DEVICE FOR FLUID-DISPENSING VESSEL

The present disclosure relates to a device for a fluid-dispensing vessel. Also provided is a clamp suitable for use with the device and a fluid-dispensing vessel comprising the device.

BACKGROUND

Fluid-dispensing vessels, for example medical syringes, are commonly used devices for administering defined quantities of a fluid, such as a drug, in a controlled manner. Pre-filled syringes are a particularly convenient way of storing a drug - an appropriate dose of the drug is ready for administration to an individual, without the inconvenience of drawing a drug into a syringe from a drug vial, or the associated risk of administering an incorrect amount of the drug.

In this respect, conventional syringes have a barrel which defines a single chamber, which only allows for the storage of one type of material.. It is not possible for example to contain two different types of material, such as two different fluids, or a combination of a fluid and a solid, without the fluids and solids mixing during storage or delivery of the syringe.

Currently there are a few companies offering dual chamber syringes for either sequential delivery of two liquids or premixing of a diluent and powdered (lyophilised) drug, most of which are not currently adopted for widespread use due to the cost One notable product is a cancer treatment product marketed under the brand name of Prostap 3. This is a bespoke design syringe device containing 4 stoppers and as a consequence is very expensive. All of the other known devices e.g. Credence Companion, Vetter Lyotwist & Lyojet and Debiotech’s Debiopass & Debioclip generally feature a custom-design syringe, which significantly increases manufacturing costs and so prohibits widespread adoption.

The present disclosure seeks to address one or more of the above problems.

SUMMARY OF INVENTION

The following paragraphs describe the present invention:

1. A device for creating two or more separate chambers in a fluid-dispensing vessel, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within the vessel, thereby defining a separate chamber on either side of the annular member; and a valve in communication with the conduit; wherein when the movement of the annular member is restrained, the application of a fluid pressure or a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit

2. A device according to paragraph 1, wherein the fluid-dispensing vessel is a syringe, such as a medical syringe, and wherein the annular member is configured to fit within a barrel of the syringe.

3. A device according to paragraphs 1 or 2, wherein the annular member defines a front chamber (for example proximal to a syringe nozzle) on one side of the annular member, and a back chamber (for example proximal to a syringe plunger) on the opposite side of the annular member.

4. A device according to any one of paragraphs 1 to 3, wherein the annular member can be positioned at any location within the vessel, for example any location within the barrel of a syringe.

5. A device according to any one of paragraphs 1 to 4, wherein the movement of the annular member is restrained either mechanically or by fluid pressure.

6. A device according to any one of paragraphs 1 to 5, wherein the annular member is restrained mechanically when the annular member contacts an end of the fluid-dispensing vessel, for example when the annular member contacts an end of a syringe barrel, such as the end of the barrel proximal to the syringe nozzle.

7. A device according to paragraph 6, wherein the annular member is restrained mechnically when the annular member contacts the end of a syringe barrel which is proximal to the syringe nozzle.

8. A device according to any one of paragraphs 1 to 5, wherein the annular member is restrained mechanically by a constriction in the vessel, for example a constriction in a barrel of a syringe.

9. A device according to paragraph 8, wherein the constriction is produced by a clamping means.

10. A device according to paragraph 9, wherein the clamping means is a clamp configured to fit around the external surface of the vessel, such as a barrel of a syringe, for example a clamp as defined in any one of paragraphs 38 to 41.

11. A device according to paragraph 8 or 9, wherein the constriction is produced by applying finger pressure (for example a pressure between about 10 to 15 N) to the vessel, for example by applying finger pressure to the barrel of a syringe.

12. A device according to any one of paragraphs 1 to 5, wherein the annular member is restrained by fluid pressure, such as a positive or a negative fluid pressure, exerted on the annular member.

13. A device according to paragraph 12, wherein the annular member is restrained by a negative fluid pressure exerted on the annular member, for example a negative fluid pressure generated in the front chamber when a syringe plunger is withdrawn from the barrel, or a negative fluid pressure generated in the back chamber when a syringe nozzle cap is pulled away/removed from a syringe nozzle.

14. A device according to paragraph 13, wherein the annular member is restrained by a positive fluid pressure exerted on the annular member, for example a positive fluid pressure generated in the back chamber when a syringe plunger is pressed into the barrel.

15. A device according to any one of paragraphs 1 to 13, wherein the annular member comprises a raised upper surface, such as a ridge, for example shaped like a pyramid, one or more protrusions, such as one or more bumps or one or more rod-like protrusions, or a dished/dish-like upper surface.

16. A device according to paragraph 15, wherein the raised upper surface is selected from the group comprising a ridge, one or more protrusions or a dished/dish-like upper surface. 17. A device according to paragraphs 15 or 16, wherein the annular member comprises a dished/dish-liked upper surface.

18. A device according to any one of paragraphs 1 to 17, wherein the annular member further comprises an annular skirt, for example a flexible skirt surrounding the annular member.

19. A device according to any one of paragraphs 1 to 18, wherein the annular member further comprises one or more ribs, such as two ribs.

20. A device according to any one of paragraphs 1 to 19, wherein the annular member further comprises a membrane which covers the opening of the conduit

21. A device according to paragraph 20, wherein the membrane is arranged to burst or rupture when a fluid pressure is applied to the membrane.

22. A device according to paragraphs 20 or 21, wherein the valve comprises a piercing means, for creating an opening in the membrane.

23. A device according to paragraph 22, wherein the piercing means is a barb (such as a flexible barb) or needle.

24. A device according to paragraphs 22 or 23, wherein the piercing means further comprises a passage, such as a tube, which allows fluid to pass through the valve.

25. A device according to any one of paragraphs 1 to 24, wherein the valve is selected from the group comprising a plug, a spherical member, a membrane, and a rod.

26. A device according to any one of paragraphs 1 to 25, wherein the valve is selected from the group comprising a plug and a rod.

27. A device according to any one of paragraphs 1 to 25, wherein the valve is a plug.

28. A device according to paragraph 27, wherein the plug further comprises one or more ribs, such as two ribs.

29. A device according to paragraphs 27 or 28, wherein the plug further comprises a stopping means for preventing the plug from falling out of the conduit

30. A device according to paragraph 29, wherein the stopping means comprises one or more arms, such as two arms, in particular two flexible arms.

31. A device according to anyone of paragraphs 1 to 25, wherein the valve is a spherical member, for example a ball, such as a ball bearing.

32. A device according to any one of paragraphs 2 to 31, wherein the valve, such as a plug, is connected to a syringe plunger, for example via the plunger seal of a syringe.

33. A device according to paragraph 32, wherein the valve is a plug which is connected to a syringe plunger, for example a plug connected to the plunger seal of a syringe.

34. A device according to any one of paragraphs 1 to 33, wherein the valve is a membrane (for example an elastomeric membrane) that covers the opening of the conduit, wherein the membrane comprises at least one self-sealing slit, such as one or two self-sealing slits.

35. A device according to any one of paragraphs 1 to 25, wherein the valve is a rod.

36. A device according to paragraph 35, wherein the rod is connected to a cap.

37. A device according to paragraphs 35 or 36, wherein the rod is connected to a syringe nozzle cap. 38. A device according to paragraph 37, wherein the rod is slidably engaged with a syringe nozzle cap, for example wherein the cap comprises a hole for accommodating the rod.

39. A device according to paragraph 38, wherein the rod further comprises a handle.

40. A device according to paragraph 39, wherein the handle further comprises a locking means, such as push fit or screw fit (for example a Luer lock), for locking the handle with the syringe nozzle cap.

41. A device according to any one of paragraphs 35 to 40, wherein the rod further comprises a waist

42. A device according to any one of paragraphs 35 to 41, wherein the rod further comprises a narrowed end.

43. A device according to any one of paragraphs 35 to 42, wherein the rod further comprises a rounded end, such as a hemi-spherical end.

44. A device according to any one of paragraphs 36 to 43, wherein the cap comprises a locking means for securing the cap to the fluid-dispensing vessel.

45. A device according to any one of paragraphs 37 to 44, wherein the syringe nozzle cap comprises a locking means, such as a push fit or screw fit (for example a Luer lock), for securing the nozzle cap to a syringe.

46. A device according to any one of paragraphs 1 to 45, wherein the conduit further comprises a stopping means for preventing the valve from falling out of the conduit.

47. A device according to paragraph 46, wherein the stopping means is a narrowed section of the conduit.

48. A device according to any one of paragraphs 1 to 47, wherein the conduit is preferentially shaped so as to optimise the mixing of two fluids, in particular two fluids having different viscosities.

49. A device according to paragraph 48, wherein one or both ends of the conduit are tapered, for example wherein one or both ends are funnel or conical shaped.

50. A device according to paragraphs 48 or 49, wherein one or both ends of the conduit are curved conical shaped.

51. A device according to paragraph 50, wherein both ends of the conduit are curved conical shaped, i.e. the conduit is double-sided conical shaped.

52. A device according to any one of paragraphs 48 to 51, wherein the conduit comprises one or more protrusions for introducing a rotational vector to a fluid flowing through the conduit.

53. A device according to paragraph 52, wherein the one or more protrusions are vane-like protrusions, such as the protrusions in an archimedes screw thread.

54. A device according to anyone of paragraphs 1 to 53, wherein the annular member, ribs, valve, membrane, piercing means, stopping means, rod, handle, syringe nozzle cap, or a combination thereof form a single part, for example are unitary.

55. A device according to any one of paragraphs 1 to 54, wherein the annular member, raised upper surface and ribs form a single part, for example are unitary.

56. A device according to any one of paragraphs 1 to 55, wherein the application of a mechanical force to the valve causes it to open. A device according to any one of paragraphs 1 to 57, wherein the application of a fluid pressure to the valve causes it to open. A device according to any one of paragraphs 1 to 57, wherein when the movement of the annular member is restrained mechanically, for example by a constriction in the vessel, such as a constriction in a barrel of a syringe, the application of a fluid pressure to the valve causes it to open; or wherein when the movement of the annular member is restrained by a fluid pressure exerted on the annular member, such as a negative or positive fluid pressure, the application of a mechanical force to the valve causes it to open. A device according to any one of paragraphs 1 to 5758 wherein when the movement of the annular member is restrained mechanically, for example by a constriction in the vessel, such as a constriction in a barrel of a syringe, the application of a fluid pressure to the valve causes it to open. A device according to any one of paragraphs 1 to 58, wherein when the movement of the annular member is restrained mechanically when the annular member contacts contacts an end of the fluid-dispensing vessel, for example when the annular member contacts an end of a syringe barrel, such as the end of the barrel proximal to the syringe nozzle, the application of a fluid pressure to the valve causes it to open. A device according to any one of paragraphs 1 to 58, wherein when the movement of the annular member is restrained mechanically when the annular member contacts contacts an end of the fluid-dispensing vessel, for example when the annular member contacts an end of a syringe barrel, such as the end of the barrel proximal to the syringe nozzle, the application of a positive fluid pressure to the valve causes it to open, for example when a plunger of a syringe is pushed into the syringe barrel. A device according to any one of paragraphs 1 to 58, wherein when the movement of the annular member is restrained by a fluid pressure exerted on the annular member, such as a negative or positive fluid pressure, the application of a mechanical force to the valve causes it to open. A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member; and a valve in communication with the conduit; wherein when the movement of the annular member is restrained, the application of fluid pressure or a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve, such as a plug, in communication with the conduit, wherein the valve is connected to a plunger of the syringe, for example connected to the plunger seal of the syringe; and wherein when the movement of the annular member is restrained by a fluid pressure, such as a negative fluid pressure, the application of a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit. A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve in communication with the conduit, wherein the valve is a plug; wherein when the movement of the annular member is restrained mechanically, such as by a constriction in the barrel of the syringe, the application of a fluid pressure to the valve causes it to open, for example by pressing/pushing a plunger of the syringe into the barrel, allowing fluid to flow from one chamber to the other chamber via the conduit A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve, such as a rod, in communication with the conduit, wherein the valve is connected to a syringe nozzle cap; and wherein when the movement of the annular member is restrained by a fluid pressure, such as a negative fluid pressure, for example when the syringe nozzle cap is removed/pulled away from the syringe nozzle, the application of a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve, such as a rod, in communication with the conduit, wherein the valve is slidably engaged with a syringe nozzle cap; and wherein when the movement of the annular member is restrained by a fluid pressure, such as a negative fluid pressure, for example when the syringe nozzle cap is removed/pulled away from the syringe nozzle, the application of a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a curved conical shaped conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve, such as a rod, in communication with the conduit, wherein the valve is slidably engaged with a syringe nozzle cap; and wherein when the movement of the annular member is restrained by a fluid pressure, such as a negative fluid pressure, for example when the syringe nozzle cap is removed/pulled away from the syringe nozzle, the application of a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit A device for creating two or more separate chambers in fluid-dispensing vessel, such as a syringe, comprising: a moveable annular member comprising a conduit that is preferentially shaped so as to optimise the mixing of a fluid and a solid or two fluids, for example wherein one or both ends of the conduit are tapered, wherein the annular member is configured to fit within the vessel, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve, in communication with the conduit, wherein the valve is a rod that is connected to a cap, such as a syringe nozzle cap, and wherein the rod comprises a rounded-end, such as a hemi-spherical end; wherein when the movement of the annular member is restrained by a fluid pressure, such as a negative fluid pressure, for example when the syringe nozzle cap is removed/pulled away from the syringe nozzle, the application of a mechanical force to the valve causes it to open, such as by pulling the rod away from the annular member, allowing fluid to flow from one chamber to the other chamber via the conduit A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit wherein both ends of the conduit are tapered, for example wherein both ends are curved conical shaped, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve, in communication with the conduit, wherein the valve is a rod that is connected to a syringe nozzle cap, and wherein the rod comprises a rounded end, such as a hemi-spherical end; wherein when the movement of the annular member is restrained by a fluid pressure, such as a negative fluid pressure, for example when the syringe nozzle cap is removed/pulled away from the syringe nozzle, the application of a mechanical force to the valve causes it to open, such as by pulling the rod away from the annular member, allowing fluid to flow from one chamber to the other chamber via the conduit

71. A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit wherein both ends of the conduit are are curved conical shaped, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve, in communication with the conduit, wherein the valve is a rod that is connected to a syringe nozzle cap, and wherein the rod comprises a hemi-spherical end; wherein when the movement of the annular member is restrained by a fluid pressure, such as a negative fluid pressure, for example when the syringe nozzle cap is removed/pulled away from the syringe nozzle, the application of a mechanical force to the valve causes it to open, such as by pulling the rod away from the annular member, allowing fluid to flow from one chamber to the other chamber via the conduit

72. A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit wherein both ends of the conduit are are curved conical shaped, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve, in communication with the conduit, wherein the valve is a rod that is connected to a syringe nozzle cap, wherein the rod comprises a hemi-spherical end; wherein when the movement of the annular member is restrained by a negative fluid pressure when the syringe nozzle cap is removed/pulled away from the syringe nozzle, the application of a mechanical force to the valve by pulling the rod away from the annular member causes the valve to open, allowing fluid to flow from one chamber to the other chamber via the conduit.

