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

• US 5,707,366 A
• Filed: 06/07/1995
• Issued: 01/13/1998
• 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): Buiz, Michael Powell
• Assistant Examiner(s): Stright, Jr., Ronald K.
• Application Number:
  US08/487,796
• Time in Patent Office: 951 Days
• Field of Search: 604/264, 604/265, 604/280, 604/266, 524/916, 524/195, 523/112, 523/122, 623/12, 427/2.1-2.3, 424/78.08, 424/81, 424/83
• 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 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• 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: 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
• CPC Class Codes: C08L 75/04 Polyurethanes

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 contacting with or inserting into living tissue, comprising a polymeric base layer having a water absorption of at least 0.6% by weight and a coating thereon, said base layer having a first increment of chlorhexidine bulk distributed throughout, and said coating including a second increment of chlorhexidine.

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

3. The article of claim 2 wherein said silver sulfadiazine is on the exterior surface of said polymer.

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 polymer.

6. The article of claim 1, wherein said coating further includes an antithrombogenic agent.

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

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

9. The article of claim 1 which is a catheter.

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

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

12. The article of claim 11, wherein said antithrombogenic agent is on a surface of said polymer.

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

14. The article of claim 12, wherein said antithrombogenic agent is on an exterior surface of said article.

15. The article of claim 11, wherein said antithrombogenic agent is bulk distributed throughout said polymer.

16. The article of claim 10, wherein said biguanide is selected from the group consisting of a chlorhexidine base and a chlorhexidine salt.

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

18. The article of claim 17, wherein said polymer is a coating.

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

20. The medical article of claim 10, wherein said article further includes an antibiotic.

21. The article of claim 20, wherein said antibiotic is on a surface of said polymer.

22. The article of claim 20, wherein said antibiotic is on an interior surface of said article.

23. The article of claim 20, wherein said antibiotic is on an exterior surface of said article.

24. The article of claim 20, wherein said antibiotic is bulk distributed throughout said polymer.

25. The article of claim 10, wherein said polymer is selected from the group consisting of polyurethane, siloxane-urethane block copolymer and polyurethaneurea.

26. The article of claim 25, wherein said polymer is a coating.

27. The article of claim 10 which is a catheter.

28. A tubular medical article for contacting with or inserting into living tissue, comprising a polymeric base layer 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 base and laminating layers each having about 0.1 to 10% by weight of a biguanide bulk distributed throughout.

29. The article of claim 28, further including silver sulfadiazine.

30. The article of claim 29, wherein said silver sulfadiazine is on the exterior surface of said article.

31. The article of claim 29, wherein said silver sulfadiazine is on the interior surface of said article.

32. The article of claim 29, wherein said silver sulfadiazine is bulk distributed throughout said laminating polymer.

33. The medical article of claim 28, wherein said article further includes an antibiotic.

34. The article of claim 33, wherein said antibiotic is on a surface of said article.

35. The article of claim 33, wherein said antibiotic is on an interior surface of said article.

36. The article of claim 33, wherein said antibiotic is on an exterior surface of said article.

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

38. The article of claim 28, further comprising an antithrombogenic agent.

39. The article of claim 38, wherein said antithrombogenic agent is on a surface of said article.

40. The article of claim 38, wherein said antithrombogenic agent is on an interior surface of said article.

41. The article of claim 38, wherein said antithrombogenic agent is on an exterior surface of said article.

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

43. The article of claim 28, wherein said biguanide is selected from the group consisting of a chlorhexidine base and a chlorhexidine salt.

44. The article of claim 43, wherein said biguanide is a salt of chlorhexidine and said salt of chlorhexidine is selected from the group consisting of the hydrochloride, acetate and gluconate salts of chlorhexidine.

45. The article of claim 28, wherein said coating further comprises a second polymer having a water absorption of at least 0.6% by weight.

46. The article of claim 28, wherein said laminating polymer is selected from the group consisting of polyurethane, siloxane-urethane block copolymer and polyurethaneurea.

47. The article of claim 28 which is a catheter.