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US5643580A Expired / Lapsed US ⏱️ 0.0 years remaining

Biocompatible coating, medical device using the same and methods

Assignee: Surface Genesis Inc
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Filing: 1994-10-17
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Granted: 1997-07-01
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Expires: 2014-10-17
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Abstract

Abstract The invention involves using a plasma to functionalize a surface of medical devices such as catheters, particularly intracardial catheters, with covalently bound thermochemically reactive groups. The surface is further contacted with a bioactive agent, particularly antithrombogenic coatings, which is thermochemically covalently coupled to the reactive group to form a therapeutically effective coating. The selected bioactive agent is then covalently bound to the surface by thermochemical reaction with the surface reactive groups. In another embodiment, the functionalizing step comprises contacting the surface with a Langmuir-Blodgett film comprising an amphipathic compound and a bioactive agent and using a plasma to covalently crosslink the Langmuir-Blodgett film to the medical device surface and to the bioactive agent. Medical devices prepared by the subject methods are also provided.

Inventors

  • 👤 Raj Subramaniam

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 22:48
CPC Classifications
A; A61; A61L; A61L33/00; A61L33/06; A61L33/12; A61L33/0005; A61L33/0011; A61L33/0076; A61L33/0094; Y; Y10; Y10S; Y10S428/00; Y10S428/922; Y10S428/9335; Y10S428/936