73. A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve, such as a plug, in communication with the conduit, wherein the valve is connected to a plunger of the syringe, for example connected to the plunger seal of the syringe; wherein when the movement of the annular member is restrained by a fluid pressure, such as a negative fluid pressure, the application of a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit.

74. A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve in communication with the conduit, wherein the valve is a plug connected to a plunger of the syringe, for example connected to the plunger seal of the syringe; wherein when the movement of the annular member is restrained by a negative fluid pressure, for example by withdrawing the plunger from the barrel of the syringe, the application of a mechanical force to the valve causes the valve to open, such as by pulling the plug away from the annular member, allowing fluid to flow from one chamber to the other chamber via the conduit. A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve in communication with the conduit, wherein the valve is a plug connected to a plunger seal of the syringe; wherein when the movement of the annular member is restrained by a negative fluid pressure, for example by withdrawing the plunger from the barrel of the syringe, the application of a mechanical force to the valve causes the valve to open, such as by pulling the plug away from the annular member, allowing fluid to flow from one chamber to the other chamber via the conduit. A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve in communication with the conduit, wherein the valve is a plug connected to a plunger seal of the syringe; wherein when the movement of the annular member is restrained by a negative fluid pressure by withdrawing the plunger from the barrel of the syringe, the application of a mechanical force by pulling the plug away from the annular member causes the valve to open, allowing fluid to flow from one chamber to the other chamber via the conduit. A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member, and wherein the annular member comprises a raised upper surface, such as a ridge, for example shaped like a pyramid, one or more protrusions, such as one or more bumps or one or more rod-like protrusions, or a dished/dish-like upper surface; and a valve in communication with the conduit, wherein the valve is a plug comprising a stopping means for preventing the plug from falling out of the conduit, for example wherein the stopping means comprises one or more arms, such as two arms, in particular two flexible arms, and wherein the conduit comprises a stopping means, such as a narrowed section of the conduit, for preventing the valve from falling out of the conduit; wherein when the movement of the annular member is restrained mechanically, for example by the annular member contacting an end of the fluid-dispensing vessel, for example when the annular member contacts an end of a syringe barrel, such as the end of the barrel proximal to the syringe nozzle, the application of a fluid pressure, such as a positive fluid pressure, to the valve causes it to open, for example by pressing/pushing a plunger of the syringe into the barrel, allowing fluid to flow from one chamber to the other chamber via the conduit. A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member, and wherein the annular member comprises a raised upper surface selected from the group comprising a ridge, for example shaped like a pyramid, one or more protrusions, such as one or more bumps or one or more rod-like protrusions, and a dished/dish-like upper surface; and a valve in communication with the conduit, wherein the valve is a plug comprising a stopping means for preventing the plug from falling out of the conduit, wherein the stopping means comprises one or more arms, such as two arms, in particular two flexible arms, and wherein the conduit comprises a stopping means, such as a narrowed section of the conduit, for preventing the valve from falling out of the conduit; wherein when the movement of the annular member is restrained mechanically by the annular member contacting an end of a syringe barrel, such as the end of the barrel proximal to the syringe nozzle, the application of a fluid pressure, such as a positive fluid pressure, to the valve causes it to open, for example by pressing/pushing a plunger of the syringe into the barrel, allowing fluid to flow from one chamber to the other chamber via the conduit. A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member, and wherein the annular member comprises a dished/dish-like upper surface; and a valve in communication with the conduit, wherein the valve is a plug comprising two arms, in particular two flexible arms, and wherein the conduit comprises a narrowed section for preventing the valve from falling out of the conduit; wherein when the movement of the annular member is restrained mechanically by the annular member contacting the end of the barrel proximal to the syringe nozzle, the application of a positive fluid pressure to the valve, for example by pressing/pushing a plunger of the syringe into the barrel, causes the valve to open, allowing fluid to flow from one chamber to the other chamber via the conduit. A device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member, and wherein the annular member comprises a dished/dish-like upper surface; and a valve in communication with the conduit, wherein the valve is a plug comprising two flexible arms, and wherein the conduit comprises a narrowed section for preventing the valve from falling out of the conduit; wherein when the movement of the annular member is restrained mechanically by the annular member contacting the end of the barrel proximal to the syringe nozzle, the application of a positive fluid pressure to the valve by pressing/pushing a plunger of the syringe into the barrel causes the valve to open, allowing fluid to flow from one chamber to the other chamber via the conduit A device according to any one of paragraphs 1 to 80, wherein the annular member is restrained by a negative fluid pressure exerted on the annular member, for example when the valve is a rod connected to a cap and the cap is pulled away from the syringe nozzle, and the application of a mechanical force to the valve causes it to open. A device according to any one of paragraphs 1 to 81, wherein the annular member is restrained mechanically, for example by a constriction in the vessel, and the application of a negative fluid pressure to the valve causes the valve to open, for example by withdrawing a plunger from the barrel of a syringe or when the syringe nozzle cap is removed/pulled away from the syringe nozzle. A device according to any one of paragraphs 1 to 82, wherein the annular member is restrained mechanically, for example by the annular member contacting an end of the fluiddispensing vessel, for example when the annular member contacts an end of a syringe barrel, such as the end of the barrel proximal to the syringe nozzle, and the application of a positive fluid pressure to the valve causes the valve to open, for example by pressing/pushing a plunger into the barrel of a syringe. A device according to any one of paragraphs 1 to 83, wherein the device does not comprise multiple annular members, i.e. only has a single annular member. 85. A device according to any one of paragraphs 1 to 84, wherein the annular member is not deformed when the valve is opened, for example the annular member does not deform when a fluid pressure is applied to the annular member.

86. A device according to any one of paragraphs 1 to 85, wherein the valve is not a membrane.

87. A device according to any one of paragraphs 1 to 86, wherein the device does not comprise a chamber for storing a solid and/or a fluid.

88. A fluid-dispensing vessel comprising a device according to any one of paragraphs 1 to 87.

89. A fluid-dispensing vessel comprising a device according to any one of paragraphs 63 to 80, such as according to paragraph 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 or 80.

90. A fluid-dispensing vessel comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within the vessel, thereby defining front chamber on one side of the annular member, and a back chamber on the opposite side of the annular member; wherein the back chamber comprises a fluid which is hydraulically locked, thus preventing the fluid from flowing to the front chamber via the conduit

91. A fluid-dispensing vessel according to any one of paragraphs 88 to 90, wherein the vessel is a syringe, such as a medical syringe.

92. A fluid-dispensing vessel according to paragraph 91, wherein the syringe is a small syringe, for example a syringe having a volume of 1 to 5 ml, such as 1, 2, 3, 4 or 5 ml.

93. A fluid-dispensing vessel according to paragraph 92, wherein the syringe is a large syringe suitable for use with a syringe pump /driver, for example a syringe having a volume of 50 ml or more, such as 50, 60, 70, 80, 90 or 100 ml, in particular 60 ml.

94. A fluid-dispensing device according to any one of paragraphs 88 to 93, wherein the syringe comprises a needle, for example a staked needle.

95. A fluid-dispensing vessel according to any one of paragraphs 88 to 90, wherein the vessel is a cartridge for an auto-injector.

96. A fluid-dispensing vessel according to any one of paragraphs 88 to 95, wherein one or more chambers (for example the front and/or back chamber) further comprises a solid, such as a dry powder/cake.

97. A fluid-dispensing vessel according to paragraph 96, wherein the front chamber (for example proximal to a syringe nozzle) further comprises a solid, such as a dry powder/cake.

98. A fluid-dispensing vessel according to paragraph 96 or 97, wherein the back chamber (for example proximal to a syringe plunger) further comprises a solid, such as a dry powder/cake.

99. A fluid-dispensing vessel according to any one of paragraphs 88 to 98, wherein one or more chambers (for example the front and/or back chamber) further comprises a fluid.

100. A fluid-dispensing vessel according to paragraph 99, wherein the front chamber (for example proximal to a syringe nozzle) further comprises a fluid.

101. A fluid-dispensing vessel according to paragraphs 99 or 100, wherein the back chamber (for example proximal to a syringe plunger) further comprises a fluid. 102. A fluid-dispensing vessel according to any one of paragraphs 88 to 101, wherein one or more chambers (for example the front and/or back chamber) further comprises a gas, for example an inert gas.

103. A fluid-dispensing vessel according to paragraph 102, wherein the front chamber (for example proximal to a syringe nozzlejfurther comprises a gas, such as an inert gas.

104. A fluid-dispensing vessel according to paragraphs 102 or 103, wherein the back chamber (for example proximal to a syringe plunger) further comprises a gas, such as an inert gas.

105. A fluid-dispensing vessel according to any one of paragraphs 103 to 104, wherein the chamber comprising a gas is at a higher pressure than the other chamber.

106. A fluid-dispensing vessel according to any one of paragraphs 88 to 105, wherein one chamber (for example the front chamber) comprises a fluid and another chamber (for example the back chamber) comprises a fluid.

107. A fluid-dispensing vessel according to any one of paragraphs 88 to 105, wherein one chamber comprises a fluid and another chamber comprises a solid.

108. A fluid-dispensing vessel according to paragraph 107, wherein the front chamber comprises a fluid and the back chamber comprises a solid.

109. A fluid-dispensing vessel according to paragraph 107, wherein the front chamber comprises a solid and the back chamber comprises a liquid.

110. A fluid-dispensing vessel according to any one of paragraphs 88 to 109, further comprising a syringe nozzle cap, for example a syringe nozzle cap as defined in any one of paragraphs 36 to 45.

111. A fluid-dispensing vessel according to any one of paragraphs 88 to 110, further comprising a clamp, for example a clamp as defined in any one of paragraphs 113 to 117.

112. A fluid-dispensing vessel according to any one of paragraphs 88 to 111, wherein the vessel comprises a single device according to any one of paragraphs 1 to 87, for example a single device only having one annular member.

113. A clamp for a syringe (for example a polymer syringe), comprising: two arms configured to receive a barrel of a syringe; wherein the arms are linked to each other via a deformable connection; wherein the connection expands to allow of insertion of the barrel into the arms, after which the connection contracts to exert a pressure on the exterior surface of the barrel to create a constriction in the barrel; wherein: the pressure exerted by clamp works co-operatively with the barrel of the syringe to: i) prevent movement of the plunger thereby locking the syringe, or ii) prevents movement of an internal body (for example a device as defined in any one of paragraphs 1 to 87) in the syringe comprising a valve, which is actuated by a change in fluid pressure or by a mechanical force.

114. A clamp according to paragraph 113, wherein the pressure exerted on the exterior surface of the barrel is about 0.8 to 1.2 MPa, such as 1 MPa.

115. A clamp according to paragraphs 113 or 114, further comprising a locking means for securing the position of a syringe plunger. 116. A clamp according to paragraph 115, wherein the locking means is a notch configured to fit around the plunger.

117. A clamp comprising a pair of clamps according to any one of paragraphs 113 to 116, wherein the pair of clamps are connected to each other, for example connected via rods or poles.

118. A method of mixing a fluid and a solid or two fluids in a fluid-dispensing vessel as defined in any one of paragraphs 88 to 112, comprising repeatedly withdrawing and releasing the syringe plunger.

119. A method of mixing a fluid and a solid or two fluids in a fluid-dispensing vessel, such as a syringe as defined above, for example according to any one of paragraphs 88 to 118, comprising the steps of: a) withdrawing/pulling the syringe plunger; b) releasing the syringe plunger; and c) repeating steps a) and b).

120. A method according to paragraph 119, wherein steps a) andb) are repeated until the fluid and solid or fluids are sufficiently mixed, for example wherein the fluid and solid or fluids are completely mixed.

121. A method according to any one of paragraphs 119 to 120, wherein the method results in the production of turbulence and/or shear in the syringe as fluid is forced back and forth through the conduit of the annular member.

122. A method according to any one of paragraphs 119 to 121, wherein the fluid-dispensing vessel comprises an annular member having a conduit that is preferentially shaped so as to optimise the mixing of a fluid and a solid or two fluids, such as two fluids.

123. A method according to paragraph 122, wherein the conduit is preferentially shaped so as to optimise the mixing of two fluids having different viscosities.

124. A method according to any one of paragraphs 119 to 123, wherein the repeated withdrawing and releasing of the syringe plunger, or steps a) to c), are performed by a syringe pump/driver.

125. A method of mixing a fluid and a solid or two fluids in a cartridge for an auto-injector, wherein the cartridge comprises a device as defined in any one of paragraphs 1 to 87 and has two or more separate chambers, and wherein the auto-injector is configured to perform multiple back-flush cycles such that a fluid repeatedly flows from one chamber to another chamber via the conduit.

126. A syringe pump comprising a fluid-dispensing vessel according to any one of paragraphs 88 to 112.

127. An auto-injector comprising a fluid-dispensing vessel according to any one of paragraphs 95 to 112.

128. A device substantially as described herein with reference to any one of the drawings.

129. A fluid-dispensing vessel substantially as described herein with reference to any one of the drawings.

130. A component substantially as described herein with reference to anyone of the drawings. The presently disclosed device, for which numerous working embodiments have been successfully tested, enables pre-mixing of two-liquids or a liquid diluent and a solid within a standard syringe. In comparison with complex prior art dual syringes, the device advantageously only requires two low-cost parts.

Thus, in one aspect, there is provided a device for creating two or more separate chambers in a fluid-dispensing vessel, such as a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within the vessel, thereby defining a separate chamber on either side of the annular member; and a valve in communication with the conduit; wherein when the movement of the annular member is restrained, the application of a fluid pressure or a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit

In one embodiment, wherein when the movement of the annular member is restrained mechanically, for example by a constriction in the vessel, such as a constriction in a barrel of a syringe, the application of a fluid pressure to the valve causes it to open; or wherein when the movement of the annular member is restrained by a fluid pressure exerted on the annular member, such as a negative or positive fluid pressure, the application of a mechanical force to the valve causes it to open. Thus, the valve is only opened after the movement of the annular member is restrained. Therefore, in one embodiment the movement of the annular member is restrained and the subsequent application of a fluid pressure or a mechanical force to the valve causes it to open.

