Chlorhexidine-containing medical devices

• US 6,872,195 B2
• Filed: 08/25/2003
• Issued: 03/29/2005
• Est. Priority Date: 01/05/1996
• Status: Expired due to Fees

• 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
• Primary Examiner(s): KENNEDY, SHARON E
• Application Number:
  US10/647,740
• Publication Number:
  US 20040039349A1
• Time in Patent Office: 582 Days
• Field of Search: 604/264, 604/265, 428/35.7, 428/36.9, 606/76, 424/422, 623/1.1, 623/1.42, 623/1.43, 623/1.45
• US Class Current: 604/265
• 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 2300/206 Biguanides, e.g. chlorohexidine
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• 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: C08L 75/04 Polyurethanes
• CPC Class Codes: C08L 83/04 Polysiloxanes
• CPC Class Codes: Y10T 428/1331 Single layer [continuous layer]
• 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 the anti-infective agents chlorhexidine and triclosan. It is based, at least in part, on the discovery that the synergistic relationship between these compounds permits the use of relatively low levels of both agents, and on the discovery that effective antimicrobial activity may be achieved when these compounds are comprised in either hydrophilic or hydrophobic polymers. It is also based on the discovery that chlorhexidine free base and triclosan, used together, are incorporated into polymeric medical articles more efficiently. Medical articles prepared according to the invention offer the advantage of preventing or inhibiting infection while avoiding undesirably high release of anti-infective agent, for example into the bloodstream of a subject.

Claims

1. A medical article wherein the internal surface of the article has been impregnated with a treatment solution comprising chlorhexidine, and wherein the chlorhexidine consists essentially of a mixture of chlorhexidine free base and a chlorhexidine salt.

2. The article of claim 1 wherein the treatment solution comprises between about one to five percent chlorhexidine.

3. The article of claim 1 further comprising silver sulfadiazine.

4. The article of claim 1 wherein the treatment solution further comprises a polymer.

5. The article of claim 4 wherein the treatment solution comprises between about one to ten percent of the polymer.

6. The article of claim 4 wherein the polymer is hydrophobic.

7. The article of claim 6 wherein the hydrophobic polymer is selected from the group consisting of polytetrafluoroethylene, DACRON, polyester fabric, polyvinylchloride, polyurethane, biomedical silicone polymer, and silicon-polyurethane copolymer.

8. The article of claim 4 wherein the polymer is hydrophilic.

9. The article of claim 8 wherein the hydrophilic polymer is selected from the group consisting of natural rubber latex and biomedical polyurethane.

10. The article of claim 1 wherein the external surface of the article has been impregnated with a treatment solution comprising chlorhexidine, and wherein the chlorhexidine consists essentially of a mixture of chlorhexidine free base and a chlorhexidine salt.

11. The article of claim 1 wherein the article is a catheter.

12. A method of preparing a medical article, the method comprising:

(i) contacting the internal surface of the article with an impregnating solution comprising a solvent and chlorhexidine, and

(ii) soaking the article in the solution for a period of time sufficient to allow the article to swell;

wherein the solvent is selected from the group consisting of water, reagent alcohol, tetrahydrofuran, and mixtures thereof; and

and wherein the chlorhexidine consists essentially of a mixture of chlorhexidine free base and a chlorhexidine salt.

13. The method of claim 12 wherein the total weight of chlorhexidine is between about one and ten percent of the weight of the solution.

14. The method of claim 12 further comprising removing the article from the solution and drying the article.

15. The method of claim 12 further comprising contacting the article with a second solution, wherein the second solution comprises a polymer.

16. A method of preparing a medical article, the method comprising:

(i) contacting the internal surface of the article with an impregnating solution comprising a solvent, chlorhexidine free base and chlorhexidine salt, and

(ii) soaking the article in the solution for a period of time sufficient to allow the article to swell;

wherein the solvent is selected from the group consisting of water, reagent alcohol, tetrahydrofuran, and mixtures thereof.

17. The method of claim 16 wherein the total weight of chlorhexidine is between about one and ten percent of the weight of the solution.

18. The method of claim 16 further comprising removing the article from the solution and drying the article.

19. The method of claim 16 further comprising contacting the article with a second solution, wherein the second solution comprises a polymer.