Antimicrobial Compositions and Methods for Locking Catheters

Abstract

Antimicrobial compositions for use in locking catheters and other devices are provided. In some embodiments, the composition includes at least one alcohol, at least one biocidal agent which is not an alcohol, and one or more poloxamers; in other embodiments, the composition comprises at least one poloxamer and at least one alcohol. The composition can provide long-lasting antimicrobial activity. Methods of using the composition are also provided.

1 . An antimicrobial composition comprising:
 at least one poloxamer;   at least 10 weight percent of at least one alcohol on a basis of total weight of the antimicrobial composition; and   at least one biocidal agent which is not an alcohol.   
     
     
         2 . The antimicrobial composition of  claim 1 , wherein the poloxamer is represented by the formula
   HO(C 2 H 4 O) a (C 3 H 6 O) b (C 2 H 4 O) a OH   
       where a is at least 12 and b is an integer such that the hydrophilic portion represented by (C 2 H 4 O) constitutes about 50 to about 90% by weight of the entire polymer. 
     
     
         3 . The antimicrobial composition of  claim 2 , wherein the average molecular weight of the poloxamer is between about 2,000 to about 18,000 daltons. 
     
     
         4 . The antimicrobial composition of  claim 3 , wherein the at least one poloxamer is selected from the group consisting of poloxamer 188, poloxamer 237 and poloxamer 407. 
     
     
         5 . The antimicrobial composition of  claim 1 , wherein the poloxamer is present in an amount of about 0.01 wt. % to about 5 wt. %, based on the weight of the antimicrobial composition. 
     
     
         6 . The antimicrobial composition of  claim 1 , wherein the biocidal agent is selected from the group consisting of β-propiolactone, α-terpineol, 1-(3-choroallyl)-3,5,7-triazo-1-azoniaadamantane chloride, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1-napthyl salicylate, 2-(methoxymethyl)-5-nitrofuran, 2,4,4′-trichloro-2′-hydroxydiphenol, 2,4,6-tribromo-m-cresol, 2-bromo-2-nitropropan-1,3-diol, 2-napthyl salicylate, 3,4,4′-trichlorocarbanilide, 3,4′,5-tribromosalicylanilide, 3′,4′,5-trichlorosalicylanilide, 3-amino-4-hydroxybutyric acid, 3-trifluoromethyl-4,4′-dichlorocarbanilide, 5-nitro-2-furaldehyde semicarbazone, 8-hydroxyquinoline sulfate, 8-hydroxyquinoline, acetic acid, acetomeroctol, acridine, acriflavine, alexidine, aluminum acetate solution, aluminum subacetate solution, aluminum sulfate, ambazone, amide, amidine, aminacrine hydrochloride, aminoquinuride, ammoniated, mercuric sodium p-phenolsulfonate, amylmetacresol, benzalkonium chloride, benzethonium chloride, benzoic acid, benzoxiquine, bisphenols, bithionol, boric acid, bornyl chloride, bromochlorobisphenol, broxyquinoline, calcium hypochlorite, calcium iodate, carbamates, carbanilide, carbanilide, carvacol, cetrimide, cetylpyridinium chloride, chelate and imidazoline biocides, chloramine, chlorasine, chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, chlorhexidine, chlorinated phenol, chlorine-releasing biocides, chloroazodin, chlorocresol, chlorophene, chlorothymol, chloroxine, chloroxylenol, chlorphenoctium amsonate, chlorquinaldol, cloflucarban, cloxyquin, cresol, crystal violet, cupric sulfate, dehydroacetic acid, dequalinium acetate, dequalinium chloride, dequalinium, dibromopropamidine, dibromsalan, dichloramine, dichlorobisphenol, dichlorodimethylhydantoin, dichloroglycoluril, dichloroisocyanurate, dichloroxylenol, domiphen bromide, EDTA, esters of p-hydroxybenzoic acid, ethylhydrocupreine, euprocin, fenticlor, flurosalan, formaldehyde, furaltadone, furazolidone, glutaraldehyde, griseofulvin, guanide, halane, halazone, halogenated dialkyl-hydantoin, halogenated diphenylalkanes, halquinol, hexachlorophene, hexamethylenetetramine, hydragaphen, hydrastine, hydrogen peroxide, hydroxyquinoline, ichthammol, iodic acid, iodine, iodochlorhydroxyquin, lactone, laurolinium acetate, laurolinium, lioquinol, magenta, m-cresyl acetate, mendalamine, meralein sodium, merbromin, mercuric succinimide, mercuric sulfide, mercurophen, mercurous acetate, mercurous chloride, mercurous iodide, metabromsalan, methenamine mandelate, methylbenzethonium chloride, myristyl-gamma-picolinium chloride, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, negatol, nidroxyzone, nifuroxime, nifurzide, nitrofurantoin, nitrofurazone, nitrofurfural, nitromersol, noxythiolin, noxytiolin, ornidazole, ortaphonium chloride, oxychlorosene, parachlorometaxylenol, paraformaldehyde polymer,pararosaniline, p-chlorophenol, pentamidine, peracetic acid, phenol, picloxydine, polynoxylen, polyoxymethylene diacetate, polyoxymethylene diester, potassium hypochlorite, povidone-iodine, p-phenylphenol, proflavin hemisulfate, propamidine isethionate, propiolactone, propionic acid, pyridinium biocides, quaternary ammonium biocides, quinaldinium, quinoline, quinone, red, rosaniline, salicylamide, salicylanilide, scarlet red, silver nitrate, silver sulfadiazine, sodium hypochlorite, sodium iodate, sodium oxychlorosene, sorbic acid, succinchlorimide, sulfa, sulfurous acid, symclosene, taurolidine, taurultam, tetrachlorosalicylanilide, thimerfonate sodium, thimerosal, thiosemicarbazone, thymol iodide, thymol, tribromsalan, trichlorocarbanilide, trichloroisocyanuric acid, trichloromelamine, triclobisonium chloride, triclocarban, triclocarbon, triclosan and troclosene potassium, trinitrophenol, triphenylmethane, and vanillic acid. 
     
