Anti-thrombogenic medical devices and methods

• US 10,258,486 B2
• Filed: 05/02/2017
• Issued: 04/16/2019
• Est. Priority Date: 11/22/2013
• Status: Active Grant

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: Covidien LP (Medtronic Plc)
• Inventors: Ma, Xiaodong, Sheu, Min-Shyan, Eramo, Lincoln, Wainwright, Jr., John, Li, Junwei
• Primary Examiner(s): Sellman, Cachet I
• Application Number:
  US15/584,077
• Publication Number:
  US 20170232156A1
• Time in Patent Office: 714 Days
• Field of Search: 427 224
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2/90 characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• 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 31/022 Metals or alloys
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/0088 by grafting of a monomer onto the substrate
• CPC Class Codes: A61L 33/064 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L33/062 takes precedence
• CPC Class Codes: B05D 1/18 performed by dipping
• CPC Class Codes: B05D 3/142 Pretreatment

Abstract

Methods for forming an expandable tubular body having a plurality of braided filaments including a first filament including platinum or platinum alloy and a second filament including cobalt-chromium alloy. The methods include applying a first phosphorylcholine material directly on the platinum or platinum alloy of the first filament and applying a silane material on the second filament followed by a second phosphorylcholine material on the silane material on the second filament. The first and second phosphorylcholine materials each define a thickness of less than 100 nanometers.

Claims

1. A method comprising:

forming an expandable tubular body comprising a plurality of braided filaments, wherein the expandable tubular body is configured to be implanted in a blood vessel, the plurality of braided filaments comprising a first filament comprising platinum or platinum alloy and a second filament comprising cobalt-chromium alloy;

applying a first phosphorylcholine material directly on the platinum or platinum alloy of the first filament;

applying a silane material to the second filament comprising the cobalt-chromium alloy, wherein the silane material comprises a silane selected from the group consisting of 3-glycidoxypropyltrimethoxysilane, 2-(3,4-epoxycyclohexyl)ethyltriethoxysilane, 2-(3,4-epoxycyclohexyl)ethyl-trimethoxysilane, (3-glycidoxypropyl)trimethoxysilane, (3-glycidoxypropyl)triethoxysilane, 5,6-epoxyhexyltriethoxysilane, (3-glycidoxypropyl)methyldiethoxysilane, (3-glycidoxypropyl)methyldimethoxysilane, (3-glycidoxypropyl)dimethylethoxysilane, 3-isocyanatopropyltriethoxysilane, (isocyanatomethyl)methyldimethoxysilane, 3-isocyanatopropyltrimethoxysilane, tris(3-trimethoxysilylpropyl)isocyanurate, (3-triethoxysilylpropyl)-t-butylcarbamate, triethoxysilylpropylethylcarbamate, 3-thiocyanatopropyltriethoxysilane, and combinations thereof; and

applying a second phosphorylcholine material on the silane material on the second filament,

wherein the first and second phosphorylcholine materials each define a thickness of less than 100 nanometers.

2. The method of claim 1, wherein the first and second phosphorylcholine materials are selected from the group consisting of 2-methacryloyloxyethyl phosphorylcholine, 2-acryloyloxyethyl phosphorylcholine, and phosphorylcholines based upon monomers including 2-(meth)acryloyloxyethyl-2′

