Systems and methods for hybrid syringe valve assemblies

Abstract

An injector mixing system is provided for receiving and mixing contents between at least two injectors. In some embodiments, an injector coupling is provided that receives a first injector and a second injector, the injector coupling including a valve member that is transitionable between a closed position and an open position. A retention system is also provided for preventing or deterring removal of at least one of the injectors after use.

Description

[0001] This international application claims priority to U.S. Provisional Patent Application No. 63 / 130,144, filed on December 23, 2020, the entire disclosure of which is incorporated herein by reference. Technical Field

[0002] This disclosure generally relates to systems and mixing syringes for mixing. More specifically, embodiments of this disclosure relate to a mixing syringe operable to store and selectively mix contents between two syringes, and include a valve assembly for separating the contents of the syringe at least prior to the mixing operation. Background Technology

[0003] It is known to store pharmaceuticals and therapeutic agents in lyophilized or powder form. For example, therapeutic proteins are often formulated as powders due to stability and shelf-life factors, which must be reconstituted in a liquid or flowable medium or substance prior to injection. Similarly, it is known to store components (whether liquid or solid) of certain complex pharmaceutical preparations in separate containers for reasons related to the stability or reactivity of the components, wherein the contents of the separate containers must be mixed prior to injection. Related methods and systems have been provided to allow users and healthcare professionals to combine and formulate pharmaceuticals prior to administration. Known systems and methods include monotube systems, such as the system shown and described in U.S. Patent No. 9,592,343 to Shetty et al., which is incorporated herein by reference. Such systems and methods typically comprise two or more contents initially separated by a valve-type stopper or similar member, and repetitive movement of said stopper and associated plunger rod is operable to mix the syringe contents and subsequently eject the solution from the device. Dual-injector systems and methods are also known, for example, in the system shown and described in U.S. Patent No. 9,220,577 to Jessop et al., the entire contents of which are incorporated herein by reference. A dual-injector system typically includes a first substance disposed in a first syringe barrel and a second substance disposed in a second syringe barrel. The two syringe barrels of such a system can be connected to each other by engaging their distal outlets, thereby enabling fluid communication between the two syringes. The sequential activation of the plunger rod of each syringe then operably forces the contents between the two syringes and provides a mixing action.

[0004] However, various known systems and devices have drawbacks, including a high level of pre-application steps that increase the likelihood of user errors, incorrect mixing, dosage errors, and unwanted migration or leakage of syringe contents. For example, existing devices may initially be provided to the user as two separate syringes, each containing separate contents, such as a liquid or flowable component and a lyophilized or other form of therapeutic agent, to reduce or eliminate the risk of harmful migration of the liquid or flowable component from the first syringe to the lyophilized or other form of therapeutic agent in the second syringe during storage. However, using such a device requires additional steps, including assembly, before mixing and application. In contrast, monotube systems reduce or eliminate the requirement to connect or assemble components before mixing, but there is a possibility that the liquid or flowable component may migrate or leak into the lyophilized or other form of therapeutic agent before the desired mixing time. Monotube systems are also limited by the viscosity of the syringe contents and are not suitable for all applications. Summary of the Invention

[0005] Therefore, there has long been a need for a method and system for mixing drugs and therapeutics while reducing the risks and drawbacks of existing technologies and systems.

[0006] One object of this disclosure is to provide a method and system for mixing contents while simultaneously reducing the number of required administration steps. Another object of this disclosure is to provide a method and system for mixing contents that reduces the risk of harmful user errors and errors associated with the management of the contents. Another object of this disclosure is to provide a method and system for mixing the contents of a container, chamber, or syringe while simultaneously preventing or reducing the risk of undesirable migration, combination, mixing, etc. Furthermore, one object of this disclosure is to provide a method and system for mixing portions of a pharmaceutical composition or formulation containing an active pharmaceutical ingredient (API) that can be used to treat a patient's disease or ailment. Another object of this disclosure is to provide a method and system for mixing substances in a pharmaceutical formulation comprising lyophilized leuprolide or a pharmaceutically acceptable salt thereof (e.g., leuprolide acetate) and a biodegradable polymer-solvent system that can be used to treat diseases or ailments, including cancers, including but not limited to prostate cancer or breast cancer.

[0007] In various embodiments, a mixing syringe system is provided, comprising a first syringe, a second syringe, and a syringe coupling or connecting device. The syringe coupling is contemplated to include means operable to interconnect the first and second syringes and, for example, to isolate the contents of the two syringes during transport and storage, and to provide a reliable seal or closure element for isolation while eliminating the need for a user to assemble the syringes prior to mixing. In some embodiments, a first syringe, a second syringe, and a syringe coupling are provided, and these components are interconnected for transport and storage, so that the user does not need to assemble the components prior to mixing for subsequent administration of a drug or therapeutic agent.

[0008] While various embodiments of this disclosure contemplate a first syringe containing a first syringe contents (e.g., a fluid) and a second syringe containing a second syringe contents (e.g., a solid), other embodiments contemplate that the first syringe may initially not contain any substance and that a second syringe containing one or more contents that need to be mixed is provided. It should be understood that embodiments of this disclosure contemplate various storage, mixing, and reconfiguration applications, and that the innovative aspects of this disclosure are not limited to any particular intended use or application.

[0009] In some embodiments, the system of this disclosure includes a user-activated element. The user-activated element preferably comprises an irreversible "one-way" configuration, wherein the user is allowed to activate the element and move it from a first state to a second state, but cannot return the element to the first state. For example, in some embodiments, a valve-activated element is provided that can be operated by a user to move from a first position (e.g., a sealed position) to a second position (e.g., a flow-allowed position), but cannot be reversed to close the element (i.e., the operation from the first position to the second position is irreversible).

[0010] In various embodiments, a syringe coupling or hub is provided, wherein at least one syringe can be connected to the syringe coupling, and wherein removal of the syringe from the coupling is prevented or blocked. For example, in some embodiments, a first syringe containing the polymer is operable to connect and / or disconnect from the syringe coupling prior to activation or adjustment of the syringe coupling. Once the syringe coupling is activated (e.g., a fluid flow path in the coupling is opened), the first syringe can no longer be removed. Preventing removal of at least one syringe from the coupling is useful, for example, for guiding the user to use a second syringe (and only the second syringe) during application after mixing is complete.

[0011] In various embodiments, the systems and apparatus of this disclosure include an elastomeric element operable to seal a fluid path between a first syringe and a second syringe. It is contemplated that the apparatus and systems of this disclosure are suitable for containing a variety of substances and reagents, including but not limited to: pharmaceuticals and other therapeutic agents (solid (e.g., lyophilized solids) or semi-solid or liquid / fluid forms); liquid or flowable diluents, excipients, or solvent systems; solvent systems also containing cosolvents; polymer-solvent systems; polymer-solvent systems containing copolymers; or any combination thereof. Non-limiting examples of solvents suitable for use in the systems and apparatus of this disclosure include N-methyl-2-pyrrolidone (NMP), a liquid organic solvent with known volatility capable of generating gaseous vapors, which can circulate within a closed space, such as an inner plastic tray shell or outer cardboard box typically associated with pharmaceutical packaging. While various embodiments of this disclosure contemplate packaging and sealing elements with secure seals for a variety of substances and uses, some embodiments contemplate and provide systems for securely containing NMP or similar solvents and separating NMP from solids (e.g., lyophilized leuprolide acetate). If NMP is allowed to migrate into solid storage or containment areas, the active pharmaceutical ingredient may degrade, thereby reducing the substance's shelf life and overall stability. It should be recognized that other substances and applications also benefit from storage and sealing elements that provide a reliable seal (at least prior to mixing), and this disclosure is not limited to NMP and / or leuprolide acetate. The embodiments of this disclosure, as shown and described herein, provide reliable physical separation and prevent the migration of vapors, liquids, and solids.

[0012] The use of various elastomers (e.g., Santoprene) in conjunction with valve assemblies of embodiments of this disclosure is contemplated to suppress or prevent the delivery of liquid or gaseous solvents. In other embodiments, it is contemplated to provide plastic components (including plastic-on-plastic components) that generate sufficient seal to prevent the delivery of liquid or gaseous solvents between the syringe and other components of this disclosure.

[0013] While various substances have been considered for use in conjunction with embodiments of this disclosure, preferred embodiments of this disclosure contemplate the use of substances operable to withstand and be compatible with end-manufacturing sterilization, such as that using electron beam radiation, gamma radiation, X-ray technology, and ethylene oxide sterilization.

[0014] In one embodiment, an inter-syringe mixing system is provided, comprising a first syringe barrel including a hollow body defining a lumen, the hollow body having a proximal end and a distal dispensing end with an outlet. The system also includes a second syringe barrel including a hollow body defining a lumen, the hollow body having a proximal end and a distal dispensing end with an outlet. Both the first and second syringe barrels include a plunger slidably disposed within the syringe barrel for pressurizing contents contained within the lumen. A syringe coupling is provided, operable to receive the first and second syringe barrels. The syringe coupling includes a displaceable seal including a flow port, wherein when the displaceable seal is positioned in a first position, the flow port is offset from the outlet of at least one of the first and second syringe barrels, and wherein when the displaceable seal is positioned in a second position, the flow port is aligned with the outlet of the first and second syringe barrels.

[0015] In another embodiment, an inter-syringe mixing system is provided, comprising a first syringe barrel having a hollow body with a proximal end and a distal dispensing end with an outlet; and a second syringe barrel having a hollow body and an outlet, the second syringe barrel including a distal dispensing end with an outlet. Both the first and second syringe barrels include a plunger slidably disposed within the syringe barrel for applying pressure to a substance contained within a lumen. A valve assembly is provided operable to receive the first and second syringe barrels. The valve assembly includes a displaceable user interface operable to receive force from a user and transmit that force to a displaceable seal, wherein the displaceable user interface is movable along a direction substantially perpendicular to the longitudinal axis of at least one of the first and second syringe barrels.

[0016] In various embodiments, a method for mixing syringe contents and preparing a therapeutic agent is provided. In one embodiment, a method for preparing a therapeutic agent is provided, the method comprising providing a first syringe barrel and a second syringe barrel. Both the first and second syringe barrels include a plunger slidably disposed therein for applying pressure to a substance contained within the syringe barrel. A syringe coupling is provided, operable to receive the first and second syringe barrels, and the syringe coupling includes a user interface and a repositionable seal. The method includes securing at least one of the first and second syringe barrels to the syringe coupling, applying force to the user interface to move the repositionable seal from a first position to a second position, and alternately applying force to the plunger of the first and second syringe barrels to mix the contents of the first and second syringe barrels.

[0017] The Summary of the Invention section is not intended, nor should it be construed, as representing the entire scope and range of this disclosure. In the Summary of the Invention section, along with the accompanying drawings and detailed description, this disclosure is described at varying levels of detail, and the inclusion or exclusion of specific elements or components in the Summary of the Invention section is not intended to limit the scope of this disclosure. Additional features of this disclosure will become more apparent from the detailed description, especially when read in conjunction with the accompanying drawings. Attached Figure Description

[0018] Those skilled in the art will understand that the following description is merely illustrative of the principles of this disclosure, and these principles can be applied in various ways to achieve many different alternative embodiments. These descriptions are intended only to illustrate the general principles of the teachings of this disclosure and are not intended to limit the inventive concepts disclosed herein.

[0019] Embodiments of the present disclosure are illustrated in conjunction with the accompanying drawings, which are incorporated in and form part of this specification, and together with the foregoing general description and the following detailed description of the drawings, serve to explain the principles of the present disclosure.

[0020] It should be understood that the accompanying drawings are not necessarily drawn to scale. In some cases, details that are not necessary for understanding this disclosure or that would make other details difficult to understand may have been omitted. Of course, it should be understood that this disclosure is not limited to the specific embodiments shown herein.

[0021] Figure 1 This is a perspective view of a mixing syringe system.

[0022] Figure 2A This is a cross-sectional perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0023] Figure 2B This is a cross-sectional perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0024] Figure 3 This is an exploded perspective view of a mixing injector system according to an embodiment of the present disclosure.

[0025] Figure 4A This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0026] Figure 4B This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0027] Figure 4C This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0028] Figure 5AThis is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0029] Figure 5B This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0030] Figure 5C This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0031] Figure 5D This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0032] Figure 6A This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0033] Figure 6B This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0034] Figure 7A This is a cross-sectional elevation view of a mixing injector system according to an embodiment of the present disclosure.

[0035] Figure 7B This is a cross-sectional elevation view of a mixing injector system according to an embodiment of the present disclosure.

[0036] Figure 8 This is an elevation view of components of a mixing injector system according to an embodiment of the present disclosure.

[0037] Figure 9 This is an elevation view of components of a mixing injector system according to an embodiment of the present disclosure.

[0038] Figure 10 This is a perspective view of a hybrid system and associated packaging according to an embodiment of this disclosure.

[0039] Figure 11A This is a cross-sectional elevation view of a component of a syringe mixing system according to an embodiment of the present disclosure.

[0040] Figure 11B yes Figure 11A The cross-sectional elevation view of the component in the second position.

[0041] Figure 12A This is a cross-sectional elevation view of a component of a syringe mixing system according to an embodiment of the present disclosure.

[0042] Figure 12B yes Figure 12A The cross-sectional elevation view of the component in the second position.

