Barrier-coated ordered stop for multi-chamber syringes

Abstract

A stop for a multi-chamber syringe includes a body including a first end surface, a second end surface, a peripheral surface extending between the first end surface and the second end surface, and at least one slit extending through the body to allow fluid flow through the body of the stop. The stopper further includes a first barrier film bonded to the first end surface of the body; and a second barrier film bonded to the second end surface of the body. The first barrier membrane and / or the second barrier membrane includes slits or openings aligned with slits extending through the body to allow fluid flow through the stop. Also provided herein are multi-chamber syringes including the stoppers and methods of making the stoppers.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. patent application No. 17 / 972,620, filed on October 25, 2022, and entitled “BarrierCoated Sequential Stopper for a Multi-Chamber Syringe,” the entire disclosure of which is incorporated herein by reference in its entirety.

[0003] Background of the Invention

[0004] Field of the Invention

[0005] The present disclosure generally relates to a stopper configured for use with a syringe containing doses of multiple fluids, and more particularly to a stopper for a syringe that sequentially discharges a first fluid or initial fluid (e.g., a first type of medical fluid) and a subsequent auxiliary fluid (e.g., another type of medical fluid or a flushing solution).

[0006] Description of related technologies

[0007] A multi-chamber syringe can be used to sequentially deliver a dose of an initial medical fluid and a subsequent dose of an auxiliary medical fluid. A conventional multi-chamber syringe typically includes a syringe barrel having a proximal chamber and a distal chamber separated by a stopper, a seal, a valve or a membrane to separate the initial fluid from the auxiliary fluid. A conventional multi-chamber syringe also includes a plunger mechanism to sequentially discharge the initial fluid and the auxiliary fluid from the syringe barrel. Examples of dual-chamber syringes are described in U.S. Patent Nos. 9,940,114 (titled "Dual-chamber syringe and associated connection system") and 9,833,572 (titled "Modular dual-chamber syringe system"), which include a conventional syringe barrel and a mechanism for discharging the initial fluid and the subsequent auxiliary fluid from the syringe barrel.

[0008] The multi-chamber syringe may include or may be connected to a needle cannula (e.g., a pen needle with a sharp tip) to inject an initial medical fluid and a subsequent auxiliary medical fluid directly into the patient's vascular system. 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 other fluid delivery device, so as to sequentially deliver the initial medical fluid and the subsequent auxiliary medical fluid through the VAD.

[0009] In some cases, a multi-chamber syringe is used to deliver a first type of therapeutic agent or drug and subsequently a second type of therapeutic agent or drug. The multi-chamber syringe can also be used to provide a flushing solution through the VAD before and / or after the therapeutic agent. In particular, a flushing procedure can be performed before or after the injection of the therapeutic agent to confirm the patency of the catheter, avoid drug incompatibilities, ensure that a complete drug dose is administered to the patient, prevent thrombosis, and / or minimize the risk of bloodstream infection due to VAD contamination. In addition, flushing can prevent blood, blood residues, and IV drugs from being deposited within the catheter or other VAD device.

[0010] The multi-chamber syringe may be provided as a pre-filled syringe in which the chambers of the syringe are filled with a primary fluid and / or a secondary fluid during manufacture and prior to shipment to a medical facility for use. In this case, it is important that the fluid contacting surfaces of the multi-chamber syringe are sealed and / or coated with a biocompatible protective coating or layer to prevent deterioration or contamination of the medical fluid contained in the syringe used in the prior art.

[0011] A problem with conventional multi-chamber syringes is that it is difficult to coat all surfaces of the syringe, stopper, and other components that may come in contact with the fluid in the pre-filled syringe to avoid contamination. The present disclosure proposes a stopper, a syringe, and an assembly method to address these problems. Summary of the invention

[0012] According to one aspect 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 end surface and the second end surface, and at least one slit extending through the body to allow fluid to flow through the body of the stopper. The stopper also includes 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 include slits or openings that align with the slits extending through the body to allow fluid to flow through the stopper.

[0013] According to another aspect of the present disclosure, a multi-chamber syringe for sequentially discharging at least an initial fluid and a subsequent auxiliary fluid comprises: a barrel having a first end, a second end, and a sidewall, the second end comprising a fluid port for discharging the initial fluid and the auxiliary fluid from the barrel, the sidewall extending between the first end and the second end of the barrel. The syringe also includes a first stopper and a second stopper, the first stopper and the second stopper being slidably positioned in the barrel. The second stopper may include the features of any of the stops described above for a multi-chamber syringe. The first stopper and the second stopper define a first chamber of the syringe barrel between the first stopper and the second stopper (the first chamber is configured to contain the auxiliary fluid), and define a second chamber between the second stopper and the second end of the syringe barrel, the second chamber being configured to contain the initial fluid.

[0014] According to another example of the present disclosure, a prefilled syringe includes the aforementioned multi-chamber syringe and a predetermined volume of the auxiliary fluid disposed in the first chamber of the prefilled syringe. The prefilled syringe is provided with the first chamber isolated from the second chamber fluid, so that the predetermined volume of the auxiliary fluid is contained in the prefilled syringe.

[0015] According to another aspect of the present disclosure, a method for sequentially discharging fluid from a prefilled syringe as previously described includes the steps of moving a plunger rod fixedly connected to the first stopper of the syringe in a proximal direction to cause the second stopper of the syringe to move in a proximal direction, thereby drawing the initial fluid into the second chamber of the syringe barrel. The method also includes: once a dose of the initial fluid is in the second chamber, moving the plunger rod in a single continuous stroke in a distal direction, thereby discharging the initial fluid and subsequent auxiliary fluid from the fluid port of the syringe barrel.

[0016] According to another example of the present disclosure, the aforementioned method of molding a stopper for a multi-chamber syringe includes the step of molding a first component and a second component of a body of the stopper into a partially molded state. The method also includes the step of connecting a first barrier membrane to a first end of the partially molded first component and connecting a second barrier membrane to a second end of the partially molded second component. The method also includes the step of bonding the first component to the second component in a finishing mold to form a stopper including a body and a first barrier membrane and a second barrier membrane laminated to the body. Finally, the method includes the step of forming a slit through the body and through the first barrier membrane and / or the second barrier membrane.

[0017] Non-limiting illustrative examples of embodiments of the present disclosure will now be described in the following numbered items.

[0018] Article 1: A stopper for a multi-chamber syringe, the stopper comprising: a body including a first end surface, a second end surface, a peripheral surface extending between the first end surface and the second end surface, and at least one slit extending through the body to allow fluid to flow through the body of the stopper; a first barrier membrane bonded to the first end surface of the body; and a second barrier membrane bonded to the second end surface of the body; wherein the first barrier membrane and / or the second barrier membrane include slits or openings that are aligned with the slits extending through the body to allow fluid to flow through the stopper.

[0019] Item 2: The stopper of Item 1, further comprising at least one protrusion extending axially from the proximal end of the body to separate the stopper from another stopper of the multi-chamber syringe.

[0020] Article 3: The stopper according to Article 1 or 2, wherein the outer peripheral surface of the body includes: at least one rib, the at least one rib is configured to contact the inner surface of the side wall of the syringe barrel; and at least one recessed portion, the at least one recessed portion is configured to be spaced apart from the inner surface of the side wall of the syringe barrel.

[0021] Article 4: A stopper according to any one of Articles 1 to 3, wherein the first stopper and / or the second stopper comprises a thermoplastic elastomer, such as silicone, polypropylene, polyethylene, or at least one of synthetic rubber, or natural rubber (e.g., isoprene).

[0022] Clause 5: The stop member of any one of Clauses 1 to 4, wherein the body further comprises a cavity extending axially through a portion of the body from the first end of the body toward the second end of the body.

[0023] Article 6: The stopper of Article 5, wherein the cavity comprises 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, wherein the annular side surface comprises a concave portion and a convex portion.

[0024] Clause 7: The stopper of Clause 6, wherein the slit extending through the body extends between the planar second surface of the cavity and the second end surface of the body.

[0025] Clause 8: The stopper of any one of Clauses 1 to 7, wherein the at least one slit extends substantially transversely to a central longitudinal axis of the body.

[0026] Clause 9: A stopper according to any one of clauses 1 to 8, wherein the body is made of two separately molded parts that are mated together by a subsequent molding process.

[0027] Clause 10: The stopper according to clause 9, wherein the two separately molded parts of the body are each formed by a one-shot injection molding process.

