ANGIOTENSIN (1-7) ELUTING STENT

• US 20100055147A1
• Filed: 10/26/2007
• Published: 03/04/2010
• Est. Priority Date: 10/27/2006
• Status: Abandoned Application

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Tijsma, Edze Jan, Driessen-Levels, Anita
• Application Number:
  US12/447,415
• Publication Number:
  US 20100055147A1
• Time in Patent Office: Days
• US Class Current: 424/423
• 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 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• 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: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C08L 33/10 Homopolymers or copolymers of methacrylic acid esters

Abstract

Medical devices with polymer coatings designed to control the release of bioactive agents in combination with angiotensin-(1-7) receptor agonists from medical devices are disclosed. Methods for treating or inhibiting post-stent implantation restenosis as well as improving vascular endothelial function in patients are also provided.

Claims

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

providing a vascular stent having a controlled-release coating thereon, said coating comprising

an amphiphilic copolymer,

an effective amount of an Ang-(1-7) peptide, and

at least one additional bioactive agent selected from the group consisting of FKBP 12 binding compounds such as zotarolimus, estrogens, chaperone inhibitors, protease inhibitors, protein-tyrosine kinase inhibitors, leptomycin B, peroxisome proliferator-activated receptor gamma ligands (PPARy), hypothemycin, bisphosphonates, epidermal growth factor inhibitors, antibodies, proteasome inhibitors, antibiotics, anti-inflammatories, anti-sense nucleotides and transforming nucleic acids; and

inhibiting restenosis in said mammal.

2. The method according to claim 1 wherein said peptide comprises SEQ ID NO:

1.

4. The method according to claim 1 wherein said vascular stent further comprises a primer coat.

5. The method according to claim 1 wherein said amphiphilic copolymer comprises a PEG methacrylate-cyclohexyl methacrylate copolymer.

6. The method according to claim 1 wherein said vascular stent further includes a polymer topcoat comprising a PEG methacrylate-cyclohexyl methacrylate copolymer or poly(butyl methacrylate).

7. The method according to claim 1 wherein said vascular stent further comprises both a primer coat and a polymer topcoat.

8. The method according to claim 1 wherein said bioactive agent is rapamycin.

3. (canceled)

9. (canceled)

10. (canceled)

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

providing a vascular stent having a controlled-release coating thereon, said coating comprising

an amphiphilic copolymer,

an effective amount of an Ang-(1-7) peptide, and

at least one additional bioactive agent selected from the group consisting of FKBP 12 binding compounds such as zotarolimus, estrogens, chaperone inhibitors, protease inhibitors, protein-tyrosine kinase inhibitors, leptomycin B, peroxisome proliferator-activated receptor gamma ligands (PPARy), hypothemycin, bisphosphonates, epidermal growth factor inhibitors, antibodies, proteasome inhibitors, antibiotics, anti-inflammatories, anti-sense nucleotides and transforming nucleic acids; and

improving at least one vascular endothelial cell function selected from the group consisting of improved vasodilation, improved vasoconstriction and increased production of endothelial progenitor cells in said mammal.

15. The method according to claim 11 wherein said vascular stent further comprises a primer coat.

16. The method according to claim 11 wherein said amphiphilic copolymer comprises a PEG methacrylate-cyclohexyl methacrylate copolymer.

17. The method according to claim 11 wherein said vascular stent further includes a polymer topcoat comprising a PEG methacrylate-cyclohexyl methacrylate copolymer or poly(butyl methacrylate).

18. The method according to claim 11 wherein said vascular stent further comprises both a primer coat and a polymer topcoat.

19. The method according to claim 11 wherein said bioactive agent is rapamycin.

12. (canceled)

13. (canceled)

14. (canceled)

20. 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, an Ang-(1-7) peptide and at least one additional bioactive agent selected from the group consisting of FKBP 12 binding compounds such as zotarolimus, estrogens, chaperone inhibitors, protease inhibitors, protein-tyrosine kinase inhibitors, leptomycin B, peroxisome proliferator-activated receptor gamma ligands (PPARy), hypothemycin, bisphosphonates, epidermal growth factor inhibitors, antibodies, proteasome inhibitors, antibiotics, anti-inflammatories, anti-sense nucleotides and transforming nucleic acids;

wherein at least one of said inner or outer surfaces are adapted to deliver an effective amount of said Ang-(1-7) peptide and said at least one bioactive agent to a tissue of a mammal.

23. The medical device of claim 20 wherein said Ang-(1-7) peptide is present on both said inner surface and said outer surface of said vascular stent.

24. The medical device of claim 20 wherein said vascular stent further comprises a primer coat.

25. The medical device of claim 20 wherein said amphiphilic copolymer comprises a PEG methacrylate-cyclohexyl methacrylate copolymer.

26. The medical device of claim 20 wherein said medical device further includes a polymer topcoat comprising a PEG methacrylate-cyclohexyl methacrylate copolymer or poly(butyl methacrylate).

27. The medical device of claim 20 wherein said vascular stent further comprises both a primer coat and a polymer topcoat.

21. (canceled)

22. (canceled)