[0043] Figure 12CThis is a side view of components of a syringe mixing system according to an embodiment of the present disclosure.

[0044] Figure 12D yes Figure 12C A front view of a component of an embodiment.

[0045] Figure 12E Provided Figure 12C Front elevation and side elevation views of the components in the embodiment.

[0046] Figure 12F Provided Figure 12C Front elevation and side elevation views of the components in the embodiment.

[0047] Figure 13 This is an exploded view of a syringe mixing system according to an embodiment of the present disclosure.

[0048] Figure 14A This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0049] Figure 14B This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0050] Figure 14C This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0051] Figure 15A This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0052] Figure 15B This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0053] Figure 15C This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0054] Figure 15D This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0055] Figure 16A This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0056] Figure 16B This is a perspective view of components of a mixing injector system according to an embodiment of the present disclosure.

[0057] Figure 17A This is a cross-sectional elevation view of a mixing injector system according to an embodiment of the present disclosure.

[0058] Figure 17BThis is a cross-sectional elevation view of a mixing injector system according to an embodiment of the present disclosure. Detailed Implementation

[0059] Figure 1 This is a perspective view of a known syringe-to-syringe mixing system. As shown, system 2 includes a first syringe 4 containing contents 6 and a second syringe 8 containing contents 10. Syringes 4 and 8 are connected at their respective distal dispensing ends. Fluids and substances contained within the syringes can be moved from one syringe to the other and can be mixed by applying force to syringe plunger rods 12 and 14. At least one plunger 16 is operable to actuate the contents between syringes 4 and 8 and produce a mixing effect. Various known syringes and systems require the first and second syringes to be directly connected by the user (e.g., by threaded connection) before mixing and application. The syringes are then disconnected from a syringe containing the mixed solution for application.

[0060] Figure 2A-2B This is a perspective view of a component of a valve assembly in a contemplated hybrid system used in conjunction with a syringe, according to an embodiment of this disclosure. As shown, a connecting element is provided as a syringe connector 18. The syringe connector 18 includes means operable to receive a first syringe and a second syringe and selectively provide fluid communication between the syringes. The syringe connector 18 includes a first end 20 operable to receive the first syringe and a second end 22 operable to receive the second syringe. The syringe (in...) Figure 2A-2B (Not shown in the image) is envisioned to include a distal end having an open outlet for dispensing and / or receiving substances. Figure 2A-2B The diagram shows a first end 20 and a second end 22 comprising internally threaded connecting members. However, it should be understood that the syringe coupling of this disclosure is not limited to a threaded connection, and one or both of the first and second ends may include alternative structures for receiving and securing the syringe. Figure 2A-2B As further shown, the syringe connector 18 includes a valve element comprising a displaceable member 24 movable relative to the connector 18. A first internal member 26 and a second internal member 28 are provided, each internal member including an orifice and engaging with the displaceable member.

[0061] like Figure 2A As shown, a closed position is provided, in which the displaceable member 24 is in a first position, and the central orifice of the displaceable member is offset from the orifices of the first inner member 26 and the second inner member 28. In this position, the flow of fluid and gaseous vapor is at least partially, preferably completely, blocked through the coupling. Therefore, the syringe connected to the coupling 18 cannot exchange substances in the closed position. The displaceable member 24 is offset and preferably includes a user-accessible surface or user interface, and is operable to receive an activation force.

[0062] An activation force on the displaceable member 24 is operable to move the displaceable member from a first position ( Figure 2A Move to the second position. Figure 2B In a first position, fluid flow through member 18 is blocked; in a second position, the orifice of displaceable member 24 aligns with the orifices of internal members 26, 28, forming a fluid flow path 30 through the device. As shown and described, syringe coupling 18 provides a means for securing at least one, preferably two, syringes, and includes a valve element to selectively allow substance delivery between syringes when the user activates the valve element.

[0063] Figure 3 This is an exploded perspective view of a mixing syringe system 40 according to another embodiment of the present disclosure. As shown, system 40 includes a first syringe 42 and a second syringe 44. It is envisioned that the first and second syringes initially contain solid or liquid contents. For example, the first syringe 42 may contain or include a polymer-solvent system, such as, but not limited to, a biodegradable polymer dissolved in NMP, and the second syringe 44 may contain a lyophilized drug, such as, but not limited to, lyophilized leuprolide acetate. While the discussion of various embodiments of the present disclosure considers and refers to a first syringe containing NMP and a second syringe containing lyophilized drugs, it should be understood that the present disclosure is not limited to this arrangement. The syringe contents may be changed, rearranged, and replaced while still remaining within the scope of the invention of the present disclosure. In fact, the innovative aspects of the present disclosure can be considered to reside in the features and components of the illustrated system, regardless of what substance (or whether any substance) is present in the components.

[0064] It has been recognized that undesirable NMP migration (i.e., accidental migration before mixing) can lead to various complications, including shortening or impairing the shelf life of the contents. The aim of various embodiments of this disclosure is to reduce or eliminate the risk of undesirable NMP migration while storing NMP and lyophilized drugs very close together before mixing.

[0065] As shown and described herein, the contents of the first syringe 42 and the second syringe 44 can be mixed to prepare a solution or suspension for administration. Figure 3 The embodiment includes a syringe coupling 46. The syringe coupling 46 of the illustrated embodiment is operable to receive and connect to a first syringe 42 and a second syringe 44, selectively preventing and allowing fluid transfer between the two syringes, and selectively preventing the removal of at least one syringe.

[0066] Each syringe 42, 44 includes a cylinder with an internal volume for receiving a plunger rod (in... Figure 3(Not shown) a proximal end and a distal end having a dispensing outlet, wherein the distal end is operable to connect to a syringe coupling 46. The syringe coupling 46 includes a valve assembly having a sealing element 48 nested within a recessed region 51 of a displaceable member 50. In some embodiments (including...) Figure 3 (As shown in the embodiment), the sealing element includes an annular sealing element. The displaceable member includes a user interface 52 and a convex extension 54, the user interface 52 being operable to be contacted by a user and to receive force from the user, and the convex extension 54 for receiving a second syringe 44. The syringe connector 46 also includes a guide member 56, within which the displaceable member is disposed. The guide member includes a user interface 57 ( Figure 5A The user interface 57 is operable to be touched by a user and to receive force from the user. A rotatable Luer locking member 58 is provided. The rotatable Luer locking member 58 of the illustrated embodiment includes a proximal end and a distal end, the proximal end having a convex connector operable to connect to a first syringe 42, and the distal end including teeth with protrusions for selectively restricting rotation of the rotatable Luer locking member 58 prior to activation.

[0067] Figures 4A-4C This is a perspective view showing the displaceable member 50 in more detail. As shown, the displaceable member 50 includes a user interface 52 operable to be controlled by a user. In a preferred embodiment, the displaceable member is capable of displacement in a downward direction (at least relative to...). Figure 4A It is preferably not operable to return to the initial or first position. A convex extension 54 is provided on one side of the member for receiving a syringe. A recess 56 is provided on the opposite side of the displaceable member relative to the convex extension 54. The recess 56 is operable to receive a sealing element, such as... Figure 3 The annular sealing element 48 has a channel passing through the displaceable member 50, wherein the channel passes through the convex extension 54 and extends into the recess 56. Preferably, the sealing element includes an orifice aligned with the channel of the displaceable member 50.

[0068] like Figures 4A-4BAs shown, a first protrusion 60 and a second protrusion 75 are provided on the displaceable member 50. Protrusions 60 and 75 are displaceable with member 50 and are at least movable relative to the rotatable Luer locking member 58 of the assembled device. In a first position, at least one protrusion contacts the rotatable Luer locking member 58 to prevent rotation of member 58. This contact and associated locking of the rotatable Luer locking member 58 allows the first syringe to be screwed onto (and unscrewed from) the rotatable Luer locking member 58 before activation of the assembled device. Movement of the displaceable member 50 caused by the user's activation operation causes protrusions 60 and 75 to displace, preventing them from contacting the Luer locking member 58. As the rotatable Luer locking member rotates, member 58 rotates freely within the displaceable member 50. Even when rotation is applied during an attempt to remove the syringe, the syringe connected to the rotatable Luer locking member 58 is prevented from separating from the syringe connector by threads without resistance. One object of this disclosure is to provide a syringe connector 46 that holds at least one syringe, thereby preventing a user from administering the mixture using a first syringe and thus giving the user the option to administer the mixture using only a second syringe.

[0069] like Figures 4A-4C As shown, the displaceable member 50 also includes clips or resilient protrusions 62a, 62b. The resilient protrusions 62a, 62b are operable to bend outwards and do not substantially impede downward movement of the displaceable member 50. However, when positioned in the second position, the resilient protrusions 62a, 62b are at least partially secured to the guide member 56 by their inherent restoring force. The resilient protrusions 62a, 62b secure the displaceable member 50 in the second position within the guide member 56 through their engagement in recesses 74a, 74b on the guide member 56, preventing or inhibiting the displaceable member from returning to the first position.

[0070] Figures 5A-5D This is a perspective view of a guide member 56 according to one embodiment, and it is envisioned that the guide member 56 is related to... Figures 4A-4C The displaceable member 50 is used in conjunction with it. As shown, the guide member 56 includes a central orifice 70 to allow fluid flow and receive a rotatable Luer locking member 58 of an embodiment of this disclosure. The guide member 56 is configured to slidably receive at least a portion of the displaceable member 50. As shown, the guide member 56 includes a receiving portion 76 having a first slot member 78a and a second slot member 78b to receive the displaceable member 50. The guide member includes a user interface 57 operable to be contacted by a user and to receive forces from the user. In some embodiments, such as Figures 5A-5D As shown, the user interface 57 is envisioned to include a grip or contact surface with ridges to reduce slippage and provide ergonomic benefits.

[0071] The surface of the guide member 56 includes a channel 72 ( Figure 5B ), to receive and guide the movement of the ramp-shaped protrusion 60 of the displaceable member 50 (e.g., as Figure 4B (As shown). During assembly of the syringe assembly connector, the guide member 56 operably receives the displaceable member 50 such that the protrusion 60 of the displaceable member 50 contacts the upper surface of the receiving portion 76 of the guide member 56 (at least relative to the upper surface of the receiving portion 76). Figure 5B The sloping protrusion 60 is directed to cause physical separation between the surface of the displaceable member 50 and the receiving portion 76 of the guide member 76. The sloping protrusion 60 allows the distal surface of the annular sealing element 48 nested within the recessed region 51 of the displaceable member 50 to slide over the distal surface of the Luer locking member 58 nested within the central aperture 70 of the guide member 56. Once the sloping protrusion 60 has passed over the distal surface of the Luer locking member 58 nested within the central aperture 70 of the guide member 56, the protrusion 60 is operably received in one of the plurality of teeth 86 of the Luer locking member 58. The ramp-shaped protrusion 60 operably engages in one of the teeth 86 of the Luer locking member 58, eliminating the physical separation caused during passage over the distal surface of the Luer locking member 58. This allows the distal surface of the annular sealing element 48, nested within the recessed region 51 of the displaceable member 50, to directly contact the distal surface of the Luer locking member 58 within the central orifice 70 of the guide member 56, resulting in compression of the annular sealing element 48. After the ramp-shaped protrusion 60 is operably received in one of the teeth 86 of the Luer locking member 58 and the annular sealing element 48 is compressed, the assembled syringe device connector is configured in a first position prior to activation. The ramp-shaped protrusion 60 is operable to allow translation of the guide member 56 over various irregular surfaces, including the central orifice of the Luer locking member 58.

[0072] In the first position before activation, the ramp-shaped protrusions 60 and 75 of the displaceable member 50 communicate with the rotatable Luer locking member 58 to prevent its rotation. In the second position after activation, the protrusion 60 of the displaceable member 50 displaces into the channel 72 of the guide member 56, while the protrusion 75 of the displaceable member displaces into the recessed area 73 on the guide member 56. Figure 9 In this recessed area, the protrusions 60 and 75 are positioned so as not to contact the rotatable Luer locking member 58 or to obstruct its rotation. The second position also includes a location forming a fluid flow channel. Specifically, the annular sealing element 48 disposed within the displaceable member 50 moves from a first position to a second position. The first position is characterized in that the channel of the annular sealing element 48 is offset from the inlet and outlet of the interconnected syringe and prevents flow between them. The second position is characterized in that the channel of the annular sealing element 48 is configured to be axially aligned with the syringe outlet and inlet.

[0073] For example, such as Figures 5A-5B As shown, the guide member 56 also includes recesses 74a, 74b operable to receive resilient protrusions 62a, 62b of the displaceable member and to secure the syringe coupling in a second position. The recesses 74a, 74b are operable to prevent, or at least hinder, the user from returning the device to the first position after activating the syringe coupling.

