Valve stopper for a multi-chamber medical injection device

Abstract

Provided herein is a valve stopper positionable within a barrel of a multi-chamber injection device. The valve stopper includes a membrane that separates a first chamber and a second chamber of the barrel. A lateral wall is joined to the membrane that includes one or more circumferential ribs configured to sealingly engage an inner surface of the barrel. The ribs may have an outer diameter that is greater than a barrel inner diameter, such that the ribs are compressed when the valve stopper is positioned within the barrel. The ribs may be spaced apart such that an axial pitch therebetween that is greater than one half of the compressed diameter of the ribs. Guiding features may be included on the valve stopper that extend axially along a length thereof, with the guiding features enabling alignment and guidance of the valve stopper when inserted into and advanced through the barrel.

Description

VALVE STOPPER FOR A MULTI-CHAMBER MEDICAL INJECTION DEVICECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to United States Provisional Patent Application No. 63 / 557,677 entitled “Valve for a Multi-Chamber Medical Injection Device” filed February 26, 2024, this application also claims priority to United States Provisional Patent Application No. 63 / 669,991 entitled “Valve for a Multi-Chamber Medical Injection Device” filed July 11, 2024, the disclosures of which are hereby incorporated by reference in their entireties.BACKGROUND OF THE INVENTIONField of the Invention

[0002] The present disclosure relates generally to a valve stopper for a medical injection device containing doses of multiple fluids and, in particular, to a valve stopper for a medical injection device that provides sequential expulsion of a first or initial fluid, such as a first type of a medical fluid, followed by a secondary fluid, such as another type of medical fluid.Description of Related Art

[0003] Prefilled injection devices are common containers used to administer liquids (e.g., medications or drugs) to a patient and include syringes, cartridges and auto-injectors or the like. They usually comprise a plunger stopper in gliding engagement within a container, the container being filled with a pharmaceutical composition in order to provide the practitioners with a ready-to-use injection device for patients.

[0004] A container has a substantially cylindrical shape, and comprises a proximal end able to be stoppered by a plunger stopper, a distal end wherein the pharmaceutical composition is expelled from the container, and a lateral wall extending between the proximal end and the distal end of the container. In practice, the plunger stopper is aimed at moving, upon the pressure exerted by a plunger rod, from a proximal end of the container towards the distal end of the container, thereby expelling the drug contained into the container.

[0005] When compared to empty injection devices that are filled with a vial-stored pharmaceutical composition just prior to the injection to the patient's body, the use of prefilled injection devices leads to several advantages. In particular, by limiting the preparation prior to the injection, the prefilled injection devices provide a reduction of medical dosing errors, aminimized risk of microbial contamination and an enhanced convenience of use for the practitioners. Furthermore, such prefilled containers may encourage and simplify selfadministration by the patients which allows reducing the cost of therapy and increasing the patient adherence. Finally, prefilled injection devices reduce loss of valuable pharmaceutical composition that usually occurs when a pharmaceutical composition is transferred from a vial to a non-prefilled injection device. This results in a greater number of possible injections for a given manufacturing batch of pharmaceutical composition, thus reducing buying and supply chain costs.

[0006] Prefilled injection devices can be used to carry out the injection of a plurality of compositions or medicaments to a patient. In such case, the container may include two chambers, including a first chamber adapted to contain a first composition and a second chamber adapted to contain a second composition. The two chambers are separated by a second stopper that may be termed as a sequential stopper that prevents, when the prefilled injection devices is stored or transported, the compositions from passing from one chamber to the other and mixing.

[0007] In some prefilled injection devices that include multiple compositions for injection to a patient, the barrel of the injection device may be modified (from a typical cylindrical barrel) to include one or more bypass channels therein The bypass channels may provide for a reconstitution of a lypholized composition (with a composition first flowing through the bypass channel) and a subsequent injection of the reconstituted mixture and / or provide for a sequential injection of the compositions in the barrel (via initial injection of a first / distal composition and a subsequent injection of a second / proximal composition that flows through the bypass (when the stopper is moved distally past the bypass channel). However, it is recognized that the manufacturing of a barrel to include such bypass channels can greatly increase the manufacturing or packaging costs thereof.

[0008] In other prefilled injection devices that include multiple compositions for injection to a patient, the sequential stopper includes an opening or slit formed therein or therethrough that functions as a valve (i.e., a “valve stopper”) to prevent the mixing of the two solutions during storage or transportation, or before the first solution has been injected, while allowing subsequent injection of the second solution. Existing valve stoppers function to effectively prevent the mixing of the two solutions and provide for a sequential injection of the fluids; however, existing valve stoppers do present a number of drawbacks therewith. As one example, the configuration of the valve stopper may be such that a sealing surface of the valvestopper exhibits large amounts of friction with the inner surface of the barrel, such that a substantial force may need to be applied onto the plunger in order for a pressure of the second solution to advance the valve stopper, which may lead to an inadvertent forcing of the second fluid through the opening / slit therein prior to injection of the first fluid. As another example, the design of existing valve stoppers may make the stoppers prone to tilting when being positioned within the container (e.g., during vent tube stoppering) and / or during distal advancement thereof when injecting the first fluid, so as to impact the valve stopper functionalities (i.e., prevent mixing of the two solutions and / or glide).

[0009] Accordingly, a need exists in the art for an injection device that includes a typical cylindrical barrel and a valve stopper that addresses the aforementioned drawbacks.SUMMARY OF THE INVENTION

[0010] Provided herein is a multi-chamber medical injection device for injecting at least one composition. The multi-chamber medical injection device includes a barrel extending from a proximal end to a distal end that comprises a cylindrical wall having a barrel inner diameter, a plunger stopper adapted to be translationally movable inside the barrel, and a valve stopper arranged between the distal end of the barrel and the plunger stopper and adapted to be translationally movable inside the barrel. The valve stopper further includes a membrane configured to separate a distal chamber of the barrel from a proximal chamber of the barrel and that comprises at least one slit extending through at least a part of a thickness of the membrane between a proximal face and a distal face thereof, with the slit configured to selectively create a fluid path through the membrane from the proximal face to the distal face depending on the pressure exerted by a composition onto the proximal face of the membrane for transferring fluid only from the proximal chamber to the distal chamber, and a lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising a sealing surface including one or more circumferential ribs configured to sealingly engage the inner surface of the barrel. At least one of the one or more circumferential ribs has a rib outer diameter that is greater than the barrel inner diameter, with the at least one of the one or more circumferential ribs having a compression rate of between 2% and 12% when positioned within the barrel.

[0011] In certain configurations, the compression rate is defined according to:Compression Rate = (l-(barrel_ID / rib_OD)) x 100,where barrel_ID is the barrel inner diameter and rib_OD is the rib outer diameter of the at least one rib.

[0012] In certain configurations, the one or more circumferential ribs comprises a first rib and a second rib.

[0013] In certain configurations, the valve stopper comprises a cylindrical stopper, with the rib outer diameter of each of the first rib and the second rib being equal.

[0014] In certain configurations, the first and second ribs are radially compressed by the barrel such that the rib outer diameter is compressed to a compressed rib diameter, and wherein the first rib and the second rib are axially spaced apart by a pitch that is greater than 30% of the compressed rib diameter, and preferably greater than 50% of the compressed rib diameter.

[0015] In certain configurations, the valve stopper comprises a conical stopper, with the rib outer diameter of the first rib being a first diameter and the second rib having a second diameter that is less than the first diameter.

[0016] In certain configurations, a conicity of the conical stopper is up to 10%, as defined by:Conicity = (((rib_OD_first - rib_OD_second) / 2) / L_pitch)) x 100, where rib_OD_first is the first diameter, rib_OD_second is the second diameter, and L_pitch is an axial distance between the first rib and the second rib.

[0017] In certain configurations, the multi-chamber medical injection device is configured to sequentially inject two compositions, with a first composition contained within the distal chamber between the valve stopper and the distal end of the barrel and a second composition contained within the proximal chamber between the valve stopper and the plunger stopper.

[0018] In certain configurations, the multi-chamber medical injection device is one of a stand-alone syringe or cartridge, or a syringe or cartridge integrated with an auto-injector, pen or safety device.

[0019] Also provided herein is a multi-chamber medical injection device for injecting at least one composition. The multi-chamber medical injection device includes a barrel extending from a proximal end to a distal end and comprising a cylindrical wall having a barrel inner diameter, a plunger stopper adapted to be translationally movable inside the barrel, and a valve stopper positioned within the barrel distally from the plunger stopper and adapted to be translationally movable inside the barrel. The valve stopper further includes a membrane configured toseparate a distal chamber of the barrel from a proximal chamber of the barrel and comprising at least one slit extending through at least a part of a thickness of the membrane between a proximal face and a distal face thereof, with the at least one slit configured to selectively create a fluid path through the membrane from the proximal face to the distal face depending on the pressure exerted by a composition onto the proximal face of the membrane for transferring fluid only from the proximal chamber to the distal chamber, and a lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising a sidewall, a first rib extending radially outward from an outer surface of the sidewall and around an outer circumference thereof, and a second rib extending radially outward from the outer surface of the sidewall and around the outer circumference thereof. At least one of the first and second ribs has a rib outer diameter that is greater than the barrel inner diameter, with the rib outer diameter being compressed to a compressed rib diameter when positioned within the barrel. The first rib and the second rib are axially spaced apart by a pitch that is greater than 30% of the compressed rib diameter.

[0020] In certain configurations, the first rib and the second rib are axially spaced apart by a pitch that is greater than 50% of the compressed rib diameter.

[0021] Also provided herein is a valve stopper configured to be positioned inside a barrel of an injection device for injecting at least one composition through a distal end of the barrel. The valve stopper includes a membrane configured to separate a distal chamber of the barrel from a proximal chamber of the barrel, the membrane comprising a at least one slit extending through at least a part of a thickness of the membrane between a proximal face and a distal face thereof, with the at least one slit configured to selectively create a fluid path through the membrane from the proximal face to the distal face depending on a pressure exerted by a fluid onto the proximal face of the membrane for transferring fluid only from the proximal chamber to the distal chamber. The valve stopper also includes a lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising a sidewall, a circumferential rib positioned at one end of the sidewall and joined to the membrane, with the circumferential rib extending out radially from the sidewall and configured to sealingly engage the inner surface of the barrel, and a plurality of guiding members extending axially along a length of the sidewall along an outer surface thereof, the plurality of guiding members spaced apart circumferentially about the sidewall.

[0022] In certain configurations, each of the plurality of guiding members comprises an elongated portion having a first end and a second end, the first end joined to the circumferentialrib, wherein the elongated portion extends radially outward from the sidewall but is radially inset from a rib outer diameter of the circumferential rib, and an end portion joined to the second end of the elongated portion, the end portion protruding radially outward from the elongated portion so that a radially outward-facing surface of the end portion is radially aligned with a radially outward-facing surface of the circumferential rib.

[0023] In certain configurations, the end portion of each of the plurality of guiding members has a shape giving a localized contact, with a point of the shape giving a localized contact presenting the radially outward-facing surface of the end portion.

[0024] In certain configurations, the plurality of guiding members comprises between three and six guiding members that are equally spaced apart circumferentially about the sidewall.

