Anti-infective antimicrobial-containing biomaterials

Abstract

Fatty acid-derived biomaterials, methods of making the biomaterials, and methods of loading them with silver compounds are described. The silver-containing biomaterials can be utilized alone or in combination with a medical device for the release and local delivery of one or more anti-infective agents. Methods of forming and tailoring the properties of said biomaterials and methods of using said biomaterials for treating injury in a mammal are also provided.

1 . A composition comprising an antimicrobial compound, a fatty acid, and a glyceride, wherein the fatty acid and glyceride components are cross-linked. 
     
     
         2 . The composition of  claim 1 , wherein the antimicrobial compound is a silver compound, and the silver compound is ionic silver or elemental silver. 
     
     
         3 . The composition of  claim 2 , wherein the silver is elemental silver and is in the form of a silver nanoparticle. 
     
     
         4 . The composition of  claim 2 , wherein the silver is ionic silver and is selected from the group consisting of silver nitrate, silver chloride, silver fluoride, silver bromide, silver oxide, silver sulfate, silver carbonate, silver cyanide, silver tetrafluoroborate, silver sulfide, silver acetate, silver lactate, silver benzoate, silver cyclohexanebutyrate, silver diethyldithiocarbamate, silver trifluoromethanesulfonate and mixtures thereof. 
     
     
         5 . The composition of  claim 2 , wherein the silver is ionic silver and is selected from the group consisting of silver nitrate, silver acetate, silver oxide, and mixtures thereof. 
     
     
         6 . The composition of  claim 1 , wherein the antimicrobial compound is selected from the group consisting of diamidines, iodine and iodophors, peroxygens, phenols, bisphenols, halophenols, biguanides and silver compounds. 
     
     
         7 . The composition of  claim 1 , wherein the antimicrobial compound is selected from the group consisting of triclosan, chlorhexidine, triclocarban, hexachlorophene, dibromopropamidine, chloroxylenol, phenol and cresol. 
     
     
         8 . The composition of  claim 1 , wherein the antimicrobial compound is an antibiotic compound. 
     
     
         9 . The composition of  claim 8 , wherein the antibiotic compound is selected from the group consisting of gentamicin sulfate, penicillin g, ephalothin, ampicillin, amoxicillin, augmentin, aztreonam, imipenem, streptomycin, gentamicin, vancomycin, clindamycin, erythromycin, azithromycin, polymyxin, bacitracin, amphotericin, nystatin, rifampicin, tetracycline, doxycycline, chloramphenicol, nalidixic acid, ciprofloxacin, sulfanilamide, gantrisin, trimethoprim, isoniazid, para-aminosalicylic acid, and minocycline. 
     
     
         10 . The composition of  claim 1 , wherein the cross-linked fatty acid and glyceride are derived from oil containing at least one omega-3 fatty acid. 
     
     
         11 . The composition of  claim 10 , wherein the oil is a fish oil. 
     
     
         12 . The composition of  claim 1 , further comprising an additional antimicrobial compound. 
     
     
         13 . The composition of  claim 12 , wherein the additional antimicrobial compound is selected from the group consisting of diamidines, iodine and iodophors, peroxygens, phenols, bisphenols, halophenols, biguanides and silver compounds. 
     
     
         14 . The composition of  claim 12 , wherein the additional antimicrobial compound is selected from the group consisting of elemental silver, silver nanoparticle, silver nitrate, silver chloride, silver fluoride, silver bromide, silver oxide, silver sulfate, silver carbonate, silver cyanide, silver tetrafluoroborate, silver sulfide, silver acetate, silver lactate, silver benzoate, silver cyclohexanebutyrate, silver diethyldithiocarbamate, silver trifluoromethanesulfonate, triclosan, chlorhexidine, triclocarban, hexachlorophene, dibromopropamidine, chloroxylenol, phenol and cresol. 
     
     
         15 . The composition of  claim 1 , further comprising an additional antibiotic compound. 
     
