Angiotensin-(1-7) eluting polymer-coated medical device to reduce restenosis and improve endothelial cell function

• US 20060088572A1
• Filed: 10/21/2005
• Published: 04/27/2006
• Est. Priority Date: 10/21/2004
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Tijsma, Edze Jan, Driessen-Levels, Anita, Hendriks, Marc
• Granted Patent: US 7,176,261 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61L 2300/25 Peptides having up to 20 amino acids in a defined sequence
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/608 having two or more layers
• 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
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

Medical devices with polymer coatings designed to control the release of angiotensin-(1-7) receptor agonists from medical devices are disclosed. The present application also discloses providing vascular stents with angiotensin-(1-7) receptor agonist-containing controlled-release coatings. Methods for treating or inhibiting post-stent implantation restenosis as well as improving vascular endothelial function in patients are also provided.

Claims

1. A medical device comprising:

a stent having a generally cylindrical shape comprising an outer surface, an inner surface, a first open end and a second open end;

a controlled-release coating comprising an amphiphilic copolymer and at least one angiotensin-(1-7) (Ang-(1-7)) receptor agonist;

wherein at least one of said inner or outer surfaces are adapted to deliver an effective amount of said at least one Ang-(1-7) receptor agonist to a tissue of a mammal; and

wherein vascular endothelial cell function is improved and/or restenosis is inhibited.

2. The medical device of claim 1 wherein said at least one Ang-(1-7) receptor agonist is a peptide having the amino acid sequence of SEQ ID NO. 1.

3. The medical device of claim 1 wherein said stent is a vascular stent.

4. The medical device of claim 1 wherein said at least one Ang-(1-7) receptor agonist is present on both said inner surface and said outer surface of said vascular stent.

5. The medical device of claim 1 wherein said vascular stent further comprises a primer coat.

6. The medical device of claim 1 wherein said amphiphilic copolymer comprises a PEG methacrylate-cyclohexyl methacrylate copolymer.

7. The medical device of claim 1 wherein said medical device further includes a polymer topcoat comprising a PEG methacrylate-cyclohexyl methacrylate copolymer or poly(butyl methacrylate).

8. The medical device of claim 1 wherein said vascular stent further comprises both a primer coat and a polymer topcoat.

9. The medical device of claim 2 wherein said peptide is in a concentration of between approximately 0.1% to 99% by weight of peptide-to-polymer.

10. A vascular stent for inhibiting restenosis in a mammal comprising:

stent having a generally cylindrical shape comprising an outer surface, an inner surface, a first open end and a second open end;

a controlled-release coating comprising a PEG methacrylate-cyclohexyl methacrylate copolymer and an anti-restenotic amount of an Ang-(1-7) receptor agonist peptide having the amino acid sequence of SEQ ID NO. 1; and

a methacrylate copolymer topcoat;

wherein said vascular stent deliver an effective amount of said Ang-(1-7) receptor agonist to a tissue of a mammal; and

wherein vascular endothelial cell function is improved and/or restenosis is inhibited.

11. The vascular stent of claim 10 wherein said vascular stent further comprises a primer coat.

12. A method for inhibiting restenosis in a mammal comprising:

providing a vascular stent having a controlled-release coating thereon wherein said coating comprises an amphiphilic copolymer and an effective amount of at least one Ang-(1-7) receptor agonist; and

inhibiting restenosis in said mammal.

13. The method according to claim 12 wherein said at least one Ang-(1-7) receptor agonist is a peptide having the amino acid sequence of SEQ ID NO. 1.

14. The method according to claim 13 wherein said peptide is in a concentration of between approximately 0.1% to 99% by weight of peptide-to-polymer.

15. The method according to claim 12 wherein said vascular stent has a generally cylindrical shape comprising an outer surface, an inner surface, a first open end and a second open end and wherein at least one of said inner or outer surfaces are coated with said controlled-release coating.

16. The method according to claim 12 wherein said vascular stent further comprises a primer coat.

17. The method according to claim 12 wherein said amphiphilic copolymer comprises a PEG methacrylate-cyclohexyl methacrylate copolymer.

18. The method according to claim 12 wherein said vascular stent further includes a polymer topcoat comprising a PEG methacrylate-cyclohexyl methacrylate copolymer or poly(butyl methacrylate).

19. The method according to claim 12 wherein said vascular stent further comprises both a primer coat and a polymer topcoat.

20. A method for improving endothelial cell function in a mammal comprising:

providing a vascular stent having a controlled-release coating thereon wherein said coating comprises an amphiphilic copolymer and an effective amount of at least one Ang-(1-7) receptor agonist; and

improving vascular endothelial cell function in said mammal.

21. The method according to claim 20 wherein said at least one Ang-(1-7) receptor agonist is a peptide having the amino acid sequence of SEQ ID NO.1.

22. The method according to claim 21 wherein said peptide is in a concentration of between approximately 0.1% to 99% by weight of peptide-to-polymer.

23. The method according to claim 20 wherein said vascular stent has a generally cylindrical shape comprising an outer surface, an inner surface, a first open end and a second open end and wherein at least one of said inner or outer surfaces are coated with said controlled-release coating.

24. The method according to claim 20 wherein said vascular stent further comprises a primer coat.

25. The method according to claim 20 wherein said amphiphilic copolymer comprises a PEG methacrylate-cyclohexyl methacrylate copolymer.

26. The method according to claim 20 wherein said vascular stent further includes a polymer topcoat comprising a PEG methacrylate-cyclohexyl methacrylate copolymer or poly(butyl methacrylate).

27. The method according to claim 20 wherein said vascular stent further comprises both a primer coat and a polymer topcoat.

28. A method for treating impaired vascular endothelial cell function in a mammal comprising:

implanting a stent having a controlled release coating and an effective amount of Ang-(1-7) disposed on at lease one surface of said medical device at a treatment site in a vessel lumen;

releasing said Ang-(1-7) from said surface of said stent such that vascular endothelial cell function is improved at said treatment site.