One-way valve stopper with reed valve for a multi-chamber medical injection device

Abstract

Provided herein is a valve stopper positionable within a barrel of an injection device. The valve stopper includes a membrane comprising a proximal face and a distal face and that separates a first chamber and a second chamber of the barrel. A lateral wall is joined to the membrane that defines at least one cavity and provides a circumferential sealing surface that sealingly engages an inner surface of the barrel. The membrane comprises a reed valve thereon that may be actuated to selectively create a fluid path through the membrane from the proximal face to the distal face. The reed valve includes a block formed integrally with the membrane and that includes one or more openings therein, and one or more flaps configured to deflect to uncover the openings to create a fluid path through the reed valve for transferring fluid only from the second chamber to the first chamber.

Description

ONE-WAY VALVE STOPPER WITH REED VALVE FOR A MULTI-CHAMBERMEDICAL INJECTION DEVICECROSS-REFERENCE TO RELATED APPLICATION

[0001] The present application claims priority to Untied States Provisional Patent Application No. 63 / 639,014, entitled “One-Way Stopper with Reed Valve for a Multi-Chamber Medical Injection Device” filed April 26, 2024, the disclosure of which is hereby incorporated by reference in its entirety.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 for 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, a minimized risk of microbial contamination and an enhanced convenience of use for the practitioners. Furthermore, such prefilled containers may encourage and simplify self-administration 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 lyophilized 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 have a number of drawbacks associated therewith. As one example, the configuration of the valve stopper may be such that a substantial force may need to be applied onto the plunger to force the second solution through the opening / slit therein and expelling it out the injection device. As another example, the structure of the valve stopper may be complex - such as being configured as a multi-component stopper where a valve isseparate from a stopper body - which may be detrimental for the functioning of the valve assembly and / or its manufacturing. As still further examples, the design of existing valve stoppers may lead to issues with opening the valve smoothly, providing a desired flux or flowrate through the stopper, and / or maintaining valve robustness or integrity until injection.

[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 valve stopper configured to be positioned inside a barrel of a multi-chamber injection device for injecting at least one fluid through a distal end of the barrel. The valve stopper comprises a membrane comprising a proximal face and a distal face, the membrane being configured to separate a first, distal chamber of the barrel from a second, proximal chamber of the barrel. The valve stopper also comprises a lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising a circumferential sealing surface configured to sealingly engage the inner surface of the barrel. The membrane includes a reed valve thereon that may be actuated to selectively create a fluid path through the membrane from the proximal face to the distal face for transferring fluid only from the second chamber to the first chamber. The reed valve includes a block formed integrally with the membrane and forming part of the proximal face and the distal face of the membrane, with the block defining an open cavity on the proximal face and protruding distally out on the distal face, and wherein the block includes one or more openings formed therein. The reed valve also includes one or more flaps positioned on the block and covering the one or more openings, with each of the one or more flaps configured to selectively deflect in a distal direction and uncover the one or more openings depending on a proximal pressure exerted by a fluid onto the reed valve, to selectively create a proximal-to-distal fluid path through the reed valve for transferring fluid only from the second chamber to the first chamber.

[0011] In certain configurations, each of the one or more flaps comprises a cantilevered flap comprising an attached proximal end and a free distal end, and wherein each cantilevered flap deflects from a first position where the flap covers a respective opening or openings of the one or more openings to a second position where the respective opening or openings of the one or more openings are uncovered.

[0012] In certain configurations, the block comprises a pair of main walls, a pair of end walls, and a distal wall.

[0013] In certain configurations, each main wall of the pair of main walls is angled away from the proximal face of membrane at an obtuse angle, with the pair of main walls angled toward each other to meet at the distal wall, with each main wall of the pair of main wall including at least one respective opening formed therein.

[0014] In certain configurations, each main wall of the pair of main wall includes two openings formed therein.

[0015] In certain configurations, the one or more flaps comprises a pair of flaps, with a respective flap positioned on each main wall of the pair of main walls.

[0016] In certain configurations, the pair of main walls comprises a first main wall and a second main wall, the first main wall angled away from the proximal face of membrane at an obtuse angle and the second main wall oriented orthogonal to the proximal face of the membrane, with the first main wall angled toward the second main wall to meet at the distal wall.

[0017] In certain configurations, the first main wall includes the one or more openings formed therein.

[0018] In certain configurations, the one or more flaps comprises a single flap positioned on the first main wall.

[0019] In certain configurations, the one or more flaps are formed integrally with the block, with an entirety of the valve stopper thus formed as a mono-component and mono-material stopper.

[0020] In certain configurations, the valve stopper is formed of an elastomer or a thermoplastic material.