[0028] Article 11: A stopper according to any one of Articles 1 to 10, wherein the stopper is configured to switch between (i) a closed position and (ii) an open position, and when the fluid pressure in the syringe barrel is lower than a predetermined opening pressure, the stopper is in the closed position, preventing the fluid from flowing through the slit of the body, and when the fluid pressure in the syringe barrel is greater than or equal to the predetermined opening pressure, the stopper is in the open position, thereby establishing fluid communication between the chambers of the syringe barrel through the stopper.

[0029] Clause 12: The stopper of any one of Clauses 1 to 11, wherein the slit of the body is biased to the closed position and is initially disposed in the closed position.

[0030] Article 13: The stopper according to any one of Articles 1 to 12, wherein the first barrier membrane and / or the second barrier membrane comprises a disc-shaped member having a diameter matching the diameter of the first end surface or the second end surface of the body.

[0031] Clause 14: The stopper of any one of Clauses 1 to 13, wherein the first barrier film extends over the annular surface of the body and the surface of the cavity defined by the body.

[0032] Clause 15: The stopper of any one of Clauses 1 to 14, wherein the second barrier film extends over a planar surface or a substantial surface of the body.

[0033] Clause 16: The stopper of any one of Clauses 1 to 15, wherein the first barrier membrane and / or the second barrier membrane comprises a fluoropolymer, such as polytetrafluoroethylene (PTFE).

[0034] Clause 17: The stopper according to any one of Clauses 1 to 16, wherein the outer peripheral surface of the body is free of a barrier film.

[0035] Clause 18: The stopper according to any one of Clauses 1 to 17, wherein the outer peripheral surface of the body is uncoated.

[0036] Clause 19: The stopper of any one of Clauses 1 to 18, wherein the thickness of the first barrier film and / or the second barrier film is about 0.013 mm to about 0.25 mm.

[0037] Article 20: A multi-chamber syringe for sequentially discharging at least an initial fluid and a subsequent auxiliary fluid, the syringe comprising: a barrel comprising a first end, a second end and a side wall, the second end comprising a fluid port, the fluid port being used to discharge the initial fluid and the auxiliary fluid from the barrel, the side wall 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 a stopper as described in any one of Articles 1 to 19, the second stopper being slidably positioned in the barrel, the first stopper and the second stopper defining a first chamber of the syringe barrel between the first stopper and the second stopper (the first chamber being configured to contain the auxiliary fluid), and defining a second chamber of the syringe barrel between the second stopper and the second end of the syringe barrel, the second chamber being configured to contain the initial fluid.

[0038] Article 21: A syringe according to Article 20, wherein the slit of the body is configured to switch between (i) a closed position and (ii) an open position, and when the fluid pressure in the first chamber is lower than a predetermined opening pressure, the stopper is in the closed position, preventing the fluid from flowing through the slit of the body, and when the fluid pressure in the first chamber is greater than or equal to the predetermined opening pressure, the slit is in the open position, thereby establishing fluid communication between the first chamber and the second chamber through the slit of the second stopper.

[0039] Clause 22: The syringe of clause 20 or clause 21, wherein movement of the first stopper in a proximal direction through the barrel causes the second stopper to move in a proximal direction to draw the initial fluid into the second chamber through the fluid port of the barrel.

[0040] Clause 23: The syringe of any one of Clauses 20 to 22, wherein advancing the first stopper through the barrel causes the second stopper to move through the barrel to expel the initial fluid from the second chamber through the fluid port of the barrel.

[0041] Clause 24: A syringe according to any one of Clauses 20 to 23, wherein, when the second stop is in the distal-most position, movement of the first stop toward the second stop causes the fluid pressure in the first chamber to increase toward a predetermined opening pressure of the slit of the body.

[0042] Article 25: A syringe according to Article 24, wherein, once the slit is opened, continued distal movement of the first stop toward the second stop causes the auxiliary fluid to move from the first chamber through the slit of the body of the second stop, the second chamber and the fluid port of the barrel, thereby expelling the second fluid from the barrel.

[0043] Article 26. The syringe of any one of Articles 20 to 25, wherein the barrel comprises at least one of polyester, polycarbonate, polypropylene, polyethylene, polyethylene terephthalate, or acrylonitrile butadiene styrene.

[0044] Article 27: A syringe according to any one of Articles 20 to 26, wherein the first stopper and / or the second stopper comprises a thermoplastic elastomer, such as silicone, polypropylene, polyethylene, or at least one of synthetic rubber, or natural rubber (e.g., isoprene).

[0045] Clause 28: The syringe of any one of Clauses 20 to 27, wherein the slit of the body of the second stopper is biased to a closed position and is initially disposed in the closed position.

[0046] Clause 29: The syringe of any one of Clauses 20 to 28, further comprising a plunger rod connected to the first stopper to move the first stopper through the barrel.

[0047] Clause 30: The syringe of Clause 29, wherein the syringe is configured such that the initial fluid and subsequently the secondary fluid are expelled from the syringe barrel by a single continuous advancement of the plunger rod distally within the syringe barrel.

[0048] Clause 31: The syringe of clause 29 or clause 30, wherein the syringe is configured such that the initial fluid and subsequently the secondary fluid are expelled from the syringe barrel by single-handed operation of the plunger rod.

[0049] Clause 32: The syringe of any one of Clauses 29 to 31, wherein the plunger rod comprises a proximal end including a press plate, a distal end including a threaded connector, and a body extending between the proximal end and the distal end.

[0050] Clause 33: The syringe of Clause 32, wherein the first stopper comprises a threaded chamber that engages the threaded connector of the plunger rod to thereby secure the plunger rod to the second stopper.

[0051] Clause 34: The syringe of any one of Clauses 29 to 33, wherein the stop is configured such that moving the plunger rod in a proximal direction or a distal direction moves both the first stop and the second stop.

[0052] Clause 35: The syringe of any one of Clauses 29 to 34, wherein the plunger rod is fixedly connected to the first stop and the plunger rod and / or the first stop are not connected to the second stop.

[0053] Clause 36: The syringe of any one 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.

[0054] Article 37: A prefilled syringe, comprising: a syringe as described in any one of Articles 20 to 36; and a predetermined volume of auxiliary fluid disposed in the first chamber of the prefilled syringe, wherein the prefilled syringe is provided with the first chamber isolated from the second chamber fluid, so that the predetermined volume of auxiliary fluid is contained in the prefilled syringe.

[0055] Clause 38: The prefilled syringe of Clause 37, wherein the auxiliary fluid comprises saline and / or heparin flush solution.

[0056] Clause 39: The prefilled syringe of clause 37 or clause 38, wherein the syringe further comprises a plunger rod connected to the first stopper to move the first stopper and / or the second stopper through the barrel.

[0057] Article 40: The prefilled syringe of Article 39 further comprising a removable plunger cap engaged between the plunger rod and the barrel of the syringe to prevent movement of the plunger rod until the cap is removed, thereby maintaining fluid isolation between the first chamber and the second chamber until the plunger cap is removed.

[0058] Article 41: A method for sequentially expelling fluid from a prefilled syringe of any one of Articles 37 to 40, the method comprising: moving a plunger rod fixedly connected to the first stop member of the syringe in a proximal direction to move the second stop member of the syringe in a proximal direction, thereby drawing the initial fluid into the second chamber of the syringe barrel; and once a dose of the initial fluid is located in the second chamber, moving the plunger rod in a single continuous stroke in a distal direction to expel the initial fluid and subsequently the auxiliary fluid from the fluid port of the syringe barrel.

[0059] Clause 42: The method of clause 41, wherein the single continuous stroke of the plunger rod is performed with a single-handed operation.

[0060] Article 43: A method according to Article 41 or Article 42, wherein drawing the initial fluid into the second chamber includes: attaching a needle to the fluid port of the syringe; inserting the needle into a fluid container; and drawing the initial fluid from the fluid container into the second chamber of the syringe.

[0061] Article 44: The method according to any one of Articles 41 to 43, further comprising attaching at least one patient line to the fluid port of the syringe barrel before moving the plunger rod in the distal direction, wherein the fluid discharged from the syringe is delivered to the patient through the at least one patient line.

[0062] Clause 45: The method of any one of Clauses 41 to 44, wherein the initial fluid comprises a therapeutic agent.

[0063] Article 46: A method for molding a stopper according to any one of Articles 1 to 19, the method comprising: molding the first component and the second component of the body of the stopper into a partially molded state; connecting the first barrier membrane to the first end of the partially molded first component; connecting the second barrier membrane to the second end of the partially molded second component; bonding the first component to the second component in a finishing mold to form the stopper, the stopper comprising the body and the first barrier membrane and the second barrier membrane laminated to the body; and forming a slit through the body and through the first barrier membrane and / or the second barrier membrane.

