoropolymer materials. Advantageously, an expanded fluoropolymer structure may be strong enough to form a thin barrier that maintains its shape during the molding process and subsequent installation of stopper 110 into syringe barrel 16. Desirably, the fluoropolymer material should not exhibit adverse effects on the therapeutic agent or other medical fluid in syringe barrel 16 and should be free of silicone-based materials, such as silicone oil. Furthermore, barrier film 122 should be biocompatible and have good mechanical properties. Furthermore, the barrier material should be inert and easy to process.

[0090] Distal stopper 112 is disposed in syringe barrel 16 and separates proximal chamber 12 from distal chamber 14. As described herein, distal stopper 112 includes a barrier layer, coating, or film on both fluid-contacting surfaces to separate the medical fluid contained in proximal chamber 12 from the medical fluid contained in distal chamber 14. In some embodiments, distal stopper 112 forms a one-way check valve to selectively control fluid flow between proximal chamber 12 and distal chamber 14. As used herein, a one-way check valve (also referred to as a check valve, retention valve, or one-way valve) refers to a valve that allows fluid to flow through the valve in only one direction. For example, distal stopper 112 can be configured to prevent fluid from flowing from distal chamber 14 to proximal chamber 12, while allowing fluid to flow from proximal chamber 12 to distal chamber 14. For example, the one-way check valve may be a ball valve, a diaphragm valve, a tilting disc valve, a clapper valve, or a duckbill valve as known in the art.

[0091] In some embodiments, the check valve of the distal stopper 112 is a disposable valve. As used herein, a "disposable" valve refers to a valve that is initially provided in a closed position and then moved to an open position once. A disposable valve does not return to the closed position after it has been opened. For example, the check valve can be configured to move from a closed position to an open position when the fluid pressure in the proximal chamber 12 exceeds the activation or opening pressure of the distal stopper 112. Once the distal stopper 112 opens, it does not return to the closed position. An advantage of a one-way check valve is that the fluid pressure in the proximal chamber 12 does not need to remain above the activation or opening pressure for the distal stopper 112 the entire time that the second fluid F2 is being pushed through the distal stopper 112 and into the distal chamber 14. Instead, the practitioner simply pushes the plunger rod coupled to the proximal stopper only once, applying enough force to create sufficient fluid pressure to open the distal stopper 112. Once the distal stopper 112 is open, the practitioner can press the plunger rod with less force to expel the second fluid F2 from the proximal chamber 12 through the distal stopper 112 and into the distal chamber 114, because the distal stopper 112 will not return to its closed position even when the fluid pressure in the proximal chamber 12 drops below the activation or opening pressure of the distal stopper 112.

[0092] 1A and 1B, as well as FIGS. 2A and 2B, distal stopper 112 comprises a body 124, which may include a first or proximal end surface 126, a second or distal end surface 128, and a peripheral surface 130 extending between proximal end surface 126 and distal end surface 128. As described in further detail herein, body 124 may be a unitary structure formed from separately molded pieces that are bonded, cured, or joined together during final molding. In some embodiments, distal end surface 128 may be conical or frustoconical to aid in the expulsion of fluid from syringe barrel 16 through fluid port 22. Alternatively, distal end surface 128 of distal stopper 112 may be substantially flat, sloped, stepped, or have another configuration, depending, for example, on the size and shape of syringe barrel 16. In some embodiments, the proximal end surface 126 of the distal stopper 112 may include a bore 140, recess, or depression extending axially through a portion of the body 124 from the proximal end surface 126 to the distal end surface 128. The bore 140 may be similar in size or shape to a bore in a conventional syringe stopper configured to couple to a plunger rod, as is known in the art. For example, as shown most clearly in FIGS. 2A and 2B , the bore 140 includes an open proximal or first end, a closed second or distal end having a substantially flat second surface, and an annular side surface between the proximal and distal ends. The annular side surface of the bore includes a recess 142 and a protrusion 144. In other embodiments, the annular side surface of the bore 140 may be cylindrical, frustoconical, or tapered.

