Medical device with a porous surface for delivery of a therapeutic agent

• US 20080243231A1
• Filed: 02/27/2008
• Published: 10/02/2008
• Est. Priority Date: 03/01/2007
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: Malone, Anthony, O'Connor, Tim, Flanagan, Aiden, McMorrow, David
• Granted Patent: US 8,070,797 B2
• Time in Patent Office: Days
• US Class Current: 623/1.16
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 31/082 Inorganic materials
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

The present invention is generally directed to implantable medical devices for delivering therapeutic agents to the body tissue of a patient and methods for making such medical devices. In particular, the present invention is directed to implantable medical devices, such as intravascular stents, having a surface that includes a plurality of cavities and a plurality of pores and a composition disposed in the pores and/or cavities, as well as, implantable medical devices, such as intravascular stents, having a surface that has a coating composition disposed on the surface, wherein the coating composition includes a plurality of cavities and a plurality of pores and another coating composition disposed in the pores and/or cavities.

Claims

1. An implantable stent comprising:

(a) a stent sidewall structure having a surface; and

(b) a coating comprising;

(i) a first coating composition disposed on at least a portion of the surface of the stent sidewall structure, wherein the first coating composition has an exposed surface and the first coating composition comprises a metal, a metal oxide, ceramic oxide, or inert carbon having a plurality of cavities therein, wherein at least some of the cavities are in fluid communication with the exposed surface, and wherein at least one of the cavities is defined by a cavity surface having a plurality of pores therein; and

(ii) a second coating composition comprising a first therapeutic agent, wherein the second coating composition is disposed within at least one of the pores.

2. The stent of claim 1, wherein the sidewall structure comprises a plurality of struts and openings in the sidewall structure.

3. The stent of claim 1, wherein the surface of the stent sidewall is the abluminal surface.

4. The stent of claim 1, wherein the first coating composition conforms to the surface of the stent so that the openings of the stent sidewall structure is preserved and, wherein the surface of the sidewall structure comprises an abluminal surface.

5. The stent of claim 1, wherein the stent is an intravascular balloon-expandable stent.

6. The sent of claim 1, wherein the stent is an intravascular self-expanding stent.

7. The stent of claim 1, wherein the first coating composition is radiopaque.

8. The stent of claim 1, wherein the first coating composition is free of any polymer.

9. The stent of claim 1, wherein at least one of the pores is in fluid communication with the cavity surface.

10. The stent of claim 1, wherein the pores are distributed throughout the first coating composition.

11. The stent of claim 10, wherein the pores are homogenously distributed throughout the first coating composition.

12. The stent of claim 1, wherein the second coating composition is also disposed within at least one of the cavities.

13. The stent of claim 1, wherein the second coating composition further comprises a polymer.

14. The stent of claim 13, wherein the polymer is biostable.

15. The stent of claim 13, wherein the polymer is bioabsorbable

16. The stent of claim 13, wherein the polymer comprises styrene-isobutylene-styrene, polylactic-co-glycolic acid (PLGA), polybutyl methacrylate (PBMA), polyvinylidene fluoride (PVDF), or a combination thereof.

17. The stent of claim 1, wherein the metal oxide or ceramic oxide comprises iridium oxide, titanium oxide, titanium dioxide, iron oxide, hydroxyapatite, calcium phosphates, alumina, zirconia, zirconium, silica based glasses, or a combination thereof.

18. The stent of claim 1, wherein the metal comprises gold, tantalum, platinum, titanium, Nitinol or a combination thereof.

19. The stent of claim 1, wherein the first coating composition is about 1 micron to about 30 microns thick.

20. The stent of claim 1, wherein the diameter of the pores is less than or equal to one micron.

21. The stent of claim 1, wherein the width of the cavities is greater than or equal to one micron.

22. The stent of claim 1, wherein the coating further comprises a third coating composition comprising a second therapeutic agent and, wherein the third coating composition is disposed within the cavities.