[0064] Article 47: The method according to Article 46, wherein the first component and the second component are molded by a one-time injection molding process.

[0065] Clause 48: The method of Clause 46 or Clause 47, wherein connecting the first barrier membrane to the first molded component comprises: attaching a flat sheet of barrier material to the first end of the first component and trimming the flat sheet to match the shape of the first end of the first component.

[0066] Clause 49: The method of Clause 48, wherein connecting the second barrier film to the second end of the second component comprises: attaching a flat sheet of barrier material to the second end of the second component and trimming the flat sheet to match the shape of the second end of the second component.

[0067] Clause 50: The method of any one of Clauses 46 to 49, wherein bonding the components together comprises curing the components to a temperature of about 50°C to about 70°C.

[0068] Clause 51: The method of any one of Clauses 46 to 50, wherein the first barrier film and / or the second barrier film comprises a fluoropolymer.

[0069] Clause 52: The method of any one of Clauses 46 to 51, wherein the first component and the second component are molded together along uncoated surfaces of the respective components.

[0070] Clause 53: The method of any one of Clauses 46 to 52, wherein bonding the first component to the second component comprises placing the first component in a first half of the mold, placing the second component in a second half of the mold, and closing the mold to fit the components together along the uncoated surfaces of the components.

[0071] Clause 54: The method of clause 53, wherein the boundary between the components is loosened by approximately 0.05 mm to approximately 0.2 mm.

[0072] Clause 55: The method of clause 53 or clause 54, wherein bonding the components together comprises applying sufficient temperature and pressure to the mold to form a single integrated body from the first component and the second component. BRIEF DESCRIPTION OF THE DRAWINGS

[0073] Figure 1A is a perspective view of a multi-chamber syringe according to one aspect of the present invention.

[0074] Figure 1B yes Figure 1A Exploded perspective view of a multi-chamber syringe.

[0075] Figure 2A According to one aspect of the present disclosure Figure 1AA three-dimensional view of a stopper of a multi-chamber syringe.

[0076] Figure 2B yes Figure 2A A top plan view of the stopper.

[0077] Figure 2C yes Figure 2A A cross-sectional view of a stopper.

[0078] Figure 3A Is in the initial position or partially filled position Figure 1A Side view of a multi-chamber syringe.

[0079] Figure 3B is in the filling position Figure 1A Side view of a multi-chamber syringe.

[0080] Figure 3C yes Figure 1A A cross-sectional view of a multi-chamber syringe with the proximal chamber filled and the distal chamber empty.

[0081] Figure 3D yes Figure 1A A side view of a multi-chamber syringe in a final position after the primary fluid and the auxiliary fluid are expelled from the syringe.

[0082] Figure 4 It shows that from Figure 1A A flow chart of a method for expelling a medical fluid from a multi-chamber syringe.

[0083] Figure 5 is a flow chart illustrating a method for forming a stopper for a barrier coating according to an aspect of the present disclosure.

[0084] FIG. 6A to FIG. 6E is a schematic diagram showing steps of a method for manufacturing a stopper with a barrier membrane according to aspects of the present disclosure, which may be used for a multi-chamber syringe. DETAILED DESCRIPTION

[0085] The following description is provided to enable those skilled in the art to make and use the described embodiments intended for implementing the present invention. However, various modifications, equivalents, variations and substitutes will be apparent to those skilled in the art. Any and all such modifications, variations, equivalents and substitutes are intended to fall within the spirit and scope of the present invention.

[0086] Hereinafter, for the purpose of description, the terms "upper", "lower", "right", "left", "vertical", "horizontal", "top", "bottom", "lateral", "longitudinal" and their derivatives shall relate to the present invention as oriented in the accompanying drawings. As used herein, the term "proximal" refers to the portion or end of a device (e.g., a syringe or catheter) that is grasped, manipulated, or used by a practitioner or other user. The term "distal" refers to the end or portion farthest 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 of the syringe that a practitioner pushes 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 includes a needle cannula configured to penetrate the patient's skin. However, it should be understood that the present invention may employ alternative variations and step sequences unless otherwise expressly stated. It should also be understood that the specific devices and processes shown in the drawings and described in the following specification are merely exemplary embodiments of the present invention. Therefore, specific dimensions and other physical characteristics associated with the embodiments disclosed herein should not be considered limiting.

[0087] Referring to the accompanying drawings, the present disclosure relates to pistons, plungers or stops 110, 112 for a multi-chamber syringe 10. One of the stops (referred to herein as a distal stop 112) can be configured to divide a drug container (e.g., a syringe barrel) into a distal chamber containing a first fluid or initial fluid to be injected into a patient and a proximal chamber containing a subsequent fluid or auxiliary fluid to be delivered to the patient after the initial fluid. In some examples, the distal stop 112 includes a built-in check valve that allows the auxiliary fluid contained in the proximal chamber of the syringe 10 to pass through the distal stop 112 only after the initial fluid is discharged from the distal chamber of the syringe 10. Therefore, the multi-chamber syringe 10 of the present disclosure can be used to sequentially deliver multiple medical fluids to the patient's vascular system through a needle cannula inserted into a patient's blood vessel, requiring only one needle stick and without the practitioner having to perform additional fluid delivery steps. In other examples, the multi-chamber syringe 10 of the present disclosure may allow for the sequential delivery of multiple medical fluids to a patient through a VAD without requiring the attachment of multiple syringes or fluid containers to the VAD.

[0088] As described in further detail herein, the distal stopper 112 may also include a leachable / extractable barrier layer, coating, or film on the fluid contacting surface of the distal stopper 112. Specifically, a first barrier coating or film, or a proximal barrier coating or film, may be positioned on the distal stopper 112 to contact the fluid contained in the proximal chamber, and a second barrier coating or film, or a distal barrier coating or film, may be positioned to contact the fluid contained in the distal chamber of the syringe 10. Including barrier layers, coatings, or films on both fluid contacting surfaces of the distal stopper 112 means that the syringe 10 may be used with sensitive medical fluids (e.g., drugs that are susceptible to degradation when exposed to other plastic materials for an extended period of time).

[0089] The present disclosure also relates to features of a pre-filled or partially pre-filled multi-chamber syringe 10, which includes a proximal stopper 110 and a distal stopper 112. In particular, the multi-chamber syringe 10 can be configured to discharge an initial fluid and a subsequent auxiliary fluid from the syringe barrel through a fluid port or nozzle of the syringe 10. As previously described, the initial fluid can be a medical fluid, which, as used herein, can refer to a drug, a total parenteral nutrition (TPN) liquid, or other therapeutic agent for treating a chronic or acute condition, as is known in the art. Exemplary therapeutic agents can include, for example, drugs, chemicals, biological substances, or biochemical substances, which achieve a desired therapeutic effect when delivered to a patient in an amount effective for treatment. The auxiliary fluid can be other medical fluids, such as other types of therapeutic agents or drugs. The auxiliary fluid can also be a flushing solution, such as saline and / or a heparin lock flushing solution. An example of a saline flushing solution is 0.9% sodium chloride USP for injection. Examples of heparin lock flush solutions are 100 UPS units of sodium heparin per milliliter or 10 UPS units of sodium heparin per milliliter in 0.9% sodium chloride.Other flush solutions as known in the art may also be used with the syringe 10 of the present disclosure.

[0090] The syringe 10 of the present disclosure allows a practitioner (e.g., a medical technician, nurse, physician assistant, physician, or other trained or untrained clinician or healthcare provider) to administer an initial fluid followed by a secondary fluid without having to replace a syringe or fluid container between the delivery of the initial and secondary fluids. In addition, the syringe 10 of the present disclosure allows a practitioner to sequentially deliver an initial fluid followed by a subsequent secondary fluid through a single, continuous advancement of the plunger rod of the syringe 10.

