CONTAINER AND CLOSURE

Abstract

A closure for dispensing one or more active agents into a container comprises a sealed or sealable chamber having a breakable wall and a hollow piston slidably mounted in a piston guide. Said hollow piston comprises an outer wall having an end in the chamber and at least one ventilation aperture. Said end has a cutting formation. Said hollow piston is slidable in the piston guide between a ventilation position in which the at least one ventilation aperture allows ventilation of the chamber and a sealed position in which the at least one ventilation aperture is sealed to prevent ventilation of the chamber and a deployed position in which the cutting formation has broken through at least a portion of the breakable wall. The outer wall has a retaining formation which engages with the piston guide to releasably resist sliding of the hollow piston between the ventilation position and the sealed position and the deployed position. The hollow piston may have an outer wall, and said outer wall has an end within the chamber, facing the breakable wall, wherein the cutting end has a first edge having a cutting formation and a gap in said cutting formation.

Claims

1-49. (canceled)

50. A closure for dispensing one or more active agents into a container, the closure comprising: a sealed or sealable chamber having a breakable wall, a hollow piston slidably mounted in a piston guide, said hollow piston comprising an outer wall, said outer wall having an end in the chamber and at least one ventilation aperture, said end having a cutting formation, said hollow piston being slidable in the piston guide between a ventilation position in which the at least one ventilation aperture allows ventilation of the chamber and a sealed position in which the at least one ventilation aperture is sealed to prevent ventilation of the chamber and a deployed position in which the cutting formation has broken through at least a portion of the breakable wall, wherein the outer wall has a retaining formation which engages with the piston guide to releasably resist sliding of the hollow piston between the ventilation position and the sealed position and the deployed position.

51. The closure according to claim 50, wherein the piston guide comprises a locating formation engageable with the retaining formation of the outer wall.

52. The closure according to claim 51, wherein the locating formation comprises at least one flanged edge portion engageable with the retaining formation of the outer wall.

53. The closure according to claim 50, wherein a gap is provided in the cutting formation.

54. The closure according to claim 53, wherein the gap in the cutting formation is formed by the at least one ventilation aperture.

55. The closure according to claim 50, wherein the breakable wall is not broken in an area proximate the gap in the cutting formation when the hollow piston is in the deployed position.

56. A container and a closure according to claim 50, for dispensing one or more active agents into said container, wherein the closure is retained within an opening of the container and the closure provides a seal for said opening of the container.

57. A pre-loaded container for use in dispensing one or more active agents comprising a container body and a closure according to claim 50.

58. The pre-loaded container according to claim 57, wherein the container body is a vial and the closure is a vial cap.

59. The pre-loaded container according to claim 58, wherein the vial further comprises a patient delivery mechanism.

60. The pre-loaded container according to claim 59, wherein the patient delivery mechanism is a dropper or a spray nozzle.

61. The pre-loaded container according to claim 57, wherein the container is an intravenous fluid bag suitable for retaining a diluent, the intravenous fluid bag having an inlet, and the closure is an inlet closure suitable for retaining one or more active agents.

62. A method of using the pre-loaded container according to claim 57, to dispense one or more active agents, the method comprising the steps of: manually sliding the hollow piston from the default position to break through a portion of the breakable wall but not in an area of said breakable wall proximate the gap in the cutting formation; agitating the contents of the pre-loaded container such that the one or more active agents mix with and dissolve into the portion of diluent.

63. The method according to claim 62, further comprising the steps of removing a covering from an external surface of the injection port; inserting a needle into the container through the injection port; and drawing a portion of a solution resulting from the dissolution of the one or more active agents into the portion of diluent from the container into a syringe through the needle.

64. The method according to claim 63, further comprising the step of administering a portion of the solution to a patient.