-(trimethylammonio)ethyl phosphate, 3-(meth)acryloyloxypropyl-2′

-(trimethylammonio)ethyl phosphate, 4-(meth)acryloyloxybutyl-2′

-(trimethylammonio)ethyl phosphate, 5-(meth)acryloyloxypentyl-2′

-(trimethylammonio)ethyl phosphate, 6-(meth)acryloyloxyhexyl-2′

-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2′

-(triethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-2′

-(tripropylammonio) ethyl phosphate, 2-(meth)acryloyloxyethyl-2′

-(tributylammonio)ethyl phosphate, 2-(meth)acryloyloxypropyl-2′

-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxybutyl-2′

-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxypentyl-2′

-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyhexyl-2′

-(trimethylammonio)ethyl phosphate, 2-(meth)acryloyloxyethyl-3′

-(trimethylammonio)propyl phosphate, 3-(meth)acryloyloxypropyl-3′

-(trimethylammonio)propyl phosphate, 4-(meth)acryloyloxybutyl-3′

-(trimethylammonio)propyl phosphate, 5-(meth)acryloyloxypentyl-3′

-(trimethylammonio)propyl phosphate, 6-(meth)acryloyloxyhexyl-3′

-(trimethylammonio)propyl phosphate, 2-(meth)acryloyloxyethyl-4′

-(trimethylammonio)butyl phosphate, 3-(meth)acryloyloxypropyl-4′

-(trimethylammonio)butyl phosphate, 4-(meth)acryloyloxybutyl-4′

-(trimethylammonio)butyl phosphate, 5-(meth)acryloyloxypentyl-4′

-(trimethylammonio)butyl phosphate, 6-(meth)acryloyloxyhexyl-4′

-(trimethylammonio)butylphosphate, and combinations thereof.

3. The method of claim 1, wherein the first and second phosphorylcholine materials each comprise a copolymer having a reactive chemical group selected from the group consisting of amine, hydroxyl, epoxy, silane, aldehyde, carboxylate and thiol.

4. The method of claim 1, wherein the first phosphorylcholine material, or a polymer or copolymer thereof, is chemically bonded directly to the first filament.

5. The method of claim 1, wherein the first phosphorylcholine material, or a polymer or copolymer thereof, is covalently bonded to the first filament.

6. The method of claim 1, wherein the second phosphorylcholine material, or a polymer or copolymer thereof, is covalently bonded to the silane material on the second filament.

7. The method of claim 1, wherein the silane material comprises 3-glycidoxypropyltrimethoxysilane.

8. The method of claim 1, wherein forming the expandable tubular body comprises braiding the plurality of braided filaments to form a sidewall having a plurality of pores therein, the plurality of pores being sized to inhibit flow of blood through the sidewall into an aneurysm to a degree sufficient to lead to thrombosis and healing of the aneurysm when the expandable tubular body is positioned in a blood vessel and adjacent to the aneurysm.

9. The method of claim 1, wherein forming the expandable tubular body comprises braiding the plurality of braided filaments to form a sidewall having a plurality of pores therein, the plurality of pores having an average pore size that is less than or equal to 500 microns.

10. The method of claim 1, further comprising heat setting the expandable tubular body prior to applying the first or second phosphorylcholine materials.

11. The method of claim 10, wherein heat setting the expandable tubular body comprises positioning the expandable tubular body in an expanded state during the heat setting.

12. The method of claim 1, wherein the first and second phosphorylcholine materials form an outermost surface of the respective first and second filaments.

13. The method of claim 1, further comprising, prior to applying the silane material or the first phosphorylcholine material, hydroxylating at least some braided filaments of the plurality of braided filaments.

14. The method of claim 1, wherein the expandable tubular body with the first and second phosphorylcholine material applied to the first and second filaments exhibits an elapsed time before peak thrombin formation that is at least 1.5 times the elapsed time before peak thrombin formation for an identical device whose braided filaments are entirely bare metal.

15. The method of claim 1, wherein the expandable tubular body with the first and second phosphorylcholine material applied to the first and second filaments exhibits a peak thrombin concentration that is less than 0.8 times the peak thrombin concentration for an identical device whose braided filaments are entirely bare metal.

16. The method of claim 1, wherein the first and second phosphorylcholine materials each define a thickness from about 1 nanometer to about 25 nanometers.

17. The method of claim 1, wherein the first and second phosphorylcholine materials each define a thickness from about 1 nanometer to about 10 nanometers.

18. The method of claim 1, wherein the expandable tubular body comprises a self-expanding stent.

19. The method of claim 1, further comprising deploying the expandable tubular body into a blood vessel of a patient so that a sidewall of the expandable tubular body extends across a neck of an aneurysm, thereby causing thrombosis within the aneurysm.

20. The method of claim 1, wherein the first and second phosphorylcholine materials comprise 2-methacryloyloxyethyl phosphorylcholine (MPC).