[0074] Figures 6A-6B This is a perspective view of a rotatable Luer locking member 58 according to an embodiment of the present disclosure. As shown, the rotatable Luer locking member 58 includes a first end having a convex Luer locking member 80 that provides means of attachment to a first syringe and a fluid flow path through a central orifice 81 of the member 58. The convex Luer locking member 80 is at least partially disposed within a threaded concave member 82 operable to engage with the first syringe by thread. A support surface 84 is provided on the exterior of the member 58. The support surface 84 is operable to be disposed in and contact with a central orifice 70 of a guide member 56. The support surface 84 of the rotatable Luer locking member 58 includes a surface on which the member 58 is rotatable (when unlocked) and contacts the central orifice 70 of the guide member 56. The rotatable Luer locking member 58 also includes a plurality of teeth 86 operable as locking members and selectively preventing rotation of the rotatable Luer locking member 58. Specifically, in the protrusions of the present disclosure (e.g. Figure 4B When the protrusion 75 is positioned in the first position, it is configured to contact at least one of the plurality of teeth 86, thereby preventing rotation of the rotatable Luer locking member 58 (at least relative to the guide member 56 and the displaceable member 50). The fixed nature or state of member 58 in the first position allows the user to screw the first syringe into the threaded concave member 82. When the displaceable member is displaced as shown and described herein, the protrusion 75 moves away from the plurality of teeth 86 of the rotatable Luer locking member 58, so that rotation is unimpeded and member 58 is allowed to rotate relative to the guide member 56 and the displaceable member. Since the rotational force applied to the syringe causes the rotatable Luer locking member 58 to rotate, this rotational freedom prevents or at least inhibits the unscrewing and removal of the first syringe. In the absence of significant reaction forces on the rotatable Luer locking member 58 or the threaded concave member 82, unscrewing does not occur, and removal of the first syringe from the syringe connector is effectively prevented.

[0075] Figures 7A-7BThis is a cross-sectional elevation view of a system according to an embodiment of this disclosure. As shown and described above, the system includes a first syringe 42 and a second syringe 44. The syringes 42 and 44 are connected to a syringe coupling that includes a displaceable member 50 having a user interface 52, an annular sealing element 48, a guide member 56, and a rotatable Luer locking member 58 at least partially disposed within the guide member 56. The system in Figure 7A The first position is shown. This first position includes a displaceable member and an associated annular sealing element 48 positioned offset from the central axis and channel of the rotatable Luer locking member 58. Specifically, the fluid flow path 90a of the second syringe 44, the convex extension 54 of the displaceable member 50, and the sealing member 48 are offset from and not in communication with the fluid flow path 90b of the first syringe 42 and the rotatable Luer locking member 58. This prevents the flow of fluid and gaseous vapor between the syringes 42 and 44.

[0076] Figure 7B The system is shown in a second position, in which, for example, the displaceable member 50 has been displaced by applying a force to the user interface 52. As shown in the figure... Figure 7A The fluid path 90a and associated components have been displaced to provide a continuous fluid path 90 and to enable fluid flow between the first syringe 42 and the second syringe 44. This allows for mixing of the contents, wherein the plunger rod associated with the first syringe 42 and the second syringe 44 (in...) Figures 7A-7B (Not shown) can be operated to push contents between syringes.

[0077] The systems, apparatus, and methods disclosed herein are not limited to any particular therapeutic agent, solution, suspension, gas, or combination thereof. For example, in some embodiments, it is contemplated to provide one or more non-lyophilized substances in the syringes of this disclosure. In some embodiments, a gas (e.g., cobalt gas) is provided in the syringe to mix with the contents of the second syringe. Such embodiments (including others) realize the mixing syringe system of this disclosure containing an impermeable material to prevent gas permeation and migration. However, in some preferred embodiments, the first syringe 42 is initially provided with a liquid formulation component, such as a polymer-solvent system, while the second syringe is provided with an API, which, in some non-limiting cases, may be present as a lyophilized powder. In such embodiments, the contents are stored separately from each corresponding syringe, which is interconnected with a syringe coupling, and a displaceable member is positioned in a first location ( Figure 7A To administer the therapeutic agent, the displaceable component can be pressed or otherwise activated, thereby producing... Figure 7BThe fluid flow path is 90. Then, the polymer-solvent from the first syringe 42 is forced into the second syringe containing the API, forcing the contents back into the first syringe, and this process is repeated until the desired mixture is achieved, thus enabling repeated mixing. As discussed, Figure 7B The second position is characterized by the presence of a fluid flow path between the two syringes 42, 44, and the disengagement of the displaceable member 50 from the rotatable Luer locking member 58. Specifically, the second position ( Figure 7B The first syringe 42 is positioned such that a rotatable Luer locking member 58 rotates freely within the syringe connector and prevents it from becoming detached or separated. Therefore, it is preferable that the second syringe 44, containing the mixed or prepared pharmaceutical agent, is separable for use as an injection syringe, while the first syringe cannot be used for this purpose.

[0078] Figure 8 This is an elevation view of components of a syringe connector according to an embodiment of the present disclosure. As shown, a displaceable member 50 and a guide member 56 are positioned in a first position. The first position is suitable for transport and storage, wherein fluid and gas vapor flow between the interconnected syringes is completely or at least partially blocked. The displaceable member 50 includes interconnected sealing elements 48. The sealing element 48 includes a central orifice, but this central orifice is offset from the fluid flow path of the guide member 56 and the rotatable Luer locking member 58, thereby blocking fluid flow through the device. The displaceable member 50 and the guide member 56 each include user interface portions 52 and 57. Force can be applied to one or more of the user interfaces 52 and 57 to transfer the device from the first position to a second position, in which the displaceable member 50 moves relative to the guide member and creates a fluid flow path (e.g., as shown in the figure). Figure 7B (As shown).

[0079] The displaceable member 50 includes a first protrusion 62a and a second protrusion 62b operable to move outward when the displaceable member moves downward. The first protrusion 62a and the second protrusion 62b are fixed within the recesses 74a, 74b of the guide member 56 and move inward based on their inherent material properties and elasticity. Placing or partially placing the first protrusion 62a and the second protrusion 62b within the recesses 74a, 74b of the guide member 56 prevents or inhibits the return movement of the displaceable member 50 to the first position.

[0080] Figure 9This is an elevation view of the mating surfaces of the displaceable member 50 and the guide member 56. As shown, the displaceable member 50 includes a ramp-shaped protrusion 60 operable to guide the mounting and interconnection of the displaceable member 50 and the guide member 56. A channel 72 is provided to receive and accommodate the protrusion 60. In a first position, rotation of the rotatable Luer locking member is substantially prevented by a second protrusion 75 in contact with a portion of the Luer locking member. In a second position, the second protrusion 75 is displaced downward (at least relative to...). Figure 9 The rotatable Luer locking member can rotate freely within the orifice 70 of the guide member 56. A second protrusion 75 is disposed on the displaceable member 50 and operable to contact at least one of the teeth of the rotatable Luer locking member 58 (not shown) in a first position and in a slot 73 on the guide member 56 in a second position. In addition to locking and unlocking the rotatable Luer locking member 58 (not shown), the protrusion 75 of the displaceable member and the corresponding configuration of the guide member 56 also serve to limit the displacement of the displaceable member and ensure that the displaceable member stops in the second position aligned with the fluid flow path.

[0081] Figure 10 This is a perspective view of a syringe mixing system disposed in a packaging pallet 100 according to an embodiment of the present disclosure. As shown, the system includes a first syringe 42 and a second syringe 44 engaged by a syringe coupling 46, which includes, for example, syringe couplings shown and described herein. The syringes 42, 44 are connected to the syringe coupling 46 for transport and storage in the packaging component 100. Figure 10 The packaging component 100 includes a clamshell-like device rotatable about a hinge 104, within which the system is stored. The contours and recesses 102 of the packaging component 100 are used to restrict the movement of certain components of the system, such as including displaceable members (e.g., Figure 3 Undesirable movement of the syringe plunger rod (50%) and / or undesirable movement of the syringe plunger rod. While various embodiments of this disclosure envision the first and second syringes being attached to the syringe connector for transport, and the system being provided to the end user in an assembled or interconnected state, alternative embodiments envision one or more syringes initially separate from the connector. In such embodiments, the user (e.g., a healthcare professional) assembles the device by connecting one or more syringes to the syringe connector prior to mixing operations.

[0082] Figure 11A This is a cross-sectional elevation view of a mixing syringe component 110 according to an embodiment of the present disclosure. As shown, component 110 includes components capable of operating at a first position ( Figure 11A ) and the second position ( Figure 11BA valve element that switches between ( ) positions. As shown, component 110 includes a first translatable component 112 and a second translatable component 114. The first translatable component 112 and the second translatable component 114 are operable to switch between a first position ( ) and a second translatable component 114. Figure 11A Relative to each other, in a first position, the conduit 116 of the first component 112 and the conduit 118 of the second component 114 are misaligned. In the first position, conduits 116 and 118 are not connected, and fluid flow between the components is substantially blocked. The first component 112 and the second component 114 are capable of displacement to a second position. Figure 11B In the second position, conduits 116 and 118 are connected and / or aligned to enable fluid flow between components 112 and 114.

[0083] In some embodiments, the proximal ends 120, 122 of the components are operable to receive a syringe. The syringe (in...) Figure 11A-11B Axial pressure on (not shown) can be operated to remove the component from Figure 11A The misaligned position was moved to Figure 11B The alignment position allows fluid to pass between the component and the associated syringe. Although in Figure 11A-11B Not shown, but the proximal ends 120, 122 of the envisioned components include a securing device for the syringe. The envisioned securing device includes a threaded connection member, a Luer locking member, and similar constructions to selectively secure the syringe to the components. In operation, the user can connect to... Figure 11A-11B The mixing syringe component 110 applies compressive force to one or more syringes to propel the device from... Figure 11A Moved to Figure 11B The mixing position. The user can then perform the mixing operation by applying force sequentially to the plunger rods of the interconnected syringes, as shown and described herein. Therefore, Figure 11A-11B The arrangement of the device reduces process steps and lowers the user's need to switch between activating valve elements and mixed operations.

[0084] I also thought of Figure 11A-11B Embodiments include stops or limiting members to prevent components from moving beyond a desired mixing position. The limiting member may also include a resilient stop or connecting member to secure the device in the mixing position and prevent reverse translation.

[0085] Figure 12A This is a cross-sectional elevation view of a mixing syringe component 130 according to an embodiment of the present disclosure. As shown, component 130 includes components capable of operating at a first position ( Figure 12A ) and the second position ( Figure 12BA valve element that switches between ( ) positions. As shown, component 130 includes a first translatable component 132 and a second translatable component 134. The first translatable component 132 and the second translatable component 134 are operable to switch between a first position ( ) and a second translatable component 134. Figure 12A With respect to each other, in a first position, the conduit 136 of the first component 132 and the conduit 138 of the second component 134 are misaligned. In the first position, conduits 136 and 138 are not connected, and fluid flow between the components is substantially blocked. The first component 132 and the second component 134 are able to move to a second position. Figure 12B In the second position, components 132, 134 are provided with inclined or cam-shaped surfaces, and conduits 132, 134 are connected and / or aligned to allow fluid flow between components 132, 134.

[0086] In some embodiments, the proximal ends 140, 142 of the components are operable to receive a syringe. The syringe (in...) Figure 12A-12B Axial pressure on (not shown) can be operated to remove the component from Figure 12A The misaligned position was moved to Figure 12B The alignment position allows fluid to pass between the component and the associated syringe. Although in Figure 12A-12B Not shown, but the proximal ends 140, 142 of the envisioned components include a securing device for the syringe. The envisioned securing device includes a threaded connection member, a Luer locking member, and similar constructions to selectively secure the syringe to the components. In operation, the user can connect to... Figure 12A-12B The mixing syringe component 130 applies compressive force to one or more syringes to propel the device from... Figure 12A Moved to Figure 12B The mixing position. The user can then perform the mixing operation by applying force sequentially to the plunger rods of the interconnected syringes, as shown and described herein. Therefore, Figure 12A-12B The arrangement of the device reduces process steps and lowers the user's need to switch between activating valve elements and mixed operations.

[0087] I also thought of Figure 12A-12B Embodiments include stops or limiting members to prevent components from moving beyond a desired mixing position. The limiting member may also include a resilient stop or connecting member to secure the device in the mixing position and prevent reverse translation.

[0088] Figure 12CA mixing injector component 300 operable to selectively allow and restrict fluid flow through a device and associated construction is shown. As shown, component 300 includes a valve element having a first portion 302 and a second portion 304. Each of the first and second portions includes an orifice or flow port 306a, 306b. Flow through component 300 is blocked when the flow ports 306a, 306b are offset or misaligned to a certain extent. The first portion 302 and the second portion 304 are at least rotatable relative to each other. Specifically, portions 302, 304 are rotatable about an axis 308. It is envisioned that pins or shaft members are provided to secure these portions and enable their rotation. Figure 12C The first part 302 and the second part 304 are shown in the disassembled state and the assembled state, respectively.

[0089] Figure 12D yes Figure 12C A front view of component 300. The first portion 302 and the second portion 304 are rotatably offset to show the motion and degrees of freedom of the device 300. The rotational motion R is operable to align the first portion 302 with the second portion 304 and selectively enable fluid flow.

[0090] Figure 12E The component 300 is shown in a closed position, where fluid flow is blocked or impeded. As shown, the second portion 304 is rotated relative to the first portion 302, causing the fluid flow ports 306a, 306b to be offset, and fluid cannot pass through the device 300. Figure 12E The location shown is considered the initial location where mixing and fluid flow are prevented.