[0091] As used herein, "a single continuous advancement of the plunger rod" means that the practitioner is able to push the plunger rod through the barrel of the syringe 10 in the distal direction to discharge the initial fluid and the subsequent auxiliary fluid from the syringe barrel in a single continuous stroke. For example, between delivering the initial fluid and the auxiliary fluid, the practitioner does not need to perform multiple acupunctures or disconnect the syringe or other device from the VAD. In addition, using the syringe 10 of the present disclosure, the practitioner does not need to perform any other actions (such as twisting, rotating or pulling the plunger rod or pressing other components or mechanisms of the syringe 10) to perform the sequential delivery of the initial fluid and the auxiliary fluid. Therefore, the fluid can be discharged from the syringe 10 in sequence only in response to a single continuous stroke of the plunger rod being moved in the distal direction by the practitioner, which can be performed as a "one-handed" operation or movement (i.e., the practitioner can hold the syringe 10 with one hand and press the plunger rod through the barrel). Therefore, compared with traditional fluid delivery practices, the syringe 10 of the present disclosure simplifies the process of administering the initial fluid and the subsequent auxiliary fluid to the VAD and / or the patient.

[0092] In some examples, the syringe 10 is provided as a partially pre-filled syringe, wherein the chamber of the syringe 10 is filled with a flushing solution or other medical fluid during manufacture. The partially pre-filled syringe 10 may include a cap, a clip, a retainer, and / or other packaging to hold the plunger rod in place and to ensure that the flushing solution does not leak from the partially pre-filled syringe 10 at unexpected times (e.g., during shipping).

[0093] In some examples, the syringe 10 of the present disclosure can be configured to allow a practitioner to draw 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 an initial fluid (e.g., a medical fluid) and then draw the medical fluid into the chamber of the syringe 10 by moving the plunger rod of the syringe 10 in a proximal direction. After the initial fluid is drawn into the chamber of the syringe 10, the initial fluid and subsequently the auxiliary fluid can be delivered in sequence by connecting a pen needle 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 in a distal direction to expel the initial fluid and subsequently the auxiliary fluid from the syringe 10 to the VAD.

[0094] By eliminating the need to use different syringes to deliver the initial fluid and the auxiliary fluid, the multi-chamber syringe 10 of the present disclosure simplifies the fluid administration procedure, saving a significant amount of time compared to traditional fluid administration practices. The syringe 10 of the present disclosure may also reduce the risk of infection and allow the VAD to be flushed immediately after the administration of the medical fluid, which may prevent drug blockage in the VAD.

[0095] The present disclosure also relates to a molding process for manufacturing a distal stopper 112 including a barrier coating or film. As described in further detail herein, the molding process can include forming separate components through a one-shot injection molding process. The injection molded components are then molded together in a finishing mold, which produces a stopper including a single integrated body having a barrier coating or film bonded to both the proximal and distal surfaces of the body.

[0096] Multi-chamber syringe for sequential delivery of medications

[0097] Figure 1A and Figure 1B An example of a multi-chamber syringe 10 is shown for sequentially ejecting at least an initial fluid F1 (eg, Figure 3B ) and the subsequent auxiliary fluid F2 contained in the first fluid chamber or the proximal fluid chamber 12 (as shown Figure 1A and FIG. 3A to FIG. 3C As previously described, the initial fluid F1 can be a medical fluid (e.g., a drug or other therapeutic agent) that is intended to be delivered to a patient through a needle cannula or through a VAD (e.g., a catheter or IV line). The auxiliary fluid F2 can be other types of therapeutic agents or flushing solutions, such as saline solution and / or anticoagulants (e.g., heparin). The type and amount of solution contained in the proximal chamber 12 and / or the distal chamber 14 may vary, depending on, for example, the specific type of needle cannula, catheter, or IV line used for injection and / or the therapeutic effect to be achieved. In some examples, the syringe 10 contains or is configured to contain between approximately 1 mL and 20 mL of the initial fluid F1 and / or the auxiliary fluid F2, or preferably, contains between approximately 5 mL and approximately 10 mL of the initial fluid F1 and / or the auxiliary fluid F2.

[0098] In some examples, the syringe 10 includes a barrel 16 having an open proximal end 18, a distal end 20, the distal end including a nozzle or fluid port 22 for discharging the initial fluid F1 and the auxiliary fluid F2 from the barrel 16, and a sidewall 24 extending between the proximal end 18 and the distal end 20 of the barrel 16. The fluid port 22 of the barrel 16 can be a connector (e.g., a Luer connector, a threaded connector, or a snap connector) configured to be connected to a needle cannula to access the interior of a medical vial containing a medical fluid, for example. The fluid port 22 of the syringe 10 can also be a needleless connector configured to be directly or indirectly connected to a fluid port, a valve, or other terminal passage portion of the VAD. For example, a conventional type of fluid port of a VAD is a pierceable septum or a pre-slit septum made of rubber or other elastomeric material that allows a sharp or blunt needle cannula to be inserted so as to inject fluid into or extract fluid from the catheter of the VAD. The other conventional fluid port of a VAD is a valve, which does not require a needle for accessing the VAD. Instead, the valve can be activated by the frustoconical end of the syringe barrel 16 to provide fluid communication between the interior of the barrel 16 and the VAD.

[0099] In some examples, as is known in the art, the barrel 16 of the syringe 10 can be substantially similar in shape, size, and construction to the barrel of a syringe for administering a flushing solution to a VAD. For example, the barrel 16 can be a cylindrical structure formed of a rigid thermoplastic material, such as polyester, polycarbonate, polypropylene, polyethylene, polyethylene terephthalate, acrylonitrile butadiene styrene, or other injection moldable or formable resin materials known in the art. For example, an exemplary barrel for a syringe is described in U.S. patent application publication number 2020 / 0061297, entitled "Flush Syringe Assembly with Controlled Pulsatile Flushing," the entire disclosure of which is incorporated herein by reference in its entirety.

[0100] The syringe 10 also includes a first stopper or proximal stopper 110 and a second stopper or distal stopper 112 slidably positioned within the barrel 16 of the syringe 10. The stops 110, 112 divide the barrel 16 into the proximal chamber 12 and the distal chamber 14. Specifically, as shown in FIG. Figure 1A As best shown, the proximal chamber 12 is located between the distal end of the proximal stop 110 and the proximal end of the distal stop 112. The distal chamber 14 (eg, Figure 3C ) is located between the distal end of the distal stop 112 and the distal end 20 of the barrel 16.

[0101] As described in further detail herein, the stops 110, 112 include many features of conventional syringe stops or plungers known in the art. For example, the stops 110, 112 can be a substantially cylindrical body formed of a flexible and / or deformable material (e.g., a thermoplastic elastomer material). Examples of thermoplastic elastomers include, but are not limited to, silicone, polypropylene, polyethylene, synthetic rubber or natural rubber (e.g., isoprene), or combinations thereof. The stops 110, 112 may include radially extending ribs 114, 132 or rings that seal against the inner surface of the syringe barrel 16 so that the stops 110, 112 can move the fluid through the syringe barrel 16 toward the distal end 20 of the barrel 16.

[0102] More specifically, if Figure 1A and Figure 1B As shown, the proximal stop 110 may include a proximal surface 116, a distal surface 118, and an outer peripheral surface 120 extending between the proximal surface 116 and the distal surface 118. The proximal stop 110 may also include one or more annular ribs 114 protruding from the outer peripheral surface 120. The annular ribs 114 are configured to seal against the inner surface of the sidewall 24 of the syringe barrel 16 to ensure that the fluid flows through the syringe barrel 16 in an intended manner. In some examples, the proximal stop 110 includes a plurality of annular ribs 114 to increase stability and prevent the proximal stop 110 from tilting, shifting, or otherwise deforming as the stop 110 moves through the syringe barrel 16. For example, as Figure 1A and Figure 1B As shown, the proximal stop 110 includes three ribs 114. In other examples, the proximal stop 110 can include less than three ribs 114 or more than three ribs 114.

[0103] like Figure 1AAs shown, the distal surface 118 of the proximal stopper 110 is a fluid contact surface that contacts the second fluid F2 contained in the proximal chamber 12 of the syringe barrel 16. The proximal surface end 116 of the first stopper 110 does not contact the fluid during normal and / or expected use of the syringe 10. In order to protect the fluid contained in the proximal chamber 12, the first stopper 110 may include a barrier coating, layer or film covering (referred to herein as a distal barrier film 122) on the fluid contacting portion of the distal surface 118 of the proximal stopper 110. An exemplary stopper including a barrier layer is described in detail in PCT application No. WO 2022 / 109214A1 (hereinafter referred to as the '214 publication) and entitled "Barrier coated stopper and method of forming same", which can be used as the proximal stopper 110 of the multi-chamber syringe 10 disclosed herein, and the entire contents of the PCT application are incorporated herein by reference in their entirety.