Claims Analysis

Total Claims: 29
Claim 1
Independent Claim 114 words
A method for treating a surface of a medical device to inhibit thrombosis comprising steps: functionalizing a surface of a medical device by contacting said surface with a low temperature plasma which surface is exposed to blood flow continuous with bodily blood circulation with a first reactive group, contacting said surface with an antithrombogenic agent capable of reacting with said first reactive group, and causing said antithrombogenic agent to react with said first reactive group to covalently bind said antithrombogenic agent to said surface to form a coating on said surface which coating is effective to inhibit the formation of thrombus when said surface is exposed to blood flow continuous with bodily blood circulation.
Claim 2
Independent Claim 114 words
A method for treating a surface of a medical device to inhibit thrombosis comprising steps: functionalizing a surface of a medical device by contacting said surface with a low temperature plasma which surface is exposed to blood flow continuous with bodily blood circulation with a first reactive group, contacting said surface with an antithrombogenic agent capable of reacting with said first reactive group, and causing said antithrombogenic agent to react with said first reactive group to covalently bind said antithrombogenic agent to said surface to form a coating on said surface which coating is effective to inhibit the formation of thrombus when said surface is exposed to blood flow continuous with bodily blood circulation.
Claim 3
Independent Claim 113 words
A method for treating a surface of a medical device to inhibit thrombosis comprising steps: contacting a surface of a medical device which surface is exposed to blood flow continuous with bodily blood circulation with a Langmuir-Blodgett film comprising an amphipathic compound; contacting said surface with an antithromobogenic agent; covalently crosslinking said antithrombogenic agent with said amphipathic compound; covalently crosslinking said amphipathic compound to said surface; to form a coating on said surface which coating is effective to inhibit the formation of thrombus when said surface is exposed to blood flow continuous with bodily blood circulation; wherein at least one of said crosslinking steps comprises contacting said surface with a low temperature plasma.
Claim 4
Independent Claim 113 words
A method for treating a surface of a medical device to inhibit thrombosis comprising steps: contacting a surface of a medical device which surface is exposed to blood flow continuous with bodily blood circulation with a Langmuir-Blodgett film comprising an amphipathic compound; contacting said surface with an antithromobogenic agent; covalently crosslinking said antithrombogenic agent with said amphipathic compound; covalently crosslinking said amphipathic compound to said surface; to form a coating on said surface which coating is effective to inhibit the formation of thrombus when said surface is exposed to blood flow continuous with bodily blood circulation; wherein at least one of said crosslinking steps comprises contacting said surface with a low temperature plasma.
Claim 5
Dependent Claim 41 words
A method according to claim 1 wherein said contacting step comprises contacting said surface with an antithrombogenic agent derivatized with a second reactive group capable of reacting with said first reactive group to covalently bind said antithrombogenic agent to said surface.
Claim 6
Dependent Claim 31 words
A method according to claim 1, wherein said contacting step comprises contacting said surface with an antithrombogenic derivatized with a label, wherein said label is capable of providing a detectable signal.
Claim 7
Dependent Claim 19 words
A method according to claim 1, wherein said contacting step comprises contacting said surface with an irreversible thrombin inhibitor.
Claim 8
Dependent Claim 19 words
A method according to claim 1, wherein said contacting step comprises contacting said surface with an reversible thrombin inhibitor.
Claim 9
Dependent Claim 17 words
A method according to claim 1, wherein said contacting step comprises contacting said surface with D-Phe-Pro-Arg-chloromethyl ketone.
Claim 10
Dependent Claim 16 words
A method according to claim 1 wherein said contacting step comprises contacting said surface with heparin.
Claim 11
Dependent Claim 23 words
A method according to claim 1 wherein said contacting step comprises contacting said surface with a polypeptide comprising the amino acid sequence Ile-Pro-Glu-Glu-Tyr-Leu-Gln.
Claim 12
Dependent Claim 23 words
A method according to claim 1 wherein said functionalizing step comprises functionalizing a surface of a catheter, stent, graft, or blood transfer device.
Claim 13
Dependent Claim 305 words
A method according to claim 1 for treating a surface of an intracardial catheter probe which is exposed to blood within a body to inhibit formation of thrombus, wherein said catheter probe is for introduction into a chamber of the heart, has proximal and distal extremities and comprises a flexible elongate tubular member having at least one lumen extending therethrough extending the length thereof and having a distal extremity, a plurality of longitudinally and radially spaced apart electrodes, expandable means secured to the distal portion of said flexible elongate tubular member and being movable between a contracted position and an expanded position, means mounting said electrodes on said expandable means whereby when said expandable means is moved to the expanded position in the chamber of the heart the electrodes are moved into engagement with the wall forming the chamber of the heart, means coupled to the expandable means for moving said expandable between said contracted and expanded positions, said expandable means including a plurality of plastic elements having surfaces exposed to the blood and said elements having spaces therebetween when in the expanded position through which the blood can flow, lead means for conducting electrical energy in contact with the electrodes and extending into said flexible elongate tubular member and electrical means connected to said lead means for performing electrical functions with respect to said electrodes, said method comprising steps: functionalizing a surface of said intracardial medical device with a first reactive group, contacting said surface with an antithrombogenic agent capable of reacting with said first reactive group, and causing said antithrombogenic agent to react with said first reactive group to covalently bind said antithrombogenic agent to said surface to form a coating on said surface which is effective to inhibit the formation of thrombus when said surface is exposed to blood within a body.
