Biobeneficial coating compostions and methods of making and using thereof

• US 20050112172A1
• Filed: 11/26/2003
• Published: 05/26/2005
• Est. Priority Date: 11/26/2003
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Pacetti, Stephen D.
• Granted Patent: US 7,807,722 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• 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 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C08L 53/02 of vinyl-aromatic monomers and conjugated dienes

Abstract

A biobeneficial coating composition for coating an implantable device, such as a drug eluting stent, and a method of coating the device with the composition, and an implantable device coated with the composition are provided.

Claims

1. A composition for coating an implantable device comprising

(1) a first block copolymer comprising a block having a glass transition temperature (T_g) below about body temperature and a second block having a T_g or a melting temperature (T_m) above about body temperature, and

(2) a material selected from the group consisting of a biobeneficial polymer capable of forming a conjugate with the first block copolymer, a second block copolymer and combination thereof, wherein the second block copolymer comprising

(i) a biobeneficial component;

and

(ii) a component selected from the group consisting of components miscible with the first block copolymer and components insoluble in water,

2. The composition of claim 1 wherein the block having a T_g above about body temperature has a structure of Formula I and the block having a T_g below about body temperature has a structure of Formula II:

3. The composition of claim 1 wherein the first block copolymer has the following structure:

4. The composition of claim 1 wherein the biobeneficial polymer is covalently attached to the first block copolymer via a chemical linkage.

5. The composition of claim 3 wherein the biobeneficial polymer is covalently attached to the phenyl ring of the structure of Formula III.

6. The composition of claim 5 wherein the biobeneficial polymer is selected from the group consisting of poly(ethylene glycol), poly(propylene glycol), PLURONIC™

surfactants, poly(tetramethylene glycol), hydroxy functional poly(vinyl pyrrolidone), dextran, dextrin, sodium hyaluronate, hyaluronic acid, heparin, Elastin, Chitosan, poly(2-hydroxyethyl methacrylate), sulphonated poly(styrene), poly(3-hydroxypropyl methacrylamide), 4-amino-2,2′

,6,6′

-tetrapiperidine oxide, stable nitroxides, super oxide dimutase mimics, free radical scavengers and combinations thereof.

7. The composition of claim 6 wherein the conjugate has the structure of Formula IV:

8. The composition of claim 6 wherein the conjugate has the structure of Formula V:

9. The composition of claim 1 wherein the component of the second block copolymer miscible with the first block copolymer is a hydrophobic material.

10. The composition of claim 1 wherein the second block copolymer is selected from the group consisting of polystyrene-polyisobutylene-polystyrene block copolymer (SIS), polystyrene, polyisobutylene, polycaprolactone (PCL), poly(L-lactide), poly(D,L-lactide), poly(lactides), poly(lactide-co-glycolide), poly(glycolide), polylactic acid (PLA), polyalkylene, polyfluoroalkylene, polyhydroxyalkanoate, poly(3-hydroxybutyrate), poly(4-hydroxybutyrate), poly(3-hydroxyvalerate), poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3-hydroxyhexanoate), poly(4-hdyroxyhexanoate), mid chain polyhydroxyalkanoate, poly(trimethylene carbonate), poly(ortho ester), polyphosphazenes, poly(phosphoester), poly(tyrosine derived arylates), poly(tyrosine derived carbonates), and a combination thereof.

11. The composition of claim 1 wherein the water insoluble component is selected from the group consisting of polydimethyloxanone (PDMS), polyvinylidene fluoride (PVDF), polyhexafluoropropylene (HFP), polydimethylsiloxane, poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP), poly(vinylidene fluoride-co-chlorotrifluoroethylene) (PVDF-CTFE), poly(butyl methacrylate), poly(methyl methacrylate), poly(methacrylates), poly(vinyl acetate), poly(ethylene-co-vinyl acetate), poly(ethylene-co-vinyl alcohol), poly(ester urethanes), poly(ether-urethanes), poly(carbonate-urethanes), poly(silicone-urethanes), and poly(urea-urethanes), and a combination thereof.

12. The composition of claim 1 wherein the biobeneficial component of the second block copolymer is selected from the group consisting of poly(ethylene glycol), poly(propylene glycol), PLURONIC™

surfactants, poly(tetramethylene glycol), hydroxy functional poly(vinyl pyrrolidone), dextran, dextrin, sodium hyaluronate, hyaluronic acid, heparin, Elastin, Chitosan, poly(2-hydroxyethyl methacrylate), sulphonated poly(styrene), poly(3-hydroxypropyl methacrylamide), 4-amino-2,2′

,6,6′

-tetrapiperidine oxide, stable nitroxides, super oxide dimutase mimics, free radical scavengers and combinations thereof.

