Random copolymers of methacrylates and acrylates

• US 20080008736A1
• Filed: 07/06/2006
• Published: 01/10/2008
• Est. Priority Date: 07/06/2006
• Status: Abandoned Application

• Current Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Glauser, Thierry
• Application Number:
  US11/483,304
• Publication Number:
  US 20080008736A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: C08F 220/14 Methyl esters , e.g. methyl (meth)acrylate
• CPC Class Codes: C08F 220/26 Esters containing oxygen in addition to the carboxy oxygen
• CPC Class Codes: C09D 133/06 of esters containing only carbon, hydrogen and oxygen, the oxygen atom being present only as part of the carboxyl radical

Abstract

A random copolymer including units derived from at least two groups of monomers (a) an alkyl acrylate or methacrylate, (b) an alkoxyalkyl acrylate or methacrylate, and (c) a hydrophilic acrylate or methacrylate and coatings formed thereof are provided.

Claims

1. A random copolymer comprising units derived from at least two of the following groups of monomers:

(a) an alkyl acrylate or metharylate,

(b) an alkoxyalkyl acrylate or methacryalte, and

(c) a hydrophilic acrylate or methacrylate;

wherein the alkyl acrylate or methacrylate has a weight ratio of the total monomers from about 0 to about 0.7,

wherein the alkoxyalkyl acrylate or methacrylate has a weight ratio of the total monomers from about 0 to about 0.9, and

wherein the hydrophilic acrylate or methacrylate has a weight ratio of the total monomers from about 0 to about 0.2.

2. The random copolymer of claim 1,

wherein the alkyl acrylate or methacrylate monomer comprises a C1-C20 straight alkyl, C1-C20 branch-chained alkyl, C1-C20 cyclic alkyl, or C1-C20 arylalkyl group,

wherein the alkoxyalkyl acrylate or methacrylate monomer comprises an alkoxy group having C1-C20 straight alkyl, C1-C20 branch-chained alkyl, C1-C20 cyclic alkyl, or phenyl group, and

wherein the hydrophilic acrylate or methacrylate monomer comprises a hydroxyl group, a carboxylic group, a sulfonate group, an amine group, a thiol group, a group that bears a charge, or a group that bears zwitterions.

3. The random copolymer of claim 2, wherein the group that bears a charge is choline or phosphoryl choline.

4. The random copolymer of claim 1, having a number average molecular weight (M_n) in the range between about 80 kDa to about 250 kDa.

5. The random copolymer of claim 1, comprising:

about 0-0.7 methyl metharylate (MMA),

about 0-0.9 methoxyethyl methacrylate (MOEMA), and

about 0-0.2 hydroxylethyl methacrylate (HEMA)

6. The random copolymer of claim 5, having a M_n in the range between about 80 kDa to about 250 kDa.

7. The random copolymer of claim 5, further comprising a peptide, a drug, an active compound or a hydrophilic side chain attached to the hydroxyl group of the HEMA.

8. The random copolymer of claim 7, 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. A coating on a medical device comprising a random copolymer according to claim 1.

10. A coating on a medical device comprising a random copolymer according to claim 2.

11. A coating on a medical device comprising a random copolymer according to claim 3.

12. A coating on a medical device comprising a random copolymer according to claim 4.

13. A coating on a medical device comprising a random copolymer according to claim 5.

14. A coating on a medical device comprising a random copolymer according to claim 6.

15. A coating on a medical device comprising a random copolymer according to claim 7.

16. A coating on a medical device comprising a random copolymer according to claim 8.

17. The coating of claim 9, further comprising a bioactive agent.

18. The coating of claim 9, 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.

19. A coating comprising the random copolymer of claim 5, further comprising a hydrophilic drug and/or hydrophobic drug, wherein the coating provides controlled release of the hydrophilic drug and/or the hydrophobic drug.

20. The coating of claim 19, wherein the hydrophilic drug is a peptide or a drug carrying a charge.

21. The coating of claim 20, wherein the hydrophilic drug is RGD, cRGD or mimetics of these.

22. The coating of claim 19, where the hydrophobic drug is everolimus.

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

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

25. A method of treating, preventing or ameliorating a medical condition, comprising implanting in a human being a medical device comprising the coating of claim 17, 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.