[0025] In certain configurations, an axial distance between the circumferential rib and the end portions of the plurality of guiding members is greater than 30% of a diameter of the circumferential rib, when retained and compressed within the barrel of the injection device, and preferably greater than 50% of the diameter of the circumferential rib, when retained and compressed within the barrel of the injection device.

[0026] In certain configurations, the slit extends completely through the membrane between the proximal face and the distal fare, to form a valve configured to open or close depending on the pressure exerted by the fluid onto the proximal face of the membrane.

[0027] In certain configurations, the membrane has a membrane diameter that is 85% or less of a rib outer diameter of the circumferential rib.

[0028] Also provided herein is a valve stopper configured to be positioned inside a barrel of an injection device for injecting at least one composition through a distal end of the barrel. The valve stopper includes a membrane configured to separate a first, distal chamber of the barrel from a second, proximal chamber of the barrel, the membrane comprising at least one slit extending through at least a part of a thickness of the membrane between a proximal face and a distal face thereof, with the at least one slit configured to selectively create a fluid path through the membrane from the proximal face to the distal face depending on a pressure exerted by a fluid onto the proximal face of the membrane for transferring fluid only from the second chamber to the first chamber. The valve stopper also includes a lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising a sidewall, a first rib positioned at a first end of the sidewall and formed around an outer circumference of the sidewall, the first rib extending radially outward from an outer surface of the sidewall, and a second rib positioned at a second end of the sidewall and formed around the outercircumference of the sidewall, the second rib extending radially outward from the outer surface of the sidewall. The first rib has a first rib outer diameter and the second rib has a second rib outer diameter that is less than the first diameter.

[0029] In certain configurations, with the first rib having the first rib outer diameter and the second rib having the second rib outer diameter that is less than the first diameter, the valve stopper has a frustoconical shape.

[0030] In certain configurations, a conicity of the conical stopper is up to 10%, as defined by:Conicity = (((rib_OD_first - rib_OD_second) / 2) / L_pitch)) x 100, where rib_OD_first is the first diameter, rib_OD_second is the second diameter, and L_pitch is an axial distance between the first rib and the second rib.

[0031] In certain configurations, the at least one slit is in the form of a line, centered on the proximal face of the membrane.

[0032] In certain configurations, the slit extends completely through the membrane between the proximal face and the distal fare, to form a valve configured to open or close depending on the pressure exerted by the fluid onto the proximal face of the membrane.

[0033] In certain configurations, the membrane has a membrane diameter that is 85% or less of a rib outer diameter of the circumferential rib.

[0034] In certain configurations, in a region of the membrane including the at least one slit, the membrane has a thickness between 0.2 mm and 3.0 mm.

[0035] Also provided herein is a pre-filled medical injection device for sequentially injecting a first liquid and a second liquid. The pre-filled medical injection device comprises a barrel extending from a proximal end to a distal end and including a cylindrical wall having a barrel inner diameter, a plunger stopper adapted to be translationally movable inside the barrel, and a valve stopper arranged between the distal end of the barrel and the plunger stopper and adapted to be translationally movable inside the barrel. The valve stopper further comprises a membrane configured to separate a distal chamber of the barrel from a proximal chamber of the barrel and including at least one slit extending through at least a part of a thickness of the membrane between a proximal face and a distal face thereof, with the slit configured to selectively create a fluid path through the membrane from the proximal face to the distal face depending on the pressure exerted by a composition onto the proximal face of the membranefor transferring fluid only from the proximal chamber to the distal chamber, along with a lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising a sealing surface including one or more circumferential ribs configured to sealingly engage the inner surface of the barrel. The pre-filled medical injection device also includes a first liquid contained within the distal chamber comprising a GLP- 1 agonist and a second liquid contained within the proximal chamber comprising an amyline analog.

[0036] In certain configurations, the GLP-1 agonist comprises a calcitonin receptor agonist and the amyline analog comprises a dual amylin.

[0037] In certain configurations, the GLP-1 agonist comprises semaglutide and the amyline analog comprises cagrilintide.

[0038] In certain configurations, the valve stopper presents the successive following positions during a sequential injection: a first position where the fluid path is closed; a second position where the valve stopper is more distal than in the first position, where the fluid path closed, with the proximal face of the membrane being subjected to a pressure that is inferior to a valve opening force of the at least one slit; and a third position, wherein the valve stopper abuts the distal end of the barrel, the fluid path being opened due to a pressure exerted on the proximal face of the membrane that is superior to the valve opening force of the at least one slot; wherein the first liquid is injected as the valve stopper moves from the second position to the third position; and wherein the second liquid is injected responsive to further distal movement of the plunger stopper with the valve stopper at the third position.BRIEF DESCRIPTION OF THE DRAWINGS

[0039] FIG. 1 is a perspective view of a multi-chamber medical injection device, according to a non-limiting embodiment described herein;

[0040] FIG. 2 is an exploded view of the multi-chamber medical injection device of FIG. 1;

[0041] FIG. 3 is a perspective view of a valve stopper for use in a medical injection device, according to a non-limiting embodiment described herein;

[0042] FIG. 4 is a sectional general view of the valve stopper of FIG. 2;

[0043] FIG. 5 is a sectional general view of a valve stopper for use in a medical injection device, according to another non-limiting embodiment described herein;

[0044] FIG. 6 is a cross-sectional view of a valve stopper for use in a medical injection device, according to another non-limiting embodiment described herein;

[0045] FIG. 7 is a is a cross-sectional view of a valve stopper for use in a medical injection device, according to another non-limiting embodiment described herein;

[0046] FIG. 8 is a cross-sectional view of a valve stopper for use in a medical injection device, according to another non-limiting embodiment described herein;

[0047] FIG. 9 is a cross-sectional view of a valve stopper for use in a medical injection device, according to another non-limiting embodiment described herein;

[0048] FIG. 10 is a cross-sectional view of a valve stopper for use in a medical injection device, according to another non-limiting embodiment described herein;

[0049] FIG. 11 is a cross-sectional view of a valve stopper for use in a medical injection device, according to another non-limiting embodiment described herein;

[0050] FIG. 12 is a cross-sectional view of a valve stopper for use in a medical injection device, according to another non-limiting embodiment described herein;

[0051] FIG. 13 is a cross-sectional view of a valve stopper for use in a medical injection device, shown positioned within a barrel of an injection device, according to another nonlimiting embodiment described herein;

[0052] FIG. 14 is a cross-sectional view of a valve stopper for use in a medical injection device, according to another non-limiting embodiment described herein;

[0053] FIG. 15 is a cross-sectional view of a valve stopper for use in a medical injection device, according to another non-limiting embodiment described herein;

[0054] FIG. 16 is a perspective view of a valve stopper for use in a medical injection device, according to another non-limiting embodiment described herein;

[0055] FIG. 17 is a cross-sectional view of the valve stopper of FIG. 16;

[0056] FIG. 18 is a top view of the valve stopper of FIG. 16;

[0057] FIGS. 19A-19D illustrate various configurations of the injection device of FIG. 1 during injection of first and second compositions from the device; and

[0058] FIGS. 20A-20C illustrate various configurations of an injection device during injection of a single composition from the device, according to another non-limiting embodiment described herein;

[0059] FIG. 21 is a cross-sectional view of a multi-chamber medical injection device, according to another non-limiting embodiment described herein;

[0060] FIG. 22 is a cross-sectional view of a multi-chamber medical injection device, according to another non-limiting embodiment described herein;

[0061] FIG. 23 is a cross-sectional view of a multi-chamber medical injection device, according to another non-limiting embodiment described herein; and

[0062] FIG. 24 is a cross-sectional view of a multi-chamber medical injection device, according to another non-limiting embodiment described herein.DESCRIPTION OF THE INVENTION

[0063] The following description is provided to enable those skilled in the art to make and use the described embodiments contemplated for carrying out the invention. Various modifications, equivalents, variations, and alternatives, however, will remain readily apparent to those skilled in the art. Any and all such modifications, variations, equivalents, and alternatives are intended to fall within the spirit and scope of the present invention.

[0064] For purposes of the description hereinafter, the terms “upper”, “lower”, “right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, “lateral”, “longitudinal”, and derivatives thereof shall relate to the invention as it is oriented in the drawing figures. However, it is to be understood that the invention may assume various alternative variations, except where expressly specified to the contrary. It is also to be understood that the specific devices illustrated in the attached drawings, and described in the following specification, are simply exemplary embodiments of the invention. Hence, specific dimensions and other physical characteristics related to the embodiments disclosed herein are not to be considered as limiting.

[0065] In the present disclosure, the distal end of a component or of a device means the end furthest away from the hand of the user and the proximal end means the end closest to the hand of the user, when the component or device is in the use position, i.e., when the user is holding a syringe or other injection device in preparation for or during use. Similarly, in this application, the terms "in the distal direction" and "distally" mean in the direction toward the distal tip of the syringe, and the terms "in the proximal direction" and "proximally" mean in the direction opposite the direction of the distal tip of the syringe.

[0066] With reference to the figures, the present disclosure is directed to a valve stopper 10 for use with a multi-chamber medical injection device 100 (“injection device 100”), with it understood that the term “injection device” as used herein is meant to refer to a syringe used for a direct injection (“naked syringe”), to a syringe or cartridge that may be used with an injection device (i.e., an auto-injector or pen), or to a container for another safety device, as non-limiting examples. The valve stopper 10 is configured to divide a container of the injection device, e.g., a barrel thereof, into a distal chamber, which contains a first or initial fluid to beinjected to a patient, and a proximal chamber, which contains a subsequent or secondary fluid to be delivered to the patient after the initial fluid. The valve stopper 10 comprises a slit therein that functions as a built-in check valve that allows the secondary fluid contained in the proximal chamber of the injection device 100 to pass through the valve stopper 10 only after the initial fluid is expelled from a distal chamber of the injection device 100. Accordingly, the multichamber injection device 100 of the present disclosure can be used for fluid delivery of multiple medical fluids to through a needle cannula inserted into a patient with only one needle stick and no additional fluid delivery steps to be performed by the practitioner. In other examples, the multi-chamber injection device 100 of the present disclosure can allow for delivery of multiple medical fluids to a patient in sequence through a VAD without needing to attach multiple syringes or fluid containers to the VAD.

[0067] As described in further detail herein, the valve stopper 10 is structured to ensure proper alignment and guiding thereof during insertion into the barrel (e.g., during vent tube stoppering) and during distal advancement within the barrel when injecting the first or initial fluid. The valve stopper 10 may also be designed to ensure proper sealing thereof with the barrel, so as to prevent leakage of the second fluid in the proximal chamber into the first fluid in the distal chamber. As described in detail here below, the valve stopper 10 may include numerous features thereon to enable such alignment, guiding, and sealing capabilities.

[0068] The present disclosure is also directed to features of a prefilled multi-chamber injection device 100 including the valve stopper 10. In particular, the multi-chamber injection device 100 can be configured to expel the initial fluid followed by the secondary fluid from a syringe barrel or cartridge through a fluid port or nozzle of the injection device 100. As previously described, the initial fluid can be a medical fluid, which, as used herein, can refer to a medication or another therapeutic agent used for treatment of chronic or acute conditions, as are known in the art. Exemplary therapeutic agents can include, for example, drugs, chemicals, biological, or biochemical substances that, when delivered in a therapeutically effective amount to the patient, achieve a desired therapeutic effect. The secondary fluid can be another medical fluid, such as another type of therapeutic agent or drug. The secondary fluid can also be a flush solution, such as saline, a heparin lock flush solution, or another flush solution, as are known in the art.