65. A method of manufacturing a pre-loaded container for use in dispensing one or more active agents comprising the steps of: providing a container body, a closure having a sealable chamber, an injection port and a hollow piston having at least one ventilation aperture slidable in a piston guide, a solution containing one or more active agents, a diluent, and an inert gas; injecting a portion of the solution containing one or more active agents into the chamber through the injection port; lyophilising the solution in the chamber; sealing the closure by sealing the at least one ventilation aperture, thereby sealing the chamber; injecting a portion of the inert gas into the chamber through the injection port; and adding a portion of the diluent to the container body and sealing the container body with the closure.

66. The method according to claim 65, wherein the step of adding a portion of the diluent to the container body and sealing the container body with the closure occurs before or after the steps of injecting a portion of the solution containing one or more active agents into the chamber and/or lyophilising the solution in the chamber and/or injecting a portion of the inert gas into the chamber.

67. The method according to claim 65, wherein the container body, the closure, the injection port and the hollow piston are sterilised before use.

68. The method according to claim 65, wherein the one or more active agents are provided in the form of a cake or tablet of lyophilised active agent.

69. The method according to claim 65, wherein the solution containing one or more active agents is provided inside a syringe.

70. The method according to claim 65, wherein the step of injecting a portion of the solution containing one or more active agents into the chamber comprises the steps of first piercing the injection port of the closure with a needle and then injecting the portion of the solution containing one or more active agents from a syringe into the chamber through the needle.

71. The method according to claim 65, wherein the step of injecting a portion of the inert gas into the chamber comprises the steps of first piercing the injection port of the closure with a needle and then injecting the portion of the inert gas into the chamber through the needle.

72. The method according to claim 65, further comprising the step of providing a sterile covering over the injection port.

73. A pre-loaded container manufactured according to the method of claim 65, the container body retaining a portion of diluent and the closure retaining one or more lyophilised active agents, wherein said closure forms a sterile seal across an opening of said container body.

74. The pre-loaded container according to claim 73, wherein the container body is a vial and the closure is a vial cap.

75. The pre-loaded container according to claim 74, wherein the vial further comprises a patient delivery mechanism.

76. The pre-loaded container according to claim 75, wherein the patient delivery mechanism is a dropper or a spray nozzle.

77. The pre-loaded container according to claim 73, wherein the container is an intravenous fluid bag suitable for retaining a diluent, the intravenous fluid bag having an inlet, and the closure is an inlet closure suitable for retaining one or more active agents

78. A method of using the pre-loaded container according to claim 73, to dispense one or more active agents, the method comprising the steps of: manually sliding the hollow piston from the default position to break through a portion of the breakable wall but not in an area of said breakable wall proximate the gap in the cutting formation; agitating the contents of the pre-loaded container such that the one or more active agents mix with and dissolve into the portion of diluent.

79. The method according to claim 78, further comprising the steps of removing a covering from an external surface of the injection port; inserting a needle into the container through the injection port; and drawing a portion of a solution resulting from the dissolution of the one or more active agents into the portion of diluent from the container into a syringe through the needle.

80. The method according to claim 79, further comprising the step of administering a portion of the solution to a patient.

Description

DESCRIPTION OF THE DRAWINGS

[0056] An example embodiment of the present invention will now be illustrated with reference to the following Figures in which:

[0057] FIG. 1 shows a cross section through a vial and a vial closure;

[0058] FIG. 2 shows a cross section through the vial of FIG. 1;

[0059] FIG. 3 shows a cross section through the vial closure of FIG. 1;

[0060] FIG. 4 shows a cross section through the vial closure of FIG. 3 in an alternative arrangement;

[0061] FIG. 5 shows a cross section through the vial closure of FIG. 3 in a further alternative arrangement;

[0062] FIG. 6 shows a cross section through a needle penetrating the vial closure of FIG. 3 retaining one or more active agents;

[0063] FIG. 7 shows a cross section through a needle penetrating the vial closure of FIG. 4 retaining one or more active agents;

[0064] FIG. 8 shows a cross section of a vial retaining a diluent and a vial closure retaining one or more active agents;

