Fluid treatment of a polymeric coating on an implantable medical device

• US 7,989,018 B2
• Filed: 03/31/2006
• Issued: 08/02/2011
• Est. Priority Date: 09/17/2001
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Esbeck, Thomas D., McNiven, Andrew F., Pacetti, Stephen, Hossainy, Syed F. A., Ding, Ni
• Primary Examiner(s): Meeks; Timothy H
• Assistant Examiner(s): Sellman; Cachet I
• Application Number:
  US11/395,014
• Publication Number:
  US 20060246209A1
• Time in Patent Office: 1,950 Days
• Field of Search: 623 142- 144, 623/1.46, 427/2.1, 427/2.24, 427/2.25, 427/333, 427/336, 427/337, 427/352
• US Class Current: 427/2.1
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: B05D 3/107 Post-treatment of applied coatings

Abstract

A method for modifying a polymeric coating on an implantable medical device, such as a stent, is disclosed. The method includes application of a fluid to a wet or dry polymeric coating with and without drugs.

Claims

1. A method of manufacturing an implantable medical device comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a semi-crystalline polymer, a first fluid, and optionally an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein the application of the second fluid causes the percent crystallinity of the semi-crystalline polymer to increase.

2. The method of claim 1 wherein the second fluid is in a vapor phase.

3. The method of claim 1 wherein the second fluid is in a liquid phase.

4. The method of claim 1 wherein the first fluid and the second fluid are the same.

5. The method of claim 1 wherein the first fluid and the second fluid are different.

6. The method of claim 1 wherein the first fluid is a blend of two or more solvents.

7. The method of claim 1 wherein the implantable medical device is a stent.

8. The method of claim 1 wherein the semi-crystalline polymer comprises a blend of two or more polymers.

9. The method of claim 1 wherein the semi-crystalline polymer comprises a copolymer.

10. The method of claim 1 wherein the wet coating has a first fluid content percentage (w/w) selected from a group consisting of greater than 10%, greater than 20%, greater than 30%, greater than 40%, and greater than 50%.

11. The method of claim 1 wherein the active agent at least partially dissolves as a result of the exposure to the second fluid.

12. The method of claim 1 wherein the second fluid is a non-solvent for the active agent.

13. The method of claim 1 wherein the second fluid does not cause the active agent to precipitate.

14. The method of claim 1 wherein the second fluid does not cause the active agent to cluster.

15. The method of claim 1 wherein the second fluid does not cause the active agent to crystallize.

16. The method of claim 1 wherein the second fluid does not cause the active agent to solidify.

17. The method of claim 1 wherein the second fluid is selected from the group consisting of chloroform, acetone, cyclohexanone, water, dimethylsulfoxide, propylene glycol methyl ether, iso-propylalcohol, n-propylalcohol, iso-propanol, methanol, ethanol, tetrahydrofuran, dimethylformamide, dimethylacetamide, benzene, toluene, xylene, hexane, cyclohexane, pentane, heptane, octane, nonane, decane, decalin, ethyl acetate, butyl acetate, isobutyl acetate, isopropyl acetate, butanol, diacetone alcohol, benzyl alcohol, 2-butanone, dioxane, methylene chloride, carbon tetrachloride, tetrachloroethylene, tetrachloroethane, chlorobenzene, 1,1,1-trichloroethane, formamide, hexafluoroisopropanol, 1,1,1-trifluoroethanol, acetonitrile, hexamethyl phosphoramide, and any mixtures thereof in any proportion.

18. The method of claim 1 wherein the second fluid is substantially or completely free from any active agents.

19. The method of claim 1 wherein the second fluid is a vapor that comprises a cycloether.

20. The method of claim 1 wherein applying the second fluid to the wet coating comprises applying the second fluid to a designated portion of the wet coating such that at least some of the wet coating does not get exposed to the second fluid.

21. The method of claim 1 wherein applying the second fluid to the wet coating comprises spraying the second fluid at a rate of about 0.1 mL/hr to about 50 mL/hr through an atomization spray nozzle with atomization gas pressures ranging from about 1 psi to about 30 psi.

22. The method of claim 1 wherein after applying the second fluid to the wet coating, the content of the active agent in the coating is at least 80% of the content of the active agent in the coating before applying the second fluid.

23. The method of claim 1 wherein after applying the second fluid to the wet coating, the content of the active agent in the coating is at least 90% of the content of the active agent in the coating before applying the second fluid.

24. The method of claim 1 wherein the duration of exposure to the second fluid is sufficient to decrease the active agent release rate from the dry coating after the implantable medical device comprising the dry coating has been implanted into a biological lumen of a patient.

25. The method of claim 1 further comprising forming a primer layer on a surface of the implantable medical device before applying the composition.