13. The composition of claim 1 wherein the second block copolymer is selected from the group consisting of SIS-PEG, polystyrene-PEG, polyisobutylene-PEG, PCL-PEG, PLA-PEG, PDMS-PEG, PVDF-PEG, SIS-hyaluronic acid (HA), polystyrene-HA, polyisobutylene-HA, PCL-HA, PLA-HA, PMMA-HA, PVDF-HA, SIS-heparin, polystyrene-heparin, polyisobutylene-heparin, PCL-heparin, PLA-heparin, PMMA-heparin, and PVDF-heparin.

14. The composition of any of claims 1-13 further comprising a bioactive agent.

15. The composition of claim 14 wherein the bioactive agent is selected from the group consisting of proteins, peptides, anti-inflammatory agents, antivirals, anticancer drugs, anticoagulant agents, free radical scavengers, Everolimus, sirolimus, sirolimus derivatives, paclitaxel, estradiol, steroidal anti-inflammatory agents, antibiotics, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl(4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, ABT-578, clobetasol, cytostatic agents, and a combination thereof.

16. The composition of claim 15 wherein the free radical scavenger is super oxide dismutase.

17. The composition of claim 15 wherein the bioactive agent is a therapeutic drug for the treatment of restenosis.

18. An implantable device comprising a coating which comprises a composition as defined in accordance with any of claims 1-13.

19. The implantable device of claim 18 further comprises a bioactive agent.

20. The implantable device of claim 18 wherein the bioactive agent is selected from the group consisting of proteins, peptides, anti-inflammatory agents, antivirals, anticancer drugs, anticoagulant agents, free radical scavengers, Everolimus, sirolimus, sirolimus derivatives, paclitaxel, estradiol, steroidal anti-inflammatory agents, antibiotics, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl(4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, ABT-578, clobetasol, cytostatic agents, and a combination thereof.

21. The implantable device of claim 19 wherein the free radical scavenger is super oxide dismutase.

22. The implantable device of claim 19 wherein the bioactive agent is a therapeutic drug.

23. The implantable device of claim 18 which is a stent.

24. The implantable device of claim 19 which is a DES.

25. The implantable device of claim 20 which is a DES.

26. The implantable device of claim 21 which is a DES.

27. The implantable device of claim 22 which is a DES.

28. A method of coating an implantable device comprising coating a composition as defined in claim 1.

29. The method of claim 28 wherein the composition further comprising a bioactive agent.

30. A method of treating a disorder in an animal by implanting in the animal the implantable device of claim 18.

31. The method of claim 30 wherein the implantable device is a stent.

32. The method of claim 30 wherein the composition further comprises a bioactive agent.

33. The method of claim 32 wherein the bioactive agent is selected from the group consisting of proteins, peptides, anti-inflammatory agents, antivirals, anticancer drugs, anticoagulant agents, free radical scavengers, Everolimus, sirolimus, sirolimus derivatives, paclitaxel, estradiol, steroidal anti-inflammatory agents, antibiotics, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl(4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, ABT-578, clobetasol, cytostatic agents, and a combination thereof.

34. The method of claim 33 wherein the free radical scavenger is super oxide dismutase.

35. The method of claim 32 wherein the bioactive agent is a therapeutic drug.

36. The method of claim 28 wherein the implantable device which is a stent.

37. The method of claim 32 which is a DES.

38. The method of claim 33 which is a DES.

39. The method of claim 34 which is a DES.

40. The method of claim 35 which is a DES.

41. The method of claim 28 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque

42. The method of claim 29 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque

43. The method of claim 30 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque

44. The method of claim 31 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque.

45. The method of claim 32 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque.

46. The method of claim 33 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque.

47. The method of claim 34 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque.

48. The method of claim 36 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque.

49. The method of claim 37 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque.

50. The method of claim 38 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque.

51. The method of claim 39 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque.

52. The method of claim 40 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque.

53. The method of claim 41 wherein the animal is a human, and

wherein disorder is selected from the group consisting of stenosis, occlusions of the arterial vasculature, and vulnerable plaque.