[0065] FIG. 9 shows a perspective view of a vial closure with an injection port and a sterile covering;

[0066] FIG. 10 shows a cross section of a vial retaining a diluent and a vial closure retaining one or more active agents with a sterile covering;

[0067] FIG. 11 shows a cross section of a vial retaining a diluent and one or more active agents falling from a vial closure into the diluent;

[0068] FIG. 12 shows a side view of a medical practitioner removing a sterile covering from a vial closure;

[0069] FIG. 13 shows a cross section of a vial retaining a solution and a needle penetrating a vial closure;

[0070] FIG. 14 shows a perspective view of a cut through a vial with a vial closure and a nozzle;

[0071] FIG. 15 shows a side view of the vial with the vial closure and the nozzle of FIG. 14;

[0072] FIG. 16 shows a perspective view of a cut through a vial with a vial closure and a dropper;

[0073] FIG. 17 shows a side view of the vial with the vial closure and the dropper of FIG. 16; and

[0074] FIG. 18 shows a cross section through a vial with a vial closure and a removable cap.

DETAILED DESCRIPTION OF AN EXAMPLE EMBODIMENT

[0075] A container 1 for use in dispensing one or more active agents as shown in FIG. 1 comprises a vial 2 and a vial closure 3. The vial 2, as shown in FIG. 2, comprises a vial body 4 comprising a generally cylindrical side wall 5 extending upwards from a generally circular base 6. A generally cylindrical opening 7 is provided opposite said circular base 6. Together the base 6 and the cylindrical side wall 7 define an internal vial chamber 8. The vial body 4 is made from glass or plastics, or any other suitable material.

[0076] The vial closure 3, as shown in FIG. 3, comprises a vial closure body 9 and a vial closure lid 10. The vial closure body 9 comprises a generally cylindrical closure wall 11 dimensioned and configured for an interference fit within the opening 7 of the vial body 4 when the vial closure 3 is fully inserted into said opening 7. The closure wall 11 is typically made of a resilient plastics material. A generally circular closure base 12 extends across the end of the vial closure body 9 which is inserted into the opening 7 of the vial body 4 when in use. The vial closure base 12 is made of a pierceable material such as a plastics material or glass (functioning as the breakable wall). A chamber 15 is defined by the cylindrical closure wall 11 and circular closure base 12.

[0077] The vial closure lid 10 comprises a generally cylindrical lid wall 13 extending from a generally circular lid cover 14. The lid wall 13 is made of a rigid plastics material. The lid cover 14 is made of a resilient plastics material, for example rubber. The lid wall 13 is dimensioned and configured to fit within the chamber 15 formed by the closure wall 11 and closure base 12. The lid wall 13 functions as the hollow piston (and as the outer wall of the hollow piston). The base edge 17 of the lid wall is at the end of the outer wall of the piston facing the breakable wall.

[0078] A gap 16 is provided in the lid wall 13. The rest of the base edge 17 functions as the cutting formation and may or may not be sharp, depending on the strength of the breakable wall. The base edge 17 of the lid wall is sloping opposite the lid cover and protrudes further towards the breakable wall on the side opposite the gap. The sloping base edge 17 of the lid wall 13 is adjacent the closure base 12 when the vial closure lid 10 is inserted into the closure chamber 15. An injection port 18 is provided in the centre of the lid cover 14 such that a needle may be removably inserted through said injection port 18 into the chamber 15 formed by the vial closure body 9 when the chamber is covered by the vial closure lid 10. The injection port 18 comprises a rubber septum.

[0079] The generally cylindrical lid wall 13 comprises an internal surface 13A and an external surface 13B. Three generally circular flanged edges extend from the external surface 13B of the lid wall 13 around the circumference of said lid wall 13. The first flanged edge 19 is positioned adjacent to and set back from the sloping base edge 17 of the lid wall. The second flanged edge 20 is positioned approximately midway between the sloping base edge 17 of the lid wall 13 and the lid cover 14. The third flanged edge 21 is positioned adjacent to the lid cover 14. The third flanged edge 21 extends substantially further outwards from the external surface 13B of the lid wall 13 than the first 19 and second 20 flanged edges. The third flanged edge 21 is configured to engage with a top surface 22 of the closure body 9 when the lid 10 is inserted into the closure chamber 15.