[0091] Figure 12F The component 300 is shown in an aligned position where fluid can flow. As shown, the first portion 302 and the second portion 304 have been rotated into an aligned state, with the flow ports 306a and 306b aligned axially and forming a flow path 312 through the component 300.

[0092] Figure 12C-12F An apparatus with sections having a linear cubic shape is conceived and illustrated. However, it should be recognized that various alternative arrangements are conceivable. For example, other arrangements could also be conceived. Figure 12C-12F The first and second parts shown are disc-shaped structures and / or have various other geometries. Furthermore, although in Figure 12C-12F Not shown, but it is conceivable to provide one or more stops or buffers to guide or limit the relative rotation between the first and second parts. For example, it is conceivable to provide one or more stops to fix or lock the device in the open position (e.g., as shown in the diagram). Figure 12F(As shown). In addition, ramps or resistance members can be considered, which provide initial resistance that must be overcome in order to open the device and prevent or reduce the risk of accidental activation.

[0093] Although Figure 12C-12F Although not shown in the diagram, various extensions or user interface sections can be conceived. For example, Figure 12C-12F The configuration shown can be located inside or in part of a larger device, and extensions or triggering configurations are provided to control the rotation of at least a portion of component 300.

[0094] Figure 13 This is an exploded perspective view of a mixing syringe system 150 according to another embodiment of the present disclosure. As shown, system 150 includes a first syringe 152 and a second syringe 154. It is envisioned that the first and second syringes initially contain solid or liquid contents. For example, the first syringe 152 may contain or include a polymer-solvent system, such as, but not limited to, a biodegradable polymer dissolved in NMP, while the second syringe 154 may contain a lyophilized product, such as, but not limited to, lyophilized leuprolide acetate. It has been recognized that undesirable NMP migration (i.e., accidental migration before mixing) can lead to various complications, including shortened or impaired shelf life of the contents. The various embodiments of the present disclosure aim to reduce or eliminate the risk of undesirable NMP migration while storing NMP and lyophilized drugs very close together before mixing.

[0095] As shown and described herein, the contents of the first syringe 152 and the second syringe 154 can be mixed to prepare a solution or suspension for administration. Figure 13 The embodiment includes a syringe coupling 156. The syringe coupling 156 of the illustrated embodiment is operable to receive and connect to a first syringe 152 and a second syringe 154, selectively preventing and allowing fluid transfer between the two syringes, and selectively preventing the removal of at least one syringe.

[0096] Each syringe 152, 154 includes a cylinder with an internal volume for receiving a plunger rod (in... Figure 13 (Not shown) a proximal end and a distal end having a dispensing outlet, wherein the distal end is operable to connect to a syringe coupling 156. The syringe coupling 156 includes a valve assembly having a sealing element 164 nested within a recessed region 159 of a displaceable member 158. In some embodiments (including...) Figure 13 (As shown in the embodiment), the sealing element includes a fluid-impermeable material with orifices to selectively allow fluid to flow through the device 156. Figure 13 The sealing element 164 includes a straight member, and it is conceivable that the sealing element 164 can have various shapes and sizes.

[0097] The displaceable member 158 includes a user interface 160 and a convex extension 162. The user interface 160 is operable to be contacted by a user and to receive force from the user. The convex extension 162 is used to receive a second syringe 154. The syringe connector 156 also includes a guide member 168 in which the displaceable member is disposed. The guide member 168 includes a user interface 178. Figure 5C The user interface 178 is operable to be contacted by a user and to receive force from the user. A rotatable member 166 is provided. In the illustrated embodiment, the rotatable member 166 includes a rotatable Luer locking member, the proximal end of which has a convex connector operable to connect to the first syringe 152, and the distal end includes a flange with multiple contact surfaces for limiting rotation of the rotatable member 166 prior to activation of the device.

[0098] Figures 14A-14C This is a perspective view showing the displaceable member 158 in more detail. As shown, the displaceable member 158 includes a user interface 160 operable to be controlled by a user. In a preferred embodiment, the displaceable member is capable of displacement in a downward direction (at least relative to...). Figure 14A It is preferably not operable to return to the initial or first position. A convex extension 162 is provided on one side of the member for receiving a syringe. A recess 159 is provided on the opposite side of the displaceable member relative to the convex extension 162. The recess 159 is operable to receive a sealing element, such as... Figure 13 The sealing element 164 has a channel passing through the displaceable member 158, wherein the channel passes through the convex extension 162 and extends into the recess 159. Preferably, the sealing element includes an orifice aligned with the channel of the displaceable member 158.

[0099] like Figure 14B-14CAs shown, a protrusion 170 is provided on the displaceable member 158. The protrusion 170 is displaceable with the member 158 and is movable at least relative to the rotatable member 166 of the assembled device. In a first position, the protrusion 170 contacts the contact surface of the flange of the rotatable member 166 to prevent the member 166 from rotating. This contact and associated locking of the rotatable member 166 allows the first syringe to be screwed onto (and unscrewed from) the rotatable member 166 before the assembled device is activated. Movement of the displaceable member 158 caused by user activation causes the protrusion 170 to displace, thus preventing it from contacting the rotatable locking member 166. As the rotatable Luer locking member rotates, the member 166 rotates freely within the syringe coupling. Even when rotation is applied while attempting to remove the syringe without resistance, the syringe connected to the rotatable Luer locking member 166 is prevented from being disengaged from the syringe coupling by threads. One object of this disclosure is to provide a syringe connector 156 that holds at least one syringe to prevent a user from administering the mixture using a first syringe, thereby giving the user the option to administer the mixture using only a second syringe.

[0100] like Figures 14A-14C As shown, the displaceable member 158 also includes clips or resilient protrusions 172a, 172b. The resilient protrusions 172a, 172b are operable to bend outwards and do not substantially impede downward movement of the displaceable member 158. However, when positioned in the second position, the resilient protrusions 172a, 172b are at least partially secured to the guide member 168 by their inherent restoring force. The resilient protrusions 172a, 172b secure the displaceable member 158 in the second position within the guide member 168 through their engagement in recesses 176a, 176b on the guide member 168, preventing or inhibiting the displaceable member from returning to the first position.

[0101] Figures 15A-15D This is a perspective view of a guide member 168 according to one embodiment, and it is envisioned that the guide member 168 is related to... Figures 14A-14C The displaceable member 158 is used in conjunction with it. As shown, the guide member 168 includes a central orifice 174 to allow fluid flow and receive a rotatable Luer locking member 166 of an embodiment of this disclosure. The guide member 168 is configured to slidably receive at least a portion of the displaceable member 158. As shown, the guide member 168 includes a receiving portion 180 having a first slot member 178a and a second slot member 178b to receive the displaceable member 158. The guide member includes a user interface 178 operable to be contacted by a user and to receive forces from the user. In some embodiments, such as Figures 15A-15D As shown, the envisioned user interface 178 includes a grip or contact surface with ridges to reduce slippage and provide ergonomic benefits.

[0102] The surface of the guide member 168 includes a recessed region 182 and a protrusion 170 of the displaceable member 158 (e.g., as shown in the image). Figure 14B (As shown) It can translate within the recessed region 182. Specifically, when the connector is activated and the displaceable member 158 is displaced downward relative to the guide member 168, the protrusion 170 moves downward in the recessed region 182 to a second position in which the protrusion 170 does not contact the rotatable member 166, regardless of the rotational position of the rotatable member 166.

[0103] The second position also includes a location that forms a fluid flow channel. Specifically, a sealing element 164 disposed within the displaceable member 158 moves from a first position to a second position. The first position is characterized in that the channel of the sealing element 164 is offset from the inlet and outlet of the interconnected syringe and prevents flow between them. The second position is characterized in that the channel of the sealing element 164 is configured to be axially aligned with the syringe outlet and inlet.

[0104] For example, such as Figures 15A-15B As shown, the guide member 168 also includes recesses 176a, 176b operable to receive resilient protrusions of the displaceable member and secure the syringe coupling in a second position. These recesses are operable to prevent, or at least hinder, the user from returning the device to the first position after activating the syringe coupling.

[0105] Figures 16A-16B This is a perspective view of a rotatable member 166 according to an embodiment of the present disclosure. As shown, the rotatable member 166 includes a first end having a convex Luer locking member 200, which provides means of attachment to a first syringe and a fluid flow path through a central orifice 202 of the member 166. The convex Luer locking member 200 is at least partially disposed within a threaded concave member 204 operable to engage with the first syringe by thread. A support surface 208 is provided on the exterior of the member 166. The support surface 208 is operable to be disposed in and contact with a central orifice 174 of a guide member 168. The support surface 208 of the rotatable member 166 includes a surface on which the member 166 is rotatable (when unlocked) and contacts the central orifice 174 of the guide member 168. The rotatable member 166 also includes a flange 206 having a plurality of contact surfaces 207 to selectively prevent rotation of the rotatable member 166. Specifically, in the protrusions of the present disclosure (e.g. Figure 14BWhen the protrusion 170 is positioned in the first position, it is configured to contact at least one contact surface 207 of the flange 206 and prevent rotation of the member 166 (at least relative to the guide member 168). The fixed nature or state of the member 166 in the first position allows the user to screw the first syringe into the threaded concave member 204. When the displaceable member is displaced as shown and described herein, the protrusion 170 moves away from the flange 206 of the member 166, so that rotation is unimpeded and the member 166 is allowed to rotate relative to the guide member 168 and the displaceable member. Since the rotational force applied to the syringe causes the rotatable member 166 to rotate, this rotational freedom prevents or at least inhibits the unscrewing and removal of the first syringe. In the absence of significant reaction forces on the rotatable Luer locking member 166 or the threaded concave member 204, unscrewing does not occur and effectively prevents the removal of the first syringe from the syringe coupling. Figures 16A-16B The flange 206 in the embodiment is shown as a hexagonal flange. However, it should be appreciated that various alternative shapes and arrangements including at least one contact surface are conceivable for selectively preventing rotation of member 166.

[0106] Figure 16B The distal end of the channel 202 of the rotatable member 166 is shown. As shown, the distal end 210 includes a beveled or truncated conical shape. The angled surface of the distal end 210 facilitates assembly of the device. Specifically, the distal end 210 is operable to communicate with the slot or bevel 171 of the displaceable member 158 (e.g., as shown in the figure). Figure 14C (As shown). The angular nature of these corresponding configurations allows the guide member 168, including the rotatable member 166, to slide relative to and assemble with the displaceable member 158. As previously described, the displaceable member is envisioned to include a sealing member 164. In addition to facilitating assembly, the communication between the distal end 210 of the guide member and the inclined surface 171 enables temporary separation of the guide member 168 and the displaceable member, and avoids undesirable contact, damage, or obstruction of the seal 164 during assembly. When the displaceable member 158 is fully inserted into the guide member 168, the distal end 210 is close to the sealing member 164.

[0107] Figures 17A-17B This is a cross-sectional elevation view of a system according to an embodiment of this disclosure. As shown and described above, the system includes a first syringe 152 and a second syringe 154. The syringes 152 and 154 are connected to a syringe coupling, which includes a displaceable member 158 having a user interface 160, a sealing element 164, a guide member 168, and a rotatable member 166 at least partially disposed within the guide member 168. The system in Figure 17AThe first position is shown. This first position includes a displaceable member and an associated sealing element 164 positioned offset from the central axis and channel of the rotatable member 166. Specifically, the fluid flow path 190a of the second syringe 154, the convex extension of the displaceable member 158, and the sealing member 164 are offset from and not in communication with the fluid flow path 190b of the first syringe 152 and the rotatable member 166. This prevents the flow of fluid and gaseous vapor between the syringes.

[0108] Figure 17B The system is shown in a second position, where, for example, the displaceable member 158 has been displaced by applying a force to the user interface 160. As shown in the figure... Figure 7A The fluid path 190a and associated components have been displaced to provide a continuous fluid path 190 and to enable fluid flow between the first syringe 152 and the second syringe 154. This allows for mixing of the contents, wherein the plunger rods associated with the first and second syringes (in...) Figures 17A-17B (Not shown) can be operated to push contents between syringes.

[0109] The systems, apparatus, and methods disclosed herein are not limited to any particular therapeutic agent, solution, suspension, gas, or combination thereof. Various embodiments include constructions and sealing elements for preventing the escape or migration of a substance from at least one syringe to another syringe. For example, in some embodiments, it is contemplated to provide one or more non-lyophilized substances in the syringes of this disclosure. In some embodiments, a gas (e.g., nitrogen or argon) is provided in the syringe to mix with the contents of a second syringe. For example, the gas may need to be provided along with an active pharmaceutical ingredient to protect that ingredient during storage. The sealing elements of this disclosure are operable and adapted to retain the gas in the syringe and prevent undesirable movement of the gas. The sealing elements are also adapted and can be used to prevent the escape or flow of liquids and solids.

