Plasma-deposited coatings, devices and methods

• US 6,613,432 B2
• Filed: 12/21/2000
• Issued: 09/02/2003
• Est. Priority Date: 12/22/1999
• Status: Expired due to Term

• Current Assignee: Biosurface Engineering Technologies, Inc. (Ferring Holding SA)
• Original Assignee: Biosurface Engineering Technologies, Inc. (Ferring Holding SA)
• Inventors: Chen, Meng, Zamora, Paul O., Osaki, Shigemasa
• Primary Examiner(s): Nakarani, D. S.
• Application Number:
  US09/746,234
• Publication Number:
  US 20020009604A1
• Time in Patent Office: 985 Days
• Field of Search: 427/2.24, 427/539, 428/409, 428/457, 428/469, 428/544, 428/685
• US Class Current: 428/409
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 29/08 Materials for coatings
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 33/0082 by reacting with an organic compound other than heparin
• CPC Class Codes: A61L 33/0088 by grafting of a monomer onto the substrate
• CPC Class Codes: C23C 16/0245 by etching with a plasma
• CPC Class Codes: Y10T 428/12 All metal or with adjacent metals
• CPC Class Codes: Y10T 428/12979 Containing more than 10% nonferrous elements [e.g., high alloy, stainless]
• CPC Class Codes: Y10T 428/31 Surface property or characteristic of web, sheet or block
• CPC Class Codes: Y10T 428/31663 As siloxane, silicone or silane
• CPC Class Codes: Y10T 428/31667 Next to addition polymer from unsaturated monomers, or aldehyde or ketone condensation product
• CPC Class Codes: Y10T 428/31678 Of metal

Abstract

Coatings, devices and methods are provided, wherein the contacting surface of a medical device with at least one contacting surface for contacting a bodily fluid or tissue is modified by plasma treatment in a plasma comprising nitrogen-containing molecules and oxygen-containing molecules. The nitrogen-containing molecules include NH₃, (NH₄)⁺, N₂O, NO, NO₂ and N₂O₄, and the oxygen-containing molecules include O₂ and O₃. The plasma-modified contacting surface exhibits decreased adhesion of at least some mammalian cells, such as platelets and leukocytes, decreased restenosis when used with stents, and increased apoptosis. Additional layers may be applied, including plasma polymerized hydrocyclosiloxane monomers, amine-providing groups such as N-trimethylsilyl-allylamine, polyoxyalkylene tethers, and bioactive compounds.

Claims

1. An implantable medical device with a plasma-modified surface, comprising

structure adapted for implantation into a patient, the structure comprising at least one metallic contacting surface for contacting a bodily fluid or tissue, wherein the metallic contacting surface is modified by plasma treatment in a plasma comprising nitrogen-containing molecules and oxygen-containing molecules.

2. The device of claim 1, wherein the nitrogen-containing molecules each comprise no more than six atoms.

3. The device of claim 2, wherein the nitrogen-containing molecules each comprise four or fewer atoms.

4. The device of claim 1, wherein the nitrogen-containing molecules are molecules selected from the group consisting of NH₃, (NH₄)⁺, N₂O, NO, NO₂ and N₂O₄.

5. The device of claim 1, wherein the oxygen-containing molecules are molecules selected from the group consisting of O₂ and O₃.

6. The device of claim 1, wherein the plasma treatment with the nitrogen-containing molecules and the oxygen-containing molecules is simultaneous.

7. The device of claim 1, wherein the plasma-modified contacting surface exhibits decreased adhesion of at least some mammalian cells, compared to a similar contacting surface that is not plasma-modified.

8. The device of claim 7, wherein the mammalian cells are cells selected from the group consisting of platelets and leukocytes.

9. The device of claim 1, wherein the medical device is a stent and wherein the at least one contacting surface comprises the lumen of the stent.

