RGD peptide attached to bioabsorbable stents

• US 8,118,863 B2
• Filed: 02/21/2008
• Issued: 02/21/2012
• Est. Priority Date: 06/14/2006
• Status: Expired due to Fees

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Inventors: Gale, David C., Huang, Bin, Klaus, Kleine
• Primary Examiner(s): Woodward, Cherie M
• Application Number:
  US12/035,392
• Publication Number:
  US 20080147169A1
• Time in Patent Office: 1,461 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 forming medical device that includes RGD attached to the device via a spacer compound. The method comprises providing a spacer compound comprising a hydrophobic moiety and a hydrophilic moiety, grafting or embedding the spacer compound to the surface layer of the polymer to cause the hydrophobic moiety to be grafted to or embedded within the surface layer of polymer, and attaching a chemo-attractant to the hydrophilic moiety.

Claims

1. A method of forming a medical device comprising a chemo-attractant attached to a surface layer of polymer on the medical device, comprising

providing a spacer compound comprising a hydrophobic moiety and a hydrophilic moiety,

grafting or embedding the spacer compound to the surface layer of the polymer to cause the hydrophobic moiety to be grafted to or embedded within the surface layer of polymer such that the hydrophilic moiety of the spacer compound projects from the surface layer of polymer, and

attaching a chemo-attractant to the hydrophilic moiety.

2. The method of claim 1 wherein the hydrophobic moiety comprises a phospholipid.

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

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

5. The method of claim 1 wherein the spacer compound is a di-block co-polymer,

wherein the hydrophobic moiety comprises a hydrophobic polymer block, and

wherein the hydrophilic moiety comprises a hydrophilic polymer block.

6. The method of claim 5 wherein the hydrophobic polymer block comprises poly(lactic acid).

7. The method of claim 6 wherein the hydrophilic polymer block comprises PEG, poly(alkylene oxide), poly(vinyl alcohol) or combinations of these.

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

9. The method of claim 5 wherein the spacer compound is poly(L-lactide-co-PEG (3000)).

10. The method of claim 1 wherein the hydrophobic moiety comprises a hydrophobic polymer block.

11. The method of claim 2 wherein the hydrophilic moiety comprises PEG.

12. The method of claim 10 wherein the hydrophilic moiety comprises PEG.

13. The method of claim 12 wherein the chemo-attractant is selected from RGD, cRGD, mimetics thereof, or combinations of these.

14. The method of claim 13 wherein the medical device is a bioabsorbable stent.

15. The method of claim 14 wherein the medical device further comprises a bioactive agent, wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, super oxide dismutase, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl(4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O -tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, midostaurin, and combinations of these.

16. The method of claim 12 wherein the chemo-attractant comprises Decoy receptor 3 (DcR3) or integrin LFA-1 (LFA-1Af).

17. The method of claim 16 wherein the medical device further comprises a bioactive agent, wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, super oxide dismutase, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl(4-amino-TEMPO), tacrolimus, dexamthasone, rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O[2-(2-hydroxy)ethoxy]lethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, midostaurin, and combinations of these.

18. The method of claim 12 wherein the chemo-attractant comprises a receptor binding to ICAM (intercellular adhesion molecule) molecules or VCAM (vascular cell adhesion molecule) molecules present on endothelial cells.

19. The method of claim 18 wherein the medical device is a bioabsorbable stent.

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

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

22. The method of claim 21 wherein the medical device further comprises a bioactive agent, wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, super oxide dismutase, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl(4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

y-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, midostaurin, and combinations of these.

23. The method of claim 1 wherein the medical device further comprises a bioactive agent, wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, super oxide dismutase, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl(4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, midostaurin, and combinations of these.

24. 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 on endothelial cells.

25. The method of claim 24 wherein the medical device is a bioabsorbable stent.

26. The method of claim 25 wherein the medical device further comprises a bioactive agent, wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, super oxide dismutase, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl(4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, midostaurin, and combinations of these.

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

28. The method of claim 27 wherein the medical device further comprises a bioactive agent, wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, super oxide dismutase, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl(4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, midostaurin, and combinations of these.