[0110] In some embodiments, the mixing syringe system of this disclosure contains an impermeable material to prevent gas permeation and migration. However, in some preferred embodiments, the first syringe 152 is initially provided with a liquid formulation component (i.e., a liquid or flowable substance), such as a polymer-solvent system, while the second syringe is provided with an API, which, in some non-limiting cases, may be present as a lyophilized powder. In such embodiments, the contents are stored separately from each corresponding syringe, which is interconnected with a syringe coupling, and a displaceable member is positioned in a first location ( Figure 17A To administer the therapeutic agent, the displaceable component can be pressed or otherwise activated, thereby producing... Figure 17BThe fluid flow path is 190. Then, the polymer-solvent from the first syringe 152 is forced into the second syringe containing the API, forcing the contents back into the first syringe, and this process is repeated until the desired mixture is achieved, thus enabling repeated mixing. As discussed, Figure 17B The second position is characterized by the presence of a fluid flow path between the two syringes and the disengagement of the displaceable member 158 from the rotatable member 166. Specifically, the second position ( Figure 17B The first syringe 152 is positioned such that the rotatable member 166 rotates freely within the syringe connector and prevents it from becoming detached or separated. Therefore, it is preferable that the second syringe, containing the mixed or prepared pharmaceutical agent, is separable for use as an injection syringe, while the first syringe cannot be used for this purpose.

[0111] As disclosed herein, the syringe mixing system of the present invention may include methods and systems for mixing components of a pharmaceutical composition or formulation comprising an API for treating a patient's disease or ailment. In some embodiments, the syringe mixing system includes a first syringe containing a first gaseous, liquid, or solid component and a second syringe containing a second gaseous, liquid, or solid component. When the syringe connector is actuated from a first closed position to a second open position, the first gaseous, liquid, or solid component of the first syringe may be mixed (or vice versa) with the second gaseous, liquid, or solid component of the second syringe until a desired mixture is formed. In some cases, the first syringe or the second syringe (but not both) may contain a gaseous component, which may be an inert or volatile gas or vapor. In some cases, the first and second syringes may contain an aqueous or organic-based liquid that forms a solution, suspension, or both. In other embodiments of the disclosed invention, the first syringe may contain a liquid formulation component or solvent system, and in some non-limiting examples, the first syringe may contain a biodegradable polymer dissolved or suspended in an aqueous, organic, or mixed aqueous-organic solvent system, which may also contain additional co-solvents. In some cases, the first or second syringe (but not both) may contain a solid, which may be an API used to treat a disease or condition or to relieve its symptoms. In other cases, the solid may be a lyophilized powder, semi-solid particles, or solid particles with different sizes, shapes, and properties (e.g., specific surface area). However, in some other non-limiting cases, the first or second syringe of the syringe device system may include lyophilized powder, semi-solid particles, or solid particles with different sizes, shapes, and properties (e.g., specific surface area), which may be prepared and / or stored in the first or second syringe in the presence of a selected gas. That is, both the lyophilized powder and the gas are contained in the first or second syringe before the component is mixed with a component stored in the opposing syringe, which may be, but is not necessarily limited to, the liquid of interest.

[0112] As disclosed herein, the syringe mixing system of the present invention may include methods and systems for mixing components of a pharmaceutical composition or formulation containing an API for treating a patient's disease or condition. Such a syringe mixing system may be referred to as a "pre-filled syringe mixing system," wherein the syringe of the syringe mixing system is pre-filled with components of the pharmaceutical composition or formulation, and the components are then mixed together using the syringe mixing system as described herein, and the mixed pharmaceutical composition or formulation can then be administered to a patient who requires such pharmaceutical composition or formulation. In some embodiments of the invention, the syringe mixing device (pre-filled syringe mixing system) may contain a pharmaceutical formulation comprising: (a) an API contained in a first syringe, and (b) a biodegradable polymer-solvent system contained in a second syringe, these components being able to mix with each other upon user activation of the syringe coupling to prepare a drug or agent that can treat a disease or condition by administering the mixed formulation to a patient in need. The syringe mixing system may be used to store and subsequently mix any pharmaceutical compositions or formulations that benefit from the advantages of the syringe mixing system of the present invention for administration, and the disease or condition to be treated naturally depends on the drug or therapeutic agent contained in the pharmaceutical composition or formulation.

[0113] In some embodiments, the API is a gonadotropin-releasing hormone (GnRH) agonist or antagonist, or a pharmaceutically acceptable salt thereof. Diseases or conditions treatable with a GnRH agonist or antagonist, or a pharmaceutically acceptable salt thereof, may include, but are not limited to, certain types of cancer, central precocious puberty (CPP), endometriosis, or uterine fibroids. In some cases, cancers treatable with a GnRH agonist or antagonist, or a pharmaceutically acceptable salt thereof, may include, but are not limited to, prostate cancer (including, but not limited to, advanced prostate cancer) or breast cancer.

[0114] Leuprorelin is a synthetic peptide analog that acts as a “super agonist” of pituitary GnRH receptors. GnRH agonists such as leuprorelin or pharmaceutically acceptable salts of it (e.g., leuprorelin acetate) are used to treat prostate cancer (including advanced prostate cancer), HR-positive breast cancer (including but not limited to HR-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer), and CPP in adult men. Administration of GnRH agonists (or GnRH) leads to downregulation of GnRH receptor activity, which in turn downregulates the GnRH-dependent secretion of gonadotropins (including but not limited to luteinizing hormone (LH) and follicle-stimulating hormone (FSH)). Downregulation of LH and FSH leads to subsequent downregulation of secondary sex hormones (including but not limited to testosterone and estradiol). Testosterone is a key metabolite driving the development and progression of prostate cancer in adult men. Therefore, lowering serum testosterone levels is an effective clinical approach to slow or inhibit prostate cancer growth. Similarly, clinical approaches that modulate the activity and / or synthesis of hormones (especially estrogens, such as estradiol) can be used to slow or inhibit the growth of hormone receptor-positive (HR-positive) breast cancer. Controlled-release formulations of leuprorelin have been developed for the treatment of prostate cancer in adult men, breast cancer, and CPP in children aged 2 years and older. For example, controlled-release formulations using compositions based on flowable biodegradable polymers to sustainably and for extended periods release leuprorelin or pharmaceutically acceptable salts thereof have been exemplified in U.S. Patents 6,565,874 and 8,470,359, WO 2020 / 2404170, and WO 2020 / 217170, the entire contents of which are incorporated herein by reference.

[0115] As disclosed herein, the syringe device or mixing system can be used to subcutaneously administer an API to a patient in need. In some embodiments, the API is a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof, and the patient may have prostate cancer, hormone receptor-positive breast cancer, or CPP. In some embodiments, the method of administering a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof comprises mixing a unit dose of the GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof with a liquid formulation component using an inter-syringe mixing system to form a reconstituted pharmaceutical composition; and administering the reconstituted pharmaceutical composition to the patient via subcutaneous injection. In some embodiments, the inter-syringe mixing system includes a first syringe barrel containing a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof, a second syringe barrel containing a liquid formulation component, and a syringe coupling including a displaceable member, wherein the displaceable member includes a seal having a flow port that, when the displaceable member is positioned in a first position, is offset from the outlet of at least one of the first and second syringe barrels, and wherein, when the displaceable member is positioned in a second position, the flow port is aligned with the outlet of the first and second syringe barrels, and wherein the displaceable member is displaceable along a direction substantially perpendicular to the longitudinal axis of at least one of the first and second syringe barrels. The mixing includes applying force to a user interface to move the displaceable seal from the first position to the second position, and alternately applying force to a plunger located in the first syringe barrel and a plunger located in the second syringe barrel to mix the contents of the first and second syringe barrels. In some cases, the GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof is leuprolide or a pharmaceutically acceptable salt thereof, such as leuprolide acetate.

[0116] In one embodiment, the syringe device system comprises a composition, which, when formulated according to the method of using the syringe device system described herein to mix the two separate components of the composition prior to administration, can be used for palliative treatment of prostate cancer, including palliative treatment of intermediate-to-advanced prostate cancer in adult male patients, said palliative treatment being administered subcutaneously approximately once monthly to reduce the patient's serum testosterone level to less than or equal to 0.5 ng / mL. According to this embodiment, the syringe device system comprises a first syringe containing a quantity of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof. In some cases, the syringe device system comprises a first syringe containing a quantity of lyophilized leuprorelin or a pharmaceutically acceptable salt thereof (e.g., lyophilized leuprorelin acetate). In some cases, the amount of leuprorelin or a pharmaceutically acceptable salt thereof in the delivered reconstituted product may be approximately 7.0 mg of leuprorelin free base equivalent. In some cases, the amount of leuprorelin acetate in the delivered reconstituted product may be approximately 7.5 mg. As used herein, the term "free base equivalent" can refer to the conjugate base or deprotonated form of an amine-containing compound or substance. For example, approximately 7.0 mg leuprolide represents a free base equivalent of approximately 7.5 mg leuprolide acetate. According to this embodiment, the syringe device system includes a second syringe comprising a polymer-solvent system containing a quantity of a biodegradable polymer, which in some cases is a poly(D,L-lactide-co-glycolic acid) initiated (i.e., PLGH) polymer dissolved in a biocompatible solvent, which in some cases is NMP. In some cases, the biodegradable PLGH polymer may contain approximately a 50:50 ratio of lactide and glycolide. In some cases, the PLGH polymer may impair copolymers containing at least one carboxyl terminus. In some cases, the PLGH polymer has a weight-average molecular weight of approximately 31 kDa to approximately 45 kDa. In some cases, the amount of PLGH polymer in the delivered reconstituted product may be approximately 82.5 mg. In some cases, the amount of NMP in the delivered reconstituted product is approximately 160 mg. Unless otherwise stated, the term "weight-average molecular weight" refers to the weight-average molecular weight measured by conventional gel permeation chromatography (GPC) instruments, such as the Agilent 1260 Infinity Quaternary LC with an Agilent G1362A refractive index detector, using polystyrene standards and tetrahydrofuran (THF) as a solvent.

[0117] According to the method for activating the syringe device system, as disclosed herein, after first equilibrating the pre-assembled syringe device system to room temperature and then removing it from its packaging, the user applies force to the user interface portions 52 and 57 of the displaceable member 50 and the guide member 56, respectively, to actuate the syringe connector from a first closed position to a second open position. The user then applies force to a second plunger slidably disposed within a second syringe to transfer the polymer-solvent system contained in the cavity of the second syringe barrel through the opened, activated syringe connector to the cavity of a first syringe containing lyophilized leuprolide acetate. When the polymer-solvent system comes into contact with the lyophilized leuprolide acetate, most of the leuprolide acetate remains in suspension, thus requiring mixing with the polymer-solvent system to ensure a homogeneous suspension is formed before administration. The user then applies force to a first plunger slidably disposed within the first syringe to transfer the partially mixed, fully mixed component back to the second syringe through the opened syringe connector. The user continues to mix the contents back and forth between the first and second syringes for approximately 15 seconds to 2 minutes. In some cases, mixing is envisioned to last approximately 25 seconds, approximately 45 seconds, or approximately 1 minute, which corresponds to approximately 30-90 complete back-and-forth cycles (approximately 60 complete back-and-forth cycles in some preferred embodiments) to ensure that the lyophilized leuprolide acetate is completely suspended in the polymer-solvent system. The fully formulated composition is then transferred to a second syringe in a final injection volume of approximately 0.25 mL, and a dose of approximately 250 mg is administered. The user then unscrews the convex extension 54 attached to the displaceable member 50 of the syringe connector to disconnect the second syringe containing the therapeutic agent from the syringe device. The user then attaches a needle (e.g., an 18G to 20G needle) to the distal dispensing outlet of the second syringe. The user then administers the full dose of the formulation subcutaneously to an adult male prostate cancer patient requiring treatment.

[0118] A method of administering a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to a prostate cancer patient using the syringe device system disclosed herein comprises administering, once monthly, subcutaneously to the patient at least one injection of a pharmaceutical composition containing a unit dose of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to suppress the patient's serum testosterone level to less than or equal to 0.5 ng / mL. Prior to administration, the pharmaceutical composition is reconstituted using the syringe device system comprising a first syringe barrel containing a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof and a second syringe barrel containing a liquid formulation component, the first and second syringe barrels being interconnected via a syringe coupling comprising a displaceable seal, wherein the displaceable seal is operable to be axially displaced from a first position to a second position under the action of a force applied to a plunger of the first syringe barrel, and wherein the first position includes a position obstructing the delivery of substance through the syringe coupling, and the second position includes a position where at least a portion of the displaceable seal is not fixed to the inner surface of the syringe coupling and allows delivery of substance through the syringe coupling. The pharmaceutical composition is reconstructed by applying force to the user interface to move the removable seal from a first position to a second position and by alternately applying force to the plungers located in the first syringe barrel and the second syringe barrel to mix the contents of the first and second syringe barrels. In some cases, the GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof is leuprolide or a pharmaceutically acceptable salt thereof, such as leuprolide acetate. In some cases, the pharmaceutical composition comprises about 7.5 mg of leuprolide acetate and, as a component of the liquid formulation, N-methyl-2-pyrrolidone and a 50:50 poly(lactic-co-glycolic acid) (PLGA) copolymer having a weight-average molecular weight of about 31 kDa to about 45 kDa and at least one terminal carboxylic acid end group.