23. The stent of claim 22, wherein the first therapeutic agent and second therapeutic agent are different.

24. The stent of claim 1, wherein the therapeutic agent comprises an anti-thrombogenic agent, anti-angiogenesis agent, anti-proliferative agent, antibiotic, anti-restenosis agent, growth factor, immunosuppressant or radiochemical.

25. The stent of claim 1, wherein the therapeutic agent comprises an anti-restenosis agent.

26. The stent of claim 1, wherein the therapeutic agent comprises paclitaxel.

27. The stent of claim 1, wherein the therapeutic agent comprises sirolimus, tacrolimus, pimecrolimus, zotarolimus or everolimus.

28. The stent of claim 22, wherein the third coating composition further comprises a polymer.

29. An implantable stent comprising:

(a) a stent sidewall structure having a surface, wherein the stent sidewall structure comprises a metal, a metal oxide, ceramic oxide, or inert carbon having a plurality of cavities therein, in which at least some of the cavities are in fluid communication with the surface and wherein at least one cavity is defined by a cavity surface having a plurality of pores therein; and

(b) a first composition comprising a first therapeutic agent, wherein the first composition is disposed within at least some of the pores.

30. The stent of claim 29, wherein the sidewall structure comprises a plurality of struts and openings in the sidewall structure.

31. The stent of claim 29, wherein the surface of the stent sidewall is the abluminal surface.

32. The stent of claim 29, wherein the stent is an intravascular stent.

33. The stent of claim 29, wherein the stent is an intravascular balloon-expandable stent, and wherein the first composition conforms to the surface of the stent so that the stent sidewall structure is preserved.

34. The stent of claim 33, wherein the surface of the sidewall structure comprises an abluminal surface.

35. The sent of claim 29, wherein the stent is an intravascular self-expanding stent.

36. The stent of claim 29, wherein at least one of the pores is in fluid communication with the cavity surface.

37. The stent of claim 29, wherein the pores are distributed throughout the stent sidewall structure.

38. The stent of claim 29, wherein the pores are homogenously distributed throughout the stent sidewall structure.

39. The stent of claim 29, wherein the first composition is also disposed within at least one of the cavities.

40. The stent of claim 29, wherein the first coating composition is radiopaque.

41. The stent of claim 29, wherein the first composition further comprises a polymer.

42. The stent of claim 41, wherein the polymer is biostable.

43. The stent of claim 41, wherein the polymer is bioabsorbable

44. The stent of claim 41, wherein the polymer comprises styrene-isobutylene-styrene, polylactic-co-glycolic acid (PLGA), polybutyl methacrylate (PBMA), polyvinylidene fluoride (PVDF), or a combination thereof.

45. The stent of claim 29, wherein the metal oxide or ceramic oxide comprises iridium oxide, titanium oxide, titanium dioxide, iron oxide, hydroxyapatite, calcium phosphates, alumina, zirconia, zirconium, silica based glasses, or a combination thereof.

46. The stent of claim 29, wherein the metal comprises gold, tantalum, platinum, titanium, Nitinol or a combination thereof.

47. The stent of claim 29, wherein the diameter of the pores is less than or equal to one micron.

48. The stent of claim 29, wherein the width of the cavities is greater than or equal to one micron.

49. The stent of claim 29, wherein the stent further comprises a second composition comprising a second therapeutic agent, wherein the second composition is disposed in at least some of the cavities.

50. The stent of claim 49, wherein the first therapeutic agent and second therapeutic agent are different.

51. The stent of claim 29, wherein the therapeutic agent comprises an anti-thrombogenic agent, anti-angiogenesis agent, anti-proliferative agent, antibiotic, anti-restenosis agent, growth factor, immunosuppressant, radiochemical, or a combination thereof.

52. The stent of claim 29, wherein the therapeutic agent comprises an anti-restenosis agent.

53. The stent of claim 29, wherein the therapeutic agent comprises paclitaxel.

54. The stent of claim 29, wherein the therapeutic agent comprises sirolimus, tacrolimus, pimecrolimus, zolarolimus or everolimus.

