Triclosan and silver compound containing medical devices

• US 20010010016A1
• Filed: 02/05/2001
• Published: 07/26/2001
• Est. Priority Date: 03/31/1999
• 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: Modak, Shanta, Sampath, Lester
• Granted Patent: US 6,843,784 B2
• Time in Patent Office: Days
• US Class Current: 623/1.42
• 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 31/08 Oxygen or sulfur directly attached to an aromatic ring system
• 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 59/16 Heavy metals; Compounds thereof
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 17/005 containing a biologically active substance, e.g. a medicament or a biocide
• CPC Class Codes: A61L 2/18 Liquid substances or solutions comprising solids or dissolved gases
• CPC Class Codes: A61L 2300/104 Silver, e.g. silver sulfadiazine
• CPC Class Codes: A61L 2300/202 with halogen atoms, e.g. triclosan, povidone-iodine
• CPC Class Codes: A61L 2300/21 Acids
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• 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: D06M 11/83 with metals; with metal-generating compounds, e.g. metal carbonyls; Reduction of metal compounds on textiles
• CPC Class Codes: D06M 13/432 : Urea, thiourea or derivatives thereof, e.g. biurets; Urea-inclusion compounds; Dicyanamides; Carbodiimides; Guanidines, e.g. dicyandiamides
• CPC Class Codes: D06M 16/00 : Biochemical treatment of fibres, threads, yarns, fabrics, or fibrous goods made from such materials, e.g. enzymatic
• CPC Class Codes: Y10T 428/1352 : Polymer or resin containing [i.e., natural or synthetic]

Abstract

The present invention relates to polymeric medical articles comprising combinations of triclosan and silver-containing compounds. It is based, at least in part, on the discovery that these agents act synergistically, thereby permitting the use of relatively low levels of both agents. While it had been previously found that triclosan can be particularly useful when used in conjunction with chlorhexidine, it has been further discovered that medical articles having suitable antimicrobial properties may be prepared, according to the present invention, which contain triclosan without chlorhexidine. Such medical articles offer the advantage of preventing or inhibiting infection while avoiding undesirable adverse reactions to chlorhexidine by individuals that may have sensitivity to chlorhexidine.

Claims

1. An anti-infective medical article prepared by exposing a polymer-containing medical article, for an effective period of time, to a treatment solution comprising between about 0.3 and 1.5 percent of a silver salt and between about 0.1 and 20 percent triclosan, where the treatment solution and the medical article do not contain chlorhexidine or a chlorhexidine salt.

2. The anti-infective medical article of

claim 1

, where the treatment solution further comprises an organic acid at a concentration of between about 0.1 and 5 percent.

3. The anti-infective medical article of

claim 2

, where the organic acid is citric acid.

4. The anti-infective medical article of

claim 1

, where the treatment solution further comprises an anti-inflammatory agent, at a concentration of between about 1 and 5 percent.

5. The anti-infective medical article of

claim 4

, where the anti-inflammatory agent is salicylic acid or a derivative thereof.

6. The anti-infective medical article of

claim 1

, where the treatment solution further comprises an additional antimicrobial agent.

7. The anti-infective medical article of

claim 6

, where the additional antimicrobial agent is selected from the group consisting of gramicidin, polymixin, norfloxacin, sulfamylon, polyhexamethylene biguanide, alexidine, minocycline, iodine, benzalkonium chloride and rifampicin.

8. The anti-infective medical article of

claim 1

, where the treatment solution further comprises between about 1 and 5 percent of one or more hydrophilic or hydrophobic polymer.

9. The anti-infective medical article of

claim 1

which is a polytetrafluoroethylene patch.

10. A polymer-containing vascular catheter comprising between about 100 and 600 micrograms of triclosan in releasable form per centimeter and between about 25 and 100 micrograms of silver atom or ion in releasable form per centimeter, where the catheter does not contain chlorhexidine or a chlorhexidine salt.

11. A method of preparing an anti-infective medical article comprising exposing a polymer-containing medical article, for an effective period of time, to a treatment solution comprising between about 0.3 and 1.5 percent of a silver salt and between about 0.1 and 20 percent triclosan, where the treatment solution and the medical article do not contain chlorhexidine or a chlorhexidine salt.

12. The method of

claim 11

, where the treatment solution further comprises an organic acid at a concentration of between about 0.1 and 5 percent.

