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EP0124200A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

Heparinization of plasma treated substrates

Assignee: Becton Dickinson and Co
•
Filing: 1984-02-08
•
Granted: —
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Expires: 2004-02-08
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Abstract

Abstract Improved antithrombogenicity results when heparin is attached to a polymeric surface activated by treatment with a plasma. The surface thus activated is rendered receptive to the binding of a surface active agent. The surface active agent in turn reacts with heparin to provide a polymeric surface of exceptional antithrombogenicity when contacted with blood for an extended period of time.

Inventors

  • 👤 Joel L. Williams
  • 👤 Terry S. Dunn
  • 👤 James P. O'connell
  • 👤 David Montgomery

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-10-24 11:36
CPC Classifications
C; C08; C08J; C08J7/00; C08J7/12; C08J7/123; A; A61; A61L; A61L33/00; A61L33/0005; A61L33/0011; A61L33/0017; A61L33/0094

Claims Analysis

Total Claims: 23
Claim 1
Independent Claim 28 words
A method of reducing thrombogenicity by attaching heparin to the surface of a polymeric substrate, characterized by subjecting the substrate to a plasma treatment before attaching the heparin.
Claim 2
Independent Claim 28 words
A method of reducing thrombogenicity by attaching heparin to the surface of a polymeric substrate, characterized by subjecting the substrate to a plasma treatment before attaching the heparin.
Claim 3
Dependent Claim 33 words
A method according to Claim 1 in which the polymeric substrate comprises silicone, polyethylene, polypropylene, polyurethane, polyacrylic, polyamide, polyester, polyvinyl pyrrolidone, polyvinyl alcohol, cellulose acetate, polyvinyl chloride or polytetrafluoroethylene, preferably polytetrafluoroethylene or polyethylene.
Claim 4
Dependent Claim 31 words
:3. A method according to Claim 1 or 2 wherein the plasma is generated from a gas which comprises oxygen, ammonia, hydrogen, helium, neon, argon, krypton, xenon, nitrogen or mixtures thereof.
Claim 5
Dependent Claim 28 words
A method according to Claim 3 wherein the gas is maintained at a chamber pressure of from 10 to 300 micron of mercury during generation of the plasma.
Claim 6
Independent Claim 23 words
A method according to any preceding Claim wherein the plasma is generated using a radio frequency discharge, preferably from 1 to 50 megahertz.
Claim 7
Dependent Claim 20 words
A method according to Claim 5 wherein the plasma is generated with a power of from 10 to 200 watts.
Claim 8
Independent Claim 26 words
A method according to any preceding Claim wherein the polymeric substrate is subjected to the plasma for a period of from for 0.1 to 30 minutes.
Claim 9
Dependent Claim 50 words
A, method according to Claim 1 wherein a polytetrafluoroethylene substrate is subjected to an oxygen plasma generated by a discharge of about 50 watts at a radio frequency of about 13.56 megahertz and maintained for about 10 minutes with the oxygen at a pressure of about 180 micron of Hg.
Claim 10
Independent Claim 62 words
A method for binding heparin to a polymeric substrate comprising the sequential steps of (1) subjecting the polymeric substrate to a plasma treatment, (2) steeping the plasma treated substrate in an aqueous dispersion of a cationic surface active agent, (3) immersing the substrate in an aqueous solution of sodium heparin, and (4) treating the substrate with an aqeuous solution of a dialdehyde.
Claim 11
Independent Claim 62 words
A method for binding heparin to a polymeric substrate comprising the sequential steps of (1) subjecting the polymeric substrate to a plasma treatment, (2) steeping the plasma treated substrate in an aqueous dispersion of a cationic surface active agent, (3) immersing the substrate in an aqueous solution of sodium heparin, and (4) treating the substrate with an aqeuous solution of a dialdehyde.
Claim 12
Dependent Claim 72 words
A method according to Claim 9 in which the cationic surface active agent is a compound of the formula R 1 R 2 R 3 R 4 N + .X - , wherein R 1 is alkyl of 12 -1 8 carbon atoms, R 2 , R 3 and R are each independently selected from hydrogen and lower alkyl of 1 to 6 carbon atoms, and X is a negative monovalent ion.
