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

• US 8,309,112 B2
• Filed: 12/24/2003
• Issued: 11/13/2012
• Est. Priority Date: 12/24/2003
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Glauser, Thierry, Kwok, Connie S., Claude, Charles D., Michal, Eugene T., Tang, Yiwen, Astafieva, Irina, Whatley, John, Pacetti, Stephen D., Shah, Ashok
• Primary Examiner(s): DICKINSON, PAUL W
• Application Number:
  US10/746,483
• Publication Number:
  US 20050147647A1
• Time in Patent Office: 3,247 Days
• Field of Search: None
• US Class Current: 424/422
• 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 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,

wherein at least one hydrophilic moiety comprises 2-acrylamido-2-methyl-1-propanesulfonic acid, 3-sulfopropyl acrylate, 3-sulfopropyl methacrylate, or 3-allyloxy-2-hydroxypropanesulfonic acid, and

wherein the coating includes a therapeutic agent incorporated or dispersed in the coating in a mass ratio of the therapeutic agent to the amphiphilic copolymer between about 1:

10 and about 1;

3.

2. The medical article of claim 1, wherein the amphiphilic copolymer comprises an acrylic copolymer.

3. The medical article of claim 2, wherein the acrylic copolymer is a block copolymer or a random copolymer.

4. The medical article of claim 3, wherein the block copolymer is an ABA block copolymer or an AB block-copolymer.

5. The medical article of claim 1, wherein the hydrophobic moiety is selected from a group consisting of methyl methacrylate, ethyl methacrylate, n-butyl methacrylate, and lauryl methacrylate.

6. The medical article of claim 1, 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.

7. The medical article of claim 1, 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.

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

9. 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,

wherein the amphiphilic copolymer has a formula

10. The medical article of claim 9, wherein the block copolymer is an ABA block copolymer or an AB block-copolymer.

11. The medical article of claim 9, wherein the amphiphilic copolymer comprises PSPMA-PBMA-PSPMA, or PSPMA-PBMA, wherein PSPMA is poly 3-sulfopropyl methacrylate, PBMA is poly(butylmethacrylate).

12. The medical article of claim 9, 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.