Non-leaching surface-active film compositions for microbial adhesion prevention

• US 20070166344A1
• Filed: 01/18/2006
• Published: 07/19/2007
• Est. Priority Date: 01/18/2006
• Status: Abandoned Application

• Current Assignee: Hydromer, Inc.
• Original Assignee: Hydromer, Inc.
• Inventors: Gruening, Rainer, Qu, Xin, Chen, Paul, Merritt, Karen, Falevich, Vitaly
• Application Number:
  US11/334,049
• Publication Number:
  US 20070166344A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61L 15/46 Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
• CPC Class Codes: A61L 15/48 Surfactants
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/452 Lubricants
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08G 18/10 Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
• CPC Class Codes: C08G 18/2815 Monohydroxy compounds
• CPC Class Codes: C08G 2290/00 Compositions for creating anti-fogging
• CPC Class Codes: C08J 2375/04 Polyurethanes
• CPC Class Codes: C08J 2475/00 Characterised by the use of polyureas or polyurethanes; Derivatives of such polymers
• CPC Class Codes: C08J 7/0427 with only one layer of a composition containing a polymer binder with more layers C08J7/042
• CPC Class Codes: C08J 7/046 Forming abrasion-resistant coatings; Forming surface-hardening coatings
• CPC Class Codes: C08J 7/054 Forming anti-misting or drip-proofing coatings
• CPC Class Codes: C08J 7/056 Forming hydrophilic coatings
• CPC Class Codes: C08L 75/04 Polyurethanes
• CPC Class Codes: C09D 175/04 : Polyurethanes

Abstract

Surface-active, non-leaching antimicrobial film forming compositions and methods for their application to preferably medical device surfaces are provided. The compositions form durable coatings with long-lasting antimicrobial efficacy without formation of a zone of inhibition. Optionally the films can be hydrophilic. Specific long-chain molecules of certain chemical reactivity are covalently bonded into a polymeric matrix. They maintain a long-term anti-microbial efficacy without being leached out into the aqueous environment. The polymeric matrix of the compositions contain functional groups, which covalently bond to an amine, thiol, carboxyl, aldehyde or hydroxyl active group of selected long chain quaternary ammonium compounds. Upon formation of a covalent bonding with the polymeric matrix the long chain compounds become immobilized but still maintain antimicrobial efficacy. They do not leach out over extended period of time into the aqueous environment and maintain an anti-microbial efficacy against microorganisms. The coating is useful to prevent bacterial colonization on a variety of surface including surfaces of medical devices.

Claims

1. A curable antimicrobial film forming composition comprising a polymeric matrix, a carrier solvent and at least one long chain compound comprising a functional group capable of forming a chemical bond with said matrix upon evaporating said carrier solvent and drying or curing of said composition, said functional group selected from the group consisting of an amine, thiol, carboxyl, aldehyde, hydroxyl and combinations thereof;

wherein said at least one long chain compound is non-leaching upon drying or curing said composition, has sufficient length to protrude through and beyond organic debris deposited over time on the surface of said cured composition, and is capable of penetrating cell walls of microbial organisms and preventing microbial colonization over the surface of said cured composition.

