Coating for use with medical devices and method of making same

• US 6,767,551 B2
• Filed: 08/15/2001
• Issued: 07/27/2004
• Est. Priority Date: 08/15/2001
• Status: Expired due to Term

• Current Assignee: Cardinal Health Ireland Unlimited Company (Cardinal Health, Inc.)
• Original Assignee: Sherwood Services AG
• Inventors: McGhee, Diane, Britton, Scott M., Lagwinska, Elizabeth
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Bennett, Rachel M.
• Application Number:
  US09/929,908
• Publication Number:
  US 20030044451A1
• Time in Patent Office: 1,077 Days
• Field of Search: 424/400, 424/422, 424/423, 424/426, 424/425, 424/484
• US Class Current: 424/426
• CPC Class Codes: A61L 2300/30 Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/606 Coatings
• 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: Y10T 428/31663 As siloxane, silicone or silane

Abstract

The inventive coating may be employed to deliver a pharmaceutical agent to a selected body area that is involved within the insertion or application of a medical device. Such medical devices may include silicone based urinary catheters and other medical implants as well as other silicone based devices having deformable portions which could benefit from the release of a pharmaceutical agent from its surface. The coating allows the introduction of the pharmacological additive having a release rate that is within acceptable pharmacokinetic criteria. The release rate is adjusted by utilizing different salt forms of the additive and adjusting the concentration of urethane and RTV silicone. The coating incorporates additive compounds such as anti-microbial, anti-fungals and other organic compounds. Methods are also provided for the manufacture of the subject coating and for the application of the same to surfaces of medical devices.

Claims

1. A flexible coating for a medical device, the coating comprising:

RTV silicone and urethane, wherein said RTV silicone is selected from the group consisting of methyltri-methoxy silane, methyltri-acetoxy silane, tetrachlorosilane, vinyl trimethoryl silane, organosilane ester tris[3-trimethoxysilyl)propyl] isocyanurate, bis[trimethoxysilyl)propyl] amine and gamma-ureidopropyl trimethoxy silane.

2. The flexible coating of claim 1, further comprising an additive.

3. The flexible coating of claim 2 wherein said additive is a pharmacological compound.

4. The flexible coating of claim 1 wherein said RTV silicone is methyltri-methoxy silane.

5. The flexible coating of claim 1 wherein said RTV silicone is methyltri-acetoxy silane.

6. The flexible coating of claim 1 wherein said urethane is selected from the group consisting of 4,4-methylenediphenol diisocyanante, 1,4-butanediol and polytetramethylene glycol.

7. The flexible coating of claim 1 further comprising a dye or pigment.

8. The flexible coating of claim 3 wherein said pharmacological compound is an anti-microbial selected from a group consisting of chorhexidene acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, chlorhexidine sulfate, silver acetate, silver benzoate, silver carbonate, silver iodate, silver iodide, silver lactate, silver chloride, silver laurate, silver nitrate, silver oxide, silver palmitate, silver protein, silver sulfadiazine, polymyxin, tetracycline, tobramycin, gentamicin, rifampician, bacitracin, neomycin, chloramphenical, oxolinic acid, norfloxacin, nalidix acid, pefloxacin, enoxacin and ciprofloxacin, ampicillin, amoxicillin, piracil, cephalosporins arid vancomycin.

9. The flexible coating of claim 3 wherein said pharmacological compound is an anti-fungal selected from a group consisting of tolnaftate, miconazole, fluconazole, clotrimazole, econazole, ketoconazole, itraconazole, terbinafine, amphotericin, nystatin and natamycin.

10. The flexible coating of claim 3 wherein said pharmacological compound is an phytochemical selected from a group consisting of grapefruit seed extract, tea tree oil and myrtle oil.

11. The flexible coating of claim 1 wherein said coating is flexible while allowing adhesion to deformable segments of a medical device.

12. The flexible coating of claim 3 wherein said coating further includes an emulsifier, wherein said emulsifier stabilizes in suspension said pharmaceutical additive.

13. The flexible coating of claim 12 wherein said emulsifier is selected from the group consisting of ethylene glycol disterate and ethylene glycol monosterate.

14. A flexible coating including RTV silicone and urethane for a silicone based medical device, the flexible coating being disposed on a deformable surface of the silicone based medical device and retaining adhesion to the deformable surface, wherein said RTV silicone is selected from the group consisting of methyltri-methoxy silane, methyltri-acetoxy silane, tetrachlorosilane, vinyl trimethoryl silane, organosilane ester tris[3-trimethoxysilyl)propyl] isocyanurate, bis[trimethoxysilyl)propyl] amine and gamma-ureidopropyl trimethoxy silane.

15. The flexible coating of claim 14, further comprising an additive.

16. The flexible coating of claim 15 wherein said additive is a medicinal compound.

23. The flexible coating of claim 16 wherein said medicinal compound is an anti-fungal selected from a group consisting of tolnaftate, miconazole, fluconazole, clotrimazole, econazole, ketoconazole, itraconazole, terbinafine, amphotericin, nystatin and natamycin.

24. The flexible coating of claim 16 wherein said medicinal compound is an phytochemical selected from a group consisting of grapefruit seed extract, tea tree oil and myrtle oil.