[0104] As described in the '214 publication, the barrier membrane 122 can optionally be formed of a fluoropolymer material, such as a polymer formed of polytetrafluoroethylene resin (PTFE), ethylenetetrafluoroethylene resin (ETFE), expanded polytetrafluoroethylene (ePTFE), or similar fluoropolymer materials. Advantageously, the expanded fluoropolymer structure can be strong enough to form a thin barrier that remains intact during molding and after the stopper 110 is installed in the syringe barrel 16. Desirably, the fluoropolymer material should also not exhibit a deleterious effect on the therapeutic agent or other medical solution in the syringe barrel 16, and should not contain silicon-based materials (e.g., silicone oil). In addition, the material of the barrier membrane 122 should be biocompatible and should have good mechanical integrity. In addition, the barrier material should be inert and easy to handle.

[0105] The distal stopper 112 is positioned in the syringe barrel 16 and separates the proximal chamber 12 from the distal chamber 14. As described herein, the distal stopper 112 includes a barrier layer, coating, or membrane located on two fluid contacting surfaces to separate the medical fluid contained in the proximal chamber 12 from the medical fluid contained in the distal chamber 14. In some examples, the distal stopper 112 forms a one-way check valve to selectively control the flow of fluid between the proximal chamber 12 and the distal chamber 14. As used herein, a one-way check valve (also known as a check valve, a retention valve, or a one-way valve) refers to a valve that allows fluid to flow through the valve in only one direction. For example, the distal stopper 112 can be configured to allow fluid to flow from the proximal chamber 12 to the distal chamber 14 while preventing fluid from flowing from the distal chamber 14 to the proximal chamber 12. The one-way check valve may be, for example, a ball valve, a diaphragm valve, a tilting disc valve, a flap valve, or a duckbill valve as known in the art.

[0106] In some examples, 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 set in a closed position and is converted to an open position once. A disposable valve cannot return to the closed position after opening. For example, the check valve can be configured to switch from a closed position to an open position when the fluid pressure of the proximal chamber 12 is equal to or greater than the activation pressure or opening pressure of the distal stopper 112. Once the distal stopper 112 is opened, the distal stopper 112 will not return to the closed position. The advantage of a disposable valve is that the fluid pressure of the proximal chamber 12 does not need to remain higher than the activation pressure or opening pressure of the distal stopper 112 throughout the time that the auxiliary fluid F2 is pushed through the distal stopper 112 into the distal chamber 14. Instead, the practitioner only needs to press the plunger rod connected to the proximal stopper 110 with sufficient force to generate a fluid pressure sufficient to open the distal stopper 112. Once the distal stopper 112 is opened, the practitioner can push the plunger rod with less force to discharge the auxiliary fluid F2 from the proximal chamber 12 through the distal stopper 112 to the distal chamber 114, because the distal stopper 112 will not return to the closed position even if the fluid pressure in the proximal chamber 12 drops below the activation pressure or opening pressure of the distal stopper 112.

[0107] In some examples, such as Figure 1A and Figure 1B As shown, and Figure 2A and Figure 2BAs shown, the distal stopper 112 includes a body 124 including a first surface or proximal surface 126, a second surface or distal surface 128, and an outer peripheral surface 130 extending between the proximal surface 126 and the distal surface 128. As further described in detail herein, the body 124 can be a unitary structure formed from separately molded components that are bonded, cured, or joined together during a final molding process. In some examples, the distal surface 128 can be conical or frusto-conical to assist in expelling fluid from the syringe barrel 16 through the fluid port 22. Alternatively, the distal surface 128 of the distal stopper 112 can be substantially flat, inclined, stepped, or other configurations depending on, for example, the size and shape of the syringe barrel 16. In some examples, the proximal surface 126 of the distal stop 112 may include a cavity 140, a recessed area, or a depression that extends axially through a portion of the body 124 from the proximal surface 126 toward the distal surface 128. The size and shape of the cavity 140 may be similar to the shape and size of a cavity of a conventional syringe stopper known in the art that is configured to be connected to a plunger rod. For example, Figure 2A and Figure 2B As most clearly shown, the cavity 140 can include an open proximal or first end, a closed second or distal end having a substantially flat distal surface, and an annular side surface between the proximal and distal ends. The annular side surface of the cavity can include a concave portion 142 and a convex portion 144. In other examples, the annular side surface of the cavity 140 can be cylindrical, frustoconical, or conical.

[0108] As with the proximal stopper 110, the peripheral surface 130 of the distal stopper 112 may also include one or more radially extending ribs 132 that are configured to contact the inner surface of the syringe barrel 16 to form a seal between the distal stopper 112 and the inner surface of the syringe barrel 16. As previously described, a plurality of ribs 132 may be provided to improve the stability of the distal stopper 112 as it is advanced or retracted in the syringe barrel 16, and to prevent the stopper 112 from tilting, shifting, or deforming during use. The peripheral surface 130 also includes one or more recessed portions 148 between the plurality of ribs 132, which are configured to be spaced apart from the inner surface of the sidewall 24 of the syringe barrel 16. For example, as Figure 2A and Figure 2B As shown, the body 124 may include two ribs 132, and the recessed portion 148 is located between the two ribs. However, within the scope of the present disclosure, the number of ribs 132 can vary. In some examples, the body 124 may include only one rib 132, while in other examples, the body 124 may include three or more ribs 132.

[0109] In some examples, the distal stop 112 also includes one or more protrusions 146 (e.g., detents or other bumps) that extend axially from the proximal surface 126 of the body 124. The protrusions 146 can be positioned on the proximal surface 126 to engage the distal stop 112 when the proximal stop 110 is pressed against the distal stop 112 (e.g., as shown in FIG. Figure 3D As shown), a small gap is created between the distal surface 118 of the proximal stop 110 and the proximal surface 130 of the distal stop 112.

[0110] In some examples, the body 124 also includes a slit 134 extending through the body 124 to allow fluid to flow through the body 124 when the distal stop 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 cavity 140 and the distal surface 128 of the body 124. In some examples, the body 124 includes a single slit 134 that extends across the distal surface 128 substantially transverse to the central longitudinal axis of the body 124. In other examples, the body 124 can include multiple slits and / or can include slits 134 located at other locations on the distal surface 128 of the body 124.

[0111] The distal stopper 112 and / or the slit 134 can be configured to transition between a closed position, in which fluid flow through the slit 134 of the body 124 and / or the distal stopper 112 is blocked, and an open position, in which fluid can flow through the distal stopper 112 and / or the slit 134, thereby establishing fluid communication between the proximal chamber 12 and the distal chamber 14 through the distal stopper 112. In some examples, the distal stopper 112 can be configured to remain in the closed position when the fluid pressure in the proximal chamber 12 of the syringe barrel 16 is less than a predetermined opening pressure. The distal stopper 112 can be configured to transition to the open position when the fluid pressure in the proximal chamber 12 of the syringe barrel 16 is greater than or equal to the predetermined opening pressure. In some examples, the slit 134 and / or the distal stop 112 are biased to a closed position and initially disposed in the closed position, which means that the distal stop 112 and / or the slit 134 are in the closed position when the fluid pressure in the proximal chamber 12 is at a nominal pressure or substantially equal to the fluid pressure in the distal chamber 14. When the fluid pressure in the proximal chamber 12 substantially increases above a predetermined activation pressure value, the distal stop 112 and / or the slit 134 transition to an open position.

[0112] The activation pressure or opening pressure of the distal stopper 112 or slit 134 can be selected based on the fluid pressure typically generated when the stopper is manually moved through the barrel of a conventional syringe at a reasonable rate (such as the fluid pressure generated when a practitioner pushes the plunger rod of the syringe through the syringe barrel). In some examples, the activation pressure or opening pressure of the slit 134 and / or the distal stopper 112 is at least 30 psi, but the activation pressure or opening pressure can be selected or optimized for different syringe designs by considering, for example, the size, shape, and material of the stops 110, 112, the syringe barrel 16, and other components of the multi-chamber syringe 10. In some examples, the syringe 10 is configured so that the activation pressure or opening pressure of the slit 134 and / or the distal stopper 112 is greater than the pressure required to infuse the drug (i.e., the pressure required to expel the initial fluid F1 from the distal chamber 14 through the fluid port 22 and through the needle cannula and / or VAD to the patient). Thus, in order to cause the distal stop 112 to open, the practitioner may need to apply a greater force to the plunger rod of the syringe 10 connected to the proximal stop 110 than is required to move the stops 110, 112 through the barrel 16. Due to these differences in the forces that must be applied to the plunger rod, the practitioner may receive feedback indicating that the initial fluid F1 has been expelled from the syringe 10 and that the distal stop 112 is in its most distal position in the barrel 16 (i.e., a sense of the need to increase the force applied to the plunger rod).