Hence, the disclosed device allows for the creation of separate chambers in a fluid-dispensing vessel, such as a syringe. Advantageously, the device has a simple design - its most basic form has only two main components, an annular member and a valve, which can either be manufactured as separate parts or as a single unitary part This has the dual benefit of lowering manufacturing costs and increasing reliability.

In addition, the device can be retrofitted to an existing fluid-dispensing vessel, such a conventional syringe or a medical syringe, resulting in significant cost savings.

Furthermore, the annular member can be positioned at any location within the vessel, for example any location within the barrel of a syringe. This allows the size of the separate chambers to be easily adjusted.

Importantly, the position at which the movement of the annular member is restrained directly affects the position where the valve opens. Thus, by controlling the position at which the annular member is restrained, the user can precisely control the position where the valve opens. This in turn makes it possible for the contents of the separate chambers to be delivered sequentially, or if desired, the contents can be pre-mixed before delivery. This provides a high degree of flexibility which renders a fluid-dispensing vessel comprising the presently disclosed device suitable for a wide range of different applications, as will be evident from the rest of the description, in particular the Examples.

For example, lyophilised drugs are generally more stable and have a better shelf-life compared to their liquid counterparts. The device could therefore be used create to two chambers in a syringe, wherein one chamber contains a lyophilised drug and the other chamber is pre-filled with an appropriate quantity of diluent. The syringe could be shipped/stored in this form, hence benefitting from the improved shelf-life and stability. At the time of use, the diluent can be introduced into the chamber with the lyophilised drug, the contents mixed to reconstitute the drug, and then an appropriate dose of the drug can be directly administered to a patient

In another aspect, there is provided a fluid-dispensing vessel comprising a device as defined above. It is further possible to install more than one device into a single fluid-dispensing vessel, such as two, three or four devices. This has the benefit of creating more than two separate chambers in the vessel - two devices would produce three chambers; three devices would produce four chambers; and four devices would produce five chambers. The skilled person thus has complete control over the desired number of chambers in a fluid-dispensing vessel.

In one embodiment, the fluid-dispensing vessel comprises a single device, for example a single device having only one annular member. Thus in one embodiment, the fluid-dispensing vessel comprises only one annular member.

In one embodiment, there is provided a device which includes a valve that is opened mechanically, whilst the device is in any position within the syringe chamber. In this device, a fluid pressure restrains the annular member during mechanical opening of the valve, as opposed to fluid pressure acting to open the valve whilst the annular member is mechanically restrained.

DETAILED DESCRIPTION

As used herein the term "fluid-dispensing vessel” refers to any vessel which is suitable for dispensing a fluid contained therein. In one embodiment, the fluid-dispensing vessel is a syringe, such as a medical syringe, and wherein the annular member is configured to fit within a barrel of the syringe. Advantageously, the present device can be installed in a range of different types of syringes, including medical syringes, oral syringes, dental syringes, laboratory syringes, syringes for applying chemical compounds such as grease, thermal paste and glues, etc.

Thus, in one embodiment, the fluid-dispensing vessel is selected from the group comprising a medical syringe, an oral syringe, a dental syringe and a laboratory syringe. In one embodiment, the fluid-dispensing vessel is a medical syringe. In one embodiment, the syringe is a polymer syringe. In another embodiment, the syringe is a glass syringe. In one embodiment, the syringe is a small syringe, for example a syringe having a volume of 1 to 5 ml, such as 1, 2, 3, 4 or 5 ml.

In one embodiment, the fluid-dispensing vessel is a syringe comprising a needle, such as a staked needle. In one embodiment, the fluid-dispensing vessel is a syringe comprising a staked needle. In another embodiment, the syringe is a large syringe having a volume of 50 ml or more, such as 50, 60, 70, 80, 90 or 100 ml, in particular 60 ml. Such syringes are particularly suitable for infusion applications, such as intravenous infusion of drugs and fluids. For reconsituted liquid-solid drugs delivered via infusion, the volume of liquid diluent is typically larger and hence large syringes are more suited for this purpose.

In addition, large syringes can be used in syringe pumps or syringe drivers for automated delivery of a fluid. Thus, in one embodiment, the syringe is a large syringe suitable for loading into a syringe pump/driver.

There are existing solutions for reconstituting a diluent and powdered drug for infusion, such as the Duplex technology (BBraun) which packages 50ml of diluent and lg of powdered antibiotic drug in a flexible bag. The person administrating the drug needs to follow a number of procedures to mix the diluent and powder within the bag before connecting to an infusion line. In comparison, the presently disclosed device may offer advantages over the Duplex technology in terms of ease of reconstitution and reduced costs, for example since the device can be used in conjunction with syringes which are typically available in clinical settings.

Thus, the present disclosure provides a device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member; and a valve in communication with the conduit; wherein when the movement of the annular member is restrained, the application of fluid pressure or a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit

In one embodiment, the device comprises only one annular member, i.e. the device only has a single annular member.

The term "annular member” as used herein refers to ring-shaped object having a generally circular shape and a smaller generally circular hole forming a conduit within the object In one embodiment, the annular member is a ring.

The annular member may be constructed from any suitable material that would be familiar to the skilled person. Desirable properties of the material may include low cost of production, low weight, and/or compatibility with biological fluids, biologies, pharmaceutical compounds and the like. Thus, the annular member could be made from a plastic or polymer, such as a thermoplastic or elastomeric material. In one embodiment, the annular member is made from an elastomeric material, for example a thermoplastic elastomer (TPE) including but not limited to Styrenic Block Copolymers (SBC), Polyolefin Blends (TPO), thermoplastic polyester copolymers (COPE) and Styrene-butadiene-styrene (SBS) rubber or any TPE blend which has been developed specifically for medical applications. In one embodiment, the annular member is not deformed when the valve is opened, i.e. the shape of the annular member remains substantially the same before, during and after the opening of the valve. In one embodiment, the annular member is not deformed when a fluid pressure is applied to the valve. Thus, in one embodiment, the annular member is made of a resilient material which is not deformable by fluid pressure.

In one embodiment, the annular member comprises a raised upper surface. The purpose of the raised upper surface is to provide space for the valve, in particular when the valve is a plug, to enter when the annular member contacts the end of a fluid-dispensing vessel, in particular the end of a syringe barrel, such as the end of the barrel proximal to the syringe nozzle.

The skilled addressed will be aware of various designs that would also fulfil the intended purpose. These include but are not limited to a ridge, for example shaped like a pyramid, one or more protrusions, such as one or more bumps or one or more rod-like protrusions, or a dished/dish- like upper surface as depicted in Figure 3B and Figure 7.

Thus, in one embodiment, the raised upper surface is selected from the group comprising a ridge, one or more protrusions, and a dished/dish-like upper surface. In one embodiment, the raised upper surface is a ridge, for example a ridge shaped like a pyramid. In one embodiment, the raised upper surface is one or more protrusions, such as a one or more bumps or rod-like protrusions. In one embodiment, the raised upper surface is a dished/dish-like upper surface. Hence, in one embodiment, the annular member comprises a dished/dish-like upper surface.

The term "conduit” as used herein refers to a passageway (such as a tube) connecting a side, such as a distal end of the annular member with the opposite side, such as a proximal end of the annular member. Within the context of the present disclosure, the conduit allows a fluid to move from one side of the annular member to its opposing side, such as from a distal end of the annular member to a proximal end of the annular member. Thus, in a fluid-dispensing vessel comprising a device of the present disclosure, the conduit provides a means for allowing a fluid to flow from one chamber to another chamber. Accordingly, in one embodiment, the conduit connects a proximal end of the annular member to a distal end of the annular member. In one embodiment, the annular member comprises a proximal end and a distal end, and a conduit extending therebetween.

The term "valve” as used herein refers to a device controls access to the conduit of the annular member. Typically, the valve will have an ‘open’ configuration in which access to the conduit is permitted, and a ‘closed’ configuration in which the valve restricts or blocks access to the conduit. Thus, in the context of the present disclosure, the valve actuates to allow or to prevent the flow of a fluid from one chamber to another chamber. Hence, in one embodiment the valve has an ‘open’ and a closed’ configuration. In one embodiment, the application of a mechanical force or a fluid pressure causes the valve to move from a ‘closed’ to an ‘open’ configuration. In one embodiment, the application of a mechanical force causes the valve to move from a ‘closed’ to an ‘open’ configuration. In one embodiment, the application of a negative fluid pressure causes the valve to move from a ‘closed’ to an ‘open’ configuration. In another embodiment, the application of a positive fluid pressure causes the valve to move from a ‘closed’ to an ‘open’ configuration.

The term "chamber” as used herein refers to an enclosed space, cavity or compartment in a fluiddispensing vessel. Advantageously, one or more chambers of the fluid-dispensing vessel can be pre-filled with a solid, fluid and/or a gas. The manufacturer/user thus has complete flexibility regarding the contents of each chamber in the vessel, hence making multiple different applications feasible.

In one embodiment, the annular member defines a front chamber (for example proximal to a syringe nozzle) on one side of the annular member, and a back chamber (for example proximal to a syringe plunger) on the opposite side of the annular member. Hence, the present device can be used to create at least two separate chambers (such as a front chamber and a back chamber) in a fluid-dispensing vessel. In the context of a syringe, the front chamber is generally the chamber proximal to the syringe nozzle while the back chamber is the chamber proximal to the syringe plunger.

In one embodiment, the annular member can be positioned at any location within the vessel, for example any location within the barrel of a syringe. This allows the size of the separate chambers to be easily adjusted. Crucially, the position of the annular member in turn affects the position where the valve opens. Thus, by controlling the position of the annular member, the user to precisely control the position where the valve opens.

In one embodiment, the presently disclosed device does not comprise a chamber. In other words, the device itself does not include a chamber for containing a fluid or solid. Thus, in one embodiment the device creates two or more separate chambers in a fluid-dispensing vessel by sub-dividing an existing chamber in the fluid-dispensing vessel. Advantageously, this results in a simpler and cheaper to manufacture design compared to other prior art devices that typically comprise a chamber. Such prior art devices generally need to be filled with fluids and/or solids using specialised equipment which further adds to the complexity of implementing these devices.

In one embodiment, the movement of the annular member is restrained either mechanically or by fluid pressure. In one embodiment, the annular member is restrained mechanically by a constriction in the vessel, for example a constriction in a barrel of a syringe. A constriction in the vessel reduces the diameter of the vessel body, such as a reduction in the diameter of a syringe barrel. Conversely, the dimensions of the annular member are unchanged. As a result, the annular member which now has a larger diameter than the vessel, can no longer move freely within the vessel (i.e. its movement is restrained), such as within the barrel of a syringe.

In one embodiment, the constriction is produced by a clamping means. In one embodiment, the clamping means is a clamp configured to fit around the external surface of the vessel, such as a barrel of a syringe, for example a clamp as defined below. The advantage using a clamp is that it can be placed anywhere along the external surface of the vessel, for example anywhere along the length of the barrel. This allows a user to precisely control the position where the annular member is restrained, which in turn determines the position where the valve opens to allow fluid to flow between the chambers.

In one embodiment, the constriction is produced by applying finger pressure (for example a pressure between about 10 to 15 N) to the vessel, for example by applying finger-pressure to the barrel of a syringe. In one embodiment, the pressure exerted is about 10, 11, 12, 13, 14 or 15 N. Advantageously, in some embodiments the pressure exerted by fingers is sufficient to create a constriction so as to mechanically restrict the movement of the annular member. Since a clamp is not required, this offers greater convenience to the user, as well as cost savings.

In one embodiment, the annular member is restrained mechanically when the annular member contacts an end of the fluid-dispensing vessel, for example when the annular member contacts an end of a syringe barrel, such as the end of the barrel proximal to the syringe nozzle. Hence, in one embodiment, the annular member is restrained mechnically when the annular member contacts the end of a syringe barrel which is proximal to the syringe nozzle. Advantageously, this allows the annular member to be mechnically restrained without the need for a clamp or the need to apply finger pressure to the vessel. This embodiment may therefore be particularly suitable for fluid-dispensing vessels for which a constriction in the vessel cannot be easily introduced, for example a syringe made of glass or a very rigid polymer.

The annular member maybe restrained in this fashion by incorporating a raised upper surface in the annular member as described above. In particular, the raised upper surface makes contact with the end of the fluid-dispensing vessel thus preventing further movement of the annular member. At the same time, the raised upper surface provides a gap for the valve to enter, in order to open the valve and allow access to the conduit. Hence, in one embodiment the annular member comprises a raised upper surface, such as a ridge, one or more protrusions, and a dished/dish- like upper surface, and the annular member is restrained mechanically when the annular member contacts contacts an end of a fluid-dispensing vessel, for example when the annular member contacts an end of a syringe barrel, such as the end of the barrel proximal to the syringe nozzle.

In one embodiment, the annular member comprises a dished/dish-like upper surface and is restrained mechnically when the annular member contacts an end of a fluid-dispensing vessel, for example when the annular member contacts an end of a syringe barrel, such as the end of the barrel proximal to the syringe nozzle. In one embodiment, the annular member comprises a dished/dish-like upper surface and is restrained mechnically when the annular member contacts an end of a fluid-dispensing vessel, for example when the annular member contacts an end of a syringe barrel, such as the end of the barrel proximal to the syringe nozzle; and wherein the valve is a plug. In one embodiment, the annular member comprises a dished/dish-like upper surface and is restrained mechnically when the annular member contacts the end of the barrel proximal to the syringe nozzle; and wherein the valve is a plug.

In one embodiment, the annular member is restrained by fluid pressure exerted on the annular member. This can be achieved by either negative or positive fluid pressure. Advantageously, the annular member can be restrained by fluid pressure instead of mechanically, thereby eliminating the requirement for a clamping means, such as an external clamp. This could potentially result in reduced costs. Hence, in one embodiment, the annular member is restrained by negative or positive fluid pressure exerted on the annular member.

In one embodiment, the annular member is restrained by a negative fluid pressure, for example a negative fluid pressure generated in the front chamber when a syringe plunger is withdrawn from the barrel. This can be achieved for example if the front chamber of a syringe contains a fluid and a syringe cap is attached to a syringe nozzle. When the syringe plunger is withdrawn (i.e. pulled), this generates a negative pressure in the front chamber, thus producing a hydraulic lock that restrains the movement of the annular member. Therefore, in one embodiment, the annular member is restrained by a negative fluid pressure generated in the front chamber when a syringe plunger is withdrawn from the barrel.

