Dual mode antimicrobial compositions

• US 6,579,539 B2
• Filed: 12/22/1999
• Issued: 06/17/2003
• Est. Priority Date: 12/22/1999
• Status: Expired due to Term

• Current Assignee: C.R. Bard, Inc. (Becton, Dickinson & Co)
• Original Assignee: C.R. Bard, Inc. (Becton, Dickinson & Co)
• Inventors: Terry, Richard, Lawson, Glenn
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): DI NOLA BARON, LILIANA
• Application Number:
  US09/469,909
• Publication Number:
  US 20020094322A1
• Time in Patent Office: 1,273 Days
• Field of Search: 427/2.1, 427/2.3, 604/265, 523/111, 523/122, 424/78.08, 424/422, 424/430, 424/78.17, 424/618
• US Class Current: 424/618
• CPC Class Codes: A61L 2300/104 Silver, e.g. silver sulfadiazine
• 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 2300/608 having two or more layers
• 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

Abstract

The present invention provides compositions which reduce the possibility of inducing microbial resistance. The compositions comprise a fast-acting antimicrobial agent and a long-lasting antimicrobial agent. The combined effect of the antimicrobial agents reduces microbial infection and resistance. Articles comprising the compositions of the present invention and methods for their manufacture are also provided.

Claims

1. An article that resists microbial infection, the article having interior and exterior surfaces, the article comprising:

a metallic silver layer on at least one of the surfaces of the article;

a polyether polyurethaneurea block copolymer layer; and

an effective amount of an antimicrobial agent incorporated into the polymer layer and being capable of diffusing from the polymer layer.

2. The article according to claim 1, wherein the copolymer layer is soluble in water.

3. The article according to claim 1, wherein the antimicrobial agent is a biquanide.

4. The article according to claim 3, wherein the biquanide is chlorhexidine.

24. The article according to claim 1, wherein the article is a catheter.

25. The article according to claim 24, wherein the article is a latex article.

5. A coated article comprising:

an article having a plurality of surfaces; and

a coating covering at least part of the surfaces,

wherein the coating comprises;

a silver layer deposited on at least part of one of the surfaces of the article; and

an outer layer, covering the silver layer, comprising a durable and lubricious polyether polyurethaneurea block copolymer and an effective amount of an antimicrobial agent and,

wherein the antimicrobial agent is capable of diffusing from the outer layer.

6. The article according to claim 5, wherein the article is comprised of a material selected from the group consisting of latex, polystyrene, polyester, polyvinylchloride, polyurethane, ABS polymers, ceramics, glass, polyamide, polyimide, polycarbonate, synthetic rubber, stainless steel, silicone and polypropylene.

7. The article according to claim 5, wherein the outer layer is soluble in water.

8. The article according to claim 5, wherein the antimicrobial agent is a biquanide.

9. The article according to claim 8, wherein the biquanide is chlorhexidine.

21. The article according to claim 5, wherein the coated article contacts a patient.

22. The article according to claim 21, wherein the coated article is for internal use.

23. The article according to claim 22, wherein the coated article is a catheter.

26. The article according to claim 5, wherein the article is a catheter.

10. A method for producing a microbe resistant article comprising:

a) depositing a layer of metallic silver on a surface of the article;

b) preparing a coating solution capable of producing a coating by dissolving polymer or monomers which react to form polymer in solvent;

c) incorporating at least one antimicrobial agent into the coating solution; and

d) coating over the metallic silver layer with the coating solution containing the antimicrobial agent such that the antimicrobial agent is capable of diffusing from the coating, and where the polymer is a polyether polyurethaneurea block copolymer.

11. The method according to claim 10, further comprising contacting the metallic silver layer with at least a portion of at least one surface of an article.

12. The method according to claim 10, wherein the polymer is water soluble after coating.

13. The method according to claim 12, wherein the antimicrobial agent is a biquanide.

14. The method according to claim 13, wherein the biquanide is chlorhexidine.

27. The method according to claim 10, wherein the article is a catheter.

28. The method according to claim 27, wherein the catheter is a latex catheter.

31. The method of claim 10, wherein depositing a layer of metallic silver on a surface of the article comprises carrying out a reduction reaction to deposit silver on the surface.

32. The method of claim 31, wherein the step of carrying out a reduction reaction comprises:

cleaning the surface of the catheter;

activating the surface of the catheter;

forming the metallic silver layer on the article by dipping the article into a bath having a silver salt such that the silver salt is reduced to a metallic silver layer that is deposited on the surface of the catheter; and

stabilizing the metal silver layer.

15. A coated article comprising:

a first antimicrobial agent disposed on a surface of the article; and

a second antimicrobial agent disposed in a coating covering the first antimicrobial agent,

wherein the first antimicrobial agent is a continuous surface-coated metallic silver that is capable of releasing silver ions and has a longer lasting antimicrobial activity than the second antimicrobial agent, and wherein the second antimicrobial agent is capable of diffusing from the coating more rapidly than the first antimicrobial agent.

16. The coated article according to claim 15, wherein the coating is a multi-layer coating.

17. The coated article according to claim 16, wherein the coating comprises a metallic silver layer and a durable and lubricious polymer layer.

18. The coated article according to claim 17, wherein the polymer layer is a hydrogel polymer.

19. The coated article according to claim 15, wherein the antimicrobial agent is a biquanide.

20. The coated article according to claim 19, wherein the biquanide is chlorhexidine.

30. The method of claim 18, wherein preparing a coating solution comprises dissolving polymer or monomers which react to form polymer in an aqueous solvent.

29. An article comprising:

a catheter having exterior and interior surfaces, the catheter being made of a polymer selected from a group consisting of;

latex and silicone;

a metallic silver layer deposited on at least one of the catheter surfaces, the layer having a thickness between about 2 angstroms and about 10 microns;

a polyether polyurethane-urea block copolymer coating disposed to cover the metallic silver layer; and

chlorhexidine, in an amount between about 1% to about 10% based on the dry weight of the block copolymer coating, releasably disposed within the block copolymer coating.

33. An article having a plurality of surfaces and comprising:

a coating including

(1) a silver layer deposited on at least part of one of the surfaces of the article,

(2) a hydrogel polymer layer covering the silver layer, and

(3) an effective amount of an antimicrobial agent disposed within the hydrogel polymer layer and capable of diffusing therefrom.

34. A method of producing a microbe resistant article, the method comprising:

a) cleaning and activating a surface of the article;

b) forming a metallic silver layer on the activated surface by dipping the article into a bath having a silver salt that is reduced to form a metallic silver layer on the activated surface;

c) stabilizing the metallic silver layer; and

d) coating the metallic silver layer with a polymer solution comprising at least one antimicrobial agent such that the antimicrobial agent is capable of diffusing therefrom.