Coatings containing polycationic peptides for cardiovascular therapy

• US 7,217,426 B1
• Filed: 06/21/2002
• Issued: 05/15/2007
• Est. Priority Date: 06/21/2002
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Hossainy, Syed F. A.
• Primary Examiner(s): Azpuru; Carlos A.
• Application Number:
  US10/177,117
• Time in Patent Office: 1,789 Days
• Field of Search: 424/426, 424/423, 514/772.3
• US Class Current: 424/426
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• 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

Abstract

Coatings for implantable medical devices and methods for fabricating the same are disclosed. The coatings include a region containing a polycationic peptide, such as, for example, the polycationic peptide known as R7.

Claims

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

(a) forming a coating on the device, the coating including a polycationic peptide; and

(b) treating the coating with a stimulus that cleaves peptide bonds for enriching a region close to the outer surface of the coating with the polycationic peptide.

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

3. 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), and a mixture of poly(L-arginine) and poly(D-arginine).

4. The method of claim 1, wherein the treating of the coating includes subjecting the device to a humid environment at a selected temperature.

5. The method of claim 4, wherein the temperature is about 50°

C. and the humidity is about 100%.

6. The method of claim 1, wherein the treating includes subjecting the device to an electronic beam or to autoclaving.

7. The method of claim 6, wherein the electronic beam has energy of about 2.5 MRad.

8. A coating for an implantable medical device, the coating comprising two regions, a first region including a polycationic peptide and a second region free from the polycationic peptide, wherein the polycationic peptide is encapsulated in particles in the coating.

9. The coating of claim 8, wherein the region free from the polycationic peptide is positioned on the surface of the device and beneath the region including the polycationic peptide.

10. The coating of claim 8, wherein the particles are fabricated of a substance selected from a group consisting of poly(glycolic acid), poly(D-lactic acid), poly(L-lactic acid), poly(butylene terephtalate-co-ethylene glycol) and mixtures thereof.

19. The coating of claim 8, wherein the implantable medical device is a stent.

20. The coating of claim 8, 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), and a mixture of poly(L-arginine) and poly(D-arginine).

11. A method of modifying a coating for an implantable medical device, the coating including a polycationic peptide, comprising exposing the coating to ethylene oxide at a selected temperature and conjugating poly(ethylene glycol) to the coating.

13. The method of claim 11, 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), and a mixture of poly(L-arginine) and poly(D-arginine).

14. The method of claim 11, wherein the device is a stent.

12. A method of fabricating a coating for a medical device, comprising forming a coating on the device, the coating including a polycationic peptide, and causing some of the peptide bonds in the polycationic peptide to be cleaved, whereby the population of free peptides in the coating is increased.

15. The method 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), and a mixture of poly(L-arginine) and poly(D-arginine).

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

17. A method of fabricating a coated stent, comprising forming a coating comprising two regions on the stent wherein the coating includes a first region containing a peptide and a second region free from the peptide wherein the peptide is encapsulated in particles in the coating.

21. The method of claim 17, wherein the implantable medical device is a stent.

22. The method of claim 17, 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), and a mixture of poly(L-arginine) and poly(D-arginine).

18. A coating for a medical device comprising a peptide that has been cleaved such that the population of the peptide is greatest at the outmost region of the coating.