MODIFIED ANTI-MICROBIAL SURFACES, DEVICES AND METHODS

• US 20110212152A1
• Filed: 12/30/2010
• Published: 09/01/2011
• Est. Priority Date: 02/28/2001
• Status: Abandoned Application

• Current Assignee: Covalon Technologies Incorporated
• Original Assignee: Covalon Technologies Incorporated
• Inventors: Ditizio, Valerio, DiCosmo, Frank
• Application Number:
  US12/982,178
• Publication Number:
  US 20110212152A1
• Time in Patent Office: Days
• US Class Current: 424/422
• CPC Class Codes: A61L 2300/104 Silver, e.g. silver sulfadiazine
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/452 Lubricants
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• 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 29/085 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: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Abstract

Methods for making modified surfaces and in particular, surfaces that may be lubricious and may be further treated to be anti-microbial are disclosed. Devices comprising modified surfaces prepared by the methods are also disclosed. An exemplary method comprises incubating a photo-initiator-coated substrate in an aqueous monomer solution that is capable of free radical polymerization, exposing the incubating substrate to ultraviolet (UV) light creating a modified surface on the substrate. An anti-microbial agent may be added to the modified surface.

Claims

1. A method for making a modified surface on a substrate comprising:

incubating a photo-initiator-coated substrate in an aqueous monomer solution capable of free radical polymerization;

exposing the incubating substrate to ultraviolet light creating a modified surface on the substrate; and

rendering the modified surface lubricious.

2. The method of claim 1, wherein the substrate comprises a polymer.

3. The method of claim 1, further comprising coating the substrate with the photo-initiator prior to the incubating.

4. The method of claim 3, wherein said coating comprises immersing the substrate in an alcoholic solution of the photo-initiator for a time sufficient for the photo-initiator to adhere to the surface of the substrate.

5. The method of claim 1, wherein the photo-initiator comprises a perester, an α

-hydroxyketone, a benzil ketal, a benzoin, any derivative thereof or any mixture thereof.

6. The method of claim 1, wherein the photo-initiator comprises 2,2-dimethoxy-2-phenyl-acetophenone, p-benzoyl tert-butylperbenzoate, benzophenone or any mixture thereof.

7. The method of claim 1, wherein said incubating comprises immersing the photo-initiator-coated substrate in the aqueous monomer solution capable of free radical polymerization.

8. The method of claim 1, wherein the aqueous monomer solution additionally comprises a photo-initiator.

9. The method of claim 8, wherein the photo-initiator comprises a perester, an α

-hydroxyketone, a benzil ketal, a benzoin, any derivative thereof or any mixture thereof.

10. The method of claim 8, wherein the photo-initiator comprises 2,2-dimethoxy-2-phenyl-acetophenone, p-benzoyl tert-butylperbenzoate, benzophenone or any mixture thereof.

11. The method of claim 1, wherein the monomer comprises acrylic acid, methacrylic acid, 2-carboxyethyl acrylate, 4-vinylbenzoic acid, itaconic acid, or any mixture thereof.

12. The method of claim 1, wherein said rendering comprises ionizing the modified surface of the substrate in an aqueous base solution so that the modified surface is negatively charged to provide a lubricious surface.

13. The method of claim 12, wherein the aqueous base has a pH of 8 or higher.

14. The method of claim 12, wherein the aqueous base comprises disodium tetraborate, sodium carbonate, ammonium hydroxide, calcium hydroxide, sodium hydroxide or any mixture thereof.

15. The method of claim 1, further comprising rendering the lubricious modified surface of the substrate anti-microbial.

16. The method of claim 15, wherein said rendering the lubricious modified surface of the substrate anti-microbial comprises incubating the substrate with the lubricious modified surface in an electrolyte solution to saturate the lubricious modified surface with cations followed by incubation with a silver salt solution.

17. The method of claim 16, wherein the silver salt comprises silver lactate, silver phosphate, silver citrate, silver acetate, silver benzoate, silver chloride, silver carbonate, silver iodide, silver iodate, silver nitrate, silver laurate, silver sulfadiazine, silver palmitate, silver salicylate, silver thiosulfate, or any mixture thereof.

18. The method of claim 16, wherein the electrolyte solution comprises sodium lactate, sodium acetate, sodium citrate, sodium benzoate, sodium salicylate, sodium thiosulfate, disodium phosphate, potassium acetate, potassium citrate, dipotassium phosphate, potassium benzoate, potassium salicylate, potassium thiosulfate or any mixture thereof.

