Anti-infective and antithrombogenic medical articles and method for their preparation

• US 6,261,271 B1
• Filed: 01/13/1998
• Issued: 07/17/2001
• Est. Priority Date: 01/18/1989
• Status: Expired due to Term

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Solomon, Donald D., Byron, M. Parke
• Primary Examiner(s): Kennedy, Sharon
• Assistant Examiner(s): WILLIAMS, CATHERINE SERKE
• Application Number:
  US09/006,677
• Time in Patent Office: 1,281 Days
• Field of Search: 604/264, 604/265, 604/280, 604/266, 604/48, 604/93.01, 623/1.38, 623/1.42, 623/1.43, 623/1-4-, 600/29-30, 524/916, 524/195, 523/112, 523/122, 427/2--, 424/78.08
• US Class Current: 604/265
• 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 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet 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 27/54 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: A61M 2025/0056 provided with an antibacterial agent, e.g. by coating, residing in the polymer matrix or releasing an agent out of a reservoir
• CPC Class Codes: C08L 75/00 Compositions of polyureas or polyurethanes; Compositions of derivatives of such polymers

Abstract

An anti-infective medical article has chlorhexidine bulk distributed throughout a polyurethane base layer and may have a coating layer on the base layer. The coating layer may be chlorhexidine permeated into the surface or it may be an antibiotic, antithrombogenic agent or a polymeric surface layer laminated onto the base layer. The invention includes a method for preparing the article wherein a homogeneous melt of polymer and chlorhexidine is prepared by twin screw compounding and the melt is extruded to give a medical article having bulk distributed chlorhexidine.

Claims

1. A tubular medical article adapted for placement in contact with or insertion into living tissue comprising a polymeric inner lumen having a water absorption of at least 0.6% by weight and an anti-infective agent comprising a biguanide bulk distributed throughout.

2. The article of claim 1 further including silver sulfadiazine.

3. The article of claim 2, wherein said silver sulfadiazine is on an exterior surface of said article.

4. The article of claim 2, wherein said silver sulfadiazine is on the interior surface of said article.

5. The article of claim 2, wherein said silver sulfadiazine is bulk distributed throughout said polymeric inner lumen.

6. The article of claim 1, wherein said article further includes an antibiotic.

7. The article of claim 6, wherein said antibiotic is on a surface of said article.

8. The article of claim 7, wherein said antibiotic is on an interior surface of said article.

9. The article of claim 8, wherein said antibiotic is on an exterior surface of said article.

10. The article of claim 9, wherein said antibiotic is bulk distributed throughout said polymeric inner lumen.

11. The article of claim 10, further comprising an antithrombogenic agent.

16. The article of claim 1, wherein said biguanide is selected from the group consisting of a chlorhexidine base and a chlorhexidine salt or mixtures thereof.

17. The article of claim 16, wherein said biguanide is a salt of chlorhexidine and said salt is selected from the group consisting of the hydrochloride, acetate and gluconate salts of chlorhexidine or mixtures thereof.

18. The article of claim 1, wherein said polymeric inner lumen is comprised of a polymer selected from the group consisting of polyurethane, siloxane-urethane block copolymer and polyurethaneurea.

19. The article of claim 16, wherein the concentration of said biguanide in said polymer is about 0.1 to 10% by weight.

20. The article of claim 1, further comprising a polymeric coating.

21. The article of claim 19, further comprising a polymeric coating.

22. The article of claim 1, which is a catheter.

12. The article of claim 12, wherein said antithrombogenic agent is on a surface of said article.

13. The article of claim 12, wherein said antithrombogenic agent is on an interior surface of said article.

14. The article of claim 13, wherein said antithrombogenic agent is on an exterior of said article.

15. The article of claim 14, wherein said antithrombogenic agent is bulk distributed throughout said polymeric inner lumen.

23. A tubular medical article for contacting with or inserting into living tissue, comprising a polyurethane inner lumen having a water absorption of at least 0.6% by weight and a coating layer, the coating layer comprising a laminating polymer having a water absorption of at least 0.6% by weight, said inner lumen and laminating polymeric layers each having about 0.1 to 10% by weight of a biguanide bulk distributed throughout.

24. The article of claim 23, wherein said coating further comprises a second polymer having a water absorption of at least 0.6% by weight.

25. The article of claim 23, further including silver sulfadiazine.

26. The article of claim 25, wherein silver sulfadiazine is on the exterior surface of said article.

27. The article of claim 25, wherein said silver sulfadiazine is on the interior surface of said article.

28. The article of claim 25, wherein said silver sulfadiazine is bulk distributed throughout said laminating polymer.

29. The method article of claim 23, wherein said article further includes an antibiotic.

30. The article of claim 29, wherein said antibiotic is on a surface of said article.

31. The article of claim 29, wherein said antibiotic is on an interior surface of said article.

32. The article of claim 29, wherein said antibiotic is on an exterior surface of said article.

33. The article of claim 29, wherein said antibiotic is bulk distributed throughout said laminating polymer.

34. The article of claim 23, further comprising an antithrombogenic agent.

35. The article of claim 34, wherein said antithrombogenic agent is on a surface of said article.

36. The article of claim 34, wherein said antithrombogenic agent is on an interior surface of said article.

37. The article of claim 34, wherein said antithrombogenic agent is on an exterior surface of said article.

38. The article of claim 34, wherein said antithrombogenic agent is bulk distributed throughout said laminating polymer.

39. The article of claim 23, wherein said biguanide is selected from the group consisting of a chlorhexidine base and a chlorhexidine salt or mixtures thereof.

40. The article of claim 39, wherein said biguanide salt of chlorhexidine and said chlorhexidine is selected from the group consisting of the hydrochloride, acetate and gluconate salts of chlorhexidine or mixtures thereof.

41. The article of claim 23, wherein said polyurethane inner lumen comprises a polymer selected from the group consisting of polyurethane, siloxane-urethane block copolymer and polyurethaneurea.

42. The article of claim 23, wherein said laminating polymer is selected from the group consisting of polyurethane, siloxane-urethane block copolymer and polyurethaneurea.

43. The article of claim 23 which is a catheter.