N-substituted monomers and polymers

• US 8,034,365 B2
• Filed: 10/16/2007
• Issued: 10/11/2011
• Est. Priority Date: 10/17/2006
• Status: Expired due to Fees

• Current Assignee: REVA Medical Inc.
• Original Assignee: REVA Medical Inc.
• Inventors: Baluca, Ernest G
• Primary Examiner(s): Wax; Robert A
• Assistant Examiner(s): Al-Awadi; Danah
• Application Number:
  US11/873,362
• Publication Number:
  US 20080112999A1
• Time in Patent Office: 1,456 Days
• Field of Search: None
• US Class Current: 424/426
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• 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: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C08G 63/6856 Dicarboxylic acids and dihydroxy compounds
• CPC Class Codes: C08G 64/045 containing aliphatic unsaturation
• CPC Class Codes: C08G 64/12 containing nitrogen
• CPC Class Codes: C08G 64/183 containing polyether sequences
• CPC Class Codes: C08G 64/186 containing polysiloxane sequences
• CPC Class Codes: C08G 79/04 Phosphorus linked to oxygen or to oxygen and carbon
• CPC Class Codes: C08L 69/00 Compositions of polycarbonates; Compositions of derivatives of polycarbonates
• CPC Class Codes: C08L 85/02 containing phosphorus

Abstract

Described herein are N-substituted monomers and polymers, methods of making such monomers and polymers, and methods of using them in various applications, such as medical devices. In preferred embodiments, the medical device is a stent.

Claims

1. A polymer that comprises a recurring unit of the formula (I):

2. The polymer according to claim 1, wherein in formula (I) is a branched or unbranched C₁-C₆ alkyl.

3. The polymer according to claim 1, wherein R^x in formula (I) is a methyl.

4. The polymer according to claim 1, wherein:

X¹ and X² in formula (I) are each I;

A¹ in formula (I) is

5. The polymer according to claim 1, wherein Q in formula (I) comprises from about 20 to about 30 carbon atoms.

6. The polymer according to claim 1, wherein Q in formula (I) is a group that comprises the formula (VII):

7. The polymer to claim 1, wherein R⁵ in formula (I) is —

CH═

CH—

or —

(CH₂)_a—

;

R⁶ in formula (I) is —

(CH₂)_a—

; and

Q in formula (I) is an ester group comprising from about 20 to about 30 carbon atoms.

8. The polymer to claim 1, wherein Z in formula (I) is O or S and J¹ and J² in formula (I) are each independently selected from the group consisting of Br and I.

9. The polymer according to claim 1, further comprising a recurring unit of the formula (II):

10. The polymer of according to claim 1, further comprising a recurring unit of the formula (III):

11. The polymer according to claim 1, further comprising a recurring unit of the formula (IV):

12. The polymer according to claim 1, further comprising a recurring unit of the formula (V):

13. The polymer according to claim 1, further comprising a recurring unit of the formula (VI):

14. A method for making a polymer of claim 1 comprising attaching an N-substituent during the synthesis of a corresponding monomer.

15. A method for making a polymer of claim 1 comprising attaching an N-substituent after polymerization of a corresponding monomer.

16. A medical device comprising a polymer of claim 1.

17. The medical device of claim 16, wherein the medical device comprises a stent.

18. The medical device of claim 17, wherein the stent is selected from the group consisting of a sheet stent, a braided stent, a self-expanding stent, a wire stent, a deformable stent, and a slide-and-lock stent.

19. The medical device of claim 18, wherein the self-expanding stent comprises a heat expandable portion that is temperature-dependent-expandable.

20. The medical device of claim 19, wherein the heat expandable portion is expandable at a temperature above a melting point of the polymer.

21. The medical device of claim 17 wherein at least a portion of the polymer is positioned at a surface of the stent.

22. The medical device of claim 16, wherein the polymer forms a coating on at least a portion of the medical device.

23. The medical device of claim 16 that further comprises an effective amount of at least one therapeutic agent.

24. The medical device of claim 23, wherein the therapeutic agent is selected from the group consisting of antiproliferative agent, anti-inflammatory agent, anti-matrix metalloproteinase agent, lipid lowering agent, cholesterol modifying agent, anti-thrombotic agent, and antiplatelet agent.

25. The medical device of claim 23, wherein the effective amount is sufficient to provide an effect selected from the group consisting of inhibition of restenosis, inhibition of thrombosis, inhibition of plaque formation, inhibition of plaque rupture, inhibition of inflammation, lowering of cholesterol, and promote healing.

26. An inherently radiopaque, biocompatible, bioresorbable polymer comprising one or more recurring units of the formula (Ia):

27. The polymer according to claim 26, wherein R^x in formula (Ia) is a branched or unbranched C₁-C₆ alkyl.

28. The polymer according to claim 26, wherein R^x in formula (Ia) is methyl.

29. The polymer according to claim 26, wherein Q¹, Q² and Q³ in formula (Ia) are each independently H or a non-crystallizable group comprising from about 1 to about 30 carbons.