[0021] In certain configurations, the one or more flaps are formed separately from the block and affixed thereto, such that the valve stopper is formed as a bi-component stopper.

[0022] In certain configurations, each of the one or openings comprises a circular opening.

[0023] In certain configurations, the membrane is positioned at a proximal end of the valve stopper, with the lateral wall extending distally from the membrane.

[0024] In certain configurations, the membrane is positioned at a distal end of the valve stopper, with the lateral wall extending proximally from the membrane.

[0025] In certain configurations, the membrane is positioned between a proximal end and a distal end of the valve stopper, with the lateral wall extending both distally and proximally from the membrane.

[0026] Also provided herein is a medical injection device for injecting at least one fluid. The medical injection device comprises a barrel extending from a proximal end to a distal end, withthe barrel comprising a cylindrical wall, an end wall positioned at the distal end, and a tip extending distally from the end wall. The medical injection device further comprises 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 comprises a membrane having a proximal face and a distal face, with the membrane being configured to separate a first, distal chamber of the barrel from a second, proximal chamber of the barrel, and with the membrane including a reed valve thereon that may be actuated to selectively create a fluid path through the membrane from the proximal face to the distal face. The valve stopper further comprises a lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising a circumferential sealing surface configured to sealingly engage the inner surface of the barrel. A first chamber is defined within the barrel between the distal end of the barrel and the valve stopper and a second chamber is defined within the barrel between the valve stopper and the plunger stopper.

[0027] In certain configurations, the medical injection device is configured to sequentially inject two fluids, with a first fluid contained within the first chamber and a second fluid contained within the second chamber, and wherein the valve stopper is spaced apart distally from the end wall to separate the first chamber from the second chamber.

[0028] In certain configurations, the medical injection device is one of a syringe or a cartridge.

[0029] In certain configurations, with the membrane positioned at a proximal end of the valve stopper, the plunger stopper comprises a protrusion formed on a distal-facing surface thereof, the protrusion having a profile that matches a profile of the open cavity formed in the proximal face of the membrane.

[0030] In certain configurations, with the membrane positioned at a distal end of the valve stopper, the barrel comprises a notch formed therein at the distal end of the barrel, the notch having a profile that matches a profile of the block that protrudes distally out from the distal face of the membrane.BRIEF DESCRIPTION OF THE DRAWINGS

[0031] FIG. 1 is a perspective view of a multi-chamber medical injection device, according to a non-limiting embodiment described herein;

[0032] FIG. 2 is an exploded view of the multi-chamber medical injection device of FIG. 1;

[0033] 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;

[0034] FIG. 4 is a cross-sectional view of the valve stopper of FIG. 3;

[0035] FIG. 5 is a cross-sectional view of a valve stopper for use in a medical injection device, according to another non-limiting embodiment described herein;

[0036] 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;

[0037] FIG. 7 is a front cross-sectional view of a membrane of a valve stopper included in a medical injection device, according to a non-limiting embodiment described herein;

[0038] FIG. 8 is a partial perspective view of the membrane of FIG. 7;

[0039] FIG. 9 is a side cross-sectional view of the membrane of FIG. 7;

[0040] FIG. 10 is a side view of the membrane of FIG. 7;

[0041] FIG. 11 is a front cross-sectional view of a membrane of a valve stopper included in a medical injection device, according to another non-limiting embodiment described herein;

[0042] FIG. 12 is a side cross-sectional view of the membrane of FIG. 11;

[0043] FIG. 13 is a side view of the membrane of FIG. 11 ;

[0044] FIG. 14 is a side cross-sectional view of a multi-chamber medical injection device, including a valve stopper therein, according to another non-limiting embodiment described herein;

[0045] FIG. 15 is a side cross-sectional view of a multi-chamber medical injection device, including a valve stopper therein, according to another non-limiting embodiment described herein;

[0046] FIGS. 16A-16D illustrate various configurations of the injection device of FIG. 1 during injection of first and second compositions from the device; and

[0047] FIGS. 17A-17C illustrate various configurations of an injection device during injection of a single composition from the device, according to another non-limiting embodiment described herein.DESCRIPTION OF THE INVENTION

[0048] 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.

[0049] 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.

[0050] 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.

[0051] 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”), or to a syringe or cartridge that may be used with an injection device (i.e., an auto-injector or pen, or another safety device), as non-limiting examples. The valve stopper 10 is configured to divide a container, such as a syringe barrel or cartridge, into a distal chamber, which contains a first or initial fluid to be injected 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 one or more slits therein that define one or more flaps that function 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 multi-chamber injection device 100 of the present disclosure can be used for fluid delivery of multiple medical fluids 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.