[0069] The injection device 100 of the present disclosure allows a practitioner, such as a medical technician, nurse, physician assistant, physician, or other trained or untrained clinicians or a patient themselves when used with an auto-injector, to administer the initial fluidfollowed by the secondary fluid without needing to change syringes or fluid containers between delivery of the initial fluid and the secondary fluid. Further, the injection device 100 of the present disclosure allows the practitioner to provide the sequential delivery of the initial fluid followed by the secondary fluid through a single continuous advancement of a plunger rod of the injection device 100. As used herein, “single continuous advancement of a plunger rod” means that the practitioner is able to push the plunger rod in a distal direction, through the barrel, as a single continuous stroke to expel the initial fluid followed by the secondary fluid from the syringe barrel. The practitioner does not need, for example, to perform multiple needle sticks or to disconnect a syringe or another device from the VAD between delivery of the initial fluid and the secondary fluid. Further, using the injection device 100 of the present disclosure, the practitioner does not need to perform any other action, such as twisting, rotating, or pulling on the plunger rod or pressing another component or mechanism of the injection device 100, in order to perform the sequential delivery of the initial fluid and the secondary fluid. Accordingly, the fluids can be expelled from the injection device 100 in sequence in response solely to the single continuous stroke of the plunger rod in the distal direction by the practitioner, which can be performed as a “single-handed” operation or movement (i.e., the practitioner can hold the injection device 100 and press the plunger rod through the barrel with one hand). Accordingly, the injection device 100 of the present disclosure simplifies processes for administering the initial fluid followed by the secondary fluid to a VAD and / or patient compared to conventional fluid delivery practices.

[0070] FIGS. 1 and 2 illustrate an example of a multi-chamber injection device 100 for sequential expulsion / injection of at least an initial fluid Fl contained in a first or distal fluid chamber 102 (shown in FIGS. 19A and 19B) followed by a secondary fluid F2 contained in a second or proximal fluid chamber 104 (shown in FIGS. 19A-19D). In the illustrated embodiment, the injection device 100 is provided as a syringe, and is thus referred to hereafter as “syringe 100”; however, it is recognized that the injection device could also be provided as a cartridge useable in a pen, according to another non-limiting embodiment.

[0071] As previously described, the initial fluid Fl can be a medical fluid, such as a drug or another therapeutic agent intended for delivery to a patient through a needle cannula or through a VAD, such as a catheter or IV line. The secondary fluid F2 can be another type of therapeutic agent or a flush solution, such as saline solution and / or an anticoagulant, such as heparin. The first fluid Fl and second fluid F2 may have similar or dissimilar properties, including a concentration, viscosity, and / or pressure of the fluids, as non-limiting examples, and the fluidin each chamber could be with a different volume injected in term of dose delivered. The type and amount of solution contained in the proximal chamber 104 and / or the distal chamber 102 may vary depending, for example, on the specific type of needle cannula, catheter, or IV line being used for an injection and / or on the therapeutic effect to be achieved. In some examples, the syringe 100 contains or is configured to contain between about 0.1 mL and 20 mL of the initial fluid Fl and / or the secondary fluid F2.

[0072] In some examples, the syringe 100 comprises a barrel 106 having an open proximal end 108 and a distal end 110. The barrel 106 may be formed of a cylindrical sidewall 112 extending between the proximal end 108 and the distal end 110, along with an end wall 114 and a tip or hub 116 at the distal end 110. The tip 116 may include a channel (not shown) formed therein within which a needle cannula 118 is secured, with the needle 118 providing for injection of the initial fluid Fl and the secondary fluid F2 from the barrel 106. In other embodiments, the tip 116 may be configured as a needleless connector configured to be connected directly or indirectly to a fluid port, valve, or another terminal access portion of a vascular access device (VAD).

[0073] The syringe 100 further comprises a plunger assembly 120 that includes a plunger rod 122 and a plunger stopper 124. The plunger rod 122 can be a conventional plunger rod used in currently available syringes. The plunger rod 122 can be, for example, an injection molded part formed from a rigid thermoplastic material, such as polyester, polycarbonate, polypropylene, polyethylene, polyethylene terephthalate, or another thermoplastic material, or may be formed of wood or metal, as are known in the art. In some embodiments, the plunger rod 122 can be connected to the plunger stopper 124 by mechanical connectors, threads, fasteners, or adhesives, while in other examples the plunger rod 122 can be integrally formed or co-molded with the plunger stopper 124. In an exemplary embodiment, the plunger rod 122 includes a distal end 126 engaged to the plunger stopper 124. For example, as most clearly seen in FIG. 2, the distal end 126 of the plunger rod 122 can include a threaded connector 128 that is inserted into a corresponding cavity (not shown) extending inwardly from a proximal surface of the plunger stopper 124. The plunger rod 122 also includes a proximal end 130 protruding proximally from the proximal end 108 of the syringe barrel 106. The proximal end 130 of the plunger rod 122 can include a thumb press plate 132 for manipulating the plunger rod 122 to move the plunger stopper through the syringe barrel 106.

[0074] The plunger stopper 124 may include many features of conventional syringe stoppers or plungers, as are known in the art. That is, the plunger stopper 124 can be a substantiallycylindrical body formed from a flexible and / or deformable material, such as an elastomer or a thermoplastic elastomer material. Examples of elastomers thermoplastic elastomers include, but are not limited to, silicone, or synthetic or natural rubber (e.g., isoprene), or combinations thereof. The plunger stopper 124 can include radially extending ribs or rings 134 that seal against an inner surface 136 of the syringe barrel 106 so that the plunger stopper 124 can move fluids through the syringe barrel 106 towards the distal end 110 of the barrel 106. In some examples, the plunger stopper 124 includes one or multiple annular ribs 134 (e.g., at least one, two or three ribs) in order to improve stability and to prevent the plunger stopper 124 from tilting, shifting, or otherwise deforming as the plunger stopper 124 moves through the syringe barrel 106, and to prevent microbial contamination of the internal volume of the barrel.

[0075] As indicated above, the syringe 100 further comprises a valve stopper 10 slidably positioned within the barrel 106 of the syringe 100. The valve stopper 10 separates the barrel 106 into the proximal chamber 104 and the distal chamber 102. Specifically, as shown most clearly in FIG. 19A, the proximal chamber 104 is between a distal end of the plunger stopper 124 and a proximal end of the valve stopper 10 and the distal chamber 102 is between a distal end of the valve stopper 10 and the distal end 110 of the barrel 106.

[0076] According to aspects of the disclosure, the valve stopper 10 is structured to prevent mixing of the second fluid initially contained in the proximal chamber 104 with the first fluid initially contained in the distal chamber 102 before complete injection of the first fluid. The valve stopper 10 may be moved distally through the barrel 106 responsive to a distal movement of the plunger stopper 124, with the valve stopper 10 moving in coordination with the plunger stopper 124, even though the stoppers 10 and 124 are not mechanically connected or engaged together. The valve stopper 10 further enables injection of the second fluid through the valve stopper 10 without requiring an excessive force to be applied to the plunger rod 122, as explained in further detail below. The valve stopper 10 may function as a one-way check valve for selectively controlling fluid flow between the proximal chamber 104 and the distal chamber 102. As used herein, a one-way check valve refers to a valve that allows a flow of fluid through the valve in only one direction. For example, the valve stopper 10 can be configured to permit fluid flow from the proximal chamber 104 to the distal chamber 102, while fluid flow from the distal chamber 102 to the proximal chamber 104 is prevented.

[0077] Referring now to FIGS. 3 and 4, shown is a non-limiting embodiment of a valve stopper 10 that may be included in injection device 100, according to one aspect of the disclosure. The valve stopper 10 generally comprises a membrane 12, and a lateral wall 14.The lateral wall 14 may extend proximally, distally, or both proximally and distally from the membrane 12 to define one or more cavities 16, with each cavity comprising a hollow volume delimited by an inner face 18 of the lateral wall, along with a proximal face 20 and / or a distal face 22 of the membrane 12.

[0078] In the embodiment represented in FIGS. 3 and 4, the membrane 12 is positioned at a distal end 23 of the valve stopper 10, such that the lateral wall 14 extends in the proximal direction only from the membrane 12, and the cavity 16 is delimited by the inner face 18 of the lateral wall 14 and the proximal face 20 of the membrane 12 that constitutes the bottom of the cavity 16.

[0079] According to another embodiment, and as shown in FIG. 5, the valve stopper 10 may be configured such that the lateral wall 14 extends both proximally and distally from the membrane 12. That is, the membrane 12 may be positioned so as to be offset proximally from the distal end 23 of the valve stopper 10, such that the lateral wall 14 extends both proximally and distally therefrom to provide two separate respective cavities 16, including a proximal cavity delimited by the inner face 18 of the lateral wall 14 and the proximal face 20 of the membrane 12, and a distal cavity delimited by the inner face 18 of the lateral wall 14 and the distal face 22 of the membrane 12.

[0080] The valve stopper 10 may be made of any material with elastomeric properties usually used to manufacture stoppers for medical injection devices. For example, the valve stopper 10 may be made of elastomer, rubber, thermoplastic elastomer, or liquid silicon rubber. In an exemplary embodiment, the valve stopper 10 is formed as a single, integral component (i.e., the membrane 12 and lateral wall 14 are integrally formed) and of a single material (i.e., a mono-component and mono-material stopper), with the elastomeric properties of the valve stopper 10 allowing for flexing and / or deformation of the membrane 12 thereof. According to some non-limiting embodiments, the membrane 12 of the valve stopper 10 may have a thickness that is between 0.2-7 mm, depending on the configuration / shape of the membrane (e.g., flat, convex, concave or other shaped face and a sizing of the valve stopper 10 (e.g., 1, 10 or 20 mL stopper), to provide for deflection / deformation thereof when forces are applied to the membrane 12. In the region of the membrane 12 that is collapsible or deformable (i.e., generally, a region that includes a slit 28 therein), the thickness of the membrane will preferably be from 0.2 to 3.0 mm.

[0081] As shown in FIGS. 3 and 4 (and FIG. 5), the valve stopper 10 has a substantially cylindrical shape, which corresponds to the shape of the barrel 106 of the injection device inwhich the valve stopper 10 is intended to be inserted. Accordingly, the lateral wall 14 of the valve stopper 10 has a generally cylindrical or tubular construction, including a cylindrical sidewall 25. The lateral wall 14 is provided with an outer sealing surface 24 that extends radially outward from the cylindrical sidewall 25, with the sealing surface 24 configured to sealingly engage the inner surface 136 of the barrel 106. The sealing surface 24 is continuous, which means that it extends continuously about the circumference of the valve stopper 10 and forms a ring. Since the continuous surface extends between the outer face of the lateral wall 14 of the valve stopper 10 and the inner surface 136 of the barrel 106 of the injection device 100, any passage of a composition between the valve stopper 10 and the barrel 106 is prevented. Optimal sealing is thus ensured.