     
         7 . The antimicrobial composition of  claim 1 , wherein the at least one biocidal agent is selected from the group consisting of benzalkonium chloride, benzethonium chloride, chlorhexidine diacetate, chlorhexidine gluconate, chloroxylenol, dequalinium chloride, triclosan, and combinations thereof. 
     
     
         8 . The antimicrobial composition of  claim 7 , wherein the at least one biocidal agent is chlorhexidine gluconate. 
     
     
         9 . The antimicrobial composition of  claim 1 , wherein the at least one biocidal agent is present in an amount of about 0.01 wt. % to about 10 wt. %, based on the weight of the antimicrobial composition. 
     
     
         10 . The antimicrobial composition of  claim 1 , wherein the alcohol is a C 1 -C 6  lower alcohol. 
     
     
         11 . The antimicrobial composition of  claim 10 , wherein the C 1 -C 6  lower alcohol is a mixture of isopropyl alcohol and ethanol. 
     
     
         12 . The antimicrobial composition of  claim 11 , wherein the at least one lower alcohol is a mixture of isopropyl alcohol and ethanol and is present in an amount of about 50 to about 95% by weight of the antimicrobial composition. 
     
     
         13 . The antimicrobial composition of  claim 1 , further comprising an additive selected from the group consisting of an anticoagulant, saline, water and combinations thereof. 
     