[0052] As described in further detail herein, the valve stopper 10 is structured to prevent mixing of the two fluids before complete injection of the first fluid, while also allowing for injection of the second solution through the valve stopper by opening the valve smoothly, providing a desired flux or flowrate through the stopper, and / or maintaining valve robustness or integrity until injection.

[0053] 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.

[0054] 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 fluid followed 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 inresponse 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.

[0055] FIGS. 1 and 2 illustrate an example of a multi-chamber injection device 100 for sequential expulsion of at least an initial fluid Fl contained in a first or distal fluid chamber 102 (shown in FIGS. 16A and 16B) followed by a secondary fluid F2 contained in a second or proximal fluid chamber 104 (shown in FIGS. 16A-16D). 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.

[0056] 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 fluid in 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.

[0057] 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 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).

[0058] 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.

[0059] 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 substantially cylindrical body formed from a flexible and / or deformable material, such as an elastomer, or a thermoplastic elastomer material. Examples of elastomers and 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.

[0060] 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. 16A, 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.

[0061] 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 by opening the valve smoothly, providing a desired flux or flowrate through the stopper, and / or maintaining valve robustness or integrity until injection, 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.

[0062] 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.

[0063] In the embodiment represented in FIGS. 3 and 4, the membrane 12 is positioned at a proximal end 23 of the valve stopper 10, such that the lateral wall 14 extends in the distal direction only from the membrane 12, and the cavity 16 is delimited by the inner face 18 of the lateral wall 14 and the distal face 22 of the membrane 12 that constitutes the bottom of the cavity 16.

[0064] 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 proximal 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 20of 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.

[0065] According to still another embodiment, and as shown in FIG. 6, the valve stopper 10 may be configured such that the membrane 12 is positioned at distal end 25 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.

[0066] 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.

[0067] As shown in FIGS. 3-6, the valve stopper 10 has a substantially cylindrical shape, which corresponds to the shape of the barrel 106 of the injection device in which 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. The lateral wall 14 is provided with an outer 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.

[0068] According to a preferred embodiment, the sealing surface 24 may comprise one or more sealing ribs 26. 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 furtheroptimize the sealing depending on the dimensions of the valve stopper 10 and the barrel 106. According to the illustrated embodiment, the valve stopper 10 comprises two ribs 26. The inclusion of two 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.

[0069] According to aspects of the disclosure, in any of the embodiments of the valve stoppers 10 shown in FIGS. 3-6, the membrane 12 may comprise a peripheral region 28 that joins the membrane 12 to the lateral wall 14 and a central region 30 that includes a reed valve 32 that may be actuated between a closed position or configuration and an open position or configuration, to permit fluid flow through the membrane 12.

[0070] The peripheral region 28 may, in some embodiments, comprise a generally flat or planar region - with each of the proximal and distal faces 22 of the membrane 12 being flat / planar in the peripheral region 28. An area of the peripheral region 28 may contribute to the robustness of valve stopper 10, with an area of the peripheral region 28 in comparison to a shape and form factor of the reed valve 32 being considered in order to ensure that the valve stopper in sufficiently robust to withstand the forces applied thereto.

[0071] The reed valve 32 is formed in central region 30 and is configured to actuate between a closed position or configuration and an open position or configuration, to permit fluid flow through the membrane 12. The reed valve 32 may be generally comprised of a reed valve block 34 (here after “block 34”) formed integrally with the membrane 12 and one or more flaps 36 that are actuatable relative to the block 34 in order to selectively cover or expose one or more openings 38 formed in the block 34. That is, the flap(s) 36 of reed valve 32 may be distally deflected to an open position or configuration, as shown in phantom in FIGS. 3-6, to permit fluid flow through the reed valve 32, and through membrane 12, with the flap(s) 36 caused to deflect responsive to a pressure applied thereto. Deflection of the flap(s) 36 may thus selectively provide a “window” or fluid path 40 through the reed valve 32 from the proximal face 20 to the distal face 22 of the membrane 12 when opened, as explained in further detail below.

[0072] According to aspects of the disclosure, the flap(s) 36 are configured to transition between a closed position (i.e., an undeflected position) where fluid flow through the reed valve 32 of membrane 12 is prevented, and an open position (i.e., a deflected position) where fluid flow through the reed valve 32 of membrane 12 can occur (as shown in phantom in FIGS. 3- 6), thereby establishing fluid communication between the proximal chamber 104 and the distal chamber 102 through the valve stopper 10. In some examples, the reed valve 32 of membrane 12 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 flap(s) 36 - which corresponds to the force / pressure that needs to be exerted onto the proximal face 20 of the membrane 12 (and a proximal face of the flap(s) 36) for deflecting or raising the flap(s) 36. The flap(s) 36 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 flap(s) 36. The flap(s) 36 are biased to and initially provided in a closed position (i.e., with flap(s) 36 covering and closing opening(s). Accordingly, 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 flap(s) 36 are in the closed position. The flap(s) 36 transition to the open position when the fluid pressure P2 in the proximal chamber 104 substantially increases above the opening force Fopof the flap(s) 36.

