Polyurethane-sealed biocompatible device and method for its preparation

Abstract

Provided is a biocompatible device which has been coated or sealed with a polyether or polyether/carbonate based urethane polymer that contains functional groups (e.g. carboxylic acid groups) which are capable of serving as anchor sites for protein binding.

1 . A biocompatible device adapted for therapeutic use within the body of a mammal, said device comprising: 
 (a) a surface layer coating said device, said surface layer coating comprising a polyether or polyether/carbonate based urethane polymer having carboxylic acid groups serving as anchor sites prepared by a method comprising the steps of: 
 (i) forming a diisocyanate terminated prepolymer based on (i) a polyether glycol or polyether/carbonate glycol having a molecular weight between about 200 to 3,000 Da and (ii) a diisocyanate having the general structure OCN—R′—NCO, wherein R′ is a hydrocarbon; and  
 (ii) chain extending said prepolymer using a dihydroxy carboxylic acid.  
   
   
   
       2 . The device of  claim 1 , wherein said device is a stent.  
   
   
       3 - 4 . (canceled)  
   
   
       5 . The device of  claim 2 , wherein said surface layer coating additionally comprises a covalently-attached protein.  
   
   
       6 . The device of  claim 5 , wherein said protein is selected from the group consisting of an anti-clotting agent, a thrombolytic agent, a mitogenic agent, a growth promoting substance, and an inhibitor.  
   
   
       7 . The device of  claim 6 , wherein said mitogenic agent is vascular endothelial growth factor (VEGF) and said anti-clotting agent is recombinant hirudin (rHir).  
   
   
       8 . The device of  claim 1 , wherein said diisocyanate is selected from the group consisting of 4,4′-diphenylmethane diisocyanate (MDI), hydrogenated methylene diisocyanate (HMDI), hexamethylene diisocyanate, toluene diisocyanates, 4,4′-tolidine diisocyanate, m-phenylene diisocyanate, 4-chloro-1,3-phenylene diisocyanate, 4,4-tetramethylene diisocyante, 1,6-hexamethylene diisocyanate, 1,10-decamethylene diisocyanate, 1,4-cyclohexylene diisocyanate, 4,4′-methylene bis (cyclohexylisocyanate), 1,4-isophorone diisocyanate, 3,3′-dimethyl-4,4′-diphenylmethane diisocyanate, and 1,5-tetrahydronaphthalene diisocyanate.  
   
   
       9 . The device of  claim 8 , wherein said diisocyanate is 4,4′-diphenylmethane diisocyanate (MDI).  
   
   
       10 . The device of  claim 1 , wherein said polyether glycol is polytetramethylene ether glycol (PTMEG 1000).  
   
   
       11 . The device of  claim 1 , wherein said polyether/carbonate glycol is polyetherpolycarbonatediol.  
   
   
       12 . The device of  claim 1 , wherein said carboxylic acid is 2,2-bis(hydroxymethyl)-propionic acid (DHMPA).  
   
   
       13 . The device of  claim 1 , wherein said molecular weight is about 1,000 Da.  
   
   
       14 - 18 . (canceled)  
   
   
       19 . The biocompatible device of  claim 1 , wherein said mammal is a human.  
   
   
       20 . The device of  claim 2 , wherein said surface layer coating coats the inner or outer surface of said stent.