Biofilm Penetrating Compositions and Methods

Abstract

Compositions are provided that have at least two of three active ingredients. The active ingredients maybe a salt having a cation N α C8-C16 alkanoyl-L di-basic amino acid —C1-C4 alkyl ester, a glycerol monoester of a fatty acid and a sugar ester of a fatty acid. The compositions are useful in methods of killing or inhibiting planktonic bacteria or fungi and bacteria or fungi embedded in a biofilm and prevention of biofilm formation on surfaces. The composition may further comprise a hydrogel and a benefit agent such as an antibiotic that can be solubilized by the hydrogel and supplied to the biofilm matrix by the active ingredients of the composition. Devices such as chronic wound coverings coated with the composition are also provided. Methods of preserving products with the composition are also provided.

1 . A method of killing or inhibiting planktonic bacteria or fungi and bacteria or fungi embedded in a biofilm comprised of at least a matrix and bacteria or fungi, the method comprising:
 applying to a surface of the biofilm a composition having an active ingredient comprising at least two or more of:   a) a salt having a cation N α C8-C16 alkanoyl-L di-basic amino acid —C1-C4 alkyl ester and an anion selected from the group consisting: of halide, nitrite, nitrate, linolenate, laurate, oleoate, phenolate, polyphenolate, carboxylate, hydroxycarboxylate, hyaluronate, antibiotic anion, resveratrol, and an amino acid, the salt being present in an amount from about 0.025 wt % to about 10 wt %;   b) a glycerol monoester of a fatty acid being present in an amount from about 0.05 wt % to about 20 wt %; and   c) a sugar ester of a fatty acid being present in an amount from about 0.075 wt % to about 30 wt %; and   optionally comprising one or more of:   d) a solvent being present in an amount from about 20 wt % to about 99.9 wt %; or   e) a thickener or carrier or gelling agent being present in an amount from about 20 wt % to about 75 wt %; or   f) a sacrificial agent being present in an amount from about 0.05 wt % to about 5 wt %; or   g) a hydrogel having a three-dimensional hydrophilic polymer network,   
       the active ingredient of the composition killing or inhibiting planktonic bacteria or fungi and penetrating the biofilm matrix and killing or inhibiting biofilm bacteria or fungi. 
     
     
         2 . The method of  claim 1 , further characterized by:
 the a) N α C8-C16 alkanoyl-L di-basic amino acid —C1-C4 alkyl ester being N α -lauroyl-L-arginine-ethyl ester; or   the b) glycerol monoester a fatty acid being monolaurin; or   the c) sugar ester of a fatty acid being sucrose laurate; or   the d) solvent being at least one of: water, 1,2-propylene glycol or 1,3-propylene glycol, 1,2-pentanediol, sorbitol, glycerol, xylitol, polyethylene glycol, polypropylene glycol, butylene glycol, pentylene glycol, hexylene glycol; or   the e) thickener or carrier or gelling agent being at least one of: a polymer, a hydrocolloid, an acrylate, an acrylamide, a carboxylated cellulose, lecithin, poly(lactic-co-glycolic acid) (PLGA), polymeric ethers, polymeric aliphatic alcohols, polyalkoxylated alcohols, naturally occurring high molecular weight substances such as sodium alginate, gums, xanthan gum, gum tragacanth, starch, collagen aluminum silicate, quince seed extract, semi-synthetic high molecular substances such as methyl cellulose, carboxymethyl cellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethyl cellulose (HPMC), soluble starch and cationized cellulose, synthetic high molecular substances such as carboxyvinyl polymer and polyvinyl alcohol, arabic gum, carbomer, polyethylene oxide, poloxamer; or   the f) sacrificial agent being at least one of: trimethyl citrate, trimethyl citrate, or zinc glycinate; or   the g) hydrogel being at least one of: polyvinyl alcohol, polyvinylpyrrolidone, polyethyleneimine, polyacrylic acid, polyhydroxyethyl-methacrylate, polyvinyl alcohol-glycine co-polymer, or polyvinyl alcohol-lysine co-polymer.   
     
     
         3 . The method of  claim 1 , the biofilm further characterized as covering a wound, or in medical tubing, or on medical instruments, or in devices, or in wound drainage tubes, or in human or animal food processing or packaging equipment, or on food conveyor belts, or on pet chew toys, or in animal water bowls, or on floating toys, or in piping or in or on contact lens. 
     