     
         16 . The composition of  claim 15 , wherein the antibiotic compound is selected from the group consisting of gentamicin sulfate, penicillin g, ephalothin, ampicillin, amoxicillin, augmentin, aztreonam, imipenem, streptomycin, gentamicin, vancomycin, clindamycin, erythromycin, azithromycin, polymyxin, bacitracin, amphotericin, nystatin, rifampicin, tetracycline, doxycycline, chloramphenicol, nalidixic acid, ciprofloxacin, sulfanilamide, gantrisin, trimethoprim, isoniazid, para-aminosalicylic acid, and minocycline. 
     
     
         17 . The composition of  claim 1 , further comprising an oil containing an omega-3 fatty acid. 
     
     
         18 . The composition of  claim 17 , wherein the oil is a fish oil, olive oil, grape oil, palm oil, or flaxseed oil. 
     
     
         19 . The composition of  claim 1 , wherein when the composition is associated with a tissue of a subject, the silver compound is released from the cross-linked fatty acid at a controlled release rate. 
     
     
         20 . A film comprising an antimicrobial compound, a fatty acid, and a glyceride, wherein the fatty acid and glyceride components are cross-linked. 
     
     
         21 . The composition of  claims 1  or  20 , wherein the composition is associated with a medical device. 
     
     
         22 . The composition of  claim 21 , wherein the composition is associated with a medical device, and the medical device is a bandage, a stent, a graft, a shunt, a catheter, a surgical mesh, or a balloon. 
     
     
         23 . A medical device at least partially coated with the composition of  claim 1 . 
     
     
         24 . The medical device of  claim 23 , wherein the medical device is a bandage, a stent, a graft, a shunt, a catheter, or a balloon. 
     
     
         25 . The medical device of  claim 23 , wherein the medical device is a surgical mesh. 
     
     
         26 . A method of forming a composition comprising an antimicrobial compound and a cross-linked fatty acid, comprising:
 curing a starting material comprising a fatty acid and a glyceride according to a first curing condition to form a second material; and associating the second material with an antimicrobial compound that is dissolved in a solution by immersing the second material in the antimicrobial compound solution or aerosolizing the antimicrobial compound solution onto the second material;   such that the composition is formed.   
     
     
         27 . The method of  claim 26 , wherein fatty acid starting material is fish oil. 
     
     
         28 . The method of  claim 26 , wherein the antimicrobial is a silver compound, and the silver compound is selected from the group consisting of a silver nanoparticle, silver nitrate, silver chloride, silver fluoride, silver bromide, silver oxide, silver sulfate, silver carbonate, silver cyanide, silver tetrafluoroborate, silver sulfide, silver acetate, silver lactate, silver benzoate, silver cyclohexanebutyrate, silver diethyldithiocarbamate, silver trifluoromethanesulfonate and mixtures thereof. 
     
     
         29 . The method of  claim 26 , wherein before curing the fatty acid starting material, the starting material is associated with a medical device. 
     
     
         30 . The method of  claim 29 , wherein the composition is associated with a medical device, and the medical device is a bandage, a stent, a graft, a shunt, a catheter, or a balloon. 
     
     
         31 . The method of  claim 29 , wherein the medical device is a surgical mesh. 
     
     
         32 . A method of forming a composition comprising an antimicrobial compound and a cross-linked fatty acid, comprising:
 curing a starting material comprising a fatty acid and a glyceride according to a first curing condition to form a second material;   associating the second material with a fatty acid-containing oil and an antimicrobial compound that is dissolved in a solution to form a third material; and   curing the third material according to a second curing condition;   such that the composition is formed.   
     
     
         33 . The method of  claim 32 , wherein a portion of the fatty acids of the second material are cross-linked. 
     
     
         34 . The method of  claim 32 , wherein fatty acid starting material and the fatty acid-containing oil are fish oil. 
     
     
         35 . The method of  claim 32 , wherein the antimicrobial compound is a silver compound, and the silver compound is selected from the group consisting of a silver nanoparticle, silver nitrate, silver chloride, silver fluoride, silver bromide, silver oxide, silver sulfate, silver carbonate, silver cyanide, silver tetrafluoroborate, silver sulfide, silver acetate, silver lactate, silver benzoate, silver cyclohexanebutyrate, silver diethyldithiocarbamate, silver trifluoromethanesulfonate and mixtures thereof. 
     
     
         36 . The method of  claim 32 , wherein before curing the third material, the third material is associated with a medical device. 
     
