Composition And Methods For Antimicrobial Articles

Abstract

A biocompatible controlled release form of complexed iodine is achieved by a complexation of polyvinyl alcohol based foam and characterized by a residual starch component to optimize iodine release profiles. The resulting iodine complexed polyvinyl alcohol foam may be utilized locally as an antimicrobial agent that releases controlled amounts of iodine sufficient to kill microbes for extended durations without excessive bulk and rigidity.

1 . A PVA foam article comprising:
 a) at least in part a pore forming carbohydrate, and   b) iodine complexed at least in part to the PVA, where the pre-iodine complexed density of the PVA foam is at least 0.074 g/cm 3 .   
     
     
         2 . The PVA foam article of  claim 1 , where the carbohydrate is a polysaccharide including starches. 
     
     
         3 . The PVA foam article of  claim 1 , where the iodine is further complexed at least in part to the carbohydrate. 
     
     
         4 . The PVA foam article of  claim 1 , further comprising a thickness of 2 mm to 6 mm. 
     
     
         5 . The PVA foam article of  claim 2 , where the article is packaged with a moisture content of at least 40% (w/w). 
     
     
         6 . The PVA foam article of  claim 1 , where the article is a sponge for disinfecting surfaces or liquids. 
     
     
         7 . The PVA foam article of  claim 1 , where the article is a sponge for treatment of diseased tissues including tissues of wounds and tissues of otitis conditions. 
     
     
         8 . The PVA foam article of  claim 7 , where the complexed foam exhibits the controlled in vitro cumulative release of iodine in distilled water at 37 C at or near sink conditions of:
 a) between 50 ppm and 175 ppm at 3 hours,   b) between 100 ppm and 300 ppm at 6 hours, and   c) between 180 ppm and 400 ppm at 12 hours.   
     
     
         9 . The PVA foam article of  claim 8 , when applied to a patient wound is capable of continuously releasing iodine for at least 24 hours. 
     
     
         10 . The PVA foam article of  claim 8 , wherein the in vitro release is measured by an iodine release test which utilizes:
 h) a shaker bath,   i) a lateral agitation distance of 0.5 inches,   j) a release media of deaerated distilled water at 37 degrees Celsius,   k) a media volume of 18 ml per vessel,   l) media/sample vessels of a 1 inch diameter glass vials of approximately 20 ml volume,   m) an agitation rate equivalent to forty 0.5 inch lateral shifts per minute, and   n) a sample as supplied to a patient, sized to a surface area of 4.5 centimeters squared.   
     
     
         11 . The PVA foam article of  claim 1 , further comprising a lipid based semi-solid added to the foam prior to packaging or at the time of application to a patient. 
     
     
         12 . A method of producing an iodine complexed PVA foam article with a pore forming carbohydrate comprising:
 a) mixing PVA resin, a carbohydrate pore former, and water,   b) polymerizing at least some of the PVA resin within the mixture,   c) curing the resulting polymerized PVA within the mixture,   d) removing a portion of the carbohydrate thereby creating a PVA foam with a density of at least 0.074 g/cm 3 , and   e) complexing the PVA foam and residual carbohydrate with iodine.   
     
     
         13 . The method of  claim 12 , where the polymerization is catalyzed by acid. 
     
     
         14 . The method of  claim 12 , where the PVA resin is polymerized via a polymerizing agent including an aldehyde. 
     
     
         15 . The method of  claim 12 , where the carbohydrate is a polysaccharide, including a starch. 
     
     
         16 . The method of  claim 12 , where the average particle size of the carbohydrate is from 0.1 to 0.6 microns prior to hydration. 
     
     
         17 . The method of  claim 12 , where the polymerized PVA is cured for at least 12 hours above 40 degrees Celsius. 
     
     
         18 . The method of  claim 12 , where greater than 25% of the carbohydrate is removed after polymerization. 
     
     
         19 . The method of  claim 12 , where the complexed PVA foam is further skived to a thickness of less than 6 mm before or after complexing with iodine. 
     
     
         20 . The method of  claim 12 , where the complexed article is further packaged with a moisture content of at least 40% (w/w). 
     
     
         21 . The method of  claim 12 , where the complexed PVA is a sponge for disinfecting surfaces or liquids. 
     
     
         22 . The method of  claim 12 , where the complexed PVA is a sponge for treatment of diseased tissues including tissues of wounds and tissues of otitis conditions. 
     
     
         23 . A method of treating a wound comprising:
 a) providing a PVA foam sponge with a density of at least 0.074 g/cm 3 ,   b) complexing the PVA foam with iodine, and   c) applying the PVA foam sponge to the wound bed, where the complexed PVA foam sponge exhibits the controlled in vitro cumulative release of iodine in distilled water at 37 C at or near sink conditions of:
 i. between 50 ppm and 175 ppm at 3 hours, 
 ii. between 100 ppm and 300 ppm at 6 hours, and 
 iii. between 180 ppm and 400 ppm at 12 hours. 
   
     
     
         24 . The method of  claim 23 , where the complexed PVA foam sponge further continuously releases iodine for at least 24 hours 
     
     
         25 . The method of  claim 23 , where the complexed PVA foam sponge is skived to a thickness of 2 mm to 6 mm. 
     
     
         26 . The method of  claim 23 , where the complexed PVA foam sponge is packaged with a moisture content of at least 40% (w/w). 
     
     
         27 . The method of  claim 23 , where the complex PVA foam sponge is used in combination with negative pressure wound therapy. 
     
     
         28 . The method of  claim 23 , wherein the in vitro release is measured by an iodine release test which utilizes:
 a) a shaker bath,   b) a lateral agitation distance of 0.5 inches,   c) a release media of deaerated distilled water at 37 degrees Celsius,   d) a media volume of 18 ml per vessel,   e) media/sample vessels of a 1 inch diameter glass vials of approximately 20 ml volume,   f) an agitation rate equivalent to forty 0.5 inch lateral shifts per minute, and   g) a sample as supplied to a patient sized to a surface area of 4.5 centimeters squared.   
     
     
         29 . The PVA foam article of  claim 23 , further comprising a lipid based semi-solid added to the foam prior to packaging or at the time of application to a patient.