[0093] As with proximal stopper 110, peripheral surface 130 of distal stopper 112 may also include one or more axially extending ribs 132 configured to contact the inner surface of syringe barrel 16 to create a seal between distal stopper 112 and the inner surface of syringe barrel 16. As noted above, multiple ribs 132 may be configured to prevent tipping, shifting, or deformation during use and improve stability of distal stopper 112 as it advances or retreats through syringe barrel 16. Peripheral surface 130 may also include one or more recessed portions 148 between ribs 132 that are spaced apart from the inner surface of sidewall 24 of syringe barrel 16. For example, as shown in FIGS. 2A and 2B , body 124 may include two ribs 132 with a recessed portion 148 between the two ribs 132. However, the number of ribs 132 may vary within the scope of this disclosure. In some embodiments, the body 124 includes only one rib 132 , while in other embodiments, the body 124 may include three or more ribs 132 .

[0094] In some embodiments, the distal stop 112 also includes one or more protrusions 146, such as detents or other raised bumps, extending axially from the proximal end surface 126 of the body 124. The protrusions 146 can be disposed on the proximal end surface 126 to create a small gap between the distal surface 118 of the proximal stop 110 and the proximal surface 130 of the distal stop 112 when the proximal stop 110 is pressed against the distal stop 112, as shown in FIG.

[0095] In some embodiments, the body 124 includes a slit 134 extending therethrough to allow fluid flow through the body 124 when the distal stopper 112 and / or the slit 134 are in the open position. The slit 134 can be an elongated narrow opening extending between the distal surface of the bore 140 and the distal end surface 128 of the body 124. In some embodiments, the body 124 includes a single slit extending across the distal end surface 128 and substantially transverse to the central longitudinal axis of the body 124. In other embodiments, the body 124 can include multiple slits 134 and / or slits 134 at different locations on the distal end surface 128 of the body 124.

[0096] Distal stopper 112 and / or slit 134 are configured to move between a closed position, in which fluid flow is prevented through distal stopper 112 and / or slit 134 in body 124, and an open position, in which fluid may flow through distal stopper 112 and / or slit 134 in body 124, thereby establishing fluid communication between proximal chamber 12 and distal chamber 14 through distal stopper 112. In some embodiments, distal stopper 112 can be configured such that when fluid pressure in proximal chamber 112 of syringe barrel 16 is below a predetermined opening pressure, distal stopper 112 remains in the closed position. Distal stopper 112 can be configured to transition to the open position when fluid pressure in proximal chamber 112 of syringe barrel 16 is at or above the predetermined opening pressure. In some embodiments, the slit 134 and / or distal stopper 112 are biased and initially provided in a closed position, meaning that the distal stopper 112 and / or slit 134 are in the closed position when the fluid pressure in the proximal chamber 112 is normal and substantially equal to the fluid pressure in the distal chamber 114. When the fluid pressure in the proximal chamber 112 increases substantially above a predetermined activation pressure value, the distal stopper 112 and / or slit 134 move to the open position.

[0097] The activation or opening pressure for distal stopper 112 and / or slit 134 can be selected based on the fluid pressure typically generated when a stopper is manually moved through the barrel of a conventional syringe at a reasonable speed, such as occurs when a practitioner pushes the syringe plunger rod through the syringe barrel. In some embodiments, the activation or opening pressure for slit 134 and / or distal stopper 112 is at least 30 psi, although the activation or opening pressure can be selected or optimized, for example, taking into account the size, shape, and materials of stoppers 110, 112, syringe barrel 16, and other components of the multi-chamber syringe, as well as different syringe designs. In some embodiments, syringe 10 has an activation or opening pressure for slit 134 and / or distal stopper 112 that is greater than the pressure required to inject medication (the pressure that expels initial fluid F1 from distal chamber 14 through fluid port 22 and into the patient through the needle cannula and / or VAD). Thus, the practitioner may need to apply a greater force to the plunger rod of the syringe 10, which is connected to the proximal stopper 110, to open the distal stopper 112 than is required to move the stoppers 110, 112 through the barrel 16. These differences in the pressure that must be applied to the plunger rod allow the practitioner to receive feedback that the first F1 is being expelled from the syringe and that the distal stopper 112 is at the most distal end of the syringe 16 (i.e., feel the need to increase the force on the plunger rod).