[0073] The activation or opening force Fopfor the flap(s) 36 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 rod of a syringe through the syringe barrel. In some examples, the activation or opening force Fopfor the flap(s) 36 may be between 2 N and 25 N, preferably between 2 N and 20 N, and even more preferably between 5 N and 20 N. However, it is recognized that the activation or opening force Fopcan 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 flap(s) 36 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 flap(s) 36 of reed valve 32 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 appliedto 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.

[0074] According to aspects of the disclosure, the reed valve 32 of membrane 12 is a oneway membrane that functions as a check valve, which means that the reed valve 32 is configured to allow a composition / fluid to pass therethrough only when the composition / fluid flows in the distal direction, i.e., the direction of injection. In other terms, the flap(s) 36 are configured to open only for allowing the second fluid F2 in proximal chamber 104 to pass through the reed valve 32 of membrane 12 in a distal direction and into the distal chamber 102, while the first fluid Fl in distal chamber 102 may not pass through the reed valve 32 of membrane 12 in a proximal direction and into the proximal chamber 104. The flap(s) 36 are configured to remain closed for preventing the first fluid Fl to pass through the membrane 12 in the proximal direction - i.e., flowing from where the fluid contacts the distal face 22 of the membrane 12 to where the composition contacts the proximal face 20 of the membrane 12.

[0075] Referring now to FIGS. 7-10 (and as also shown in FIGS. 4-6), a structure of a reed valve 32a is shown according to an embodiment of the disclosure. The reed valve 32a includes a block 34a that is formed integrally with the membrane 12. The block 34a forms part of the proximal face 20 and distal face 22 of membrane 12, with the block 34a defining an open cavity 42 on the proximal face 20 and protruding distally out on the distal face 22. That is, on the distal face 22 of membrane 12, the block 34a protrudes distally out from a remainder of the distal face 22 (i.e., protrudes out distally from the surrounding peripheral region 28).

[0076] In the illustrated embodiment, the block 34a is configured as a wedge-shaped trapezoidal prism comprising a pair of angled main walls 44 and a pair of end walls 46. Each of the main walls 44 may be angled away from the proximal face 20 of membrane 12 at an obtuse angle, AA, with the main walls 44 angled toward each other to meet at a narrow distal wall 48 of the block 34a. In some embodiments, the end walls 46 may be formed at a right angle relative to the proximal face 20 of membrane 12, so as to be perpendicular to each other at opposing ends of the main walls 44.

[0077] According to embodiments, each of the main walls 44 includes one or more openings 38 therein that extend through the respective main wall 44. In the illustrated embodiment, each main wall 44 includes a pair of circular openings 38 in a side-by-side arrangement, but it is recognized that a different number of openings 38 could be formed in each main wall 44, including a greater number of openings 38 (i.e., three or more openings 38) or a lesser number of openings 38 (i.e., one opening), according to desired characteristics of a fluid path 40 to beprovided through reed valve 32a. Additionally, the shape of the openings 38 can vary, with openings alternatively provided as rectangular openings, triangular openings, or openings of another shape.

[0078] The reed valve 32a also includes a pair of flaps 36 that are provided on the block 34a to cover at least a majority of a distal-facing surface 50 of the main walls 44 and cover the openings 38 therein. The flaps 36 may be configured as cantilevered flaps that each include a fixed proximal end 52 and a free distal end 54, with the proximal end 52 joined to the block 34a adjacent an intersection of the main walls 44 and the membrane 12 (i.e., peripheral region 28 of membrane 12). Each flap 36 is configured to lay flat against its respective main wall 44 in an initial (undeflected) configuration, such that the flap 36 covers the openings 38 formed in the main wall 44. In this initial position with the flaps 36 covering the openings 38, a fluid path 40 through the reed valve 32a is closed, such that a fluid flow distally through the openings 38 is prevented. Upon a sufficient fluid pressure being applied onto a proximal-facing surface of each flap 36, as previously described, the flaps 36 are forced to deflect in the distal direction, such that the free distal end 54 of the flaps 36 separate away from the main walls 44 and from over the openings 38, as shown in phantom in FIG. 7. With the flaps 36 deflected and separated away from the openings 38, a fluid path 40 through the reed valve 32a is opened, such that a fluid flow distally through the openings 38 is allowed.