[0080] The generally cylindrical closure wall 11 also comprises an internal surface 11A and an external surface 11B. The internal surface 11A of the closure wall 11 comprises a flexible seal 23 adjacent to the end of the closure wall 11 which is proximate the lid cover 14 when the vial closure lid 10 is inserted into the closure chamber 15. The flexible seal 23 is made from a resilient plastics material, for example rubber. The flexible seal and in some embodiments the internal surface 11 of the closure wall 11, functions as the piston guide. The hollow piston formed by lid wall 13 and its base edge 17 is slidably mounted in the piston guide. The flexible seal 23 is positioned, dimensioned and configured to be releasably engageable with the first 19 and second 20 flanged edges of the lid wall 13 to releasably retain the vial closure lid 10 in two possible positions such that the vial closure lid 10 is moveable into, out of and between said two positions. In the first position illustrated in FIG. 3, the first flanged edge 19 engages the flexible seal 23. In such a position, the vial closure lid 10 is held apart from the vial closure body 9 such that the aperture 16 in the lid wall 13 permits fluid communication between the closure chamber 15 and the surroundings. In the second position illustrated in FIG. 4, the second flanged edge 20 engages with the flexible seal 23. In such a position, the vial closure lid 10 has been inserted into the closure chamber 15 such that the aperture 16 is covered by the closure wall 11 and no fluid communication between the closure recess 15 and the surroundings is permitted. The pierceable closure base 12 remains intact in both the first and second positions.

[0081] The vial closure seal is also moveable from the second position illustrated in FIG. 4 (where the closure chamber 15 is sealed from the surroundings and the pierceable vial closure base 12 is intact) to a third position illustrated in FIG. 5 where the third flanged edge 21 of the lid wall 13 engages with the top surface 22 of the closure body 9. In such a third position, the sloping base edge 17 of the lid wall 13 pierces the pierceable closure base 12 and extends beyond it such that the previously sealed closure chamber 15 is brought into fluid communication with the surroundings. The placement of the aperture 16 ensures that only a portion of the circumference of the pierceable base 12 is cut when the vial closure lid 10 is held in the third position. The aperture 16 therefore performs a dual role in both permitting fluid communication between the closure chamber 15 and the surroundings in the first position and also by ensuring that only a portion of the circumference of the pierceable base 12 is cut when the vial closure lid 10 is held in the third position, while retaining the mechanical strength and integrity of the lid wall 13 and thus the reliability of the vial closure 3.

[0082] When the vial closure lid 10 is retained in the third position, the third flanged edge 21 of the lid wall 13 engages with the top surface 22 of the vial closure body 9. The first flanged edge 19 also engages with a newly-formed bottom edge of the closure wall 11 (formed by the cut through the pierceable base 12). The vial closure lid 10 is, therefore, locked into the third position, since the combined action of the first 19 and third 21 flanged edges prevents further movement of the vial closure lid 10 into or out of the vial closure chamber 15.

[0083] In use, the circumference of the pierceable base 12 is not cut in an area proximate the gap 16 in the lid wall 13. The pierceable base 12, therefore, remains hingedly attached to the vial closure wall 11 in the area proximate the gap 16 in the lid wall 13. The vial closure lid 10 therefore acts as a piston 10, cutting through the pierceable wall 12, and bringing the closure chamber 15 into fluid communication with the vial chamber 8.