     
         14 . The antimicrobial composition of  claim 13 , wherein the anticoagulant is selected from the group consisting of acetylsalicylic acid, anti-thrombin III, citric acid disodium salt, citric acid monopotassium salt, citric acid monosodium salt, citric acid tripotassium salt, citric acid trisodium salt, citric acid, coumadin, coumarin, di-ammonium hydrogen citrate, di-ammonium tartrate, EDTA diammonium salt, EDTA dipotassium salt, EDTA disodium salt, EDTA tetrasodium salt, EDTA tripotassium salt, EDTA trisodium salt, ethylene glycol-O,O′-bis(2-aminoethyl)-N,N,N′,N′-tetraacetic acid, ethylenebis(oxyethylenenitrilo)tetraacetic acid, ethylenediaminetetraacetic acid (EDTA), heparin, hirudin, hirulog,ibuprofen, indomethacin, L-tartaric acid dipotassium salt, L-tartaric acid disodium salt, L-tartaric acid monosodium salt, N-(2-hydroxyethyl)ethylenediamine-N,N′,N′-triacetic acid trisodium salt, nicoumalone, nitrilotriacetic acid, phenprocoumon, potassium hydrogen D-tartrate, potassium sodium tartrate, prostaglandins, protamine sulfate, protein C/protein S, streptokinase, sulfmpyrazone, tissue plasminogen activator (TPA), urokinase and warfarin. 
     
     
         15 . The antimicrobial composition of  claim 13 , wherein the anticoagulant is ethylenediaminetetraacetic acid. 
     
     
         16 . A catheter containing the antimicrobial composition of  claim 1 . 
     
     
         17 . A catheter having at least one interior surface coated with the antimicrobial composition of  claim 1 . 
     
     
         18 . A catheter coating comprising an antimicrobial composition comprising:
 at least one poloxamer;   at least 10 weight percent of at least one alcohol on a basis of total weight of the antimicrobial composition; and   at least one biocidal agent which is not an alcohol.   
     
     
         19 . A method for providing disinfection of an implanted catheter, comprising introducing an antimicrobial composition into a lumen of the catheter, the antimicrobial composition comprising at least one biocidal agent that is not an alcohol, at least 10 weight percent of at least one alcohol on a basis of total weight of the antimicrobial composition, and at least one poloxamer. 
     
     
         20 . The method of  claim 19 , wherein the at least one biocidal agent is present in an amount of about 0.01 wt. % to about 10 wt. %, and the at least one poloxamer is present in an amount of about 0.01 wt. % to 5 wt. %, based on the total weight of the antimicrobial composition. 
     
     
         21 . The method of  claim 19 , wherein the alcohol is a C 1 -C 6  lower alcohol. 
     
     
         22 . The method of  claim 21 , wherein the C 1 -C 6  lower alcohol is a mixture of isopropyl alcohol and ethanol. 
     
     
         23 . The method of  claim 21 , wherein the at least one lower alcohol is a combination of isopropyl alcohol and ethanol to a total in the range of 50 to 95 wt %, based on the weight of the antimicrobial composition. 
     
     
         24 . The method of  claim 19 , wherein the antimicrobial composition is maintained in the lumen of the catheter for a period of time ranging from about 48 hours to about one week. 
     
     
         25 . A method for providing disinfection of an implanted catheter, comprising coating at least a portion of an interior surface of a catheter with an antimicrobial composition comprising at least one biocidal agent that is not an alcohol, at least 10 weight percent of at least one alcohol on a basis of total weight of the antimicrobial composition, and at least one poloxamer. 
     
     
         26 . An antimicrobial composition comprising:
 at least one poloxamer; and   at least 10% by weight of at least one alcohol on a basis of total weight of the antimicrobial composition.   
     
     
         27 . The antimicrobial composition of  claim 26 , wherein the poloxamer is represented by the formula
   HO(C 2 HO) a (C 3 H 6 O) b (C 2 H 4 O) a OH   
       where a is at least 12 and b is an integer such that the hydrophilic portion represented by (C 2 H 4 O) constitutes about 50 to about 90 % by weight of the entire polymer. 
     
     
         28 . The antimicrobial composition of  claim 26 , wherein the average molecular weight of the poloxamer is between about 2,000 to about 18,000 daltons. 
     
     
         29 . The antimicrobial composition of  claim 26 , wherein the at least one poloxamer is selected from the group consisting of poloxamer 188, poloxamer 237 and poloxamer 407. 
     
     
         30 . The antimicrobial composition of  claim 26 , wherein the poloxamer is present in an amount of about 0.01 wt. % to about 5 wt. %, based on the weight of the antimicrobial composition. 
     