[0098] The distal stopper 112 further comprises a film, layer, or another barrier between the fluid chambers 12, 14 and the proximal and distal end surfaces 126, 128 of the distal stopper 112. In particular, the distal stopper 112 comprises a first or proximal barrier film 136 attached to the proximal end surface 126 of the body 124 and a second or distal barrier film 138 attached to the distal end surface 128 of the body 124. In some embodiments, the proximal barrier film 136 also covers the inner surface of the hole 140 in the body 124. Alternatively, the proximal barrier film 136 can extend through the proximal end surface 126 of the body 124 to cover the open end or portion of the hole 140. In some embodiments, the proximal barrier film 136 and / or the distal barrier film 138 can comprise slits or openings that coincide with the slits 134 extending through the body 124 to allow fluid flow through the distal stopper 124.

[0099] The barrier films 136, 138 can be formed of a material similar to or the same as the distal barrier film 122 of the proximal stopper 110. For example, the barrier films 136, 138 of the distal stopper 112 can be formed of any of the barrier materials described in the above-referenced U.S. Patent Application Publication No. 2007 / 0122999 or another biocompatible, fluid-impermeable and / or hydrophobic material known in the art. In some embodiments, the barrier films 136, 138 can be formed of a fluoropolymer material, such as a polymer formed from polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), expanded polytetrafluoroethylene (ePTFE), or similar fluoropolymer materials.

[0100] In some embodiments, the barrier films 136, 138 are sized or trimmed to cover only the fluid-contacting surfaces of the distal stopper 112. For example, the proximal barrier film 136 and the distal barrier film 138 can be trimmed into disk-shaped members having diameters that match or substantially match (e.g., within 5%) the outer diameters of the proximal and / or distal end surfaces 126, 128 of the distal stopper 112. The barrier films 136, 138 can be attached or secured to the proximal and distal end surfaces 126, 128 of the distal stopper 112 by a variety of lamination and adhesive methods known in the art. For example, the barrier films 136, 138 can be secured to the surfaces 126, 128 of the distal stopper 112 using a curable polymeric material and / or a biocompatible adhesive. The peripheral surface 30 of the distal stopper 112, including the ribs 132 that contact the sidewall of the barrel 16, can be free of a barrier layer or coating, thereby not interfering with the ability of the distal stopper 112 to seal and / or slide against the sidewall 24 of the barrel 16. In some embodiments, the thickness of the barrier films 136, 138 can affect the fluid pressure required to move the distal stopper 112 to the open position. Thus, the thickness of the barrier films can be selected or modified to adjust the fluid pressure required to open or close the stopper 112. For example, the thickness of the proximal barrier film 136 and / or the distal barrier film 138 can be between about 0.013 mm and about 0.025 mm. In some configurations, melt-processable films can be used for thermoforming, which simultaneously performs rubber vulcanization and / or molding processes.

[0101] 1A and 1B, as well as FIGS. 3A-3D, the stoppers 110, 112 of the syringe 10 of the present disclosure are configured to move cooperatively through the barrel 16 simultaneously, even though the stoppers 110, 112 are not mechanically linked or engaged together. This simultaneous movement occurs due to the compressibility-resistant properties of a liquid, such as a second fluid F2 (e.g., a second therapeutic agent or flushing fluid), in the proximal chamber 12 of the barrel 16. More specifically, pressure applied to the proximal stopper 110 is transferred to a fluid column of the second fluid F2 in the proximal chamber 12. This fluid column both exerts pressure on the distal stopper 112, causing the distal stopper 112 to move to its distal-most position through the syringe barrel 16 (as shown in FIGS. 3C and 3D), thereby expelling the first fluid F1 from the distal chamber 14 of the syringe barrel 16. When distal stopper 112 is in its most distal position, distal end 20 of syringe barrel 16 prevents further movement of distal stopper 112, and continued application of pressure to proximal stopper 110 increases fluid pressure in proximal chamber 12. This increase in fluid pressure moves distal stopper 112 to an open position, thereby allowing second fluid F2 to be expelled from syringe 10 through distal stopper 112 and through fluid port 22 of barrel 16.

