Method of removing beta-2 microglobulin from blood

• US 5,904,663 A
• Filed: 07/30/1997
• Issued: 05/18/1999
• Est. Priority Date: 07/30/1997
• Status: Expired due to Term

• Current Assignee: Donald Brodie, RenalTech International LLC, Stefan Brodie
• Original Assignee: Advanced Renal Technologies Inc,
• Inventors: Davankov, Vadim, Braverman, Andrew
• Primary Examiner(s): Weiss, John G.
• Assistant Examiner(s): O YONG, KI
• Application Number:
  US08/902,727
• Time in Patent Office: 657 Days
• Field of Search: 604/4-6, 502/400-402, 521/30-32, 521/33, 521/73-75, 525/332.2, 428/394
• US Class Current: 604/5.01
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61M 2202/0057 retained by adsorption
• CPC Class Codes: A61M 2202/0421 Beta-2-microglobulin
• CPC Class Codes: B01J 20/261 obtained by reactions only involving carbon to carbon unsaturated bonds macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F
• CPC Class Codes: B01J 20/264 derived from different types of monomers, e.g. linear or branched copolymers, block copolymers, graft copolymers
• CPC Class Codes: B01J 20/267 Cross-linked polymers
• CPC Class Codes: B01J 20/28019 Spherical, ellipsoidal or cylindrical
• CPC Class Codes: B01J 20/2808 being less than 2 nm, i.e. micropores or nanopores
• CPC Class Codes: B01J 20/28085 being more than 50 nm, i.e. macropores
• CPC Class Codes: B01J 20/3092 Packing of a container, e.g. packing a cartridge or column of chromatography columns B01D15/206
• CPC Class Codes: B01J 20/321 consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3217 Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond
• CPC Class Codes: B01J 20/3221 the chemical bond being an ionic interaction
• CPC Class Codes: B01J 20/3272 Polymers obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3274 Proteins, nucleic acids, polysaccharides, antibodies or antigens
• CPC Class Codes: B01J 20/3276 Copolymers
• CPC Class Codes: B01J 20/3278 Polymers being grafted on the carrier
• CPC Class Codes: B01J 2220/58 Use in a single column
• CPC Class Codes: B01J 2220/62 In a cartridge

Abstract

A method of removing beta-2 microglobulin from blood has the steps of removing blood from a patient, passing the blood through a material with a size and a structure selected so as to remove beta-2 microglobulin from the blood, and re-entering the blood from which the beta-2 microglobulin is removed into the patient.

Claims

1. A method of removing beta-2 microglobulin from blood, comprising the steps of removing blood from a patient, passing the blood through a material with a size and a structure selected so as to remove beta-2 microglobulin from the blood, re-entering the blood from which the beta-2 microglobulin is removed into the patient, wherein said material includes a hypercrosslinked polystyrene-type resins with surface of the beads modified so as to prevent absorption of large proteins and platelet and to minimize activation of blood complement system without affecting noticeably accessibility of an inner absorption space of the beads for small and middle-sized toxicant molecules.

2. A method as defined in claim 1, wherein said beads are modified beads of styrene-divinylbenzene copolymers subjected to an extensive crosslinking in a swollen state with bifunctional crosslinking agents.

3. A method as defined in claim 2, wherein said bifunctional crosslinking agent is an agent selected from the group consisting of monochlorodimethyl ether and p-xylylene dichloride.

4. A method as defined in claim 1, wherein said beads are modified beads of styrene-divinylbenzene copolymers subjected to chloromethylation and post-crosslinking.

5. A method as defined in claim 1, wherein said modifying includes depositing on the surface of the beads high molecular weight poly(N-trifluoroalkoxy) phosphazene, by treating the beads with a solution of phosphazene in an organic solvent and evaporating the solvent.

6. A method as defined in claim 1, wherein said modifying includes electrostatically binding of heparin from its aqueous solution onto the beads whose chloromethyl groups have been substituted by amino functions through a reaction with an amine.

7. A method as defined in claim 6, wherein said amine is 2-ethanol amine.

8. A method as defined in claim 1, wherein said modifying includes substituting chloromethyl groups on the surface of the beads with 2-ethanol amine ligands and covalently binding heparin to the ligands via a material selected from the group consisting of a glutare dialdehyde and hexamethylene diisocyanate moiety and coupling groups selected from the group consisting of excessive pendant aldehyde groups and isocyanate groups with L-aspartic acid.

9. A method as defined in claim 1, wherein said modifying includes substituting chloromethyl groups with a material selected from the group consisting of 2-ethanol amine and ethylene glycol ligands, activating the ligands with a material selected from the group consisting of glutare dialdehyde and hexamethylene diisocynate, and covalently binding hydrophilic polyethylene glycol chains.

10. A method as defined in claim 1, wherein said modifying includes covalently binding hydrophilic polyethylene glycol chains through reacting of sodium alcoholates of the latter with polystyrene chloromethyl groups.

11. A method as defined in claim 1, wherein said modifying includes covalently binding hydrophilic chains of chitosan through reacting of amino groups of the latter with polystyrene chloromethyl groups.

12. A method as defined in claim 1, wherein said modifying includes substituting chloromethyl groups with ligands selected from the group consisting of 2-ethanol amine ligands or ethylene glycol ligands, activating the ligands with phosphorus oxychloride, and covalently binding hydrophilic moieties selected from the group consisting of choline, serine and 2-ethanol amine.

13. A method as defined in claim 1, wherein said passing includes passing through the material which is a porous hydrophobic acrylic polymer.

14. A method as defined in claim 1, wherein said passing includes passing through a material which is a mesoporous ethylstyrene-divinylbenzene copolymer.