Drug-Delivery Endovascular Stent and Method for Treating Restenosis

Abstract

An intravascular stent and method for inhibiting restenosis, following vascular injury, is disclosed. The stent has an expandable, linked-filament body and a drug-release coating formed on the stent-body filaments, for contacting the vessel injury site when the stent is placed in-situ in an expanded condition. The coating releases, for a period of at least 4 weeks, a restenosis-inhibiting amount of the macrocyclic triene immunosuppressive compound everolimus. The stent, when used to treat a vascular injury, gives good protection against clinical restenosis, even when the extent of vascular injury involves vessel overstretching by more than 30% diameter. Also disclosed is a stent having a drug-release coating composed of (i) 10 and 80 weight percent of a polymer substrate and (ii) 20-90 weight percent of an anti-restenosis compound.

1 . An endovascular stent for placement at a vascular injury site, for inhibiting restenosis at the site, comprising 
 a body having an open-lattice structure formed of linked filaments, and    carried on the one or more filaments, a drug-release coating having a thickness of between 3-30 microns, and composed of (i) 20-80 weight percent polymer substrate and (ii) 20-80 weight percent macrocyclic triene compound having the form:                          where R is CH 2 —CH 2 —OH,    said stent being expandable from a contracted condition in which the stent can be delivered to a vascular injury site via catheter, and an expanded condition in which the stent coating can be placed in contact with the vessel at the injury site,    said coating being effective to release an amount of the compound to inhibit restenosis at the site.    
     
     
         2 . The stent of  claim 1 , wherein the stent body is a metal-filament structure and the polymer substrate in the coating is selected from the group consisting of polymethylmethacrylate, ethylene vinyl alcohol, poly-lactide polymers, ε-caprolactone, ethyl vinyl acetate, polyvinyl alcohol, and polyethylene oxide.  
     
     
         3 . The stent of  claim 1 , wherein the polymer substrate in the coating is formed of poly-dl-lactide having a thickness between 3-20 microns.  
     
     
         4 . The stent of  claim 1 , which further includes a parylene polymer undercoat having a thickness of between 1-3 microns, disposed between the filaments of the stent body and said coating.  
     
     
         5 . The stent of  claim 1 , further comprising a polymer undercoat disposed between the filaments of the stent body and said drug-release coating.  
     
     
         6 . The stent of  claim 5 , wherein said polymer undercoat is formed of a polymer selected from the group consisting of ethylene vinyl alcohol, parylast, silicone, a fluoropolymer, and parylene.  
     
     
         7 . The stent of  claim 1 , wherein said coating further includes a bioactive agent selected from the group consisting of antiplatelet agents, fibrinolytic agents, and thrombolytic agents.  
     
     
         8 . The stent of  claim 1 , wherein the stent body is a polymer-filament structure, said polymer filaments formed from a biodegradable polymer.  
     
     
         9 . An apparatus for delivery of a stent according to  claim 1 , comprising 
 a catheter;    a stent according to  claim 1 .    
     
     
         10 . A method for inhibiting restenosis at a vascular injury site, comprising 
 delivering to the vascular injury site, an endovascular stent having an open-lattice structure formed of linked filaments, and carried on the one or more filaments, a drug-release coating having a thickness of between 3-30 microns, and composed of (i) 20-80 weight percent polymer substrate and (ii) 20-80 weight percent macrocyclic triene compound having the form:                          where R is CH 2 —CH 2 —OH; and    expanding the stent at the vascular injury site, to bring the drug-release coating in contact with the vessel at the injury site,    said coating being effective to release an amount of the compound to inhibit restenosis at the site.    
     
     
         11 . The method of  claim 10 , wherein the stent body is a metal-filament structure and the polymer substrate in the coating is selected from the group consisting of polymethylmethacrylate, ethylene vinyl alcohol, poly-lactide polymers, ε-caprolactone, ethyl vinyl acetate, polyvinyl alcohol, and polyethylene oxide.  
     
     
         12 . The method of  claim 11 , wherein the polymer substrate in the coating is formed of poly-dl-lactide having a thickness between 3-20 microns.  
     
     
         13 . The method of  claim 10 , wherein the stent further includes a polymer undercoat disposed between the filaments of the stent body and said drug-release coating.  
     
     
         14 . The method of  13 , wherein said polymer undercoat is formed of a polymer selected from the group consisting of ethylene vinyl alcohol, parylast, silicone, a fluoropolymer, and parylene.  
     
     
         15 . The method of  claim 12 , wherein the stent further includes a parylene polymer undercoat having a thickness of between 1-3 microns, disposed between the filaments of the stent body and said poly-dl-lactide coating substrate.  
     
     
         16 . The method of  10 , wherein said coating further includes a bioactive agent selected from the group consisting of an antiplatelet agent, a fibrinolytic agent, and a thrombolytic agent.  
     
     
         17 . The method of  claim 10 , wherein the stent body is a polymer-filament structure, said polymer-filament structure formed of a bioerodable polymer.  
     
     
         18 . In a method for inhibiting restenosis at a vascular injury site, by placement at the site an intravascular stent designed to release a macrocyclic triene compound over an extended period, an improvement comprising employing as the macrocyclic triene compound, a compound having the formula:  
       
         
           
           
               
               
           
         
         where R is CH 2 —CH 2 —OH, and  
         wherein said compound is carried on said stent in a drug-release coating having a thickness of between 3-30 microns composed of a polymer substrate and having between 20-80 weight percent of said compound.  
       
     
     
         19 . The method of  claim 18 , for use where the vascular injury is produced during an angiographic procedure in which a vessel region is overstretched at least 30% in diameter.