[0119] In another embodiment, the syringe device system comprises a composition, which, when formulated according to the method of using the syringe device system described herein to mix the two separate components of the composition prior to administration, can be used for palliative treatment of prostate cancer, including palliative treatment of intermediate-to-advanced prostate cancer in adult male patients, said palliative treatment being a subcutaneous injection (once every three months) to reduce the patient's serum testosterone level to less than or equal to 0.5 ng / mL. According to this embodiment, the syringe device system comprises a first syringe containing a quantity of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof. In some cases, the syringe device system comprises a first syringe containing a quantity of lyophilized leuprorelin or a pharmaceutically acceptable salt thereof (e.g., lyophilized leuprorelin acetate). In some cases, the amount of leuprorelin or a pharmaceutically acceptable salt thereof in the delivered reconstituted product may be approximately 21.0 mg of leuprorelin free base equivalent. In some cases, the amount of leuprorelin acetate in the delivered reconstituted product may be approximately 22.5 mg. According to this embodiment, the syringe device system includes a second syringe containing a quantity of a polymer-solvent system containing a quantity of a biodegradable polymer, which in some cases is a poly(D,L-lactide-co-glycolic acid) (i.e., PLG) polymer dissolved in a biocompatible solvent, which in some cases is NMP. In some cases, the biodegradable PLG polymer may contain lactide and glycolide in an approximately 75:25 ratio. In some cases, the PLG polymer may be initiated with hexanediol. In some cases, the PLG polymer may damage copolymers containing two primary hydroxyl terminal groups. In some cases, the weight-average molecular weight of the PLG polymer ranges from approximately 17 kDa to approximately 21 kDa. In some cases, the amount of PLG polymer in the delivered reconstituted product may be approximately 158.6 mg. In some cases, the amount of NMP in the delivered reconstituted product is approximately 193.9 mg.

[0120] According to the method for activating the syringe device system, as disclosed herein, after first equilibrating the pre-assembled syringe device system to room temperature and then removing it from its packaging, the user applies force to the user interface portions 52 and 57 of the displaceable member 50 and the guide member 56, respectively, to actuate the syringe connector from a first closed position to a second open position. The user then applies force to a second plunger slidably disposed within a second syringe to transfer the polymer-solvent system contained in the cavity of the second syringe barrel to the cavity of a first syringe containing lyophilized leuprolide acetate via the opened, activated syringe connector. When the polymer-solvent system comes into contact with the lyophilized leuprolide acetate, most of the leuprolide acetate remains in suspension, thus requiring mixing with the polymer-solvent system to ensure a homogeneous suspension is formed before administration. The user then applies force to a first plunger slidably disposed within the first syringe to transfer a portion of the partially mixed component back to the second syringe via the opened syringe connector. The user continues to mix the contents from the first and second syringes back and forth, sometimes for about 1 minute, which equates to about 60 complete cycles, to ensure that the lyophilized leuprolide acetate is completely suspended in the polymer-solvent system. The fully formulated composition is then transferred to the second syringe in a final injection volume of about 0.375 mL, and a dose of about 375 mg is administered. The user then unscrews the convex extension 54 attached to the displaceable member 50 of the syringe connector to disconnect the second syringe containing the therapeutic agent from the syringe device. The user then attaches a needle (e.g., an 18G to 20G needle) to the distal dispensing outlet of the second syringe. The user then administers one dose of the formulation subcutaneously to an adult male prostate cancer patient requiring treatment.

[0121] A method of administering a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to a prostate cancer patient using the syringe device system disclosed herein comprises subcutaneously administering, once every three months, at least one injection of a pharmaceutical composition containing a unit dose of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to the patient to suppress the patient's serum testosterone level to less than or equal to 0.5 ng / mL. Prior to administration, the pharmaceutical composition is reconstituted using the syringe device system comprising a first syringe barrel containing a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof and a second syringe barrel containing a liquid formulation component, the first and second syringe barrels being interconnected by a syringe coupling comprising a displaceable seal, wherein the displaceable seal is operable to be axially displaced from a first position to a second position under the action of a force applied to a plunger of the first syringe barrel, and wherein the first position includes a position obstructing the delivery of substance through the syringe coupling, and the second position includes a position where at least a portion of the displaceable seal is not fixed to the inner surface of the syringe coupling and allows delivery of substance through the syringe coupling. The pharmaceutical composition is reconstructed by applying force to the user interface to move a removable seal from a first position to a second position and by alternately applying force to the plungers located in the first syringe barrel and the second syringe barrel to mix the contents of the first and second syringe barrels. In some cases, the GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof is leuprorelin or a pharmaceutically acceptable salt thereof, such as leuprorelin acetate. In some cases, the pharmaceutical composition comprises about 22.5 mg of leuprorelin acetate and, as a liquid formulation component, N-methyl-2-pyrrolidone and a 75:25 poly(lactide-co-glycolic acid) (PLG) copolymer having a weight-average molecular weight of about 17 kDa to about 21 kDa and hydroxyl-terminated end groups.

[0122] In another embodiment, the syringe device system comprises a composition that, when formulated according to the method of using the syringe device system described herein to mix the two separate components of the composition prior to administration, can be used for palliative treatment of prostate cancer, including palliative treatment of intermediate-to-advanced prostate cancer in adult male patients, said palliative treatment being administered subcutaneously approximately every four months to reduce the patient's serum testosterone level to less than or equal to 0.5 ng / mL. According to this embodiment, the syringe device system comprises a first syringe containing a quantity of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof. In some cases, the syringe device system comprises a first syringe containing a quantity of lyophilized leuprorelin or a pharmaceutically acceptable salt thereof (e.g., lyophilized leuprorelin acetate). In some cases, the amount of leuprorelin or a pharmaceutically acceptable salt thereof in the delivered reconstituted product may be approximately 28.0 mg of leuprorelin free base equivalent. In some cases, the amount of leuprorelin acetate in the delivered reconstituted product may be approximately 30.0 mg. According to this embodiment, the syringe device system includes a second syringe containing a quantity of a polymer-solvent system containing a quantity of a biodegradable polymer, which in some cases is a poly(D,L-lactide-co-glycolic acid) (i.e., PLG) polymer formulation dissolved in a biocompatible solvent, which in some cases is NMP. In some cases, the biodegradable PLG polymer may contain lactide and glycolide in an approximately 75:25 ratio. In some cases, the PLG polymer may be initiated with hexanediol. In some cases, the PLG polymer may damage copolymers containing two primary hydroxyl terminal groups. In some cases, the weight-average molecular weight of the PLG polymer ranges from approximately 17 kDa to approximately 21 kDa. In some cases, the amount of PLG polymer in the delivered reconstituted product may be approximately 211.5 mg. In some cases, the amount of NMP in the delivered reconstituted product is approximately 258.5 mg.

[0123] According to the method for activating the syringe device system, as disclosed herein, after first equilibrating the pre-assembled syringe device system to room temperature and then removing it from its packaging, the user applies force to the user interface portions 52 and 57 of the displaceable member 50 and the guide member 56, respectively, to actuate the syringe connector from a first closed position to a second open position. The user then applies force to a second plunger slidably disposed within a second syringe to transfer the polymer-solvent system contained in the cavity of the second syringe barrel to the cavity of a first syringe containing lyophilized leuprolide acetate via the opened, activated syringe connector. When the polymer-solvent system comes into contact with the lyophilized leuprolide acetate, most of the leuprolide acetate remains in suspension, thus requiring mixing with the polymer-solvent system to ensure a homogeneous suspension is formed before administration. The user then applies force to a first plunger slidably disposed within the first syringe to transfer a portion of the partially mixed component back to the second syringe via the opened syringe connector. The user continues to mix the contents from the first and second syringes back and forth, sometimes for about 1 minute, which equates to about 60 complete cycles, to ensure that the lyophilized leuprolide acetate is completely suspended in the polymer-solvent system. The fully formulated composition is then transferred to the second syringe in a final injection volume of about 0.5 mL, and a dose of about 500 mg is administered. The user then unscrews the convex extension 54 on the removable member 50 attached to the syringe connector to disconnect the second syringe containing the therapeutic agent from the syringe device. The user then attaches a needle (e.g., an 18G to 20G needle) to the distal dispensing outlet of the second syringe. The user then administers the full dose of the formulation subcutaneously to an adult male prostate cancer patient requiring treatment.

[0124] A method of administering a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to a prostate cancer patient using the syringe device system disclosed herein comprises administering, once every four months, subcutaneously to the patient at least one injection of a pharmaceutical composition containing a unit dose of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to suppress the patient's serum testosterone level to less than or equal to 0.5 ng / mL. Prior to administration, the pharmaceutical composition is reconstituted using the syringe device system comprising a first syringe barrel containing a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof and a second syringe barrel containing a liquid formulation component, the first and second syringe barrels being interconnected by a syringe coupling comprising a displaceable seal, wherein the displaceable seal is operable to be axially displaced from a first position to a second position under the action of a force applied to a plunger of the first syringe barrel, and wherein the first position includes a position obstructing the delivery of substance through the syringe coupling, and the second position includes a position where at least a portion of the displaceable seal is not fixed to the inner surface of the syringe coupling and allows delivery of substance through the syringe coupling. The pharmaceutical composition is reconstructed by applying force to the user interface to move a removable seal from a first position to a second position and by alternately applying force to the plungers located in the first syringe barrel and the second syringe barrel to mix the contents of the first and second syringe barrels. In some cases, the GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof is leuprorelin or a pharmaceutically acceptable salt thereof, such as leuprorelin acetate. In some cases, the pharmaceutical composition comprises about 30 mg of leuprorelin acetate and, as a liquid formulation component, N-methyl-2-pyrrolidone and a 75:25 poly(lactide-co-glycolic acid) (PLG) copolymer having a weight-average molecular weight of about 17 kDa to about 21 kDa and hydroxyl-terminated end groups.

[0125] In another embodiment of the invention, the syringe device system comprises a composition that, when formulated according to the method of using the syringe device system described herein to mix the two separate components of the composition prior to administration, can be used for palliative treatment of prostate cancer, including palliative treatment of intermediate-to-advanced prostate cancer in adult male patients, said palliative treatment being a subcutaneous injection (once every six months) administered approximately every six months to reduce the patient's serum testosterone level to less than or equal to 0.5 ng / mL. According to this embodiment, the syringe device system comprises a first syringe containing a quantity of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof. In some cases, the syringe device system comprises a first syringe containing a quantity of lyophilized leuprorelin or a pharmaceutically acceptable salt thereof (e.g., lyophilized leuprorelin acetate). In some cases, the amount of leuprorelin or a pharmaceutically acceptable salt thereof in the delivered reconstituted product may be approximately 42.0 mg of leuprorelin free base equivalent. In some cases, the amount of leuprorelin acetate in the delivered reconstituted product may be approximately 45.0 mg. According to this embodiment, the syringe device system includes a second syringe containing a quantity of a polymer-solvent system containing a quantity of a biodegradable polymer, which in some cases is a poly(D,L-lactide-co-glycolic acid) (i.e., PLG) polymer formulation dissolved in a biocompatible solvent, which in some cases is NMP. In some cases, the biodegradable PLG polymer may contain lactide and glycolide in an approximately 85:15 ratio. In some cases, the PLG polymer may be initiated with hexanediol. In some cases, the PLG polymer may damage copolymers containing two primary hydroxyl terminal groups. In some cases, the weight-average molecular weight of the PLG polymer ranges from approximately 20 kDa to approximately 26 kDa. In some cases, the amount of PLG polymer in the delivered reconstituted product may be approximately 165 mg. In some cases, the amount of NMP in the delivered reconstituted product is approximately 165 mg.

[0126] According to the method for activating the syringe device system, as disclosed herein, after first equilibrating the pre-assembled syringe device system to room temperature and then removing it from its packaging, the user applies force to the user interface portions 52 and 57 of the displaceable member 50 and the guide member 56, respectively, to actuate the syringe connector from a first closed position to a second open position. The user then applies force to a second plunger slidably disposed within a second syringe to transfer the polymer-solvent system contained in the cavity of the second syringe barrel to the cavity of a first syringe containing lyophilized leuprolide acetate via the opened, activated syringe connector. When the polymer-solvent system comes into contact with the lyophilized leuprolide acetate, most of the leuprolide acetate remains in suspension, thus requiring mixing with the polymer-solvent system to ensure a homogeneous suspension is formed before administration. The user then applies force to a first plunger slidably disposed within the first syringe to transfer a portion of the partially mixed component back to the second syringe via the opened syringe connector. The user continues to mix the contents from the first and second syringes back and forth, sometimes for about 1 minute, which equates to about 60 complete cycles, to ensure that the lyophilized leuprolide acetate is completely suspended in the polymer-solvent system. The fully formulated composition is then transferred to the second syringe in a final injection volume of about 0.375 mL, and a dose of about 375 mg is administered. The user then unscrews the convex extension 54 attached to the displaceable member 50 of the syringe connector to disconnect the second syringe containing the therapeutic agent from the syringe device. The user then attaches a needle (e.g., an 18G to 20G needle) to the distal dispensing outlet of the second syringe. The user then administers the full dose of the formulation subcutaneously to an adult male prostate cancer patient requiring treatment.