A negative fluid pressure can also be generated in the back chamber, for example when the back chamber of a syringe contains a fluid and a syringe cap is attached to a syringe nozzle. When the nozzle cap is pulled away from the nozzle, this generates a negative pressure in the back chamber, thereby also restraining the movement of the annular member. Thus, in another embodiment, the annular member is restrained by a negative fluid pressure generated in the back chamber when a syringe nozzle cap is removed/pulled away from the syringe nozzle. In one embodiment, the annular member is restrained by a positive fluid pressure, for example a positive fluid pressure generated in the back chamber when a syringe plunger is pressed/pushed into the barrel. For example, an annular skirt, such as a flexible skirt could be added to the annular member. When the plunger is pushed into the barrel, this causes the skirt to expand radially, thereby increasing the diameter of the annular member and preventing it from moving freely within the barrel. Thus, in one embodiment, the annular member is restrained by a positive fluid pressure generated in the back chamber when a syringe plunger is pressed into the barrel.

In one embodiment, the annular member further comprises an annular skirt, for example a flexible skirt surrounding the annular member.

In another embodiment, the annular member is restrained by a positive fluid pressure generated in the front chamber, for example by introducing a gas (such as an inert gas) into the front chamber. Thus, in one embodiment, the annular member is restrained by a positive fluid pressure generated in the front by introducing a gas into the front chamber of a syringe.

In one embodiment, the annular member comprises one or more ribs, such as one, two or three ribs. In one embodiment, the annular member comprises two ribs. The ribs help to ensure that the annular member fits firmly within the fluid-dispensing vessel, for example within the barrel of a syringe. The ribs can be a separate component added to the annular member, or the ribs can be molded as part of the annular member itself, i.e., the annular member and one or more ribs are unitary. In one embodiment, the annular member further comprises a membrane which covers the opening of the conduit. Advantageously, the membrane may act as a physical barrier to prevent moisture from passing through the conduit of the annular member from one chamber to another. This might be useful for example in an arrangement where one chamber comprises a solid and the other chamber comprises a diluent. The membrane therefore helps to ensure that the solid remains dry during storage or transportation.

In one embodiment, the membrane is arranged to burst or rupture when a fluid pressure is applied to the membrane, i.e. the membrane is burstable or rupturable. This feature is useful because the membrane can act as a physical barrier during storage or transportation but when ready for us, the membrane can rupture to allows access to the conduit of the annular member, thereby permitting the flow of a fluid from one chamber to another chamber. To facilitate this feature, the membrane may be manufactured from a frangible material such as a thermoplastic elastomer (TPE). A blend of TPE which has the lowest tear resistance may facilitate the selfrupturing nature of the membrane.

Thus, in one embodiment, the membrane is manufactured from a thermoplastic elastomer (TPE) including but not limited to Styrenic Block Copolymers (SBC), Polyolefin Blends (TPO), thermoplastic polyester copolymers (COPE) and Styrene-butadiene-styrene (SBS) rubber or any TPE blend which has been developed specifically for medical applications.

Alternatively, the membrane could be made sufficiently fine or thin, such that it would burst or rupture when sufficient fluid pressure is exerted on the annular member. The thickness could for example be as little as a few microns, provided the membrane adequately seals the opening and is readily achievable via the injection moulding process.

In one embodiment, the annular membrane further comprises an annular skirt, for example a flexible skirt surrounding the circumference of the annular member. Such a flexible skirt could be made from a range of suitable materials such as, but not limited to polyisoprene, Styrene Butadiene Rubber (SBR) Nitrile Butadiene Rubber (NBR), Ethylene Propylene Diene Monomer Rubber (EPDM) or Silicone Rubber. In one embodiment, the flexible skirt is made from a thermoplastic elastomer (TPE) including but not limited to Styrenic Block Copolymers (SBC), Polyolefin Blends (TPO), thermoplastic polyester copolymers (COPE) and Styrene-butadiene- styrene (SBS) rubber or any TPE blend which has been developed specifically for medical applications.

In one embodiment, the valve comprises a piercing means for creating an opening or hole in the membrane. This embodiment advantageously allows for a more durable membrane (such as a thicker membrane) which does not rupture under fluid pressure to be used. Hence, the valve’s piercing means is used to create an opening in the membrane to allow access to the annular member’s conduit, thus permitting the flow of a fluid from one chamber to another chamber.

In one embodiment, the piercing means is a barb (such as a flexible barb) or a needle. In one embodiment, the piercing means is a flexible barb. The barb may optionally comprise a passage, for example a tube, which allows fluid to pass through the valve. Hence, in one embodiment, the barb comprises a passage, such as a tube.

Advantageously, the barb could be incorporated as part of the valve itself, i.e., the barb could be unitary or a single part together with the valve. This could be readily achieved for example by manufacturing the valve from plastic or some other polymer.

In one embodiment, the valve does not comprise a piercing means. In one embodiment, the piercing means is not a barb.

In one embodiment, the valve is selected from the group comprising a plug, a rod, a spherical member and a membrane. In one embodiment, the valve is selected from the group comprising a plug and a rod. In one embodiment, the valve is selected from the group comprising a spherical member and a membrane.

In one embodiment, the valve is a plug. In one embodiment, the valve is not a plug.

As used herein, the term "plug” refers to an object which is appropriately dimensioned such that it moves within the conduit of the annular member and is able to adopt an ‘open’ configuration in which access to the conduit is permitted, and a ‘closed’ configuration in which the plug restricts or blocks access to the conduit.

Advantageously, the plug may be manufactured with appropriate dimensions such that it fits snugly within the conduit without impending its ability is able to move freely within the conduit This has the benefit of eliminating gaps between the valve and conduit without adversely affecting the proper function of the valve, which helps to prevent leakage of fluid from one chamber to another.

In one embodiment, the plug further comprises one or more ribs, such as one, two or three ribs. In one embodiment, the plug comprises two ribs. The ribs help to ensure that the plug fits firmly within the conduit of the annular member. The ribs can be a separate component added to the plug, or the ribs can be molded as part of the plug itself, i.e. the plug and one or more ribs are unitary.

In one embodiment, the valve is a plug comprising a piercing means, such as a barb (for example a flexible barb) or a needle.

In one embodiment, the plug further comprises one or more stopping means, such as one or two stopping means, for preventing the plug from falling out of the conduit This feature has the advantage of preventing the plug from being completely separated from the conduit, and by extension prevents the valve being separated from the annular member.

The stopping means can be achieved by various methods, such as a simple lip, such as an annular lip surrounding one or both ends of the plug, wherein the plug has a larger diameter than the conduit. Thus, in one embodiment, the stopping means is a lip. In one embodiment, the plug comprises one lip located at one end of the plug. In another embodiment, the plug comprises one lip located at one end of the plug and another lip located at the opposite end of the plug.

In one embodiment, the stopping means comprises one or more arms, such as one, two, three or four arms. In one embodiment, the stopping means comprises two arms, example two flexible arms. The use of the arms as a stopping means has one or more of the following benefits:

First, the flexible arms can collapse to allow the plug to be fully inserted into the conduit, after which the arms can expand back out, thereby preventing the plug from dropping out of the conduit. This allows the annular member and plug to be easily assembled together. Second, when employed in a syringe for example, as the plunger is pushed/inserted into the barrel to expel a fluid, the arms will flatten out as the plunger seal coalesces with the back of the valve. This helps to maximise the amount of fluid expelled from the syringe.

In one embodiment, the valve is a spherical member. The term "spherical member” as used herein refers to an object having a spherical shape, such as a ball. Hence, in one embodiment, the spherical member is a ball. Examples of suitable spherical members include but are not limited to a plastic ball, such as a ball made from thermoplastic, or a ball made from a metal, such as a ball bearing. Accordingly, in one embodiment, the spherical member is a ball bearing, for example a metal ball bearing. In one embodiment, the valve is not a spherical member. In another embodiment, the valve is not a ball bearing, such as a metal ball bearing.

Advantageously, a spherical member such as a ball bearing could function both as a valve to control the flow of fluid via the conduit of the annular member, and also function as an agitator to help ensure that the contents of a chamber are properly mixed. This could be particularly useful where one chamber for example contains a dry drug powder and the other chamber contains a diluent for reconstituting the drug.

In one embodiment, the valve is connected to a syringe plunger, for example via the plunger seal of a syringe. Hence, in one embodiment, the valve is connected to a plunger seal of a syringe. This can be advantageous because the movement of the plunger directly controls the movement of the valve. This could potentially more reliably move the valve (compared for example to using fluid pressure alone) and/or provide a more instantaneous actuation of the valve when the plunger is moved. This embodiment is particularly suitable for use in a syringe with a prefitted needle, such as a staked needle.

Thus, in one embodiment, the valve, such as a plug, is connected to a syringe plunger and the fluiddispensing vessel is a syringe comprising a needle, such as a staked needle. In one embodiment, the valve is a plug connected to a syringe plunger. In one embodiment, the fluid dispensing vessel is a syringe comprising a needle, such as a staked needle, and the valve is a plug connected to a syringe plunger. In one embodiment, the fluid-dispensing vessel is a syringe comprising a staked needle. In one embodiment, the valve is a membrane (for example an elastomeric membrane) that covers the opening of the conduit, wherein the membrane comprises at least one self-sealing slit, such as one, two or three self-sealing slits. Advantageously, the membrane could function as a valve to control the flow of fluid between one chamber to another via the conduit of the annular member. For example, the slit(s) is normally closed (i.e. the valve is closed) but may be opened by the application of fluid pressure or a mechanical force to the membrane. To close the valve, the fluid pressure or mechanical force would be removed, whereupon the slit(s) would revert to its closed state because the slit(s) is self-sealing. In one embodiment, the valve is not a membrane.

To facilitate the self-sealing function, the membrane may be made from an elastomeric material, such as but not limited to any natural or synthetic elastomer such as Polyisoprene, Styrene Butadiene Rubber (SBR) Nitrile Butadiene Rubber (NBR), Ethylene Propylene Diene Monomer Rubber (EPDM) or Silicone Rubber. In one embodiment, the membrane is made from a thermoplastic elastomer (TPE) including but not limited to Styrenic Block Copolymers (SBC), Polyolefin Blends (TPO), thermoplastic polyester copolymers (COPE) and Styrene-butadiene- styrene (SBS) rubber or any TPE blend which has been developed specifically for medical applications.

In one embodiment, the membrane comprises one self-sealing slit In one embodiment, the membrane comprises two self-sealing slits. In one embodiment, the membrane comprises three self-sealing slits. The slits may be of any shape arranged such that the slits respond preferentially to fluid pressure to open and close the slits. In one embodiment, the slit is crescent-shaped. The present inventors have determined that a crescent shape design works particularly well to reliably open and close the valve.

In one embodiment, the valve is a rod. In one embodiment, the valve is not a rod.

The term "rod” as used herein refers to a generally straight bar, which is typically cylindrical. However, the skilled person would be aware that the rod need not be completely straight and that non-cylindrical shapes can also be used, provided the rod is appropriately dimensioned such that it can fit and move within the conduit of the annular member, and is able to form an adequate seal to close off access to the conduit.

In one embodiment, the rod is connected to a cap. In one embodiment, the fluid-dispensing vessel comprises a cap. In one embodiment, the fluid-dispensing vessel is a syringe comprising a cap.

The term "cap” as used herein refers to a covering used to seal off an opening in a fluid-dispensing vessel. The cap would therefore be appropriately dimensioned to the opening of the fluiddispensing vessel. It may be constructed from a plastic or polymer, such as a thermoplastic or elastomeric material, which is able to provide an adequate seal for the opening of the fluiddispensingvessel. In one embodiment, the cap is made from an elastomeric material, for example a thermoplastic elastomer (TPE) including but not limited to Styrenic Block Copolymers (SBC), Polyolefin Blends (TPO), thermoplastic polyester copolymers (COPE) and Styrene-butadiene- styrene (SBS) rubber or any TPE blend which has been developed specifically for medical applications.

In one embodiment, the cap is a syringe nozzle cap. Hence, in one embodiment, the rod is connected to a syringe nozzle cap. Advantageously, this arrangement allows for a mechanical force to be directly applied to the rod by moving the nozzle cap, which in turn allows the valve to be opened or closed. Thus, in one embodiment, the fluid-dispensing vessel is a syringe comprising a syringe nozzle cap.

In another embodiment, the rod is slidably engaged with a syringe nozzle cap. This can be achieved for example, by using a syringe nozzle cap that comprises a hole which can accommodate the rod. The syringe cap preferably forms an interference fit with the rod, thereby sealing the front chamber of the syringe when the nozzle cap is attached to the syringe nozzle. Thus, in one embodiment, the rod is slidably engaged with a syringe nozzle cap, wherein the syringe nozzle cap forms an interference fit with the rod.

In one embodiment, the rod further comprises a handle. The advantage of the handle is that it makes it easier to grip the rod, thus allowing the rod to be more easily moved relative to the syringe nozzle cap.

In one embodiment, the handle further comprises a locking means, such as push fit or screw fit (for example a Luer lock), for locking the handle with the syringe nozzle cap. Thus, in one embodiment the handle further comprises a push fit for locking the handle with the syringe nozzle cap. In another embodiment, the handle further comprises a screw fit (such as a Luer lock) for locking the handle with the syringe nozzle cap. Advantageously, this feature secures the rod, which helps to prevent any accidental movement of the valve during storage or delivery of the syringe.

In one embodiment, the rod further comprises a waist The term "waist” as used herein refers to a narrowed section located anywhere along the length of the rod, with the proviso that the narrowed section is not located at the extreme ends of the rod.

The waist has the benefit of allowing the front chamber of a syringe to be sealed or unsealed depending on the position of the rod relative to the syringe nozzle. This for example facilitates the mixing of a fluid and a solid or two fluids in the front chamber of a syringe, following the opening of the valve. The waist in particular allows the front chamber to be completely sealed, which, when used in conjunction with the presently disclosed method of mixing a fluid and a solid or two fluids in a fluid-dispensing vessel, helps to enhance the mixing action.

Alternatively, the waist can be omitted, thereby preventing the front chamber from being completely sealed, if a more gentle mixing action is desired. This may be desirable for instance when mixing biologic freeze-dried drugs which typically need to be mixed more gently. Thus in one embodiment, the rod does not comprise a waist In one embodiment, the rod further comprises a narrowed end. Advantageously, the narrowed end makes it easier to relocate the rod in the conduit of the annular member, thereby helping to seal the front chamber of a syringe after the valve has been opened.

