Antimicrobial coatings for medical devices

Abstract

Antimicrobial formulations and coatings for medical devices and processes therefor are disclosed. The formulations include at least one water permeable polymer with at least one antimicrobial agent in a liquid medium and are prepared by wet milling the components and can form antimicrobial coatings having uniformly dispersed particles having an average size of no greater than 50 microns.

1 . A medical device comprising an antimicrobial coating formed from an antimicrobial formulation, the antimicrobial formulation formed by a process comprising:
 milling at least one water permeable polymer which is dissolved in a liquid medium with at least one antimicrobial agent which is insoluble in the liquid medium to form the antimicrobial formulation in which the at least one water permeable polymer encapsulates the at least one antimicrobial agent; and   adding a primary C1-6 alcohol to the antimicrobial formulation;   wherein the at least one antimicrobial agent includes a silver-based antimicrobial agent, and   wherein the at least one water permeable polymer includes at least one of a polyurethane or a thermoplastic polyurethane elastomer.   
     
     
         2 . The medical device of  claim 1 , wherein the at least one water permeable polymer has a weight average molecular weight of from about 70,000 to about 120,000 Daltons. 
     
     
         3 . The medical device of  claim 1 , wherein the at least one antimicrobial agent includes the silver-based antimicrobial agent and a second antimicrobial agent which is a polybiguanide or salt thereof. 
     
     
         4 . The medical device of  claim 1 , wherein the at least one antimicrobial agent includes silver sulfadiazine, as the silver-based antimicrobial agent, and a second antimicrobial agent which is chlorhexidine diacetate. 
     
     
         5 . The medical device of  claim 1 , wherein the liquid medium includes one or more of an alcohol; an ether; a ketone; an organic acid; an organic ester; an amide; a hydrocarbon; or a halogenated solvent or liquid. 
     
     
         6 . The medical device of  claim 1 , wherein the liquid medium includes an ether and a primary C1-6 alcohol. 
     
     
         7 . The medical device of  claim 1 , wherein the at least one antimicrobial agent is insoluble in the formulation and the formulation is milled until the insoluble antimicrobial agent has a mean particle size of no greater than 50 microns. 
     
     
         8 . The medical device of  claim 1 , wherein the process comprises:
 initially preparing a polymer solution having a viscosity of from about 100 centipoise (cP) to about 1000 cP by dissolving the at least one water permeable polymer in the liquid medium and then adding the antimicrobial agent to the solution followed by milling the formulation; and   adding a second antimicrobial agent to the formulation after milling, and further milling the formulation with the second antimicrobial agent,   wherein the primary C1-6 alcohol is methanol, ethanol, n-propanol, n-butanol, n-pentanol, and/or n-hexanol.   
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . The medical device of  claim 1 , wherein the antimicrobial coating is formed at least by applying the antimicrobial formulation on the medical device. 
     
     
         12 . The medical device of  claim 11 , wherein the antimicrobial coating has a thickness of between about 20 microns to about 80 microns. 
     
     
         13 . The medical device of  claim 11 , wherein applying the antimicrobial formulation on the medical device comprises dip-coating the medical device in the formulation and then drying the antimicrobial formulation by driving off the liquid medium to form the antimicrobial coating on the medical device. 
     
     
         14 . (canceled) 
     
     
         15 . The medical device of  claim 1 , wherein the medical device comprises a catheter. 
     
     
         16 . The medical device of  claim 1 , wherein the medical device comprises at least one of a dialysis catheter, a urological catheter, an enteral feeding tube, a surgical staple, a trocar, an implant, a suture, a respiratory tube, a surgical plate, a surgical screw, a wire, or a hernia mesh. 
     
     
         17 . A medical device comprising an antimicrobial coating,
 wherein the coating comprises at least one water permeable polymer and uniformly dispersed particles therein of at least one antimicrobial agent,   wherein the at least one water permeable polymer encapsulates the at least one antimicrobial agent by milling of the at least one water permeable polymer and the at least one antimicrobial agent together in a liquid medium,   wherein the at least one water permeable polymer comprises at least one of a polyurethane or a thermoplastic polyurethane elastomer and is soluble in the liquid medium,   wherein the at least one antimicrobial agent comprises silver sulfadiazine and is insoluble in the liquid medium, and   wherein the particles and any agglomerations of the antimicrobial agent have an average size of no greater than 20 microns.   
     
     
         18 - 20 . (canceled) 
     
     
         21 . The medical device of  claim 17 , wherein the coating has a release profile wherein at least 0.50 micrograms per centimeter (µg/cm) of silver is continuously released after 72 hours. 
     
     
         22 . The medical device of  claim 17 , wherein the coating further comprises chlorhexidine diacetate, and at least 10 µg/cm of chlorhexidine diacetate is continuously released after 72 hours. 
     
     
         23 . The medical device of  claim 17 ,
 wherein the at least one antimicrobial agent comprises chlorhexidine diacetate, a   wherein the coating comprises from about 2 weight percent (wt. %) to about 10 wt. % of silver sulfadiazine,   wherein the coating comprises at least 9 wt. % of chlorhexidine diacetate, and   wherein the coating comprises from about 70 wt. % to about 90 wt. % of the water permeable polymer.   
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . The medical device of  claim 23 ,
 wherein the coating comprises from about 3.5 wt. % to about 7 wt. % silver sulfadiazine, and   wherein the coating has a release profile wherein at least 0.50 µg/cm of silver is continuously released after 150 hours.   
     
     
         27 . (canceled) 
     
     
         28 . The medical device of  claim 23 ,
 wherein the coating comprises at least 11 wt. % of chlorhexidine diacetate, and   wherein the coating has a release profile wherein at least 10 µg/cm of chlorhexidine diacetate is continuously released after about 150 hours.   
     
     
         29 - 33 . (canceled) 
     
     
         34 . An antimicrobial coating composition comprising at least one water permeable polymer and uniformly dispersed particles therein of at least one antimicrobial agent,
 wherein the at least one water permeable polymer encapsulates the at least one antimicrobial agent by milling of the at least one water permeable polymer and the at least one antimicrobial agent together in a liquid medium,   wherein the at least one water permeable polymer comprises at least one of a polyurethane or a thermoplastic polyurethane elastomer and is soluble in the liquid medium,   wherein the at least one antimicrobial agent comprises silver sulfadiazine and is insoluble in the liquid medium, and   wherein the particles and any agglomerations of the antimicrobial agent have an average size of no greater than 20 microns.