[0127] A method of administering a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to a prostate cancer patient using the syringe device system disclosed herein comprises administering, once every six months, to the patient subcutaneously at least one injection of a pharmaceutical composition containing a unit dose of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to suppress the patient's serum testosterone level to less than or equal to 0.5 ng / mL. Prior to administration, the pharmaceutical composition is reconstituted using the syringe device system comprising a first syringe barrel containing a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof and a second syringe barrel containing a liquid formulation component, the first and second syringe barrels being interconnected by a syringe coupling comprising a displaceable seal, wherein the displaceable seal is operable to be axially displaced from a first position to a second position under the action of a force applied to a plunger of the first syringe barrel, and wherein the first position includes a position obstructing the delivery of substance through the syringe coupling, and the second position includes a position where at least a portion of the displaceable seal is not fixed to the inner surface of the syringe coupling and allows delivery of substance through the syringe coupling. The pharmaceutical composition is reconstructed by applying force to the user interface to move a removable seal from a first position to a second position and by alternately applying force to the plungers located in the first syringe barrel and the second syringe barrel to mix the contents of the first and second syringe barrels. In some cases, the GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof is leuprorelin or a pharmaceutically acceptable salt thereof, such as leuprorelin acetate. In some cases, the pharmaceutical composition comprises approximately 45 mg of leuprorelin acetate and, as a liquid formulation component, N-methyl-2-pyrrolidone and an 85:15 poly(lactide-co-glycolic acid) (PLG) copolymer having a weight-average molecular weight of approximately 20 kDa to approximately 26 kDa and hydroxyl-terminated end groups.

[0128] In another embodiment, the syringe device system comprises a composition that, when formulated according to the method of using the syringe device system described herein to mix the two separate components of the composition prior to administration, can be used to suppress ovarian function in patients with HR-positive breast cancer. The composition can also be used to suppress the patient's estradiol (E2) levels to below 20 picograms / mL, the patient's follicle-stimulating hormone (FSH) levels to below 40 IU / L, and the patient's mean serum luteinizing hormone (LH) levels. In some cases, the composition can be administered concurrently with one or more other treatments for HR-positive breast cancer, including but not limited to endocrine therapy, chemotherapy, and / or radiotherapy. In some cases, the composition is administered via subcutaneous injection approximately every three months. According to this embodiment, the syringe device system comprises a first syringe containing a quantity of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof. In some cases, the syringe device system comprises a first syringe containing a quantity of lyophilized leuprorelin or a pharmaceutically acceptable salt thereof (e.g., lyophilized leuprorelin acetate). In some cases, the amount of leuprorelin or a pharmaceutically acceptable salt thereof in the delivered reconstituted product may be from about 26 mg to about 30 mg, preferably 28 mg of leuprorelin free base equivalent. In some cases, the amount of leuprorelin acetate in the delivered reconstituted product may be from about 28 mg to about 32 mg, preferably 30 mg. According to this embodiment, the syringe device system includes a second syringe containing a polymer-solvent system containing a amount of a biodegradable polymer, which in some cases is a poly(D,L-lactide-co-glycolic acid) (i.e., PLG) polymer formulation dissolved in a biocompatible solvent, which in some cases is NMP. In some cases, the biodegradable PLG polymer may contain lactide and glycolide in a ratio of about 70:30 to about 80:20, preferably about 75:25. In some cases, the PLG polymer may be initiated with hexanediol. In some cases, the PLG polymer may damage copolymers containing two primary hydroxyl end groups. In some cases, the PLG polymer can be initiated with dodecanol. In some cases, the PLG polymer may damage copolymers containing hydroxyl and ester terminal groups. In some cases, the weight-average molecular weight of the PLG polymer ranges from about 15 kDa to about 45 kDa, preferably from about 17 kDa to about 21 kDa. In some cases, the amount of PLG polymer in the delivered reconstituted product can be about 158.6 mg. In some cases, the amount of NMP in the delivered reconstituted product is about 193.9 mg.

[0129] According to the method for activating the syringe device system, as disclosed herein, after first equilibrating the pre-assembled syringe device system to room temperature and then removing it from its packaging, the user applies force to the user interface portions 52 and 57 of the displaceable member 50 and the guide member 56, respectively, to actuate the syringe connector from a first closed position to a second open position. The user then applies force to a second plunger slidably disposed within a second syringe to transfer the polymer-solvent system contained in the cavity of the second syringe barrel to the cavity of a first syringe containing lyophilized leuprolide acetate via the opened, activated syringe connector. When the polymer-solvent system comes into contact with the lyophilized leuprolide acetate, most of the leuprolide acetate remains in suspension, thus requiring mixing with the polymer-solvent system to ensure a homogeneous suspension is formed before administration. The user then applies force to a first plunger slidably disposed within the first syringe to transfer a portion of the partially mixed component back to the second syringe via the opened syringe connector. The user continues to mix the contents from the first and second syringes back and forth, sometimes for about 1 minute, which equates to about 60 complete cycles, to ensure that the lyophilized leuprolide acetate is completely suspended in the polymer-solvent system. The fully formulated composition is then transferred to the second syringe in a final injection volume of about 0.375 mL, and a dose of about 375 mg to about 400 mg is administered. The user then unscrews the convex extension 54 attached to the displaceable member 50 of the syringe connector to disconnect the second syringe containing the therapeutic agent from the syringe device. The user then attaches a needle (e.g., an 18G to 20G needle) to the distal dispensing outlet of the second syringe. The user then administers the full dose of the formulation subcutaneously to an adult breast cancer patient requiring treatment.

[0130] A method of administering a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to a patient with hormone receptor-positive breast cancer using the syringe device system disclosed herein comprises administering, once every three months, a subcutaneous injection of at least one syringe containing a unit dose of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to the patient to suppress ovarian function. In some cases, the patient is given, once every three months, an injection of at least one syringe containing a unit dose of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to suppress the patient's estradiol (E2) level to below 20 picograms / mL, the patient's follicle-stimulating hormone (FSH) level to below 40 IU / L, and the patient's mean serum luteinizing hormone (LH) level. Prior to administration, a pharmaceutical composition is reconstituted using a syringe device system comprising a first syringe barrel containing a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof, and a second syringe barrel containing a liquid formulation component. The first and second syringe barrels are interconnected via a syringe coupling comprising a repositionable seal operable to be axially displaced from a first position to a second position under the action of a force applied to a plunger of the first syringe barrel. The first position includes a location that obstructs the delivery of substance through the syringe coupling, and the second position includes a location where at least a portion of the repositionable seal is not fixed to the inner surface of the syringe coupling and allows delivery of substance through the syringe coupling. The pharmaceutical composition is reconstituted by applying force to a user interface to move the repositionable seal from the first position to the second position and by alternately applying force to a plunger located in the first syringe barrel and a plunger located in the second syringe barrel to mix the contents of the first and second syringe barrels. In some cases, the GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof is leuprorelin or a pharmaceutically acceptable salt thereof, such as leuprorelin acetate. In some cases, the pharmaceutical composition comprises about 30 mg of leuprolide acetate and N-methyl-2-pyrrolidone and a 75:25 poly(lactide-co-glycolic acid) copolymer as a liquid formulation component, the copolymer having a weight-average molecular weight of about 17 kDa to about 21 kDa, and a hydroxyl-terminated distal group and another hydroxyl-terminated or ester-terminated distal group.

[0131] In another embodiment of the invention, the syringe device system comprises a composition, formulated according to the method of using the syringe device system described herein to mix the two separate components of the composition before administration, and administered by subcutaneous injection once every six months. This composition can be used to treat CPP in pediatric patients aged 2 years and older to reduce the stimulating serum LH peak concentration in pediatric patients to a prepubertal level below 4 IU / L. According to this embodiment, the syringe device system comprises a first syringe containing a quantity of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof. In some cases, the syringe device system comprises a first syringe containing a quantity of lyophilized leuprorelin or a pharmaceutically acceptable salt thereof (e.g., lyophilized leuprorelin acetate). In some cases, the amount of leuprorelin or a pharmaceutically acceptable salt thereof in the delivered reconstituted product may be approximately 42.0 mg of leuprorelin free base equivalent. In some cases, the amount of leuprorelin acetate in the delivered reconstituted product may be approximately 45.0 mg. According to this embodiment, the syringe device system includes a second syringe containing a quantity of a polymer-solvent system containing a quantity of a biodegradable polymer, which in some cases is a poly(D,L-lactide-co-glycolic acid) (i.e., PLG) polymer formulation dissolved in a biocompatible solvent, which in some cases is NMP. In some cases, the biodegradable PLG polymer may contain lactide and glycolide in an approximately 85:15 ratio. In some cases, the PLG polymer may be initiated with hexanediol. In some cases, the PLG polymer may damage copolymers containing two primary hydroxyl end groups. In some cases, the PLG polymer may be initiated with dodecanol. In some cases, the PLG polymer may damage copolymers containing hydroxyl and ester end groups. In some cases, the weight-average molecular weight of the PLG polymer is in the range of approximately 20 kDa to approximately 26 kDa. In some cases, the amount of PLG polymer in the delivered reconstituted product may be approximately 165 mg. In some cases, the amount of NMP in the delivered reconstituted product is approximately 165 mg.

[0132] According to the method for activating the syringe device system, as disclosed herein, after first equilibrating the pre-assembled syringe device system to room temperature and then removing it from its packaging, the user applies force to the user interface portions 52 and 57 of the displaceable member 50 and the guide member 56, respectively, to actuate the syringe connector from a first closed position to a second open position. The user then applies force to a second plunger slidably disposed within a second syringe to transfer the polymer-solvent system contained in the cavity of the second syringe barrel to the cavity of a first syringe containing lyophilized leuprolide acetate via the opened, activated syringe connector. When the polymer-solvent system comes into contact with the lyophilized leuprolide acetate, most of the leuprolide acetate remains in suspension, thus requiring mixing with the polymer-solvent system to ensure a homogeneous suspension is formed before administration. The user then applies force to a first plunger slidably disposed within the first syringe to transfer a portion of the partially mixed component back to the second syringe via the opened syringe connector. The user continues to mix the contents from the first and second syringes back and forth, sometimes for about 1 minute, which corresponds to about 60 complete cycles, to ensure that the lyophilized leuprolide acetate is completely suspended in the polymer-solvent system. The fully formulated composition is then transferred to the second syringe in a final injection volume of about 0.375 mL, and a dose of about 375 mg is administered. The user then unscrews the convex extension 54 attached to the removable member 50 of the syringe connector to disconnect the second syringe containing the therapeutic agent from the syringe device. The user then attaches a needle (e.g., an 18G to 20G needle) to the distal dispensing outlet of the second syringe. The user then administers the full dose of the formulation subcutaneously to a pediatric patient aged 2 years or older requiring treatment.

[0133] The method disclosed herein for administering a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to a pediatric patient aged 2 years or older with central precocious puberty (CPP) using a syringe device system comprises administering, once every 6 months, to the pediatric patient subcutaneously an injection of at least one syringe containing a unit dose of a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof to reduce the pediatric patient’s stimulating serum LH peak concentration to a prepubertal concentration of less than 4 IU / L. Prior to administration, a pharmaceutical composition is reconstituted using a syringe device system comprising a first syringe barrel containing a GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof, and a second syringe barrel containing a liquid formulation component. The first and second syringe barrels are interconnected via a syringe coupling comprising a repositionable seal operable to be axially displaced from a first position to a second position under the action of a force applied to a plunger of the first syringe barrel. The first position includes a location that obstructs the delivery of substance through the syringe coupling, and the second position includes a location where at least a portion of the repositionable seal is not fixed to the inner surface of the syringe coupling and allows delivery of substance through the syringe coupling. The pharmaceutical composition is reconstituted by applying force to a user interface to move the repositionable seal from the first position to the second position and by alternately applying force to a plunger located in the first syringe barrel and a plunger located in the second syringe barrel to mix the contents of the first and second syringe barrels. In some cases, the GnRH agonist or antagonist or a pharmaceutically acceptable salt thereof is leuprolide or a pharmaceutically acceptable salt thereof, such as leuprolide acetate. In some cases, the pharmaceutical composition comprises approximately 45 mg of leuprolide acetate and N-methyl-2-pyrrolidone and an 85:15 poly(lactide-co-glycolic acid) copolymer as a liquid formulation component, the copolymer having a weight-average molecular weight of approximately 20 kDa to approximately 26 kDa, and a hydroxyl-terminated distal group and another hydroxyl-terminated or ester-terminated distal group.

[0134] This document provides a pre-connected syringe compartment device and various features and embodiments of a system and method using the pre-connected syringe compartment device. However, it should be understood that these features are not necessarily specific to certain embodiments and may be provided in any one or more embodiments. The disclosure and embodiments described herein are not mutually exclusive but may be combined, substituted, and omitted. Therefore, the scope of the invention described herein is not limited to any particular embodiment, drawing, or specific arrangement of features.

[0135] While numerous embodiments of the present disclosure have been described in detail above, it will be apparent to those skilled in the art that various modifications and variations can be made to these embodiments. However, it should be clearly understood that such modifications and variations are within the scope and spirit of this disclosure. Furthermore, the invention described herein may have other embodiments and may be implemented or practiced in various ways. Additionally, it should be understood that the wording and terminology used herein are for illustrative purposes only and should not be construed as constituting any limitation. The use of words such as “comprising,” “including,” or “adding,” and variations thereof, means to cover the items listed thereafter and their equivalents, as well as additional items.