[0079] According to embodiments, parameters / characteristics of the block 34a and the flaps 36 may be selected during manufacturing in order to set / control the opening force Fopof the flaps 36 - i.e., the force / pressure that needs to be exerted onto the proximal-facing surface of the flaps 36) for deflecting the flaps 36 and uncovering openings 38. According to some embodiments, the stiffness of the flap 36 (including material, thickness, and or size (area - e.g., height x width) of the flaps 36) may be selected to control the opening force Fopof the flaps 36. According to other embodiments, the angle of the main walls 44 of block 34a, and the angle of the flaps 36 applied thereon, may be selected to control the opening force Fopof the flaps 36, for controlling a fluid flow through the reed valve 32a.

[0080] In addition to the parameters / characteristics of the block 34a and the flaps 36 being selected to set / control the opening force Fopof the flaps 36, the robustness of the valve stopper 10 may be set / controlled based on the construction of the membrane 12, including reed valve 32a. In some embodiments, robustness of the valve stopper 10 may be preserved by having an optimized ratio between the overall membrane diameter and the shape and form factor of the reed valve block 34a.

[0081] In one embodiment, robustness of the valve stopper 10 may be preserved by having an optimized ratio according to:ISv / (7t*(ODv / 2)2), where ISv is the internal surface area of the valve block 34a and ODv is the outer diameter of the membrane.

[0082] In another embodiment, robustness of the valve stopper 10 may be preserved by having an optimized ratio according to:ISv / ( 7t *(IDv / 2)2) where ISv is the internal surface area of the valve block 34a and IDv is the internal diameter of the membrane.

[0083] Referring now to FIGS. 11-13, a structure of reed valve 32b is shown according to another embodiment of the disclosure. The reed valve 32b includes a block 34b that is formed integrally with the membrane 12 as a single component. The block 34b forms part of the proximal face 20 and distal face 22 of membrane 12, with an arrangement of walls 58, 60 that form the block 34b defining an open cavity 62 on the proximal face 20 and protruding distally out on the distal face 22. That is, on the distal face 22 of membrane 12, the walls 58, 60 of block 34b protrude distally out from a remainder of the distal face 22 (i.e., protrude out distally from the surrounding peripheral region 28).

[0084] In the illustrated embodiment, the walls 58, 60 of block 34b form a right triangular prism comprising a pair of main walls 58 and a pair of end walls 60. A first main wall 58a may be angled away from the proximal face 20 of membrane 12 at an obtuse angle, AA, while a second main wall 58b may extend away from the proximal face 20 of membrane 12 at a right angle (i.e., orthogonal to the proximal face 20), AB, with a rounded corner / transition between the second main wall 58b and the proximal face 20 of membrane 12. The first main wall 58a is angled toward the second main wall 58b to meet at a narrow distal wall 64 of the block 34b. In some embodiments, the end walls 60 may be formed at a right angle relative to the proximal face 20 of membrane 12, so as to be perpendicular to each other at opposing ends of the main walls 58.

[0085] According to embodiments, the first main wall 58a includes one or more openings 38 therein that extend through the first main wall 58a. In the illustrated embodiment, the firstmain wall 58a includes a pair of circular openings 38 in a side-by-side arrangement, but it is recognized that a different number of openings 38 could be formed in the first main wall 58a, including a greater number of openings 38 (i.e., three or more openings 38) or a lesser number of openings 38 (i.e., one opening), according to desired characteristics of a fluid path 40 to be provided through reed valve 32b. Additionally, the shape of the openings 38 can vary, with opening alternatively provided as rectangular openings, triangular openings, or openings of another shape.

[0086] The reed valve 32b also includes a single flap 36 that is provided on the block 34b to cover at least a majority of a distal-facing surface 66 of the first main wall 58a and cover the openings 38 therein. The flap 36 may be configured as a cantilevered flap 36 that includes a fixed proximal end 52 and a free distal end 54, with the proximal end 52 joined to the block 34b adjacent an intersection of the first main wall 58a and the membrane 12 (i.e., peripheral region 28 of membrane 12). The flap 36 is configured to lay flat against the first main wall 58a in an initial (undeflected) configuration, such that the flap 36 covers the openings 38 formed in the first main wall 58a. In this initial position with the flap 36 covering the openings 38, a fluid path 40 through the reed valve 32b is closed, such that a fluid flow distally through the openings 38 is prevented. Upon a sufficient fluid pressure being applied onto a proximal- facing surface of the flap 36, as previously described, the flap 36 is forced to deflect in the distal direction, such that the distal end 54 of the flap 36 separates from the first main wall 58a and from over the openings 38, as shown in phantom in FIG. 11. With the flap 36 deflected and separated away from the openings 38, a fluid path 40 through the reed valve 32b is opened, such that a fluid flow distally through the openings 38 is allowed.