The rod may be made of any suitable material which will be known to the skilled person. For example the rod may be made from the same material as the syrine nozzle cap, such as Nylon (PA6) or polypropylene or medical grades of similar polymers used for other parts of a syringe.

The conduit generally has a cylindrical or tube shape. However, the skilled person will appreciate that shape of the conduit can be configured to receive the valve depending on its shape. Thus, in one embodiment the conduit is configured to receive a plug. In one embodiment, the conduit is configured to receive a spherical member, such as a ball bearing. In one embodiment, the conduit is configured to receive a plug comprising a piercing means, such as a flexible barb. In another embodiment, the conduit is configured to receive a rod, including a rod further comprising a waist, a rod further comprising a narrowed end, or a rod comprising both a waist and a narrowed end.

The conduit may also be preferentially shaped so as to optimise the mixing of a fluid and solid or two fluids, for example by increasing the amount of turbulence and shear produced when a fluid flows through the conduit This may be of particular advantage when mixing two fluids with dissimilar viscosities in the front chamber of a fluid-dispensing vessel, such as a syringe, following the opening of the valve. For example, one or both ends of the conduit may be tapered to produce a funnel or conical shape. Thus, in one embodiment, one or both ends of the conduit are tapered, for example wherein one or both ends are funnel or conical shaped. In another embodiment, one or both ends of the conduit are curved conical shaped.

In one embodiment, both ends of the conduit are tapered, for example wherein both ends are funnel, conical shaped or curved conical shaped, such as shown in Figures ID and IE. This has at least the following benefits:First, when both ends are tapered, this typically provides better mixing. Second, since the conduit is symmetrical (and by extension the annular member is also symmetrical), the annular member can be inserted into the fluid-dispensing vessel in either orientation. This both simplifies and reduces the cost of assembly. Third, the symmetrical conduit acts as a self-centering mechanism when the valve is a rod - the annular member will help ensure that the rod is centralised during assembly as the annular member is inserted into the fluiddispensing vessel to engage with the annular member.

Accordingly, examples of suitable shapes are depicted in Figures 1C to IE and include but are not limited to: a conical shaped conduit, a curved conical shaped conduit, a double-sided conical shaped conduit, and a double-sided curved conical shaped conduit Hence, in one embodiment, the conduit has a shape selected from the group comprising: conical shaped, curved conical shaped, double-sided conical shaped, and double-sided curved conical shaped.

The conduit may also comprise protrusions for introducing a rotational vector to a fluid flowing through the conduit This has the advantage of further improving the mixing of a fluid and solid or two fluids. Thus, in one embodiment the conduit comprises one or more protrusions for introducing a rotational vector to a fluid flowing through the conduit.

Protrusions that may be suitable for achieving this effect include but are not limited to bumps or vane-like protrusions, such as the protrusions found in an archimedes screw thread. Accordingly, in one embodiment, the protrusions are vane-like protrusions, such as those found in an archimedes screw thread.

In one embodiment, the conduit further comprises a stopping means for preventing the valve from falling out of the conduit This feature has the advantage of preventing the valve from being completely separated from the conduit, and by extension prevents the valve being separated from the annular member. The stopping means can take various forms that would be familiar to the skilled person. For example, a section of the conduit could be narrowed (i.e. the width of the conduit is reduced) such that the valve is prevent from passing beyond the point where the conduit begins to narrow. Thus, in one embodiment, a section of the conduit is narrowed.

In one embodiment, the application of a mechanical force to the valve causes it to open. The mechanical force may be any suitable force (for example a pulling or pushing action) for dislodging the valve from the annular member. In one embodiment, the valve is a rod and a mechanical force is applied to the rod to open the valve. In one embodiment, the valve is a rod connected to a cap, such as a syringe nozzle cap and a mechnical force is appled to the rod to open the valve. In one embodiment, the mechanical force is applied by pulling the rod away from the annular member. This can be achieved for example in the case where the rod is connected to a cap, by continuing to pull the cap away from the syringe nozzle, thereby pulling the rod away from the annular member. Thus, in one embodiment, the mechanical force is applied by pulling the cap, such as a syringe cap away from the syringe nozzle, thereby pulling the rod away from the annular member. In one embodiment, the valve is opened by pulling the rod away from the annular member. In one embodiment, the valve is a rod connected to a cap, such as a syringe cap, and the valve is opened by continuing to pull the cap away from the syringe nozzle, thereby pulling the rod away from the annular member.

In one embodiment, the valve is a plug connected to a syringe plunger, such as the plunger seal, and a mechanical force is applied to the plug to open the valve. In one embodiment, the mechanical force is applied by pulling the plug away from the annular member, which can be achieved for example by further withdrawing the plunger from the barrel of the syringe. Thus, in one embodiment, the valve is a plug connected to a syringe plunger, such as the plunger seal, and the valve is opened by pulling the plug way from the annular member. In one embodiment, the In one embodiment, the valve is a membrane and a mechanical force is applied to the membrane to open the valve. In one embodiment, the valve is opened by piercing the membrane, for example by using a plug comprising a piercing means, such as a barb. In another embodiment, the valve is a membrane and a fluid pressure is applied to the membrane to open the valve. In one embodiment, the application of a fluid pressure to the valve causes it to open. In one embodiment, the valve is a plug and a fluid pressure is applied to the plug to open the valve. In another embodiment, the valve is a ball bearing and a fluid pressure is applied to the ball bearing to open the valve.

In one embodiment, the valve is not opened by the application of a fluid pressure. In one embodiment, the valve is not opened by the application of a mechanical force. In one embodiment, the movement of the annular member is restrained by fluid pressure and the application of a mechanical force to the valve causes it to open; or the movement of the annular member is restrained mechanically and the application of a fluid pressure to the valve causes it to open.

In one embodiment, the movement of the annular member is restrained by fluid pressure and the application of a mechanical force to the valve causes it to open. In one embodiment, the movement of the annular member is restrained mechanically and the application of a fluid pressure to the valve causes it to open. In one embodiment, the movement of the annular member is restrained by fluid pressure and the application of a fluid pressure to the valve causes it to open. In one embodiment, the movement of the annular member is restrained mechanically and the application of a mechanical force to the valve causes it to open.

In one embodiment, the annular member, ribs, valve, membrane, piercing means, stopping means or a combination thereof form a single part, i.e. are unitary. In one embodiment, the annular member, ribs, valve, membrane, piercing means, stopping means, rod, syringe nozzle cap, or a combination thereof form a single part, i.e. are unitary. This feature could be beneficial in terms of ease of construction, improved reliability and could also result in manufacturing cost-savings.

Thus, in one embodiment, the annular member and ribs form a single part In one embodiment, the annular member, raised upper surface and ribs form a single part. In one embodiment, the valve and stopping means form a single part In one embodiment, the valve and piercing means form a single part In one embodiment, the annular member and valve form a single part In one embodiment, the annular member and the membrane form a single part In one embodiment, the annular member, valve and also the membrane form a single part. In one embodiment, the rod and syringe nozzle cap form a single part. In another emboidment, the rod and handle form a single part

Alternatively, if a two-part design for the annular member and valve (for example) is preferred, then the annular member may be made from an elastomeric material (such as a material mentioned above) and the plug may be made from a thermoplastic, preferably the same polyethylene grade as the syringe barrel.

In one embodiment, there is provided a device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member; and a valve in communication with the conduit; wherein when the movement of the annular member is restrained, the application of fluid pressure or a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit

In one embodiment there is provided a device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve, such as a plug, in communication with the conduit, wherein the valve is connected to a plunger of the syringe, for example connected to the plunger seal of the syringe; and wherein when the movement of the annular member is restrained by a fluid pressure, such as a negative fluid pressure, the application of a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit

In one embodiment, there is provided a device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve in communication with the conduit, wherein the valve is connected to the plunger seal of the syringe and wherein the valve is a plug; and wherein when the movement of the annular member is restrained by a negative fluid pressure, the application of a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit

In one embodiment, there is provided a device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve, such as a rod, in communication with the conduit, wherein the valve is connected to a syringe nozzle cap; and wherein when the movement of the annular member is restrained by a fluid pressure, such as a negative fluid pressure, the application of a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit. In one embodiment, there is provided a device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve in communication with the conduit, wherein the valve is connected to a syringe nozzle cap and wherein the valve is a rod; and wherein when the movement of the annular member is restrained by a negative fluid pressure, for example caused when the syringe nozzle cap is removed/pulled away from the syringe nozzle, the application of a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit

In one embodiment, there is provided a device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a separate chamber on either side of the annular member, for example a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve, such as a rod, in communication with the conduit, wherein the valve is slidably engaged with a syringe nozzle cap; and wherein when the movement of the annular member is restrained by a fluid pressure, such as a negative fluid pressure, the application of a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit.

In one embodiment, there is provided a device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve in communication with the conduit, wherein the valve is slidably engaged with a a syringe nozzle cap and wherein the valve is a rod; and wherein when the movement of the annular member is restrained by a negative fluid pressure, for example caused when the syringe nozzle cap is pulled away/removed from the syringe nozzle, the application of a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit

In one embodiment, there is provided a device for creating two or more separate chambers in a syringe, comprising: a moveable annular member comprising a conduit which has a curved conical shape, wherein the annular member is configured to fit within a barrel of the syringe, thereby defining a chamber proximal to a nozzle of the syringe on one side of the annular member, and another chamber proximal to a plunger of a syringe on the opposite side of the annular member; and a valve in communication with the conduit, wherein the valve is slidably engaged with a a syringe nozzle cap and wherein the valve is a rod; and wherein when the movement of the annular member is restrained by a negative fluid pressure, for example caused when the syringe nozzle cap is pulled away/removed from the syringe nozzle, the application of a mechanical force to the valve causes it to open, allowing fluid to flow from one chamber to the other chamber via the conduit

In one aspect, there is provided a fluid-dispensing vessel comprising: a moveable annular member comprising a conduit, wherein the annular member is configured to fit within the vessel, thereby defining front chamber on one side of the annular member, and a back chamber on the opposite side of the annular member; wherein the back chamber comprises a fluid which is hydraulically locked, thus preventing the fluid from flowing to the front chamber via the conduit.

Advantageously, in this aspect the annular member does not have a physical valve per se. This significantly simplifies the design of the device, thereby reducing manufacturing time and costs. The drawback is that the lack of a physical valve may decrease the stability of the fluid-dispensing vessel during storage and transport, particularly in the case of a dispensing vessel having a chamber pre-filled with a fluid. This drawback can be mitigated by further incorporating one or both of the following modifications:

1. During filling introduce a small positive pressure with inert gas (e.g. nitrogen or argon) in the front chamber where the solid drug is stored in order to prevent the fluid from entering the front chamber.

2. Introduce a fine membrane across the orifice as a physical barrier to prevent moisture from the diluent being absorbed by the dried drug which readily bursts under the influence of a plunging action.

Thus, in one embodiment the fluid-dispensing vessel further comprises a gas, such as a gas in the front chamber. In one embodiment, the gas is an inert gas. In one embodiment, the inert gas is selected from the group comprising nitrogen (N), helium (He), neon (Ne), argon (Ar), krypton (Kr), xenon (Xe), radon (Rn) or oganesson (Og). In one embodiment, the inert gas is nitrogen, helium or argon. In one embodiment, the gas is nitrogen. In one embodiment, the gas is helium. In one embodiment, the gas is argon.

In one embodiment, the fluid-dispensing vessel further comprises a burstable membrane which covers the opening of the conduit, such as a burstable membrane as described above.

In one embodiment, the fluid-dispensing vessel further comprises a gas, such as a gas in the front chamber; and further comprises a membrane which covers the opening of the conduit In one embodiment, the membrane is arranged to burst or rupture when a fluid pressure is applied to the membrane.

In one embodiment, the fluid-dispensing vessel further comprises a cap. Thus, in one embodiment, the fluid-dispensing vessel further comprises a syringe nozzle cap. This feature could be particularly beneficial for pre-filled fluid-dispensing vessels because it helps to keep the contents of the vessel sterile. Furthermore, in applicable embodiments, the nozzle helps to seal the front chamber which helps to generate a negative fluid pressure when a syringe plunger is withdrawn from the barrel.

In one embodiment, the syringe nozzle cap comprises a locking means, such as a push fit or screw fit (for example a Luer lock), for securing the cap to a syringe. Advantageously, the locking means helps to maintain the sterility of the syringe front chamber and further provides a locking mechanism (as the front chamber is air-locked) to prevent unintended movement of the plunger when the syringe is in storage or during transportation.

In one embodiment, the fluid-dispensing vessel further comprises a clamp, for example a clamp as defined below.

In one embodiment the fluid-dispensing vessel comprises one to four devices. In one embodiment, the fluid-dispensing vessel comprises one device. In one embodiment, the fluiddispensing vessel comprises two devices. In one embodiment, the fluid-dispensing vessel comprises three devices. In one embodiment, the fluid-dispensing vessel comprises four devices.

In one embodiment, one or more chambers (for example the front and/or back chamber) further comprises a solid, such as a dry powder/cake. In one embodiment, the front chamber (for example proximal to a syringe nozzle) further comprises a solid, such as a dry powder/cake. In one embodiment, the back chamber (for example proximal to a syringe plunger) further comprises a solid, such as a dry powder/cake.

In one embodiment, one or more chambers (for example the front and/or back chamber) further comprises a fluid. In one embodiment, the front chamber (for example proximal to a syringe nozzle) further comprises a fluid. In one embodiment, the back chamber (for example proximal to a syringe plunger) further comprises a fluid.

In one embodiment, one or more chambers (for example the front and/or back chamber) further comprises a gas, for example an inert gas. In one embodiment, the front chamber (for example proximal to a syringe nozzle)further comprises a gas, such as an inert gas. In one embodiment, the back chamber (for example proximal to a syringe plunger) further comprises a gas, such as an inert gas.

In one embodiment, the chamber comprising a gas is at a higher pressure than the other chamber. This feature has the benefit of preventing moisture from the other chamber (for example if the other chamber comprises a fluid) from leaking across to the chamber comprising the gas via the conduit of the annular member. Examples of solids include but are not limited to powders and cakes. These for example could be lyophilised drugs, powdered chemicals and the like. Examples of fluids include but are not limited to buffers, such as biological buffers, and pharmaceutically acceptable diluents or carriers, which could be used to reconstitute lyophilised drugs for example. Excipients may include but are not limited to lactose, dextrin, glucose, sucrose, sorbitol, starch, sugars, sugar alcohols and cellulose.

