Methods and devices for improving biofixation of implantable vascular devices

Abstract

Methods and devices for improving biofixation of implantable vascular devices are provided. The methods and devices improve biofixation of implantable vascular devices by providing one or more thrombus-eliminating agents at a treatment site before and/or during and/or after vascular device implantation.

1 . A method comprising: 
 providing a vascular device comprising a thrombus-eliminating agent; and    positioning said vascular device at a treatment site wherein said vascular device releases said thrombus-eliminating agent at said treatment site and wherein said thrombus-eliminating agent eliminates one or more thrombi at said treatment site.    
     
     
         2 . The method according to  claim 1 , wherein said thrombus-eliminating agent is an anti-coagulant.  
     
     
         3 . The method according to  claim 1 , wherein said thrombus-eliminating agent is selected from the group consisting of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors, fibrinolytic agents, tPA, tenectplase, reteplase, flaxidel, aspirin, heparin, unfractionated heparin (UFH), low molecular weight heparin, (LMWH), ultra-LMWH, pentasaccharide, direct anti-Xa, direct anti-IX/IXa, direct anti-IIa (thrombin), tissue factor pathway inhibitor (TFPI), hirudins, hirudin derivatives, antithrombin (AT), activated protein C (APC), lipoproteins, sphingosine, thrombomodulin (TM), cellular Marcks protein, chlorophacinone, diphacinone, pindone, clopidogrel bisulfate, coumarin derivatives, coumadin, plasmins, microplasmins, fibrolases, alfimeprase, metalloproteinases and desmetoplase.  
     
     
         4 . The method according to  claim 1 , wherein said vascular device further comprises and releases a biofixation factor.  
     
     
         5 . The method according to  claim 4 , wherein said biofixation factor is selected from the group consisting of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), plated-derived epidermal growth factor (PDEGF), fibroblast growth factors (FGFs), transforming growth factor-beta (TGF-β), platelet-derived angiogenesis growth factor (PDAF), autologous platelet gel (APG) including platelet rich plasma (PRP), platelet poor plasma (PPP) and thrombin, and autologous platelet releasates.  
     
     
         6 . The method according to  claim 1 , wherein said treatment site is selected from the group consisting of an aneurysm site, a site of vessel narrowing, within 2 cm of an aneurysm site and within 2 cm of a site of vessel narrowing.  
     
     
         7 . The method according to  claim 6 , wherein said treatment site is within 2 cm of an aneurysm site or within 2 cm of a site of vessel narrowing.  
     
     
         8 . The method according to  claim 6 , wherein when said treatment site is a site of vessel narrowing, said vascular device further comprises and releases one or more agents selected from the group consisting of anti-restenosis agents and RCT agents.  
     
     
         9 . The method according to  claim 8 , wherein said anti-restenosis agent is selected from the group consisting of paclitaxel, rapamycin, tacrolimus, actinomycin D, vincristine, sirolimus, everolimus, biolimus, mycophenolic acid, ABT-578, cervistatin, simvastatin, methylprednisolone, dexamethasone, angiopeptin, L-arginine, estradiol, 17-β-estradiol, tranilast, methotrexate, batimistat, halofuginone, BCP-671, QP-2, lantrunculin D, cytochalasin A and nitric oxide and said RCT agent is selected from the group consisting of surface constituents of plasma lipoproteins, apolipoprotein A1 (apo-A1), apo-A1's mutation apo-A1-milano, apoE, cholesterol ester transport protein (CETP)), liver X receptors, the ATP binding cassette (ABC) superfamily of transporter proteins, ABCA1 and ABCG1.  
     
     
         10 . The method according to  claim 1 , wherein said vascular device is a stent graft or a stent.  
     
     
         11 . A method comprising: 
 administering a thrombus-eliminating agent at a treatment site;    providing a vascular device comprising a biofixation factor; and    implanting said vascular device at said treatment site;    wherein said administered thrombus-eliminating agent eliminates a thrombus at said treatment site and wherein said biofixation factor stimulates cell growth at said treatment site.    
     
     
         12 . A method comprising: 
 administering a thrombus-eliminating agent at a treatment site;    providing a vascular device comprising a thrombus-eliminating agent and/or a biofixation factor; and    positioning said vascular device at said treatment site;    wherein said administered and provided thrombus-eliminating agent eliminates a thrombus at said treatment site and/or wherein said biofixation factor stimulates cell growth at said treatment site.    
     
     
         13 . A vascular device comprising a thrombus-eliminating agent.  
     
     
         14 . The vascular device according to  claim 13 , wherein said thrombus-eliminating agent is an anti-coagulant.  
     
     
         15 . The vascular device according to  claim 14 , wherein said thrombus-eliminating agent is selected from the group consisting of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors, fibrinolytic agents, tPA, tenectplase, reteplase, flaxidel, aspirin, heparin, unfractionated heparin (UFH), low molecular weight heparin, (LMWH), ultra-LMWH, pentasaccharide, direct anti-Xa, direct anti-IX/IXa, direct anti-IIa (thrombin), tissue factor pathway inhibitor (TFPI), hirudins, hirudin derivatives, antithrombin (AT), activated protein C (APC), lipoproteins, sphingosine, thrombomodulin (TM), cellular Marcks protein, chlorophacinone, diphacinone, pindone, clopidogrel bisulfate, coumarin derivatives, coumadin, plasmins, microplasmins, fibrolases, alfimeprase, metalloproteinases and desmetoplase.  
     
     
         16 . The vascular device according to  claim 13 , wherein said vascular device further comprises a biofixation factor.  
     
     
         17 . The vascular device according to  claim 16 , wherein said biofixation factor is selected from the group consisting of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), plated-derived epidermal growth factor (PDEGF), fibroblast growth factors (FGFs), transforming growth factor-beta (TGF-β), platelet-derived angiogenesis growth factor (PDAF), autologous platelet gel (APG) including platelet rich plasma (PRP), platelet poor plasma (PPP) and thrombin, and autologous platelet releasates.  
     
     
         18 . The vascular device according to  claim 13 , wherein said vascular device further comprises one or more anti-restenosis agents or RCT agents.  
     
     
         19 . The vascular device according to  claim 18 , wherein said anti-restenosis agent is selected from the group consisting of paclitaxel, rapamycin, tacrolimus, actinomycin D, vincristine, sirolimus, everolimus, biolimus, mycophenolic acid, ABT-578, cervistatin, simvastatin, methylprednisolone, dexamethasone, angiopeptin, L-arginine, estradiol, 17-β-estradiol, tranilast, methotrexate, batimistat, halofuginone, BCP-671, QP-2, lantrunculin D, cytochalasin A and nitric oxide and said RCT agent is selected from the group consisting of surface constituents of plasma lipoproteins, apolipoprotein A1 (apo-A1), apo-A1's mutation apo-A1-milano, apoE, cholesterol ester transport protein (CETP)), liver X receptors, the ATP binding cassette (ABC) superfamily of transporter proteins, ABCA1 and ABCG1.  
     
     
         20 . The vascular device according to  claim 13 , wherein said thrombus-eliminating agent is found within a coating on said vascular device.  
     
     
         21 . The vascular device according to  claim 20 , wherein said coating is a polymer coating, a collagen coating or a fibrin coating.  
     
     
         22 . The vascular device according to  claim 13 , wherein said vascular device is a stent graft or a stent.