30. The polymer according to claim 26, wherein at least one of Q¹, Q² and Q³ in formula (Ia) is a group comprising from about 20 to about 30 carbons.

31. The polymer according to claim 26, wherein at least one of Q′

, Q² and Q³ in formula (Ia) is a group comprising the formula (VIIa);

32. The polymer according to claim 26, wherein:

X¹ and X² in formula (Ia) are each I;

R¹ in formula (Ia) is

33. The polymer according to claim 26, further comprising one or more recurring units of the formula (IIa):

34. The polymer of claim 26, further comprising one or more recurring units of the formula (Ib):

35. The polymer of claim 26, wherein R¹ in formula (Ia) is

36. The polymer of claim 26, wherein R¹ in formula (Ia) is

37. The polymer of claim 26, wherein R¹ in formula (Ia) is

38. A method for making a polymer of claim 26 comprising attaching an N-substituent during the synthesis of a corresponding monomer.

39. A method for making a polymer of claim 26 comprising attaching an N-substituent during polymerization of a corresponding monomer.

40. A method for making a polymer of claim 26 comprising attaching an N-substituent after polymerization of a corresponding monomer.

41. A medical device comprising a polymer of claim 26.

42. The medical device of claim 41, wherein the medical device comprises a stent.

43. The medical device of claim 42, wherein the stent is selected from the group consisting of a sheet stent, a braided stent, a self-expanding stent, a wire stent, a deformable stent, and a slide-and-lock stent.

44. The medical device of claim 43, wherein the self-expanding stent comprises a heat expandable portion that is temperature-dependent-expandable.

45. The medical device of claim 44, wherein the heat expandable portion is expandable at a temperature above a melting point of the polymer.

46. The medical device of claim 42 wherein at least a portion of the polymer is positioned at a surface of the stent.

47. The medical device of claim 41, wherein the polymer forms a coating on at least a portion of the medical device.

48. The medical device of claim 41 that further comprises an effective amount of at least one therapeutic agent.

49. The medical device of claim 48, wherein the therapeutic agent is selected from the group consisting of antiproliferative agent, anti-inflammatory agent, anti-matrix metalloproteinase agent, lipid lowering agent, cholesterol modifying agent, anti-thrombotic agent, and antiplatelet agent.

50. The medical device of claim 48, wherein the effective amount is sufficient to provide an effect selected from the group consisting of inhibition of restenosis, inhibition of thrombosis, inhibition of plaque formation, inhibition of plaque rupture, inhibition of inflammation, lowering of cholesterol, and promote healing.

51. A polymer that comprises a recurring unit of the formula (XI):

52. The polymer according to claim 51, wherein R^x in formula (XI) is a branched or unbranched C₁-C₆ alkyl.

53. The polymer according to claim 51, wherein R^x in formula (XI) is methyl.

54. The polymer according to claim 51, wherein M₁, M₂, and M₃ in formula (XI) are each independently selected from O or NH.

55. The polymer according to claim 51, further comprising one or more recurring units of the formula (XII):

56. The polymer according to claim 51, further comprising one or more recurring units of the formula (XIII):

57. The polymer according to claim 51, further comprising one or more recurring units of the formula (XIV):

58. A method for making a polymer of claim 51 comprising attaching an N-substituent during the synthesis of a corresponding monomer.

59. A method for making a polymer of claim 51 comprising attaching an N-substituent during polymerization of a corresponding monomer.

60. A method for making a polymer of claim 51 comprising attaching an N-substituent after polymerization of a corresponding monomer.

61. A medical device comprising a polymer of claim 51.

62. The medical device of claim 61, wherein the medical device comprises a stent.

63. The medical device of claim 62, wherein the stent is selected from the group consisting of a sheet stent, a braided stent, a self-expanding stent, a wire stent, a deformable stent, and a slide-and-lock stent.

64. The medical device of claim 63, wherein the self-expanding stent comprises a heat expandable portion that is temperature-dependent-expandable.

65. The medical device of claim 64, wherein the heat expandable portion is expandable at a temperature above a melting point of the polymer.

66. The medical device of claim 62 wherein at least a portion of the polymer is positioned at a surface of the stent.

67. The medical device of claim 61, wherein the polymer forms a coating on at least a portion of the medical device.

68. The medical device of claim 61 that further comprises an effective amount of at least one therapeutic agent.

69. The medical device of claim 68, wherein the therapeutic agent is selected from the group consisting of antiproliferative agent, anti-inflammatory agent, anti-matrix metalloproteinase agent, lipid lowering agent, cholesterol modifying agent, anti-thrombotic agent, and antiplatelet agent.

70. The medical device of claim 68, wherein the effective amount is sufficient to provide an effect selected from the group consisting of inhibition of restenosis, inhibition of thrombosis, inhibition of plaque formation, inhibition of plaque rupture, inhibition of inflammation, lowering of cholesterol, and promote healing.