In one embodiment, the gas is an inert gas. In one embodiment, the inert gas is selected from the group comprising nitrogen (N), helium (He), neon (Ne), argon (Ar), krypton (Kr), xenon (Xe), radon (Rn) or oganesson (Og). In one embodiment, the inert gas is nitrogen, helium or argon. In one embodiment, the gas is nitrogen. In one embodiment, the gas is helium. In one embodiment, the gas is argon.

In one aspect, there is provided a clamp for a syringe (for example a polymer syringe), comprising: two arms configured to receive a barrel of a syringe; wherein the arms are linked to each other via a deformable connection; wherein the connection expands to allow of insertion of the barrel into the arms, after which the connection contracts to exert a pressure on the exterior surface of the barrel to create a constriction in the barrel; wherein: the pressure exerted by clamp works co-operatively with the barrel of the syringe to: prevent movement of the plunger thereby locking the syringe, or prevents movement of an internal body (for example a device as defined above) in the syringe comprising a valve, which is actuated by a change in fluid pressure or by a mechanical force.

The clamp is designed to work in conjunction with the device of the present disclosure. Advantageously, the clamp’s arms are appropriately dimensioned to receive the barrel of the syringe to be used in conjunction with the clamp. The dimensions of the arms can be adjusted and adapted as necessary depending on the dimensions of the syringe.

Further advantageously, the clamp is configured to apply just the right amount of pressure to constrict the syringe barrel, but when the clamp is removed the barrel returns to its original dimensions. In other words, the clamp is able to introduce a temporary constriction in the barrel, without permanently altering the dimensions of the barrel, i.e. without deforming the barrel, which could negatively impact the normal function of the syringe.

In one embodiment, the pressure exerted on the exterior surface of the barrel is about 0.8 to 1.2 MPa, such as 1 MPa. In one embodiment, the pressure is about 0.9 to 1.1 MPa. In one embodiment, the pressure is about 0.8, 0.85, 0.9, 0.95, 1.00, 1.05, 1.10, 1.15 or 1.20 MPa. In one embodiment, the pressure is about 1 MPa.

In one embodiment, the clamp further comprises a locking means for securing the position of a syringe plunger. In one embodiment, the locking means is a clip configured to fit around the plunger. The benefit of the clip is that it is a simple and effective means for locking the position of the syringe plunger. For example, the clip can be as simple as a notch in the clamp which is designed to snap-fit around the plunger, thereby locking it in place. Thus, in one embodiment, the locking means is a notch in the clamp. In one embodiment, the locking means, such as a notch is unitary or a single part with the clamp.

In one aspect, there is further provided a clamp comprising a pair of clamps as defined above, wherein the pair of clamps are connected to each other. The advantage of such a clamp is that it locks the position of the plunger more securely given there are a pair of clamps attached to the plunger instead of a single clamp. The clamps can be connected to each other using various connected, including but not limited to rods, poles and the like. Hence, in one embodiment, the clamps are connected to each other via rods or poles.

In one aspect, there is provided a method of mixing a fluid and a solid or two fluids in a fluiddispensing vessel as defined above, comprising repeatedly withdrawing/pulling and releasing the syringe plunger, thereby creating turbulence and shear to aid in the mixing of the fluid and solid or fluids. Additionally, the present inventors have found that the presently disclosed device allows for an air-tight seal to be formed in the front chamber of the syringe, which allows the front chamber to function as a pneumatic spring. By repeatedly plunging against this spring, extreme turbulence and shear can be created in the syringe as the fluid is forced back and forth through the conduit of the annular member, which helps to accelerate the mixing process.

For example, in an experiment a 1/4 dental disclosure tablet was dissolved in 2.5 ml of water, first by drawing up 2.5ml into a syringe containing the solid and shaking the entire syringe until the tablet dissolved - this took around 3-4 minutes. The experiment was then repeated using the disclosed method and this time complete dissolution took only around 20 seconds. Hence, the presently disclosed method significantly improves the efficiency of mixing a fluid and solid (or two fluids) in a fluid dispensing vessel compared to normal agitation of the fluid dispensing vessel.

Thus, in one embodiment, there is provided a method of mixing a fluid and a solid or two fluids in a fluid-dispensing vessel, such as a syringe as defined above, comprising the steps of: a) withdrawing/pulling the syringe plunger; b) releasing the syringe plunger; and c) repeating steps a) and b).

In one embodiment, steps a) and b) are repeated until the fluid and solid or fluids are sufficiently mixed. In one embodiment, steps a) and b) are repeated until the fluid and solid or fluids are completely mixed.

In one embodiment, the method results in the production of turbulence and/or shear in the syringe as fluid is forced through the conduit ("back-flushing”). In one embodiment, the fluiddispensing vessel is a syringe, such as a polymer or glass syringe, in particular a fluid-dispensing vessel comprising a device wherein the valve is a rod. In one embodiment, the method is for mixing a fluid and a solid or two fluids in a small syringe, for example a 1 ml syringe. Advantageously, because the space within the chamber of a small syringe is so small, inverting or agitating the syringe will not mix a liquid and fluid well. This is because the small volume of fluid does not have enough natural inertia to overcome the hydraulic lock created in the long thin front chamber. Thus, the presently disclosed method of mixing is the only way to effectively mix in a long series 1ml syringe, which is the most common size for prefilled syringe).

As described above, the conduit may be preferentially shaped, for example wherein one or both ends of the conduit are tapered to produce a funnel or conical shape, so as to optimise the mixing of a fluid and solid or two fluids. Such a conduit may be especially useful when employed in the above method in order to increase the amount of turbulence and/or shear.

For example, tests were performed to compare the mixing of two liquids in 5 ml syringes comprising an annular member with cylindrical conduit (Figure 1A) vs an annular member with a curved conical conduit (Figure 1C). 1.6ml of coloured water was placed in the back chamber and 1ml of coloured glycerol of higher viscosity 1500cps was placed in the front chamber of each syringe. The syringe with the cylindrical conduit required 5 back-flushes for effective mixing whereas the curved conical conduit only required 2 back-flushes to achieve the same level of mixing based on the appearance of the homogeneity of the two liquids. The experiment was also repeated with a higher viscosity liquid (honey 5000cps) and water, with a similar reduction in number of required back- flushes observed for the curved conical conduit vs cylindrical conduit.

Thus, in one embodiment, the method of mixing is employed in a fluid-dispensing vessel comprising a device comprising a conduit that is preferentially shaped so as to optimise the mixing of a fluid and solid or two fluids. In one embodiment, the conduit is curved conical shaped, for example wherein the conduit has a double-sided curved conical shape.

The disclosed method of mixing may be automated by a syringe driver which has been configured to withdraw/pull and release the syringe plunger or to perform steps a) to c) as described above. Therefore, in one embodiment, the withdrawing and releasing of the syringe plunger or steps a) to c) are performed by a syringe pump/driver.

Alternatively, in the case where the fluid-dispensing vessel is a cartridge for an auto-injector, the auto-injector may be configured to perform multiple back-flush cycles in order to mimic the aforementioned action of withdrawing/pulling and releasing a syringe plunger. Hence, the disclosed method of mixing is also applicable to a catridge with auto-injector set-up.

Accordingly, in one embodiment, there is provided a method of mixing a fluid and a solid or two fluids in a cartridge for an auto-injector, wherein the cartridge comprises a device as defined above and has two or more separate chambers, and wherein the auto-injector is configured to perform multiple back-flush cycles such that fluid repeatedly flows from one chamber to another chamber via the conduit. Also provided are a syringe pump comprising a fluid-dispensing vessel, such as a syringe as defined above and an auto-injector comprising a fluid-dispensing vessel, such as an auto-injector catridge as defined above.

Comprising in the context of the present specification is intended to mean "including”.

Where technically appropriate, embodiments of the invention may be combined. Embodiments are described herein as comprising certain features/elements. The disclosure also extends to separate embodiments consisting or consisting essentially of said features/elements.

Technical references such as patents and applications are incorporated herein by reference.

The application claims priority from GB2212155.2 filed on 22 Aug 2022, GB2215071.8 filed on 13 Oct 2022 and GB2308015.3 filed on 30 May 2023, all of which are incorporated herein by reference, and any of which may be employed to correct errors in the present specification.

The figures may be used as basis to amend the claims. Individual features in a given figure may be used in a general amendment of the claims without reference to the other components of the figure.

Any embodiments specifically and explicitly recited herein may form the basis of a disclaimer either alone or in combination with one or more further embodiments.

BRIEF DESCRIPTION OF DRAWINGS

The present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

Figure 1A shows an annular member of the present disclosure

Figure IB shows an annular member of the present disclosure with a dished upper surface

Figure 1C shows an annular member of the present disclosure with a curved conical conduit

Figure ID shows an annular member of the present disclosure with a double-sided curved conical conduit

Figure IE shows an annular member of the present disclosure with a double-sided (noncurved) conical conduit

Figure 2A shows a plug of the present disclosure

Figure 2B shows a plug of the present disclosure comprising a piercing means

Figure 3A shows device of the present disclosure wherein the valve is a plug

Figure 3B shows device of the present disclosure wherein the valve is a plug and the annular member has a dished upper surface as shown in Figure IB.

Figure 3C shows device of the present disclosure wherein the valve is a spherical member

Figure 3D shows device of the present disclosure wherein the valve is a plug comprising a piercing means of the present disclosure

Figure 3E shows a device of the present disclosure wherein the valve is a self-sealing membrane Figure 3F shows a device of the present disclosure wherein the valve is a burstable membrane

Figure 4A shows a clamp of the present disclosure

Figure 4B shows a clamp of the present disclosure when attached to a syringe

Figure 4C shows a clamp of the present disclosure when attached to a syringe plunger

Figure 5 A shows an alternative clamp of the present disclosure

Figure 5B shows an alternative clamp of the present disclosure attached to a syringe plunger

Figure 6 shows a fluid-dispensing vessel of the present disclosure employing the device of Figure 3A wherein the vessel is pre-filled for dual stage dispensation

Figure 7 shows a fluid-dispensing vessel of the present disclosure employing the device of Figure 3B wherein the vessel is pre-filled for dual stage dispensation

Figure 8 shows a fluid-dispensing vessel of the present disclosure employing the device of Figure 3A wherein the vessel is pre-filled with two fluids that are pre-mixed before dispensation

Figure 9 shows a fluid-dispensing vessel of the present disclosure employing the device of Figure 3A wherein the vessel is pre-filled with a fluid and solid that are pre-mixed before dispensation

Figure 10A shows a fluid-dispensing vessel of the present disclosure wherein the valve is a plug connected to a syringe plunger, and wherein the vessel pre-filled with a fluid and solid that are pre-mixed before dispensation

Figure 1OB shows a fluid-dispensing vessel with a staked needle of the present disclosure wherein the valve is a plug connected to a syringe plunger, and wherein the vessel pre-filled with a fluid and solid that are pre-mixed before dispensation

Figure IOC shows a fluid-dispensing vessel with a staked needle of the present disclosure wherein the valve is a plug connected to a syringe plunger, and wherein the vessel pre-filled with two fluids that are pre-mixed before dispensation

Figure 11 shows a fluid-dispensing vessel of the present disclosure employing the device of Figure 3B, wherein the vessel is pre-filled with a fluid and solid that are pre-mixed before dispensation

Figure 12 shows a fluid-dispensing vessel of the present disclosure employing the device of Figure 3D, wherein the vessel is pre-filled with a fluid and solid that are pre-mixed before dispensation

Figure 13 shows a fluid-dispensing vessel of the present disclosure employing the device of Figure 3E, wherein the vessel is pre-filled with a fluid and solid that are pre-mixed before dispensation

Figure 14 shows a fluid-dispensing vessel of the present disclosure employing the device of Figure 3C, wherein the vessel is pre-filled with a fluid and solid that are pre-mixed before dispensation

Figure 15 shows a fluid-dispensing vessel of the present disclosure wherein the annular member comprises a flexible skirt, and wherein the vessel is pre-filled with a fluid and solid that are pre-mixed before dispensation Figure 16 shows a fluid-dispensing vessel of the present disclosure wherein a fluid in the back chamber is hydraulically locked, and wherein the vessel is pre-filled with a fluid and solid that are pre-mixed before dispensation

Figure 17A shows a valve of the present disclosure comprising a syringe nozzle cap and rod with a waist,

Figure 17B shows a valve of the present disclosure comprising a syringe nozzle cap and rod with narrowed end

Figure 18 shows a valve of the present disclosure comprising a syringe nozzle cap, rod and handle

Figure 19A-E shows a fluid-dispensing vessel of the present disclosure employing the valve of Figure 17A in conjunction with the annular member of Figure 1A, and wherein the vessel is pre-filled with a fluid and solid that are pre-mixed before dispensation

Figure 20A-D shows a fluid-dispensing vessel of the present disclosure employing the valve of Figure 17B in conjunction with the annular member of Figure 1A, and wherein the vessel is pre-filled with a fluid and solid that are pre-mixed before dispensation

Figure 21A-D shows a fluid-dispensing vessel of the present disclosure employing the valve of Figure 18 in conjunction with the annular member of Figure 1A, and wherein the vessel is pre-filled with a fluid and solid that are pre-mixed before dispensation Figure 22A-C shows a fluid-dispensing vessel of the present disclosure employing a valve comprising a syringe nozzle cap and rod in conjunction with the annular member of Figure 1C, and wherein the vessel is pre-filled with two different fluids that are pre-mixed before dispensation

Figure 23A-D shows a fluid-dispensing vessel of the present disclosure employing a valve comprising a syringe nozzle cap and rod with rounded end in conjunction with the annular member of Figure ID, and wherein the vessel is pre-filled with a fluid and solid that are pre-mixed before dispensation

Figure 23E shows a comparison between insertion of a rod with a rounded end vs a rod without a rounded end into the conduit of the annular member of Figure ID.

