Plasma-deposited coatings, devices and methods

Abstract

Coatings, devices and methods are provided, wherein the contacting surface of a medical device with at least one contacting surface for contacting a bodily fluid or tissue is modified by plasma treatment in a plasma including nitrogen-containing molecules and oxygen-containing molecules and by application of a biologically compatible coating, preferably by plasma treatment in a plasma including polymerized hydrocyclosiloxane monomers. The nitrogen-containing molecules include NH 3 , (NH 4 ) + , N 2 O, NO, NO 2 and N 2 O 4 , and the oxygen-containing molecules include O 2 and O 3 . The plasma-modified contacting surface exhibits decreased adhesion of at least some mammalian cells, such as platelets and leukocytes, decreased restenosis when used with stents, and increased apoptosis. Additional layers may be applied, including amine-providing groups such as N-trimethylsilyl-allylamine, polyoxyalkylene tethers, and bioactive compounds.

What is claimed is:  
     
         1 . An implantable medical device with a plasma-modified surface, comprising: 
 a structure adapted for implantation into a patient, the structure comprising at least one contacting surface for contacting a bodily fluid or tissue, wherein the contacting surface is modified by plasma treatment in a plasma comprising nitrogen-containing molecules and oxygen-containing molecules and by a biologically compatible coating.    
     
     
         2 . The device of  claim 1 , wherein the nitrogen-containing molecules are molecules selected from the group consisting of NH 3 , (NH 4 ) + , N 2 O, NO, NO 2  and N 2 O 4 .  
     
     
         3 . The device of  claim 1 , wherein the oxygen-containing molecules are molecules selected from the group consisting of O 2  and O 3 .  
     
     
         4 . The device of  claim 1 , wherein the plasma treatment with the nitrogen-containing molecules and the oxygen-containing molecules is sequential.  
     
     
         5 . The device of  claim 1 , wherein the plasma treatment is for less than about two minutes.  
     
     
         6 . The device of  claim 5 , wherein the plasma treatment is for between about thirty seconds and about one minute.  
     
     
         7 . The device of  claim 1 , wherein the plasma treatment is of a plasma wherein the nitrogen-containing molecules are NH 3  and the oxygen-containing molecules are O 2 .  
     
     
         8 . The device of  claim 1 , wherein the plasma treatment is of a plasma wherein the nitrogen-containing molecules are N 2 O and the oxygen-containing molecules are O 2 .  
     
     
         9 . The device of  claim 1 , where the device is a member selected from the group consisting of stents, catheters, balloons, shunts, grafts, valves, pacemakers, pulse generators, cardiac defibrillators, spinal stimulators, brain stimulators, sacral nerve stimulators, leads, inducers, sensors, seeds, screws, anchors, anti-adhesion sheets, plates and joints.  
     
     
         10 . The device of  claim 1 , wherein the at least one contacting surface comprises a metallic material.  
     
     
         11 . The device of  claim 1 , wherein the at least one contacting surface comprises a polymeric material.  
     
     
         12 . The device of  claim 1 , wherein the biologically compatible coating is a membrane formed from the plasma polymerization of a hydrocyclosiloxane monomer of the general formula:  
       
         
           
           
               
               
           
         
         wherein R is an aliphatic group having 1 to about 5 carbon atoms and n is an integer from 2 to about 10.  
       
     
     
         13 . The device of  claim 12 , wherein the hydrocyclosiloxane monomer is selected from the group consisting of 1,3,5,7-tetramethylhydrocyclotetrasiloxane, 1,3,5,7,9-pentamethylhydrocyclopentasiloxane, 1,3,5,7,9,11-hexamethylhydrocyclohexasiloxane, and a mixture of 1,3,5,7,9-pentamethylcyclopentasiloxane and 1,3,5,7,11-hexamethylcyclohexasiloxane monomers.  
     
     
         14 . The device of  claim 1  wherein the biologically compatible coating is a polymer or co-polymer selected from the group consisting of poly acrylate, poly bisphenol A carbonate, polybutadiene, polycarbonate, poly butylene terephthalate, poly butryl methacrylate, polydimethyl siloxane, polyester, polyethyleneimine, poly methyl methacrylate, polypropylene, polystyrene, polysulfone, polyurethane, poly vinyl, poly vinyl acetate polylactide, polyglycolide, polycaprolactone, and polyvinylidine fluoride.  
     
     
         15 . A coating for an implantable medical device with at least one contacting surface for contacting a bodily fluid or tissue, comprising: 
 the product of plasma treatment of a plasma comprising nitrogen-containing molecules and oxygen-containing molecules; and    the product of plasma polymerization of a hydrocyclosiloxane monomer of the general formula:                          wherein R is an aliphatic group having 1 to about 5 carbon atoms and n is an integer from 2 to about 10.    
     
     
         16 . The coating of  claim 15 , wherein the hydrocyclosiloxane monomer is selected from the group consisting of 1,3,5,7-tetramethylhydrocyclotetrasiloxane, 1,3,5,7,9-pentamethylhydrocyclopentasiloxane, 1,3,5,7,9,11-hexamethylhydrocyclohexasiloxane, and a mixture of 1,3,5,7,9-pentamethylcyclopentasiloxane and 1,3,5,7,11-hexamethylcyclohexasiloxane monomers.  
     