     
         4 . The method of  claim 1  further comprising delivering an antibiotic, an antimicrobial, or a benefit agent to planktonic bacteria or fungi or biofilm bacteria or fungi, the method comprising:
 adding to the composition comprising at least two of a), b) or c) and optionally d)-g):
 h) a benefit agent comprising an antibiotic, an antimicrobial, or a drug; and 
 
 applying the composition comprising a)-h) to a biofilm, 
 the composition of a) through g) acting as a delivery means for the benefit agent of h) to both planktonic bacteria or fungi and to biofilm bacteria or fungi by penetrating the biofilm matrix to deliver the benefit agent. 
 
     
     
         5 . The method of  claim 4 , the benefit agent being water soluble or water insoluble and the benefit agent being solubilized in the g) hydrogel and added in combination with the composition comprising at least two of a), b) or c) and optionally d)-f). 
     
     
         6 . A method of preserving a surface or product by preventing or inhibiting biofilm formation by bacteria or fungi, the method comprising:
 applying to a surface or adding to a product a composition having an active ingredient comprising at least two or more of:   a) a salt having a cation N α C8-C16 alkanoyl-L di-basic amino acid —C1-C4 alkyl ester and an anion selected from the group consisting of: halide, nitrite, nitrate, linolenate, laurate, oleoate, phenolate, polyphenolate, carboxylate, hydroxycarboxylate, hyaluronate, antibiotic anion, resveratrol, and an amino acid, the salt being present in an amount from about 0.025 wt % to about 10 wt %;   b) a glycerol monoester of a fatty acid being present in an amount from about 0.05 wt % to about 10 wt %; and   c) a sugar ester of a fatty acid being present in an amount from about 0.075 wt % to about 20 wt %; and   optionally comprising one or more of:   d) a solvent being present in an amount from about 20 wt % to about 99.9 wt %; or   e) a thickener or carrier or gelling agent being present in an amount from about 20 wt % to about 75 wt %; or   f) a sacrificial agent being present in an amount from about 0.05 wt % to about 5 wt %; or   g) a hydrogel having a three-dimensional hydrophilic polymer network;   the active ingredient of the composition preventing or inhibiting bacteria or fungi from forming a biofilm on a surface or in a product.   
     
     
         7 . The method of  claim 6 , further characterized by
 the a) N α C8-C16 alkanoyl-L di-basic amino acid —C1-C4 alkyl ester being N α -lauroyl-L-arginine-ethyl ester; or   the b) glycerol monoester a fatty acid being monolaurin; or   the c) sugar ester of a fatty acid being sucrose laurate; or   the d) solvent being at least one of: water, ethanol, 1,2-propylene glycol or 1,3-propylene glycol, 1,2-pentanediol, sorbitol, glycerol, xylitol, polyethylene glycol, polypropylene glycol, butylene glycol, pentylene glycol, hexylene glycol; or   the e) thickener or carrier or gelling agent being at least one of: a polymer, a hydrocolloid, an acrylate, an acrylamide, a carboxylated cellulose, lecithin, poly(lactic-co-glycolic acid) (PLGA), polymeric ethers, polymeric aliphatic alcohols, polyalkoxylated alcohols, naturally occurring high molecular weight substances such as sodium alginate, gums, xanthan gum, gum tragacanth, starch, collagen aluminum silicate, quince seed extract, semi-synthetic high molecular substances such as methyl cellulose, carboxymethyl cellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethyl cellulose (HPMC), soluble starch and cationized cellulose, synthetic high molecular substances such as carboxyvinyl polymer and polyvinyl alcohol, arabic gum, carbomer, polyethylene oxide, poloxamer; or   the f) sacrificial agent being at least one of: triethyl citrate, trimethyl citrate, or zinc glycinate; or   the g) hydrogel being at least one of: polyvinyl alcohol, polyvinylpyrrolidone, polyethyleneimine, polyacrylic acid, polyhydroxyethyl-methacrylate, polyvinyl alcohol-glycine co-polymer, or polyvinyl alcohol-lysine co-polymer.   
     
     
         8 . The method of  claim 6 , the surface being selected from the group consisting of: microcapsules, wound dressings, implants, wound closures, staples, meshes, controlled drug delivery systems, wound coverings, fillers, sutures, tissue adhesives, tissue sealants, absorbable and non-absorbable hemostats, catheters, wound drainage tubes, arterial grafts, soft tissue patches, gloves, shunts, stents, guide wires and prosthetic devices, contact lens, medical devices, food processing equipment, food conveyor belts, food packaging equipment, pet or animal food, pet chew toys, pet or animal water bowls, and floating toys. 
     