Figure 24A shows the test setup for the experiment described in Example 19 for a 1 ml syringe

Figure 24B shows the test setup for the experiment described in Example 19 for a 2.5 ml syringe

Figure 25A shows the force vs plunge distance graph for a 1 ml syringe comprising liquid in one chamber, solid in the other chamber, premixed before dispensation

Figure 25B shows the force vs plunge distance graph for a 1 ml syringe comprising liquid in one chamber, a different liquid in the other chamber, premixed before dispensation

Figure 25C shows the force vs plunge distance graph for a 1 ml syringe comprising liquid in one chamber, a different liquid in the other chamber, dispensed sequentially Figure 25D shows the force vs plunge distance graph for a 2.5 ml syringe comprising liquid in one chamber, solid in the other chamber, premixed before dispensation

Figure 25E shows the force vs plunge distance graph for a 2.5 ml syringe comprising liquid in one chamber, a different liquid in the other chamber, premixed before dispensation

Figure 25F shows the force vs plunge distance graph for a 2.5 ml syringe comprising liquid in one chamber, a different liquid in the other chamber, dispensed sequentially

EXAMPLES

Example 1 - Device of the present disclosure

Figure 1A shows annular member 2 having conduit 3 and ribs 7. The sectional view shows conduit 3 in greater detail. In the figure, conduit 3 is configured specifically for wherein the valve is a plug 4. In this respect, conduit 3 has a narrowing that prevents plug 4 from falling out of the conduit when plug 4 is inserted into the conduit

Figure IB shows the annular member of Figure 1A with a dished upper surface 48. The dished upper surface 48 provides space for the plug 4 to enter when the annular member contacts the end of the syringe barrel and the fluid pressure acts to move the plug 4 (see Figure 7)

Figures 1C to ID show annular member 2 having conduit 3 which has been modified to optimise the mixing of a fluid and a solid or two fluids.

Figure 2A shows a plug 4 having lip 11, ribs 7 and flexible arms 9. The flexible arms 9 can fold to facilitate the assembly of plug 4 with annular member 2 to produce device 1 shown in Figure 3 A.

Figure 2B shows an alternative plug 5 having a barb 13 and ribs 7. The barb 13 has a passage 11 which allows fluid to pass through the plug 5.

Figures 3A to 3F show various embodiments of the presently disclosed device 1.

Figure 3A shows device 1 comprising the plug of Figure 2A. Note that the plug 4 cannot fall out of the conduit 3 because of the narrowed section of conduit 3. At the same time, arms 9 prevent plug 4 from being pulled upwards out of the conduit 3.

Figure 3B shows device 1 comprising the plug of Figure 2A and the annular member of Figure

IB.

Figure 3C shows device 1 wherein ball 6 functions as a valve. Like in Figure 3A and 3B, conduit 3 has a narrowed section which prevents ball 6 from falling out of conduit 3.

Figure 3D shows device 1 comprising the plug of Figure 2B. The diagram on the right shows the position ofplug 4 when the barb 13 is used to pierce a burstable membrane 10 as shown in Figure 14.

Figure 3E shows device 1 wherein self-sealing membrane 8 functions as a valve. Self-sealing membrane 8 has a slit 15 which opens or closes (i.e. the slit is resealable) to allow or restrict the flow of fluid through conduit 3. Figure 3F shows device 1 wherein burstable membrane 10 function as a valve. Unlike the selfsealingmembrane 8, the burstable membrane 10 cannot be resealed to close off access to conduit 3 once it has ruptured, i.e., the valve cannot be closed once it is opened.

Example 2 - Clamp of the present disclosure

Figure 4A shows an embodiment of the presently disclosed clamp 12. The clamp 12 has clamp arms 17 which are appropriately dimensioned for the barrel and the plunger 16 of syringe 14. Notch 21 is appropriately dimensioned to attach to and secure plunger 16.

Figure 4B shows clamp 12 when attached to the barrel of syringe 14. Clamp arms 17 are configured to apply an appropriate amount of pressure to syringe 14 to constrict the barrel of syringe 14 when clamp 12 is attached. When clamp 12 is removed from the syringe, the barrel reverts to its original dimensions. Thus, clamp 12 is designed to apply sufficient pressure to constrict the syringe barrel without permanently deforming the syringe.

Figure 4C shows clamp 12 when attached to the plunger 16 of syringe 14. When attached to the plunger, clamp 12 locks the position of plunger 16. Notch 21 helps to provide a tight and secure fit.

Figure 5A and 5B show alternative clamp 18. This alternative clamp consists of a pair of the clamps of Figure 4A which are linked by rods 19. When attached to plunger 16, clamp 18 further prevents plunger 16 from being pushed into the syringe barrel.

The following examples demonstrate various uses of the presently disclosed device and fluiddispensing vessel comprising the device.

Example 3 - Dual-stage fluid dispensation using device comprising plug

Figure 6 shows an embodiment of the presently disclosed fluid-dispensing vessel employing the device of Figure 3 A.

The syringe 14 is pre-filled with two different fluids 20 and 21. Fluid 20 is located in the front chamber (proximal to the nozzle), whereas fluid 21 is located in the back chamber (proximal to the plunger 16). The presence of the presently disclosed device prevents the fluids from mixing during storage and/or delivery of the syringe. Syringe nozzle cap 30 helps to ensure sterility of the contents.

When ready to be used, clamp 12 is attached to the syringe barrel, thereby introducing a constriction in the barrel, and syringe nozzle cap 30 is removed. As plunger 16 is pushed into the barrel, annular member 2 moves and fluid 20 is dispensed. Fluid 22 does not flow through conduit 3 because plug 4 is blocking access to conduit 3, i.e. the valve is closed. This allows fluid 20 to be fully dispensed without any dispensation of fluid 22.

When annular member 2 reaches the position of the clamp, its movement is mechanically restrained due to the constriction in the barrel. When this happens, the application of fluid pressure to plug 4 by further depressing the plunger 16 causes the plug to move upwards, thereby opening the valve and allowing access to conduit 3. This in turn allows fluid 22 to be dispensed by depressing plunger 16. Hence, this example demonstrates how two different fluids can be sequentially dispensed using a device or fluid-dispensing vessel of the present disclosure.

Example 4 - Dual-stage fluid dispensation using device comprising plug and annular member with dished upper surface

Figure 7 shows an embodiment of the presently disclosed fluid-dispensing vessel employing the device of Figure 3B.

The syringe 14 is pre-filled with two different fluids 20 and 21. Fluid 20 is located in the front chamber (proximal to the nozzle), whereas fluid 21 is located in the back chamber (proximal to the plunger 16). The presence of the presently disclosed device prevents the fluids from mixing during storage and/or delivery of the syringe. Syringe nozzle cap 30 helps to ensure sterility of the contents.

When ready to be used, the syringe nozzle cap 30 is removed. As plunger 16 is pushed into the barrel, annular member 2 moves and fluid 20 is dispensed. Fluid 22 does not flow through conduit 3 because plug 4 blocks access to conduit 3, i.e. the valve is closed. This allows fluid 20 to be fully dispensed without any dispensation of fluid 22.

When annular member 2 reaches the end of the barrel, its movement is mechanically restrained due to the contact between the annular member and the narrower end of the syringe barrel. When this happens, the application of fluid pressure to plug 4 by further depressing the plunger 16 causes the plug to move upwards, thereby opening the valve and allowing access to conduit 3. This in turn allows fluid 22 to be dispensed by depressing plunger 16.

Hence, this example demonstrates how two different fluids can be sequentially dispensed using a device or fluid-dispensing vessel of the present disclosure without the use of a clamp.

Example 5 - Combination (fluid-fluid) pre-mixed before dispensation using device comprising plug

Figure 8 shows another embodiment of the presently disclosed fluid-dispensing vessel employing the device of Figure 3A. The upper surface of the annular member 2 in this embodiment may be dished (see Figure 1A) or flat (as shown in Figure IB and depicted in Figure 8)

This embodiment shows a setup which is similar to Example 3. The key difference is the position of clamp 12 - in this case clamp 12 is attached to the middle of the syringe barrel instead of near the syringe nozzle as shown in Figure 7. The position of the clamp affects the location of the constriction in the barrel, which in turn affects the position at which the movement of the annular member 2 is restrained. This in turn determines the position where the plug 4 moves to allow access to conduit 3, i.e. it determines the position where the valve is opened.

Thus, because the annular member is restrained earlier, the valve is opened earlier. This allows fluid 22 to enter the front chamber via conduit 3, where it mixes with fluid 20 to form mixed fluid 24. The syringe 14 can optionally be shaken to aid in the mixing. When mixed fluid 24 is ready for dispensation, clamp 12 is removed from the syringe barrel. This allows annular member 2 to move freely again, allowing the plunger 16 to be further depressed and mixed fluid 24 to be dispensed.

Hence, this example demonstrates how two different fluids can be kept separate during storage and/or delivery, and pre-mixed before dispensation. This could be useful for example where two different liquid drugs need to be combined to form a final combined product before administration, particularly whereby the final combined product has low stability, and hence it is especially desirable for the final combined product to be generated just prior to dispensation.

Example 6 - Combination (fluid-solid) pre-mixed before dispensation using device comprising plug

Figure 9 shows yet another embodiment of the presently disclosed fluid-dispensing vessel employing the device of Figure 3A. The upper surface of the annular member 2 in this embodiment may be dished (see Figure 1A) or flat (as shown in Figure IB and depicted in Figure 9)

Here the setup is similar to Example 5. However, instead of two fluids, the front chamber of the syringe 14 is pre-filled with solid 26 and the back chamber is pre-filled with fluid 22. Fluid 22 and solid 26 can thus be pre-mixed to form mixed fluid 28, which can then be dispensed as per Example 5.

Therefore, this example demonstrates how a solid and fluid can be kept separate during storage and/or delivery, and pre-mixed to form a final fluid before dispensation. This allows for a syringe for example to be pre-filled with a lyophilised drug and a suitable diluent for reconstituting the drug when ready for use. Since lyophilised drugs tend to be more stable than their liquid counterparts, this could result in a longer shelf-life for the pre-filled syringe compared to prefilling the syringe with the liquid form of the drug.

Example 7 - Combination (fluid-solid) pre-mixed before dispensation using backpressure and plug connected to plunger

Figure 10A shows an embodiment of the presently disclosed fluid-dispensing vessel wherein the plug 4 is connected to the plunger via plunger seal 32.

Like in Example 9, the syringe 14 is pre-filled with a fluid 20 and a solid 26. However, this time the location of the fluid and solid are swapped around - fluid 20 is in the front chamber whereas solid 26 is in the back chamber.

When fluid 20 and solid 26 are ready to be combined, nozzle cap 30 is kept on the syringe and the plunger is withdrawn instead of pushed into the barrel. This creates a negative fluid pressure in the front chamber as the plunger is withdrawn, which restrains the movement of annular member 2. As the plunger is further withdrawn, plug 4 which is connected to plunger 16 via plunger seal 32 is separated from conduit 3. This opens the valve, which allows fluid 20 to flow into the back chamber via conduit 3. This in turn allows fluid 20 and solid 26 to be mixed thus producing mixed fluid 28. The syringe 14 can optionally be shaken to aid in the mixing.

Finally, when final fluid 28 is ready to be dispensed, nozzle cap 30 is removed. This relieves the fluid pressure exerted on annular member 2 and allows it to move freely again. Mixed fluid 28 can then be dispensed by depressing plunger 16.

Figures 10B (depicting a fluid and solid premixed before dispensation) and IOC (depicting two fluids premixed before dispensation) feature embodiments that are similar to the embodiment of Figure 10A. The main difference between them and Figure 10A is the presence of staked needle 44 attached to the fluid dispensing vessel. Nonetheless, the method for using the embodiments of Figures 10B and 9C is the same as that of Figure 10A.

Hence, this example demonstrates that versatility of the presently disclosed device, wherein the location of the solid and fluid in the chambers adjusted as desired; and fluid pressure as opposed to a clamp can be used to restrain the annular member.

Example 8 - Combination (fluid-solid) pre-mixed before dispensation using device comprising ball

Figure 11 shows an embodiment of the presently disclosed fluid-dispensing vessel employing the device of Figure 3C.

The setup is similar to Example 5, however here the device employs a ball 6 instead of a plug as a valve. When solid 26 and fluid 22 are ready to be mixed, nozzle cap 30 is removed and a constriction in the barrel is introduced by using finger-pressure as indicated by the arrows. This restrains the movement of annular member 2, whereupon the application of fluid pressure to ball 6 causes it to be dislodged from conduit 3. This in turn opens the valve and permits the flow of fluid 22 into the front chamber via conduit 3 for mixing with solid 26 to form mixed fluid 28. As a bonus, the ball 6 serves as an agitator which helps to thoroughly mix fluid 22 and solid 26 as syringe 14 is shaken.

Finally, when mixed fluid 28 is ready to be dispensed, the finger pressure is released, thus allowing annular member 2 to freely move once more. Mixed fluid 28 can then be dispensed by depressing plunger 16.

Example 9 - Combination (fluid-solid) pre-mixed before dispensation using device comprising self-sealing membrane

Figure 12 shows an embodiment of the presently disclosed fluid-dispensing vessel employing the device of Figure 3E. The setup is similar to Example 7, however here the device employs selfsealing membrane 8 instead of a ball as a valve.

When solid 26 and fluid 22 are ready to be mixed, nozzle cap 30 is removed and a constriction in the barrel is introduced by using finger-pressure as indicated by the arrows. This restrains the movement of annular member 2, whereupon the application of fluid pressure to self-sealing membrane 8 by further depressing plunger 16 causes slit 15 to open, i.e., causes the valve to open. This in turn permits the flow of fluid 22 into the front chamber via conduit 3 for mixing with solid 26 to form mixed fluid 28. The syringe 14 can be optionally shaken to aid in mixing fluid 22 with solid 26.

Finally, when mixed fluid 28 is ready to be dispensed, the finger pressure is released, thus allowing annular member 2 to freely move once more. Mixed fluid 28 can then be dispensed by depressing plunger 16.

Example 10 - Combination (fluid-solid) pre-mixed before dispensation using device comprising burstable membrane

Figure 13 shows an embodiment of the presently disclosed fluid-dispensing vessel employing the device of Figure 3F. The setup is similar to Example 9, however here the device employs burstable membrane 10 instead of a self-sealing membrane 8 as a valve.

When solid 26 and fluid 22 are ready to be mixed, nozzle cap 30 is removed and a constriction in the barrel is introduced by using finger-pressure as indicated by the arrows. This restrains the movement of annular member 2, whereupon the application of fluid pressure to burstable membrane 10 by further depressing the plunger 16 causes the membrane 10 to burster rupture. This causes the valve to open, thereby allowing the flow of fluid 22 into the front chamber via conduit 3 for mixing with solid 26 to form final fluid 28. The syringe 14 can be optionally shaken to aid in mixing fluid 22 with solid 26.

Finally, when mixed fluid 28 is ready to be dispensed, the finger pressure is released, thus allowing annular member 2 to freely move once more. Mixed fluid 28 can then be dispensed by depressing plunger 16.

Example 11 - Combination (fluid-solid) pre-mixed before dispensation using device with plug comprising piercing means

Figure 14 shows another embodiment of the presently disclosed fluid-dispensing vessel employing the device of Figure 3D.