55. The stent of claim 49, wherein the second composition further comprises a polymer.

56. A method of coating an implantable stent having a surface comprising:

(a) disposing a first coating composition on the surface, wherein the first coating composition comprises a metal, a metal or ceramic oxide, or inert carbon;

(b) creating a plurality of cavities in the first coating composition, wherein the cavities have a cavity surface;

(c) creating a plurality of pores within the cavity surface; and

(d) disposing a second coating composition within at least one of the pores, wherein the second coating composition comprises a first therapeutic agent.

57. The method of claim 56, further comprising disposing the second coating composition within at least some of the cavities.

58. The method of claim 56, further comprising disposing a third coating composition within at least some of the cavities, wherein the third coating composition comprises a second therapeutic agent.

59. The method of claim 56, further comprising disposing a third coating composition within at least some of the cavities, wherein the third coating composition comprises a polymer.

60. The method of claim 56, wherein the second coating composition further comprises a polymer.

61. The method of claim 56, wherein the cavities are formed by laser ablation, drilling, chemical etching or a combination thereof.

62. A method of coating an implantable stent having a surface comprising:

(a) disposing a first coating composition on the surface, wherein the first coating composition comprises a metal, a metal or ceramic oxide, or inert carbon, and wherein the first coating composition comprises a plurality of pores therein.

(b) creating a plurality of cavities in the first coating composition; and

(c) disposing a second coating composition within at least one of the pores, wherein the second coating composition comprises a first therapeutic agent.

63. The method of claim 62, further comprising disposing the second coating composition within at least some of the cavities.

64. The method of claim 62, further comprising disposing a third coating composition within at least some of the cavities, wherein the third coating composition comprises a second therapeutic agent.

65. The method of claim 62, further comprising disposing a third coating composition within at least some of the cavities, wherein the third coating composition comprises a polymer.

66. The method of claim 62, wherein the second coating composition further comprises a polymer.

67. The method of claim 62, wherein the cavities are formed by laser ablation, drilling, chemical etching or a combination thereof.

68. A method of coating an implantable stent having a surface comprising a metal, a metal or ceramic oxide, or inert carbon having a plurality of pores therein, the method comprising:

(a) creating a plurality of cavities in the surface, wherein the cavities have a cavity surface and wherein at least some of the pores are in fluid communication with a portion of the cavity surface; and

(b) disposing a first composition comprising a first therapeutic agent within at least some of the pores.

69. The method of claim 68, further comprising disposing the first composition within at least some of the cavities.

70. The method of claim 68, further comprising disposing a second coating composition within at least some of the cavities, wherein the second composition comprises a second therapeutic agent.

71. The method of claim 68, further comprising disposing a second composition within at least some of the cavities, wherein the second coating composition comprises a polymer.

72. The method of claim 68, wherein the first composition further comprises a polymer.

73. The method of claim 68, wherein the cavities are formed by laser ablation, drilling, chemical etching or a combination thereof.

74. A method of coating an implantable stent having a surface comprising a metal, a metal or ceramic oxide or inert carbon, the method comprising:

(a) creating a plurality of cavities in the metal or ceramic oxide or inert carbon, wherein the cavities have a cavity surface;

(b) creating a plurality of pores in the metal or ceramic oxide or inert carbon and wherein at least some of the pores are in fluid communication with a portion of the cavity surface; and

(c) disposing a first composition comprising a first therapeutic agent within at least some of the pores.

75. The method of claim 74, further comprising disposing the first composition within at least some of the cavities.

76. The method of claim 74, further comprising disposing a second composition within at least some of the cavities, wherein the second composition comprises a second therapeutic agent.

77. The method of claim 74, further comprising disposing a second composition within at least some of the cavities, wherein the second composition comprises a polymer.

78. The method of claim 74, wherein the cavities are formed by laser ablation, drilling, chemical etching or a combination thereof.