Composition and method for preparing biocompatible surfaces

Abstract

The invention provides methods and compositions for providing biocompatible surfaces to medical articles. In particular the invention provides biocompatible coatings with heparin activity. In some aspects, the biocompatible coatings of the invention are able to release a bioactive agent. The coatings can be formed using biostable or biodegradable polymeric material and photoreactive groups. The invention also provides methods for improving the quality of bioactive agent-containing coatings by performing pre-irradiation of biocompatible coating compositions.

1 . A method for providing a biocompatible coating to a surface of a medical article, comprising the steps of: 
 (a) irradiating a composition comprising (i) a first polymer, (ii) photoreactive groups, and (iii) a biocompatible agent selected from the group consisting of polysaccharides and polypeptides, wherein irradiating activates the photoreactive groups; and    (b) after step (a), disposing the irradiated composition on the medical article.    
     
     
         2 . The method of  claim 1  where, in the step of irradiating, the first polymer comprises a hydrophobic polymer.  
     
     
         3 . The method of  claim 2  where, in the step of irradiating, the first polymer is selected from the group consisting of poly(alkyl(meth)acrylates).  
     
     
         4 . The method of  claim 3  where, in the step of irradiating, the first polymer is poly(butyl(meth)acrylate).  
     
     
         5 . The method of  claim 1  where, in the step of irradiating, the first polymer is present in the composition in the range of 1-20 mg/mL.  
     
     
         6 . The method of  claim 1  where, in the step of irradiating, the composition comprises a polysaccharide selected from the group consisting of heparin, hyaluronic acid, chondroitin, keratan, and dermatan.  
     
     
         7 . The method of  claim 1  where, in the step of irradiating, the composition comprises a polypeptide selected from the group consisting of fibronectin, laminin, collagen, elastin, vitronectin, tenascin, fibrinogen, albumin, thrombospondin, osteopontin, von Willibrand Factor, bone sialoprotein, and active domains thereof.  
     
     
         8 . The method of  claim 1  where, in the step of irradiating, biocompatible agent is present in the composition in the range of 0.1 mg/mL -10.0 mg/mL  
     
     
         9 . The method of  claim 1  where, in the step of irradiating, the photoreactive groups are pendent from the biocompatible agent.  
     
     
         10 . The method of  claim 1  where, in the step of irradiating, the composition further comprises a component selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, polyethylene glycol sulfonates, fatty quaternary amines, fatty sulfonates, fatty acids, dextran, dextrin, and cyclodextrin.  
     
     
         11 . The method of  claim 10  where, in the step of irradiating, the component is present in the composition in the range of 0.1 mg/mL to 2.5 mg/mL.  
     
     
         12 . The method of  claim 10  where, in the step of irradiating, the component comprises polyvinylpyrrolidone.  
     
     
         13 . The method of  claim 10  where, in the step of irradiating, photoreactive groups are pendent from the component selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, polyethylene glycol sulfonates, fatty quaternary amines, fatty sulfonates, fatty acids, dextran, dextrin, and cyclodextrin.  
     
     
         14 . The method of  claim 13  where, in the step of irradiating, the photoreactive groups are pendent from both heparin and poly(vinylpyrrolidone).  
     
     
         15 . The method of  claim 1  where, in the step of irradiating, the composition comprises a first liquid selected from THF or acetone.  
     
     
         16 . The method of  claim 15  where, in the step of irradiating, the composition comprises a second liquid selected from diethylene glycol, methanol, ethanol, n-propanol, isopropanol (IPA), n-butanol, chloroform, methylene chloride, 2-pyrrolidone, polyethylene glycol, propylene glycol, 1,4-butanediol, glycerol, triethanolamine, propionic acid, and acetic acid.  
     
     
         17 . The method of  claim 1  where, in step (b), the irradiated composition is disposed on the medical article comprising an intermediate coated layer comprising a second polymer.  
     
     
         18 . The method of  claim 17 , where, in the step of irradiating, the second polymer is different than the first polymer.  
     
     
         19 . The method of  claim 18 , where, in the step of irradiating, the second polymer and the first polymer are hydrophobic.  
     
     
         20 . The method of  claim 17 , where, in the step of irradiating, the second polymer is selected from the group consisting of poly(alkyl(meth)acrylates), and poly(aromatic(meth)acrylates), poly(ethylene-co-vinyl acetate), diolefin derived non-aromatic polymers and copolymers, and poly(vinylpyrrolidone).  
     
     
         21 . The method of  claim 1  where, in step (b), the medical article comprises an intraluminal prosthesis.  
     
     
         22 . The method of  claim 21  where, in step (b), the intraluminal prosthesis is self-expanding.  
     
     
         23 . The method of  claim 22  where, in step (b), the intraluminal prosthesis comprises a metal alloy.  
     
     
         24 . The method of  claim 23  where, in step (b), wherein the intraluminal prosthesis comprises nitinol.  
     
     
         25 . The method of  claim 23  where, in step (b), the composition is disposed on a portion of the intraluminal prosthesis that will come in contact with bodily fluids.  
     
     
         26 . The method of  claim 1 , in step (b), the composition is disposed on a medical article selected from the group consisting of diagnostic articles and sensors.  
     
     
         27 . A method for preparing a medical article having a biocompatible surface, comprising the steps of: 
 (a) irradiating a composition comprising a biocompatible agent, photoreactive groups, a hydrophobic polymer, and a component selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, polyethylene glycol sulfonates, fatty quaternary amines, fatty sulfonates, fatty acids, dextran, dextrin, and cyclodextrin, to activate the photoreactive groups;    (b) after step (a), disposing the irradiated composition on a medical article.    
     
     
         28 . A method for preparing a medical article having a surface having heparin or collagen activity comprising the steps of: 
 (a) irradiating a composition comprising heparin or collagen, photoreactive groups, a first polymer that is hydrophobic, and a second polymer that is different than the first polymer;    (b) after step (a), disposing the irradiated composition on a medical article.