Medicated coatings for implantable medical devices including polyacrylates

• US 20060062824A1
• Filed: 09/22/2004
• Published: 03/23/2006
• Est. Priority Date: 09/22/2004
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Glauser, Thierry, Pacetti, Stephen Dirk
• Granted Patent: US 8,110,211 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• 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: C08L 33/10 Homopolymers or copolymers of methacrylic acid esters

Abstract

A polymer for a medical device, particularly for a drug eluting stent, is described. The polymer can be derived from n-butyl methacrylate and can have a degree of an elongation at failure from about 20% to about 500%

Claims

1. A medical article comprising an implantable medical device having a base-polymer-unit-derived polymer with a degree of an elongation at failure from about 20% to about 500%.

2. The medical article of claim 1 wherein the implantable medical device is a stent.

3. The medical article of claim 1 wherein the polymer is a base polymer having a weight average molecular weight of about 200,000 Daltons to about 1,000,000 Daltons.

4. The medical article of claim 3 wherein the polymer comprises a base polymer having a polydispersity index of about 3 to about 6.

5. The medical article of claim 1 wherein the polymer comprises a base polymer having a polydispersity index of about 3 to about 6.

6. The medical article of claim 1 wherein the polymer includes a first acrylic monomer.

7. The medical article of claim 6 wherein the polymer is a copolymer of the base polymer and the first acrylic monomer.

8. The medical article of claim 7 wherein the first acrylic monomer is at least one of n-hexyl methacrylate, 2-ethylhexyl methacrylate, lauryl methacrylate (dodecyl methacrylate), n-octyl methacrylate, n-heptyl methacrylate, n-nonyl methacrylate, 2-ethoxyethyl methacrylate, 2-methoxyethyl methacrylate, pentyl methacrylate, iso-decyl methacrylate, n-decyl methacrylate, n-dodecyl methacrylate), 1-hexadecyl methacrylate, undecyl methacrylate, or 3,5,5-trimethylhexyl methacrylate.

9. The medical article of claim 6 wherein the polymer has a glass transition temperature below about 20°

C.

10. The medical article of claim 9 wherein the glass transition temperature is about −

30°

C. to about 20°

C.

11. The medical article of claim 1 wherein the polymer has the formulas

wherein X and X₁ are each, independently, a hydrogen atom or an alkyl group, R and R₁ are each, independently, a C₁ to C₁₂ straight chained or branched aliphatic radical, and m, n, and p are each integers in which m>

0, n>

0, and p≧

0.

12. The medical article of claim 10 having a glass transition temperature below about 20°

C.

13. The medical article of claim 11 having a glass transition temperature of −

30°

C. to about 20°

C.

14. The medical article of claim 1 wherein the polymer comprises poly(n-butyl methacrylate) and a second polymeric material wherein the polymer has a substantially single glass transition temperature that is below about 20°

C.

15. The medical article of claim 14 wherein the glass transition temperature of about −

30°

C. to about 20°

C.

16. The medical article of claim 14 wherein the second polymeric material is at least one of poly(n-hexyl methacrylate), poly(n-heptyl methacrylate), poly(2-ethylhexyl methacrylate), poly(n-octyl methacrylate), poly(n-nonyl methacrylate), poly(2-ethoxyethyl methacrylate), poly(2-methoxyethyl methacrylate), poly(pentyl methacrylate), poly(isodecyl methacrylate), poly(n-decyl methacrylate), poly(1-hexadecyl methacrylate), poly(undecyl methacrylate), poly(3,5,5-trimethylhexyl methacrylate, or poly(lauryl methacrylate).

17. The medical article of claim 14 wherein the second polymeric material is a non-acrylic polymer with a Tg below that of the base polymer.

18. The medical article of claim 1 wherein the medical device additionally comprises one or any combination of vascular-smooth-muscle-cell-activity inhibitors, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants, and any prodrugs, metabolites, analogs, homologues, congeners, derivatives, or salts of these.

19. The medical article of claim 6 wherein the medical device additionally comprises one or any combination of vascular-smooth-muscle-cell-activity inhibitors, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants, and any prodrugs, metabolites, analogs, homologues, congeners, derivatives, or salts of these.

20. The medical article of claim 9 wherein the medical device additionally comprises one or any combination of vascular-smooth-muscle-cell-activity inhibitors, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants, and any prodrugs, metabolites, analogs, homologues, congeners, derivatives, or salts of these.

21. The medical article of claim 13 wherein the medical device additionally comprises one or any combination of vascular-smooth-muscle-cell-activity inhibitors, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants, and any prodrugs, metabolites, analogs, homologues, congeners, derivatives, or salts of these.

22. The medical article of claim 15 wherein the medical device additionally comprises one or any combination of vascular-smooth-muscle-cell-activity inhibitors, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants, and any prodrugs, metabolites, analogs, homologues, congeners, derivatives, or salts of these.

23. The medical article of claim 15 wherein the medical device additionally comprises one or any combination of vascular-smooth-muscle-cell-activity inhibitors, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants, and any prodrugs, metabolites, analogs, homologues, congeners, derivatives, or salts of these.

47. The medical device of claim 1 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

48. The medical device of claim 47 wherein the base polymer is poly(n-butyl methacrylate).

49. The medical device of claim 4 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

50. The medical device of claim 49 wherein the base polymer is poly(n-butyl methacrylate).

51. The medical device of claim 7 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

52. The medical device of claim 51 wherein the base polymer is poly(n-butyl methacrylate).

53. The medical device of claim 10 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

54. The medical device of claim 53 wherein the base polymer is poly(n-butyl methacrylate).

55. The medical device of claim 11 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

56. The medical device of claim 55 wherein the base polymer is poly(n-butyl methacrylate).

57. The medical device of claim 14 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

58. The medical device of claim 57 wherein the base polymer is poly(n-butyl methacrylate).

59. The medical device of claim 17 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

60. The medical device of claim 59 wherein the base polymer is poly(n-butyl methacrylate).

61. The medical device of claim 18 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

62. The medical device of claim 61 wherein the base polymer is poly(n-butyl methacrylate).

24. A method comprising depositing a coating on an implantable medical device wherein the coating has an base-polymer-unit-derived polymer with a degree of an elongation at failure of about 20% to about 500%.

