Method and devices for lyophilizing, reconstituting, and administering a reconstituted agent

• US 20090131864A1
• Filed: 10/25/2005
• Published: 05/21/2009
• Est. Priority Date: 10/25/2004
• Status: Active Grant

• Current Assignee: Pharma Consult Ges.m.b.H. & Co Nfg KG
• Original Assignee: Pharma Consult Ges.m.b.H. & Co Nfg KG
• Inventors: Pickhard, Ewald
• Granted Patent: US 8,814,823 B2
• Time in Patent Office: Days
• US Class Current: 604/83
• CPC Class Codes: A61J 1/2089 Containers or vials which are to be joined to each other in order to mix their contents combinations of vial and syringe for mixing their contents A61J1/2096
• CPC Class Codes: A61M 2005/2451 preventing delivery before mixing is completed, e.g. by locking mechanisms
• CPC Class Codes: A61M 2005/3104 Caps for syringes without needle
• CPC Class Codes: A61M 2005/3106 Plugs for syringes without needle
• CPC Class Codes: A61M 2005/3121 via the proximal end of a syringe, i.e. syringe end opposite to needle cannula mounting end
• CPC Class Codes: A61M 2005/3123 having air entrapping or venting means, e.g. purging channels in pistons
• CPC Class Codes: A61M 2005/3142 Modular constructions, e.g. supplied in separate pieces to be assembled by end-user
• CPC Class Codes: A61M 2005/31598 having multiple telescopically sliding coaxial pistons encompassing volumes for components to be mixed
• CPC Class Codes: A61M 5/2448 comprising means for injection of two or more media, e.g. by mixing
• CPC Class Codes: A61M 5/284 comprising means for injection of two or more media, e.g. by mixing
• CPC Class Codes: A61M 5/286 upon internal pressure increase, e.g. pierced or burst A61M5/283 takes precedence
• CPC Class Codes: A61M 5/502 for blocking the piston
• CPC Class Codes: A61M 5/5086 for indicating if defective, used, tampered with or unsterile

Abstract

The invention relates to a method and a device for lyophilizing, reconstituting and administering a reconstituted substance. The device has an elongate housing comprising a dispensing-side front housing end and a housing end lying opposite it. A first chamber with a lyophilizate contained in it is disposed in the housing in the region of the front housing end, which is tightly sealed at its end facing the front housing end by means of a removable closure and in the direction of the rear housing end by means of a plunger. A second chamber is provided or formed in the housing in the region of the rear housing end, which is connected by means of at least one opening to the ambient atmosphere. This opening is closed by a membrane which is permeable to gas but not to bacteria.

Claims

1. Device for lyophilising, reconstituting and administering a reconstituted substance, with an elongate housing (3) comprising a dispensing-side front housing end (6) and a rear housing end (7) lying opposite it, and a first chamber (1) with a lyophilisate contained in it is provided or formed in the housing (3) in the region of the front housing end (6), which first chamber (1) is tightly sealed at its end facing the front housing end (6) by means of a removable closure (9) and by means of a plunger (11) in the direction of the rear housing end (7), and a second chamber (2) is provided or formed in the housing (3) in the region of the rear housing end (7), and at least one opening (13) connects the second chamber (2) to the ambient atmosphere and is closed by a membrane (14;

55) which is permeable to gas but not to bacteria, wherein a cartridge (12) containing a diluent is disposed in the second chamber (2) which is tightly sealed at its end remote from the front housing end (6) by means of a cartridge stopper (31) displaceable in the cartridge (12), and operating means (29) designed to co-operate with the cartridge stopper (31) are disposed on the rear housing end (7) which are provided with catch means (40, 41) which permit a movement of the operating means (29) in the direction towards the front housing end (6) only and prevent a movement in the opposite direction.

2. Device as claimed in claim 1, wherein the plunger (11) is disposed on the side of the membrane (55) facing the first chamber (1) and close to it.

3. Device as claimed in claim 2, wherein the plunger (11) is disposed at a distance of 0.1 to 30 mm, preferably 0.1 to 5 mm, from the membrane (55).

