Local delivery of drugs from self assembled coatings

Abstract

The invention relates to oligofluorinated coatings and their use in drag delivery. The oligofluorinated coatings are compositions comprising formula (XVII). These coatings are used in a method of delivering a biologically active agent to a tissue surface in a mammalian tissue. This method occurs by contacting the surface with the coating including an oligofluorinated oligomer and a biologically active agent wherein the coating resides on the tissue surface and release the biologically active agent to the tissue surface.

What is claimed is: 
     
         1 . A composition of formula (XV): 
       
         
           
           
               
               
           
         
       
       wherein
 m and n are both 0, or m and n are both 1; 
 each A and A 2  is a trifunctional monomer having a molecular weight between 50-3,500 Da; 
 each L and L A  is, independently, a linker; 
 each R X1A , R X1B , R X2A , and R X2B  is, independently, a water insoluble segment having a molecular weight between 200-3,500 Da; and 
 R Y1  is a non-halogenated organic segment having a molecular weight between 100-3,500 Da; and 
 when m and n are both 1, each of R Z1  and R Z2  is, independently, a difunctional water insoluble segment having a molecular weight between 50-3500 Da, or 
 when m and n are both 0, each of R Z1  and R Z2  is, independently a water insoluble segment having a molecular weight between 200-3,500 Da. 
 
     
     
         2 - 10 . (canceled) 
     
     
         11 . The composition of  claim 1 , wherein said composition is described by the following formula, 
       
         
           
           
               
               
           
         
         wherein 
         F T  is a polyfluoroorgano group; 
         L is a linker; 
         X 1  is H, CH 3 , or CH 2 CH 3 ; 
         X 2  is H, CH 3 , or CH 2 CH 3 ; and 
         n is an integer from 5 to 50. 
       
     
     
         12 - 69 . (canceled) 
     
     
         70 . A transient medical device having a surface with a self assembling coating deposited thereon, said self assembling coating comprising (i) an oligofluorinated oligomer and (ii) a biologically active agent, wherein said transient medical device comprises an energy generating element, said energy generating element being capable of disrupting said self assembling coating when activated. 
     
     
         71 - 102 . (canceled) 
     
     
         103 . A method for delivering sirolimus to a site in a vessel, said method comprising:
 (i) providing a balloon catheter having a surface with a coating thereon, said coating comprising sirolimus and an oligofluorinated oligomer of formula (III):
   F T —[B(oligo)] n -B—F T   (III),
 
   wherein oligo is polytetramethyleneoxide or polypropylene oxide, B is a hard segment formed from hexamethylene diisocyanate, n is an integer from 1 to 10, and F T  is a polyfluoroorgano group;   (ii) inserting said balloon catheter into said vessel;   (iii) positioning said balloon catheter near said site;   (iv) delivering sirolimus to a wall of said vessel by deploying said balloon catheter into a deformed and expanded configuration to contact said wall; and   (v) removing said balloon catheter from said vessel with at least a portion of said coating remaining at said site in the absence of an implanted medical device,   wherein prior to step (iv) from 45 to 95% (w/w) of said sirolimus is retained on said balloon.   
     
     
         104 . A method for inhibiting restenosis at a site in a vessel, said method comprising:
 (i) providing a balloon catheter having a surface with a coating thereon, said coating sirolimus and an oligofluorinated oligomer of formula (III):
   F T —[B(oligo)] n -B—F T   (III),
 
   wherein oligo is polytetramethyleneoxide or polypropylene oxide, B is a hard segment formed from hexamethylene diisocyanate, n is an integer from 1 to 10, and F T  is a polyfluoroorgano group;   (ii) inserting said balloon catheter into said vessel;   (iii) positioning said balloon catheter near said site;   (iv) applying sirolimus to a wall of said vessel by deploying said balloon catheter into a deformed and expanded configuration to contact said wall; and   (v) removing said balloon catheter from said vessel with at least a portion of said coating remaining at said site,   wherein prior to step (iv) from 45 to 95% (w/w) of said sirolimus is retained on said balloon.   
     
     
         105 . The method of  claim 103 , wherein said vessel is a bifurcated vessel. 
     
     
         106 . The method of  claim 103 , wherein said coating on the surface of said balloon catheter has a thickness of from 0.01 to 250 microns. 
     
     
         107 . The method of  claim 103 , wherein said coating consists of components having a molecular weight of from 1 kDa to 60 kDa. 
     
     
         108 . The method of  claim 103 , wherein said oligofluorinated oligomer has a theoretical molecular weight of 2 kDa to 30 kDa. 
     
     
         109 . The method of  claim 103 , wherein said coating comprises from 0.5 to 50% (w/w) sirolimus. 
     
     
         110 . The method of  claim 103 , wherein said vessel is a blood vessel, a vein graft, or a synthetic graft. 
     
     
         111 . The method of  claim 103 , wherein from 35 to 65% (w/w) sirolimus is delivered to said vessel. 
     
     
         112 . The method of  claim 103 , wherein said coating has a glass transition of from 80 to 40° C. 
     
     
         113 . The method of  claim 103 , wherein said coating has a tack of from 1.0 to 200 g. 
     
     
         114 . The method of  claim 103 , wherein said coating has a viscosity of from 0.04 to 130 cps. 
     
     
         115 . The method of  claim 103 , wherein said coating has a contact angle hysteresis of the surface of from 20-120°. 
     
     
         116 . The method of  claim 103 , wherein said oligofluorinated oligomer comprises from 5 to 80% (w/w) of said hard segment, from 10 to 90% (w/w) of polyalkylene oxide, and from 5 to 80% (w/w) of said polyfluoroorgano group. 
     
     
         117 . The method of  claim 103 , wherein the average molecular weight of the oligofluorinated oligomer is from 2 kDa to 50 kDa. 
     
     
         118 . The method of  claim 103 , wherein oligo is polytetramethyleneoxide. 
     
     
         119 . The method of  claim 103 , wherein oligo is polypropylene oxide.