2. A curable antimicrobial film forming composition according to claim 1, further comprising a hydrophilic organic monomer, oligomer, prepolymer, polymer or copolymer derived from vinyl alcohol, N-vinylpyrrolidone, N-vinyl lactam, acrylamide, amide, styrenesulfonic acid, combination of vinylbutyral and N-vinylpyrrolidone, hydroxyethyl methacrylate, acrylic acid, vinylmethyl ether, vinylpyridylium halide, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl ethyl cellulose, hydroxypropylmethyl cellulose, cellulose acetate, cellulose nitrate, starch, gelatin, albumin, casein, gum, alginate, hydroxyethyl(meth)acrylate, hydroxypropyl (meth)acrylate, ethylene glycol (meth)acrylates (e.g. triethylene glycol (meth)acrylate) and meth)acrylamide), N-alkyl(meth) acrylamides (e.g. N-methyl (meth)acrylamide and N-hexyl(meth)acrylamide), N,N-dialkyl(meth)acrylamides (e.g. N,N-dimethyl(meth)acrylamide and poly-N,N-dipropyl(meth)acrylamide), N-hydroxyalkyl (meth)acrylamide polymers, such as poly-N-methylol (meth)acrylamide and poly-N-hydroxy ethyl(meth)acrylamide, and N,N-dihydroxyalkyl (meth)acrylamide polymers, such as poly-N,N-dihydroxyethyl(meth)acrylamide, ether polyols, polyethylene oxide, polypropylene oxide, and poly(vinyl ether), alkylvinyl sulfones, alkylvinylsulfone-acrylates or a combination thereof.

3. A curable antimicrobial film forming composition according to claim 2, wherein said polymeric matrix comprises at least one polyurethane prepolymer comprising at least one functional group capable of forming a chemical bond with the functional group of said long chain corn pound, either directly or through a cross-linker, upon drying or curing of said coating composition.

4. A curable antimicrobial film forming composition according to claim 3, wherein said long chain compound is a surfactant of a type selected from the group consisting of an anionic, cationic and non-ionic surfactant.

5. A curable antimicrobial film forming composition according to claim 4, wherein said surfactant is a cationic surfactant.

6. A curable antimicrobial film forming composition according to claim 5, wherein said cationic surfactant is a quaternary ammonium compound.

7. A curable antimicrobial film forming composition according to claim 6, wherein said quaternary ammonium compound is selected from the group consisting of an alkyl hydroxyethyl dimethyl ammonium chloride;

polyquaternium 11;

a quaternized copolymer of vinylpyrrolidone and dimethylaminoethylmethacrylate;

polyquaternium 16;

polyquaternium 44;

a combination of a vinylpyrrolidone and quaternized vinylimidazol;

polyquaternium-55;

a quaternized copolymer of vinylpyrrolidone and dimethylaminoethyl;

N,N-Dimethyl-N-dodecyl-N-(2-hydroxy-3-sulfopropyl)ammonium betaine;

N-alkyl acid amidopropyl-N,N-dimethyl-N-(3-sulfopropyl)-ammonium betaine;

3-chloro-2-hydroxypropyl-alkyl-dimethylammonium chloride with a long chain alkyl group; and

combinations thereof.

8. A curable antimicrobial film forming composition according to claim 3, wherein said film forming composition further comprises a combination of at least two surfactants.

9. A curable antimicrobial film forming composition according to claim 3, wherein said surfactant projects at least about 15 Å

away from the surface of said cured coating.

10. A curable antimicrobial film forming composition according to claim 9, wherein said surfactant projects at least about 30 Å

away from the surface of said cured coating.

11. A curable antimicrobial film forming composition according to claim 10, wherein said surfactant projects at least about 60 Å

away from the surface of said cured coating.

12. A curable antimicrobial film forming composition according to claim 2, wherein said organic debris is selected from the group consisting of dead microbial cells, proteinaceous buildup and a combination thereof.

13. A curable antimicrobial film forming composition according to claim 2, wherein said hydrophilic water-soluble organic monomer, oligomer, prepolymer, polymer or copolymer is present in an amount sufficient to provide said cured composition with a reduction in friction of at least about 70% compared to the uncoated surface when each are wetted with water or an aqueous solution.

14. An antimicrobial film forming composition according to claim 13, wherein said reduction in friction is at least about 80%.

15. An antimicrobial film forming composition according to claim 14, wherein said reduction in friction is at least about 90%.

16. An antimicrobial film forming composition according to claim 15, wherein said reduction in friction is at least about 95%.

