ANTI-THROMBOGENIC MEDICAL DEVICES AND METHODS

• US 20150148882A1
• Filed: 11/22/2013
• Published: 05/28/2015
• 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, John, Li, Junwei
• Granted Patent: US 9,668,890 B2
• Time in Patent Office: Days
• US Class Current: 623/1.2
• 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 applying layers to medical devices and related devices are provided. Such devices can include stents. For example, the device can include a sidewall and a plurality of pores in the sidewall that are 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 tubular member is positioned in a blood vessel and adjacent to the aneurysm. The device can have an anti-thrombogenic outer layer distributed over at least a portion of the device.

Claims

1. A medical device, comprising:

an expandable tubular body comprising a plurality of braided filaments configured to be implanted in a blood vessel, the braided filaments comprising a metal selected from the group consisting of platinum, cobalt, chromium, nickel, alloys thereof, and combinations thereof;

wherein the filaments have an outer surface comprising a phosphorylcholine; and

wherein the phosphorylcholine has a thickness of less than 100 nanometers.

2. The medical device of claim 1, wherein the phosphorylcholine is 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 medical device of claim 1, wherein the phosphorylcholine comprises a copolymer having a reactive chemical group.

4. The medical device of claim 3, wherein the reactive chemical group is selected from the group consisting of amine, hydroxyl, epoxy, silane, aldehyde, carboxylate and thiol.

5. The medical device of claim 1, further comprising a silane layer between the metal and the phosphorylcholine.

6. The medical device of claim 5, wherein the silane is selected from the group consisting of 3-glycidoxypropyltrimethoxysilane, 2-(3,4-epoxycyclohexyl)ethyl-triethoxysilane, 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.

7. The medical device of claim 1, wherein the tubular body comprises (a) platinum or platinum alloy filaments, combined with (b) cobalt-chromium alloy filaments.

8. The medical device of claim 7, wherein the platinum or platinum alloy filaments possess a layer of the phosphorylcholine, and wherein the cobalt-chromium alloy filaments possess an intermediate layer between the cobalt-chromium alloy filaments and the phosphorylcholine.

9. The medical device of claim 7, wherein the phosphorylcholine, or a polymer or copolymer thereof, is chemically bonded directly to the platinum or platinum alloy filaments.

10. The medical device of claim 7, wherein the phosphorylcholine, or a polymer or copolymer thereof, is covalently bonded to the platinum or platinum alloy filaments.

11. The medical device of claim 7, wherein the phosphorylcholine, or a polymer or copolymer thereof, is chemically bonded to a silane over the cobalt-chromium alloy filaments.

12. The medical device of claim 11, wherein the phosphorylcholine, or the polymer or copolymer thereof, is covalently bonded to a silane over the cobalt-chromium alloy filaments.

13. The medical device of claim 1, wherein the tubular body comprises platinum or platinum alloy filaments.

14. The medical device of claim 13, wherein the phosphorylcholine, or a polymer or copolymer thereof, is covalently bonded to the platinum or platinum alloy filaments.

15. The medical device of claim 13, wherein the phosphorylcholine, or a polymer or copolymer thereof, is chemically bonded to the platinum or platinum alloy filaments.

16. The medical device of claim 1, wherein the tubular body has a sidewall formed by the braided filaments, the 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 tubular body is positioned in a blood vessel and adjacent to the aneurysm.

17. The medical device of claim 1, wherein the tubular body has a sidewall formed by the braided filaments, the 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.

18. The medical device of claim 1, wherein the tubular body is heat set so that the filaments are at their least-stressed configuration in the tubular body.

19. The medical device of claim 1, wherein the outer surface is an outermost surface of the filaments.

20. The medical device of claim 1, wherein the medical device comprises a stent.

21. The medical device of claim 1, wherein the phosphorylcholine has a thickness from about 1 to about 100 nanometers.

22. The medical device of claim 1, wherein the tubular body is self-expanding.

23. The medical device of claim 1, wherein the device is less thrombogenic than an identical device whose braided filaments are entirely bare metal.

24. The medical device of claim 1, wherein the device 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.

25. The medical device of claim 1, wherein the device 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.

26. The medical device of claim 8, wherein the intermediate layer comprises a silane intermediate layer.