Medical devices having antimicrobial coatings thereon

Abstract

The present invention provides a medical device, preferably a contact lens, which comprises an antimicrobial coating including at least one layer of polyquat of formula (I) or (II). The antimicrobial coating on the medical device of the invention has a high antimicrobial efficacy against microorganisms including Gram-positive and Gram-negative bacterial, a low toxicity, low coefficient of friction, and increased hydrophilicity while maintaining the desired bulk properties such as oxygen permeability and ion permeability of lens material. Such lenses are useful as extended-wear contact lenses. In addition, the invention provides a method for making a medical device, preferably a contact lens, having an antimicrobial coating thereon.

1 - 17 . (canceled) 
     
     
         18 . A method for producing a medical device having an antimicrobial coating, comprising the steps of:
 (a) functionalizing the surface of the medical device; and   (b) covalently coupling polyquats of formula (I) or (II) to the functionalized surface of the medical device to form the antimicrobial coating on the medical device   
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3  and R 4 , independently of one another, are C 1 -C 10  hydrocarbon radicals, preferably C 1  to C 6  alkyl radicals or C 1  to C 6  alkyl radicals having one or more hydroxyl groups, more preferably methyl, ethyl, or benzyl radicals, even more preferably methyl radicals, wherein A and B, independently of one another, are n-alkylene groups having 3 to 15 carbon atoms or n-alkylene groups having 3 to 15 carbon atoms and one or more hydroxyl groups, wherein the index y is a number from about 10 to 500, preferably a number from 25 to 400, and more preferably a number from 50 to 300, wherein X is chlorine, bromine, or iodine, wherein the index n is a number from about 100 to 5000, preferably a number from 500 to 4000, and more preferably a number from 500 to 3000, wherein R 5  and R 6 , independently of one another, are n-alkyl groups having 1 to 10 carbon atoms or n-alkyl groups having 1 to 10 carbon atoms and one or more hydroxyl groups. 
       
     
     
         19 . A method of  claim 18 , wherein said medical device is an ophthalmic device. 
     
     
         20 . A method of  claim 19 , wherein said ophthalmic lens is a contact lens. 
     
     
         21 . A method of  claim 20 , wherein the contact lens is functionalized with a diazirine compound. 
     
     
         22 . A method for producing a medical device having a core material and an antimicrobial coating, comprising applying at least one layer of polyquats of formula (I) or (II) onto the medical device 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3  and R 4 , independently of one another, are C 1 -C 10  hydrocarbon radicals, preferably C 1  to C 6  alkyl radicals or C 1  to C 6  alkyl radicals having one or more hydroxyl groups, more preferably methyl, ethyl, or benzyl radicals, even more preferably methyl radicals, wherein A and B, independently of one another, are n-alkylene groups having 3 to 15 carbon atoms or n-alkylene groups having 3 to 15 carbon atoms and one or more hydroxyl groups, wherein the index y is a number from about 10 to 500, preferably a number from 25 to 400, and more preferably a number from 50 to 300, wherein X is chlorine, bromine, or iodine, wherein the index n is a number from about 100 to 5000, preferably a number from 500 to 4000, and more preferably a number from 500 to 3000, wherein R 5  and R 6 , independently of one another, are n-alkyl groups having 1 to 10 carbon atoms or n-alkyl groups having 1 to 10 carbon atoms and one or more hydroxyl groups. 
       
     
     
         23 . A method of  claim 22 , comprising applying at least one layer of polyquats of formula (I) in which one of A and B is hexamethylene radical (—CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 —) and the respective other one is an n-alkylene group having 6 to 12 carbon atoms. 
     
     
         24 . A method of  claim 22 , wherein the layer of polyquats is applied onto the medical device by immersing said medical device in a first solution of polyquat of formula (I) or (II) or by spraying a second solution of polyquat of formula (I) or (II) onto the surface of said medical device. 
     