     
         9 . The method of  claim 6 , the product being selected from the group consisting of: cosmetics and personal care items. 
     
     
         10 . A composition for penetrating a biofilm matrix and killing both planktonic and biofilm bacteria or fungi, the composition having an active ingredient comprising at least two or more of:
 a) a salt having a cation N α C8-C16 alkanoyl-L di-basic amino acid —C1-C4 alkyl ester and an anion selected from the group consisting of: halide, nitrite, nitrate, linolenate, laurate, oleoate, phenolate, polyphenolate, carboxylate, hydroxycarboxylate, hyaluronate, antibiotic anion, resveratrol, and an amino acid, the salt being present in an amount from about 0.025 wt % to about 10 wt %;   b) a glycerol monoester of a fatty acid being present in an amount from about 0.05 wt % to about 10 wt %; and   c) a sugar ester of a fatty acid being present in an amount from about 0.075 wt % to about 20 wt %; and   optionally comprising one or more of:   d) a solvent being present in an amount from about 20 wt % to about 99.9 wt %; or   e) a thickener or carrier or gelling agent being present in an amount from about 20 wt % to about 75 wt %; or   f) a sacrificial agent being present in an amount from about 0.05 wt % to about 5 wt %; or   g) a hydrogel having a three-dimensional hydrophilic polymer network.   
     
     
         11 . The composition of  claim 9 , further characterized by:
 the a) N α C8-C16 alkanoyl-L di-basic amino acid —C1-C4 alkyl ester being N α -lauroyl-L-arginine-ethyl ester; or   the b) glycerol monoester a fatty acid being monolaurin; or   the c) sugar ester of a fatty acid being sucrose laurate; or   the d) solvent being at least one of: water, 1,2-propylene glycol or 1,3-propylene glycol, 1,2-pentanediol, sorbitol, glycerol, xylitol, polyethylene glycol, polypropylene glycol, butylene glycol, pentylene glycol, hexylene glycol; or   the e) thickener or carrier or gelling agent being at least one of: a polymer, a hydrocolloid, an acrylate, an acrylamide, a carboxylated cellulose, lecithin, poly(lactic-co-glycolic acid) (PLGA), polymeric ethers, polymeric aliphatic alcohols, polyalkoxylated alcohols, naturally occurring high molecular weight substances such as sodium alginate, gums, xanthan gum, gum tragacanth, starch, collagen aluminum silicate, quince seed extract, semi-synthetic high molecular substances such as methyl cellulose, carboxymethyl cellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethyl cellulose (HPMC), soluble starch and cationized cellulose, synthetic high molecular substances such as carboxyvinyl polymer and polyvinyl alcohol, arabic gum, carbomer, polyethylene oxide, poloxamer; or   the f) sacrificial agent being at least one of: triethyl citrate, trimethyl citrate, or zinc glycinate; or   the g) hydrogel being at least one of: polyvinyl alcohol, polyvinylpyrrolidone, polyethyleneimine, polyacrylic acid, polyhydroxyethyl-methacrylate, polyvinyl alcohol-glycine co-polymer, or polyvinyl alcohol-lysine co-polymer.   
     
     
         12 . The composition of  claim 10  further comprising h) at least one bioactive agent. 
     
     
         13 . A treated device or treated product comprising a device or product and the composition of  claim 10 , the treated device made by a process comprising impregnating, dipping, coating, brushing or soaking the device with the composition or the treated product made by a process of mixing the composition with the product. 
     
     
         14 . The device of  claim 10 , the device being selected from the group consisting of: microcapsules, wound dressings, surgical implants, wound closures, staples, meshes, controlled drug delivery systems, wound coverings, medical fillers, sutures, tissue adhesives, tissue sealants, absorbable and non-absorbable hemostats, catheters, wound drainage tubes, arterial grafts, soft tissue patches, gloves, shunts, stents, surgical guide wires, prosthetic devices, contact lens, endoscopes, dentures, medical devices, food processing equipment, food conveyor belts, food packaging equipment, pet or animal food, pet chew toys, pet or animal water bowls, and floating toys. 
     
     
         15 . The device of  claim 14  being a wound covering for chronic wounds that does not adhere to the wound surface, is held stable at the wound site, and has water absorbing properties, the wound covering further comprising:
 an outer flexible, water-resistant protective covering that does not contact the surface of the chronic wound; 
 means for securing dressing to a wound site; and 
 a surface that is in contact with the chronic wound comprising synthetic polymers, natural polymers or a combination thereof that absorb water and release the composition to the surface of the chronic wound.