4. Device as claimed in one of claims 1 to 3, wherein the volume of the first chamber (1) is greater than the volume of the lyophilised substance.

5. Device as claimed in one of claims 1 to 4, wherein the air pressure in the first chamber (1) is higher than 1 bar or ambient air pressure.

6. Device as claimed in one of claims 1 to 4, wherein the air pressure in the first chamber (1) is lower than 1 bar or ambient air pressure.

7. Device as claimed in claim 1, wherein connection means (16;

75) are disposed between the first chamber (1) and the cartridge (12) which are designed to establish a connection between the interior of the cartridge (12) and the first chamber (1).

8. Device as claimed in claim 7, wherein the connection means (16;

75) comprise a cannula guide (17) displaceable in the housing (3), in which a connecting cannula (18) with one cannula end (19) directed towards the plunger (11) and one cannula end (20) directed towards the cartridge (12) is accommodated, and the connecting cannula (18) is a double-ended needle which can be secured by its middle region in the cannula guide and is retained by gluing, forming or by a press-fit seating, for example.

9. Device as claimed in claim 7, wherein the connection means (16;

75) comprise a connecting cannula (18) which is accommodated in the plunger (11) at one cannula end (19), and the other cannula end (20) is directed towards the cartridge (12).

10. Device as claimed in claim 9, wherein the cannula end (20) directed towards the cartridge (12) is covered by a cap (21) made from a rubber elastic material and the cap (21) is connected to the plunger (11) in a sealed arrangement.

11. Device as claimed in claim 9, wherein the cannula end (20) directed towards the cartridge (12) is disposed in a recess (22) of the plunger (11) and this recess (22) is closed by another membrane (15) which is permeable to gas but not to bacteria.

12. Device as claimed in one of the preceding claims, wherein the first chamber (1) is formed by a glass cylinder (23) which is in turn accommodated in the housing (3).

13. Device as claimed in claim 12, wherein the glass cylinder (23) has a tapered opening (24) at the dispensing-side end, which supports an adapter (25) fitted on the closure (9).

14. Device as claimed in one of the preceding claims, wherein the closure (9) contains a seal element (10) made from a rubber elastic material, which closes off an opening orifice of the first chamber (1) when the closure (9) is fitted.

15. Device as claimed in one of the preceding claims, wherein the closure (9) is secured by a catch connection to prevent it from being inadvertently released.

16. Device as claimed in one of the preceding claims, wherein the closure (9) has an outlet communicating with the interior of the first chamber (1) which can be closed, through which air can pass but not liquids.

17. Device as claimed in claim 16, wherein the outlet can be closed to prevent ingress by bacteria.

18. Device as claimed in one of claims 16 to 17, wherein the outlet is connected to the closure (9) or to the housing (3) by an anti-tamper device.

19. Device as claimed in one of the preceding claims, wherein the closure (9) is connected to the housing (3), the opening orifice or the glass cylinder (23) by an anti-tamper device.

20. Device as claimed in one of the preceding claims, wherein the housing (3) comprises two housing parts (4, 5) disposed axially one behind the other and connected to one another at a connection point (8), and the connection point (8) is disposed between the first chamber (1) and the second chamber (2).

21. Device as claimed in claim 20, wherein the connection point (8) is provided in the form of a thread connection.

22. Device as claimed in claim 21, wherein the connection point (8) is secured by an anti-tamper device, for example a label (35).

23. Device as claimed in one of the preceding claims, wherein the first chamber (1) has longitudinal grooves (45) in the diameter towards the interior at its end remote from the front housing end (6).

24. Device as claimed in one of claims 1 to 22, wherein the plunger (11) is made from a rubber elastic material and has a bigger diameter than the internal diameter of the first chamber (1) and has at least one axially extending venting passage disposed in the region of its circumference, the cross-section of which is dimensioned so that it is closed by the elastic deformation of the plunger (11) when the latter is fully accommodated in the first chamber (1).

