MEDICAL DEVICES HAVING A COATING OF INORGANIC MATERIAL

• US 20090264975A1
• Filed: 04/17/2009
• Published: 10/22/2009
• Est. Priority Date: 04/22/2008
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: O'BRIEN, Barry, O'CONNOR, Tim, KILCOOLEY, John, WEBER, Jan, FLANAGAN, Aiden, SCHEUERMANN, Torsten, SEIDEL, Dominique, KUEHLING, Michael
• Granted Patent: US 8,920,491 B2
• Time in Patent Office: Days
• US Class Current: 623/1.200
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/61 containing two or more active agents in different layers
• CPC Class Codes: A61L 29/10 Inorganic materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/082 Inorganic materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

In one aspect, a medical device has a first configuration and a second configuration, a reservoir containing a therapeutic agent, and a barrier layer disposed over the reservoir, wherein the barrier layer comprises an inorganic material. In another aspect, a medical device has a reservoir containing a therapeutic agent, a barrier layer disposed over the reservoir, wherein the barrier layer comprises an inorganic material, and a swellable material disposed between the barrier layer and a surface of the medical device, wherein the swellable material is a material that swells upon exposure to an aqueous environment. In yet another aspect, a medical device has a multi-layered coating having alternating reservoir layers and barrier layers, and a plurality of excavated regions penetrating through at least a partial thickness of the multi-layered coating. In yet another aspect, a medical device has a polymer layer comprising a block co-polymer, wherein the polymer layer contains a therapeutic agent, and a barrier layer disposed over the polymer layer, wherein the barrier layer comprises an inorganic material, and wherein the barrier layer has a plurality of discontinuities. Methods of forming coatings on medical devices and methods of delivering therapeutic agents to body sites are also disclosed.

Claims

1. A medical device having a first configuration and a second configuration, wherein the medical device comprises:

a reservoir containing a therapeutic agent; and

a barrier layer disposed over the reservoir, wherein the barrier layer comprises an inorganic material;

wherein the barrier layer has a first permeability to the therapeutic agent when the medical device is in the first configuration and a second permeability to the therapeutic agent when the medical device is in the second configuration, and wherein the second permeability is greater than the first permeability.

2. The medical device of claim 1, wherein the medical device is an expandable medical device, and wherein the first configuration is an unexpanded configuration and the second configuration is an expanded configuration.

3. The medical device of claim 2, wherein the barrier layer has a plurality of regions of structural weakness.

4. The medical device of claim 3, wherein the regions of structural weakness are regions where the barrier layer has reduced thickness.

5. The medical device of claim 3, wherein the regions of structural weakness form a pre-determined fracture pattern for the barrier layer.

6. The medical device of claim 3, wherein discontinuities are formed in the regions of structural weakness when the configuration of the medical device changes from the unexpanded configuration to the expanded configuration.

7. The medical device of claim 4, wherein the regions of reduced thickness are excavated regions in which material has been removed from the barrier layer.

8. The medical device of claim 7, wherein the excavated regions contain a biodegradable filler material.

9. The medical device of claim 8, wherein the filler material is released from the excavated regions when the configuration of the medical device changes from the unexpanded configuration to the expanded configuration in an aqueous environment.

10. The medical device of claim 4, wherein the barrier layer is disposed on a textured surface, and wherein the regions of reduced thickness are located over the protruding features of the textured surface.

11. The medical device of claim 4, wherein the barrier layer is formed by a layer deposition process, and wherein the regions of reduced thickness are formed during the layer deposition process.

12. The medical device of claim 3, wherein the regions of structural weakness in a first portion of the medical device have a different characteristic than the regions of structural weakness in a second portion of the medical device.

13. The medical device of claim 12, wherein the second portion has a greater density of regions of structural weakness than the first portion.

14. The medical device of claim 12, wherein the regions of structural weakness are regions where the barrier layer has reduced thickness, and wherein the regions of reduced thickness are thinner in the second portion than in the first portion.

