Block copolymers of acrylates and methacrylates with fluoroalkenes

• US 20050107531A1
• Filed: 11/14/2003
• Published: 05/19/2005
• Est. Priority Date: 11/14/2003
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Claude, Charles D.
• Granted Patent: US 7,261,946 B2
• Time in Patent Office: Days
• US Class Current: 525/88
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• 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 2420/00 Materials or methods for coatings medical devices
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 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: C08F 293/00 Macromolecular compounds obtained by polymerisation on to a macromolecule having groups capable of inducing the formation of new polymer chains bound exclusively at one or both ends of the starting macromolecule on to polymers modified by introduction of unsaturated end groups C08F290/02
• CPC Class Codes: C08F 293/005 using free radical "living" or "controlled" polymerisation, e.g. using a complexing agent
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 53/00 Compositions of block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers
• CPC Class Codes: C09D 153/00 Coating compositions based on block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Coating compositions based on derivatives of such polymers
• CPC Class Codes: Y10T 428/31855 Of addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 428/31938 Polymer of monoethylenically unsaturated hydrocarbon

Abstract

A block copolymer comprising a fluorinated block and a non-fluorinated block and method of making the block copolymer are provided. Also provided herein are a coating on an implantable device comprising the block copolymer and method of using the implantable device.

Claims

1. A block copolymer comprising a fluorinated block and at least one non-fluorinated block, wherein the fluorinated block has the following structure:

2. The block copolymer of claim 1 having a formula of the following structure:

3. The block copolymer of claim 2 wherein R₁′

is —

CH₃, —

CH₂CH₃, —

CH₂CH₂CH₃, —

CH₂CH₂CH₂CH₃, —

CH₂CH₂OH, or -PEG, and

wherein R₂ is —

H or —

CH₃.

4. A block copolymer comprising a fluorinated block and at least one non-fluorinated block, wherein the fluorinated block has the following structure:

5. A polymeric coating composition comprising a block copolymer which comprises a fluorinated block and at least one non-fluorinated block, wherein the fluorinated block has the following structure:

6. The coating composition of claim 5 wherein the block copolymer has a formula of the following structure:

7. The coating composition of claim 6 wherein R₁′

is selected from the group consisting of —

CH₃, —

CH₂CH₃, —

CH₂CH₂CH₃, —

CH₂CH₂CH₂CH₃, —

CH₂CH₂OH, or -PEG, and

wherein R₂ is —

H or —

CH₃.

9. The coating composition of claim 5 further comprising a bioactive agent.

10. The coating composition of claim 6 further comprising a bioactive agent.

11. The coating composition of claim 7 further comprising a bioactive agent.

13. The coating composition of claim 9 wherein the bioactive agent is selected from the group consisting of tacrolimus, dexamethasone, rapamycin, Everolimus, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin.

14. The coating composition of claim 10 wherein the bioactive agent is selected from the group consisting of tacrolimus, dexamethasone, rapamycin, Everolimus, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin.

15. The coating composition of claim 11 wherein the bioactive agent is selected from the group consisting of tacrolimus, dexamethasone, rapamycin, Everolimus, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapainycin, and 40-O-tetrazole-rapamycin.

8. A polymeric coating composition comprising a block copolymer which comprises a fluorinated block and at least one non-fluorinated block, wherein the fluorinated block has the following structure:

12. The coating composition of claim 8 further comprising a bioactive agent.

16. An implantable device comprising a coating which comprises a block copolymer, the block copolymer comprising a fluorinated block and at least one non-fluorinated block.

17. The implantable device of claim 16, wherein the fluorinated block has the following structure:

18. The implantable device of claim 17, wherein the block copolymer has a formula of the following structure:

19. The implantable device of claim 18 wherein R₁′

is selected from the group consisting of —

CH₃, —

CH₂CH₃, —

CH₂CH₂CH₃, —

CH₂CH₂CH₂CH₃, —

CH₂CH₂OH, or -PEG, and

wherein R₂ is —

H or —

CH₃.

20. The implantable device of claim 16, wherein the fluorinated block has the following structure:

21. The implantable device of claim 16, which is a drug-eluting stent, wherein the coating further comprises a bioactive agent.

22. The implantable device of claim 17, which is a drug-eluting stent, wherein the coating further comprises a bioactive agent.

23. The implantable device of claim 18, which is a drug-eluting stent, wherein the coating further comprises a bioactive agent.

24. The implantable device of claim 19, which is a drug-eluting stent, wherein the coating further comprises a bioactive agent.

25. The implantable device of claim 20, which is a drug-eluting stent, wherein the coating further comprises a bioactive agent.

26. The implantable device of claim 21, wherein the bioactive agent is selected from the group consisting of tacrolimus, dexamethasone, rapamycin, Everolimus, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin.

27. The implantable device of claim 22, wherein the bioactive agent is selected from the group consisting of tacrolimus, dexamethasone, rapamycin, Everolimus, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin.

28. The implantable device of claim 23, wherein the bioactive agent is selected from the group consisting of tacrolimus, dexamethasone, rapamycin, Everolimus, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin.

29. The implantable device of claim 24, wherein the bioactive agent is selected from the group consisting of tacrolimus, dexamethasone, rapamycin, Everolimus, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin.

30. The implantable device of claim 25, wherein the bioactive agent is selected from the group consisting of tacrolimus, dexamethasone, rapamycin, Everolimus, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin.

31. A method of treating restenosis or vulnerable plaque, comprising implanting in a human being in need thereof the implantable device of claim 16.

32. A method of treating restenosis or vulnerable plaque, comprising implanting in a human being in need thereof the implantable device of claim 17.

33. A method of treating restenosis or vulnerable plaque, comprising implanting in a human being in need thereof the implantable device of claim 26.

34. A method of treating restenosis or vulnerable plaque, comprising implanting in a human being in need thereof the implantable device of claim 27.

35. A method of treating restenosis or vulnerable plaque, comprising implanting in a human being in need thereof the implantable device of claim 28.

36. A method of synthesizing a block copolymer comprising a fluorinated block and at least a block of the following structure:

37. The method of claim 36 wherein the di-halo macromer is formed by polymerizing a fluorinated olefin in the presence of a dihalide.

38. The method of claim 37 wherein the fluorinated olefin is selected from the group consisting of vinylidene fluoride, hexafluoropropylene, tetrafluoroethylene, and a combination thereof.

39. The method of claim 38 wherein the di-halo macromer is prepared by polymerizing a mixture of vinylidene fluoride and 1,1,2,3,3,3-hexafluoropropylene in the presence of 1,2-diiodo-1,1,2,2-difluoroethylene.

40. The method of claim 39 the di-halo macromer has a structure of