When solid 26 and fluid 22 are ready to be mixed, nozzle cap 30 is removed and a constriction in the barrel is introduced by using finger-pressure as indicated by the arrows. This restrains the movement of annular member 2, whereupon the application of fluid pressure to the plug 5 by further depressing the plunger 16 causes plug 5 to move upwards. This causes the barb 13 to pierce the membrane, creating an opening in the membrane. This in turn causes the valve to open, thereby allowing the flow of fluid 22 into the front chamber for mixing with solid 26, to form final fluid 28. The passage 11 in plug 5 helps to ensure smooth flow of the fluid through conduit 3. The syringe 14 can be optionally shaken to aid in mixing fluid 22 with solid 26.

Finally, when mixed fluid 28 is ready to be dispensed, the finger pressure is released, thus allowing annular member 2 to freely move once more. Mixed fluid 28 can then be dispensed by depressing plunger 16. Accordingly, Examples 8 to 11 demonstrates that different embodiments of the disclosed device can be used and that finger pressure can be used as an alternative to a clamp.

Example 12 - Combination (fluid-solid) pre-mixed before dispensation using device with annular member comprising flexible skirt

Figure 15 shows yet another embodiment of the presently disclosed fluid-dispensing vessel employing a device with an annular member 2 comprising a flexible skirt 23.

When solid 26 and fluid 22 are ready to be mixed, nozzle cap 30 is removed and the plunger 16 is depressed. This creates a positive fluid pressure in the back chamber of the syringe which acts on the annular member 2. This causes the flexible skirt 23 to expand radially (as indicated by the small arrows), which in turn restrains the movement of annular member 2. As plunger 16 is further depressed, this exerts a positive fluid pressure on plug 4, causing it to move upwards, thereby opening the valve. Fluid 22 is subsequently able to flow into the front chamber via conduit 3 for mixing with solid 26 to form mixed fluid 28. The syringe 14 can be optionally shaken to aid in mixing fluid 22 with solid 26.

The opening of the valve results in a reduction in the radial pressure exerted by the flexible skirt 23, which permits annular member 2 to freely move once again. Mixed fluid 28 can then be dispensed by depressing plunger 16.

Example 13 - Combination (fluid-solid) pre-mixed before dispensation using an annular member in combination with a hydraulically locked conduit

Figure 16 shows a fluid dispensing vessel of the present disclosure with a hydraulically locked back chamber.

Fluid 22 in the back chamber of the syringe 14 is hydraulically locked by introducing a small positive pressure with inert gas in the front chamber of syringe 14 during filling. Due to the hydraulic lock, fluid 22 cannot flow through conduit 3 to access the front chamber where solid 26 is located.

When solid 26 and fluid 22 are ready to be mixed, the nozzle cap 30 is removed, this releases the pressure in the front chamber, hence releasing the hydraulic lock. Following this, plunger 16 can be depressed to cause fluid 22 to flow into the front chamber for mixing with solid 26 to produce mixed fluid 28. The syringe 14 can be optionally shaken to aid in mixing fluid 22 with solid 26. Plunger 16 can then be depressed to dispense fluid 28.

Example 14 - Combination (fluid-solid) pre-mixed before dispensation using device comprising syringe nozzle cap and rod with waist

Figures 19A to 19E shows a fluid dispensing vessel of the present disclosure with a device comprising annular member 2 and a syringe nozzle cap 30 comprising a rod 34 and waist 36 of Figure 17A.

Rod 34 has a slight interference with the nozzle of the syringe 14 such that even when the nozzle cap 30 is pulled away from the syringe 14, rod 34 will maintain an airtight seal with the nozzle of syringe 14. Rod 34 contains a section of reduced diameter to form a waist 36. As the cap 30 is pulled away from syringe 14, rod 34 creates a sliding seal with the nozzle of syringe 14 until the waist 36 is coincident with the nozzle outlet of syringe 14. In this position the air in the front chamber can be expelled through the nozzle of syringe 14.

As the base of rod 34 is an interference fit with the conduit 3 of annular member 2, this creates a seal with the internal diameter of the barrel of syringe 14. Thus, the action of pulling the cap 30 away from the nozzle of syringe 14 creates a negative fluid pressure in the back chamber, thereby restraining annular member 2. By continuing to pull nozzle cap 30 to the position where the waist 36 is coincident with the nozzle outlet of syringe 14 (thereby applying a mechanical force to rod 34), this opens the valve and allows fluid 22 to enter the front chamber via conduit 3 to mix with solid 26 as shown in Figure 19B .

Once all of fluid 22 has been plunged into the front chamber (see Figure 19C), the cap 30 can be pulled away further from the syringe 14 to re-engage the full diameter of the rod 34 to restore an airtight seal. In this position the syringe 14 can be agitated to mix solid 26 with fluid 22 in order to produce mixed fluid 28.

Alternatively, as shown in Figure 19D, in this position plunger 16 can be displaced downwards to draw fluid 22 and solid 26 through the conduit 3 into the back chamber, this action causes a negative air pressure in the front chamber which, when plunger 16 is released, will immediately pull the mixture back through conduit 3 into the front chamber. The significant increase of velocity of the fluid mixture through the conduit 3 creates turbulence and shear to aid the mixing of fluid 22 and solid 26, and can be repeated until complete dissolution of solid 26 has taken place, creating mixed fluid 28.

Thus, this embodiment allows for an improved method of mixing a solid and fluid (or two fluids) in a fluid dispensing vessel before dispensation.

Regardless of the method used to mix solid 26 with fluid 22, the cap 30 and rod 34 can now be fully retracted from the nozzle of syringe 14 and mixed fluid 26 can be administered from the syringe in the usual manner (see Figure 19E).

For glass syringes, there may be insufficient compliance in the nozzle of syringe 14 to create a sliding seal with the rod 34 and so there are provided two further embodiments which work particularly well for glass syringes, as depicted in Examples 14 and 15.

Example 15 - Combination (fluid-solid) pre-mixed before dispensation using device comprising syringe nozzle cap and rod with narrowed end

Figures 20A to 20D shows a fluid dispensing vessel of the present disclosure with a device comprising annular member 2 and a syringe nozzle cap 30 comprising a rod 34 with narrowed end 38 of Figure 17B.

This setup is similar to Example 14 in thatthe nozzle cap 30 also contains a rod 34 to create a seal with the annular member 2 by having a slight interference fit of the rod 34 in the conduit 3 (see Figure 20A). As in Example 14, pulling cap 30 away from the nozzle of syringe 14 creates a negative fluid pressure in the back chamber, thereby restraining annular member 2. Applying a mechnical force to rod 34, i.e. by continuing to pull cap 30, opens the valve and allows fluid 22 to enter the front chamber via conduit 3 to mix with solid 26 (see Figure 20B).

In this embodiment, the narrowed end 38 of rod 34 facilitates replacing nozzle cap 30 and relocating rod 34 in conduit 3, which also aids in the re-sealing the front chamber so that syringe 14 may be agitated to mix the solid 26 with fluid 22, as shown in Figure 20C. Once fully dissolved the cap 30 with rod 34 can be removed completely and the mixed fluid 28 can be dispensed from syringe 14 in the usual manner as shown in Figure 20D.

Example 16 - Combination (fluid-solid) pre-mixed before dispensation using device comprising syringe nozzle cap and rod with handle

Figure 21A to 2 ID shows a fluid dispensing vessel of the present disclosure with a device comprising annular member 2, and a syringe nozzle cap 30 and rod 34 with handle 40 of Figure 18.

In Figure 21A, in contrast to Examples 13 and 14, rod 34 further includes handle 40 which facilitates gripping the rod 34 to slide rod 34 relative to nozzle cap 30 (see Figure 18). In addition, whereas rod 34 is connected to cap 30 in Figures 17A and 17B, rod 34 is not connected to cap 30 in Figure 18. Instead, rod 34 slidably engages with cap 30 to form an interference fit which maintains the seal of the front chamber of syringe 14.

As shown in Figure 21B, pulling handle 40 away from cap 30 creates a negative fluid pressure in the back chamber, thereby restraining annular member 2. Applying a mechnical force to rod 34, i.e. by continuing to pull up handle 40, opens the valve and allows fluid 22 to enter the front chamber via conduit 3 to mix with solid 26.

Since cap 30 remains in place over the nozzle of syringe 14 (in contrast with Examples 14 and 15), the front chamber remains sealed. Hence, the air within the front chamber will be pressurised and when the plunger 16 is released the air pressure will push fluid 22 and solid 26 back through conduit 3 into the back chamber. Repeated plunging against the air pressure will again use the turbulence and shear generated by this action to facilitate the mixing of fluid 22 and solid 26 (see Figure 21C). Once complete dissolution has taken place to form mixed fluid 28, this can then be dispensed from syringe 14 in the usual manner (see Figure 2 ID).

This particular embodiment may be particularly suitable for glass syringes, where it is desirable to employ the improved method of pre-mixing a solid and fluid (or two different fluids) in a fluid dispensing vessel before dispensation.

Example 17 - Combination (fluid-fluid) pre-mixed before dispensation using device comprising syringe nozzle cap and rod, and annular member with curved conical conduit Figures 22A to 22C shows a fluid dispensing vessel of the present disclosure with a device comprising annular member 2 with curved conical conduit (Figure 1C) and a syringe nozzle cap 30 comprising a rod 34 .

The setup and operation is similar to Example 14. As in Example 14, pulling cap 30 away from the nozzle of syringe 14 creates a negative fluid pressure in the back chamber, thereby restraining annular member 2. Applying a mechanical force to rod 34, i.e. by continuing to pull cap 30, opens the valve and allows fluid 22 to enter the front chamber via conduit 3 to mix with fluid 20. Next plunger 16 can be repeated displaced downwards to use the improved method of mixing described in Example 13. See Figure 22B.

However, in this embodiment, in contrast to Example 13, annular member 2 comprises a curved conical conduit 3 as depicted in Figure 1C. The curved conical conduit 3 has the technical benefit of increasing the turbulence and shear created when fluid 22 is pulled and pushed through the conduit 3 during the mixing. This results in a significantly improved mixing action, which is particular useful when attempting to pre-mix two fluids, wherein one or both of the fluids have a high viscosity. Once complete dissolution has taken place to form mixed fluid 28, this can then be dispensed from syringe 14 in the usual manner (see Figure 22C).

This Example thus demonstrates the benefits of an annular member 2 comprising a conduit 3 that has been modified to further improve the mixing action achievable using the disclosed method of mixing.

Example 18 - Combination (fluid-solid) pre-mixed before dispensation using device comprising syringe nozzle cap and rod with rounded end, and annular member with double tapered conduit

Figures 23A to 23C shows a fluid dispensing vessel of the present disclosure with a device comprising annular member 2 with curved conical conduit (Figure ID) and a syringe nozzle cap 30 comprising a rod 34 with hemi-spherical end 46.

The setup and operation is similar to Example 17. As in Example 17, pulling cap 30 away from the nozzle of syringe 14 creates a negative fluid pressure in the back chamber, thereby restraining annular member 2. Applying a mechanical force to rod 34, i.e. by continuing to pull cap 30, opens the valve and allows fluid 22 to enter the front chamber via conduit 3 to mix with solid 26. See Next plunger 16 can be repeated displaced downwards to use the improved method of mixing described in Example 13. See Figure 23B.

However, in this embodiment, in contrast to Example 17, annular member 2 comprises a double curved conical conduit 3 as depicted in Figure ID. The double curved conical conduit 3 has the technical benefit of further increasing the turbulence and shear created when fluid 22 is pulled and pushed through the conduit 3 during the mixing. This results in an even better mixing action. In addition, the hemi-spherical end 46 of the rod 34 reduces the likelihood of the rod snagging on conduit 3 during initial assembly and filling of the syringe or during insertion of the rod into the conduit to reseal nozzle cap 30. See Figure 23E

Once complete dissolution has taken place to form mixed fluid 28, the nozzle cap 30 can be replaced as shown in Figure 23C to keep mixed fluid 28 sterile until mixed fluid 28 is ready for administration from syringe 14 in the usual manner (see Figure 23D).

This Example thus demonstrates the benefits of an annular member 2 comprising a conduit 3 and rod 34 that have been modified to further improve the mixing action achievable using the disclosed method of mixing and to improve the ease of re-sealing the nozzle cap 30 after the contents of the fluid-dispensing vessel have been mixed.

Example 19 - Experiments to test load vs plunge distance for presently disclosed device in 1 ml and 2.5 ml syringes

A series of experiments were conducted to test the load vs plunge distance for the presently disclosed device when employed in 1 ml and 2.5 syringes.

Figures 24A and B show the test equipment and bespoke jig used to generate load versus plunge distance for 6 different test configurations:

1. Liquid in one chamber, solid in the other chamber, premixed before dispensation in 1ml syringe (Figure 25 A)

2. Liquid in one chamber, a different liquid in the other chamber, premixed before dispensation in 1ml syringe (Figure 25B)

3. Liquid in one chamber, a different liquid in the other chamber, sequential dispensation in 1 ml syringe (Figure 25C)

4. Liquid in one chamber, solid in the other chamber, premixed before dispensation in 2.5 ml syringe (Figure 25D)

5. Liquid in one chamber, a different liquid in the other chamber, premixed before dispensation in 2.5 ml syringe (Figure 25E)

6. Liquid in one chamber, a different liquid in the other chamber, sequential dispensation in 2.5 ml syringe (Figure 25F)

3 samples were tested for each test configuration.

Figures 25A to F shows the results of the experiments. The degree of variance observed for the variance for the three samples tested for each embodiment is likely to be due to the devices being prototypes which were constructed using donor parts obtained from disassembled syringes. In particular, the disassembly process would have disrupted the finely dispersed silicon coating applied to the internal surface of the barrel of the syringe when these were originally manufactured, and would have also disrupted the silicon oil that was applied to the syringe stoppers. Hence, the variability observed between samples is likely to decrease substantially in the final product. Nonetheless, the break-loose and glide forces meausred are well below (typically 50% or less) the maximum permissible values of 15N break-loose and ION glide force according to the BS EN ISO 11608-3-2012 accepted specification for medical syringes.

Accordingly, these experiments demonstrate that the presently disclosed devices perform their intended function while adhering to the required standards for medical syringes. In particular, when employed in fluid-dispensing vessels, the devices enable the creation of two separate chambers in the fluid-dispensing vessel, allow the contents of the chambers to be dispensed either after they have been pre-mixed or allow for sequential dispensation.