26. The method of claim 1 wherein the wet coating

does not comprise an active agent;

is applied to a reservoir layer comprising an active agent, the reservoir layer being on the implantable medical device; and

forms a barrier layer over the reservoir layer.

27. The method of claim 1 wherein the second fluid is a volatile fluid having a boiling point below 60°

C. at atmospheric pressure.

28. The method of claim 1 wherein the second fluid is a more effective solvent for the active agent than the second fluid is for the semi-crystalline polymer.

29. The method of claim 1 wherein the second fluid at least partially dissolves in the active agent, but does not dissolve in the semi-crystalline polymer.

30. The method of claim 1 wherein the second fluid is chilled.

31. The method of claim 1 wherein the temperature of the second fluid is below 25°

C.

32. The method of claim 1 wherein the temperature of the second fluid is equal to or greater than the glass transition temperature of the semi-crystalline polymer.

33. The method of claim 1 wherein the temperature of the second fluid is below the melting temperature of the semi-crystalline polymer.

34. The method of claim 1 wherein the temperature of the second fluid is equal to or greater than the glass transition temperature of the semi-crystalline polymer and below the melting temperature of the semi-crystalline polymer.

35. The method of claim 1 wherein the temperature of the second fluid is at or about the crystallization temperature of the semi-crystalline polymer.

36. A method of manufacturing an implantable medical device comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid which is a blend of two or more solvents, and optionally an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating.

37. The method of claim 36, wherein the second fluid is in a liquid phase.

38. A method of manufacturing an implantable medical device comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid, and an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein the active agent at least partially dissolves as a result of the exposure to the second fluid.

39. The method of claim 38, wherein the second fluid is in a liquid phase.

40. A method of manufacturing an implantable medical device comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid, and optionally an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein applying the second fluid to the wet coating comprises applying the second fluid to a designated portion of the wet coating such that at least some of the wet coating does not get exposed to the second fluid.

41. The method of claim 40, wherein the second fluid is in a liquid phase.

42. A method of manufacturing an implantable medical device comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid, and optionally an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein applying the second fluid to the wet coating comprises spraying the second fluid at a rate of about 0.1 mL/hr to about 50 mL/hr through an atomization spray nozzle with atomization gas pressures ranging from about 1 psi to about 30 psi.

43. A method of manufacturing an implantable medical device comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid, and an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein the duration of exposure to the second fluid is sufficient to decrease the active agent release rate from the dry coating after the implantable medical device comprising the dry coating has been implanted into a biological lumen of a patient.

44. The method of claim 43, wherein the second fluid is in a liquid phase.

45. A method of manufacturing an implantable medical device comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid, and optionally an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein the second fluid is a volatile fluid having a boiling point below 60°

C. at atmospheric pressure.

46. The method of claim 45, wherein the second fluid is in a liquid phase.

47. A method of manufacturing an implantable medical device comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid, and an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein the second fluid is a more effective solvent for the active agent than the second fluid is for the polymer.

48. The method of claim 47 wherein the second fluid at least partially dissolves the active agent, but does not dissolve the polymer.

49. The method of claim 47, wherein the second fluid is in a liquid phase.

50. A method of manufacturing an implantable medical device comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid, and optionally an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein the second fluid is chilled.

51. The method of claim 50, wherein the second fluid is in a liquid phase.

52. A method of manufacturing an implantable medical device, comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid, and optionally an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein the temperature of the second fluid is below 25°

C.

53. The method of claim 52, wherein the temperature of the second fluid is below 0°

C.

54. The method of claim 53, wherein the second fluid is in a liquid phase.

55. The method of claim 52, wherein the second fluid is in a liquid phase.

56. A method of manufacturing an implantable medical device comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid, and optionally an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein the temperature of the second fluid is equal to or greater than the glass transition temperature of the polymer.

57. The method of claim 56, wherein the temperature of the second fluid is below the melting temperature of the polymer.

58. The method of claim 56, wherein the temperature of the second fluid is at or about the crystallization temperature of the polymer.

59. The method of claim 56, wherein the second fluid is in a liquid phase.

60. A method of manufacturing an implantable medical device, the method comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid, and an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein the second fluid does not cause the active agent to precipitate.

61. A method of manufacturing an implantable medical device, the method comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid, and an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein the second fluid does not cause the active agent to crystallize.

62. A method of manufacturing an implantable medical device, the method comprising:

1) applying a composition to an implantable medical device to form a wet coating, the composition comprising a polymer, a first fluid, and an active agent;

2) applying a second fluid to the wet coating, the second fluid being substantially or completely free from any polymers; and

3) removing the first fluid and the second fluid to form a dry coating;

wherein the second fluid does not cause the active agent to solidify.