19. The method of claim 15, wherein said rendering the lubricious modified surface of the substrate anti-microbial comprises coating the substrate with the lubricious modified surface with a polyethylene oxide hydrogel having a silver salt incorporated therein.

20. The method of claim 19, wherein the hydrogel is covalently bound to the lubricious modified surface.

21. The method of claim 19, wherein the hydrogel comprises a crosslinked matrix of gelatin and polyethylene oxide sequestering the silver salt.

22. The method of claim 21, wherein the silver salt comprises silver lactate, silver phosphate, silver citrate, silver acetate, silver benzoate, silver chloride, silver carbonate, silver iodide, silver iodate, silver nitrate, silver laurate, silver sulfadiazine, silver palmitate, silver salicylate, silver thiosulfate, or any mixture thereof.

23. The method of claim 1, wherein the substrate is provided as a medical device.

24. The method of claim 23, wherein the medical device is an implantable medical device.

25. The method of claim 24, wherein the implantable medical device comprises a dressing, a pin, a clip, a catheter, a stent, an implant, a tubing, a rod, a prosthesis, a screw, a plate, a stent, an endotracheal tube, a heart valve or a dental implant.

38. An implantable medical device comprising a substrate with a modified surface prepared according to the method of claim 1.

39. The implantable medical device of claim 38, wherein the modified surface is hydrophilic.

40. The implantable medical device of claim 38, wherein the modified surface is bio-compatible.

41. The implantable medical device of claim 38, wherein the modified surface is anti-microbial.

26. A method for making a modified surface on a substrate comprising:

coating the substrate with a photo-initiator;

incubating the photo-initiator-coated substrate in an aqueous monomer solution capable of free radical polymerization; and

exposing the incubating substrate to ultraviolet light creating a modified surface on the substrate.

27. The method of claim 26, further comprising rendering the modified surface anti-microbial.

28. The method of claim 26, wherein said rendering the modified surface anti-microbial comprising providing a silver agent to the modified surface.

29. The method of claim 28, wherein said providing a silver agent to the modified surface comprises ionizing the modified surface in an aqueous base solution so that the modified surface is negatively charged, followed by incubation with a silver salt solution.

30. The method of claim 28, wherein said providing a silver agent to the modified surface comprises coating the substrate with the modified surface with a polyethylene oxide hydrogel having a silver salt incorporated therein.

42. An implantable medical device comprising a substrate with a modified surface prepared according to the method of claim 26.

43. The implantable medical device of claim 42, wherein the modified surface is hydrophilic.

44. The implantable medical device of claim 42, wherein the modified surface is polyacrylic acid.

45. The implantable medical device of claim 42, further comprising an anti-microbial agent on the modified surface.

31. A method for making a modified surface on a substrate comprising:

coating the substrate with a photo-initiator;

incubating the photo-initiator-coated substrate in an aqueous monomer solution capable of free radical polymerization;

exposing the incubating substrate to ultraviolet light creating a modified surface on the substrate; and

rendering the modified surface anti-microbial.

32. A method for making a modified surface on a substrate comprising:

coating the substrate with a photo-initiator;

incubating the photo-initiator-coated substrate in an aqueous monomer solution capable of free radical polymerization;

exposing the incubating photo-initiator-coated substrate to ultraviolet light creating a modified surface on the substrate; and

ionizing the modified surface in an aqueous base solution so that the modified surface is negatively charged, followed by incubation with a silver salt solution.

33. A method for making a modified surface on a substrate comprising:

coating the substrate with a photo-initiator;

incubating the photo-initiator-coated substrate in an aqueous monomer solution capable of free radical polymerization;

exposing the incubating substrate to ultraviolet light creating a modified surface on the substrate; and

coating the substrate with the modified surface with a polyethylene oxide hydrogel having a silver salt incorporated therein.

34. A method for making a modified surface on a substrate comprising:

immersing a substrate in an alcoholic solution of a photo-initiator for a time sufficient for the photo-initiator to adhere to the surface of the substrate;

incubating the photo-initiator-coated substrate in an aqueous monomer solution capable of free radical polymerization;

subjecting the incubating substrate to ultraviolet (UV) light at a suitable wavelength to initiate polymerization of the monomer on the surface of the substrate, creating a modified surface on the substrate; and

rendering the modified surface anti-microbial.

35. The method of claim 34, wherein the UV wavelength is in the range of about 100 nm to about 400 nm.

36. The method of claim 34, wherein the UV wavelength is in the range of about 200 nm to about 400 nm.

37. The method of claim 34, wherein the UV wavelength is in the range of about 300 nm to about 400 nm.