Poly(hydroxyalkanoate-co-ester amides) and agents for use with medical articles

• US 7,202,325 B2
• Filed: 01/14/2005
• Issued: 04/10/2007
• Est. Priority Date: 01/14/2005
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Pacetti, Stephen D., Hossainy, Syed F. A.
• Primary Examiner(s): BOYKIN, TERRESSA M
• Application Number:
  US11/035,816
• Publication Number:
  US 20060160985A1
• Time in Patent Office: 816 Days
• Field of Search: 424/423, 424/78.3, 525/54.1, 525/54.2, 528/272
• US Class Current: 528/272
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• 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: C08G 63/6852 derived from hydroxy carboxylic acids
• CPC Class Codes: C08G 69/44 Polyester-amides
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 77/12 Polyester-amides
• CPC Class Codes: C09D 167/00 Coating compositions based on polyesters obtained by reactions forming a carboxylic ester link in the main chain based on polyester-amides C09D177/12; based on polyester-imides C09D179/08; Coating compositions based on derivatives of such polymers

Abstract

Polymers containing poly(hydroxyalkanoate-co-ester amides) and agents for use with medical articles are disclosed along with methods of fabricating medical articles comprising these polymers. The medical articles generally comprise an implantable substrate having a coating containing a poly(hydroxyalkanoate-co-ester amide).

Claims

1. A composition comprising a polymer consisting of a poly(hydroxyalkanoate-co-ester amide) copolymer represented by a formula:

2. The composition of claim 1, wherein the polymer comprises a hydroxyalkanoate selected from the group consisting of 3-hydroxybutyrate, 4-hydroxybutyrate, 3-hydroxyvalerate, 3-hydroxybutyrate-co-valerate, caprolactone, lactide, glycolide, lactide-co-glycolide, and combinations thereof.

3. The composition of claim 1, wherein at least one of L₁, B, L₂ or X comprises an agent.

4. The composition of claim 1, wherein the agent is connected to the polymer.

5. The composition of claim 1, wherein the agent is blended with the polymer.

6. The composition of claim 3, wherein the agent comprises a component selected from a group consisting of poly(alkylene glycols), phosphorylcholine, N-vinyl pyrrolidone, poly(ethylene oxide), poly(acrylamide methyl propane sulfonic acid), poly(styrene sulfonate), polysaccharides, poly(ester amides), peptides, non-thrombotics, antimicrobials, and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

7. The composition of claim 6, wherein the poly(alkylene glycol) comprises a component selected from a group consisting of poly(ethylene glycol), poly(propylene glycol), and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

8. The composition of claim 6, wherein the polysaccharide comprises a component selected from a group consisting of carboxymethylcellulose, sulfonated dextran, sulfated dextran, dermatan sulfate, chondroitin sulfate, hyaluronic acid, heparin, hirudin, and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

9. The composition of claim 1, wherein the poly(ester amide) comprises a component selected from a group consisting of

10. The composition of claim 9, wherein the polymer comprises

11. The composition of claim 10, wherein R₇ comprises a functionalized alkylene radical, wherein the functional group forms a linkage with X.

12. The composition of claim 9, wherein the polymer comprises

13. The composition of claim 12, wherein R₇ comprises a functionalized alkylene radical, wherein the functional group forms a linkage with X.

14. The composition of claim 1, wherein the polymer comprises

15. The composition of claim 14, wherein R₇ comprises a functionalized alkylene radical, wherein the functional group forms a linkage with X.

16. The composition of claim 1, wherein the polymer comprises

17. The composition of claim 16, wherein R₇ comprises a functionalized alkylene radical and the functional group forms a linkage with X.

18. The composition of claim 1, wherein the polymer comprises

19. The composition of claim 18, wherein R₇ comprises a functionalized alkylene radical and the functional group forms a linkage with X.

20. The composition of claim 6, wherein the peptide comprises a component selected from a group consisting of elastin, silk-elastin, collagen, atrial natriuretic peptide (ANP), Arg-Gly-Asp (RGD);

and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

21. The composition of claim 3, wherein the agent comprises a component selected from a group consisting of a free radical scavenger, a nitric oxide donor, rapamycin, methyl rapamycin, 42-Epi-(tetrazoylyl) rapamycin, everolimus, tacrolimus, paclitaxel, docetaxel, estradiol, clobetasol, idoxifen, tazarotene and any prodrugs, metabolites, analogs, homologues, congeners, and any derivatives, salts and combinations thereof.