15. The medical device of claim 1, wherein the reservoir containing the therapeutic agent is a polymer layer.

16. The medical device of claim 1, wherein the inorganic material is a metal or metal oxide.

17. The medical device of claim 1, wherein the first permeability is negligible or zero.

18. The medical device of claim 1, wherein the first permeability does not provide a therapeutically effective release profile of the therapeutic agent, and wherein the second permeability provides a therapeutically effective release profile of the therapeutic agent.

66. The medical device of claim 2, wherein the medical device is a balloon.

67. The medical device of claim 2, wherein the medical device is a stent.

19. A method of forming a coating on a medical device, comprising:

providing a medical device;

disposing a therapeutic agent over a surface of the medical device;

disposing a barrier layer over the therapeutic agent, wherein the barrier layer comprises an inorganic material; and

removing portions of the barrier layer to form regions of structural weakness in the barrier layer.

20. The method of claim 19, wherein the step of removing is performed using an energetic beam.

21. The method of claim 20, wherein the step of removing is performed by laser ablation.

22. The method of claim 19, wherein the step of disposing the barrier layer comprises depositing the inorganic material over the therapeutic agent by a layer deposition process.

23. The method of claim 22, wherein the layer deposition process is a nanoparticle deposition process.

24. The method of claim 19, wherein more material is removed from the barrier layer at a first portion of the medical device than at a second portion of the medical device.

68. The method of claim 19, wherein the medical device is a balloon.

69. The method of claim 19, wherein the medical device is a stent.

25. A medical device comprising:

a reservoir containing a therapeutic agent;

a barrier layer disposed over the reservoir, wherein the barrier layer comprises an inorganic material; and

a swellable material disposed between the barrier layer and a surface of the medical device, wherein the swellable material is a material that swells upon exposure to an aqueous environment.

26. The medical device of claim 25, wherein the barrier layer has a first permeability to the therapeutic agent prior to swelling of the swellable material and a second permeability to the therapeutic agent after swelling of the swellable material, and wherein the second permeability is greater than the first permeability.

27. The medical device of claim 26, wherein the first permeability is provided by one or more discontinuities in the barrier layer.

28. The medical device of claim 27, wherein the swelling of the swellable material causes the formation of further discontinuities in the barrier layer.

29. The medical device of claim 25, wherein the medical device further comprises an intermediate layer disposed between the medical device and the barrier layer, wherein the intermediate layer comprises a polymeric material.

30. The medical device of claim 29, wherein the intermediate layer contains the reservoir containing the therapeutic agent.

31. The medical device of claim 30, wherein the medical device further comprises a swellable layer disposed between the medical device and the barrier layer, and wherein the swellable layer contains the swellable material.

32. The medical device of claim 30, wherein the intermediate layer further comprises the swellable material.

33. The medical device of claim 32, wherein the swellable material is contained in capsules.

34. The medical device of claim 25, wherein the barrier layer has a plurality of regions of structural weakness.

35. The medical device of claim 25, wherein the swellable material is a water-swellable polymer.

36. The medical device of claim 25, wherein the swellable material is an oxidizable metal that swells upon oxidation.

37. The medical device of claim 27, wherein the one or more discontinuities are created by cooling the barrier layer.

38. The medical device of claim 37, wherein the barrier layer is cooled by exposure to a cryogenic liquid.

39. The medical device of claim 27, wherein the one or more discontinuities are created by at least one cycle of heating and then cooling the barrier layer, or at least one cycle of cooling and then heating the barrier layer.

70. The medical device of claim 25, wherein the medical device is a balloon.

71. The medical device of claim 25, wherein the medical device is a stent.

40. A medical device having a multi-layered coating, wherein the multi-layered coating comprises:

a first reservoir layer over a surface of the medical device, wherein the first reservoir layer comprises a first therapeutic agent;

a first barrier layer over the first reservoir layer, wherein the first barrier layer comprises a first inorganic material;

a second reservoir layer over the first barrier layer, wherein the second reservoir layer comprises a second therapeutic agent;

a second barrier layer over the second reservoir layer, wherein the second barrier layer comprises a second inorganic material; and

a plurality of excavated regions penetrating through at least a partial thickness of the multi-layered coating.

