Novel antiseptic derivatives with broad spectrum antimicrobial activity for the impregnation of surfaces

• US 20030078242A1
• Filed: 01/11/2002
• Published: 04/24/2003
• Est. Priority Date: 01/12/2001
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Raad, Issam, Nabulsi, Nabeel, Hanna, Hend A.
• Granted Patent: US 7,713,472 B2
• Time in Patent Office: Days
• US Class Current: 514/150
• 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 31/12 Bis-chlorophenols
• CPC Class Codes: A01N 31/16 with two or more oxygen or sulfur atoms directly attached to the same aromatic ring system
• CPC Class Codes: A01N 33/06 Nitrogen directly attached to an aromatic ring system
• CPC Class Codes: A01N 33/26 containing nitrogen-to-nitrogen bonds, e.g. azides, diazo-amino compounds, diazonium compounds, hydrazine derivatives
• CPC Class Codes: A01N 43/16 with oxygen as the ring hetero atom
• CPC Class Codes: A01N 43/38 condensed with carbocyclic rings
• CPC Class Codes: A01N 43/40 six-membered rings
• CPC Class Codes: A01N 43/42 condensed with carbocyclic rings
• CPC Class Codes: A01N 43/90 having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
• CPC Class Codes: A01N 47/44 Guanidine; Derivatives thereof
• CPC Class Codes: A61L 2/16 using chemical substances
• CPC Class Codes: A61L 2300/206 Biguanides, e.g. chlorohexidine
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/442 Colorants, dyes
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C02F 1/50 : by addition or application of a germicide or by oligodynamic treatment C02F1/4606, C02F1/467, C02F1/76 take precedence

Abstract

The present invention provides novel broad spectrum antiseptic compounds that further have properties that allow them to be coated/impregnated into polymer surfaces. Methods for coating these antiseptic compounds onto medical devices especially in-dwelling medical devices to prevent the growth of pathogens in such devices and hence, to prevent infection to patients via such devices are provided. The invention also provides antiseptics that are useful as general surface disinfectants and sterilizers, fluid disinfectants and biocide preservatives.

Claims

1. An antiseptic composition comprising a basic reagent and a dye.

2. The antiseptic composition of claim 1, wherein a basic reagent and a dye are bonded.

3. The antiseptic composition of claim 2, wherein a basic reagent and a dye are linked by ionic bonding.

4. The antiseptic composition of claim 2, wherein a basic reagent and a dye are linked by covalent bonding.

5. The antiseptic composition of claim 1, wherein the dye is a triarylmethane dye.

6. The antiseptic composition of claim 1, wherein the dye is a monoazo dye.

7. The antiseptic composition of claim 1, wherein the dye is a diazo dye.

8. The antiseptic composition of claim 1, wherein the dye is an indigoid dye.

9. The antiseptic composition of claim 1, wherein the dye is a xanthene dye.

10. The antiseptic composition of claim 1, wherein the dye is an anthraquinone dye.

11. The antiseptic composition of claim 1, wherein the dye is a quinoline dye.

12. The antiseptic composition of claim 1, wherein the dye is gentian violet or crystal viol et, ethyl violet, brilliant green, an FD&

C dye, or a D&

C dye.

13. The antiseptic composition of claim 12, wherein the FD&

C dye is Blue No. 1 or Green No. 3.

14. The antiseptic composition of claim 5, wherein the triarylmethane dye is gentian violet.

15. The antiseptic composition of claim 6, wherein the monoazo dye is FD&

C Yellow No. 5 or FD&

C Yellow No. 6.

16. The antiseptic composition of claim 7, wherein the diazo dye is D&

C Red No. 17.

17. The antiseptic composition of claim 8, wherein the indigoid dye is FD&

C Blue No. 2.

18. The antiseptic composition of claim 9, wherein the xanthene dye is FD&

C Red No. 3.

19. The antiseptic composition of claim 10, wherein the anthraquinone dye is D&

C Green No. 6.

20. The antiseptic composition of claim 11, wherein the quinoline dye is D&

C Yellow No. 1.

21. The antiseptic composition of claim 1, wherein the basic reagent is a guanidium compound, a biguanide, a bipyridine, a phenoxide antiseptic, an alkyl oxide, an aryl oxide, a thiol, a halide, an aliphatic amine, or an aromatic amine.

22. The antiseptic composition of claim 21, wherein the basic reagent is a guanidium compound.

23. The antiseptic composition of claim 22, wherein the guanidium compound is chlorhexidine.

24. The antiseptic composition of claim 22, wherein the guanidium compound is alexidine.

25. The antiseptic composition of claim 22, wherein the guanidium compound is hexamidine.

26. The antiseptic composition of claim 21, wherein the basic reagent is a bipyridine.

27. The antiseptic composition of claim 26, wherein the bipyridine is octenidine.

28. The antiseptic composition of claim 21, wherein the basic reagent is a phenoxide antiseptic.

29. The antiseptic composition of claim 28, wherein the phenoxide antiseptic is clofoctol.

30. The antiseptic composition of claim 28, wherein the phenoxide antiseptic is chloroxylenol.

31. The antiseptic composition of claim 28, wherein the phenoxide antiseptic is triclosan.

69. A method for disinfecting and/or sterilizing a surface comprising applying a composition comprising a basic reagent and a dye of claim 1 to the surface.

