RGD peptide attached to bioabsorbable stents

• US 8,062,350 B2
• Filed: 02/21/2008
• Issued: 11/22/2011
• Est. Priority Date: 06/14/2006
• Status: Expired due to Fees

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Klaus, Kleine, Gale, David C., Huang, Bin
• Primary Examiner(s): STANFIELD, CHERIE MICHELLE
• Application Number:
  US12/035,391
• Publication Number:
  US 20080147176A1
• Time in Patent Office: 1,370 Days
• Field of Search: None
• US Class Current: 623/1.38
• CPC Class Codes: A61L 31/047 Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

Provided herein is a method of using a bioabsorbable medical device that includes RGD attached to the device via a spacer compound. The method comprises implanting in a human being a bioaborbable device, e.g., a bioabsorbable stent, including a chemo-attractant for endothelial progenitor cells (EPCs).

Claims

1. A method comprising implanting in a human being a medical device comprising

a chemo-attractant attached to a surface layer of polymer on the medical device, wherein the chemo-attractant is attached to the surface layer through a spacer compound comprising a hydrophobic moiety and a hydrophilic moiety, said hydrophobic moiety comprising a phospholipid,

wherein the chemo-attractant is attached to the hydrophilic moiety of the spacer compound,

wherein the hydrophobic moiety of the spacer compound is grafted to or embedded within the surface layer of polymer on the medical device, and

wherein the hydrophilic moiety of the spacer compound projects from the surface layer of polymer,

wherein the method treats or ameliorates a medical condition selected from atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, urethra obstruction, tumor obstruction, diabetic vascular disease, and combinations thereof.

2. The method of claim 1, wherein the phospholipid comprises distearoylphosphatidylethanolamine (DSPE) or 1,2-Dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE).

3. The method of claim 1 wherein the spacer compound is DMPE-PEG.

4. The method of claim 1 wherein the spacer compound is a di-block copolymer,

wherein the phospholipid comprises a hydrophobic polymer block, and

wherein the hydrophilic moiety comprises a hydrophilic polymer block.

5. The method of claim 4 wherein the hydrophilic polymer block comprises PEG, poly(alkylene oxide), poly(vinyl alcohol) or combinations of these.

6. The method of claim 1, wherein the hydrophilic moiety comprises PEG.

7. The method of claim 5 wherein the chemo-attractant is selected from RGD, cRGD, mimetics thereof, or combinations of these.

8. The method of claim 7 wherein the medical device is a bioabsorbable stent.

9. The method of claim 8 wherein the medical device further comprising a bioactive agent.

10. The method of claim 9 wherein the bioactive agent is selected from paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutses, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, or midostaurin, or prodrugs, co-drugs, or combinations of these.

11. The method of claim 5 wherein the chemo-attractant comprises Decoy receptor 3 (DcR3) or integrin LFA-1 (LFA-1Af).

12. The method of claim 11 further comprising a bioactive agent.

13. The method of claim 12 wherein the bioactive agent is selected from paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutses, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxyethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, or midostaurin, or prodrugs, co-drugs, or combinations of these.

14. The method of claim 5 wherein the chemo-attractant comprises a receptor binding to ICAM (intercellular adhesion molecule) molecules or VCAM (vascular cell adhesion molecule) molecules present in the endothelial cells.

15. The method of claim 14 wherein the medical device is a bioabsorbable stent.

16. The method of claim 1 wherein the chemo-attractant is selected from RGD, cRGD, mimetics thereof, or combinations of these.

17. The method of claim 1 wherein the chemo-attractant comprises Decoy receptor 3 (DcR3) or integrin LFA-1 (LFA-1Af).

18. The method of claim 17 further comprising a bioactive agent.

19. The method of claim 18 wherein the bioactive agent is selected from paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutses, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, or midostaurin, or prodrugs, co-drugs, or combinations of these.

20. The method of claim 1 further comprising a bioactive agent.

21. The method of claim 20 wherein the bioactive agent is selected from paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutses, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, or midostaurin, or prodrugs, co-drugs, or combinations of these.

22. The method of claim 1 wherein the chemo-attractant comprises a receptor binding to ICAM (intercellular adhesion molecule) molecules or VCAM (vascular cell adhesion molecule) molecules present in the endothelial cells.

23. The method of claim 22 wherein the medical device is a bioabsorbable stent.

24. The method of claim 23 further comprising a bioactive agent.

25. The method of claim 24 wherein the bioactive agent is selected from paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutses, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, or midostaurin, or prodrugs, co-drugs, or combinations of these.

26. The method of claim 1 wherein the medical device is a bioabsorbable stent.

27. The method of claim 26 further comprising a bioactive agent.

28. The method of claim 27 wherein the bioactive agent is selected from paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutses, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxyethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, or midostaurin, or prodrugs, co-drugs, or combinations of these.