Micronized peptide coated stent

• US 8,506,617 B1
• Filed: 06/21/2002
• Issued: 08/13/2013
• Est. Priority Date: 06/21/2002
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Michal, Eugene T, Ding, Ni, Shah, Ashok A
• Primary Examiner(s): Nguyen, Victor
• Application Number:
  US10/177,942
• Time in Patent Office: 4,071 Days
• Field of Search: 623/1.15, 623/1.42, 623/1.43, 424/423, 424/484, 424/486
• US Class Current: 623/1.15
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61L 2300/25 Peptides having up to 20 amino acids in a defined sequence
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• 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

A coating for an implantable device such as a stent is provided including micronized peptides. A method of making the same is also provided.

Claims

1. A stent comprising:

a stent body;

a coating on a surface of the stent body, the coating comprising a polymer, and;

an unencapsulated micronized peptide or protein dispersed in the polymer, wherein;

the peptide or protein comprises from 5 to 1000 L-arginine subunits, or analogs or derivatives thereof.

2. The stent of claim 1, wherein the peptide or protein has an average particle size of less than 2 microns.

3. The stent of claim 1, wherein the solubility profile of the peptide or protein is incompatible with the solubility profile of the polymer.

4. The stent of claim 1, wherein the polymer is a hydrophobic polymer.

5. The stent of claim 1, wherein the peptide is L-heptaarginine, or analogs or derivatives thereof.

6. The stent of claim 1, wherein the polymer comprises a component selected from the group consisting of poly(vinylidene fluoride), poly(butyl methacrylate), poly(isocyanate), poly(ethylene glycol), poly(vinyl pyrrolidone), poly(ethylene-co-vinyl alcohol), poly(2-hydroxyethyl methacrylate), poly(acrylic acid), and combinations thereof.

7. The stent of claim 1, wherein the coating includes an additional active agent for inhibiting migration or proliferation of vascular smooth muscle cells.

8. The stent of claim 7, wherein the active agent comprises a component selected from the group consisting of heparin, heparin sulfate, heparin having a hydrophobic counterion, mannose-6-phosphate, superoxide dismutase, retinoic acid, rapamycin, rapamycin analogs and derivatives, suramin, asiaticoside, hyaluronan and combinations thereof.

9. The stent of claim 1, wherein the peptide or protein includes a component selected from a group consisting of poly(L-arginine), poly(D-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), mixtures of poly(L-arginine) and poly(D-arginine), chitosan, and combinations thereof.

10. The stent of claim 1, wherein the peptide is an oligopeptide or a polypeptide.

11. The stent of claim 1, wherein the peptide or protein includes from 5 to about 20 arginine subunits.

12. The stent of claim 1, wherein the peptide consists of 5 to 20 L-arginine subunits.

13. The stent of claim 1, wherein the polymer is hydrophobic.

14. The stent of claim 1, wherein the peptide or protein is hydrophilic.

15. The stent of claim 1, wherein the peptide or protein is hydrophilic, and the polymer is hydrophobic.

16. A stent, comprising:

a stent substrate;

a coating on a surface of the stent substrate, the coating comprising a polymer, and;

an unencapsulated micronized peptide or protein having an average particle size of less than 2 microns dispersed in the polymer.

17. The stent of claim 16, wherein the peptide or protein includes a component selected from a group consisting of poly(L-arginine), poly(D-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), mixtures of poly(L-arginine) and poly(D-arginine), chitosan, and combinations thereof.

18. The stent of claim 16, wherein the peptide is an oligopeptide or a polypeptide.

19. The stent of claim 16, wherein the peptide or protein includes from 5 to about 20 arginine subunits.

20. The stent of claim 16, wherein the peptide consists of 5 to 20 L-arginine subunits.

21. The stent of claim 16, wherein the peptide is L-heptaarginine, or analogs or derivatives thereof.

22. The stent of claim 16, wherein the polymer is hydrophobic.

23. The stent of claim 16, wherein the peptide or protein is hydrophilic.

24. The stent of claim 16, wherein the peptide or protein is hydrophilic, and the polymer is hydrophobic.

25. An implantable medical device comprising:

a substrate;

a coating on the substrate, the coating comprising a hydrophobic polymer, and;

an unencapsulated micronized polycationic peptide or protein dispersed in the hydrophobic polymer, wherein the micronized polycationic peptide or protein has an average particle size of less than 5 microns.

26. The implantable medical device of claim 25, wherein the device comprises a stent.

27. The implantable medical device of claim 25, wherein the peptide or protein includes components selected from a group consisting of poly(L-arginine), poly(D-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), mixtures of poly(L-arginine) and poly(D-arginine), chitosan, and combinations thereof.

28. The implantable medical device of claim 25, wherein the peptide is L-heptaarginine, or analogs or derivatives thereof.

29. The implantable medical device of claim 25, wherein the peptide consists of 5 to 20 L-arginine subunits.

30. The implantable medical device of claim 25, wherein the peptide includes oligopeptides and polypeptides.

31. The implantable medical device of claim 25, wherein the polymer comprises a component selected from the group consisting of poly(vinylidene fluoride), poly(butyl methacrylate), poly(isocyanate), poly(ethylene glycol), poly(vinyl pyrrolidone), poly(ethylene-co-vinyl alcohol), poly(2-hydroxyethyl methacrylate), poly(acrylic acid), and combinations thereof.

32. The implantable medical device of claim 25, wherein the coating includes an additional active agent.

33. The implantable medical device of claim 25, wherein the active agent comprises a component selected from the group consisting of heparin, heparin sulfate, heparin having a hydrophobic counterion, mannose-6-phosphate, superoxide dismutase, retinoic acid, rapamycin, rapamycin analogs and derivatives, suramin, asiaticoside, hyaluronan, and combinations thereof.