[0102] Similarly, stoppers 110, 112 may move together proximally through barrel 16 even though stoppers 110, 112 are not mechanically linked or engaged together. In particular, movement of proximal stopper 110 creates a vacuum or negative pressure in syringe barrel 16 that pulls distal stopper 112 proximally through barrel 16 along with proximal stopper 110. Thus, as shown by arrow P in FIG. 3b, movement of distal stopper 112 proximally through barrel 16 causes a first fluid F1 to be drawn through fluid port 22 of barrel 16 and into distal chamber 14, in a manner similar to that which occurs when drawing fluid from a vial into a conventional syringe.

[0103] The stoppers 110, 112 are configured to move between several positions or configurations during a fluid delivery procedure. The syringe 10 may initially be provided in a partially filled configuration, as shown in FIG. 3A, with a second fluid F2, such as a second therapeutic agent or flushing solution, in the proximal chamber 12. In this initial or partially filled position, the stoppers 110, 112 are separated from one another by a distance D2 (shown in FIG. 3B) sufficient to contain a volume of the second fluid F2 in the proximal chamber 12 of approximately 1 mL to 20 mL, or preferably, approximately 5 mL to 10 mL. When ready for use, if the distal stopper 112 is not in its distal-most position in the barrel 16, the practitioner can move the stopper 112 distally through the barrel 16 to seal the distal stopper 112 against the distal end 20 of the barrel 16. The operator can move the stoppers 110, 112 in a proximal direction (indicated by arrow P in FIG. 3B) to draw the first fluid F1 into the distal chamber 14, thereby completely filling the syringe 10, as shown in FIG. 3B.

[0104] When the syringe 10 is fully filled, the distal stopper 112 is a distance D1 (shown in FIG. 3B ) from the distal end 20 of the barrel 16. Once the syringe 10 is fully filled, moving the stoppers 110, 112 distally (as indicated by arrow D in FIG. 3C ) moves the distal stopper 112 toward the distal end 20 of the barrel 16, thereby expelling the first fluid F1 from the distal chamber 14. The syringe 10 is shown in FIG. 13C in an intermediate position with a filled proximal chamber 12 and an empty distal chamber 14. Continued distal movement of the stoppers 110, 112 increases the fluid pressure in the proximal chamber 12 toward an activation or opening pressure for the distal stopper 112. When fluid pressure in the proximal chamber 12 exceeds a pressure that activates or opens the distal stopper 112, fluid communication is established between the proximal chamber 12 and the distal chamber 14 through the slit 134 in the body 124 of the distal stopper 112. Once fluid communication is established between the chambers 12, 14, the second fluid F2 is then expelled from the syringe 10 by movement of the proximal stopper 110 toward the distal stopper 112. In particular, movement of the proximal stopper 110 toward the distal stopper 112 moves the second fluid F2 from the proximal chamber 12 to the distal chamber 14, and then out of the distal chamber 14 through the fluid port 22. FIG. 3D shows the syringe 10 in an end-user or final position after fluids F1 and F2 have been expelled from the syringe barrel 16. When in the end user or final position, the distal barrier film 138 attached to the distal end surface 128 of the distal stopper 112 contacts or is in proximal contact with the distal end 20 of the barrel 16. Additionally, the distal end surface 118 of the proximal stopper 110 contacts or is in proximal contact with the proximal end surface 126 of the distal stopper 112.

[0105] 1A and 1B, as well as FIGS. 3A-3D, the syringe 10 further includes a plunger rod 26 coupled to the proximal stopper 110 for moving the proximal stopper 110 through the syringe barrel 16. As noted above, although the stoppers 110, 112 are not mechanically coupled or engaged together, moving the proximal stopper 110 through the barrel 16 simultaneously moves the distal stopper 112 through the barrel 16 in conjunction with the proximal stopper 110. For example, the plunger rod 26 can be an injection-molded part formed from a rigid thermoplastic material, such as polyester, polycarbonate, polypropylene, polyethylene, polyethylene terephthalate, or another thermoplastic material known in the art. The plunger rod 26 can be a conventional plunger used in currently available syringes and can be connected to the proximal stopper by a standard mechanical connector, fastener, or adhesive. In another embodiment, the plunger rod 26 can be integrally molded or integrally molded with the proximal stopper.