17. A medical device for introduction into a human or animal body, comprising an antimicrobial coating on at least one surface of said device, said antimicrobial coating comprising:

a polymeric matrix which comprises a polyurethane component; and

at least one long chain surfactant chemically bonded to said polyurethane component, said surfactant projecting away from the surface of said antimicrobial coating and having sufficient length to protrude through organic debris deposited over time on the surface of said antimicrobial coating as a result of being introduced into a human or animal body, and

wherein said surfactant is non-leaching and is capable of penetrating cell walls of microbial organisms and preventing microbial colonization over the surface of said antimicrobial coating.

18. A medical device according to claim 17, further comprising a hydrophilic component comprising a hydrophilic organic monomer, oligomer, prepolymer, polymer or copolymer derived from vinyl alcohol, N-vinylpyrrolidone, N-vinyl lactam, acrylamide, amide, styrenesulfonic acid, combination of vinylbutyral and N-vinylpyrrolidone, hydroxyethyl methacrylate, acrylic acid, vinylmethyl ether, vinylpyridylium halide, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl ethyl cellulose, hydroxypropylmethyl cellulose, cellulose acetate, cellulose nitrate, starch, gelatin, albumin, casein, gum, alginate, hydroxyethyl(meth)acrylate, hydroxypropyl (meth)acrylate, ethylene glycol (meth)acrylates (e.g. triethylene glycol (meth)acrylate) and meth)acrylamide), N-alkyl(meth) acrylamides (e.g. N-methyl (meth)acrylamide and N-hexyl(meth)acrylamide), N,N-dialkyl(meth)acrylamides (e.g. N,N-dimethyl(meth)acrylamide and poly-N,N-dipropyl(meth)acrylamide), N-hydroxyalkyl (meth)acrylamide polymers, such as poly-N-methylol (meth)acrylamide and poly-N-hydroxy ethyl(meth)acrylamide, and N,N-dihydroxyalkyl (meth)acrylamide polymers, such as poly-N,N-dihydroxyethyl(meth)acrylamide, ether polyols, polyethylene oxide, polypropylene oxide, and poly(vinyl ether), alkylvinyl sulfones, alkylvinylsulfone-acrylates or a combination thereof.

19. A medical device according to claim 18, wherein said surfactant is a type selected from the group consisting of an anionic, cationic and non-ionic surfactant.

20. A medical device according to claim 19, wherein said surfactant is a cationic surfactant.

21. A medical device according to claim 20, wherein said cationic surfactant is a quaternary ammonium compound.

22. A medical device according to claim 21, wherein said quaternary ammonium compound is selected from the group consisting of an alkyl hydroxyethyl dimethyl ammonium chloride;

polyquaternium 11;

a quaternized copolymer of vinylpyrrolidone and dimethylaminoethylmethacrylate;

polyquaternium 16;

polyquaternium 44;

a combination of a vinylpyrrolidone and quaternized vinylimidazol;

polyquaternium-55;

a quaternized copolymer of vinylpyrrolidone and dimethylaminoethyl;

N,N-Dimethyl-N-dodecyl-N-(2-hydroxy-3-sulfopropyl) ammonium betaine;

N-alkyl acid amidopropyl-N,N-dimethyl-N-(3-sulfopropyl)-ammonium betaine;

3-chloro-2-hydroxypropyl-alkyl-dimethylammonium chloride with a long chain alkyl group; and

combinations thereof.

23. A medical device according to claim 18, wherein said antimicrobial coating further comprises a combination of at least two surfactants.

24. A medical device according to claim 18, wherein said surfactant projects at least about 15 Å

away from the surface of said antimicrobial coating.

25. A medical device according to claim 24, wherein said surfactant projects at least about 30 Å

away from the surface of said antimicrobial coating.

26. A medical device according to claim 25, wherein said surfactant projects at least about 60 Å

away from the surface of said antimicrobial coating.

27. A medical device according to claim 18, wherein said organic debris is selected from the group consisting of dead microbial cells, proteinaceous buildup and a combination thereof.