41. The medical device of claim 40, wherein at least one of the plurality of excavated regions penetrates through the full thickness of the multi-layered coating.

42. The medical device of claim 40, wherein at least one of the plurality of excavated regions penetrates through only a partial thickness of the multi-layered coating.

43. The medical device of claim 40, wherein at least one of the plurality of excavated regions has a slanted geometry with respect to the plane of the multi-layered coating.

44. The medical device of claim 40, wherein the first therapeutic agent is different from the second therapeutic agent.

45. The medical device of claim 40, wherein the first reservoir layer or the second reservoir layer is formed of a polymeric material.

46. The medical device of claim 40, wherein the thickness of the first reservoir layer is different from the thickness of the second reservoir layer.

47. The medical device of claim 40, further comprising a third reservoir layer disposed over the second barrier layer, wherein the third reservoir layer comprises a third therapeutic agent, and a third barrier layer disposed over the third reservoir layer, wherein the third barrier layer comprises a third inorganic material.

48. The medical device of claim 47, wherein the multi-layered coating comprises a plurality of alternating reservoir layers and barrier layers.

49. The medical device of claim 40, wherein at least one characteristic of the excavated regions on one portion of the medical device is different from that of the excavated regions on another portion of the medical device.

50. The medical device of claim 49, wherein the size of the excavated regions on one portion of the medical device is different from the size of the excavated regions on another portion of the medical device.

51. The medical device of claim 49, wherein the geometry of the excavated regions on one portion of the medical device is different from the geometry of the excavated regions on another portion of the medical device.

52. The medical device of claim 40, wherein the excavated regions are created using an energetic beam.

72. The medical device of claim 40, wherein the medical device is a balloon.

73. The medical device of claim 40, wherein the medical device is a stent.

53. A medical device comprising:

a polymer layer comprising a block co-polymer, wherein the polymer layer contains a therapeutic agent; and

a barrier layer disposed over the polymer layer, wherein the barrier layer comprises an inorganic material, and wherein the barrier layer has a plurality of discontinuities.

54. The medical device of claim 53, wherein the polymer layer has a surface morphology comprising a plurality of microphase-separated domain structures.

55. The medical device of claim 54, wherein the discontinuities in the barrier layer follow the surface morphology of the polymer layer.

56. The medical device of claim 54, wherein the surface morphology of the barrier layer follows the surface morphology of the polymer layer.

57. The medical device of claim 53, wherein the surface morphology of the barrier layer is adapted to promote endothelial cell attachment and/or growth.

58. The medical device of claim 53, wherein the surface morphology of the barrier layer comprises a plurality of feature elements or feature domains that promote endothelial cell attachment and/or growth.

59. The medical device of claim 58, wherein the feature elements or feature domains have an average size of less than 200 nm.

60. The medical device of claim 59, wherein the feature elements or feature domains have an average size in the range of 30 nm to 90 nm.

74. The medical device of claim 53, wherein the medical device is a balloon.

75. The medical device of claim 53, wherein the medical device is a stent.

76. The medical device of claim 60, wherein the medical device is a balloon.

77. The medical device of claim 60, wherein the medical device is a stent.

61. A method of forming a coating in a medical device, comprising:

providing a medical device;

disposing a polymer layer over a surface of the medical device, wherein the polymer layer comprises a polymeric material and a therapeutic agent, wherein the polymeric material comprises a block copolymer, and wherein the polymer layer has a surface morphology comprising a plurality of microphase-separated domain structures; and

disposing a barrier layer over the polymer layer, wherein the barrier layer comprises an inorganic material, and wherein the barrier layer has a plurality of discontinuities that follow the surface morphology of the polymer layer.

62. The method of claim 61, further comprising removing the polymeric material from the polymer layer.

63. The method of claim 62, wherein the step of removing the polymeric material comprises exposing the polymer layer to a solvent.

64. The method of claim 62, further comprising depositing additional inorganic material over the barrier layer after the step of removing the polymeric material.

65. The method of claim 61, wherein the step of disposing a barrier layer comprises depositing the inorganic material over the polymer layer.