Antimicrobial Compositions and Methods for Locking Catheters

• US 20070202177A1
• Filed: 02/27/2007
• Published: 08/30/2007
• Est. Priority Date: 02/28/2006
• Status: Abandoned Application

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Hoang, Minh Quang
• Application Number:
  US11/679,230
• Publication Number:
  US 20070202177A1
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 25/10 Macromolecular compounds
• CPC Class Codes: A01N 25/30 characterised by the surfactants
• CPC Class Codes: A01N 31/02 Acyclic compounds
• CPC Class Codes: A01N 47/44 Guanidine; Derivatives thereof
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/205 Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/612 having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid fosfosal A61K31/661
• CPC Class Codes: A61K 33/38 Silver; Compounds thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61L 2/0088 Liquid substances
• CPC Class Codes: A61L 2/186 : Peroxide solutions
• CPC Class Codes: A61L 2202/24 : Medical instruments, e.g. endoscopes, catheters, sharps
• CPC Class Codes: A61L 2300/206 : Biguanides, e.g. chlorohexidine
• CPC Class Codes: A61L 2300/21 : Acids
• CPC Class Codes: A61L 2300/214 : Amino acids
• CPC Class Codes: A61L 2300/216 : with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
• CPC Class Codes: A61L 2300/404 : Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/42 : Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 29/08 : Materials for coatings
• CPC Class Codes: A61L 29/085 : Macromolecular materials
• CPC Class Codes: A61L 29/106 : Inorganic materials other than carbon
• CPC Class Codes: A61L 29/14 : Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61L 29/16 : Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 2025/0056 : provided with an antibacterial agent, e.g. by coating, residing in the polymer matrix or releasing an agent out of a reservoir
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides

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.

Claims

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(C₂H₄O)_a(C₃H₆O)_b(C₂H₄O)_aOH

where a is at least 12 and b is an integer such that the hydrophilic portion represented by (C₂H₄O) 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 C₁-C₆ lower alcohol.

11. The antimicrobial composition of claim 10, wherein the C₁-C₆ 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 C₁-C₆ lower alcohol.

22. The method of claim 21, wherein the C₁-C₆ 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(C₂HO)_a(C₃H₆O)_b(C₂H₄O)_aOH

where a is at least 12 and b is an integer such that the hydrophilic portion represented by (C₂H₄O) 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 C₁-C₆ lower alcohol.

32. The antimicrobial composition of claim 31, wherein the C₁-C₆ 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 C₁-C₆ lower alcohol.

43. The method of claim 42, wherein the C₁-C₆ 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.