Antimicrobial Compositions Containing Free Fatty Acids

Abstract

The invention concerns antimicrobial compositions comprising free fatty acids emulsified with membrane lipids or hydrolysed derivatives thereof, and pharmaceutical formulations comprising same. The compositions can be used in the treatment or prophylaxis of microbial infections. They can also regulate the rate of blood clotting rendering them suitable for incorporation in catheter locking solutions and for use in wound care.

1 .- 31 . (canceled) 
     
     
         32 . An antimicrobial and blood-clotting regulatory composition for use in blood contact applications selected from the group consisting of surgical irrigation, wound care, catheter locking solutions, and the coating of catheters and other medical devices for insertion through the skin or into a bodily orifice or cavity, the composition comprising:
 (a) one or more saturated or unsaturated free fatty acids having from 4 to 22 carbon atoms or a pharmaceutically acceptable salt or ester thereof; and   (b) one or more membrane lipids or a hydrolysed derivative thereof, as emulsifying agent for the free fatty acid(s) or the salt or ester thereof.   
     
     
         33 . The composition of  claim 32 , wherein the free fatty acid is selected from valeric, caproic, caprylic, pelargonic, capric, undecanoic, undecylenic, lauric, myristic, palmitic, stearic, oleic, linoleic and linolenic acids and mixtures thereof, and pharmaceutically acceptable salts and esters thereof. 
     
     
         34 . The composition of  claim 32 , wherein the free fatty acid is selected from one or more of caproic, caprylic, pelargonic, capric, undecylenic and lauric acids, especially caprylic acid. 
     
     
         35 . The composition of  claim 32 , wherein the membrane lipid is selected from one or more of phospholipids, lecithin, glycerophospholipids, sphingolipids, glycosphingolipids, glycoglycerolipids and cholesterols, and hydrolysed derivatives thereof. 
     
     
         36 . The composition of  claim 32 , wherein the membrane lipid is selected from one or more of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, lecithin, ceramide, sphingomyelin, glycolipids, glycosphingolipids, cerebrosides, gangliosides, glycoglycerolipids, mono-galactosyl diglyceride, lanosterol and cholesterol. 
     
     
         37 . The composition of  claim 32 , wherein the membrane lipid is a phosopholipid selected from one or more of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine and lecithin, especially lecithin. 
     
     
         38 . The composition of  claim 32 , wherein the membrane lipid or hydrolysed derivative thereof is delipidised. 
     
     
         39 . The composition of  claim 32 , comprising a free fatty acid selected from one or more of caproic, caprylic, pelargonic, capric, undecylenic and lauric acids, in combination with a membrane lipid selected from one or more phosopholipids, especially caprylic acid in combination with delipidised lecithin. 
     
     
         40 . The composition of  claim 32 , wherein the ratio of component (a) to component (b) is from about 0.25:1 to about 10:1; or from about 0.5:1 to about 10:1, or from about 0.5:1 to about 5.0:1, or from about 1.0:1 to about 2.5:1, or from about 1.25:1 to about 2.5:1, on a weight for weight basis. 
     
     
         41 . The composition of  claim 32 , further comprising one or more pharmaceutically acceptable organic acids or a pharmaceutically acceptable salt or ester thereof and/or one or more pharmaceutically acceptable inorganic acid salts. 
     
     
         42 . The composition of  claim 41 , wherein the organic acid is selected from acetic, pyruvic, propionic, glycolic, oxalic, lactic, glyceric, tartronic, malic, maleic, ascorbic, fumaric, tartaric, malonic, glutaric, propenoic, cis or trans butenoic and citric acids and mixtures thereof, and pharmaceutically acceptable salts and esters thereof. 
     
     
         43 . The composition of  claim 41 , wherein the organic acid is citric or lactic acid or the sodium or potassium salt thereof or wherein the organic acid salt is sodium citrate. 
     
     
         44 . The composition of  claim 32  for use in a catheter locking solution. 
     
     
         45 . The composition of  claim 32  for use as an antimicrobial and blood-clotting regulatory agent in a formulation for coating the surface of a catheter or other medical device for insertion through the skin or into a bodily orifice or cavity. 
     
     
         46 . The composition of  claim 32  for use in a surgical irrigation fluid. 
     
     
         47 . An antimicrobial and blood-clotting regulatory catheter locking solution comprising:
 (a) one or more saturated or unsaturated free fatty acids having from 4 to 22 carbon atoms or a pharmaceutically acceptable salt or ester thereof; and   (b) one or more membrane lipids or a hydrolysed derivative thereof, as emulsifying agent for the free fatty acid(s) or the salt or ester thereof.   
     
     
         48 . The catheter locking solution of  claim 47 , wherein the membrane lipid or hydrolysed derivative thereof is delipidised. 
     
     
         49 . The catheter locking solution of  claim 47 , wherein the free fatty acid is selected from one or more of caproic, caprylic, pelargonic, capric, undecylenic and lauric acids, and the membrane lipid is selected from one or more phosopholipids; or wherein the free fatty acid is caprylic acid and the membrane lipid is delipidised lecithin. 
     
     
         50 . The catheter locking solution of  claim 47 , further comprising a pharmaceutically acceptable viscosity-enhancing agent wherein, preferably, the viscosity-enhancing agent is dextran. 
     
     
         51 . The catheter locking solution of  claim 47 , further comprising one or more pharmaceutically acceptable organic acids or a pharmaceutically acceptable salt or ester thereof, wherein the organic acid is citric acid or lactic acid or the sodium or potassium salt thereof; or wherein the organic acid salt is sodium citrate.