[0106] In some embodiments, plunger rod 26 includes a distal end 28 engaged with proximal stopper 110. For example, as most clearly seen in FIGS. 1B and 3C , distal end 28 of plunger rod 26 may include a thread connector 30 that is inserted into a corresponding bore 150 (shown in FIGS. 1B and 3C ) extending inwardly from the proximal surface of proximal stopper 110. Plunger rod 26 also includes a proximal end 32 that protrudes proximally from proximal end 18 of syringe barrel 16, and a body extending between proximal end 32 and distal end 28 of plunger rod 26. Proximal end 32 of plunger rod 26 may include a thumb plate 36 for manipulating plunger rod 26 to move stoppers 110, 112 through syringe barrel 16. Body 34 of plunger rod 26 may have a variety of cross-sectional shapes and configurations within the scope of the present disclosure. For example, the body 34 may have a generally cross-shaped cross section. In other embodiments, the cross section of the plunger rod 26 may be I-beam shaped, circular, square, L-shaped, or another conventional shape that may be formed by injection molding methods known in the art. In some embodiments, the syringe 10 may also include a removable plunger rod cap 38, such as a partially cylindrical (e.g., a cylindrical body with an axial slot for removing the cap 38 from the syringe 10) or a c-shaped space (shown in FIG. 3A ) between the thumb plate 36 of the plunger rod 26 and the proximal end 18 of the barrel 16, to prevent movement of the plunger rod 26 until the removable plunger rod cap 38 is removed from the syringe 10. The plunger rod cap 38 prevents the plunger rod 26 from being pushed into the syringe barrel 16 at inappropriate times, such as during transportation of the pre-filled syringe from a manufacturing facility to a consumer. (Method of discharging fluid from a multi-chamber syringe)

[0107] As noted above, syringe 10 may be used for sequential fluid delivery, such as delivery of a medical fluid followed by delivery of another type of medical fluid or flushing solution from syringe 10 into a needle cannula or VAD. A flow chart illustrating the steps for sequential fluid delivery from syringe 10 is shown in FIG.

[0108] As shown in FIG. 4, in step 210, a practitioner initially obtains a partially filled syringe 10, in which the proximal chamber of the syringe 10 is filled with a predetermined amount of a second fluid, such as a second type of medical agent or flushing solution. For example, the partially filled syringe 10 may contain about 1 mL to about 20 mL, or preferably about 5 mL to 10 mL of medical agent or flushing solution. An initial or partially filled, configured syringe 10 is shown in FIG. 3A. In step 212, the practitioner prepares the syringe 10 for use by, for example, removing any packaging from the syringe 10 and removing the plunger rod cap 38 that holds the plunger rod 26 in place. If the syringe 10 is not initially provided with a distal stopper 112 in its distal-most position, the practitioner may move the plunger rod 26 distally to completely seal the distal stopper of the syringe 10 in its distal-most position. In step 214, the practitioner places syringe barrel 16 in fluid communication with the interior of a container containing the medical fluid to be delivered to the patient. For example, the practitioner may attach a needle (not shown) to fluid port 22 at distal end 20 of syringe barrel 16 and insert the needle into a container, such as a medical vial, containing the medical fluid to be injected into the patient.

[0109] In step 216, the practitioner aspirates a first fluid F1 (e.g., a medical fluid) into the distal chamber of barrel 16. For example, the practitioner grasps plunger rod 26 and moves plunger rod 26 proximally, as shown by arrow P in FIG. 3B, which moves stoppers 110, 112 proximally, thereby aspirating or drawing first fluid F1 from the interior of the container into distal chamber 14 of syringe barrel 16, as shown by arrow A in FIG. 3A. Syringe 10 is shown in its fully filled configuration in FIG. 3B with first fluid F1 in distal chamber 14 and second fluid F2 in proximal chamber 12.

