Bio-Film Resistant Surfaces

• US 20090029961A1
• Filed: 06/06/2008
• Published: 01/29/2009
• Est. Priority Date: 06/20/2007
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Citron, Ronald, Modak, Shanta M., Geraldo, Ingrid, Caraos, Lauserpina A.
• Granted Patent: US 8,932,624 B2
• Time in Patent Office: Days
• US Class Current: 514/184
• 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 25/34 Shaped forms, e.g. sheets, not provided for in any other sub-group of this main group
• CPC Class Codes: A01N 37/36 containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
• CPC Class Codes: A01N 47/44 Guanidine; Derivatives thereof
• CPC Class Codes: A01N 59/16 Heavy metals; Compounds thereof
• CPC Class Codes: A61L 15/46 Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
• CPC Class Codes: A61L 2300/104 Silver, e.g. silver sulfadiazine
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61P 31/02 Local antiseptics

Abstract

The present invention relates to methods and compositions for rendering a surface resistant to bio-film formation by a combination of an alkanediol and an antimicrobial agent (and, optionally, an organic hydroxy acid). The invention provides for compositions which may be used to render surfaces bio-film resistant, articles having bio-film resistant surfaces, and methods for their preparation. The present invention may be advantageously applied to medical articles as well as articles used in non-medical contexts, such as child care or food preparation.

Claims

1. A composition for preparing a bio-film resistant surface comprising a biguanide, an alkanediol, and a solvent, where the biguanide is present at between about 0.1 and 5 percent (weight/volume), the alkanediol is present at between about 0.5 and 5 percent (volume/volume), and the solvent is selected from the group consisting of an alcohol, tetrahydrofuran, and mixtures thereof.

2. The composition of claim 1, wherein the biguanide is selected from the group consisting of chlorhexidine free base, chlorhexidine diacetate, chlorhexidine gluconate, polyhexamethylene biguanide, and a mixture thereof.

3. The composition of claim 1, wherein the alkanediol is selected from the group consisting of octanediol, 1,2-decanediol, 1,2-dodecanediol, 1,12-dodecanediol and 1,2 tetradecanediol.

4. The composition of claim 1, further comprising an additional antimicrobial agent in an amount between about 0.05 and 3 percent (weight/volume).

5. The composition of claim 4, wherein the additional antimicrobial agent is a silver compound.

6. The composition of claim 5, wherein the silver compound is silver sulfadiazine.

7. The composition of claim 1 or 4, further comprising one or more hydroxy acid in an amount between about 0.5 and 3 percent (volume/volume).

8. The composition of claim 7, wherein the hydroxy acid is selected from the group consisting of lactic acid, citric acid, and salicylic acid.

9. The composition of claim 1, comprised in a wipe.

10. The composition of claim 2, comprised in a wipe.

11. The composition of claim 3, comprised in a wipe.

12. The composition of claim 4, comprised in a wipe.

13. The composition of claim 5, comprised in a wipe.

14. The composition of claim 6, comprised in a wipe.

15. The composition of claim 7, comprised in a wipe.

16. The composition of claim 8, comprised in a wipe.

17. The composition of claim 1, comprised in a wound dressing.

18. The composition of claim 2, comprised in a wound dressing.

19. The composition of claim 3, comprised in a wound dressing.

20. The composition of claim 4, comprised in a wound dressing.

21. The composition of claim 5, comprised in a wound dressing.

22. The composition of claim 6, comprised in a wound dressing.

23. The composition of claim 7, comprised in a wound dressing.

24. The composition of claim 8, comprised in a wound dressing.

43. The composition of claim 1, further comprising a polymer.

44. The composition of claim 43, comprised in a wipe.

45. The composition of claim 43, comprised in a wound dressing.

46. The composition of claim 4, wherein the additional antimicrobial agent is a chlorinated phenol.

47. The composition of claim 4, wherein the additional antimicrobial agent is triclosan.

25. A method of producing a bio-film resistant surface, comprising exposing the surface to a composition for preparing a bio-film resistant surface comprising a biguanide, an alkanediol, and a solvent, where the biguanide is present at between about 0.1 and 5 percent (weight/volume), the alkanediol is present at between about 0.5 and 5 percent (volume/volume), and the solvent is selected from the group consisting of an alcohol, tetrahydrofuran, and mixtures thereof.

