Methods of forming a micronized peptide coated stent

• US 9,084,671 B2
• Filed: 07/15/2013
• Issued: 07/21/2015
• Est. Priority Date: 06/21/2002
• 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., Ding, Ni
• Primary Examiner(s): Nguyen, Victor
• Application Number:
  US13/942,474
• Publication Number:
  US 20130317599A1
• Time in Patent Office: 736 Days
• Field of Search: 623/1.15, 623/1.42, 623/1.43, 424/423
• US Class Current: 1/1
• 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 method of coating a stent comprising:

applying a composition to a stent;

wherein the composition comprises;

a micronized L-arginine polymer of formula;

H—

[NH—

CHX—

CO]_p—

OH;

wherein p is from 5 to 1,000 and X is —

(CH₂)₃—

NH—

C(NH₂)═

NH; and

a fluid; and

essentially removing the fluid from the composition on the stent to form a coating.

2. The method of claim 1, wherein the micronized L-arginine polymer has an average particle size of less than 2 microns.

3. The method of claim 1, wherein the composition comprises a second polymer, and wherein the second polymer dissolves in the fluid.

4. The method of claim 3, wherein the solubility profile of the micronized L-arginine polymer is incompatible with the solubility profile of the second polymer.

5. The method of claim 3, wherein the second polymer is a hydrophobic polymer.

6. The method of claim 1, wherein the fluid is substantially an organic solvent.

7. The method of claim 1, wherein the fluid is chloroform, acetone, dimethylsulfoxide, propylene glycol methyl ether, iso-propylalcohol, tetrahydrofuran, dimethylformamide, dimethyl acetamide, benzene, toluene, xylene, hexane, cyclohexane, heptane, octane, nonane, decane, decalin, ethyl acetate, butyl acetate, cyclohexanone, cyclohexanol, 1,4-dioxane, isobutyl acetate, isopropyl acetate, butanol, diacetone alcohol, benzyl alcohol, 2-butanone, dioxane, methylene chloride, carbon tetrachloride, tetrachloroethylene, tetrachloro ethane, chlorobenzene, 1,1,1-trichloroethane, formamide, hexafluoroisopropanol, 1,1,1-trifluoroethanol, hexamethyl phosphoramide or a combination thereof.

8. The method of claim 1, wherein the micronized L-arginine polymer is L-heptaarginine, or an analog or derivative thereof.

9. The method of claim 1, wherein the L-arginine polymer is micronized by a process including:

providing a solution containing the L-arginine polymer;

atomizing the solution to produce an aerosol; and

directing the aerosol into a supercritical fluid to produce micronized particles.

10. The method of claim 9, wherein the supercritical fluid comprises carbon dioxide, sulfur hexafluoride, a chlorofluorocarbon, a fluorocarbon, nitrous oxide, xenon, propane, n-pentane, ethanol, nitrogen, water, or a combination thereof.

11. The method of claim 1, wherein the L-arginine polymer is micronized by a process including:

providing a solution containing the L-arginine polymer;

atomizing the solution to produce an aerosol; and

directing the aerosol into a liquid gas to produce micronized particles.

12. The method of claim 11, wherein the liquid gas comprises liquid nitrogen, liquid argon, liquid helium, liquid hydrogen, or liquid oxygen.

13. The method of claim 1, wherein the micronized L-arginine polymer is produced by a process of wet milling or dry milling.

14. The method of claim 1, wherein the composition further includes an active agent for inhibiting migration or proliferation of vascular smooth muscle cells.