[0110] Once the initial dose of fluid F1 to be delivered to the patient has been aspirated into distal chamber 14, in step 218, the practitioner removes the needle from fluid port 22 of syringe barrel 16 and couples another needle cannula having a sharp tip to fluid port 22 for injecting the fluid into the patient or VAD. For example, the practitioner may insert the nozzle of syringe barrel 16 into a corresponding port or valve of the VAD, thereby establishing fluid communication between syringe barrel 16 and the lumen of the VAD. In step 220, once syringe 10 is suitably coupled to the needle cannula or VAD, the practitioner grasps plunger rod 26 and pushes plunger rod 26 distally (indicated by arrow D in FIG. 3B ), which moves stoppers 110, 112 distally through syringe barrel 16. Distal movement of distal stopper 112 expels initial fluid F1 (e.g., medical fluid) in the distal chamber of syringe barrel 16 from syringe barrel 16 through fluid port 22 or the nozzle of syringe barrel 16 and into the needle cannula or VAD, as shown by arrow A2 in FIG. 3B. The practitioner continues to move plunger rod 26 distally until distal stopper 112 is sealed within syringe barrel 16 at its distal-most position. Distal stopper 112 is shown in FIG. 3C in its distal-most position with stopper 112 in the closed position.

[0111] The practitioner continues to move the plunger rod 26 in a distal direction to move the distal stopper 112 to the open position and establish fluid communication between the proximal chamber 12 and the distal chamber 14. As discussed above, the force required to open the stopper 112 may be greater than the force required to move the stoppers 110, 112 through the barrel 16. Thus, when the distal stopper 112 is at its most distal, the practitioner may need to apply additional force to the plunger rod 26 to open the distal stopper 112. Further, as discussed above, the distal movement of the plunger rod 26 can be one continuous movement in the distal direction performed using one hand (e.g., one-handed operation). In this manner, the practitioner does not need to perform any additional operations beyond the continuous distal movement of the plunger rod 26 to automatically open the distal stopper 112. More specifically, with distal stopper 112 at its distal-most position, continued distal movement of plunger rod 26 moves proximal stopper 110 distally through barrel 16 toward distal stopper 112. This distal movement of proximal stopper 110 increases the fluid pressure in proximal chamber 12 toward the activation or opening pressure of distal stopper 112. When the fluid pressure in proximal chamber 12 reaches or exceeds the activation or opening pressure of distal stopper 112, distal stopper 112 opens, establishing fluid communication between proximal chamber 12 and distal chamber 14 through the distal stopper.

[0112] Once fluid communication between proximal chamber 12 and distal chamber 14 is established in step 222, the practitioner continues to push plunger rod 26 distally, which moves proximal stopper 110 distally through syringe barrel 16 toward proximal surface 126 of distal stopper 112. As shown by arrow A3 (in FIG. 3C ), movement of proximal stopper 110 toward distal stopper 112 forces second fluid F2, such as a second therapeutic agent or flushing solution, in proximal chamber 12, through distal stopper 112 and into distal chamber 14. Second fluid F2 then passes through distal chamber 14 and is expelled from syringe barrel 16 through fluid port 22 at the distal end 20 of syringe barrel 16 into a needle cannula or VAD. The syringe 10 is shown in an end or final position of use in FIG. 3D with the distal surface end 118 of the proximal stopper 110 in contact or proximally contacting the proximal end surface 126 of the distal stopper 112. (Method for molding a stopper for a multi-chamber syringe)

[0113] The distal stopper 112 for a multi-chamber syringe of the present disclosure may be manufactured by a modified one-piece molding method that produces a molded stopper with a one-piece body 124 formed from two or more pieces or sections. As noted above, the stopper 112 also includes a proximal barrier film 136 applied or laminated to the proximal end surface 126 of the one-piece body 124 and a distal barrier film 138 applied or laminated to the distal end surface 128 of the one-piece body 124. Figure 5 is a flow chart illustrating the steps of the molding method for making the distal stopper. Figures 6A-6E are schematic diagrams illustrating the steps of the molding method.