22. The composition of claim 21, wherein the free radical scavenger comprises a component selected from a group consisting of 2,2′

,6,6′

-tetramethyl-1-piperinyloxy, free radical;

4-amino-2,2′

,6,6′

-tetramethyl-1-piperinyloxy, free radical;

4-hydroxy-2,2′

,6,6′

-tetramethyl-piperidene-1-oxy, free radical;

4-carboxy-2,2′

,6,6′

-tetramethyl-1-piperinyloxy, free radical;

2,2′

,3,4,5,5′

-hexamethyl-3-imidazolinium-1-yloxy methyl sulfate, free radical;

16-doxyl-stearic acid, free radical;

superoxide dismutase mimic; and

any analogs, homologues, congeners, derivatives, salts and combinations thereof.

23. The composition of claim 21, wherein the free radical scavenger comprises a component selected from a group consisting of TEMPO and any analogs, homologues, congeners, derivatives, salts or combinations thereof.

24. The composition of claim 21, wherein the nitric oxide donor comprises a component selected from the group consisting of S-nitrosothiols, nitrites, N-oxo-N-nitrosamines, substrates of nitric oxide synthase, diazenium diolates and any analogs, homologues, congeners, derivatives, salts and combinations thereof.

25. The composition of claim 3 further comprising an additional agent that may be combined with the composition.

26. The composition of claim 25, wherein the additional agent comprises an essential oil.

27. The composition of claim 26, wherein the essential oil comprises garlic oil.

28. The composition of claim 25, wherein the additional agent comprises a component selected from a group consisting of castor oil, fish oil, ethanol, xylene, dimethyl formamide, glycerol, and combinations thereof.

29. The composition of claim 1, wherein L₁ or L₂ comprises a component selected from a group consisting of ethers, amides, esters, anhydrides, orthoesters, all-aromatic carbonates, acetals, ketals, urethanes, ureas, glycosides, disulfides, siloxanes, and combinations thereof.

30. A medical article comprising the composition of claim 1.

31. The medical article of claim 30 comprising a stent.

32. A coating comprising the composition of claim 1, wherein the coating is for a medical article.

33. A stent comprising the coating of claim 32.

64. A drug-eluting stent comprising a poly(hydroxyalkanoate-co-ester amide) copolyester of claim 1.

65. The drug-eluting stent of claim 64 comprising a coating, wherein the coating includes an agent.

66. The drug-eluting stent of claim 65, wherein the agent comprises a component selected from a group consisting of a free radical scavenger, a nitric oxide donor, rapamycin, methyl rapamycin, 42-Epi-(tetrazoylyl) rapamycin, everolimus, tacrolimus, paclitaxel, docetaxel, estradiol, clobetasol, idoxifen, tazarotene and any prodrugs, metabolites, analogs, homologues, congeners, and any derivatives, salts and combinations thereof.

67. A method of treating a disorder in a patient comprising implanting in the patient the stent of claim 64, wherein the disorder is selected from the group consisting of atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, and combinations thereof.

34. A method comprising fabricating (i) a medical article comprising an implantable substrate or (ii) a coating for the medical article, wherein said fabricating comprises:

(a) preparing a polymer composition consisting of a poly(hydroxyalkanoate-co-ester amide) copolymer represented by a formula;

35. The method of claim 34, wherein said medical article comprises a stent.

36. The method of claim 34, wherein the polymer comprises a hydroxyalkanoate selected from the group consisting of 3-hydroxybutyrate, 4-hydroxybutyrate, 3-hydroxyvalerate, 3-hydroxybutyrate-co-valerate, caprolactone, lactide, glycolide, lactide-co-glycolide, and combinations thereof.