26. The method of claim 25, wherein the biguanide is selected from the group consisting of chlorhexidine free base, chlorhexidine diacetate, chlorhexidine gluconate, polyhexamethylene biguanide, and a mixture thereof.

27. The method of claim 25, wherein the alkanediol is selected from the group consisting of octanediol, 1,2-decanediol, 1,2-dodecanediol, 1,12-dodecanediol and 1,2 tetradecanediol.

28. The method of claim 25, said composition further comprising an additional antimicrobial agent in an amount between about 0.05 and 3 percent (weight/volume).

29. The method of claim 28, wherein the additional antimicrobial agent is a silver compound.

30. The method of claim 29, wherein the silver compound is silver sulfadiazine.

31. The method of claim 25 or 28, further comprising one or more hydroxy acid in an amount between about 0.5 and 3 percent (volume/volume).

32. The method of claim 31, wherein the hydroxy acid is selected from the group consisting of lactic acid, citric acid, and salicylic acid.

33. An article having a surface rendered bio-film resistant by the method of claim 25.

34. An article having a surface rendered bio-film resistant by the method of claim 26.

35. An article having a surface rendered bio-film resistant by the method of claim 27.

36. An article having a surface rendered bio-film resistant by the method of claim 28.

37. An article having a surface rendered bio-film resistant by the method of claim 29.

38. An article having a surface rendered bio-film resistant by the method of claim 30.

39. An article having a surface rendered bio-film resistant by the method of claim 31.

40. An article having a surface rendered bio-film resistant by the method of claim 32.

48. The method of claim 25, said composition further comprising a polymer.

49. The method of claim 28, wherein the additional antimicrobial agent is a chlorinated phenol.

50. The method of claim 28, wherein the additional antimicrobial agent is triclosan.

52. An article having a surface rendered bio-film resistant by the method of claim 48.

53. An article having a surface rendered bio-film resistant by the method of claim 49.

54. An article having a surface rendered bio-film resistant by the method of claim 50.

55. The article of claim 33, 34, 35, 36, 37, 38, 40, 51, 52, 53 or 54 which is a wound dressing.

56. The article of claim 33, 34, 35, 36, 37, 38, 40, 51, 51, 52, 53 or 54 which is selected from the group consisting of a vascular catheter, a urinary catheter, a wound drainage tube and a tracheal catheter.

57. The article of claim 33, 34, 35, 36, 37, 38, 40, 51, 51, 52, 53 or 54 which is selected from the group consisting of an arterial graft, a soft tissue patch, a glove, a shunt, a stent, an intravaginal device, a suture, a staple, a guide wire, a heart valve, and a left ventricular assist device.

41. A method of rendering a surface of an article resistant to bio-film formation, comprising:

(i) applying a first solution to the surface, said first solution comprising an antimicrobial agent, other than a biguanide, at a concentration of between about 0.05 and 3 percent (w/v), and optionally further comprising a hydroxy acid at a concentration between about 0.5 and 3 percent (v/v), in a solvent selected from the group consisting of an alcohol (e.g. methanol, ethanol, isopropanol, and mixtures thereof), tetrahydrofuran and mixtures thereof;

(ii) allowing the first solution to dry;

(iii) applying a second solution to the surface, said second solution comprising a biguanide at a concentration between about 0.1 and 5 percent (weight/volume), alkanediol at a concentration between about 0.5 and 5 percent (volume/volume), polymer at a concentration between about 1 and 20 percent (weight) volume, a solvent selected from the group consisting of an alcohol (e.g. methanol, ethanol, isopropanol, and mixtures thereof), tetrahydrofuran and mixtures thereof; and

optionally hydroxy acid in an amount of between about 0.5 and 3 percent (volume/volume).

51. An article having a surface rendered bio-film resistant by the method of claim 41.

42. An article having at least one surface comprising, as active agents, a biguanide at between about 250 and 5000 μ

g/cm² of surface and an alkanediol at between about 200 and 1500 μ

g/cm² of surface, and optionally a hydroxy acid at between about 100 and 800 μ

g/cm² of surface, and/or optionally a silver compound at between about 0-200 μ

g/cm² of surface.