     
         37 . The method of  claim 32 , wherein the medical device is a bandage, a stent, a catheter, a surgical mesh, or a balloon. 
     
     
         38 . A method of forming a composition comprising an antimicrobial compound and a cross-linked fatty acid, comprising:
 associating a fatty acid- and glyceride-containing oil with an antimicrobial compound to form a second material; and   curing the second material according to a first curing condition;   such that the silver-containing composition is formed.   
     
     
         39 . The method of  claim 38 , wherein the fatty acid-containing oil is a fish oil. 
     
     
         40 . The method of  claim 38 , wherein the fatty acid- and glyceride-containing oil is a mixture of fish oil, and pre-cured fish oil. 
     
     
         41 . The method of  claim 38 , wherein the antimicrobial compound is a silver compound, and the silver compound is ionic silver in aqueous solution. 
     
     
         42 . The method of  claim 38 , wherein the antimicrobial compound is a silver compound, and the silver compound is in the form of a silver nanoparticle. 
     
     
         43 . The method of  claim 38 , wherein an additional antimicrobial compound is dissolved in solvent to form a third composition, and the third composition is coated onto the outer surface of the silver-containing composition. 
     
     
         44 . The method of  claim 43 , wherein the third composition is coated onto the outer surface of the antimicrobial-containing composition by spraying the third composition or submerging the antimicrobial-containing composition in the third composition. 
     
     
         45 . The method of  claim 43 , wherein the additional compound is an antimicrobial compound, and the antimicrobial compound is selected from the group consisting of diamidines, iodine and iodophors, peroxygens, phenols, bisphenols, halophenols, biguanides and silver compounds. 
     
     
         46 . The method of  claim 43 , wherein the additional compound is an antimicrobial compound, and the antimicrobial compound is selected from the group consisting of elemental silver, silver nanoparticle, silver nitrate, silver chloride, silver fluoride, silver bromide, silver oxide, silver sulfate, silver carbonate, silver cyanide, silver tetrafluoroborate, silver sulfide, silver acetate, silver lactate, silver benzoate, silver cyclohexanebutyrate, silver diethyldithiocarbamate, silver trifluoromethanesulfonate, triclosan, chlorhexidine, triclocarban, hexachlorophene, dibromopropamidine, chloroxylenol, phenol and cresol. 
     
     
         47 . The method of  claim 43 , wherein the additional compound is an antibiotic compound, and wherein the antibiotic compound is selected from the group consisting of gentamicin sulfate, penicillin g, ephalothin, ampicillin, amoxicillin, augmentin, aztreonam, imipenem, streptomycin, gentamicin, vancomycin, clindamycin, erythromycin, azithromycin, polymyxin, bacitracin, amphotericin, nystatin, rifampicin, tetracycline, doxycycline, chloramphenicol, nalidixic acid, ciprofloxacin, sulfanilamide, gantrisin, trimethoprim, isoniazid, para-aminosalicylic acid, and minocycline. 
     
     
         48 . The method of  claim 38 , wherein before curing the second material, the second material is associated with a medical device. 
     
     
         49 . The method of  claim 48 , wherein the medical device is a bandage, a stent, a catheter, a surgical mesh, or a balloon. 
     
     
         50 . The composition comprising an antimicrobial compound, a fatty acid, and a glyceride, wherein the fatty acid and glyceride components are cross-linked, formed from the methods of  claims 26 ,  32  or  38 . 
     
     
         51 . The composition of  claim 50 , wherein when the composition is associated with a tissue of a subject, the antimicrobial compound is released from the cross-linked fatty acid at a controlled release rate. 
     
     
         52 . A method of treating or preventing tissue adhesion in a subject in need thereof, comprising administering the subject the composition of  claim 1 . 
     
     
         53 . A method of treating or preventing a bacterial infection in a subject in need thereof, comprising administering the subject the composition of  claim 1 . 
     
     
         54 . An emulsion comprising an antimicrobial compound, a fatty acid, and a glyceride, wherein the fatty acid and glyceride components are cross-linked. 
     
     
         55 . A composition comprising a silver compound, a fatty acid, and a glyceride, wherein the fatty acid and glyceride components are cross-linked.