17. A flexible silicon based medical device coating comprising RTV silicone and urethane said coating being adherently disposed on a deformable surface of said device, wherein said RTV silicone is selected from the group consisting of methyltri-methoxy silane, methyltri-acetoxy silane, tetrachlorosilane, vinyl trimethoryl silane, organosilane ester tris[3-trimethoxysilyl)propyl], isocyanurate, bis[trimethoxysilyl)propyl] amine and gamma-ureidopropyl trimethoxy silane.

18. The flexible coating of claim, 17 wherein said RTV silicone is methyltri-methoxy silane.

19. The flexible coating of claim 17 wherein said RTV silicone is methyltriacetoxy silane.

20. The flexible coating of claim 17 wherein said urethane is selected from the group consisting of 4,4-methylenediphenol diisocyanante, 1,4-butanediol and polytetramethylene glycol.

21. The flexible coating of claim 17 further comprising a dye or pigment.

22. The flexible coating of claim 17 further comprising a medicinal compound, wherein said medicinal compound is an anti-microbial selected from a group consisting of chorhexidene acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, chlorhexidine sulfate, silver acetate, silver benzoate, silver carbonate, silver iodate, silver iodide, silver lactate, silver chloride, silver laurate, silver nitrate, silver oxide, silver palmitate, silver protein, silver sulfadiazine, polymyxin, tetracycline, tobramycin, gentamicin, rifampician, bacitracin, neomycin, chloramphenical, oxolinic acid, norfloxacin, nalidix acid, pefloxacin, enoxacin and ciprofloxacin, ampicillin, amoxicillin, piracil, cephalosporins and vancomycin.

25. The flexible coating of claim 17 wherein said coating further includes an emulsifier, wherein said emulsifier stabilizes in suspension said medicinal additive.

26. The flexible coating of claim 25 wherein said emulsifier is selected from the group consisting of ethylene glycol disterate and ethylene glycol monostearate.

27. The flexible coating of claim 25 wherein said coating contains between 30 to 70 percent by weight urethane, between 10 to 30 percent by weight RTV silicone, between 15 to 50 percent by weight medicinal agent and between 2 to 6 percent by weight emulsifier.

28. A method for producing a coating for a medical article comprising:

blending RTV silicone, urethane, in a solvent until dissolved, wherein said RTV silicone is selected from the group consisting of methyltri-methoxy silane, methyltri-acetoxy silane, tetrachlorosilane, vinyl trimethoryl silane, organosilane ester tris[3-(trimethoxysilyl)propyl] isocyanurate, bis[trimethoxysilyl)propyl] amine and gamma-ureidopropyl trimethoxy silane.

29. The method of claim 28 further comprising the step of blending an additive until dissolved.

30. The method of claim 29 wherein said additive is a medicinal compound.

31. The method of claim 28 wherein said RTV silicone is methyltri-methoxy silane.

32. The method of claim 28 wherein said RTV silicone is methyltriacetoxy silane.

33. The method of claim 28 wherein said solvent is selected from the group consisting of ethyl lactate, methylbenzoate, propolyacrylate and n-Methypyrrolidinone.

34. The method of claim 28 further comprising the step of blending into said coating an emulsifier wherein said emulsifier stabilizes in suspension said pharmacological compound.

35. The method of claim 28 wherein said solvent is selected from the group consisting of toluene, hexane, xylene, tetrahydrofuran and cyclohexanone.

36. The method of claim 28 wherein said solvent is selected from the group consisting of C1-12 alkylesters of carboxylic acids.

37. The method of claim 28 wherein said urethane is selected from the group consisting of 4,4-methylenediphenol diisocyanante, 1,4-butanediol and polytetramethylene glycol.

38. The method of claim 28 further comprising a medicinal compound, wherein said medicinal compound is selected from a group consisting of chorhexidene acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, chlorhexidine sulfate, silver acetate, silver benzoate, silver carbonate, silver iodate, silver iodide, silver lactate, silver chloride, silver laurate, silver nitrate, silver oxide, silver palmitate, silver protein, silver sulfadiazine, polymyxin, tetracycline, tobramycin, gentamicin, rifampician, bacitracin, neomycin, chloramphenical, quinolone, oxolinic acid, norfloxacin, nalidix acid, pefloxacin, enoxacin, ciprofloxacin, ampicillin, amoxicillin, piracil, cephalosporins and vancomycin.

39. The method of claim 30 wherein said medicinal compound is an anti-fungal selected from a group consisting of tolnaftate, miconazole, fluconazole, clotrimazole, econazole, ketoconazole, itraconazole, terbinafine, amphotericin, nystatin and natamycin.

40. The method of claim 30 wherein said medicinal compound is a phytochemical selected from a group consisting of grapefruit seed extract, tea tree oil and myrtle oil.

41. A method of controlling the release rate of a medicinal additive from a coating vehicle comprising:

providing a coating vehicle including urethane, RTV silicone and a medicinal additive, wherein said RTV silicone is selected from the group consisting of methyltri-methoxy silane, methyltri-acetoxy silane, tetrachlorosilane, vinyl trimethoryl silane, organosilane ester tris[3-(trimethoxysilyl)propyl] isocyanurate, bis[trimethoxysilyl)propyl] amine and gamma-ureidopropyl trimethoxy silane;

determining a therapeutic dosing range of the pharmacological additive;

determining pharmacokinetic properties of the pharmacological additive; and

adjusting concentration of the urethane to the RTV silicone to achieve a desired release rate.