Absorbent of .beta..sub.2 -microglobulin

• US 5,051,185 A
• Filed: 04/19/1990
• Issued: 09/24/1991
• Est. Priority Date: 11/06/1987
• Status: Expired due to Term

• Current Assignee: Asahi Medical Co. Ltd. (Asahi Kasei Corporation)
• Original Assignee: Asahi Medical Co. Ltd. (Asahi Kasei Corporation), Asahi Kasei Kogyo Kabushiki Kaisha
• Inventors: Yokoyama, Tadashi, Yamawaki, Naokuni, Watanabe, Hiroyuki
• Primary Examiner(s): JONES, WILLIAM G
• Application Number:
  US07/512,629
• Time in Patent Office: 523 Days
• Field of Search: 210/635, 210/660, 210/679, 210/690, 210/691, 210/502.1, 210/905, 210/692, 502/401, 502/402, 502/403, 502/404, 530/394, 530/412, 530/415, 530/354, 530/356, 530/811, 530/813, 530/814, 530/815, 530/413, 525/54.1, 604/4, 604/5, 604/6
• US Class Current: 210/635
• 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 20/262 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. obtained by polycondensation macromolecular compounds obtained otherwise than by reactions only involving unsaturated carbon-to-carbon bonds per se C08G
• 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 20/28004 Sorbent size or size distribution, e.g. particle size
• CPC Class Codes: B01J 20/28016 Particle form
• CPC Class Codes: B01J 20/28023 Fibres or filaments fibres or filaments in the form of membranes B01J20/28038; B01J20/28007 takes precedence
• CPC Class Codes: B01J 20/28033 Membrane, sheet, cloth, pad, lamellar or mat
• CPC Class Codes: B01J 20/28059 being less than 100 m2/g
• CPC Class Codes: B01J 20/28078 Pore diameter
• 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 20/3219 involving a particular spacer or linking group, e.g. for attaching an active group
• CPC Class Codes: B01J 20/3255 comprising a cyclic structure containing at least one of the heteroatoms nitrogen, oxygen or sulfur, e.g. heterocyclic or heteroaromatic structures
• CPC Class Codes: B01J 20/3274 Proteins, nucleic acids, polysaccharides, antibodies or antigens
• CPC Class Codes: B01J 20/3289 Coatings involving more than one layer of same or different nature
• CPC Class Codes: B01J 2220/58 Use in a single column
• CPC Class Codes: G03C 2001/0471 Isoelectric point of gelatine
• CPC Class Codes: Y10S 210/905 : Protein
• CPC Class Codes: Y10S 530/813 : Carrier is a saccharide
• CPC Class Codes: Y10S 530/815 : Carrier is a synthetic polymer

Abstract

An adsorbent for β₂ -microglobulin is disclosed, which comprises a water-insoluble carrier having supported thereon, as a ligand, at least one electrolyte selected from the group consisting of a polyamino acid, a polysaccharide, a synthetic high polymer, collagen having an isoelectric point of 9.5 or more, and gelatin having an isoelectric point of 6.5 or more, wherein said electrolyte has a molecular weight not less than 1,000 and an X value of more than 2.0, wherein X is a relationship regarding the skeleton structure of said electrolyte and is the sum of A and B, wherein A represents (the number of carbon atoms of the skeleton structure)-(the number of hydrophilic groups)/(the number of hydrophilic groups); and B represents |(the number of cationic groups)-(the number of anionic groups)|/(the number of hydrophilic groups). The adsorbent exhibits adsorptivity for β₂ -microglobulin at high efficiency and high selectivity.

Claims

1. An adsorbent for β

₂ -microglobulin which comprises a water-insoluble carrier having supported thereon, as a ligand, at least one electrolyte selected from the group consisting of a polyamino acid, a polysaccharide, a synthetic high polymer, collagen having an isoelectric point of 9.5 or more, and gelatin having an isoelectric point of 6.5 or more, wherein said electrolyte contains at least one group exhibiting a positive or negative charge in a neutral electrolytic solution and has a molecular weight of not less than 1,000 and an X value or more than 2.0, wherein X is a relationship regarding the skeleton structure of said electrolyte and is the sum of A and B, wherein A represents (the number of carbon atoms of the skeleton structure)-(the number of hydrophilic groups)/(the number of hydrophilic groups); and

B represents|(the number of cationic groups)-(the number of anionic groups)|/(the number of hydrophilic groups).

