Block copolymers of acrylates and methacrylates with fluoroalkenes

• US 7,875,073 B2
• Filed: 11/21/2006
• Issued: 01/25/2011
• 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.
• Primary Examiner(s): Mullis; Jeffrey C
• Application Number:
  US11/603,851
• Publication Number:
  US 20070065480A1
• Time in Patent Office: 1,526 Days
• Field of Search: 525/243, 525/244, 525/276, 623/1.42, 623/1.44, 623/1.49
• US Class Current: 623/1.42
• 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. An implantable device which is a drug-eluting stent, comprising a coating that comprises a bioactive agent and a block copolymer, the block copolymer comprising a fluorinated block and at least one non-fluorinated block, wherein the fluorinated block is a poly(fluoroalkene) having repeating units of the following structure:

2. The implantable device of claim 1,

wherein the non-fluorinated block is a polymer selected from the group consisting of polyesters, polyethers, polyanhydrides, polyglycols, poly(alkylene oxides), polyhydroxyalkanoates, polyphosphazenes, and polyurethanes.

3. The implantable device of claim 2, wherein the bioactive agent is everolimus.

4. The implantable device of claim 3, 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.

5. The implantable device of claim 1, wherein R₁ is selected from the group consisting of COOR₃, and —

CONR₃R₄;

wherein R₂ is selected from the group consisting of —

H, —

CH₃, and -phenyl; and

wherein R₃ and R₄ are selected from the group consisting of —

CH₃, —

CH₂CH₃, —

CH₂CH₂CH₃, —

CH₂CH₂CH₂CH₃, —

CH₂CH₂OH, and -PEG.

6. The implantable device of claim 5, 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.

7. A method of treating restenosis or vulnerable plaque, comprising implanting in a human being in need thereof the implantable device of claim 6.

8. The implantable device of claim 1, wherein the block copolymer has a formula comprising three blocks, the middle block having repeating units of the following structure:

9. The implantable device of claim 8, 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.

10. A method of treating restenosis or vulnerable plaque, comprising implanting in a human being in need thereof the implantable device of claim 9.

11. The implantable device of claim 1, wherein the R₁′

is selected from the group consisting of —

CH₃, —

CH₂CH₃, —

CH₂CH₂CH₃, —

CH₂CH₂CH₂CH₃, —

CH₂CH₂OH, and -PEG, and

wherein R₂ is —

H or —

CH₃.

12. The implantable device 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-rapamycin, and 40-O-tetrazole-rapamycin.

13. The implantable device of claim 1, 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. A method of treating restenosis or vulnerable plaque, comprising implanting in a human being in need thereof the implantable device of claim 13.

15. A method of treating restenosis or vulnerable plaque, comprising implanting in a human being in need thereof 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, wherein the fluorinated block is a poly(fluoroalkene) having repeating units of the following structure:

16. The method of claim 15, wherein R₁ is selected from the group consisting of COOR₃, and —

CONR₃R₄;

wherein R₂ is selected from the group consisting of —

H, —

CH₃, and -phenyl; and

wherein R₃ and R₄ are selected from the group consisting of —

CH₃, —

CH₂CH₃, —

CH₂CH₂CH₃, —

CH₂CH₂CH₂CH₃, —

CH₂CH₂OH, and -PEG.