[0087] As previously described for the embodiment of FIGS. 7 and 8, parameters / characteristics of the block 34b and the flap 36 may be selected during manufacturing in order to set / control the opening force Fopof the flap 36 - i.e., the force / pressure that needs to be exerted onto the proximal-facing surface of the flap 36 for deflecting the flap 36 and uncovering openings 38. According to some embodiments, the stiffness of the flap 36 (including material, thickness, and or size (area - e.g., height x width) of the flaps 36) may be selected to control the opening force Fopof the flap 36. According to other embodiments, the angle of the first main wall 58a of block 34b, and the angle of the flap 36 applied thereon, may be selected to control the opening force Fopof the flap 36, for controlling a fluid flow through the reed valve 32b.

[0088] In addition to the reed valves 32a, 32b shown and described in FIGS. 7-13, it is recognized that reed valves of other suitable constructions may be provided in valve stopper10. In particular, the reed valve block 34 may have other configurations or constructions other than the wedge-shaped trapezoidal prism and right triangular prism previously described. According to additional embodiments, the block 34 may instead have a circular or elliptical shape, as non-limiting examples, with other configurations or constructions also being suitable, providing such configurations or constructions allow for easy demolding during manufacturing of the valve stopper.

[0089] For each of the reed valves 32a, 32b of FIGS. 7-13, the particular structure of the reed valve 32 and the formation thereof relative to a remainder of the valve stopper 10 may vary, according to embodiments of the disclosure. That is, in each of the embodiments previously described, the reed valve block 34 is formed integrally with the membrane 12 (i.e., as a monocomponent and mono-material component), such as by being molded therewith from an elastomer, or a thermoplastic elastomer material (e.g., silicone or synthetic or natural rubber (e.g., isoprene), or combinations thereof). However, according to various embodiments, the flap(s) 36 of the reed valve 32 may be formed integrally with the block 34 or may be formed as a separate component that is affixed to the block 34 (so as to form a bi-component and / or bi-material reed valve). In one embodiment, the flap(s) 36 is / are formed integrally with the block 34, such that the entirety of the reed valve 32 is formed with a remainder of the membrane 12 as single, integral component and of a single material (i.e., a mono-component and monomaterial valve stopper), such as being molded from an elastomer, or a thermoplastic elastomer material (e.g., silicone or synthetic or natural rubber (e.g., isoprene), or combinations thereof). In another embodiment, the flap(s) 36 may be initially provided as a separate element or elements that is / are joined to the block 34 during manufacturing of the valve stopper 10, such as via an appropriate welding or joining process, with the flap(s) 36 formed of a desired material (e.g., an elastomer or a thermoplastic elastomer material). In still another embodiment, the flap(s) 36 may be part of an overall shell that is separate from the block 34 and that is secured thereto during manufacturing of the valve stopper, such as via an appropriate welding or joining process. For example, the shell may be a separate molded component that includes flap(s) 36 formed therein, with the shell having a hollow construction and a shape that generally matches an outer profile of the block 34 (e.g., each of the block 34 and shell having a “duckbill” type configuration), with the shell being placed over the block 34 to align the flap(s) 36 with the openings 38 in block 34.

[0090] Additionally, it is recognized that the overall configuration of the valve stopper 10 - i.e., the location of the membrane 12 at the proximal or distal end of the valve stopper 10, and inclusion of the reed valve 32 in the membrane 12 - may dictate other changes in the syringe100. For example, it may be desired to change a configuration of the syringe barrel 102 or the plunger stopper 124 based on the location of the membrane 12 / reed valve 32, in order to limit the dead volume in the syringe 100. In one embodiment, where the membrane 12 is at the proximal end 23 of the valve stopper 10 (as in FIG. 4), a distal face of the plunger stopper 124 may be reconfigured, so as to include a protrusion 70 thereon that matches a shape of an open cavity 42, 62 on the proximal face 20 of the membrane 12 defined by the block 34 of reed valve 32, as shown in FIG. 14. In another embodiment, where the membrane 12 is at the distal end 25 of the valve stopper 10 (as in FIG. 6), a distal end 110 of the syringe barrel 102 may be reconfigured, so as to include a notch 72 formed therein shaped to accommodate the block 34 of reed valve 32 that extends out distally from the membrane 12, as shown in FIG. 15.

[0091] Referring now to FIGS. 16A-16D, functioning of an injection device including a valve stopper 10 is illustrated, in accordance with an embodiment of the disclosure. In some embodiments, the injection device may be a pre-filled, multi-chamber syringe 100 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 may be a prefilled cartridge (stand-alone cartridge or integrated in an auto-injector or safety device), with the cartridge including barrel 106, valve stopper 10, and a plunger stopper 124.