2. The adsorbent for β

₂ -microglobulin as claimed in claim 1, wherein said ligand is at least one electrolyte selected from the group consisting of a polyamino acid, a polysaccharide and a synthetic high polymer.

3. The adsorbent for β

₂ -microglobulin as claimed in claim 2, wherein said ligand has a molecular weight of from 1,000 to 1,000,000.

4. The adsorbent for β

₂ -microglobulin as claimed in claim 2, wherein said ligand has an X value of from greater than 2 but not more than 15.

5. The adsorbent for β

₂ -microglobulin as claimed in claim 2, wherein said ligand is a polyamino acid electrolyte.

6. The adsorbent for β

₂ -microglobulin as claimed in claim 5 wherein said polyamino acid electrolyte is poly(glutamic acid-alanine) or poly-(glutamic acid-alanine-tyrosine).

7. The adsorbent for β

₂ -microglobulin as claimed in claim 2, wherein said ligand is a polysaccharide electrolyte.

8. The absorbent for β

₂ -microglobulin as claimed in claim 7, wherein said polysaccharide electrolyte is diethylaminoethyl-dextran.

9. The adsorbent for β

₂ -microglobulin as claimed in claim 1, wherein said ligand is a synthetic high polymer electrolyte.

10. The adsorbent for β

₂ -microglobulin as claimed in claim 9, wherein said synthetic high polymer electrolyte is sodium sulfonated polystyrene or styrene-maleic acid copolymer.

11. The adsorbent for β

₂ -microglobulin as claimed in claim 1, wherein said water-insoluble carrier has a double-layered structure composed of a water-insoluble material having a contact angle with air bubble in water of at least 20° and

a polymer compatible with blood.

12. The adsorbent for β

₂ -microglobulin as claimed in claim 11, wherein said water-insoluble material is an organic polymer.

13. The adsorbent for β

₂ -microglobulin as claimed in claim 11, wherein said water-insoluble material has a contact angle with air bubble in water of at least 40°

.

14. The adsorbent for β

₂ -microglobulin as claimed in claim 11, wherein said polymer compatible with blood is a polymer having a nitrogen-containing basic functional group.

15. The adsorbent for β

₂ -microglobulin as claimed in claim 14, wherein said polymer having a nitrogen-containing basic functional group is 2-hydroxyethyl methacrylate-diethylaminoethyl methacrylate copolymer.

16. The adsorbent for β

₂ -microglobulin as claimed in claim 1, wherein said water-insoluble carrier is activated using an epoxide.

17. The adsorbent for β

₂ -microglobulin as claimed in claim 1, wherein said water-insoluble carrier is activated using an epichlorohydrin.

18. The adsorbent for β

₂ -microglobulin as claimed in claim 1, wherein said ligand is a collagen electrolyte.

19. The absorbent for β

₂ -microglobulin as claimed in claim 18, wherein said collagen electrolyte is methylated atelocollagen Type-I.

20. The adsorbent for β

₂ -microglobulin as claimed in claim 1, wherein said ligand is a gelatin electrolyte.

21. The adsorbent for β

₂ -microglobulin as claimed in claim 20, wherein said gelatin electrolyte is an electrolyte obtained by the heat treatment under an acidic condition of collagen obtained by treating under an acidic condition.

22. The adsorbent for β

₂ -microglobulin as claimed in claim 1, wherein said ligand is a collagen or gelatin electrolyte.

23. The adsorbent for β

₂ =microglobulin as claimed in claim 22, wherein said collagen or gelatin electrolyte has molecular weight of from 10,000 to 500,000.

24. The adsorbent for β

₂ -microglobulin as claimed in claim 22, wherein said collagen or gelatin electrolyte has an X value for from greater than 2 but not more than 25.

25. A method for cleaning or regenerating a body fluid derived from patients suffering from renal insufficiency or malignant tumor which comprises contacting said body fluid taken from the body with the adsorbent defined in claim 1, adsorbing and removing β

₂ -microglobulin at a high efficiency and with specificity, and then returning the cleaned body fluids into the body.

26. The method as claimed in claim 25, wherein said body fluid is blood, plasma, serum, ascites or hydrothorax.