Claim 13
Dependent Claim 32 words
A method according to Claim 10 wherein R 2 is lower alkyl of 1 to 6 carbon atoms, R 3 and R4 are each hydrogen and X - is halide, preferably chloride.
Claim 14
Dependent Claim 26 words
A method according to Claim 11 wherein the surface active agent comprises dodecylmethylammonium chloride, tetradecylmethylammonium chloride, hexadecylmethylammonium chloride, octadecylmethylammonium chloride or dodecylhexylammonium chloride, preferably dodecylmethylammonium chloride.
Claim 15
Independent Claim 25 words
A method according to any of Claims 9 to 12 wherein the aqueous concentration of the cationic surface active agent is from 0.01 to 2.0%.
Claim 16
Independent Claim 58 words
A method according to any of Claims 9 to 13 wherein the steeping of the substrate in the aqueous dispersion of the surface active agent is carried out for 1 to 24 hours and/or the steeping is carried out at ambient temperature or at an elevated temperature up to or slightly above the softening temperature of the substrate.
Claim 17
Independent Claim 28 words
A method according to any of Claims 9 to 14 wherein the substrate is immersed in aqueous solution of from 1 to 15 per cent of sodium heparin.
Claim 18
Independent Claim 31 words
A method according to any of claims 9 to 15 wherein the immersion is carried out at a temperature from ambient temperature to 80°C and/or for 1 hour to 24 hours.
Claim 19
Independent Claim 24 words
A method according to any of claims 9 to 16 wherein the dialdehyde contains from 2 to 6 carbon atoms and is preferably glutaraldehyde.
Claim 20
Independent Claim 38 words
A method according to any of claims 9 to 17 wherein the dialdehyde is used in an aqueous solution of from 0.01 to 5% and/or the temperature of the dialdehyde aqueous solution is from ambient temperature to 80°C.
Claim 21
Independent Claim 26 words
A method according to any of claims 9 to 18 wherein the substrate is contacted with the dialdehyde aqueous solution for from 1 to 6 hours.
Claim 22
Independent Claim 153 words
A method for reducing thrombogenicity of a substrate, the method comprising the sequential steps of: (1) subjecting a polytetrafluoroethylene substrate to an oxygen plasma wherein the plasma is generated by a discharge of about 50 watts at a radio frequency of about 13.56 megahertz, the discharge being maintained for about 10 minutes with the oxygen at a pressure of about 180 micron of Hg; (2) steeping the substrate in an aqueous solution of dodecylmethyl ammonium chloride of about 15% concentration for about 16 hours at about 65°C; (3) washing the substrate thoroughly in distilled water: (4) immersing the substrate in an aqueous solution of sodium heparin of about 9% concentration for about 16 hours at about 65°C; (5) washing the substrate thoroughly in distilled water; (6) digesting the substrate in an aqueous solution of glutaraldehyde of about 1% concentration for about 2 hours at about 60°C; (7) washing the substrate in distilled water.
Claim 23
Independent Claim 153 words
A method for reducing thrombogenicity of a substrate, the method comprising the sequential steps of: (1) subjecting a polytetrafluoroethylene substrate to an oxygen plasma wherein the plasma is generated by a discharge of about 50 watts at a radio frequency of about 13.56 megahertz, the discharge being maintained for about 10 minutes with the oxygen at a pressure of about 180 micron of Hg; (2) steeping the substrate in an aqueous solution of dodecylmethyl ammonium chloride of about 15% concentration for about 16 hours at about 65°C; (3) washing the substrate thoroughly in distilled water: (4) immersing the substrate in an aqueous solution of sodium heparin of about 9% concentration for about 16 hours at about 65°C; (5) washing the substrate thoroughly in distilled water; (6) digesting the substrate in an aqueous solution of glutaraldehyde of about 1% concentration for about 2 hours at about 60°C; (7) washing the substrate in distilled water.

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