[0084] The method of manufacturing the pre-loaded container ready for use in dispensing one or more active agents is illustrated in FIGS. 6, 7 and 8. The vial closure body 9 and vial closure lid 10 are sterilised and then placed in the first position (as shown in FIG. 6), where the first flanged edge 19 engages with the flexible seal 22. The gap 16 in the lid wall 13 is uncovered. A solution is prepared comprising one or more active agents. A syringe 25 is used to inject a portion of the solution 24 containing one or more active agents into the chamber 15 formed between the vial closure body 9 and vial closure lid 10 by piercing the injection port 18 with a needle 26 (as illustrated in FIG. 6). The one or more active agents are then lyophilised within the chamber. The lyophilisation step comprises the steps of freezing the solution 24 within the recess and then heating the frozen solution under vacuum conditions such that the solvent sublimes. Solvent molecules are able to escape from the chamber 15 to the surroundings through the gap 16. The lyophilised one or more active agents 27 remain inside the chamber 15. The vial closure lid 10 is then moved either manually or mechanically to the second position (shown in FIG. 4), where the second flanged 20 edge engages with the flexible seal 23. The gap 16 in the lid wall 13 is now covered such that the chamber 15 is no longer ventilated. An inert gas, such as nitrogen gas, is then injected into the chamber 15 from a syringe 25 by piercing the injection port with a needle 26 (FIG. 7). The inert gas fills the remaining space inside the chamber 15 so that air or other fluids are not drawn into the chamber 15 through the injection port 15 as the surrounding vacuum conditions are removed. This ensures the contents of the chamber 15 remain sterile. The advantage provided by lyophilisation is that the one or more active agents 27 retained in the chamber 15 are not structurally altered but are more stable than in solution. A portion of a suitable diluent 28 is then provided inside the chamber 8 of the sterilised vial body 4 and the filled vial closure 3 (comprising the vial closure body 9, the vial closure lid 10 in the second position and the lyophilised one or more active agents 27 retained within the closure chamber 15) is inserted into the opening 7 of the vial body 4 with an interference fit such that the opening 7 is sealed, as illustrated in FIG. 8. This ensures that the diluent 28 and the one or more active agents 27 are sealed from external contaminants and from one another.

[0085] As illustrated in FIG. 9, a removable sterile covering 29 is provided on top of the injection port 18 of the vial closure lid 10. The sterile covering 29 is made of a plastics material and is attached to the vial closure lid 10 by means of an adhesive. A portion of the sterile covering, a tab 30, is not coated in adhesive, to facilitate subsequent removal of said sterile covering 29 by a medical practitioner during use.

[0086] A preloaded container 31 so manufactured can be transported or stored safely within a refrigerator, or according to the recommended storage conditions for the diluent 28 and the one or more active agents 27, to await use.

[0087] The use of a pre-loaded container 31 for dispensing one or more active agents 27 so manufactured is illustrated in FIGS. 10, 11, 12 and 13. A medical practitioner receives the pre-loaded container 31 in a first state illustrated by FIG. 10, where the vial chamber 8 retains a diluent 28, the closure chamber 15 retains one or more lyophilised active agents 27, the vial closure 3 seals the opening 7 to the vial body 4, and the vial closure lid 10 is in its second position such that the closure chamber 15 is sealed from the surroundings while the pierceable closure base 12 is intact. When the pre-loaded container 31 is ready to be used, the medical practitioner manually depresses the top surface of the vial closure lid 10, moving the vial closure lid 10 to the third position where the third external flange 21 engages with the top surface 22 of the vial closure body 9. The vial closure lid 10 acts like a piston, cutting through a portion of the circumference of the pierceable closure base 12 and bringing the closure chamber 15 into fluid communication with the vial chamber 8 (see FIG. 11). The lyophilised one or more active agents 27 fall into the diluent 28. Agitation of the contents of the pre-loaded container 31 ensures thorough dissolution of the one or more active agents 27 into the diluent 28. As illustrated in FIG. 12, the medical practitioner then removes the sterile covering 29 provided on top of the injection port 18 by peeling back said covering 29 by means of the non-adhered tab 30. The solution 32, resulting from the dissolution of the one or more active agents 27 into the diluent 28, is extracted from the pre-loaded container 31 for administration to a patient using a syringe 25 by piercing the injection port 18 with a needle 26 (FIG. 13). The solution 32 is drawn into the syringe 25. The closure base 12 remains hingedly attached to the closure wall 11 and does not fall into the solution 32 and, therefore, does not interfere with the syringe 25.

