US2012135131A1PendingUtilityA1

Rgd peptide attached to bioabsorbable stents

Assignee: GALE DAVID CPriority: Jun 14, 2006Filed: Feb 3, 2012Published: May 31, 2012

Est. expiryJun 14, 2026(expired)· nominal 20-yr term from priority

Inventors:David C. Gale Bin Huang Kleine Klaus

A61L 31/10A61L 31/047

PatentIndex Score

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Claims

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

exact text as granted — not AI-modified

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, 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 copolymer,
 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 comprising a bioactive agent. 
     
     
         16 . The method of  claim 15  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. 
     
     
         17 . The method of  claim 12  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 12  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. 
     
     
         21 . The method of  claim 20  wherein the medical device is a bioabsorbable stent. 
     
     
         22 . The method of  claim 1  wherein the chemo-attractant is selected from RGD, cRGD, mimetics thereof, or combinations of these. 
     
     
         23 . The method of  claim 1  wherein the chemo-attractant comprises Decoy receptor 3 (DcR3) or integrin LFA-1 (LFA-1Af). 
     
     
         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  further comprising a bioactive agent. 
     
     
         27 . The method of  claim 26  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. 
     
     
         28 . 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. 
     
     
         29 . The method of  claim 28  wherein the medical device is a bioabsorbable stent. 
     
     
         30 . The method of  claim 29  further comprising a bioactive agent. 
     
     
         31 . The method of  claim 30  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. 
     
     
         32 . The method of  claim 1  wherein the medical device is a bioabsorbable stent. 
     
     
         33 . The method of  claim 32  further comprising a bioactive agent. 
     
     
         34 . The method of  claim 33  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.

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