[0113] The distal stopper 112 also includes a film, coating, layer, or other barrier between the fluid chambers 12, 14 and the proximal and distal surfaces 126, 128 of the distal stopper 112. Specifically, the distal stopper 112 can include a first barrier film or proximal barrier film 136 bonded to the proximal surface 126 of the body 124 and a second barrier film or distal barrier film 138 bonded to the distal surface 128 of the body 124. In some examples, the proximal barrier film 136 also covers the inner surface of the cavity 140 of the body 124. Alternatively, the proximal barrier film 136 can extend over or cover multiple portions of the open end of the cavity 140 that extends through the proximal surface 126 of the body 124. In some examples, the proximal barrier membrane 136 and / or the distal barrier membrane 138 may include slits or openings that align with the slits 134 extending through the body 124 to allow fluid to flow through the distal stop 124 .

[0114] The barrier membranes 136, 138 may be formed of a material similar to or the same as the distal barrier membrane 122 of the proximal stopper 110. For example, the barrier membranes 136, 138 of the distal stopper 112 may be formed of any barrier material described in the aforementioned '214 publication, or other biocompatible and fluid-impermeable and / or hydrophobic materials known in the art. In some examples, the barrier membranes 136, 138 may be formed of a fluoropolymer material, such as a polymer formed of polytetrafluoroethylene resin (PTFE), ethylene tetrafluoroethylene resin (ETFE), expanded polytetrafluoroethylene (ePTFE), or a similar fluoropolymer material.

[0115] In some examples, the barrier films 136, 138 are sized or trimmed to cover only the fluid contacting surface of the distal stopper 112. For example, the proximal barrier film 136 and the distal barrier film 138 can be trimmed into a disc-shaped member having a diameter that matches or substantially matches (e.g., within about 5%) the outer diameter of the proximal surface 126 and / or the distal surface 128 of the distal stopper 112. The barrier films 136, 138 can be mounted or secured to the proximal surface 126 and the distal second surface 128 of the distal stopper 112 by various lamination and bonding methods known in the art. For example, a curable polymer material and / or a biocompatible adhesive can be used to secure the barrier films 136, 138 to the surfaces 126, 128 of the distal stopper 112. The outer peripheral surface 130 of the distal stopper 112 includes a rib 132 that contacts the side wall of the barrel 16, and the rib may be free of a barrier layer, coating, or film so as not to affect the ability of the distal stopper 112 to seal against the side wall 24 of the syringe barrel 16 and / or slide against the side wall of the syringe barrel. In some examples, the thickness of the barrier membranes 136, 138 can affect the fluid pressure required to convert the distal stopper 112 to the open position. Therefore, the thickness of the barrier membrane 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 membrane 136 and / or the distal barrier membrane 138 can be about 0.013 mm to about 0.25 mm. In one configuration, a melt-processable film can be used so that the film can be thermoformed simultaneously with the rubber vulcanization and / or molding steps.

[0116] Continue to refer Figure 1A and Figure 1B ,as well as FIG. 3A to FIG. 3D, the stops 110, 112 of the syringe 10 of the present disclosure are configured to move through the barrel 16 simultaneously and in a coordinated manner, even though the stops 110, 112 are not mechanically connected or engaged together. This simultaneous movement occurs due to the incompressible nature of the liquid (e.g., auxiliary fluid F2 (e.g., a second therapeutic agent or flushing solution)) in the proximal chamber 12 of the barrel 16. More specifically, pressure applied to the proximal stop 110 is transferred to a fluid column of auxiliary fluid F2 in the proximal chamber 12. This fluid column applies pressure to both the distal stop 112, causing the distal stop 112 to move toward a distal-most position (e.g., Figure 3C and Figure 3D 1 (shown) moves through the syringe barrel 16, thereby expelling the initial fluid F1 from the distal chamber 14 of the syringe barrel 16. When the distal stopper 112 is in the most distal position, the distal end 20 of the barrel 16 prevents further movement of the distal stopper 112, which means that continued application of pressure to the proximal stopper 110 causes an increase in fluid pressure in the proximal chamber 12. The increase in fluid pressure causes the distal stopper 112 to switch to the open position, thereby allowing the auxiliary fluid F2 to pass through the distal stopper 112 and be discharged from the syringe 10 through the fluid port 22 of the barrel 16.

[0117] In a similar manner, although the stops 110, 112 are not mechanically connected or engaged together, the stops 110, 112 also move together in the proximal direction through the barrel 16. Specifically, the movement of the proximal stop 110 in the proximal direction creates a vacuum or negative pressure in the syringe barrel 16, which attracts the distal stop 112 along with the proximal stop 110 through the barrel 16 in the proximal direction. Figure 3B Movement of the distal chamber 14 (indicated by arrow P) draws initial fluid F1 into the distal chamber 14 through the fluid port 22 of the barrel 16 in a manner similar to the manner in which fluid is drawn from a vial into a conventional syringe.

[0118] The stops 110, 112 are configured to move between several positions or configurations during the fluid expulsion process. The syringe 10 may be initially disposed in a partially filled configuration, such as Figure 3A As shown, there is an auxiliary fluid F2 (e.g., a second therapeutic agent or flushing solution) in the proximal chamber 12. In this initial position or partially filled position, the stoppers 110, 112 are spaced apart from each other by a distance D2 (e.g., Figure 3B), which is sufficient to contain a volume of about 1 mL to 20 mL (or preferably about 5 mL to 10 mL) of auxiliary fluid F2 in the proximal chamber 12. When ready for use, if the distal stopper 112 is not in the most distal position within the barrel 16, the practitioner can move the distal stopper 112 distally through the barrel 16 so that the distal stopper 112 abuts the distal end 20 of the barrel 16. The practitioner can then move the distal stopper 112 in the proximal direction ( Figure 3B The stoppers 110 and 112 are moved as shown by the arrow P in the middle, and the initial fluid F1 is sucked into the distal chamber 14, thereby completely filling the syringe 10, as shown in FIG. Figure 3B shown.

[0119] When the syringe 10 is fully filled, the distal stop 112 is a distance D1 (eg, Figure 3B Once the syringe 10 is fully filled, the stops 110, 112 are moved in the distal direction (as shown). Figure 3C The movement of the distal stopper 112 (indicated by the arrow D in the middle) moves the distal stopper 112 toward the distal end 20 of the barrel 16, thereby discharging the initial fluid F1 from the distal chamber 14. Figure 3C , the syringe 10 is shown in an intermediate position with a filled proximal chamber 12 and an empty distal chamber 14. Continued distal movement of the stops 110, 112 causes the fluid pressure in the proximal chamber 12 to increase toward the activation pressure or opening pressure of the distal stop 112. Once the fluid pressure in the proximal chamber 12 exceeds the activation pressure or opening pressure of the distal stop 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 stop 112. Once fluid communication between the chambers 12, 14 is established, the auxiliary fluid F2 is expelled from the syringe 10 by moving the proximal stop 110 toward the distal stop 112. Specifically, movement of the proximal stopper 110 toward the distal stopper 112 causes the auxiliary fluid F2 to move from the proximal chamber 12 to the distal chamber 14 , and then from the distal chamber 14 through the fluid port 22 . Figure 3D The syringe 10 is shown in an end-of-use or final position after the fluids F1, F2 are expelled from the syringe barrel 16. In the end-of-use or final position, the distal barrier membrane 138 bonded to the distal surface 128 of the distal stopper 112 is in contact or nearly in contact with the distal end 20 of the barrel 16. In addition, the distal surface 118 of the proximal stopper 110 is in contact or nearly in contact with the proximal surface 126 of the distal stopper 112.

[0120] Reference again Figure 1A and Figure 1B ,as well as FIG. 3A to FIG. 3D, the syringe 10 also includes a plunger rod 26, which is connected to the proximal stopper 110 to move the proximal stopper 110 through the syringe barrel 16. As previously described, the movement of the proximal stopper 110 through the barrel 16 causes the distal stopper 112 to move through the barrel 16 in coordination with the proximal stopper 110, although the stops 110, 112 are not mechanically connected or joined together. The plunger rod 26 can be, for example, an injection molded component formed of a rigid thermoplastic material, such as polyester, polycarbonate, polypropylene, polyethylene, polyethylene terephthalate, or other thermoplastic materials known in the art. The plunger rod 26 can be a conventional plunger rod used in currently available syringes and can be connected to the proximal stopper 110 by a standard mechanical connector, fastener, or adhesive. In other examples, the plunger rod 26 can be integrally formed or co-molded with the proximal stopper 110.