[0082] According to a preferred embodiment, the sealing surface 24 may comprise one or more sealing ribs 26 that extend radially outward from an outer surface of the cylindrical sidewall 25 and around an outer circumference thereof. The number of ribs 26 as well as the dimensions of each rib 26, such as height, width, and the distance between two adjacent ribs, may be adapted to as to further optimize the sealing depending on the dimensions of the valve stopper 10 and the barrel 106, as described in further detail below. According to the embodiment of FIGS. 3-5, the valve stopper 10 comprises two ribs 26 - i.e., a distal first rib 26a and a proximal second rib 26b. In other embodiments, and as shown in FIG. 6, the valve stopper 10 may comprise three ribs 26 - i.e., a distal first rib 26a, a proximal second rib 26b, and a center rib 26c. As indicated above, in some embodiments, the valve stopper 10 has a substantially cylindrical shape, and in such an embodiment, the first rib 26a and the second rib 26b (and the center rib 26c) are formed to have an identical construction - i.e., a same outer diameter, rib_OD. In still other embodiments, and as described below regarding FIGS. 10-12, a valve stopper may comprise a single rib 26, in combination with other guiding features.

[0083] The inclusion of two (or three) ribs 26 on sealing surface 24 reduces the contact surface between the lateral wall 14 of the valve stopper 10 and the inner surface 136 of the barrel 106 of the injection device 100, compared to a plane lateral wall of the valve stopper 10, thus improving the gliding performance of the valve stopper 10 relative to the barrel 106. As a result, the force that needs to be exerted onto the valve stopper 10 for displacing it inside the barrel 106 is reduced, which makes the injection easier for the user. Additionally, the inclusion of the pair of spaced apart ribs 26 on valve stopper 10 increases the stability of the valve stopper 10 during insertion thereof into barrel 106 (e.g., during vent tube stoppering) and during injection of the first fluid.

[0084] In some embodiments, and as shown in FIGS. 4 and 5, the valve stopper 10 may further include films, coatings, layers, or other barriers on distal- and proximal-facing sides thereof. Specifically, the valve stopper 10 may include a first or distal barrier film 27 applied to a distal-facing side of the valve stopper 10 and a second or proximal barrier film 29 applied to a proximal-facing side of the valve stopper 10. In some embodiments, the first or distal barrier film 27 may be applied to the distal face 22 of the membrane and a distal-most rib 26. In some embodiments, the second or proximal barrier film 29 may be applied to the proximal face 20 of the membrane and to the inner face 18 of the lateral wall 14 that defines the cavity 16. The barrier films 27, 29 can be formed from the same or different materials, with the material(s) being biocompatible and inert, so as to not exhibit detrimental effects to the therapeutic agents or other medical solutions in the syringe barrel 106. Thus, according to nonlimiting embodiments, the barrier films 27, 29 can optionally be formed from a fluoropolymer material, such as a polymer formed from a polytetrafluoroethylene resin (PTFE), an ethylenetetrafluoroethylene resin (ETFE), expanded polytetrafluoroethylene (ePTFE), or may be formed from an alternative to a fluropolymer, such as an ultra-high-molecular-weight polyethylene (UHMWPE), silicone, or a thermoplastic elastomer (TPE) free of per- and poly- fluoroalkyl substances (PFAS). Alternatively, gliding properties and integrity of the valve stopper 10 may be ensured without any film.

[0085] According to some embodiments of the disclosure, the proximal face 20 of the membrane 12 may present a flat or planar surface, as shown in FIGS. 3-6. In other embodiments, it is recognized that the proximal face 20 of the membrane 12 may present a convex surface, a concave surface, or another “shaped” surface (e.g., a duckbill shape) that extends or protrudes proximally or distally.

[0086] The term “convex”, as relates to a face of the membrane 12, means that the face is curved, and that the apex of the curvature extends away from a plane orthogonal to the distal- proximal direction and comprising the middle of the thickness of the membrane 12 in the thinnest region thereof. Hence, the apex of the curvature of the proximal face 20 of the membrane 12, presenting a convex shape, extends away from the distal face 22 of the membrane 12.

[0087] The term “concave”, as relates to a face of the membrane 12, means that the face is curved and that the apex of the curvature is directed towards a plane orthogonal to the distal- proximal direction and comprising the middle of the thickness of the membrane 12 in the thinnest region thereof. Hence, the apex of the curvature of the proximal face 20 of themembrane 12, presenting a concave shape, extends toward the distal face 22 of the membrane 12.

[0088] Similar to the proximal face, the distal face 22 of the membrane 12 may comprise one of a flat / planar surface, a convex surface, a concave surface, or another “shaped” surface. According to some embodiments of the disclosure, the distal face 22 of the membrane 12 may present a flat or planar surface, as shown in FIGS. 3-6.

[0089] While FIGS. 3-6 illustrate that the membrane 12 is provided at or adjacent the distal end 23 of the valve stopper 10, it is recognized that other embodiments may have the membrane 12 at the proximal end 31 of the valve stopper 10, or at a location between the distal and proximal ends, according to embodiments of the disclosure.

[0090] Referring now to FIGS. 7-12, still additional embodiments of a valve stopper 10 are shown. The valve stopper in each of the embodiments of FIGS. 7-12 is similar to the valve stopper 10 of FIG. 5, in that the membrane 12 is positioned so as to be offset from the distal end 23 and the proximal end 31 of the valve stopper 10, such that the lateral wall 14 extends both proximally and distally from the membrane 12. However, in the embodiments of FIGS. 7-12, the valve stopper 10 is configured as a “symmetrical stopper,” where the membrane 12 is identically shaped on both sides - i.e., the proximal face 20 and distal face 22 are symmetrical - and the membrane 12 is centered lengthwise between the distal end 23 and the proximal end 31.

[0091] Referring first to FIGS. 7 and 8, valve stoppers 10 are shown where a symmetrical membrane 12 is centered lengthwise between the distal end 23 and the proximal end 31 and where the membrane 12 has a flat proximal face 20 and flat distal face 22. In the embodiment of FIG. 7, the valve stopper 10 includes two annular ribs 134, with the membrane 12 positioned at a lengthwise location equidistant between the two ribs 134. In the embodiment of FIG. 8, the valve stopper 10 includes three annular ribs 134, with the membrane 12 positioned at a lengthwise location that is aligned with the center rib 134.

[0092] Referring next to FIGS. 9 and 10, valve stoppers 10 are shown where a symmetrical membrane 12 is centered lengthwise between the distal end 23 and the proximal end 31 and where the membrane 12 has a convex proximal face 20 and convex distal face 22. In the embodiment of FIG. 9, the valve stopper 10 includes two annular ribs 134, with the membrane 12 positioned at a lengthwise location equidistant between the two ribs 134. In the embodiment of FIG. 13, the valve stopper 10 includes three annular ribs 134, with the membrane 12 positioned at a lengthwise location that is aligned with the center rib 134.

[0093] Referring to FIGS. 11 and 12, valve stoppers 10 are shown where a symmetrical membrane 12 is centered lengthwise between the distal end 23 and the proximal end 31 and where the membrane 12 has a concave proximal face 20 and concave distal face 22. In the embodiment of FIG. 11, the valve stopper 10 includes two annular ribs 134, with the membrane 12 positioned at a lengthwise location equidistant between the two ribs 134. In the embodiment of FIG. 12, the valve stopper 10 includes three annular ribs 134, with the membrane 12 positioned at a lengthwise location that is aligned with the center rib 134.

[0094] According to aspects of the disclosure, the membrane 12 comprises at least one slit 28 formed therein for permitting fluid flow through the membrane 12 when the slit is in an open position / configuration. The slit 28 extends through at least a part of the thickness of the membrane 12 between the proximal face 20 and the distal face 22 of the membrane 12 and is configured to create a fluid path 30 through the membrane 12 from the proximal face 20 to the distal face 22 of the membrane 12 when the slit 28 is opened.

[0095] According to aspects of the disclosure, the slit 28 is configured to transition between a closed position, where fluid flow through the membrane 12 is prevented, and an open position, where fluid flow through the membrane 12 can occur, thereby establishing fluid communication between the proximal chamber 104 and the distal chamber 102 through the valve stopper 10. In some examples, the valve stopper 10 can be configured to remain in the closed position when a fluid pressure P2 in the proximal chamber 104 of the syringe barrel 106 is below a predetermined opening force Fopof the slit 28 - which corresponds to the force / pressure that needs to be exerted onto the proximal face 20 of the membrane 12 for opening the slit 28. The slit 28 of valve stopper 10 can be configured to transition to the open position when the fluid pressure P2 in the proximal chamber 104 of the syringe barrel 106 is greater than or equal to the predetermined opening force Fopof the slit 28. In some examples, the slit 28 is biased to and initially provided in the closed position (i.e., maintained closed under radial compression of the valve stopper 10 within the barrel 106), meaning that when fluid pressure P2 in the proximal chamber 104 is nominal or is substantially equal to fluid pressure Pi in the distal chamber 102, the slit 28 is in the closed position. The slit 28 transitions to the open position when the fluid pressure P2 in the proximal chamber 104 substantially increases above the opening force Fopof the slit 28.

[0096] The activation or opening force Fopfor the slit 28 can be selected based on fluid pressures / forces that commonly occur when a stopper is manually moved through a barrel of a conventional syringe at a reasonable rate, as occurs when a practitioner pushes a plunger rodof a syringe through the syringe barrel. In some examples, the activation or opening force Fopfor the slit 28 may be between 2 N and 25 N, preferably between 2 N and 20 N, and even more preferably between 5N and 20N. However, it is recognized that the activation or opening force FOp can be selected or optimized for different syringe designs taking into account, for example, the size, shape, and materials of the valve stopper 10, the syringe barrel 106, and other components of the multi-chamber syringe 10. In some examples, the syringe 10 is configured such that the activation or opening pressure for the slit 28 is greater than a pressure required to infuse the drug (i.e., the pressure required to expel the first fluid from the distal chamber 102 through the tip 116 and to the patient through the needle cannula and / or through the VAD). Accordingly, the practitioner may be required to apply a greater force to a plunger rod 122 of the syringe 10 connected to the plunger stopper 124 in order to cause the slit 28 of valve stopper 10 to open than is required to move the valve stopper 10 (and plunger stopper 124) through the barrel 106. Due to these differences in the force that must be applied to the plunger rod 122, the practitioner can receive feedback (i.e., a feeling that increased force on the plunger rod is needed) indicating that the initial fluid has been expelled from the syringe 10 and that the valve stopper 10 is in its distal-most position in the barrel 106.

[0097] As previously described, the membrane 12 is a one-way membrane that functions as a check valve, which means that the membrane 12 is configured to allow a composition / fluid to pass through the membrane 12 via the open slit 28 only when the composition flows in the distal direction, i.e., the direction of injection. In other terms, the slit 28 is configured to open only for allowing the composition to pass through the membrane 12 from one side of the valve stopper 10 where the composition contacts the proximal face 20 of the membrane 12, to another side of the valve stopper 10 where the composition contacts the distal face 22 of the membrane 12 - i.e., the second fluid F2 in proximal chamber 104 may pass through the membrane 12 into the distal chamber 102, while the first fluid Fl in distal chamber 102 may not pass through the membrane 12 into the proximal chamber. The slit 28 is configured to remain closed for preventing a composition to pass through the membrane 12 in the proximal direction - i.e., flowing from where the composition contacts the distal face 22 of the membrane 12 to where the composition contacts the proximal face 20 of the membrane 12.