     
         31 . The antimicrobial composition of  claim 26 , wherein the alcohol is a C 1 -C 6  lower alcohol. 
     
     
         32 . The antimicrobial composition of  claim 31 , wherein the C 1 -C 6  lower alcohol is a mixture of isopropyl alcohol and ethanol. 
     
     
         33 . The antimicrobial composition of  claim 26 , wherein the at least one lower alcohol is a mixture of isopropyl alcohol and ethanol and is present in an amount of about 50 to about 95% by weight of the antimicrobial composition. 
     
     
         34 . The antimicrobial composition of  claim 26 , further comprising an additive selected from the group consisting of an anticoagulant, saline, water and combinations thereof. 
     
     
         35 . The antimicrobial composition of  claim 34 , wherein the anticoagulant is selected from the group consisting of acetylsalicylic acid, anti-thrombin m, citric acid disodium salt, citric acid monopotassium salt, citric acid monosodium salt, citric acid tripotassium salt, citric acid trisodium salt, citric acid, coumadin, coumarin, di-ammonium hydrogen citrate, di-ammonium tartrate, EDTA diammonium salt, EDTA dipotassium salt, EDTA disodium salt, EDTA tetrasodium salt, EDTA tripotassium salt, EDTA trisodium salt, ethylene glycol-O,O′-bis(2-aminoethyl)-N,N,N′,N′-tetraacetic acid, ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), ethylenediaminetetraacetic acid (EDTA), heparin, hirudin, hirulog,ibuprofen, indomethacin, L-tartaric acid dipotassium salt, L-tartaric acid disodium salt, L-tartaric acid monosodium salt, N-(2-hydroxyethyl)ethylenediamine-N,N′,N′-triacetic acid trisodium salt, nicoumalone, nitrilotriacetic acid, phenprocoumon, potassium hydrogen D-tartrate, potassium sodium tartrate, prostaglandins, protamine sulfate, protein C/protein S, streptokinase, sulfinpyrazone, tissue plasminogen activator (TPA), urokinase and warfarin. 
     
     
         36 . The antimicrobial composition of  claim 34 , wherein the anticoagulant is ethylenediaminetetraacetic acid. 
     
     
         37 . A catheter containing the antimicrobial composition of  claim 26 . 
     
     
         38 . A catheter having at least one interior surface coated with the antimicrobial composition of  claim 26 . 
     
     
         39 . A catheter coating comprising an antimicrobial composition comprising:
 at least one poloxamer; and   at least 10% by weight of at least one alcohol on a basis of total weight of the antimicrobial composition.   
     
     
         40 . A method for providing long term disinfection of an implanted catheter, comprising introducing an antimicrobial composition into a lumen of the catheter, the antimicrobial composition comprising at least 10% by weight of at least one alcohol on a basis of total weight of the antimicrobial composition, and at least one poloxamer. 
     
     
         41 . The method of  claim 40 , wherein the at least one poloxamer is present in an amount of about 0.01 wt. % to 5 wt. %, based on the total weight of the antimicrobial composition. 
     
     
         42 . The method of  claim 40 , wherein the alcohol is a C 1 -C 6  lower alcohol. 
     
     
         43 . The method of  claim 42 , wherein the C 1 -C 6  lower alcohol is a mixture of isopropyl alcohol and ethanol. 
     
     
         44 . The method of  claim 43 , wherein the at least one lower alcohol is a combination of isopropyl alcohol and ethanol to a total in the range of 50 to 95 wt %, based on the weight of the antimicrobial composition. 
     
     
         45 . The method of  claim 40 , wherein the antimicrobial composition is maintained in the lumen of the catheter for a period of time ranging from about 48 hours to about one week. 
     
     
         46 . A method for providing disinfection of an implanted catheter, comprising coating at least a portion of an interior surface of a catheter with an antimicrobial composition comprising at least 10% by weight of at least one alcohol on a basis of total weight of the antimicrobial composition, and at least one poloxamer.