Drug/Drug Delivery Systems for the Prevention and Treatment of Vascular Disease

Abstract

A drug and drug delivery system may be utilized in the treatment of vascular disease. A local delivery system is coated with rapamycin or other suitable drug, agent or compound and delivered intraluminally for the treatment and prevention of neointimal hyperplasia following percutaneous transluminal coronary angiography. The local delivery of the drugs or agents provides for increased effectiveness and lower systemic toxicity.

1 . A drug delivery device comprising: an intraluminal stent; a biocompatible, nonerodible polymeric coating affixed to the intraluminal stent; and a dose of from about 64 μg to about 197 μg of rapamycin or a macrocyclic triene analog thereof that binds FKBP12 incorporated into the polymeric coating, wherein said device releases a portion of said dose of rapamycin or a macrocyclic triene analog thereof on any of days three to about fifty-six following intraluminal implantation.  
     
     
         2 . A drug delivery device according to  claim 1  that releases a portion of said dose of rapamycin or a macrocyclic triene analog thereof on day fifty-six following intraluminal implantation.  
     
     
         3 . A drug delivery device according to  claim 1  that releases a portion of said dose of rapamycin or a macrocyclic triene analog thereof during a period of about two weeks to about six weeks following intraluminal implantation.  
     
     
         4 . A drug delivery device according to  claim 3  that releases a portion of said dose of rapamycin or a macrocyclic triene analog thereof at about six weeks following intraluminal implantation.  
     
     
         5 . A drug delivery device according to any one of  claims 1  to  4 , containing from about 64 μg to about 125 μg of said rapamycin or a macrocyclic triene analog thereof.  
     
     
         6 . A method of inhibiting neointimal proliferation in a coronary artery resulting from percutaneous transluminal coronary angioplasty comprising implanting a drug delivery device according to any one of  claims 1  to  4  in the lumen of said coronary artery.  
     
     
         7 . A method according to  claim 6 , wherein said drug delivery device contains from about 64 μg to about 125 μg of said rapamycin or a macrocyclic triene analog thereof.  
     
     
         8 . A drug delivery device comprising: an intraluminal stent; a biocompatible, nonerodible polymeric coating affixed to the intraluminal stent; and rapamycin or a macrocyclic triene analog thereof that binds FKBP12 incorporated into the polymeric coating, wherein said rapamycin or a macrocyclic triene analog thereof is present at a dose of from about 2 μg to about 30 μg per millimeter of stent length and said drug delivery device releases a portion of said rapamycin or a macrocyclic triene analog thereof on any of days three to about fifty-six following intraluminal implantation.  
     
     
         9 . A drug delivery device according to  claim 8  that releases a portion of said dose of rapamycin or a macrocyclic triene analog thereof on day fifty-six following intraluminal implantation.  
     
     
         10 . A drug delivery device according to  claim 8  wherein said device releases a portion of said dose of rapamycin or a macrocyclic triene analog thereof during a period of about two weeks to about six weeks following intraluminal implantation.  
     
     
         11 . A drug delivery device according to  claim 10  that releases a portion of said dose of rapamycin or a macrocyclic triene analog thereof at about six weeks following intraluminal implantation.  
     
     
         12 . A drug delivery device according to any one of  claims 8  to  11 , wherein said rapamycin or a macrocyclic triene analog thereof is present at a dose of from about 3 μg to about 13 μg per millimeter of stent length.  
     
     
         13 . A method of inhibiting neointimal proliferation in a coronary artery resulting from percutaneous transluminal coronary angioplasty comprising implanting a drug delivery device according to any one of  claims 8  to  11  in the lumen of said coronary artery.  
     
     
         14 . A method according to  claim 13 , wherein said rapamycin or a macrocyclic triene analog thereof is present on said on said drug delivery device at a dose of from about 3 μg to about 13 μg per millimeter of stent length.