[0098] As shown in FIGS. 3-12, in some embodiments, the slit 28 is formed to extend through an entirety of the membrane 12, between the proximal face 20 and the distal face 22 thereof, so as to form or provide a split 28a through the membrane 12. In some examples, the split 28a may be formed as a single line or line segment that extends substantially transverseto a central longitudinal axis of the valve stopper 10. The length of the split 28a is preferably greater than a quarter of the diameter of the cavity 16 in valve stopper 10, but less than the full diameter of the cavity 16. A length less than a quarter of the diameter of the cavity 16 would require a very high force from the user for opening the split 28a, thereby making an injection harder to carry out. On the contrary, a length greater than the diameter of the cavity 16 would render the parts of the split 28a that do not lead to the cavity 16 useless, and may deteriorate the functioning of the split 28a.

[0099] In other examples, the split 28a can include multiple segments that collectively form a split of a desired configuration. In any configuration, the split 28a functions as a valve configured to open or close the fluid path 30 depending on the pressure exerted by a composition onto the proximal face 20 of the membrane 12, as described in detail above.

[0100] While the slit 28 is described above as a split 28a that extends through a full thickness of the membrane 12, between the proximal face 20 and the distal face 22 thereof, it is recognized that in other embodiments, the slit 28 may extend through only a part of the thickness of the membrane 12. In such embodiments, the membrane 12 is configured as a tearapart membrane that is configured to tear along the slit 28 under a determined pressure exerted by the composition, so as to create the fluid path 30 through the membrane 12 from the proximal face 20 to the distal face 22. To do so, the slit 28 forms a notch that is aligned with a localized weakened zone in the membrane 12, i.e., a tear apart portion, which causes the membrane 12 to tear when a determined pressure is applied onto the proximal face 20 by the composition to be injected. When the tear apart portion is tom, the notch acts as a guide for the flow of the composition along the fluid path 30 thus formed. The tear apart portion forms a valve configured to open or close the fluid path 30 depending on the pressure exerted by the composition onto the proximal face 20 of the membrane 12. The depth of the notch is preferably comprised between about 20% and 100% of the thickness of the membrane, more preferably between 50% and 100% of the thickness of the membrane.

[0101] According to aspects of the disclosure, the valve stopper 10 may be designed to ensure proper alignment and guiding thereof during insertion into the barrel 106 (e.g., during vent tube stoppering) and during distal advancement within the barrel 106 when injecting the first or initial fluid. The valve stopper 10 may also be designed to ensure proper sealing thereof with the barrel 106, i.e., between the ribs 26 and the inner surface 136 of the barrel 106, so as to prevent leakage of the second fluid in the proximal chamber 104 into the first fluid in the distalchamber 102. As described in detail here below, the valve stopper 10 may include numerous features thereon to enable such alignment, guiding, and sealing capabilities.

[0102] Referring to FIG. 13, according to one aspect of the disclosure, the structure of each of first rib 26a and second rib 26b may be controlled to achieve a desired interaction between the valve stopper 10 and the barrel 106. According to one aspect, the first and second ribs 26a, 26b extend radially outward a desired distance from the cylindrical sidewall 25 (i.e., a rib thickness) of valve stopper 10 to act as bearing points against the inner surface 136 of the syringe barrel 106. In some embodiments, an outer diameter of the ribs, rib_OD, is controlled based on an inner diameter of the barrel 106, barrel_ID, to provide a desired amount of compression of the ribs 26a, 26b or, put differently, to provide a desired amount of interference between the valve stopper 10 and the barrel 106. As one example, the rib thickness and the outer diameter of the ribs, rib_OD, is such that a compression rate of the ribs 26a, 26b is between 1% and 20%, and preferably between 2% and 12%, as defined according to:Compression Rate = (1 - (barrel_ID / rib_OD)) x 100.

[0103] With a compression rate of the ribs 26a, 26b within the range specified above, the ribs 26a, 26b function to maintain a consistent contact pressure against the syringe barrel 106, so as to prevent leakage of the second fluid in the proximal chamber 104 into the first fluid in the distal chamber 102, while not presenting an excessive amount of friction between the valve stopper 10 and inner surface 136 of the barrel 106 as the valve stopper 10 is moved distally through the syringe barrel, such that a gliding force for advancing the valve stopper 10 is kept at an acceptable level.

[0104] According to another aspect of the disclosure, the first rib 26a and the second rib 26b (of either the two rib stopper of FIGS. 3-5, 7, 9 and 11 or the three rib stopper of FIGS. 6, 8, 10 and 12) are formed on valve stopper 10 so as to be spaced apart by at least a minimum axial distance (i.e., a minimum pitch), as compared to a largest (compressed) outer diameter of one or more of the ribs 26a, 26b. That is, it is recognized that it is desirable to provide a minimum pitch between the ribs 26a, 26b, in order provide proper guiding and alignment of the valve stopper 10 within the barrel 106, so as to ensure proper sealing between the stopper 10 and syringe barrel 106 and provide leak resistance between the first chamber 102 and the second chamber 104.

[0105] As shown in FIG. 13, the first rib 26a and the second rib 26b are spaced apart on valve stopper 10 in a longitudinal direction by an axial length, i.e., a rib pitch length, L_pitch, as measured between a longitudinal centerline of the first rib 26a and a longitudinal centerline of the second rib 26b. A desired minimum pitch between the first rib 26a and the second rib 26b depends on an outer diameter of the ribs 26a, 26b, and more specifically an outer diameter of the ribs 26a, 26b with the valve stopper 10 positioned within barrel 106 and the ribs 26a, 26b compressed by the barrel - i.e., a compressed rib diameter, rib_OD_compressed.

[0106] According to an exemplary embodiment, the valve stopper 10 is constructed such that the pitch length, L_pitch, between the first rib 26a and the second rib 26b (or between a single rib 26 and a guiding feature 52, as described below in FIGS. 10-12) is equal to or greater than 30% of the compressed rib diameter, rib_OD_compressed, of the first and second ribs 26a, 26b, and preferably equal to or greater than 50% (i.e., one half) of the compressed rib diameter, rib_OD_compressed, as defined byL_pitch > rib_OD_compressed x 0.3.

[0107] With the first rib 26a and the second rib 26b spaced axially apart along the valve stopper 10 as specified above, the ribs 26a, 26b function as a stabilizing feature configured to maintain an axial guiding and aligning of the valve stopper 10 within the syringe barrel 106. That is, it is recognized that there is a risk that the valve stopper 10 may tilt or become misaligned as it is initially stoppered within syringe barrel 106 (via a vent tube stoppering process where an insertion rod pushes the valve stopper 10 out of a vent tube and into the syringe barrel 106) or is advanced distally through the syringe barrel 106 during use of injection device 100 (responsive to a pressure P2 exerted by the second fluid onto the proximal face 20 of the membrane 12 of the valve stopper 10, which causes the valve stopper 10 to be advanced / displaced distally within barrel 106), with the spacing apart of ribs 26a, 26b on valve stopper 10 helping to prevent such tilting / misalignment. When the pitch between the ribs 26a, 26b (or between a rib 26 and an end member of a guiding feature, as in FIG. 17) is sized so as to be at least 30% of the compressed outer diameter of the ribs 26a, 26b, such tilting / misalignment of the valve stopper 10 may be prevented due to the valve stopper 10 having a greater axial contact area with the syringe barrel 106, which enables the valve stopper 10 to maintain better isostatism with the syringe barrel 106. With the axial guiding and aligning of the valve stopper 10 within the syringe barrel 106 being maintained, the ribs 26a, 26b ofvalve stopper 10 are able to apply a consistent contact pressure against syringe barrel 106, so as to guarantee proper sealing therewith and maintain leak resistance between the first chamber 102 and second chamber 104 of the barrel 106.

[0108] While the valve stopper 10 has been described above as having a substantially cylindrical shape - i.e., having a cylindrical sidewall 25 and first and second ribs 26a, 26b having an equal outer diameter, rib_OD - other embodiments of the valve stopper 10 may have different profiles or shapes, according to additional aspects of the disclosure. That is, and as shown in FIGS. 14 and 15, the valve stopper 10 may be constructed to have what may generally be described as a frustoconical shape. In such an embodiment, the sidewall 25 may still have a generally cylindrical profile, but the first rib 26a and the second rib 26b are constructed to have different outer diameters. In one embodiment, and as shown in FIG. 14, the distal first rib 26a is formed to have a first outer diameter, rib_OD_first, and the proximal second rib 26b is formed to have a second outer diameter, rib_OD_second, with first outer diameter being greater than the second outer diameter. In another embodiment, and as shown in FIG. 15, the distal first rib 26a is formed to have a second outer diameter, rib_OD_second, and the proximal second rib 26b is formed to have a first outer diameter, rib_OD_first, with the first outer diameter being greater than the second outer diameter.

[0109] With the outer diameter of the first rib 26a and the second rib 26b being different, the valve stopper 10 exhibits a generally frustoconical profile, as indicated by lines 32 in FIGS. 8 and 9. According to embodiments, a difference between the first outer diameter, rib_OD_first, of first rib 26a and the second outer diameter, rib_OD_second, of the second rib 26b may be controlled to provide a desired conicity of the valve stopper 10. According to aspects of the disclosure, the valve stopper 10 may be constructed so that the conicity thereof is up to 10%, as defined by:Conicity = (((rib_OD_first - rib_OD_second) / 2) / L_pitch)) x 100, where rib_OD_first is the first diameter, rib_OD_second is the second diameter, and L_pitch is the axial distance / length between the first rib 26a and the second rib 26b.

[0110] With a conicity of the valve stopper 10 within the range specified above, the valve stopper may be configured to provide adequate guidance / alignment of the valve stopper 10 within the barrel 106 and ensure adequate sealing therebetween, while also reducing the amount of friction between the valve stopper 10 and inner surface 136 of the barrel 106 as thevalve stopper 10 is moved distally through the syringe barrel (as compared to the cylindrical stoppers of FIGS. 3-12). That is, a valve stopper 10 having a low conicity provides stability inside the syringe barrel 106 and in guiding and distribution during assembly process (distribution bowl, distribution rails, insertion device), with a balanced force distribution on the contact points when the stopper is compressed, to prevent a tilting behavior / tendency for the stopper when sized with an un-favorable ratio between its axial length and outer diameter(s).

[0111] Referring now to FIGS. 16-18, a valve stopper 40 is illustrated according to another aspect of the disclosure. The valve stopper 40 of FIGS. 16-18 differs from the valve stopper 10 of FIGS. 3-15 in that the valve stopper 40 includes only a single circumferential rib 26, as compared to the two (or three) ribs 26 of those valve stoppers 10. However, in order to ensure that the valve stopper 40 is aligned and guided properly within barrel 106 during insertion and advancement thereof, the valve stopper 40 includes a plurality of guiding members 42 thereon. The guiding members 42 extend axially along a length of the cylindrical sidewall 25, along an outer surface thereof, from the single rib 26 to the opposite end of the valve stopper 40. The plurality of guiding members 42 are spaced apart circumferentially about the cylindrical sidewall 25, such as being equidistantly spaced apart, to ensure that the valve stopper 40 remains properly oriented within barrel 106. In the illustrated embodiment, the valve stopper 40 includes three (3) guiding members 42 that are equidistantly spaced apart circumferentially about the cylindrical sidewall 25; however, it is recognized that a greater number of guiding members 42 may be provided on valve stopper 40, such as from four (4) to six (6) guiding members 42, as non-limiting examples.