[0121] In some examples, the plunger rod 26 includes a distal end 28 that engages a proximal stop 110. For example, Figure 1B and Figure 3C As best shown in FIG. 1 , the distal end 28 of the plunger rod 26 may include a portion of a housing 150 (eg, Figure 1B and Figure 3C 110 , 112 . The syringe 10 also includes a threaded connector 30 (shown in FIG. 1 ) with a cavity extending inwardly from the proximal surface of the proximal stop 110. The plunger rod 26 also includes a proximal end 32 that protrudes proximally from the proximal end 18 of the syringe barrel 16, and a body 34 that extends between the proximal end 32 and the distal end 28 of the plunger rod 26. The proximal end 32 of the plunger rod 26 may include a thumb pressure plate 36 that is used to manipulate the plunger rod 26 to move the stops 110, 112 through the syringe barrel 16. The body 34 of the 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 examples, the cross-section of the plunger rod 26 may be I-shaped, circular, square, L-shaped, or other conventional shapes known in the art that can be formed by an injection molding process. In some examples, the syringe 10 may also include a removable plunger cap 38 (such as Figure 3A The removable plunger cap 38 is a removable plunger cap that is engaged between the thumb plate 36 of the plunger rod 26 and the proximal end 18 of the barrel 16 to prevent the plunger rod 26 from moving until the removable plunger cap 38 is removed from the syringe 10. The plunger rod cap 38 prevents the plunger rod 26 from being pressed into the syringe barrel 16 at an inappropriate time, such as during transportation of the prefilled syringe from a manufacturing facility to a customer.

[0122] Method for discharging fluid from a multi-chamber syringe

[0123] As previously described, the syringe 10 is used to sequentially discharge fluids from the syringe 10 into a needle cannula or VAD, such as discharging a medical fluid and then discharging another type of medical fluid or a flushing solution. Figure 4 A flow chart showing the steps for sequentially expelling fluid from the syringe 10 is shown.

[0124] like Figure 4 As shown, at step 210, the practitioner initially obtains a partially filled syringe 10 in which the proximal chamber 12 of the syringe 10 is filled with a predetermined volume of an auxiliary fluid F2 (e.g., a second type of therapeutic 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 the therapeutic agent or flushing solution. Figure 3A The syringe 10 in the initial configuration or partially filled configuration is shown. At step 212, the practitioner prepares the syringe 10 for use by, for example, removing all packaging from the syringe 10 and removing the plunger rod cap 38 that fixes the plunger rod 26 in a suitable position. When the distal stopper 112 of the syringe 10 is not initially disposed in the distal most position, the practitioner can also move the plunger rod 26 in the distal direction so that the distal stopper 112 of the syringe 10 is completely placed in its distal most position. At step 214, the practitioner communicates the syringe barrel 16 with the internal fluid of the container containing the medical fluid to be delivered to the patient. For example, the practitioner can attach a needle (not shown) to the fluid port 22 at the distal end 20 of the syringe barrel 16 and insert the needle into a container (e.g., a medical vial) containing the medical fluid to be injected into the patient.

[0125] At step 216, the practitioner draws an initial fluid F1 (eg, a medical fluid) into the distal chamber 14 of the barrel 16. For example, the practitioner may grasp the plunger rod 26 and move the plunger rod 26 in a proximal direction (eg, Figure 3B The stoppers 110 and 112 are moved in the proximal direction, thereby sucking or drawing the initial fluid F1 from the interior of the container into the distal chamber 14 of the syringe barrel 16, as shown in FIG. Figure 3A As shown by the arrow A1. Figure 3B The syringe 10 is shown in a fully filled configuration with the distal chamber 14 having the initial fluid F1 therein and the proximal chamber 12 having the auxiliary fluid F2 therein.

[0126] Once an initial dose of fluid F1 to be delivered to the patient is drawn into the distal chamber 14, at step 218, the practitioner removes the needle from the fluid port 22 of the syringe barrel 16 and connects the fluid port 22 to another needle cannula having a sharp tip to inject the fluid into the patient or VAD. For example, the practitioner can insert the nozzle of the syringe barrel 16 into a corresponding port or valve of the VAD to establish fluid communication between the syringe barrel 16 and the tubing chamber of the VAD. At step 220, once the syringe 10 is properly connected to the needle cannula or VAD, the practitioner grasps the plunger rod 26 and moves in the distal direction ( Figure 3B The plunger rod 26 is pushed by the distal stopper 110 (as indicated by the arrow D), which causes the stoppers 110, 112 to move distally through the syringe barrel 16. The distal movement of the distal stopper 112 causes the initial fluid F1 (e.g., medical fluid) in the distal chamber 14 of the syringe barrel 16 to be discharged from the syringe barrel 16 (e.g., Figure 3B The practitioner continues to move the plunger rod 26 in the distal direction until the distal stopper 112 is placed in its most distal position in the syringe barrel 16. Figure 3C , the distal stopper 112 is shown in a distal-most position, wherein the stopper 112 is in a closed position.

[0127] In order to convert the distal stopper 112 to the open position and establish fluid communication between the proximal chamber 12 and the distal chamber 14, the practitioner continues to move the plunger rod 26 in the distal direction. As previously described, 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. Therefore, once the distal stopper 112 is in the most distal position, the practitioner may need to apply additional force to the plunger rod 26 to open the distal stopper 112. In addition, as previously described, the distal movement of the plunger rod 26 can be a single continuous stroke in the distal direction performed with one hand (e.g., a one-handed operation). In this way, the practitioner does not need to perform any other actions to automatically open the distal stopper 112 except for continuously moving the plunger rod 26 distally. More specifically, when the distal stopper 112 is in the distal-most position, continued distal movement of the plunger rod 26 causes the proximal stopper 110 to move distally through the barrel 16 toward the distal stopper 112. This distal movement of the proximal stopper 110 causes the fluid pressure in the proximal chamber 12 to increase toward the activation pressure or opening pressure of the distal stopper 112. Once the fluid pressure in the proximal chamber 12 reaches or exceeds the activation pressure or opening pressure of the distal stopper 112, the distal stopper 112 opens to establish fluid communication between the proximal chamber 12 and the distal chamber 14 through the distal stopper.

[0128] At step 222, once fluid communication between the proximal chamber 12 and the distal chamber 14 is established, the practitioner continues to push the plunger rod 26 in the distal direction, causing the proximal stopper 110 to move through the syringe barrel 16 in the distal direction toward the proximal surface 126 of the distal stopper 112. As shown by arrow A3 (at Figure 3C ), the movement of the proximal stopper 110 toward the distal stopper 112 causes the auxiliary fluid F2 (e.g., a second therapeutic agent or flushing solution) in the proximal chamber 12 to pass through the distal stopper 112 and enter the distal chamber 14. The auxiliary fluid F2 then passes through the distal chamber 14 and is discharged from the syringe barrel 16 to the needle cannula or VAD through the fluid port 22 at the distal end 20 of the syringe barrel 16. Figure 3D 1. The syringe 10 is shown in an end-of-use or final position, wherein the distal surface 118 of the proximal stopper 110 is in contact or nearly in contact with the proximal surface 126 of the distal stopper 112.

[0129] Method for molding a stopper for a multi-chamber syringe

[0130] The distal stopper 112 for the multi-chamber syringe 10 of the present disclosure can be manufactured by a modified one-shot injection molding method that produces a molded stopper that includes an integrated body 124 formed of two or more parts or sections. As previously described, the stopper 112 also includes a proximal barrier film 136 bonded or laminated to the proximal surface 126 of the integrated body 124 and a distal barrier film 138 bonded or laminated to the distal surface 128 of the integrated body 124. Figure 5 is a flow chart showing the steps of a molding method for making the distal stop 112 . FIG. 6A to FIG. 6E is a schematic diagram showing the steps of the molding method.

