Composition compatible with blood

• US 5,541,305 A
• Filed: 03/29/1995
• Issued: 07/30/1996
• Est. Priority Date: 01/16/1991
• Status: Expired due to Term

• Current Assignee: Toyoda Gosei Company Limited (Toyota Motor Corporation)
• Original Assignee: Toyoda Gosei Company Limited (Toyota Motor Corporation)
• Inventors: Yokota, Hideyuki, Tanaka, Masakazu
• Primary Examiner(s): Kunz, Gary L.
• Assistant Examiner(s): Fonda, Kathleen Kahler
• Application Number:
  US08/412,513
• Time in Patent Office: 489 Days
• Field of Search: 514/54, 514/56, 523/112, 536/21, 536/112, 536/122
• US Class Current: 536/21
• CPC Class Codes: A61L 33/0023 using a quaternized group or a protonated amine group of the substrate

Abstract

A material compatible with blood obtained by heparinizing a polymer having quarternary ammonium groups with an alkali metal salt or an alkaline earth metal salt of heparin or the analog by ion exchange is provided. The equivalent ratio (M/S) of alkali metal atoms or alkaline earth metal atoms (M) in the heparin or the analog bonded to the polymer to sulfur atoms (S) in heparin or the analog bonded to the polymer is 0.4 or less.

Claims

1. A composition compatible with blood prepared by ion exchange complexation of a polymer having quaternary ammonium groups with an alkali metal salt of a polyanion selected from the group consisting of heparin, chondroitin sulfate, dextran sulfate, and polyvinyl alcohol sulfate,

wherein said polymer having quaternary ammonium groups is prepared by quaternizing a polymer containing tertiary amino groups with a quaternizing agent, and

wherein the equivalent ratio, M/S, of alkali metal atoms (M) to sulfur atoms (S) in the composition is 0.4 or less.

2. A composition compatible with blood according to claim 1, wherein the polymer having quaternary ammonium groups is a polyurethane or polyurethaneurea having quaternary ammonium groups obtained by quaternizing the tertiary amino groups of a polyurethane or polyurethaneurea,

wherein the polyurethane or the polyurethaneurea is obtained by reacting a polyaminoetherpolyol that has at least two functional groups that react with isocyanato groups with a polyisocyanate, and

wherein the polyaminoetherpolyol is obtained by condensation of diols containing at least 30 mol % amino alcohol represented by a structure selected from the group consisting of ##STR7## wherein R₂ is an alkyl group having 1 to 15 carbon atoms.

3. A composition compatible with blood according to claim 1, wherein the polymer having quaternary ammonium groups is a polyurethane or polyurethaneurea having quaternary ammonium groups obtained by quaternizing at least a part of the tertiary amino groups in a polyurethane or polyurethaneurea with an alkyl halide or an active ester,

wherein the polyurethane or the polyurethaneurea is prepared by reacting a diisocyanate, a polysiloxane having a hydroxyl group or an amino group at one or more of its molecular termini, and a polyaminoetherpolyol having tertiary amino groups.

4. A composition compatible with blood according to claim 1, wherein the polymer having quaternary ammonium groups contains either a polyurethane or a polyurethaneurea having quaternary ammonium groups, and a polytetramethylene glycol.

5. A composition compatible with blood according to claim 2, wherein the total number of carbon atoms of two side chains bonded to a quaternary nitrogen atom of a polymer having quaternary ammonium groups is 5 to 16, in which one chain is bonded to a tertiary nitrogen atom of the polymer having tertiary amino groups and the other side chain is derived from the quaternizing agent.

6. A composition compatible with blood according to claim 1, wherein the ion exchange complexation is carried out in a mixed solvent of a water-soluble organic solvent and water.

20. A composition compatible with blood according to claim 1, wherein the polymer having quaternary ammonium groups is a film.

7. A composition compatible with blood obtained by ion exchange complexation of a polymer having quaternary ammonium groups with an alkali metal salt of a polyanion selected from the group consisting of heparin, chondroitin sulfate, dextran sulfate, and polyvinyl alcohol sulfate,

wherein the polymer is a polyurethane or a polyurethaneurea obtained by quaternizing at least a part of the tertiary amino groups in the polymer with an alkyl halide having 1 to 10 carbon atoms,

wherein the polyurethane or the polyurethaneurea is obtained by reacting a polyaminoetherpolyol that has at least two functional groups that react with isocyanato groups with a polyisocyanate, and

wherein the polyaminoetherpolyol contains, as a diol component, at least 30 mol % of an amino alcohol represented by the structure ##STR8## wherein R₁ and R₃ are independently alkyl groups with 1 to 5 carbon atoms, and R₂ is an alkyl groups with 1 to 15 carbon atoms, an aralkyl group with 7 to 15 carbon atoms, or an aryl group with 6 to 15 carbon atoms,

wherein the total number of carbon atoms of two side chains bonded to a quaternary nitrogen atom of a polymer having quaternary ammonium groups is 5 to 16, in which one chain is bonded to a tertiary nitrogen atom of the polymer having tertiary amino groups and the other side chain is derived from the quaternizing agent, and

wherein the equivalent ratio, M/S, of alkali metal atoms (H) to sulfur atoms (S) in the composition is 0.4 or less.

8. A composition compatible with blood according to claim 7, wherein the alkyl halide has 2 to 8 carbon atoms.

9. A composition compatible with blood according to claim 7, wherein the total number of carbon atoms of said two side chains bonded to a quaternary nitrogen atom of a polymer having quaternary ammonium groups is 6 to 14.

10. A composition compatible with blood according to claim 7, wherein the polyaminoetherpolyol has a molecular weight of from 200 to 8,000.

11. A composition compatible with blood according to claim 7, wherein the polyaminoetherpolyol has a molecular weight of from 500 to 4,000.

12. A composition compatible with blood according to claim 7, wherein the tertiary amino groups of the polyaminoetherpolyol precursor of the polyurethane or the polyurethaneurea are present in an amount of 0.05 to 5.00 mmol/g.

13. A composition compatible with blood according to claim 7, wherein the tertiary amino groups of the polyaminoetherpolyol precursor of the polyurethane or the polyurethaneurea are present in an amount of 0.1 to 3.0 mmol/g.

14. A composition compatible with blood according to claim 7, wherein 10% or more of the tertiary amino groups are quaternized.

15. A composition compatible with blood according to claim 7, wherein 20% or more of the tertiary amino groups are quaternized.

16. A composition compatible with blood according to claim 7, wherein the alkali metal salt of heparin is selected from the group consisting of a sodium salt of heparin and a potassium salt of heparin.

17. A composition compatible with blood according to claim 7, wherein the ion exchange complexation is carried out in a mixed solvent of a water-soluble organic solvent and water.

18. A composition compatible with blood according to claim 17, wherein the water-soluble organic solvent is tetrahydrofuran, and the ratio of the water to the tetrahydrofuran is from 20/1 to 3/7.

19. A composition compatible with blood according to claim 18, wherein the ratio of the water to the tetrahydrofuran is from 10/1 to 3/5.

21. A composition compatible with blood according to claim 7, wherein the polymer having quaternary ammonium groups is a film.