28. A medical device according to claim 18, wherein said hydrophilic component is present in an amount sufficient to provide said coating with a reduction in friction of at least 80% compared to the uncoated surface when each are wetted with water or an aqueous solution.

29. A medical device according to claim 28, wherein said reduction in friction is at least about 90%.

30. A medical device according to claim 29, wherein said reduction in friction is at least about 95%.

31. A medical device according to claim 18, wherein said hydrophilic component, comprises a hydrophilic polymer, copolymer or prepolymer selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, alkylpolyol, alkoxypolyol, polysaccharide, polyglucosamid, polyglucosamine and combinations thereof.

32. A curable antimicrobial coating composition comprising:

(a) at least one polyurethane prepolymer present in an amount from about 0.01% to about 20% based on the weight of the composition;

(b) at least one carrier solvent capable of at least partially dissolving said polyurethane prepolymer, present in an amount from about 99.89% to about 75% based on the weight of the composition;

(c) a hydrophilic component comprising a hydrophilic organic monomer, oligomer, prepolymer, polymer or copolymer derived from vinyl alcohol, N-vinylpyrrolidone, N-vinyl lactam, acrylamide, amide, styrenesulfonic acid, combination of vinylbutyral and N-vinylpyrrolidone, hydroxyethyl methacrylate, acrylic acid, vinylmethyl ether, vinylpyridylium halide, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl ethyl cellulose, hydroxypropylmethyl cellulose, cellulose acetate, cellulose nitrate, starch, gelatin, albumin, casein, gum, alginate, hydroxyethyl(meth)acrylate, hydroxypropyl (meth)acrylate, ethylene glycol (meth)acrylates (e.g. triethylene glycol (meth)acrylate) and meth)acrylamide), N-alkyl(meth) acrylamides (e.g. N-methyl(meth)acrylamide and N-hexyl(meth)acrylamide), N,N-dialkyl(meth)acrylamides (e.g. N,N-dimethyl(meth)acrylamide and poly-N,N-dipropyl(meth)acrylamide), N-hydroxyalkyl (meth)acrylamide polymers, such as poly-N-methylol (meth)acrylamide and poly-N-hydroxy ethyl(meth)acrylamide, and N,N-dihydroxyalkyl(meth)acrylamide polymers, such as poly-N,N-dihydroxyethyl (meth)acrylamide, ether polyols, polyethylene oxide, polypropylene oxide, and poly(vinyl ether), alkylvinyl sulfones, alkylvinylsulfone-acrylates or a combination thereof, present in an amount from about 0.01 to about 40% based on the weight of the composition; and

(d) at least one quaternary ammonium compound present in an amount from about 0.01% to about 5% based on the weight of the composition and having the following formula;

 

wherein;

L represents a hydrocarbon group which comprises at least one functional group capable of forming a chemical bond with said polyurethane prepolymer, upon curing of said coating composition by evaporation of said carrier solvent, and having sufficient length to allow said at least one quaternary ammonium compound to protrude through and beyond organic debris deposited over time on the surface of said cured coating composition, wherein said functional group is capable of reacting with the polyurethane prepolymer directly or with a crosslinker that is capable of crosslinking the quaternary ammonium compound with the polyurethane prepolymer upon evaporation of said carrier solvent; and

at least one of R₁, R₂ and R₃ represents a hydrocarbon group which is capable of penetrating cell walls of a microbial organism and killing said organism.

33. A coating composition according to claim 32, wherein said polyurethane prepolymer contains at least one functional group selected from the group consisting of a reactive isocyanate, blocked isocyanate, thioisocyanate, carboxyl, amino, vinyl and combinations thereof.

34. A coating composition according to claim 33, wherein said at least one functional group is selected from the group consisting of a reactive isocyanate, blocked isocyanate and thioisocyanate.