[0092] 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 and reed valve 32 thereof - 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 a configuration and sizing of the reed valve 32.

[0093] 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 orcategories may include analgesics, vitamins, vaccines (and boosters), monoclonal antibodies, diabetes and obesity treatments, and the like.

[0094] One exemplary embodiment of a liquid- liquid combination of a first fluid Fl and second fluid F2 that may be sequentially injected from the distal chamber 102 and proximal 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.

[0095] 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.

[0096] 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 distal chamber 102 and proximal 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.

[0097] FIG. 16A corresponds to the configuration of the injection device 100 before injection of the first 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 flap(s) 36 of reed valve 32 being maintained closed by a biasing of the flap(s) 36 to their closed position, such that the fluid path 40 is closed. 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 FOp of the flap(s) 36, so that the flap(s) 36 of reed valve 32 thus remain closed (i.e., the flap(s) 36 are not distally deflected or “raised”). The closed flap(s) 36 prevent the mixing of the first and second fluid, by preventing the first fluid from entering the proximal chamber 104 and the second fluid from entering the distal chamber 102. Additionally, the ribs 26 of thevalve 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.

[0098] Referring now to FIG. 16B, 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 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 in the distal direction, so that the first / initial fluid is expelled from the injection device 100 through the channel 118 of tip 116.

[0099] In the configuration of FIG. 16B, the valve stopper 10 is in a sealing position, with the flap(s) 36 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 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 and the second fluid 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 flap(s) 36. 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 flap(s) 36. The flap(s) 36 thus remain closed, so that openings 38 of the reed valve 32 remain 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. 16B.

[0100] Referring now to FIG. 16C, 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 flap(s) 36. As a result, the flap(s) 36 in reed valve 32 of membrane 12 are caused to deflect, thereby moving the flap(s) 36 to the open position and uncovering the openings 38 in the block 34 of the reed valve 32, so as to allow the second fluid to pass through the openings 38 (i.e., alongfluid path 40) and to / through the channel 118 in tip 116 for the injection. In this configuration, the valve stopper 10 is in an injection position.

[0101] As shown in FIG. 16D, at the end of the injection of the second fluid, the plunger stopper 124 abuts the valve stopper 10.

[0102] 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.

[0103] Referring now to FIG. 17A, inclusion of a valve stopper 10 (as previously described) 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. 16A-16D 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.

[0104] The functioning of the valve stopper 10 and the injection device comprising the valve stopper 10 will now be described here below, in reference to FIGS. 17A to 17C.

[0105] FIG. 17A 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 flap(s) 36 of reed valve 32 being maintained closed by a biasing of the flap(s) 36 to their closed position, such that the fluid path 40 is closed. 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 flap(s) 36, so that flap(s) 36 thus remains closed. The closed flap(s) 36 prevent the single fluid from leaking into channel 118 of tip 116.

[0106] Referring now to FIG. 17B, 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-facing surface of the flap(s) 36 of reed valve 32 of the membrane 12 thatbecomes superior to the valve opening force Fop. As a result, the flap(s) 36 of reed valve 32 is / are caused to deflect, thereby moving the flap(s) 36 to the open position and uncovering the openings 38 in the block 34 of the reed valve 32, so as to allow the single fluid to pass through the openings 38 (i.e., along fluid path 40) and to / through the channel 118 in tip 116 for the injection.

[0107] As shown in FIG. 17C, at the end of the injection of the single fluid, the plunger stopper 124 abuts the valve stopper 10.

[0108] Beneficially, embodiments of the invention thus are directed to a valve stopper and associated injection device. The valve stopper includes a membrane having a proximal face and a distal face, with the membrane including a reed valve formed therein / thereon. The reed valve include a reed valve block having opening formed therein, along with flaps that cover the openings and are deflectable to uncover the opening and create a fluid path or paths through the membrane from the proximal face to the distal face, depending on the pressure exerted by a fluid onto the flaps of the reed valve. By selectively providing a fluid path through the membrane from a proximal side to a distal side, the reed valve of the membrane provides for the sequential injection of multiple fluids from the injection device, with the reed valve preventing mixing of the fluids.