Claims

1. A syringe mixing system, comprising: A first syringe comprising a hollow body having a proximal and a distal dispensing end; A second syringe including a hollow body, the second syringe having a distal dispensing end; Both the first syringe and the second syringe include a syringe barrel and a plunger for applying pressure to the contents of the syringe; A valve assembly operable to receive a first syringe and a second syringe, wherein the valve assembly includes at least one resilient member biased toward a locked position; The valve assembly includes a displaceable member, the displaceable member including a user interface and a guide member, the displaceable member being slidable relative to the guide member, the user interface being operable to receive force from a user and transmit the force to a movable seal, and the movable seal being movable in a direction substantially perpendicular to the longitudinal axis of at least one of the first and second syringes. A selectively rotating member operable to receive at least one of a first syringe and a second syringe; The valve assembly includes a first position and a second position. In the first position, fluid flow between the first and second syringes via a movable seal is completely blocked. In the second position, fluid is allowed to flow through the movable seal and between the first and second syringes. When the displaceable member is in the first position, the displaceable member includes at least one protrusion communicating with the selective rotation member, and when the displaceable member is in the second position, the at least one protrusion is spaced apart from the selective rotation member, and when the displaceable member is in the second position, the selective rotation member is freely rotatable.

2. The syringe mixing system as claimed in claim 1, wherein, At least one of the first syringe and the second syringe is movable together with the valve assembly.

3. The syringe mixing system of claim 1, wherein one of the first syringe and the second syringe contains a drug, and wherein the other syringe contains a liquid formulation component.

4. The syringe mixing system of claim 1, wherein at least one of the first syringe and the second syringe comprises leuprolide acetate.

5. The syringe mixing system of claim 1, wherein the selective rotating member comprises a threaded member operable to receive at least one of a first syringe and a second syringe.

6. A syringe mixing system, comprising: A first syringe comprising a hollow body defining an inner lumen, the hollow body having a proximal end and a distal dispensing end with an outlet; A second syringe includes a hollow body defining an inner cavity, the hollow body of the second syringe having a proximal end and a distal dispensing end with an outlet; Both the first syringe and the second syringe include a plunger slidably disposed within the syringe for applying pressure to the contents of the syringe; A syringe connector operable to receive a first syringe and a second syringe; The syringe connector includes a displaceable member that engages with a guide member. The displaceable member includes a seal with a flow port. When the displaceable member is positioned in a first position, the flow port is offset from the outlet of at least one of the first and second syringes. When the displaceable member is positioned in a second position, the flow port is aligned with the outlet of both the first and second syringes. The displaceable member includes at least one elastic protrusion, and the guiding member includes at least one recess for receiving the at least one elastic protrusion; and The at least one elastic protrusion is operable to move during movement of the displaceable member, and wherein when the at least one elastic protrusion is disposed in at least one recess of the guide member, the at least one elastic protrusion prevents or inhibits the displaceable member from returning to the first position. The syringe connector includes a rotatable Luer locking member that is able to rotate freely within the syringe connector when the displaceable member is in the second position.

7. The syringe mixing system of claim 6, wherein the syringe coupling includes a user interface operable to receive force from a user and transmit that force to a seal.

8. The syringe mixing system of claim 6, wherein the displaceable member is displaceable relative to the guide member in a direction substantially perpendicular to the longitudinal axis of at least one of the first and second syringes.

9. The syringe mixing system of claim 6, wherein at least one of the first syringe and the second syringe comprises leuprolide acetate.

10. The syringe mixing system of claim 6, wherein, The at least one elastic protrusion includes first and second elastic protrusions biased toward a locked position, and the guide member includes first and second recesses for receiving the elastic protrusions in a second position.

11. The syringe mixing system of claim 1, wherein the syringe mixing system contains a pharmaceutical composition, and the pharmaceutical composition comprises 7.5 mg of leuprolide acetate as an active pharmaceutical ingredient, and N-methyl-2-pyrrolidone and a 50:50 poly(lactic acid-co-glycolic acid) (PLGA) copolymer as a liquid formulation component, said copolymer having a weight-average molecular weight of 31 kDa to 45 kDa and at least one terminal carboxylic acid end group.

12. The syringe mixing system of claim 1, wherein the syringe mixing system contains a pharmaceutical composition, and the pharmaceutical composition comprises 22.5 mg of leuprolide acetate as an active pharmaceutical ingredient and N-methyl-2-pyrrolidone and a 75:25 poly(lactide-co-glycolic acid) copolymer as a liquid formulation component, said copolymer having a weight-average molecular weight of 17 kDa to 21 kDa and hydroxyl-terminated end groups.

13. The syringe mixing system of claim 1, wherein the syringe mixing system contains a pharmaceutical composition, and the pharmaceutical composition comprises 30 mg of leuprolide acetate as an active pharmaceutical ingredient and N-methyl-2-pyrrolidone and a 75:25 poly(lactide-co-glycolic acid) copolymer as a liquid formulation component, said copolymer having a weight-average molecular weight of 17 kDa to 21 kDa, and a hydroxyl-terminated distal group and another hydroxyl-terminated or ester-terminated distal group.

14. The syringe mixing system of claim 1, wherein the syringe mixing system contains a pharmaceutical composition, and the pharmaceutical composition comprises 45 mg of leuprolide acetate as an active pharmaceutical ingredient and N-methyl-2-pyrrolidone and an 85:15 poly(lactide-co-glycolic acid) copolymer as a liquid formulation component, said copolymer having a weight-average molecular weight of 20 kDa to 26 kDa, and a hydroxyl-terminated distal group and another hydroxyl-terminated or ester-terminated distal group.

15. A method of mixing a pharmaceutical composition, comprising: A syringe mixing system is provided, comprising a valve assembly having a displaceable member including a user interface and a guide member, wherein the displaceable member is slidable relative to the guide member, and wherein the user interface is operable to receive force from a user and transmit that force to a movable seal; Operable to receive a selectively rotating component of a syringe; The valve assembly includes a first position and a second position, in which fluid flow through the assembly is completely blocked, and in the second position, fluid flow is permitted. The displaceable member includes at least one protrusion that communicates with the selective rotation member when the displaceable member is in a first position, and wherein the at least one protrusion is spaced apart from the selective rotation member when the displaceable member is in a second position, and the selective rotation member is freely rotatable when the displaceable member is in the second position. A first syringe and a second syringe are coupled to the valve assembly, wherein both the first syringe and the second syringe include a syringe barrel having a hollow body defining an inner cavity, wherein the syringe barrel has a proximal end and a distal dispensing end having an outlet, and a plunger slidably disposed within the hollow body for applying pressure to syringe contents contained in the inner cavity; The movable member is movable relative to the guide member in a direction substantially perpendicular to the longitudinal axis of at least one of the first and second syringes; and The contents are mixed cyclically between the first and second syringes in preparation for delivery to the patient.

16. The method of claim 15, wherein the syringe mixing system contains a pharmaceutical composition, and the pharmaceutical composition comprises 7.5 mg of leuprolide acetate as an active pharmaceutical ingredient, and N-methyl-2-pyrrolidone and a 50:50 poly(lactic acid-co-glycolic acid) (PLGA) copolymer as a liquid formulation component, said copolymer having a weight-average molecular weight of 31 kDa to 45 kDa and at least one terminal carboxylic acid end group.

17. The method of claim 15, wherein the syringe mixing system contains the pharmaceutical composition, and the pharmaceutical composition comprises 22.5 mg of leuprolide acetate as the active pharmaceutical ingredient and N-methyl-2-pyrrolidone and a 75:25 poly(lactide-co-glycolic acid) copolymer as a liquid formulation component, the copolymer having a weight-average molecular weight of 17 kDa to 21 kDa and hydroxyl-terminated end groups.

18. The method of claim 15, wherein the syringe mixing system contains a pharmaceutical composition, and the pharmaceutical composition comprises 30 mg of leuprolide acetate as an active pharmaceutical ingredient and N-methyl-2-pyrrolidone and a 75:25 poly(lactide-co-glycolic acid) copolymer as a liquid formulation component, said copolymer having a weight-average molecular weight of 17 kDa to 21 kDa, and a hydroxyl-terminated distal group and another hydroxyl-terminated or ester-terminated distal group.

19. The method of claim 15, wherein the syringe mixing system contains a pharmaceutical composition, and the pharmaceutical composition comprises 45 mg of leuprolide acetate as an active pharmaceutical ingredient and N-methyl-2-pyrrolidone and an 85:15 poly(lactide-co-glycolic acid) copolymer as a liquid formulation component, said copolymer having a weight-average molecular weight of 20 kDa to 26 kDa, and a hydroxyl-terminated distal group and another hydroxyl-terminated or ester-terminated distal group.

20. A method of mixing a pharmaceutical composition, comprising: A syringe mixing system is provided, comprising a valve assembly having a displaceable member including a user interface and a guide member, wherein the displaceable member is slidable relative to the guide member, and wherein the user interface is operable to receive force from a user and transmit that force to a movable seal; The displaceable member includes at least one elastic protrusion, and the guiding member includes at least one recess for receiving at least one elastic protrusion; and The at least one elastic protrusion is operable to displace as the displaceable member moves, and wherein when the at least one elastic protrusion is disposed in the at least one recess of the guide member, the at least one elastic protrusion prevents or inhibits the displaceable member from returning to the first position; The valve assembly includes a rotatable Luer locking member that is able to rotate freely within the valve assembly when the displaceable member is in the second position. A first syringe and a second syringe are coupled to the valve assembly, wherein both the first syringe and the second syringe include a syringe barrel having a hollow body defining an inner cavity, wherein the syringe barrel has a proximal end and a distal dispensing end having an outlet, and a plunger slidably disposed within the hollow body for applying pressure to syringe contents contained in the inner cavity; The movable member is movable relative to the guide member in a direction substantially perpendicular to the longitudinal axis of at least one of the first and second syringes; and The contents are cyclically mixed between the first and second syringes to prepare the contents for delivery to the patient.

21. The method of claim 20, wherein the pharmaceutical composition comprises 7.5 mg of leuprolide acetate as an active pharmaceutical ingredient, and N-methyl-2-pyrrolidone and a 50:50 poly(lactic acid-co-glycolic acid) (PLGA) copolymer as a liquid formulation component, said copolymer having a weight-average molecular weight of 31 kDa to 45 kDa and at least one terminal carboxylic acid end group.

22. The method of claim 20, wherein the pharmaceutical composition comprises 22.5 mg of leuprolide acetate as an active pharmaceutical ingredient and N-methyl-2-pyrrolidone and a 75:25 poly(lactide-co-glycolic acid) copolymer as a liquid formulation component, the copolymer having a weight-average molecular weight of 17 kDa to 21 kDa and hydroxyl-terminated end groups.

23. The method of claim 20, wherein the pharmaceutical composition comprises 30 mg of leuprolide acetate as an active pharmaceutical ingredient and N-methyl-2-pyrrolidone and a 75:25 poly(lactide-co-glycolic acid) copolymer as a liquid formulation component, said copolymer having a weight-average molecular weight of 17 kDa to 21 kDa, and a hydroxyl-terminated distal group and another hydroxyl-terminated or ester-terminated distal group.

24. The method of claim 20, wherein the pharmaceutical composition comprises 45 mg of leuprolide acetate as an active pharmaceutical ingredient and N-methyl-2-pyrrolidone and an 85:15 poly(lactide-co-glycolic acid) copolymer as a liquid formulation component, said copolymer having a weight-average molecular weight of 20 kDa to 26 kDa, and a hydroxyl-terminated distal group and another hydroxyl-terminated or ester-terminated distal group.

25. A syringe coupling operable to receive a first syringe barrel and a second syringe barrel associated with a syringe mixing system, the syringe coupling comprising: A displaceable member operable to be selectively contacted by a user to change the syringe coupling from a first position to a second position; A seal with a flow port that can move with a displaceable member; A first syringe receiving component and a second syringe receiving component, wherein at least one of the first syringe receiving component and the second syringe receiving component includes a threaded component; The displaceable member includes a protrusion that selectively communicates with the threaded member, so that the threaded member can rotate freely when the displaceable member is positioned in the second position. When the displaceable member is positioned in the first position, the threaded member is substantially prevented from rotating relative to the syringe coupling; and When the displaceable member is positioned in the second position, the threaded member can rotate freely.

26. The syringe connector of claim 25, wherein the first position includes a closed position in which fluid flow through the connector is blocked, and wherein the second position includes an open position in which fluid can flow through the connector.

27. The syringe coupling of claim 25, wherein the threaded member further comprises a contact surface operable to be engaged by a portion of the syringe coupling when the syringe coupling is positioned in a first position.

28. The syringe coupling of claim 25, wherein the threaded member includes a flow port, and wherein in a first position, the flow port of the seal and the flow port of the threaded member are offset relative to each other.

29. The syringe coupling of claim 25, wherein the threaded member includes a flow port, and wherein in a second position, the flow port of the seal is aligned with the flow port of the threaded member.

30. The syringe coupling of claim 25, wherein the syringe coupling includes at least one resilient member to secure the syringe coupling in a second position and substantially prevent the syringe coupling from returning to a first position.

31. The syringe connector of claim 25, wherein both the first syringe receiving member and the second syringe receiving member include a Luer locking member operable to receive the distal end of the syringe.

32. The syringe connector of claim 25, further comprising a first syringe and a second syringe fixed to the syringe connector, wherein at least one of the first syringe and the second syringe comprises leuprorelin or a pharmaceutically acceptable salt thereof.

33. The syringe connector as claimed in claim 25, wherein, The displaceable member further includes at least one elastic protrusion.

Images