Anti-thrombogenic medical devices and methods
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.
1. A medical device, comprising:
an expandable tubular body comprising a plurality of braided filaments configured to be implanted in a blood vessel, the plurality of braided filaments comprising:
a first filament comprising platinum or platinum alloy and a first coating comprising a first phosphorylcholine applied directly on the first filament; and
a second filament comprising cobalt-chromium alloy, a second coating comprising a second phosphorylcholine, and a silane layer between the second filament and the second coating;
wherein the first and second coatings each define a thickness of less than 100 nanometers; and
wherein the silane layer 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.
2. The medical device of claim 1 , wherein the first and second phosphorylcholines 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 medical device of claim 1 , wherein the first and second phosphorylcholines comprise 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 , wherein the silane layer comprises 3-glycidoxypropyltrimethoxysilane.
6. The medical device of claim 1 , wherein the first phosphorylcholine, or a polymer or copolymer thereof, is chemically bonded directly to the first filament.
7. The medical device of claim 1 , wherein the first phosphorylcholine, or a polymer or copolymer thereof, is covalently bonded to the first filament.
8. The medical device of claim 1 , wherein the second phosphorylcholine, or a polymer or copolymer thereof, is covalently bonded to the silane layer on the second filament.
9. The medical device of claim 1 , wherein the expandable tubular body has a sidewall formed by the plurality of 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 expandable tubular body is positioned in a blood vessel and adjacent to the aneurysm.
10. The medical device of claim 1 , wherein the expandable tubular body has a sidewall formed by the plurality of 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.
11. The medical device of claim 1 , wherein the expandable tubular body is heat set so that the plurality of braided filaments are at their least-stressed configuration in the expandable tubular body.
12. The medical device of claim 1 , wherein the first and second coatings form an outermost surface of the respective first and second filaments.
13. The medical device of claim 1 , wherein the medical device comprises a stent.
14. The medical device of claim 1 , wherein the expandable tubular body is self-expanding.
15. The medical device of claim 1 , wherein the medical device is less thrombogenic than an identical device whose braided filaments are entirely bare metal.
16. The medical device of claim 1 , wherein the medical 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.
17. The medical device of claim 1 , wherein the medical 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.
18. The medical device of claim 1 , wherein the first and second coatings each define a thickness from about 1 nanometer to about 25 nanometers.
19. The medical device of claim 1 , wherein the first and second coatings each define a thickness from about 1 nanometer to about 10 nanometers.