35. A coating composition according to claim 32, further comprising a modifying polymer selected from the group consisting of polyester, polyalkyd, maleic anhydride polymer, maleic anhydride copolymer, polyol, polyamine, polyamid, polyacrylate, polyvinyl alcohol, polyvinyl acetate, polyglucosamid, polyglucosamine, polyvinylpyrrolidone, their copolymers and combinations thereof.

36. A coating composition according to claim 32, wherein said hydrophilic polymer, copolymer or prepolymer is present in an amount from about 0.2% to about 15% based on the weight of the composition in replacement of said carrier solvent.

37. A coating composition according to claim 36, wherein said hydrophilic polymer, copolymer or prepolymer is N-polyvinylpyrrolidone.

38. A coating composition according to claim 32, further comprising a crosslinker selected from the group consisting of an aziridine, carbodiimide, melamine, multifunctional alcohol, multifunctional aldehyde, multifunctional amine, multifunctional isocyanate and combinations thereof.

39. A coating composition according to claim 38, wherein said crosslinker is present in an amount from about 0.001% to about 5% based on the weight of the composition in replacement of said carrier solvent.

40. A coating composition according to claim 32, further comprising a reaction enhancing catalyst.

41. A coating composition according to claim 40, wherein said catalyst is selected from the group consisting of tin organic compounds, cobalt organic compounds, triethylamine and combinations thereof.

42. A coating composition according to claim 32, wherein said carrier solvent is selected from the group consisting of water, methyl ethyl ketone, N-methylpyrrolidone, tetrahydrofuran, dichloromethane, chloroform, ethyl acetate, propylene glycol methyl ether, propylene glycol methyl ether acetate, diacetone alcohol, ether, ester, aromatic hydrocarbon, chlorinated hydrocarbon, linear hydrocarbon and combinations thereof.

43. A coating composition according to claim 32, wherein L is of sufficient length to allow a substantial number of positively charged nitrogen atoms to remain above any dead microogranisms or debris that accumulates on the surface of the cured composition when in use.

44. A coating composition according to claim 32, wherein said at least one quaternary ammonium compound is selected from the group consisting of an alkyl hydroxyethyl dimethyl ammonium chloride;

polyquaternium 11;

a quaternized copolymer of vinylpyrrolidone and dimethylaminoethylmethacryiate;

polyquaternium 16;

polyquaternium 44;

a combination of a vinylpyrrolidone and quaternized vinylimidazol;

polyquaternium-55;

a quaternized copolymer of vinylpyrrolidone and dimethylaminoethyl;

N,N-Dimethyl-N-dodecyl-N-(2-hydroxy-3-sulfopropyl) ammonium betaine;

N-alkyl acid amidopropyl-N,N-dimethyl-N-(3-sulfopropyl)-ammonium betaine;

3-chloro-2-hydroxypropyl-alkyl-dimethylammonium chloride with a long chain alkyl group; and

combinations thereof.

45. A coating composition according to claim 32 further comprising an additional component intended to leach out of the cured coating composition or to be bonded with a crosslinker selected from the group consisting of an antimicrobial compound, biocide, antibiotic, drug, vitamin, fungicide, fungistat, virucide, germicide, spermacide, therapeutic agent, heparin, plant extract and combinations thereof.

46. A non-leaching antimicrobial solid surface coating comprising a solid polymeric matrix covalently bound to an antimicrobial compound having the following formula:

47. A curable coating composition comprising:

a polymeric matrix which comprises at least one polyurethane prepolymer;

a carrier solvent;

at least one long chain cationic surfactant compound comprising a functional group capable of forming a chemical bond with said polyurethane prepolymer upon evaporating said carrier solvent and drying or curing of said composition, said functional group selected from the group consisting of an amine, thiol, carboxyl, aldehyde, hydroxyl and combinations thereof; and