[0114] At step 310, the molding method includes initially molding a first or proximal component 124a and a second or distal component 124b, which together will form the body 124 of the distal stopper 112. Schematic diagrams of components 124a and 124b are shown in FIGS. 6A-6D. Components 124a and 124b may be molded by one-shot injection molding in separate molds from precursor materials that can be cured to form thermoplastic elastomer components. As noted above, the thermoplastic elastomer may include at least one of silicone, polypropylene, polyethylene, or synthetic or natural rubber (e.g., isoprene), or a combination thereof. In some embodiments, first or proximal component 124a includes two annular ribs 132 with a recessed portion 148 between ribs 132. Distal component 124b may be narrow, having a peripheral surface not wide enough to contact the inner surface of the syringe barrel 16. For example, the outer diameter of distal component 124b may be approximately the same as the outer diameter of recessed portion 148 of proximal component 124a. Components 124a, 124b are partially cured so that they are solid enough to be removed from the mold, but tacky enough to be joined together in a subsequent final molding step. At step 310, each component is cured to its rheological point. At step 318, this curing cycle is repeated.

[0115] After the components 124a, 124b are formed and partially cured in step 312, the method further includes adhering sheets of barrier material to the components 124a, 124b to form the proximal barrier film 136 and the distal barrier film 138. In particular, as shown in FIG. 6A , a sheet of barrier material is applied onto the proximal end surface 126 of the first component 124a, and a second sheet of barrier material is applied onto the distal end surface 128 of the second component. For example, the barrier sheets may be adhered to the components 124a, 124b by the adhesive properties of the partially cured components 124a, 124b. The sheets may also be adhered to the components 124a, 124b with a biocompatible adhesive or with an amount of uncured polymeric material applied to the surfaces 126, 128 of the components 124a, 124b.

[0116] At step 314, the method trims the barrier sheets to form barrier films 136, 138. For example, as shown in FIGURE 6B, the sheet on the proximal end surface 126 of the proximal component 124a can be trimmed to a diameter that matches the proximal end surface 126 to form the proximal barrier film 136. The sheet covering the distal end surface 128 of the distal component 124b can be trimmed to a diameter that matches the distal end surface 128 of the distal component 124b to form the distal barrier film 138.

[0117] In step 316, the parts 124a, 124b and the barrier films 136, 138 adhered thereto are then placed into the mating halves or parts 102a, 102b of the final mold, as shown in FIG. 6C. Specifically, the parts 124a, 124b are placed with the barrier films 136, 138 in contact with the surfaces of the molded parts and the uncured surfaces of the parts 124a, 124b disposed inside the mold. In step 318, as shown in FIG. 6D, the molded parts 102a, 102b are brought together so that the uncured surfaces of the parts 124a, 124b contact each other along the parting line PL (shown in FIGS. 6C and 6D). In some embodiments, the parting line of the mold may be slightly loose, such as by about 0.05 mm to about 0.2 mm. The molded article is then cured at a temperature of about 50°C to about 70°C to fully cure the parts 124a, 124b, thereby forming the integrated body 124 from the parts 124a, 124b. Optionally, a pressure of about 30 to 250 bar is applied to the molded article to fully cure the parts, depending on the size and shape. Typically, the butyl blend may take a total of about 2-8 minutes and may be divided between the first and last molding steps.

[0118] At step 320, after curing, the molded part is removed from the final molded article, as shown in Figure 6E. In particular, the molded part is a stopper 112 comprising an integrally molded body 124 having a proximal barrier film 136 adhered or laminated to the proximal end surface 128 of the body 124 and a distal barrier film 138 adhered or laminated to the distal end surface 128. At step 322, the method may further comprise forming a slit 134 in the distal end surface 128 of the body 124, thereby forming the stopper 112, for example, as shown in Figures 2A and 2B.

[0119] While embodiments of the stopper, multi-chamber syringe, and method of the present disclosure have been illustrated in the accompanying drawings and described in detail above, alternative embodiments will be apparent to, and can be readily made by, those skilled in the art without departing from the spirit and scope of the appended claims. Accordingly, the foregoing description is intended to be illustrative rather than limiting. The invention as described above is defined by the appended claims, and all modifications of the invention that come within the scope of the claims and equivalents thereof are intended to be embraced therein.

Claims

1. 1. A stopper for a multi-chamber syringe, said stopper comprising: a body having a first end surface, a second end surface, a peripheral surface extending between the first and second end surfaces, and at least one slit extending through the body for permitting fluid flow through the body of the stopper; a first barrier film adhered to a first end surface of the body; and a second barrier film adhered to a second end surface of the body; A stopper in which the first barrier film and / or the second barrier film have a slit or opening that coincides with a slit extending through the body to allow fluid to flow through the stopper.