     
         17 . The coating of  claim 15 , further comprising the product of plasma polymerization of a monomer selected from the group consisting of fluorocarbon monomers, organo-based monomers selected from the group consisting of ethylene, allylamine, N-trimethylsilyl-allylamine, hydrocarbons, N-protected unsaturated amines, N-unprotected unsaturated amines, N-protected cyclic aliphatic amines, N-unprotected cyclic aliphatic amines, mercaptans, nitriles and organophosphorus compounds; and functionalizing monomers selected from the group consisting of N 2 , CO 2 , NH 3  and SO 2 .  
     
     
         18 . The coating of  claim 17 , further comprising a polyoxyalkylene tether of the formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1  is selected from an N-benzotriazole group, an N-2-pyrrolidinone group, or an 2-oxypyrimidine group; R 2 , R 3  and R 4  are independently selected alkylene groups of about 2 to about 3 carbon atoms and may be the same or different; R 5  is selected from hydrogen, methyl, a carbonyloxy-N-benzotriazole group, a carbonyloxy-N-2-pyrrolidinone group, and a carbonyl-2-oxypyrimidine group; a is an integer from 1 to 1000 and each of b and c is an integer from 0 to 1000, where a+b+c is an integer from 3 to 1000, under conditions whereby the R 5  group reacts with a free amino group of the third layer thereby forming a covalent bond to give a modified polymeric surface having activated polyoxyalkylene groups covalently bonded thereto.  
     
     
         19 . The coating of  claim 15 , wherein the nitrogen-containing molecules are molecules selected from the group consisting of NH 3 , (NH 4 ) + , N 2 O, NO, NO 2  and N 2 O 4 .  
     
     
         20 . The coating of  claim 15 , wherein the oxygen-containing molecules are molecules selected from the group consisting of O 2  and O 3 .  
     
     
         21 . The coating of  claim 15 , wherein the plasma treatment is of a plasma wherein the nitrogen-containing molecules are NH 3  and the oxygen-containing molecules are O 2 .  
     
     
         22 . The coating of  claim 15 , wherein the plasma treatment is with a plasma wherein the nitrogen-containing molecules are N 2 O and the oxygen-containing molecules are O 2 .  
     
     
         23 . An implantable medical device with at least one contacting surface for contacting a bodily fluid or tissue, wherein the contacting surface comprises a coating of  claim 15 .  
     
     
         24 . The device of  claim 23 , where the device is a member selected from the group consisting of stents, catheters, balloons, shunts, grafts, valves, pacemakers, pulse generators, cardiac defibrillators, spinal stimulators, brain stimulators, sacral nerve stimulators, leads, inducers, sensors, seeds, screws, anchors, anti-adhesion sheets, plates and joints.  
     
     
         25 . A method of imparting bioactive properties to a surface, comprising: 
 modifying the surface by plasma treatment of a plasma comprising nitrogen-containing molecules and oxygen-containing molecules; and    applying a biologically compatible coating to the surface.    
     
     
         26 . The method of  claim 25 , wherein applying the biologically compatible coating comprises plasma polymerization of a hydrocyclosiloxane monomer of the general formula:  
       
         
           
           
               
               
           
         
       
       wherein R is an aliphatic group having 1 to about 5 carbon atoms and n is an integer from 2 to about 10.  
     
     
         27 . The method of  claim 26 , wherein the hydrocyclosiloxane monomer is selected from the group consisting of 1,3,5,7-tetramethylhydrocyclotetrasiloxane, 1,3,5,7,9-pentamethylhydrocyclopentasiloxane, 1,3,5,7,9,11-hexamethylhydrocyclohexasiloxane, and a mixture of 1,3,5,7,9-pentamethylcyclopentasiloxane and 1,3,5,7,11-hexamethylcyclohexasiloxane monomers.  
     
     
         28 . The method of  claim 25 , wherein the biologically compatible coating is a polymer or co-polymer selected from the group consisting of poly acrylate, poly bisphenol A carbonate, polybutadiene, polycarbonate, poly butylene terephthalate, poly butryl methacrylate, polydimethyl siloxane, polyester, polyethyleneimine, poly methyl methacrylate, polypropylene, polystyrene, polysulfone, polyurethane, poly vinyl, poly vinyl acetate and polyvinyledine fluoride.  
     
     
         29 . The method of  claim 25 , wherein the nitrogen-containing molecules are molecules selected from the group consisting of NH 3 , (NH 4 ) + , N 2 O, NO, NO 2  and N 2 O 4 .  
     
     
         30 . The method of  claim 25 , wherein the oxygen-containing molecules are selected from the group consisting of O 2  and O 3 .  
     
     
         31 . The method of  claim 25 , wherein the plasma treatment with the nitrogen-containing molecules and the oxygen-containing molecules is sequential.  
     
     
         32 . The method of  claim 31 , wherein the plasma treatment is for less than about two minutes.  
     
     
         33 . The method of  claim 32 , wherein the plasma treatment is for between about thirty seconds and about one minute.  
     
     
         34 . The method of  claim 25 , wherein the plasma treatment is of a plasma wherein the nitrogen-containing molecules are NH 3  and the oxygen-containing molecules are O 2 .  
     
     
         35 . The method of  claim 25 , wherein the plasma treatment is with a plasma wherein the nitrogen-containing molecules are N 2 O and the oxygen-containing molecules are O 2 .