Polycationic peptide coatings and methods of coating implantable medical devices

• US 7,803,406 B2
• Filed: 08/26/2005
• Issued: 09/28/2010
• 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., Roorda, Wouter E., Pacetti, Stephen D., Hossainy, Syed F. A., Ding, Ni
• Primary Examiner(s): Azpuru; Carlos A
• Application Number:
  US11/213,288
• Publication Number:
  US 20060198897A1
• Time in Patent Office: 1,859 Days
• Field of Search: None
• US Class Current: 424/499
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 31/737 Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate A61K31/727 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00

Abstract

Methods of forming coatings comprising a polycationic peptide for medical devices are disclosed. Also disclosed is a coating comprising a polycationic peptide.

Claims

1. A method of coating an implantable medical device comprising:

(a) incorporating a polycationic peptide into polymeric microspheres or beads;

(b) adding the microspheres or beads to a composition comprising a polymer; and

(c) applying the composition to a medical device,

wherein the microspheres or beads are obtained by suspension polymerization of monomers.

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

3. The method of claim 1, wherein the monomers comprise styrene, divinyl benzene, and combinations thereof.

8. The method of claim 1, wherein the polycationic peptide comprises a component selected from a group consisting of poly(L-arginine), poly(D-arginine), poly(D,L-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), a mixture of poly(L-arginine) and poly(D-arginine), chitosan, and a combination thereof.

10. A coating for an implantable medical device, wherein the coating comprises a component fabricated by the method of claim 1.

11. The coating of claim 10, wherein the device comprises a stent.

4. A method of coating an implantable medical device comprising:

(a) incorporating a polycationic peptide into polymeric microspheres or beads;

(b) adding the microspheres or beads to a composition comprising a polymer; and

(c) applying the composition to a medical device,

wherein the microspheres or beads are obtained by emulsion copolymerization of at least one neutral monomer, at least one anionic monomer, at least one cross-linking monomer, or a combination thereof.

5. The method of claim 4, wherein the neutral monomer comprises a component selected from a group consisting of acrylamide, methyl methacrylate, ethyl methacrylate, butyl methacrylate, 2-hydroxyethyl methacrylate, styrene, PEG-acrylate, PEG-methacrylate, and combinations thereof.

6. The method of claim 4, wherein the anionic monomer comprises a component selected from a group consisting of acrylic acid, methacrylic acid, ethyl acrylic acid, propyl acrylic, a carboxylated styrene, a sulfonated styrene, or a combination thereof.

7. The method of claim 4, wherein the cross-linking monomer comprises a component selected from a group consisting of propyleneglycol dimethacrylate, divinyl benzene, N,N′

-methylenebisacrylamide, trimethylolpropane triacrylate, propyleneglycol diacrylate, PEG-diacrylate, PEG-dimethacrylate, and a combination thereof.

17. The method of claim 4, wherein the medical device comprises a stent.

18. The method of claim 4, wherein the polycationic peptide comprises a component selected from a group consisting of poly(L-arginine), poly(D-arginine), poly(D,L-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), a mixture of poly(L-arginine) and poly(D-arginine), chitosan, and a combination thereof.

9. A method of coating an implantable medical device comprising:

(a) incorporating a polycationic peptide into polymeric microspheres or beads;

(b) adding the microspheres or beads to a composition comprising a polymer; and

(c) applying the composition to a medical device,

wherein the polycationic peptide comprises heptaarginine.

19. The method of claim 9, wherein the medical device comprises a stent.

12. A coating for an implantable medical device, wherein the coating is UV-curable and comprises a hydrogel polymer and a polycationic peptide incorporated into the hydrogel polymer, wherein the polycationic peptide comprises heptaarginine.

13. The coating of claim 12, wherein the polycationic peptide comprises a component selected from a group consisting of poly(L-arginine), poly(D-arginine), poly(D,L-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), a mixture of poly(L-arginine) and poly(D-arginine), chitosan, and a combination thereof.

14. The coating of claim 12, wherein the device comprises a stent.

15. The coating of claim 12, wherein the hydrogel polymer has the solubility parameter of 11 (cal/cm3)½

or more.

16. The coating of claim 12, wherein the hydrogel polymer is made by homopolymerization or copolymerization of one or plurality of acrylate, methacrylate, allyl or vinyl monomers and/or oligomers.