Process for preparing surface modification substances
First Claim
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1. A method for producing a substrate surface modification having an improved non-thrombogenic activity comprising at least the step of reacting:
- (A) functional groups on a surface to be rendered non-thrombogenic, with (B) heparin, modified to contain complementary functional groups, so as to form covalent bonds, wherein said heparin is activated to enhance its activity when surface bound, in a step before reacting (A) with (B), through a procedure selected from the group consisting of;
(i) heating in a solvent in the range from 40°
C. to the boiling temperature of the solvent;
(ii) treatment at a pH in the range of 9-14; and
(iii) treatment with at least one nucleophilic catalyst.
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Abstract
The present invention relates to a process for preparing surface modifications having an improved antithrombogenic activity, whereby the improvement is achieved by treating heparin at a temperature above 40° C. or a pH in the rage of 9-14 or in contact with nucleophilic catalysts before attaching said heparin to the surface to be modified.
116 Citations
10 Claims
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1. A method for producing a substrate surface modification having an improved non-thrombogenic activity comprising at least the step of reacting:
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(A) functional groups on a surface to be rendered non-thrombogenic, with (B) heparin, modified to contain complementary functional groups, so as to form covalent bonds, wherein said heparin is activated to enhance its activity when surface bound, in a step before reacting (A) with (B), through a procedure selected from the group consisting of;
(i) heating in a solvent in the range from 40°
C. to the boiling temperature of the solvent;
(ii) treatment at a pH in the range of 9-14; and
(iii) treatment with at least one nucleophilic catalyst. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
(A);
(a) adding a layer of a polymer comprising amino groups to the surface to be modified, (b) optionally cross-linking the layer of step (a) with a bifunctional cross-linking agent, (c) adding a layer of an anionic polymer to the layer of step (b), (d) optionally repeating the steps (a), (b) and (c) at least one time, (e) followed by a final step (a), and (B);
(f) modifying heparin through nitrous acid or periodate oxidation to comprise aldehyde groups, (g) activating the aldehyde containing heparin in a further step to enhance its activity when surface bound, said activating step (g) being selected from the group consisting of;
(i) heating in a solvent in the range from 40°
C. to the boiling temperature of the solvent;
(ii) treatment at a pH in the range of pH 9-14; and
(iii) treatment with at least one nucleophilic catalyst, and finally (h) reacting the layer resulting from step (a) or (e) with the further treated aldehyde heparin from step (g).
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8. A surface modified substrate produced according to claim 2.
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9. A method according to claim 2, which comprises forming a layer on the surface by
(A): -
(a) adding a layer of a polymer comprising amino groups to the surface to be modified, (b) optionally cross-linking the layer of step (a) with a bifunctional cross-linking agent, c) adding a layer of an anionic polymer to the layer of step (b), (d) optionally repeating the steps (a), (b) and (c) at least one time, (e) followed by a final step (a), and (B);
(f) modifying heparin through nitrous acid or periodate oxidation to comprise aldehyde groups, (g) activating the aldehyde containing heparin in a further step to enhance its activity when surface bound, said activating step (g) being selected from the group consisting of;
(i) treatment at a pH in the range of pH 9-14;
(ii) treatment with at least one nucleophilic catalyst; and
(iii) heating in the range from 40°
C. to the boiling temperature of the solvent in combination with step (i) and/or step (ii).
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10. A method for producing a substrate surface modification having an improved non-thrombogenic activity comprising at least the step of reacting
(A) functional groups on a surface to be rendered non-thrombogenic, with (B) heparin, modified to contain complementary functional groups, so as to form covalent bonds, wherein said heparin is activated to enhance its activity when surface bound, in a step before reacting (A) with (B), through a procedure selected from the group consisting of: -
(i) treatment at a pH in the range of pH 9-14;
(ii) treatment with at least one nucleophilic catalyst; and
(iii) heating in the range from 40°
C. to the boiling temperature of the solvent in combination with step (i) and/or step (ii).
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Specification