70. The method of claim 69, wherein the surface is an organic surface.

71. The method of claim 70, wherein the organic surface is selected from a group comprising, skin, a mucosal surface, and a wound surface.

72. The method of claim 69, wherein the surface is an inorganic surface.

73. The method of claim 72, wherein the inorganic surface is selected from a group comprising a floor, a table-top, a counter-top, hospital equipment, a wheel chair, gauze, cotton.

74. A method for disinfecting and/or sterilizing a fluid comprising adding a composition comprising a basic reagent and a dye of claim 1 into the fluid.

75. The method of claim 74, wherein said fluid is water.

76. The method of claim 74 wherein said fluid is a metal working fluid.

77. The method of claim 74, wherein said fluid is petroleum.

32. An antiseptic compound comprising a basic reagent bound to a dye.

33. The antiseptic compound of claim 32, wherein the basic reagent and the dye are bound ionically.

34. The antiseptic compound of claim 32, wherein the basic reagent and the dye are bound covalently.

35. The antiseptic compound of claim 32, wherein the composition is gendine, genlenol, genlosan, or genfoctol.

36. The antiseptic compound of claim 32, further defined by its ability to impregnate and/or coat a surface.

37. The antiseptic compound of claim 36, wherein the surface is composed of a polymer.

38. The antiseptic compound of claim 37, wherein the polymer is polyvinyl chloride, polyurethane, polyethylene, silastic elastomers, polytetrafluoroethylene, dacron, collodion, carboethane or nylon.

39. The antiseptic compound of claim 36, wherein said surface is composed of silicone.

40. The antiseptic compound of claim 36, wherein said surface is a silk suture.

41. The antiseptic compound of claim 36, wherein the surface is an organic surface.

42. The antiseptic compound of claim 41, wherein the organic surface is skin.

43. The antiseptic compound of claim 41, wherein the organic surface is a mucosal surface.

44. The antiseptic compound of claim 41, wherein the organic surface is a wound.

45. The antiseptic compound of claim 36, wherein the surface is an inorganic surface.

46. The antiseptic compound of claim 45, wherein the inorganic surface is a floor.

47. The antiseptic compound of claim 45, wherein the inorganic surface is a table-top.

48. The antiseptic compound of claim 45, wherein the inorganic surface is a counter-top.

49. The antiseptic compound of claim 45, wherein the inorganic surface is the surface of a hospital equipment.

50. The antiseptic compound of claim 45, wherein the inorganic surface is a wheelchair surface.

52. The medical device of claim 50, wherein a basic reagent and a dye are bonded.

53. The medical device of claim 52 wherein the basic reagent and the dye are bound ionically.

54. The medical device of claim 52, wherein the basic reagent and the dye are bound covalently.

55. The medical device of claim 52, further selected from the group comprising an endotracheal tube, a vascular catheter, an urinary catheter, a nephrostomy tube, a biliary stent, a peritoneal catheter, an epidural catheter, a central nervous system catheter, an orthopedic device, a prosthetic valve, and a medical implant.

56. The medical device of claim 55, wherein said vascular catheter is a central venous catheter, an arterial line, an pulmonary artery catheter, and a peripheral venous catheter.

57. The medical device of claim 55, wherein said central nervous system catheter is a intraventricular shunt.

51. A medical device coated with a basic reagent and a dye.

58. A method for coating a medical device with an antiseptic composition comprising:

a) immersing said medical device in a solvent comprising a basic reagent and a dye.

b) drying the device; and

c) washing off excessive composition.

59. The method of claim 58, wherein the solvent comprises methylene chloride, methanol, or a combination thereof.

60. A method for preventing nosocomial infections in a subject comprising coating a medical device that the subject is required to use with a composition comprising a basic reagent and to a dye.

61. The method of claim 60, wherein said subject is human.

62. The method of claim 60, wherein said nosocomial infection is pneumonia, bacteremia, fungimia, candidemia, a urinary tract infection, a catheter-exit site infection, and a surgical wound infection.

63. The method of claim 60, wherein said nosocomial infection is caused by a bacterium.

64. The method of claim 63, wherein said bacterium is a resistant bacterium.

65. The method of claim 64, wherein said resistant bacterium is selected from a group comprising methicillin-resistant staphylococci, vancomycin-resistant enterococci, and resistant Pseudomonas aeruginosa.

66. The method of claim 60, wherein said nosocomial infection is caused by a fungus.

67. The method of claim 66, wherein said fungus is a resistant fungus.

68. The method of claim 67, wherein said resistant fungus belongs to Candida species.

78. A method for preserving a substance comprising applying a composition comprising a basic reagent and a dye on the substance.

79. The method of claim 78, wherein the substance is selected from the group comprising wood, paint, plastic and paper.