10. The device of claim 9, wherein the plasma-modified contacting surface comprising the lumen of the stent exhibits decreased restenosis subsequent to placement in a blood vessel, compared to a similar stent that is not plasma-modified.

11. The device of claim 1, wherein the plasma treatment is for less than about five minutes.

12. The device of claim 11, wherein the plasma treatment is for less than about two minutes.

13. The device of claim 11, wherein the plasma treatment is for less than about one minute.

14. The device of claim 11, wherein the plasma treatment is for between about thirty seconds and about one minute.

15. The device of claim 1, wherein the plasma treatment is of a plasma wherein the nitrogen-containing molecules are NH₃ and the oxygen-containing molecules are O₂.

16. The device of claim 15, wherein the mass flow rate during plasma treatment of each of NH₃ and of O₂ is a between a ratio of about 1.5:

1 and about 1;

1.5.

17. The device of claim 1, wherein the plasma treatment is of a plasma wherein the nitrogen-containing molecules are N₂O and the oxygen containing molecules are O₂.

18. The device of claim 17, wherein the mass flow rate during plasma treatment of each or N₂O and of O₂ is between a ratio of about 1.5:

1 and about 1;

1.5.

19. The implantable medical device of claim 1, where the implantable medical device is a member selected from the group comprising stents, catheters, balloons, shunts, grafts, valves, pacemakers, pulse generators, cardiac defibrillators, spinal stimulators, brain stimulators, sacral nerve stimulators, leads, inducers, sensors, seeds, screws, anchors, anti-adhesion sheets, plates and joints.

20. A method of imparting bioactive properties to a contacting surface for contacting a bodily fluid or tissue of an implantable medical device, comprising

providing a structure adapted for implantation into a patient, the structure comprising a metallic contacting surface for contacting a bodily fluid or tissue;

and

modifying the metallic contacting surface by plasma treatment with a plasma comprising nitrogen-containing molecules and oxygen-containing molecules.

21. The method of claim 20, wherein the nitrogen-containing molecules comprise no more than six atoms.

22. The method of claim 21, wherein the nitrogen-containing molecules comprises four or fewer atoms.

23. The method of claim 21, wherein the nitrogen-containing molecules are molecules selected from the group consisting of NH₃, (NH₄)⁺, N₂O, NO, NO₂ and N₂O₄.

24. The method of claim 20, wherein the oxygen-containing molecules are selected from the group consisting of O₂ and O₃.

25. The method of claim 20, wherein the plasma treatment with the nitrogen-containing molecules and the oxygen-containing molecules is simultaneous.

26. The method of claim 20, wherein the plasma treatment is for less than about five minutes.

27. The method of claim 26, wherein the plasma treatment is for less than about two minutes.

28. The method of claim 26, wherein the plasma treatment is for less than about one minute.

29. The method of claim 26, wherein the plasma treatment is for between about thirty seconds and about one minute.

30. The method of claim 20, wherein the plasma treatment is of a plasma wherein the nitrogen-containing molecules are NH₃ and the oxygen-containing molecules are O₂.

31. The method of claim 30, wherein the mass flow rate during plasma treatment with each of NH₃ and of O₂ is between a ratio of about 1.5:

1 and about 1;

1.5.

32. The method of claim 20, wherein the plasma treatment is with a plasma wherein the nitrogen-containing molecules are N₂O and the oxygen-containing molecules are O₂.

33. The method of claim 32, wherein the mass flow rate during plasma treatment with each of N₂O and of O₂ is between a ratio of about 1.5:

1 and about 1;

1.6.

34. The method of claim 20, wherein the bioactive properties comprise inhibiting adhesion of mammalian calls.

35. The method of claim 34, wherein the mammalian cells are cells selected from the group consisting of platelets and leukocytes.

36. The method of claim 20, wherein the bioactive properties comprise increased apoptosis of mammalian cells.

37. The method of claim 20, wherein the bioactive properties comprise decreased restenosis.