Process for preparing of non-thrombogenic substrates

Claim 2

A process for the preparation of a non-thrombogenic substance comprising binding HS I to a polymer substrate having a surface, said polymer being selected from the group consisting of a biopolymer, a synthetic polymer, a copolymer thereof, and a derivative thereof; said binding of HS I to said polymer is by means selected from the group consisting of salt-bridges, covalent bonds, ionic bonds, hydrophobic interactions, hydrogen bonds, Van der Waals forces, adsorption, microencapsulation, and network enclosure; and wherein HS I is a specific endothelial cell surface proteo polysaccharide produced by the cell and having three to four polysaccharide side-chains which have a molecular weight of about 35,000 each, and a central protein core of a molecular weight of about 55,000, said polysaccharide side-chains having no interaction with blood coagulation factors and no other biological activity as observed for a substance selected from the group consisting of glycosaminoglycans, heparins, and heparan sulfates.

Claim 3

A process according to claim 1 comprising binding said HS I to said polymer substrate by said protein core of the HS I.

Claim 4

A process according to claim 1, comprising covalently binding said HS I to said polymer.

Claim 5

A process according to claim 1, comprising activating said HS I and then binding it to said polymer substrate, or activating said polymer substrate and then binding said HS I to the polymer substrate, or activating said HS I and activating said polymer substrate and then binding HS I to the polymer substrate.

Claim 6

A process according to claim 1, wherein binding of said HS I to said polymer occurs directly by participation of functional groups of the polymer substrate and HS I or with bifunctional molecules which bind to HS I and to the polymer substrate thereby linking said HS I to said polymer and which have a distance between the HS I binding site and the polymer binding site within the bifunctional molecule ranging from 0.2 to 5 nm.

Claim 7

A process according to claim 1, wherein said polymer has a backbone; and said ionic bonds occur by direct involvement of charged groups of said HS I and charged groups of said polymer, or by participation of charged substances which form ionic bonds to the polymer and to HS I thereby linking HS I to the polymer and which have a distance between the HS I binding site and the polymer binding site within the charged substance ranging from 0.15 to 200 nm.

Claim 8

A process according to claim 1, wherein said polymer has a backbone and carries covalently linked side chains of a length between 0.15 to 200 nm with charged groups and wherein said ionic bonds occur by direct interaction of charged groups of said HS I and charged groups of the polymer side chains.

Claim 9

A process according to claim 1, comprising first binding HS I to the charged groups, of a hydrophobic chain molecule of a length between 0.15 and 200 nm and then binding the so modified HS I to hydrophobic parts of the polymer substrate.

Claim 10

A process according to claim 1, comprising binding said HS I to a polymer substrate by ionic bonds, hydrophobic interactions, hydrogen bonds, and Van der Waals forces and then covalently binding HS I to the polymer by participation of functional groups of HS I and the polymer.

Claim 11

A process according to claim 1, comprising: covalently binding HS I to vinyl monomer to form HS I - vinyl monomer and then copolymerizing said HS I - vinyl monomer together with vinyl monomer.

Claim 12

A process according to claim 1, wherein the concentration of HS I is of 1 μg-1000 μg per square centimeter polymer surface.

Claim 13

A process for the preparation of a non-thrombogenic substance comprising: binding HS I to a polymer substrate having a surface, said polymer being selected from the group consisting of a bipolymer, a synthetic polymer, a copolymer thereof, and a derivative thereof; said binding being about 0.01-100 μg HS I per square centimeter covalently to said polymer surface and wherein between 1 and 80 covalent binding places or cross-linking bridges between HS I and said polymer exist; and wherein HS I is a specific endothelial cell surface proteo polysaccharide produced by the cell and having three to four polysaccharide side-chains which have a molecular weight of about 35,000 each, and a central protein core of a molecular weight of about 55,000, said polysaccharide side-chains having no interaction with blood coagulation factors and no other biological activity as observed for a substance selected from the group consisting of glycosaminoglycans, heparins, and heparan sulfates.

