Plasma modified medical devices and methods

• US 10,016,533 B2
• Filed: 03/13/2017
• Issued: 07/10/2018
• Est. Priority Date: 08/17/2011
• Status: Active Grant

• Current Assignee: Meng Chen
• Original Assignee: Meng Chen
• Inventors: Chen, Meng
• Primary Examiner(s): Sellman, Cachet I
• Application Number:
  US15/457,575
• Publication Number:
  US 20170296708A1
• Time in Patent Office: 484 Days
• Field of Search: 427 224, 427 225, 427569, 427532, 427533, 427535, 427539
• CPC Class Codes: A61L 2300/204 with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• 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 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/022 Metals or alloys
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/0094 Physical treatment, e.g. plasma treatment
• CPC Class Codes: A61L 33/068 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L33/062 takes precedence
• CPC Class Codes: B05D 1/62 Plasma-deposition of organic layers plasma deposition in general C23C14/00, C23C16/00
• CPC Class Codes: B05D 3/148 affecting the surface properties of the coating
• CPC Class Codes: B05D 5/00 Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
• CPC Class Codes: B82Y 40/00 Manufacture or treatment of nanostructures
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C08L 83/04 Polysiloxanes
• CPC Class Codes: C23C 16/30 : Deposition of compounds, mixtures or solid solutions, e.g. borides, carbides, nitrides
• CPC Class Codes: C23C 16/56 : After-treatment
• CPC Class Codes: Y10T 428/265 : 1 mil or less
• 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, wherein long-lasting and durable bioactive agents or functional groups are deposited on the contacting surface through a unique two-step plasma coating process with deposition of a thin layer of plasma coating using a silicon-containing monomer in the first step and plasma surface modification using a mixture of nitrogen-containing molecules and oxygen-containing molecules in the second step. The two-step plasma coating process enables the implantable medical device to prevent both restenosis and thrombosis under clinical conditions. The invention also relates to surface treatment of metallic and polymeric biomaterials used for making of medical devices with significantly improved clinical performance and durability.

Claims

1. A method of making a medical device adapted for implantation into a human or animal host wherein the medical device comprises at least one contacting surface for contacting a bodily fluid or tissue, the method comprising:

(a) depositing a plasma coating of less than 100 nm thickness on the at least one contacting surface using a silicon-containing monomer selected from trimethylsilane (TMS), vinyltrichlorosilane, tetraethoxysilane, vinyltriethoxysilane, hexamethyldisilazane, tetramethylsilane, vinyldimethylethoxysilane, vinyltrimethoxysilane, tetravinylsilane, vinyltriacetoxysilane, or methyltrimethoxysilane to produce a plasma surface; and

(b) covalently bonding nitric oxide functional groups to the plasma surface using a plasma comprising a mixture of nitrogen-containing and oxygen-containing molecules.

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

3. The method of claim 1 wherein the nitrogen-containing molecules each comprise no more than four atoms.

4. The method of claim 1 wherein the nitrogen-containing molecules comprise NH₃, NH₄, N₂O, NO, NO₂, or N₂O₄.

5. The method of claim 1 wherein the oxygen-containing molecules comprise O₂ or O₃.

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

7. The method of claim 1 wherein the silicon-containing monomer is (CH₃)₃—

SiH.

8. The method of claim 1 wherein the medical device is selected from stents, catheters, balloons, shunts, grafts, valves, pacemakers, pulsed generators, cardiac defibrillators, spinal stimulators, brain stimulators, leads, screws, and sensors.

9. A method of making a medical device adapted for implantation into a human or animal host wherein the medical device comprises at least one contacting surface for contacting a bodily fluid or tissue, the method comprising:

(a) depositing a first plasma coating of less than 100 nm thickness on the contacting surface using a silicon-containing monomer selected from trimethylsilane (TMS), vinyltrichlorosilane, tetraethoxysilane, vinyltriethoxysilane, hexamethyldisilazane, tetramethylsilane, vinyldimethylethoxysilane, vinyltrimethoxysilane, tetravinylsilane, vinyltriacetoxysilane, or methyltrimethoxysilane to produce a first plasma surface; and

(b) depositing a second plasma coating on the first plasma coating using a mixture of nitrogen-containing and oxygen-containing molecules, thereby covalently bonding nitric oxide functional groups to the first plasma surface and resulting in a plasma-modified contacting surface.

10. The method of claim 9, wherein the plasma-modified contacting surface exhibits increased adhesion of at least some mammalian cells compared to a similar contacting surface that is not plasma-modified.

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

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

13. The method of claim 9, wherein the first plasma coating thickness is less than 60 nm.

14. The method of claim 9, wherein the first plasma coating thickness is less than 20 nm.

15. The method of claim 9, wherein the first plasma coating thickness is between 10 and 20 nm.

16. The method of claim 9, wherein the first plasma coating is deposited in less than about 10 minutes.

17. The method of claim 9, wherein the silicon-containing monomer is trimethylsilane (TMS).

18. The method of claim 9, wherein the plasma is fabricated by a glow discharge plasma deposition process.

19. The method of claim 9, wherein the contacting surface is a metallic or polymeric surface.

20. The method of claim 9, wherein the medical device is selected from stents, catheters, balloons, shunts, grafts, valves, pacemakers, pulsed generators, cardiac defibrillators, spinal stimulators, brain stimulators, leads, screws, and sensors.