Coatings for implantable medical devices comprising hydrophilic substances and methods for fabricating the same

• US 20050147647A1
• Filed: 12/24/2003
• Published: 07/07/2005
• Est. Priority Date: 12/24/2003
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Kwok, Connie S., Michal, Eugene T., Tang, Yiwen, Shah, Ashok, Glauser, Thierry, Claude, Charles D., Pacetti, Stephen D., Whatley, John, Astafieva, Irina
• Granted Patent: US 8,309,112 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/606 Coatings
• 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 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: C08L 75/04 Polyurethanes

Abstract

A segmented polyurethane and an amphiphilic random or block copolymer are disclosed. The segmented polyurethane and the amphiphilic random or block copolymer can be used for fabricating a coating for an implantable medical device such as a stent.

Claims

1. A medical article, comprising an implantable substrate and a polymer coating disposed at least on a portion of the substrate, the coating including a segmented polyurethane comprising a soft segment and a hard segment.

2. The medical article of claim 1, wherein the substrate is a stent.

3. The medical article of claim 1, wherein the soft segment is derived from a polyol.

4. The medical article of claim 3, wherein the polyol is selected from a group consisting of poly(ethylene glycol), poly(propylene glycol), poly(tetramethylene glycol), poly(ethylene glycol-co-propylene glycol), poly(ethylene oxide-co-propylene oxide), and blends thereof.

5. The medical article of claim 1, wherein the hard segment is derived from an isocyanate.

6. The medical article of claim 1, wherein the isocyanate comprises aromatic diisocyanates, cycloaliphatic diisocyanates, or aliphatic diisocyanates.

7. The medical article of claim 6, wherein the aromatic diisocyanate is selected from 2,4-toluene diisocyanate and diphenylmethane diisocyanate.

8. The medical article of claim 6, wherein the cycloaliphatic isocyanates are selected from a group consisting of 1,4-cyclohexane diisocyanate, methylene dicyclohexyl diisocyanate, 1,6-hexamethylene diisocyanate, and blends thereof.

9. The medical article of claim 6, wherein the aliphatic isocyanates are selected from a group consisting of 1,6-diisocyanato hexane and 1,6-diisocyanato dodecane.

10. The medical article of claim 1, wherein the segmented polyurethane is poly(urethane-urea), poly(ether urethane) or poly(carbonate urethane).

11. The medical article of claim 10, wherein in poly(urethane-urea) the soft segment is a moiety derived from poly(tetramethylene oxide) and the hard segment is a moiety derived from diphenylmethane diisocyanate.

12. The medical article of claim 1, wherein the coating includes a hydrophilic therapeutic agent.

13. The medical article of claim 12, wherein the therapeutic agent is selected from a group consisting of cyclic-RGD peptide, poly(L-arginine), poly(D-arginine), poly(D,L-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), a racemic mixture of poly(L-arginine) with poly(D-arginine), elastin mimetic polypeptides, and combinations thereof.

14. The medical article of claim 1, wherein the coating includes a small-molecule water soluble drug.

15. A medical article, comprising an implantable substrate and a coating disposed at least on a portion of the substrate, the coating including an amphiphilic copolymer comprising at least one hydrophobic moiety and at least one hydrophilic moiety.

16. The medical article of claim 15, wherein the amphiphilic copolymer comprises an acrylic copolymer.

17. The medical article of claim 15, wherein the acrylic copolymer is a block copolymer or a random copolymer.

18. The medical article of claim 17, wherein the block copolymer is an ABA block copolymer or an AB block-copolymer.

19. The medical article of claim 15, wherein the hydrophobic moiety is selected from a group consisting of methyl methacrylate, ethyl methacrylate, n-butyl methacrylate, lauryl methacrylate, and styrene.

20. The medical article of claim 15, wherein the hydrophilic moiety comprises unsubstituted or substituted acrylates or vinyl monomers having a general formula CH₂═

CX-M, wherein X is hydrogen or methyl and M is a substituted or unsubstituted aromatic group or an ester group O═

C(OR)—

, and wherein R is hydrogen or a hydroxyalkyl group.

21. The medical article of claim 15, wherein the hydrophilic moiety is selected from a group consisting of 2-hydrohyethyl methacrylate, acrylic acid, methacrylic acid, N-vinyl pyrrolidone, poly(ethylene glycol)-acrylate, 2-acrylamido-2-methyl-1-propanesulfonic acid, 3-sulfopropyl acrylate, 3-sulfopropyl methacrylate, vinylsulfonic acid, 4-styrenesulfonic acid and 3-allyloxy-2-hydroxypropanesulfonic acid.

22. The medical article of claim 15, wherein the amphiphilic copolymer has a formula

23. The medical article of claim 15, wherein the amphiphilic copolymer is a product of living free radical copolymerization of plurality of monomers with initiation-transfer agent termination of the living macro-chains.

24. The medical article of claim 23, wherein the monomers comprise acrylates.

25. The medical article of claim 15, wherein the coating additionally includes a therapeutic agent.

26. The medical article of claim 25, wherein the therapeutic agent is selected from a group consisting of cyclic-RGD peptide, poly(L-arginine), poly(D-arginine), poly(D,L-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), a racemic mixture of poly(L-arginine) with poly(D-arginine), elastin mimetic polypeptides, and blends thereof.

27. The medical article of claim 15, wherein the coating comprises a small-molecule water soluble drug.