[0109] 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 valve stopper configured to be positioned inside a barrel of a multichamber injection device for injecting at least one fluid through a distal end of the barrel, the valve stopper comprising: a membrane comprising a proximal face and a distal face, the membrane being configured to separate a first, distal chamber of the barrel from a second, proximal chamber of the barrel; and a lateral wall joined to the membrane to define at least one cavity, the lateral wall comprising a circumferential sealing surface configured to sealingly engage the inner surface of the barrel; wherein the membrane comprises a reed valve thereon that may be actuated to selectively create a fluid path through the membrane from the proximal face to the distal face for transferring fluid only from the second chamber to the first chamber, the reed valve including: a block formed integrally with the membrane and forming part of the proximal face and the distal face of the membrane, with the block defining an open cavity on the proximal face and protruding distally out on the distal face, and wherein the block includes one or more openings formed therein; and one or more flaps positioned on the block and covering the one or more openings, each of the one or more flaps configured to selectively deflect in a distal direction and uncover the one or more openings depending on a proximal pressure exerted by a fluid onto the reed valve, to selectively create a proximal-to-distal fluid path through the reed valve for transferring fluid only from the second chamber to the first chamber.

2. The valve stopper of claim 1, wherein each of the one or more flaps comprises a cantilevered flap comprising an attached proximal end and a free distal end, and wherein each cantilevered flap deflects from a first position where the flap covers a respective opening or openings of the one or more openings to a second position where the respective opening or openings of the one or more openings are uncovered.

3. The valve stopper of claim 1 , wherein the block comprises a pair of main walls, a pair of end walls, and a distal wall.

4. The valve stopper of claim 3, wherein each main wall of the pair of main walls is angled away from the proximal face of membrane at an obtuse angle, with the pair of main walls angled toward each other to meet at the distal wall, with each main wall of the pair of main wall including at least one respective opening formed therein.

5. The valve stopper of claim 4, wherein each main wall of the pair of main wall includes two openings formed therein.

6. The valve stopper of claim 4, wherein the one or more flaps comprises a pair of flaps, with a respective flap positioned on each main wall of the pair of main walls.

7. The valve stopper of claim 3, wherein the pair of main walls comprises a first main wall and a second main wall, the first main wall angled away from the proximal face of membrane at an obtuse angle and the second main wall oriented orthogonal to the proximal face of the membrane, with the first main wall angled toward the second main wall to meet at the distal wall.

8. The valve stopper of claim 7, wherein the first main wall includes the one or more openings formed therein.

9. The valve stopper of claim 8, wherein the one or more flaps comprises a single flap positioned on the first main wall.

10. The valve stopper of claim 1, wherein the one or more flaps are formed integrally with the block, with an entirety of the valve stopper thus formed as a monocomponent and mono-material stopper.

11. The valve stopper of claim 10, wherein the valve stopper is formed of an elastomer or a thermoplastic material.

12. The valve stopper of claim 1, wherein the one or more flaps are formed separately from the block and affixed thereto, such that the valve stopper is formed as a bicomponent stopper.

13. The valve stopper of claim 1, wherein each of the one or openings comprises a circular opening.

14. The valve stopper of claim 1, wherein the membrane is positioned at a proximal end of the valve stopper, with the lateral wall extending distally from the membrane.

15. The valve stopper of claim 1, wherein the membrane is positioned at a distal end of the valve stopper, with the lateral wall extending proximally from the membrane.

16. The valve stopper of claim 1, wherein the membrane is positioned between a proximal end and a distal end of the valve stopper, with the lateral wall extending both distally and proximally from the membrane.

17. A medical injection device for injecting at least one fluid, comprising: a barrel extending from a proximal end to a distal end, the barrel comprising a cylindrical wall, an end wall positioned at the distal end, and a tip extending distally from the end wall; a plunger stopper adapted to be translationally movable inside the barrel; and the valve stopper of claim 1, arranged between the distal end of the barrel and the plunger stopper, and adapted to be translationally movable inside the barrel, wherein the lateral wall of the valve stopper sealingly engages the inner surface of the barrel; wherein a first chamber is defined within the barrel between the distal end of the barrel and the valve stopper and a second chamber is defined within the barrel between the valve stopper and the plunger stopper.

18. The medical injection device of claim 17, wherein the medical injection device is configured to sequentially inject two fluids, with a first fluid contained within the first chamber and a second fluid contained within the second chamber, and wherein the valve stopper is spaced apart distally from the end wall to separate the first chamber from the second chamber.

19. The medical injection device of claim 17, being one of a syringe or a cartridge.

20. The medical injection device of claim 17, wherein with the membrane positioned at a proximal end of the valve stopper, the plunger stopper comprises a protrusion formed on a distal-facing surface thereof, the protrusion having a profile that matches a profile of the open cavity formed in the proximal face of the membrane.

21. The medical injection device of claim 17, wherein with the membrane positioned at a distal end of the valve stopper, the barrel comprises a notch formed therein at the distal end of the barrel, the notch having a profile that matches a profile of the block that protrudes distally out from the distal face of the membrane.

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