25. The method of claim 24 wherein the implantable medical device is a stent.

26. The method of claim 24 wherein the polymer comprises a base polymer having a weight average molecular weight of about 200,000 Daltons to about 1,000,000-Daltons.

27. The method of claim 26 wherein the base polymer has a polydispersity index of about 3 to about 6.

28. The method of claim 24 wherein the base polymer has a polydispersity index of about 3 to about 6.

29. The method of claim 24 wherein the polymer includes a first acrylic monomer.

30. The method of claim 29 wherein the polymer is a copolymer of a base polymer and the first acrylic monomer.

31. The method of claim 29 wherein the first acrylic monomer is at least one of n-hexyl methacrylate, 2-ethylhexyl methacrylate, lauryl methacrylate (dodecyl methacrylate), n-octyl methacrylate, n-heptyl methacrylate, n-nonyl methacrylate, 2-ethoxyethyl methacrylate, 2-methoxyethyl methacrylate, pentyl methacrylate, iso-decyl methacrylate, n-decyl methacrylate, n-dodecyl methacrylate), 1-hexadecyl methacrylate, undecyl methacrylate, or 3,5,5-trimethylhexyl methacrylate.

32. The method of claim 29 wherein the polymer has a glass transition temperature below about 20°

C.

33. The method of claim 32 wherein the glass transition temperature of about −

30°

C. to about 20°

C.

34. The method of claim 24 wherein the polymer has at least one of the formulas:

wherein X and X₁ are each, independently, a hydrogen atom or an alkyl group, R and R₁ are each, independently, a C₁ to C₁₂ straight chained or branched aliphatic radical, and m, n, and p are each integers in which m>

0, n>

0, and p≧

0.

35. The method of claim 34 wherein the polymer has a glass transition temperature below about 20°

C.

36. The method of claim 35 wherein the glass transition temperature of −

30°

C. to about 20°

C.

37. The method of claim 24 wherein the polymer comprises a base polymer and a second polymer wherein the polymer substantially has a single glass transition temperature that is below about 20°

C.

38. The method of claim 37 wherein the glass transition temperature of −

30°

C. to about 20°

C.

39. The method of claim 37 wherein the second polymer is at least one of poly(n-hexyl methacrylate), poly(n-heptyl methacrylate), poly(2-ethylhexyl methacrylate), poly(n-octyl methacrylate), poly(n-nonyl methacrylate), poly(2-ethoxyethyl methacrylate), poly(2-methoxyethyl methacrylate), poly(pentyl methacrylate), poly(iso-decyl methacrylate), poly(n-decyl methacrylate), poly(1-hexadecyl methacrylate), poly(undecyl methacrylate), poly(3,5,5-trimethylhexyl methacrylate, or poly(lauryl methacrylate).

40. The method of claim 37 wherein the second polymer is a non-acrylic polymer with a Tg below that of the base polymer.

41. The method of claim 24 wherein the medical device additionally comprises one or any combination of vascular-smooth-muscle-cell-activity inhibitors, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants, and any prodrugs, metabolites, analogs, homologues, congeners, derivatives, or salts of these.

42. The method of claim 29 wherein the medical device additionally comprises one or any combination of vascular-smooth-muscle-cell-activity inhibitors, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants, and any prodrugs, metabolites, analogs, homologues, congeners, derivatives, or salts of these.

43. The method of claim 33 wherein the medical device additionally comprises one or any combination of vascular-smooth-muscle-cell-activity inhibitors, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants, and any prodrugs, metabolites, analogs, homologues, congeners, derivatives, or salts of these.

44. The method of claim 36 wherein the medical device additionally comprises one or any combination of vascular-smooth-muscle-cell-activity inhibitors, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants, and any prodrugs, metabolites, analogs, homologues, congeners, derivatives, or salts of these.

45. The method of claim 37 wherein the medical device additionally comprises one or any combination of vascular-smooth-muscle-cell-activity inhibitors, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants, and any prodrugs, metabolites, analogs, homologues, congeners, derivatives, or salts of these.

46. The method of claim 39 wherein the medical device additionally comprises one or any combination of vascular-smooth-muscle-cell-activity inhibitors, antiproliferatives, antineoplastics, antimitotics, anti-inflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antibiotics, antiallergics, antioxidants, and any prodrugs, metabolites, analogs, homologues, congeners, derivatives, or salts of these.

63. The method of claim 24 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

65. The method of claim 27 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

66. The method of claim 65 wherein the base polymer is poly(n-butyl methacrylate).

67. The method of claim 33 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

68. The method of claim 67 wherein the base polymer is poly(n-butyl methacrylate).

69. The method of claim 34 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

70. The method of claim 69 wherein the base polymer is poly(n-butyl methacrylate).

71. The method of claim 38 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

72. The method of claim 71 wherein the base polymer is poly(n-butyl methacrylate).

73. The method of claim 41 wherein the base polymer is at least one of or any combination of poly(n-butyl methacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), or poly(n-propyl methacrylate).

74. The method of claim 73 wherein the base polymer is poly(n-butyl methacrylate).

64. The method of claim 64 wherein the base polymer is poly(n-butyl methacrylate).