[0112] As shown best in FIGS. 16 and 17, each of the guiding members 42 may be characterized as generally including an elongated portion 44 and an end portion 46. The elongated portion 44 extends longitudinally along at least a majority of the cylindrical sidewall 25, with a first end 48 of the elongated portion 44 joined to the rib 26. The elongated portion 44 may have any a rectangular, triangular or semi-cylindrical profile, according to various embodiments, but regardless of exact shape, the elongated portion 44 is configured to extend radially outward from the cylindrical sidewall 25 by an amount that structures the elongated portion 44 to be radially inset from the outer diameter of the rib 26, rib_OD (FIG. 17). Thus, when the valve stopper 40 is positioned within barrel 106, the elongated portion 44 of the guiding members 42 does not come into contact with the inner surface 136 of the barrel 106.

[0113] The end portion 46 of each guiding member 42 is joined to a second end 50 of its respective elongated portion 44. The end portion 46 is configured to protrude radially outward from the elongated portion 44, so that a radially outward-facing surface of the end portion 46 is radially aligned with a radially outward-facing surface of the rib 26, as best shown in FIG. 18. The end portion 46 of each guiding member 42 may have a shape / configuration that provide or gives a localized contact between the guiding member 42 and the barrel 106. In the illustrated embodiment, the end portion 46 of each guiding member 42 is shown as having a triangular shape, with a point 52 of the triangular shape presenting the radially outward-facing surface of the end portion 46 and providing the localized contact. However, as described above regarding the elongated portion 44, the end portion 46 may be constructed to have another, alternative shape, such as a semi-cylindrical shape, according to another non-limiting embodiment. With the outward-facing surface of each end portion 46 being radially aligned with the radially outward-facing surface of the rib 26, the end portion 46 of each guiding member 42 may be placed in contact with the inner surface 136 of the barrel 106, thus functioning to provide guiding and alignment for the valve stopper 40 during insertion and advancement thereof into / through barrel 106.

[0114] Similar as to described above regarding the valve stopper(s) 10 of FIGS. 3-15, where the valve stopper 10 is configured to have a minimum pitch length between the first rib 26a and the second rib 26b, valve stopper 40 is configured to have a minimum pitch, L_pitch, between the single rib 26 and the end portion 46 of the guiding members 42. According to embodiments, a pitch between the rib 26 and the end portion 46 of the guiding members 42 is sized so as to be at least 30%, and preferably at least 50% (one half), of the compressed outer diameter of the rib 26. With a pitch equal to or greater than this amount, tilting / misalignment of the valve stopper 40 may be prevented due to the valve stopper 40 having a greater axial contact area with the syringe barrel 106, which enables the valve stopper 40 to maintain better isostatism with the syringe barrel 106.

[0115] With the valve stopper 40 including a plurality of guiding members 42 thereon structured as described above, the valve stopper 40 may be configured to provide adequate guidance / alignment thereof within the barrel 106 and ensure adequate sealing therebetween, while also reducing the amount of friction between the valve stopper 40 and inner surface 136 of the barrel 106 as the valve stopper 40 is moved distally through the syringe barrel 106 (as compared to the cylindrical stopper of FIGS. 3-15). That is, due to there being a reduced area of engagement between the guiding members 42 (i.e., the end portions 46 thereof) and thebarrel 106 as compared to between a second rib 26b and the barrel 106, the friction between the valve stopper 40 and the barrel 106 can be maintained at / below a desirable level, while the guiding members 42 still ensure that the valve stopper 40 is aligned and oriented properly within the barrel 106 - with the guiding members 42 preventing tilting of the valve stopper 40 during insertion and advancement thereof.

[0116] Referring now to FIGS. 19A-19D, functioning of an injection device including any of the valve stoppers 10, 40 of FIGS. 3-18 is illustrated, in accordance with an embodiment of the disclosure. In some embodiments, the injection device 100 may be a pre-filled, multichamber syringe as previously shown and described in FIGS. 1 and 2, including barrel 106, valve stopper 10 and a plunger assembly 120 (including plunger rod 122 and plunger stopper 124), with the syringe being manually actuated by a user. In other embodiments, the injection device 100 may be a pre-filled cartridge for use in an auto-injector, with the cartridge including barrel 106, valve stopper 10, and a plunger stopper 124, with the cartridge being activated by an actuator included in the auto-injector.

[0117] As previously described, the injection device 100 enables the sequential delivery of an initial fluid Fl and a second fluid F2 through a single continuous advancement of a plunger rod 122 of the injection device 100. The first fluid Fl and second fluid may have similar or dissimilar properties, including a concentration, viscosity, and / or pressure of the fluids, as nonlimiting examples. The type and amount of solution contained in the proximal chamber 104 and / or the distal chamber 102 may vary depending, for example, on the specific configuration of the injection device 100 and / or on the therapeutic effect to be achieved. In some examples, the injection device 100 contains or is configured to contain between about 0.1 mL and 20 mL of the initial fluid Fl and / or the secondary fluid F2. Additionally, the structure of the valve stopper 10 - in particular membrane 12 - may be specifically configured based on properties of the fluids Fl, F2 contained within the syringe. That is, the pressure and / or viscosity of the fluids Fl, F2 may dictate the thickness of the membrane 12 and / or a configuration and sizing of the slit 28.

[0118] According to aspects of the disclosure, the first fluid Fl and the second fluid F2 may - in general - comprise a liquid-liquid combination of pharmaceuticals in one of a number of drug classes or categories designed to treat a recognized condition. Such drug classes or categories may include analgesics, vitamins, vaccines (and boosters), monoclonal antibodies, diabetes and obesity treatments, and the like.

[0119] One exemplary embodiment of a liquid- liquid combination of a first fluid Fl and second fluid F2 that may be sequentially injected from the first chamber 102 and second chamber 104 comprises a fixed-dose combination of diabetes / obesity drugs - where the first fluid Fl and the second fluid F2 contained within the distal chamber 102 and the proximal chamber 104 of injection device may comprise a GLP-1 agonist and an amyline analog, respectively. The GLP-1 agonist may be a calcitonin receptor agonist, including any of Dulaglutide, Exenatide, Semaglutide, or Liraglutide, as non-limiting examples. The amyline analog may be dual amylin, including any of Cagrilintide or pramlintide, as non-limiting examples.

[0120] In one exemplary embodiment, the injection device 100 enables a delivery / injection of CagriSema to a patient, with the first fluid Fl comprising cagrilintide and the second fluid F2 comprising semaglutide, and with the cagrilintide and semaglutide being sequentially delivered / injected through a single continuous advancement of the plunger rod 122 of the injection device 100.

[0121] Injection of a medication / treatment such as CagriSema - where a GLP-1 agonist and an amyline analog are sequentially injected (via injection device 100) - is provided only a nonlimiting example, and it is recognized that other liquid-liquid combinations of a first fluid Fl and second fluid F2 may be sequentially injected from the first chamber 102 and second chamber 104 of the injection device 100. As indicated above, injection device 100 may also be utilized for sequential injections of other liquid-liquid combination of pharmaceuticals, including analgesics, vitamins, vaccines (and boosters), monoclonal antibodies, and the like.

[0122] FIG. 19A corresponds to the configuration of the injection device 100 before injection of the first fluid Fl. In this configuration, the plunger stopper 124 is in a proximal position and the valve stopper 10 is in a rest position, with the slit 28 (i.e., split 28a or tear apart notch) being maintained closed under radial compression of the valve stopper, such that the fluid path 30 is closed. That is, when the valve stopper 10 is inserted in the barrel 106 of the injection device 100, the slit 28 is maintained closed under radial compression of the valve stopper 10, the valve stopper 10 being itself subjected to radial compression of the barrel 106. With the plunger stopper 124 in the proximal position, the pressure Pi in the distal chamber 102 and the pressure P2 in the proximal chamber 104 are substantially equal, such that the differential pressure AP=P2-PI is substantially null, and thus much lower than the valve opening force Fopof the slit 28, so that the slit 28 thus remains closed. The closed slit 28 prevents the mixing of the first fluid Fl and second fluid F2, by preventing the first fluid Fl from entering the proximalchamber 104 and the second fluid F2 from entering the distal chamber 102. Additionally, the ribs 26 of the valve stopper 10 sealingly engage the inner surface 136 of the barrel 106, so that the first and the second fluids cannot pass from a chamber to another via a passage between the valve stopper 10 and the barrel 106.

[0123] Referring now to FIG. 19B, the injection device 100 is shown being actuated by a user to perform the injection of the first fluid. The force applied to the plunger stopper 124 is transmitted to the second fluid F2 in the proximal chamber 104 and then to the valve stopper 10, which results in a pressure P2 exerted by the second fluid onto the proximal face 20 of the membrane 12 of the valve stopper 10 - which causes the valve stopper 10 to be advanced / displaced distally within barrel 106. The displacement of the valve stopper 10 in the distal direction pushes the first / initial fluid Fl in the distal direction, so that the first / initial fluid is expelled from the injection device 100 through the channel 118 of tip 116.

[0124] In the configuration of FIG. 19B, the valve stopper 10 is in a sealing position, with the slit 28 remaining closed. That is, the displacement of the valve stopper 10 builds up pressure in the distal chamber 102, since the diameter of the channel 118 is much smaller than the diameter of the barrel 106. This increase of the pressure Pi not only forces the first fluid Fl through the channel 118 for injection, but also applies force onto the distal face 22 of the membrane 12 of the valve stopper 10 in opposition to the displacement of the valve stopper 10. As a result, the valve stopper 10 is subjected to substantially equal and opposite pressures Pi and P2 respectively exerted by the first fluid Fl and the second fluid F2 onto the proximal face 20 and the distal face 22 of the membrane 12. As a consequence, the differential pressure AP is substantially null, and thus much lower than the valve opening force Foprequired to open the slit 28. During the displacement of the valve stopper 10, the differential pressure AP may not be substantially null but remains lower than the valve opening force Fopof the slit 28. The slit 28 thus remains closed. The injection continues until the valve stopper 10 abuts the end wall 114 at the distal end 108 of the barrel 106, as illustrated in FIG. 19B.

[0125] Referring now to FIG. 19C, the user continues to apply a distally directed force to the plunger stopper 124. Since the valve stopper 10 cannot move further distally, the pressure P2 in the proximal chamber 104 increases as the plunger stopper 124 continues to advance distally, and thus the force differential AP becomes superior to the valve opening force Fopof slit 28. As a result, the slit 28 in membrane 12 is caused to open (or a tear-apart portion is caused to tear), thereby allowing the second fluid F2 to pass through the slit 28 and to / through the channel118 in tip 116 for the injection. In this configuration, the valve stopper 10 is in an injection position.