Claim 14
Dependent Claim 13 words
A method according to claim 2, wherein said coating steps are performed simultaneously.
Claim 15
Dependent Claim 13 words
A method according to claim 2, wherein said crosslinking steps are performed simultaneously.
Claim 16
Dependent Claim 41 words
A method according to claim 2, further comprising prior to said coating said surface with a Langmuir-Blodgett film: functionalizing said surface with a first reactive group capable of reacting with at least one of said amphipathic compound and said antithrombogenic agent.
Claim 17
Dependent Claim 25 words
A method according to claim 14 wherein said antithrombogenic agent is derivatized with a second reactive group capable of reacting with said first reactive group.
Claim 18
Dependent Claim 35 words
A method according to claim 1, wherein contacting said surface with an antithrombogenic agent comprises contacting said surface with an antithrombogenic derivatized with a label, wherein said label is capable of providing a detectable signal.
Claim 19
Independent Claim 192 words
A method for treating a surface of a medical device to inhibit thrombosis comprising steps: contacting an antithrombogenic agent with a surface of a medical device which surface is exposed to blood flow continuous with bodily blood circulation; thereafter causing said antithrombogenic agent to become covalently bound to said surface using a low temperature plasma; thereafter, washing said surface to remove from said surface any of said antithrombogenic agent which is not covalently bound to said surface; thereafter, contacting said surface with a reagent capable of selectively, non-covalently binding said antithrombogenic agent; causing said reagent to become selectively and noncovalently bound to said antithrombogenic agent; thereafter, washing said surface to remove from said surface any of said reagent which is not selectively bound to said antithrombogenic agent; thereafter, detecting a radiative signal at an intensity which meets or exceeds a predetermined intensity, wherein a radiative signal at said predetermined intensity correlates with the presence of coating of a predetermined amount of said antithrombogenic agent covalently bound to said surface, said coating being effective to inhibit the formation of thrombus when said surface is exposed to blood flow continuous with bodily blood circulation.
Claim 20
Independent Claim 192 words
A method for treating a surface of a medical device to inhibit thrombosis comprising steps: contacting an antithrombogenic agent with a surface of a medical device which surface is exposed to blood flow continuous with bodily blood circulation; thereafter causing said antithrombogenic agent to become covalently bound to said surface using a low temperature plasma; thereafter, washing said surface to remove from said surface any of said antithrombogenic agent which is not covalently bound to said surface; thereafter, contacting said surface with a reagent capable of selectively, non-covalently binding said antithrombogenic agent; causing said reagent to become selectively and noncovalently bound to said antithrombogenic agent; thereafter, washing said surface to remove from said surface any of said reagent which is not selectively bound to said antithrombogenic agent; thereafter, detecting a radiative signal at an intensity which meets or exceeds a predetermined intensity, wherein a radiative signal at said predetermined intensity correlates with the presence of coating of a predetermined amount of said antithrombogenic agent covalently bound to said surface, said coating being effective to inhibit the formation of thrombus when said surface is exposed to blood flow continuous with bodily blood circulation.
Claim 21
Dependent Claim 18 words
A method according to claim 17, wherein said reagent is an antibody and said radiative signal is fluorescence.
Claim 22
Independent Claim 109 words
A method for treating a surface of a medical device to provide said surface with a therapeutic coating comprising steps: functionalizing a surface of a medical device which surface is exposed to blood flow continuous with bodily blood circulation with a first reactive group using a low temperature plasma, contacting said surface with a bioactive agent capable of reacting with said first reactive group, and causing said bioactive agent to react with said first reactive group to covalently bind said bioactive agent to said surface to form a coating on said surface which coating is therapeutic when said surface is exposed to blood flow continuous with bodily blood circulation.
Claim 23
Independent Claim 109 words
A method for treating a surface of a medical device to provide said surface with a therapeutic coating comprising steps: functionalizing a surface of a medical device which surface is exposed to blood flow continuous with bodily blood circulation with a first reactive group using a low temperature plasma, contacting said surface with a bioactive agent capable of reacting with said first reactive group, and causing said bioactive agent to react with said first reactive group to covalently bind said bioactive agent to said surface to form a coating on said surface which coating is therapeutic when said surface is exposed to blood flow continuous with bodily blood circulation.
Claim 24
Independent Claim 118 words
