Block copolymers including a methoxyethyl methacrylate midblock

• US 20080003253A1
• Filed: 06/29/2006
• Published: 01/03/2008
• Est. Priority Date: 06/29/2006
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Glauser, Thierry
• Granted Patent: US 8,956,640 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08F 293/005 using free radical "living" or "controlled" polymerisation, e.g. using a complexing agent
• 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

Abstract

A block copolymer comprising a methoxyethyl methacrylate (MOEMA) midblock is provided for forming a coating a medical device for controlled release of a bioactive agent.

Claims

1. An block copolymer comprising a methoxyethyl methacrylate (MOEMA) midblock and A and B end blocks, the copolymer having a general formula of A-[MOEMA]_n-B, wherein n is a positive integer from 1 to about 100,000.

2. The block copolymer of claim 1, wherein the midblock has a number average molecular weight (M_n) from about 30 kDa to about 100 kDa.

3. The block copolymer of claim 1, wherein the A and B end blocks independently have a number average molecular weight (M_n) from about 5 kDa to about 40 kDa

4. The block copolymer of claim 1, wherein the midblock comprises units derived from monomers having a hydrophilic pendant group.

5. The block copolymer of claim 4, wherein the units derived from monomers having a hydrophilic pendant group comprises up to about 15 wt % of the midblock.

6. The block copolymer of claim 5, wherein the hydrophilic pendant group is a hydroxyl group or an amino group.

7. The block copolymer of claim 5, wherein the monomers having a hydrophilic pendant group is hydroxyethyl methacrylate (HEMA) or aminoethyl methacrylate (AEMA).

8. The block copolymer of claim 6, further comprising a peptide, a drug, an active compound or a hydrophilic side chain attached to the midblock via the hydroxyl group or the amino group.

9. The block copolymer of claim 1, which is an amphiphilic copolymer comprising a hydrophilic domain(s) and a hydrophobic domain(s).

10. A coating on a medical device comprising a block copolymer according to any of claims 1-9.

11. The coating of claim 10, further comprising a bioactive agent.

12. The coating of claim 10, further comprising a bioactive agent selected from paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy] ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, or midostaurin, or prodrugs, co-drugs, or combinations of these.

13. A coating comprising the amphiphilic block copolymer of claim 9, further comprising a hydrophilic drug and a hydrophobic drug, wherein the coating provides controlled release of the hydrophilic drug and the hydrophobic drug.

14. The coating of claim 13, wherein the hydrophilic drug is a peptide or a drug carrying a charge.

15. The coating of claim 14, wherein the hydrophilic drug is RGD, cRGD or mimetics of these.

16. The coating of claim 12, wherein the medical device is a stent.

17. The coating of claim 12, wherein the medical device is a bioabsorbable stent.

18. The coating of claim 13, wherein the medical device is a stent.

19. The coating of claim 13, wherein the medical device is a bioabsorbable stent.

20. A method of treating, preventing or ameliorating a medical condition, comprising implanting in a human being a medical device comprising the coating of claim 10, wherein the medical condition is selected from 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, urethra obstruction, tumor obstruction, diabetic vascular disease, and combinations thereof.