[0126] As shown in FIG. 19D, at the end of the injection of the second fluid F2, the plunger stopper 124 abuts the valve stopper 10. At this stage, a fraction of the second fluid may remain in a “dead volume” of the proximal chamber 104 - i.e., within the cavity 16 of valve stopper 10, which is open to the proximal chamber 104. This fraction of the second fluid F2 may be forced out from the proximal chamber 104 by collapsing the valve stopper 10 (i.e., collapsing the lateral wall 14) under the pressure exerted by the plunger stopper 124, which reduces the volume of the cavity 16, and the dead volume is thus injected.

[0127] As shown in the embodiment of FIGS. 19A-19D, the valve stopper 10 is oriented / arranged within the barrel 106 of injection device 100 such that the membrane 12 is at a distal end of the valve stopper 10. With the membrane 12 positioned as such, the valve stopper 10 may more easily be positioned within the barrel 106 during an initial insertion, such as may be performed via a vent tube stoppering process. That is, with the membrane 12 positioned at the distal end of the valve stopper 10, an insertion rod (not shown) of a vent tube stoppering system may be engaged with cavity 16, to proper for precise insertion of the valve stopper 10 within barrel 106 and to prevent tilting thereof during insertion.

[0128] While embodiments of the disclosure described above are directed to use of a valve stopper 10 in a multi-chamber injection device 100 for performing of a sequential injection of a first fluid and a second fluid therefrom, it is recognized that valve stopper 10 may also be used in an injection device 100 for the injection of a single fluid therefrom.

[0129] Referring now to FIG. 20A, inclusion of a valve stopper - such as any of the valve stoppers 10, 40 of FIGS. 3-18 - in an injection device 100 for injecting a single fluid is illustrated, in accordance with another embodiment of the disclosure. The structure of injection device 100 may be identical to that previously described in FIGS. 19A-19C regarding barrel 106 (including end wall 114 and tip 116) and plunger stopper 124; however, the valve stopper 10 is initially positioned at the far distal end 108 of the barrel 106, so as to abut the end wall 114. In this position, the valve stopper 10 separates two “chambers” of the barrel 106, including a distal chamber 102 defined as the channel 118 within tip 116, and a proximal chamber 104 between the valve stopper 10 and the plunger stopper 124. In some embodiments, the distal chamber 102 (i.e., channel 118) may be empty, i.e., the “first fluid” in the distal chamber 102 is air, while the proximal chamber 104 contains a single pharmaceutical fluid.

[0130] As shown in FIG. 20A, the valve stopper 10 is oriented / arranged within barrel 106 such that the membrane 12 is at the proximal end of the valve stopper 10. In other embodiments, the valve stopper 10 may be constructed and arranged within barrel such that the membrane 12 is adjacent the distal end of the valve stopper 10, but proximally offset from a distal edge of the valve stopper 10, such as previously shown in FIG. 5. In either configuration / arrangement, the membrane 12 of the valve stopper 10 will be proximally offset from the end wall 114 of barrel 106, so as to allow for deflection / deformation of the membrane 12 for purposes of opening the slit 28 therein.

[0131] The functioning of the valve stopper 10 and the injection device comprising the valve stopper 10 will now be described herebelow, in reference to FIGS. 20A to 20C.

[0132] FIG. 20A corresponds to the configuration of the injection device 100 before injection of the single fluid. In this configuration, the plunger stopper 124 is in a proximal position and the valve stopper 10 is in a rest position, with the slit 28 being maintained closed under radial compression of the valve stopper 10, such that the fluid path 30 is closed. That is, when the valve stopper 10 is inserted in the barrel 106 of the injection device 100, the slit 28 is maintained closed under radial compression of the valve stopper 10, the valve stopper 10 being itself subjected to radial compression of the barrel 106. With the plunger stopper 124 in the proximal position, the pressure P2 in the in the proximal chamber 104 is much lower than the valve opening force Fopof the split, so that the slit 28 thus remains closed. The closed slit 28 prevents the single fluid from leaking into channel 118 of tip 116.

[0133] Referring now to FIG. 20B, the injection device 100 is shown being actuated by a user to perform the injection of the single fluid. The force applied to the plunger stopper 124 causes the pressure P2 in the proximal chamber 104 to increase as the plunger stopper 124 continues to advance distally, which results in a pressure P2 being applied by the single fluid onto the proximal face 20 of the membrane 12 of the valve stopper 10 that becomes superior to the valve opening force Fop. As a result, the slit 28 in membrane 12 is caused to open, thereby allowing the single fluid to pass through the slit 28 and to / through the channel 118 in tip 116 for the injection. In this configuration, the valve stopper 10 is in an injection position.

[0134] As shown in FIG. 20C, at the end of the injection of the single fluid, the plunger stopper 124 abuts the valve stopper 10. At this stage, a fraction of the single fluid may remain in a “dead volume” of the proximal chamber 104 - i.e., within the cavity 16 of valve stopper 10. This fraction of the single fluid may be forced out from the proximal chamber 104 by collapsing the valve stopper 10 (i.e., collapsing the lateral wall 14) under the pressure exertedby the plunger stopper 124, which reduces the volume of the cavity 16, and the dead volume is thus injected.

[0135] While embodiments of the injection device 100 described above include only a single valve stopper 10 therein, it is recognized that other embodiments of injection devices may include one or more additional valve stoppers 10 therein - such that a multi-chamber injection device may be used to sequentially inject a plurality of different fluids.

[0136] Referring now to FIGS. 21 and 22, embodiments of a multi-chamber injection device 100 are shown that include two separate valve stoppers 10a, 10b therein for separating a plurality of fluids and allow for sequential injection of those fluids.

[0137] In FIG. 21, the multi-chamber injection device 100 includes a first valve stopper 10a and a second valve stopper 10b that - along with plunger stopper 124 and barrel 106 - define a first chamber 140 that contains a first fluid Fl, a second chamber 142 that contains a second fluid F2, and a third chamber 144 that contains a third fluid F3.

[0138] In an initial configuration before injection of the first fluid Fl, the plunger stopper 124 is in a proximal position and the valve stoppers 10a, 10b are in a rest position, with the slit 28 in each valve stopper 10a, 10b being maintained closed under radial compression thereof.

[0139] The injection device 100 may then be actuated by a user to perform the injection of the first fluid Fl - with a distally directed force applied to the plunger stopper 124. The force applied to the plunger stopper 124 is transmitted to the valve stoppers 10a, 10b via pressure from the second and third fluids F2, F3, which causes the stoppers 10a, 10b to be advanced / displaced distally within barrel 106. The displacement of the stoppers 10a, 10b in the distal direction pushes the first fluid Fl in the distal direction, so that the first fluid Fl is expelled from the injection device 100 through the channel 118 of tip 116. During expulsion of the first fluid Fl, the stoppers 10a, 10b remain in a sealing position - with the slit 28 in each valve stopper remaining closed. The injection of the first fluid Fl continues until the valve stopper 10a abuts the end wall 114 at the distal end 108 of the barrel 106.

[0140] The injection device 100 may then be actuated by a user to perform the injection of the second fluid F2 - with a distally directed force applied to the plunger stopper 124. Since the valve stopper 10a cannot move further distally, the pressure in the second chamber 142 increases as the plunger stopper 124 continues to advance distally, and thus the force differential AP becomes superior to the valve opening force Fopof slit 28 in the membrane 12 of first valve stopper 10a. As a result, the slit 28 in membrane 12 is caused to open, thereby allowing the second fluid F2 to pass through the slit 28 and to / through the channel 118 intip 116 for the injection. At the same time that the second fluid F2 is flowing through slit 28 of valve stopper 10a, the valve stopper 10b is displaced in the distal direction. During expulsion of the second fluid F2, the stopper 10b remains in a sealing position. The injection of the second fluid F2 continues until the valve stopper 10b abuts the valve stopper 10a.

[0141] As the user continues to apply a further distally directed force to the plunger stopper 124, pressure in the third chamber 144 increases as the plunger stopper 124 continues to advance distally, and thus the force differential AP becomes superior to the valve opening force FOp of slit 28 in both the valve stoppers 10a, 10b. As a result, the slit 28 in the membrane 12 of each valve stopper 10a, 10b is caused to open, thereby allowing the third fluid F3 to pass through the slits 28 and to / through the channel 118 in tip 116 for the injection.

[0142] In FIG. 22, the multi-chamber injection device 100 includes a first valve stopper 10a and a second valve stopper 10b that - along with plunger stopper 124 and barrel 106 - define a first chamber 140 that remains empty, a second chamber 142 that contains a first fluid Fl, and a third chamber 144 that contains a second fluid F2. In this embodiment, valve stopper 10a is initially positioned at the far distal end 108 of the barrel 106, such that first chamber 140 is defined as the channel 118 within tip 116.

[0143] Operation of the injection device 100 in FIG. 22 may proceed similarly to as previously described for the injection devices of FIGS. 19A-19D, 20A-20C and 21, and thus is not described in detail herein.

[0144] Referring now to FIGS. 23 and 24, embodiments of a multi-chamber injection device 100 are shown that include three separate valve stoppers 10a, 10b, 10c therein for separating a plurality of fluids and allow for sequential injection of those fluids.

[0145] In FIG. 23, the multi-chamber injection device 100 includes a first valve stopper 10a, a second valve stopper 10b, and a third valve stopper 10c that - along with plunger stopper 124 and barrel 106 - define a first chamber 140 that contains a first fluid Fl, a second chamber 142 that contains a second fluid F2, a third chamber 144 that contains a third fluid F3, and a fourth chamber 146 that contains a fourth fluid F4.

[0146] Operation of the injection device 100 in FIG. 23 may proceed similarly to as previously described for the injection device of FIG. 21, except that an additional round of valve stopper advancement and opening is included, due to the additional valve stopper and fluid provided.

[0147] In FIG. 24, the multi-chamber injection device 100 includes a first valve stopper 10a, a second valve stopper 10b, and a third valve stopper 10c that - along with plunger stopper 124 and barrel 106 - define a first chamber 140 that remains empty, a second chamber 142 thatcontains a first fluid Fl, and a third chamber 144 that contains a second fluid F2, and a fourth chamber 146 that contains a third fluid F3.

[0148] Operation of the injection device 100 in FIG. 24 may proceed similarly to any of the previously described injection devices of FIGS. 19-23, and thus is not described in detail herein.

[0149] While the injections devices 100 shown and described in FIGS. 21-24 are illustrated as including valve stoppers 10 configured as “symmetrical stoppers” such as shown and described in FIG. 10, it is recognized that that the valve stoppers 10 may have any suitable description previously described in the present disclosure, including the valve stoppers 10 in any of FIGS. 3-18, according to embodiments of the disclosure.

[0150] Beneficially, embodiments of the invention thus are directed to a valve stopper and associated multi-chamber injection device, for the injection of one or more fluids therefrom. The valve stopper is structured to ensure proper alignment and guiding thereof during insertion into the barrel of a medical injection device (e.g., during vent tube stoppering) and during distal advancement within the barrel when injecting a first fluid from a distal chamber. The valve stopper may also be designed to ensure proper sealing thereof with the barrel, so as to prevent leakage of a second fluid in a proximal chamber into the first fluid in the distal chamber. The valve stopper may include numerous features thereon to enable such alignment, guiding, and sealing capabilities.