A method for treating a surface of a medical device to provide said surface with a therapeutic coating comprising steps: contacting a surface of a medical device which surface is exposed to blood flow continuous with bodily blood circulation with a Langmuir-Blodgett film comprising an amphipathic compound; contacting said surface with an antithromobogenic agent; covalently crosslinking said bioactive agent with said amphipathic compound; covalently crosslinking said amphipathic compound to said surface; to form a coating on said surface which coating is effective to inhibit the formation of thrombus when said surface is exposed to blood flow continuous with bodily blood circulation; wherein at least one of said crosslinking steps comprises contacting said surface with a low temperature plasma.
Claim 25
Independent Claim 118 words
A method for treating a surface of a medical device to provide said surface with a therapeutic coating comprising steps: contacting a surface of a medical device which surface is exposed to blood flow continuous with bodily blood circulation with a Langmuir-Blodgett film comprising an amphipathic compound; contacting said surface with an antithromobogenic agent; covalently crosslinking said bioactive agent with said amphipathic compound; covalently crosslinking said amphipathic compound to said surface; to form a coating on said surface which coating is effective to inhibit the formation of thrombus when said surface is exposed to blood flow continuous with bodily blood circulation; wherein at least one of said crosslinking steps comprises contacting said surface with a low temperature plasma.
Claim 26
Independent Claim 191 words
A method for treating a surface of a medical device to provide said surface with a therapeutic coating comprising steps: contacting an bioactive agent with a surface of a medical device which surface is exposed to blood flow continuous with bodily blood circulation; thereafter causing said bioactive agent to become covalently bound to said surface using a low temperature plasma; thereafter, washing said surface to remove from said surface any of said bioactive agent which is not covalently bound to said surface; thereafter, contacting said surface with a reagent capable of selectively, non-covalently binding said bioactive agent; causing said reagent to become selectively and noncovalently bound to said bioactive agent; thereafter, washing said surface to remove from said surface any of said reagent which is not selectively bound to said bioactive agent; thereafter, detecting a radiative signal at an intensity which meets or exceeds a predetermined intensity, wherein a radiative signal at said predetermined intensity correlates with the presence of coating of a predetermined amount of said bioactive agent covalently bound to said surface, said coating is therapeutic when said surface is exposed to blood flow continuous with bodily blood circulation.
Claim 27
Independent Claim 191 words
A method for treating a surface of a medical device to provide said surface with a therapeutic coating comprising steps: contacting an bioactive agent with a surface of a medical device which surface is exposed to blood flow continuous with bodily blood circulation; thereafter causing said bioactive agent to become covalently bound to said surface using a low temperature plasma; thereafter, washing said surface to remove from said surface any of said bioactive agent which is not covalently bound to said surface; thereafter, contacting said surface with a reagent capable of selectively, non-covalently binding said bioactive agent; causing said reagent to become selectively and noncovalently bound to said bioactive agent; thereafter, washing said surface to remove from said surface any of said reagent which is not selectively bound to said bioactive agent; thereafter, detecting a radiative signal at an intensity which meets or exceeds a predetermined intensity, wherein a radiative signal at said predetermined intensity correlates with the presence of coating of a predetermined amount of said bioactive agent covalently bound to said surface, said coating is therapeutic when said surface is exposed to blood flow continuous with bodily blood circulation.
Claim 28
Independent Claim 117 words
A method for treating a surface of a medical device to promote thrombosis comprising steps: functionalizing a surface of a medical device by contacting said surface with a low temperature plasma which surface is exposed to blood not in continuous flow with bodily blood circulation with a first reactive group, contacting said surface with an thrombogenic agent capable of reacting with said first reactive group, and causing said thrombogenic agent to react with said first reactive group to covalently bind said thrombogenic agent to said surface to form a coating on said surface which is effective to promote the formation of thrombus when said surface is exposed to blood not in continuous flow with bodily blood circulation.
Claim 29
Independent Claim 117 words
A method for treating a surface of a medical device to promote thrombosis comprising steps: functionalizing a surface of a medical device by contacting said surface with a low temperature plasma which surface is exposed to blood not in continuous flow with bodily blood circulation with a first reactive group, contacting said surface with an thrombogenic agent capable of reacting with said first reactive group, and causing said thrombogenic agent to react with said first reactive group to covalently bind said thrombogenic agent to said surface to form a coating on said surface which is effective to promote the formation of thrombus when said surface is exposed to blood not in continuous flow with bodily blood circulation.

References Cited (Backward Citations)

US4973493A Cited
US5002582A Cited
US5217492A Cited
US5258041A Cited
US4979959A Cited
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US5324647A Cited

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3.5 Years (Year 4) 2000-06-30 2000-12-30 2001-07-01 $2000.00 Window Closed / Lapsed
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