Claim 14

A process for the preparation of a non-thrombogenic substance comprising: binding HS I to a polymer substrate having a surface, said polymer being selected from the group consisting of a bipolymer, a synthetic polymer, a copolymer thereof, and a derivative thereof; said binding being about 0.01-100 μg HS I per square centimeter covalently to said polymer surface and wherein between 1 and 80 covalent binding places or cross-linking bridges between HS I and said polymer exist; and wherein HS I is a specific endothelial cell surface proteo polysaccharide produced by the cell and having three to four polysaccharide side-chains which have a molecular weight of about 35,000 each, and a central protein core of a molecular weight of about 55,000, said polysaccharide side-chains having no interaction with blood coagulation factors and no other biological activity as observed for a substance selected from the group consisting of glycosaminoglycans, heparins, and heparan sulfates.

Claim 15

A process for the preparation of a non-thrombogenic substance comprising: binding HS I to a polymer substrate having a surface, said polymer being selected from the group consisting of a biopolymer, a synthetic polymer, a copolymer thereof, and a derivative thereof; wherein HS I is a specific endothelial cell surface proteo polysaccharide produced by the cell and having three to four polysaccharide side-chains which have a molecular weight of about 35,000 each, and a central protein core of a molecular weight of about 55,000, said polysaccharide side-chains having no interaction with blood coagulation factors and no other biological activity as observed for a substance selected from the group consisting of glycosaminoglycans, heparins, and heparan sulfates; and wherein said binding comprises binding said HS I polysaccharide chain covalently to the polymer substrate.

Claim 16

A process for the preparation of a non-thrombogenic substance comprising: binding HS I to a polymer substrate having a surface, said polymer being selected from the group consisting of a biopolymer, a synthetic polymer, a copolymer thereof, and a derivative thereof; wherein HS I is a specific endothelial cell surface proteo polysaccharide produced by the cell and having three to four polysaccharide side-chains which have a molecular weight of about 35,000 each, and a central protein core of a molecular weight of about 55,000, said polysaccharide side-chains having no interaction with blood coagulation factors and no other biological activity as observed for a substance selected from the group consisting of glycosaminoglycans, heparins, and heparan sulfates; and wherein said binding comprises binding said HS I polysaccharide chain covalently to the polymer substrate.

Claim 17

In a process for providing a substrate having a surface for being contacted by blood, the improvement which comprises utilizing the non-thrombogenic substance as said substrate, which is prepared by a process for the preparation of a non-thrombogenic substance comprising: binding HS I to a polymer substrate having a surface, said polymer being selected from the group consisting of a biopolymer, a synthetic polymer, a copolymer thereof, and a derivative thereof; said binding of HS I to said polymer by means is selected from the group consisting of salt-bridges, covalent bonds, ionic bonds, hydrophobic interactions, hydrogen bonds, Van der Waals forces, adsorption, microencapsulation, and network enclosure; and wherein HS I is a specific endothelial cell surface proteo polysaccharide produced by the cell and having three to four polysaccharide side-chains which have a molecular weight of about 35,000 each, and a central protein core of a molecular weight of about 55,000, said polysaccharide side-chains having no interaction with blood coagulation factors and no other biological activity as observed for a substance selected from the group consisting of glycosaminoglycans, heparins, and heparan sulfates.

Claim 18

In a process for providing a substrate having a surface for being contacted by blood, the improvement which comprises utilizing the non-thrombogenic substance as said substrate, which is prepared by a process for the preparation of a non-thrombogenic substance comprising: binding HS I to a polymer substrate having a surface, said polymer being selected from the group consisting of a biopolymer, a synthetic polymer, a copolymer thereof, and a derivative thereof; said binding of HS I to said polymer by means is selected from the group consisting of salt-bridges, covalent bonds, ionic bonds, hydrophobic interactions, hydrogen bonds, Van der Waals forces, adsorption, microencapsulation, and network enclosure; and wherein HS I is a specific endothelial cell surface proteo polysaccharide produced by the cell and having three to four polysaccharide side-chains which have a molecular weight of about 35,000 each, and a central protein core of a molecular weight of about 55,000, said polysaccharide side-chains having no interaction with blood coagulation factors and no other biological activity as observed for a substance selected from the group consisting of glycosaminoglycans, heparins, and heparan sulfates.

Claim 19

The process according to claim 14, wherein the concentration of HS I is of 1 μg-1000 μg per square centimeter polymer surface.