[0151] Although the present disclosure has been described in detail for the purpose of illustration based on what is currently considered to be the most practical and preferred embodiments or aspects, it is to be understood that such detail is solely for that purpose and that the present disclosure is not limited to the disclosed embodiments or aspects, but, on the contrary, is intended to cover modifications and equivalent arrangements that are within the spirit and scope of the appended claims. For example, it is to be understood that the present disclosure contemplates that, to the extent possible, one or more features of any embodiment may be combined with one or more features of any other embodiment.

Claims

THE INVENTION CLAIMED IS1. A multi-chamber medical injection device for injecting at least one composition, comprising: a barrel extending from a proximal end to a distal end, the barrel comprising a cylindrical wall having a barrel inner diameter; a plunger stopper adapted to be translationally movable inside the barrel; and a valve stopper arranged between the distal end of the barrel and the plunger stopper and adapted to be translationally movable inside the barrel, the valve stopper comprising: a membrane configured to separate a distal chamber of the barrel from a proximal chamber of the barrel, the membrane comprising at least one slit extending through at least a part of a thickness of the membrane between a proximal face and a distal face thereof, with the slit configured to selectively create a fluid path through the membrane from the proximal face to the distal face depending on the pressure exerted by a composition onto the proximal face of the membrane for transferring fluid only from the proximal chamber to the distal chamber; and a lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising a sealing surface including one or more circumferential ribs configured to sealingly engage the inner surface of the barrel; wherein at least one of the one or more circumferential ribs has a rib outer diameter that is greater than the barrel inner diameter, with the at least one of the one or more circumferential ribs having a compression rate of between 2% and 12% when positioned within the barrel.

2. The multi-chamber medical injection device of claim 1, wherein the compression rate is defined according to:Compression Rate = (l-(barrel_ID / rib_OD)) x 100, where barrel_ID is the barrel inner diameter and rib_OD is the rib outer diameter of the at least one rib.

3. The multi-chamber medical injection device of claim 1, wherein the one or more circumferential ribs comprises a first rib and a second rib.

4. The multi-chamber medical injection device of claim 3, wherein the valve stopper comprises a cylindrical stopper, with the rib outer diameter of each of the first rib and the second rib being equal.

5. The multi-chamber medical injection device of claim 1 , wherein the first and second ribs are radially compressed by the barrel such that the rib outer diameter is compressed to a compressed rib diameter, and wherein the first rib and the second rib are axially spaced apart by a pitch that is greater than 30% of the compressed rib diameter, and preferably greater than 50% of the compressed rib diameter.

6. The multi-chamber medical injection device of claim 3, wherein the valve stopper comprises a conical stopper, with the rib outer diameter of the first rib being a first diameter and the second rib having a second diameter that is less than the first diameter.

7. The multi-chamber medical injection device of claim 6, wherein a conicity of the conical stopper is up to 10%, as defined by:Conicity = (((rib_OD_first - rib_OD_second) / 2) / L_pitch)) x 100, where rib_OD_first is the first diameter, rib_OD_second is the second diameter, and L_pitch is an axial distance between the first rib and the second rib.

8. The multi-chamber medical injection device of claim 1, wherein the multi-chamber medical injection device is configured to sequentially inject two compositions, with a first composition contained within the distal chamber between the valve stopper and the distal end of the barrel and a second composition contained within the proximal chamber between the valve stopper and the plunger stopper.

9. The multi-chamber medical injection device of claim 1, being one of a stand-alone syringe or cartridge, or a syringe or cartridge integrated with an auto-injector, pen or safety device.

10. A multi-chamber medical injection device for injecting at least one composition, comprising: a barrel extending from a proximal end to a distal end, the barrel comprising a cylindrical wall having a barrel inner diameter; a plunger stopper adapted to be translationally movable inside the barrel; and a valve stopper positioned within the barrel distally from the plunger stopper and adapted to be translationally movable inside the barrel, the valve stopper comprising: a membrane configured to separate a distal chamber of the barrel from a proximal chamber of the barrel, the membrane comprising at least one slit extending through at least a part of a thickness of the membrane between a proximal face and a distal face thereof, with the at least one slit configured to selectively create a fluid path through the membrane from the proximal face to the distal face depending on the pressure exerted by a composition onto the proximal face of the membrane for transferring fluid only from the proximal chamber to the distal chamber; and a lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising: a sidewall; a first rib extending radially outward from an outer surface of the sidewall and around an outer circumference thereof; and a second rib extending radially outward from the outer surface of the sidewall and around the outer circumference thereof; wherein at least one of the first and second ribs has a rib outer diameter that is greater than the barrel inner diameter, with the rib outer diameter being compressed to a compressed rib diameter when positioned within the barrel; and wherein the first rib and the second rib are axially spaced apart by a pitch that is greater than 30% of the compressed rib diameter.

11. The multi-chamber medical injection device of claim 10, wherein the first rib and the second rib are axially spaced apart by a pitch that is greater than 50% of the compressed rib diameter.

12. A valve stopper configured to be positioned inside a barrel of a multichamber injection device for injecting at least one composition through a distal end of the barrel, the valve stopper comprising: a membrane configured to separate a distal chamber of the barrel from a proximal chamber of the barrel, the membrane comprising a at least one slit extending through at least a part of a thickness of the membrane between a proximal face and a distal face thereof, with the at least one slit configured to selectively create a fluid path through the membrane from the proximal face to the distal face depending on a pressure exerted by a fluid onto the proximal face of the membrane for transferring fluid only from the proximal chamber to the distal chamber; and a lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising: a sidewall; a circumferential rib positioned at one end of the sidewall and joined to the membrane, the circumferential rib extending out radially from the sidewall and configured to sealingly engage the inner surface of the barrel; and a plurality of guiding members extending axially along a length of the sidewall along an outer surface thereof, the plurality of guiding members spaced apart circumferentially about the sidewall.

13. The valve stopper of claim 12, wherein each of the plurality of guiding members comprises: an elongated portion having a first end and a second end, the first end joined to the circumferential rib, wherein the elongated portion extends radially outward from the sidewall but is radially inset from a rib outer diameter of the circumferential rib; and an end portion joined to the second end of the elongated portion, the end portion protruding radially outward from the elongated portion so that a radially outward-facing surface of the end portion is radially aligned with a radially outward-facing surface of the circumferential rib.

14. The valve stopper of claim 13, wherein the end portion of each of the plurality of guiding members has a shape giving a localized contact, with a point of the shape giving a localized contact presenting the radially outward-facing surface of the end portion.

15. The valve stopper of claim 12, wherein the plurality of guiding members comprises between three and six guiding members that are equally spaced apart circumferentially about the sidewall.

16. The valve stopper of claim 12, wherein an axial distance between the circumferential rib and the end portions of the plurality of guiding members is greater than 30% of a diameter of the circumferential rib, when retained and compressed within the barrel of the injection device, and preferably greater than 50% of the diameter of the circumferential rib, when retained and compressed within the barrel of the injection device.

17. The valve stopper of claim 12, wherein the slit extends completely through the membrane between the proximal face and the distal fare, to form a valve configured to open or close depending on the pressure exerted by the fluid onto the proximal face of the membrane.

18. The valve stopper of claim 12, wherein the membrane has a membrane diameter that is 85% or less of a rib outer diameter of the circumferential rib.

19. A valve stopper configured to be positioned inside a barrel of a multichamber injection device for injecting at least one composition sequentially through a distal end of the barrel, the valve stopper comprising: a membrane configured to separate a first, distal chamber of the barrel from a second, proximal chamber of the barrel, the membrane comprising at least one slit extending through at least a part of a thickness of the membrane between a proximal face and a distal face thereof, with the at least one slit configured to selectively create a fluid path through the membrane from the proximal face to the distal face depending on a pressure exerted by a fluid onto the proximal face of the membrane for transferring fluid only from the second chamber to the first chamber; anda lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising: a sidewall; a first rib positioned at a first end of the sidewall and formed around an outer circumference of the sidewall, the first rib extending radially outward from an outer surface of the sidewall; and a second rib positioned at a second end of the sidewall and formed around the outer circumference of the sidewall, the second rib extending radially outward from the outer surface of the sidewall; wherein the first rib has a first rib outer diameter and the second rib has a second rib outer diameter that is less than the first diameter.

20. The valve stopper of claim 19, wherein with the first rib having the first rib outer diameter and the second rib having the second rib outer diameter that is less than the first diameter, the valve stopper has a frustoconical shape.

21. The valve stopper of claim 20, wherein a conicity of the conical stopper is up to 10%, as defined by:Conicity = (((rib_OD_first - rib_OD_second) / 2) / L_pitch)) x 100, where rib_OD_first is the first diameter, rib_OD_second is the second diameter, and L_pitch is an axial distance between the first rib and the second rib.

22. The valve stopper of claim 19, wherein the at least one slit is in the form of a line, centered on the proximal face of the membrane.

23. The valve stopper of claim 19, wherein the slit extends completely through the membrane between the proximal face and the distal fare, to form a valve configured to open or close depending on the pressure exerted by the fluid onto the proximal face of the membrane.

24. The valve stopper of claim 19, wherein the membrane has a membrane diameter that is 85% or less of a rib outer diameter of the circumferential rib.

25. The valve stopper of claim 19, wherein in a region of the membrane including the at least one slit, the membrane has a thickness between 0.2 mm and 3.0 mm.

26. A pre-filled medical injection device for sequentially injecting a first liquid and a second liquid, the injection device comprising: a barrel extending from a proximal end to a distal end, the barrel comprising a cylindrical wall having a barrel inner diameter; a plunger stopper adapted to be translationally movable inside the barrel; and a valve stopper arranged between the distal end of the barrel and the plunger stopper and adapted to be translationally movable inside the barrel, the valve stopper comprising: a membrane configured to separate a distal chamber of the barrel from a proximal chamber of the barrel, the membrane comprising at least one slit extending through at least a part of a thickness of the membrane between a proximal face and a distal face thereof, with the slit configured to selectively create a fluid path through the membrane from the proximal face to the distal face depending on the pressure exerted by a composition onto the proximal face of the membrane for transferring fluid only from the proximal chamber to the distal chamber; and a lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising a sealing surface including one or more circumferential ribs configured to sealingly engage the inner surface of the barrel; a first liquid contained within the distal chamber, the first liquid comprising a GLP-1 agonist; and a second liquid contained within the proximal chamber, the second liquid comprising an amyline analog.

27. The pre-filled medical injection device of claim 26, wherein the GLP-1 agonist comprises a calcitonin receptor agonist and the amyline analog comprises a dual amylin.

28. The pre-filled medical injection device of claim 26, wherein the GLP-1 agonist comprises semaglutide and the amyline analog comprises cagrilintide.

29. The pre-filled medical injection device of claim 26, wherein the valve stopper presents the successive following positions during a sequential injection: a first position where the fluid path is closed; a second position where the valve stopper is more distal than in the first position, where the fluid path closed, with the proximal face of the membrane being subjected to a pressure that is inferior to a valve opening force of the at least one slit; and a third position, wherein the valve stopper abuts the distal end of the barrel, the fluid path being opened due to a pressure exerted on the proximal face of the membrane that is superior to the valve opening force of the at least one slot; wherein the first liquid is injected as the valve stopper moves from the second position to the third position; and wherein the second liquid is injected responsive to further distal movement of the plunger stopper with the valve stopper at the third position.

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