13. The method of

claim 12

, where the organic acid is citric acid.

14. The method of

claim 11

, where the treatment solution further comprises an anti-inflammatory agent, at a concentration of between about 1 and 5 percent.

15. The method of

claim 14

, where the anti-inflammatory agent is salicylic acid or a derivative thereof.

16. The method of

claim 11

, where the treatment solution further comprises an additional antimicrobial agent.

17. The method of

claim 14

, where the additional antimicrobial agent is selected from the group consisting of gramiciain, polymixin, norfloxacin, sulfamylon, polyhexamethylene biguanide, alexidine, minocycline, iodine, benzalkonium chloride and rifampicin.

18. The method of

claim 11

, where the treatment solution further comprises between about 1 and 5 percent of one or more hydrophilic or hydrophobic polymer.

19. The method of

claim 11

, where the polymer-containing medical article is a polytetrafluoroethylene patch.

20. An anti-infective medical article prepared by exposing a polymer-containing medical article, for an effective period of time, to a treatment solution comprising between about 0.3 and 1.5 percent of a silver compound and between about 0.1 and 20 percent of a chlorinated phenol, where the chlorinated phenol is not triclosan.

21. The anti-infective medical article of

claim 20

, where the chlorinated phenol is parachlorometaxylenol.

22. An anti-infective medical article prepared by exposing a polymer-containing medical article, for an effective period of time, to a treatment solution comprising between about 0.1 and 5 percent of a metal compound, between about 0.1 and 20 percent triclosan, and between about 0.5 and 10 percent of a hydrogel.

23. The anti-infective medical article of

claim 22

, where the metal compound is a silver compound.

24. The anti-infective medical article of

claim 22

, where the hydrogel comprises polyvinyl pyrrolidone.

25. An anti-infective medical article prepared by exposing a polymer-containing medical article, for an effective period of time, to a treatment solution comprising between about 0.1 and 5 percent of a silver compound, between about 0.1 and 20 percent of triclosan, and between about 1 and 5 percent of an anti-inflammatory agent.

26. The anti-infective medical article of

claim 25

, where the anti-inflammatory agent is salicylic acid or a derivative thereof.

27. The anti-infective medical article of

claim 25

, where the treatment solution further comprises an additional antimicrobial agent.

28. The anti-infective medical article of

claim 27

, where the additional antimicrobial agent is selected from the group consisting of chlorhexidine, a chlorhexidine salt, gramicidin, polymixin, norfloxacin, sulfamylon, polyhexamethylene biguanide, alexidine, minocycline, iodine benzalkonium chloride and rifampicin.

29. The anti-infective medical article of

claim 25

which is a polytetrafluoroethylene graft.

30. A method of preparing an anti-infective medical article, comprising exposing a polymer-containing medical article, for an effective period of time, to a treatment solution comprising between about 0.3 and 1.5 percent of a silver compound and between about 0.1 and 20 percent of a chlorinated phenol, where the chlorinated phenol is not triclosan.

31. The method of

claim 30

, where the chlorinated phenol is parachlorometaxylenol.

32. A method of preparing an anti-infective medical article comprising exposing a polymer-containing medical article, for an effective period of time, to a treatment solution comprising between about 0.1 and 5 percent of a metal compound, between about 0.1 and 20 percent triclosan, and between about 0.5 and 10 percent of a hydrogel.

33. The method of

claim 32

, where the metal compound is a silver compound.

34. The method of

claim 32

, where the hydrogel comprises polyvinylpyrrolidone.

38. The method of

claim 34

, where the additional antimicrobial agent is selected from the group consisting of chlorhexidine, a chlorhexidine salt, gramicidin, polymixin, norfloxacin, sulfamylon, polyhexamethylene biguanide, alexidine, minocycline, iodine benzalkonium chloride and rifampicin.

35. A method of preparing an anti-infective medical article comprising exposing a polymer-containing medical article, for an effective period of time, to a treatment solution comprising between about 0.1 and 5 percent of a silver compound, between about 0.1 and 20 percent of triclosan, and between about 1 and 5 percent of an anti-inflammatory agent.

36. The method of

claim 35

, where the anti-inflammatory agent is salicylic acid or a derivative thereof.

37. The method of

claim 35

, where the treatment solution further comprises an additional antimicrobial agent.