Coatings for implantable medical device containing polycationic peptides

• US 7,094,256 B1
• Filed: 12/16/2002
• Issued: 08/22/2006
• Est. Priority Date: 12/16/2002
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Michal, Eugene T., Shah, Ashok A.
• Primary Examiner(s): TARAZANO, DONALD LAWRENCE
• Application Number:
  US10/320,899
• Time in Patent Office: 1,345 Days
• Field of Search: 623/1.46, 623/1.48, 623/1.49, 428/523, 428/522, 428/476.3, 428/476.6, 427/2.24
• US Class Current: 623/1.46
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: C08L 33/10 Homopolymers or copolymers of methacrylic acid esters
• CPC Class Codes: C08L 77/04 Polyamides derived from alpha-amino carboxylic acids C08L77/10 takes precedence
• CPC Class Codes: Y10T 428/3175 Next to addition polymer from unsaturated monomer[s]
• CPC Class Codes: Y10T 428/31754 Natural source-type polyamide
• CPC Class Codes: Y10T 428/31935 Ester, halide or nitrile of addition polymer

Abstract

Coatings for implantable medical devices and methods for fabricating the same are disclosed. The coatings include carboxylated acrylates and polycationic peptides, for example R7.

Claims

1. A method for fabricating a coating for an implantable medical device, comprising:

(a) depositing a layer including a polycationic peptide on the device; and

(b) depositing a layer including a carboxylated acrylic polymer over the layer including the polycationic peptide.

2. The method of claim 1, additionally including depositing a primer layer on the surface of the device and beneath the layer including the polycationic peptide.

3. The method of claim 1, additionally including depositing a layer including the carboxylated acrylic polymer beneath the layer including the polycationic peptide.

4. The method of claim 1, additionally including depositing a topcoat layer over the layer including the carboxylated acrylic polymer.

5. The method of claim 4, wherein the topcoat layer is fabricated of a polymer selected from a group consisting of poly(ethylene-co-vinyl alcohol), polyacrylates, and blends thereof.

6. The method of claim 1, wherein the implantable medical device is a stent.

7. The method of claim 1, wherein the polycationic peptide includes poly(L-arginine), poly(D-arginine), poly(D,L-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), or a mixture of poly(L-arginine) and poly(D-arginine).

8. The method of claim 1, wherein the carboxylated acrylic polymer has a formula

wherein each X, X′

, and X″

is independently, a hydrogen atom or an alkyl group;

Q is an alkoxy group or 2-amino-2-methyl propane sulfonyl group;

Q′

is an unsubstituted or substituted phenyl group or a carboxy group;

each R and R′

is independently a C₁ to C₁₂ straight chained or branched aliphatic radical; and

x, y, and z are integers, where y≠

0.

9. The method of claim 1, wherein the carboxylated acrylic polymer includes units derived from heparin.

10. The method of claim 1, additionally including blending the carboxylated acrylic polymer with a compound selected from a group consisting of a sulfonated acrylic polymer, heparin, and mixtures thereof, prior to depositing the layer including the carboxylated acrylic polymer.

11. The method of claim 10, wherein the sulfonated acrylic polymer is poly(acrylamidomethyl propane sulfonic acid).

12. A coating for an implantable medical device, comprising a region including a carboxylated acrylic polymer disposed over a region including a polycationic peptide.

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

14. The coating of claim 12, wherein the carboxylated acrylic polymer has a formula

wherein each X, X′

, and X″

is independently a hydrogen atom or an alkyl group;

Q is an alkoxy group or 2-amino-2-methyl propane sulfonyl group;

Q′

is an unsubstituted or substituted phenyl group or a carboxy group;

each R and R′

is independently a C₁ to C₁₂ straight chained or branched aliphatic radical; and

x, y, and z are integers, where y≠

0.

15. The coating of claim 12, wherein the carboxylated acrylic polymer includes units derived from heparin.

16. The coating of claim 12, additionally including a compound selected from a group consisting of a sulfonated acrylic polymer, heparin, and mixtures thereof, blended with the carboxylated acrylic polymer.

17. The coating of claim 16, wherein the sulfonated acrylic polymer is poly(acrylamidomethyl propane sulfonic acid).

18. The coating of claim 12, wherein the polycationic peptide includes poly(L-arginine), poly(D-arginine), poly(D,L-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), or a mixture of poly(L-arginine) and poly(D-arginine).

19. The coating of claim 12, additionally including a polymeric region free from any polycationic peptides disposed beneath the region including the polycationic peptide.

20. The coating of claim 19, wherein the polymeric region includes a carboxylated acrylic polymer.

21. The coating of claim 20, wherein the carboxylated acrylic polymer has a formula

wherein each X, X′

, and X″

is independently, a hydrogen atom or an alkyl group;

Q is an alkoxy group or 2-amino-2-methyl propane sulfonyl group;

Q′

is an unsubstituted or substituted phenyl group or a carboxy group;

each R and R′

is independently a C₁ to C₁₂ straight chained or branched aliphatic radical; and

x, y, and z are integers, where y≠

0.

22. The coating of claim 19, wherein the polymeric region is disposed on a surface of the implantable medical device.