25. Device as claimed in one of claims 1 to 10, wherein the opening (13) closed by the membrane (14) is disposed at the end of the rear housing end (7).

26. Device as claimed in claim 25, wherein a coupling part (58) is provided which can be fitted on the rear housing end (7), by means of which operating means (29) are connected, and cutting or severing means (57) are provided on the coupling part or on the operating means which pierce the membrane (14) when the coupling part (58) is fitted on the rear housing end (7).

27. Device as claimed in one of claims 1 to 25, wherein the operating means (29) are accommodated in a protective tube (30) which is releasably and sealingly attached to the housing (3).

28. Device as claimed in claim 27, wherein the opening (13) closed by the membrane (14) is disposed in the protective tube.

29. Device as claimed in one of claims 7 to 28, wherein the connection means (16;

75) of the plunger stopper (31) and the plunger (11) are dimensioned so that whilst the operating means (29) is being moved in the direction towards the front housing end (6), the connection means (16;

75) is operated first of all so that a flow connection is established from the cartridge (12) to the first chamber (1), the cartridge stopper is then moved in the direction towards the front housing end (6) so that the diluent flows from the cartridge (12) into the first chamber where it is mixed with the lyophilisate, and the plunger (11) in the first chamber (1) is then moved in the direction towards the front housing end (6) so that the reconstituted substance is ejected from the first chamber (1).

30. Device as claimed in claim 29, wherein a plurality of catch means (40) are disposed one immediately after the other in the direction of movement of the operating means (29).

31. Device as claimed in claim 30, wherein the catch means are provided in the form of a catch pawl arrangement (40, 41).

32. Device as claimed in claim 31, wherein the operating means (29) comprise a plunger rod with deformable webs extending along it which can elastically rebound in the direction extending radially with respect to the longitudinal mid-axis of the plunger rod, and the catch means have catches (40) formed on the terminal end of the webs facing the internal face of the housing.

33. Device as claimed in one of claims 29 to 32, wherein the connection means (16;

75) are retained in the interior of the housing by means of a first retaining mechanism (47, 48;

76, 77, 78) in the housing (3) with a pre-definable retaining force.

34. Device as claimed in claim 33, wherein the first retaining mechanism is provided in the form of a groove (48) in the internal wall of the housing extending around at least a part of the circumference and catch arms disposed on the connection means (16) biased in the direction of the internal wall of the housing with catch projections (47) locating in the groove.

35. Device as claimed in one of the preceding claims, wherein the plunger (11) is provided with or connected to a retaining mechanism with a pre-definable retaining force in an arrangement sealing off the first chamber (1).

36. Device as claimed in claim 35, wherein the retaining mechanism is provided in the form of a brake bead (43) disposed on the plunger (11) which has an external diameter of a bigger diameter than the internal diameter of the housing.

37. Device as claimed in claim 36, wherein several brake beads are disposed one after the other in the direction of forward movement.

38. Device as claimed in one of claims 36 to 37, wherein the brake bead (43) or the brake beads locate in recesses in the internal wall of the housing.

39. Device as claimed in one of the preceding claims, wherein biased spring means (64) are provided which cause the movement of the operating means (29) when they are relaxed.

40. Device as claimed in claim 33, wherein the first retaining mechanism (76, 77, 78) has a first catch position (77) and a second catch position (78).

41. Device as claimed in claim 40, wherein the connection means (75) have a second retaining mechanism (74) which opposes a relative movement between the cartridge (12) and the connection means (75) by applying a pre-defined retaining force.

42. Device as claimed in one of claims 40 to 41, wherein active catch means (81, 82) are provided between the connection means (75) and the plunger (11), which prevent the connection means (75) from being separated from the plunger (11) once the flow connection has been established between the cartridge (12) and the first chamber (1).

43. Method of containing a substance in a device as claimed in one of the preceding claims, wherein the end of the first chamber (1) lying opposite the dispensing end is tightly sealed by the plunger (11) first of all, this first chamber (1) is filled with the substance through the dispensing-end opening (24) which is lyophilised in the chamber, and the opening is then tightly sealed by means of the closure (9).