     
         25 . A method of  claim 24 , further comprising applying at least one layer of polyanionic materials. 
     
     
         26 . A method of  claim 25 , wherein the layer of polyanionic materials is applied onto the medical device by immersing said medical device in a first solution of polyanionic materials or by spraying a second solution of polyanionic materials onto the surface of said medical device. 
     
     
         27 . A method of  claim 26 , further comprising the steps of:
 (a) contacting the core material with a solution of the first polyionic material to form a layer of the first polyionic material;   (b) optionally rinsing said medical device by contacting said medical device with a rinsing solution;   (c) contacting said medical device with a solution of a second polyionic material to a layer of the second polyionic material on top of the layer of the first polyionic material, wherein said second polyionic material has charges opposite of the charges of the first polyionic material; and   (d) optionally rinsing said medical device by contacting said lens with the rinsing solution.   
     
     
         28 . A method of  claim 27 , wherein at least one of said contacting occurs by immersion said medical device in a solution. 
     
     
         29 . A method of  claim 27 , wherein at least one of said contacting occurs by spraying a solution onto the medical device. 
     
     
         30 . A method of  claim 27 , wherein said method comprises repeating steps (a) through (D between 3 to 20 times. 
     
     
         31 . A method of  claim 26 , wherein said method comprises dipping said medical device in a solution containing a polyanionic material and polycationic material in an amount such that the molar charge ratio of said solution is from about 3:1 to about 100:1. 
     
     
         32 . A method of  claim 31 , wherein said molar charge ratio of said solution is 10:1. 
     
     
         33 . A method for producing a contact lens having an antimicrobial coating, comprising the steps of:
 (a) forming a mold for making the contact lens, wherein the mold comprises a first mold portion defining a first optical surface and a second mold portion defining a second optical surface, wherein said first mold portion and said second mold portion are configured to receive each other such that a contact lens-forming cavity is formed between said first optical surface and said second optical surface;   (b) applying a transferable antimicrobial coating, using a layer-by-layer polyelectrolyte deposition technique, onto at least one of said optical surface, wherein the transferable antimicrobial coating comprises at least one layer of polyquat of formula (I) or (II)   
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3  and R 4 , independently of one another, are C 1 -C 10  hydrocarbon radicals, preferably C 1  to C 6  alkyl radicals or C 1  to C 6  alkyl radicals having one or more hydroxyl groups, more preferably methyl, ethyl, or benzyl radicals, even more preferably methyl radicals, wherein A and B, independently of one another, are n-alkylene groups having 3 to 15 carbon atoms or n-alkylene groups having 3 to 15 carbon atoms and one or more hydroxyl groups, wherein the index y is a number from about 10 to 500, preferably a number from 25 to 400, and more preferably a number from 50 to 300, wherein X is chlorine, bromine, or iodine, wherein the index n is a number from about 100 to 5000, preferably a number from 500 to 4000, and more preferably a number from 500 to 3000, wherein R 5  and R 6 , independently of one another, are n-alkyl groups having 1 to 10 carbon atoms or n-alkyl groups having 1 to 10 carbon atoms and one or more hydroxyl groups; 
         (c) positioning said first mold portion and said second mold portion such that said mold portions receive each other and said optical surfaces define said contact lens forming cavity; 
         (d) dispensing a polymerizable composition into said contact lens-forming cavity; 
         (e) curing said polymerizable composition within said contact lens-forming cavity such that the contact lens is formed, whereby at least a portion of said transferable coating detaches from said at least one optical surface of said mold portion and reattaches to said formed contact lens such that said contact lens becomes coated with the antimicrobial coating. 
       
     
     
         34 . A method of  claim 32 , wherein said transferable antimicrobial coating is applied onto at least one of said optical surfaces by immersing said mold in a first solution of polyquat of formula (I) or (II) or by spraying a second solution of polyquat of formula (I) or (II) onto at least one of said optical surfaces. 
     
     
         35 - 46 . (canceled)