[0131] At step 310, the molding method initially includes molding a first component or proximal component 124a and a second component or distal component 124b, which will be joined together to form the body 124 of the distal stop 112. A schematic diagram of the components 124a, 124b is shown in FIG. FIG. 6A to FIG. 6DAs shown. Components 124a, 124b can be formed from a precursor material in a separate mold by a one-shot injection molding process, and the precursor material can be cured to form a thermoplastic elastomer component. As previously described, the thermoplastic elastomer can include silicone, polypropylene, polyethylene, or synthetic rubber or natural rubber (e.g., isoprene), or a combination thereof. In some examples, the first component or proximal component 124a includes two annular ribs 132, and the recessed portion 148 is located between these ribs 132. The distal component 124b can be narrower, and the width of the outer peripheral surface of the distal component is not enough to make the outer peripheral surface contact the inner surface of the syringe barrel 16. For example, the diameter of the distal component 124b can be approximately the same as the diameter of the recessed portion 148 of the proximal component 124a. Components 124a, 124b can be partially cured so that components 124a, 124b are strong enough to be removed from the mold, but are sticky enough to be joined together in the subsequent final molding step. At step 310, each part is cured to the flow point. At step 318, the curing cycle is repeated.

[0132] In step 312, after molding and partially curing the components 124a, 124b, the method further includes bonding sheets of barrier material to the components 124a, 124b to form the proximal barrier membrane 136 and the distal barrier membrane 138. Fig. 6A As shown, a sheet of barrier material is applied to the proximal surface 126 of the first component 124a, and a second sheet of barrier material is applied to the distal surface 128 of the second component. For example, the barrier sheet can be bonded to the components 124a, 124b by the adhesiveness of the partially cured components 124a, 124b. The sheets can also be bonded to the components 124a, 124b using a biocompatible adhesive or a certain amount of uncured polymer material applied to the surfaces 126, 128 of the components 124a, 124.

[0133] At step 314, the method further includes trimming the barrier sheet to form barrier films 136, 138. For example, Figure 6B As shown, the sheet material on the proximal surface 126 of the proximal component 124a can be trimmed to a diameter matching the proximal surface 126 to form a proximal barrier membrane 136. The sheet material covering the distal surface 128 of the distal component 124b can be trimmed to a diameter matching the distal surface 128 of the distal component 124b to form a distal barrier membrane 138.

[0134] At step 316, the components 124a, 124b and the barrier films 136, 138 bonded thereto are then positioned in the opposing halves or components 102a, 102b of the finishing mold, as shown. Figure 6CSpecifically, components 124a, 124b are positioned so that barrier films 136, 138 are in contact with the surfaces of the mold components, and the uncured surfaces of components 124a, 124 are positioned inside the mold. At step 318, as shown Fig.6D As shown, mold parts 102a, 102b are brought together so that the uncured surfaces of parts 124a, 124b are aligned along parting line PL (eg, Figure 6C and Fig.6D 124a, 124b) are in contact with each other. In some examples, the parting line of the mold can be slightly loosened, for example, by about 0.05 mm to about 0.2 mm. The mold is then cured to a temperature of about 50° C. to about 70° C. to completely cure the parts 124a, 124b, thereby forming an integrated body 124 from the parts 124a, 124b. Optionally, the pressure applied to the mold to completely cure the parts is about 30 bar to 250 bar, depending on the size and shape. Typically, the butyl mixture may take a total of about 2 minutes to 8 minutes and can be divided into a first molding step and a final molding step.

[0135] At step 320, after curing, the molded part is removed from the finishing mold, such as Fig. 6E Specifically, the molded component is a stopper 112, which includes an integrated molded body 124, wherein a proximal barrier film 136 is bonded or laminated to a proximal surface 126 of the body 124, and a distal barrier film 138 is bonded or laminated to a distal surface 128. At step 322, the method further includes: forming a slit 134 in the distal surface 128 of the body 124, thereby forming, for example, Figure 2A and Figure 2B The stopper 112 is shown.

[0136] Although examples of the stoppers, multi-chamber syringes, and methods of the present disclosure are shown in the accompanying drawings and described in detail above, other examples will be apparent to and readily made by those skilled in the art without departing from the scope and spirit of the invention. Therefore, the above description is intended to be illustrative rather than restrictive. The invention described above is defined by the appended claims, and all changes to the invention that fall within the equivalent meaning and equivalent range of the claims will be included within the scope of the claims.

Claims

1. A stopper for a multi-chamber syringe, the stopper comprising: a body including a first end surface, a second end surface, a peripheral surface extending between the first end surface and the second end surface, and at least one slit extending through the body to allow fluid to flow through the body of the stopper; a first barrier film bonded to the first end surface of the body; as well as a second barrier film bonded to the second end surface of the body; Wherein, the first barrier membrane and / or the second barrier membrane comprises a slit or an opening which is aligned with the slit extending through the body to allow fluid to flow through the stopper.

2. The stopper of claim 1, further comprising at least one protrusion extending axially from the proximal end of the body to separate the stopper from another stopper of a multi-chamber syringe.

3. The stopper according to claim 1, wherein: The outer peripheral surface of the body includes: at least one rib, the at least one rib being configured to contact the inner surface of the side wall of the syringe barrel; and at least one recessed portion, the at least one recessed portion being configured to be spaced apart from the inner surface of the side wall of the syringe barrel.

4. The stopper according to claim 1, wherein: The first stopper and / or the second stopper comprises a thermoplastic elastomer, and the thermoplastic elastomer comprises at least one of the following: silicone, polypropylene, polyethylene, synthetic rubber, natural rubber or a combination thereof.

5. The stopper according to claim 1, wherein: The body also includes a cavity extending axially through a portion of the body from the first end surface of the body toward the second end surface of the body.

6. The stopper according to claim 5, wherein: The cavity includes an open first end, a closed second end having a substantially planar second surface, and an annular side surface between the first end and the second end, wherein the annular side surface includes a concave portion and a convex portion.

7. The stopper according to claim 6, wherein: The slot extending through the body extends between the planar second surface of the cavity and the second end surface of the body.

8. The stopper according to claim 1, wherein: The body is made from two separately moulded parts that are fitted together by a subsequent moulding process.

9. The stopper according to claim 1, wherein: The stopper is configured to switch between (i) a closed position and (ii) an open position. When the fluid pressure in the syringe barrel is lower than a predetermined opening pressure, the stopper is in the closed position to prevent the fluid from flowing through the slit of the body. When the fluid pressure in the syringe barrel is greater than or equal to the predetermined opening pressure, the stopper is in the open position to establish fluid communication between the chambers of the syringe barrel through the stopper.

10. The stopper according to claim 1, wherein: The slit of the body is biased to the closed position and is initially disposed in the closed position.

11. The stopper according to claim 1, wherein: The first barrier membrane and / or the second barrier membrane comprises a disk-shaped member, a diameter of which matches a diameter of the first end surface or the second end surface of the main body.

12. The stopper according to claim 1, wherein: The first barrier membrane extends over an annular surface of the body and a surface of a cavity defined by the body.

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

14. The stopper according to claim 1, wherein: The outer peripheral surface of the body is free of a barrier film.

15. The stopper according to claim 1, wherein: The outer peripheral surface of the body is uncoated.

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

17. A multi-chamber syringe for sequentially ejecting at least an initial fluid and subsequently an auxiliary fluid, the syringe comprising: a barrel, the barrel comprising a first end, a second end and a sidewall, the second end comprising a fluid port, the fluid port being used to discharge the initial fluid and the auxiliary fluid from the barrel, the sidewall extending between the first end and the second end of the barrel; a first stopper slidably positioned in the barrel; as well as a second stopper, the second stopper comprising the stopper according to claim 1, the second stopper being slidably positioned in the barrel, Wherein, the first stopper and the second stopper define a first chamber of the syringe barrel between the first stopper and the second stopper, and a second chamber of the syringe barrel is defined between the second stopper and the second end of the syringe barrel, the first chamber being configured to contain the auxiliary fluid, and the second chamber being configured to contain the initial fluid.

18. A molding method for the stopper according to claim 1, the method comprising: molding the first and second parts of the body of the stopper into a partially molded state; attaching a first barrier membrane to a first end of the partially molded first component; attaching a second barrier membrane to a second end of the partially molded second component; bonding the first component to the second component in a finishing mold to form the stopper, the stopper comprising the body and the first and second barrier films laminated to the body; as well as A slit is formed through the body and through the first barrier film and / or the second barrier film.

19. The method according to claim 18, wherein: The first component and the second component are molded by a one-time injection molding process.

20. The method according to claim 18, wherein: Connecting the first barrier film to the molded first component includes attaching a flat sheet of barrier material to the first end of the first component and trimming the flat sheet to match the shape of the first end of the first component, and Wherein connecting the second barrier film to the second end of the second component comprises: attaching a flat sheet of barrier material to the second end of the second component and trimming the flat sheet to match the shape of the second end of the second component.

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