[0088] In variations of the invention, the vial body further comprises a patient delivery mechanism. In one such variation, for example, as shown in FIGS. 14 and 15, the generally circular base 6 of the vial body 4 of the container 1 as described previously is replaced with a pump-action nozzle 33. The nozzle comprises a nozzle head 34 extending from a nozzle seal 35. The nozzle seal 35 is dimensioned and configured for an interference fit within a second opening 36 of the vial body 4. A nozzle tube 37 extends between the nozzle head 34 and the vial chamber 8, through the nozzle seal 35, such that the nozzle head 34 is in fluid communication with the vial chamber 8. A removable lid 38 is provided over the nozzle head 34. When in use, once the one or more active agents 27 have been released into the vial chamber 8 and combined with the diluent 28, the resulting solution 32 may be administered directly to a patient by means of the pump-action nozzle 33, once the lid 38 has been removed. This removes the possibility of external contamination of the solution by the introduction of a needle through the injection port. A pump-action nozzle 33 is suitable for, for example, topical or nasal administration of the one or more active agents. In another variation, as shown in FIGS. 16 and 17, the generally circular base 6 of the vial body 4 of the container 1 as described previously is replaced with a dropper 39. The dropper 39 comprises a dropper bulb 40 extending from a dropper seal 41. The dropper seal 41 is dimensioned and configured for an interference fit within a second opening 36 of the vial body 4. A dropper tube 42 extends between the dropper bulb 40 and the vial chamber 8, through the dropper seal 41, such that the dropper bulb 40 and dropper tube 42 are in fluid communication with the vial chamber 8. A removable lid 43 is provided over the dropper bulb 40. When in use, once the one or more active agents 27 have been released into the vial chamber 8 and combined with the diluent 28, the resulting solution 32 may be administered directly to a patient by means of the dropper 39 once the lid 43 has been removed. This removes the possibility of external contamination of the solution by the introduction of a needle through the injection port. A dropper 39 is suitable for, for example, topical, oral or ocular administration of the one or more active agents.

[0089] FIG. 18 shows a variation of the invention which further includes a removable cap 44 positioned over the vial closure 3. A flange 45 of the removable cap 44 engages with a flange 46 of the vial 2, thereby retaining the removable cap over the vial closure 3. The removable cap 44 may for example be formed by crimping. The removable cap 44 protects the vial closure 3. The removable cap 44 restricts depression of the piston 13. The removable cap 44 therefore reduces the likelihood that the piston 13 is inadvertently depressed (resulting in breaking of the breakable wall 12). The injection port 18 is, in addition, covered by adhesive injection port cover 47, underneath the cap. Adhesive injection port cover 47 protects injection port 18 during manual depression of the piston 13 once removable cap 44 has been removed. Adhesive injection port cover 47 ensures that injection port 18 remains sterile. Removal of adhesive injection port cover 47 allows a user to access the sterile injection port 18.

[0090] The removable cap 44 is made of a plastics material. The plastics material is flexible enough that the removable cap 44 may be deformed in order to remove said removable cap 44 from the closure 3. However, the plastics material is also rigid enough that the removable cap 44 is typically retained on the closure 3 unless deliberately removed. The removable cap 44 may also be releasably connected to the closure 3 by other means. For example, the removable cap 44 may be sealed to the vial closure 3 by way of an adhesive, such as an adhesive strip, or by way of a removable connecting strip integrally formed with the removable cap 44.

[0091] Further modifications and variations may be made within the scope of the invention herein disclosed.