37. The method of claim 34, wherein at least one of L₁, B, L₂ or X comprises an agent.

38. The method of claim 37, wherein the agent is connected to the polymer.

39. The method of claim 37, wherein the agent is blended with the polymer.

40. The method of claim 37, wherein the agent comprises a component selected from a group consisting of poly(alkylene glycols), phosphorylcholine, poly(N-vinyl pyrrolidone), poly(ethylene oxide), poly(ester amide), poly(acrylamide methyl propane sulfonic acid), poly(styrene sulfonate), polysaccharides, peptides, non-thrombotics, antimicrobials, and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

41. The method of claim 40, wherein the poly(alkylene glycol) comprises a component selected from a group consisting of poly(ethylene glycol), poly(propylene glycol), and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

42. The method of claim 40, wherein the polysaccharide comprises a component selected from a group consisting of carboxymethylcellulose, sulfonated dextran, sulfated dextran, dermatan sulfate, chondroitin sulfate, hyaluronic acid, heparin, hirudin, and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

43. The method of claim 40, wherein the poly(ester amide) comprises a component selected from a group consisting of

44. The method of claim 43, wherein the polymer comprises

45. The method of claim 44, wherein R₇ comprises a functionalized alkylene radical, wherein the functional group forms a linkage with X.

46. The method of claim 43, wherein the polymer comprises

47. The method of claim 46, wherein R₇ comprises a functionalized alkylene radical, wherein the functional group forms a linkage with X.

48. The method of claim 34, wherein the polymer comprises

49. The method of claim 48, wherein R₇ comprises a functionalized alkylene radical, wherein the functional group forms a linkage with X.

50. The method of claim 34, wherein the polymer comprises

51. The method of claim 50, wherein R₇ comprises a functionalized alkylene radical and the functional group forms a linkage with X.

52. The method of claim 34, wherein the polymer comprises

53. The method of claim 52, wherein R₇ comprises a functionalized alkylene radical and the functional group forms a linkage with X.

54. The method of claim 40, wherein the peptide comprises a component selected from a group consisting of elastin, silk-elastin, collagen, atrial natriuretic peptide (ANP), Arg-Gly-Asp (RGD);

and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

55. The method of claim 37, wherein the agent comprises a component selected from a group consisting of a free radical scavenger, a nitric oxide donor, rapamycin, methyl rapamycin, 42-Epi-(tetrazoylyl) rapamycin, everolimus, tacrolimus, paclitaxel, docetaxel, estradiol, clobetasol, idoxifen, tazarotene and any prodrugs, metabolites, analogs, homologues, congeners, and any derivatives, salts and combinations thereof.

56. The method of claim 55, wherein the free radical scavenger comprises a component selected from a group consisting of 2,2′

,6,6′

-tetramethyl-1-piperinyloxy, free radical;

4-amino-2,2′

,6,6′

-tetramethyl-1-piperinyloxy, free radical;

4-hydroxy-2,2′

,6,6′

-tetramethyl-piperidene-1-oxy, free radical;

4-carboxy-2,2′

,6,6′

-tetramethyl-1-piperinyloxy, free radical;

2,2′

,3,4,5,5′

-hexamethyl-3-imidazolinium-1-yloxy methyl sulfate, free radical;

16-doxyl-stearic acid, free radical;

superoxide dismutase mimic; and

any analogs, homologues, congeners, derivatives, salts and combinations thereof.

57. The method of claim 55, wherein the free radical scavenger comprises a component selected from a group consisting of TEMPO and any analogs, homologues, congeners, derivatives, salts or combinations thereof.

58. The method of claim 55, wherein the nitric oxide donor comprises a component selected from the group consisting of S-nitrosothiols, nitrites, N-oxo-N-nitrosamines, substrates of nitric oxide synthase, diazenium diolates and any analogs, homologues, congeners, derivatives, salts and combinations thereof.

59. The method of claim 37, wherein the fabricating further comprises combining an additional agent with the composition.

60. The method of claim 59, wherein the additional agent comprises an essential oil.

61. The method of claim 60, wherein the essential oil comprises garlic oil.

62. The method of claim 59, wherein the additional agent comprises a component selected from a group consisting of castor oil, fish oil, ethanol, xylene, dimethyl formamide, glycerol, and combinations thereof.

63. The method of claim 34, wherein L₁ or L₂ comprises a component selected from a group consisting of ethers, amides, esters, anhydrides, orthoesters, all-aromatic carbonates, acetals, ketals, urethanes, ureas, glycosides, disulfides, siloxanes, and combinations thereof.