2. 10. The stopper of claim 1, further comprising at least one protruding portion extending axially from the proximal end of the body for separating the stopper from another stopper of a multi-chamber syringe.

3. 10. The stopper of claim 1, wherein the peripheral surface of the body includes at least one rib configured to contact the inner surface of the sidewall of the syringe barrel and at least one recessed portion configured to be spaced apart from the inner surface of the sidewall of the syringe barrel.

4. 10. The stopper of claim 1, wherein the first stopper and / or the second stopper comprise a thermoplastic elastomer including at least one of silicone, polypropylene, polyethylene, synthetic rubber, natural rubber, or a combination thereof.

5. 10. The stopper of claim 1, wherein the body further comprises a bore extending axially through a portion of the body from the first end surface toward the second end surface of the body.

6. 6. The stopper of claim 5, wherein the hole has an open first end, a closed second end having a substantially flat second surface, and an annular side surface between the first and second ends, the annular side surface having a recessed portion and a protruding portion.

7. 7. The stopper of claim 6, wherein the slit extending through the body extends between the planar second surface of the bore and the second end surface of the body.

8. 10. The stopper of claim 1, wherein the body is made of two separately molded parts joined together by a continuous molding process.

9. 10. The stopper of claim 1, wherein the stopper is configured to move between (i) a closed position, wherein the stopper prevents fluid from passing through the slit in the body when fluid pressure in the syringe barrel is equal to or less than a predetermined opening pressure, and (ii) an open position, wherein the stopper establishes fluid communication between the chambers of the syringe barrel through the stopper when fluid pressure in the syringe barrel is at or above a predetermined opening pressure.

10. 10. The stopper of claim 1, wherein the slit in the body is offset and is initially provided in a closed position.

11. 10. The stopper of claim 1, wherein the first barrier film and / or the second barrier film comprises a disk having a diameter that matches the diameter of the first end surface or the second end surface of the body.

12. 10. The stopper of claim 1, wherein the first barrier film extends over an annular surface of the body and a surface of the aperture defined by the body.

13. The stopper of claim 1 , wherein the first barrier film and / or the second barrier film comprises a fluoropolymer.

14. 10. The stopper of claim 1, wherein the peripheral surface of the body is free of the barrier film.

15. 10. The stopper of claim 1, wherein the peripheral surface of the body is uncoated.

16. The stopper of claim 1 , wherein the first barrier film and / or the second barrier film has a thickness of about 0.013 mm to about 0.25 mm.

17. 1. A multi-chamber syringe for sequentially discharging at least a first fluid followed by a second fluid, said syringe comprising: a barrel having a first end, a second end with fluid ports for discharging a first fluid and a second fluid from the barrel, and a sidewall extending between the first end and the second end of the barrel; a first stopper slidably positioned in the barrel; and a second stopper comprising the stopper of claim 1 slidably positioned in the barrel; The syringe, wherein the first stopper and the second stopper define a first chamber in the syringe barrel between the first stopper and the second stopper configured to contain a second fluid, and a second chamber in the syringe barrel between the second stopper and the second end of the syringe barrel configured to contain a first fluid.

18. 10. The molding method for a stopper of claim 1, said method comprising the steps of: molding a first part and a second part of a body of the stopper in a partially molded state; connecting a first barrier film to a first end of the partially formed first part; connecting a second barrier film to a first end of the partially formed second part; bonding the first part to the second part in a final molding step, thereby forming a stopper comprising a body having first and second barrier films laminated to the body; and A molding method comprising forming a slit through the body and through the first barrier film and / or the second barrier film.

19. 20. The method of claim 18, wherein the first component and the second component are molded by one-shot injection molding.

20. The step of connecting the first barrier film to the first molded part includes adhering a flat sheet of barrier material to a first end of the first part and trimming the flat sheet to match the shape of the first end of the first part; and 20. The method of claim 18, wherein the step of connecting the second barrier film to the second molded part comprises adhering a flat sheet of barrier material to the second end of the second part and trimming the flat sheet to match the shape of the second end of the second part.

Images