at least one hydrophilic organic monomer, oligomer, prepolymer, polymer or copolymer derived from vinyl alcohol, N-vinylpyrrolidone, N-vinyl lactam, acrylamide, amide, styrenesulfonic acid, combination of vinylbutyral and N-vinylpyrrolidone, hydroxyethyl methacrylate, acrylic acid, vinylmethyl ether, vinylpyridylium halide, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl ethyl cellulose, hydroxypropylmethyl cellulose, cellulose acetate, cellulose nitrate, starch, gelatin, albumin, casein, gum, alginate, hydroxyethyl(meth)acrylate, hydroxypropyl (meth)acrylate, ethylene glycol (meth)acrylates (e.g. triethylene glycol (meth)acrylate) and meth)acrylamide), N-alkyl(meth) acrylamides (e.g. N-methyl (meth)acrylamide and N-hexyl(meth)acrylamide), N,N-dialkyl(meth)acrylamides (e.g. N,N-dimethyl(meth)acrylamide and poly-N,N-dipropyl(meth)acrylamide), N-hydroxyalkyl (meth)acrylamide polymers, such as poly-N-methylol (meth)acrylamide and poly-N-hydroxy ethyl(meth)acrylamide, and N,N-dihydroxyalkyl (meth)acrylamide polymers, such as poly-N,N-dihydroxyethyl(meth)acrylamide, ether polyols, polyethylene oxide, polypropylene oxide, and poly(vinyl ether), alkylvinyl sulfones, alkylvinylsulfone-acrylates or a combination thereof;

wherein said long chain cationic surfactant compound is non-leaching upon drying or curing said composition and has sufficient length to protrude through and beyond organic debris deposited over time on the surface of said cured composition; and

wherein said cured composition exhibits reduced blood coagulation of blood in contact with said cured coating compared to a similar coating without said at least one long chain cationic surfactant compound.

48. A curable coating composition according to claim 47, wherein said at least one polyurethane prepolymer comprises at least one functional group capable of forming a covalent bond with the functional group of said long chain compound, either directly or through a cross-linker, upon drying or curing of said coating composition.

49. A curable coating composition according to claim 47, wherein said cationic surfactant is a quaternary ammonium compound.

50. A curable coating composition according to claim 49, wherein said quaternary ammonium compound is selected from the group consisting of an alkyl hydroxyethyl dimethyl ammonium chloride;

polyquaternium 11;

a quaternized copolymer of vinylpyrrolidone and dimethylaminoethylmethacrylate;

polyquaternium 16;

polyquaternium 44;

a combination of a vinylpyrrolidone and quaternized vinylimidazol;

polyquaternium-55;

a quaternized copolymer of vinylpyrrolidone and dimethylaminoethyl;

N,N-Dimethyl-N-dodecyl-N-(2-hydroxy-3-sulfopropyl) ammonium betaine;

N-alkyl acid amidopropyl-N,N-dimethyl-N-(3-sulfopropyl)-ammonium betaine;

3-chloro-2-hydroxypropyl-alkyl-dimethylammonium chloride with a long chain alkyl group; and

combinations thereof.

51. A curable coating composition according to claim 47, wherein said surfactant projects at least about 15 Å

away from the surface of said cured coating.

52. A curable coating composition according to claim 51, wherein said surfactant projects at least about 30 Å

away from the surface of said cured coating.

53. A curable coating composition according to claim 52, wherein said surfactant projects at least about 60 Å

away from the surface of said cured coating.

54. A curable coating composition according to claim 47, wherein said organic debris is selected from the group consisting of dead microbial cells, proteinaceous buildup and a combination thereof.

55. A curable coating composition according to claim 47, wherein said at least one hydrophilic water-soluble organic monomer, oligomer, prepolymer, polymer or copolymer is in an amount sufficient to provide said cured composition with a reduction in friction of about 70% compared to the uncoated surface when each are wetted with water or an aqueous solution.

56. A curable coating composition according to claim 55, wherein said reduction in friction is at least about 80%.

57. A curable coating composition according to claim 56, wherein said reduction in friction is at least about 90%.

58. A curable coating composition according to claim 57, wherein said reduction in friction is at least about 95%.