Biocompatible cellulose dialysis membrane with increased adsorption of beta-2-microglobulin

• US 4,872,983 A
• Filed: 12/09/1988
• Issued: 10/10/1989
• Est. Priority Date: 12/11/1987
• Status: Expired due to Term

• Current Assignee: Membrana GmbH (Asahi Kasei Corporation)
• Original Assignee: AKZO NV (Nouryon BV)
• Inventors: Dimantoglou, Michael, Kuhne, Helmut
• Primary Examiner(s): Sever, Frank
• Application Number:
  US07/281,762
• Time in Patent Office: 305 Days
• Field of Search: 536/20, 210/679, 210/646, 210/647, 210/645, 210/649, 210/259, 210/321.71, 210/500.27, 210/500.28, 210/500.29, 210/500.3, 210/500.31, 210/500.32
• US Class Current: 210/500.29
• CPC Class Codes: A61L 33/0082 by reacting with an organic compound other than heparin
• CPC Class Codes: B01D 71/08 Polysaccharides
• CPC Class Codes: B01D 71/10 Cellulose; Modified cellulose
• CPC Class Codes: C08B 15/00 Preparation of other cellulose derivatives or modified cellulose , e.g. complexes
• CPC Class Codes: C08B 15/06 containing nitrogen , e.g. carbamates

Abstract

A dialysis membrane for hemodialysis with improved biocompatibility is composed of a modified cellulose which has a structure represented by the formula ##STR1## Cell is the framework of the unmodified cellulose molecule or of the chitin molecule, in each case without hydroxyl groups. Z is an atom of group V or VI (except oxygen) of the periodic system. Where Z is an atom of group V, T is a hydrogen atom or (X-Y). Where Z is an atom of group VI, T is omitted. (n+s) indicates the mean degree of substitution with 0<n<m and 0≦s<m and n+s<m. m=3 in the case of the unmodified cellulose molecule and m=2 in the case of the chitin molecule. -X- can be omitted as desired or -X- and -X'"'"'- denote specific divalent groups. -Y and -Y'"'"' denote -H and/or specified univalent radicals. X is identical to or different from X'"'"' and Y is identical to or different from Y'"'"'.

Claims

1. A dialysis membrane for hemodialysis in the form of flat films, tubular films or hollow filaments, composed of substitution-modified cellulose, wherein the modified cellulose has a molecular structure which substantially adsorbs beta- 2-microglobulin present in blood plasma and is effective to reduce carpal tunnel syndrome and is represented by the formula ##STR3## wherein:

Cell is a framework of an unmodified cellulose molecule or of a chitin molecule, in each case without hydroxyl groups;

A is selected from the group consisting of

and Z-B;

Z is an atom of group V or VI or the Periodic System other than oxygen;

In the case where Z is an atom of group V, A is

and T is a hydrogen atom or (X-Y);

in the case where Z is an atom of group VI, A is

(n+s) is the mean degree of substitution;

0<

n<

m and 0≦

s<

m and n+s<

m;

m=3 in the case of the unmodified cellulose molecule and m=2 in the case of the chitin molecule;

B is selected from the group consisting of Y and X-Y;

--X-- and --X'"'"'-- are each at least one member selected from the group consisting of a substituted or unsubstituted, straight or branched chain alkylene, alkenylene or alkynylene radical in which the carbon chain may be interrupted by hetero atoms or be CO--, CONR-- or COO--groups, a substituted or unsubstituted cycloalkylene which may contain hetero atoms, a substituted or unsubstituted arylene, arylalkylene, arylalkenylene or arylalkynlene radical which may contain hetero atoms, a substituted or unsubstituted bisarylalkylene or bisarylene radical, a substituted bisarylalkylene or bisarylene radical of a condensed aromatic compound, and a substituted or unsubstituted readical of a heterocylic compound;

--Y and --Y'"'"' are each at least one member selected from the group consisting of --H, --NR₂ --N⁺ R₃, --COOH or a salt thereof, --COOR, --CONR₂, --CO--R, --CS--R, --CSOH or a salt thereof, --CSOR, --CSNR₂, --SO₃ H or a salt thereof, --SO₃ R, --SO₂ R, --SO₂ NR₂, --SR, --SOR, --SON R₂, --PO₃ H₂ or a salt thereof, --PO(OR)₂, --PO₂ H(NR₂), --PO(NR₂)₂, --PO₂ H₂, --POH(OR), --CN, --NO₂, --OR, halogen and Si(OR)₃ ;

R is at least one member selected from the group consisting of a hydrogen atom, a straight or branched chain alkyl, alkenyl or alkynyl group having 1 to 36 atoms in which the carbon chain may be interrupted by hetero atoms or by CO--, CONR-- or COO-- groups, a substituted or unsubstituted cycloalkyl group which may contain hetero atoms, a substituted or unsubstituted aryl, arylalkyl, arylalkenyl or arylalkynyl radical which may contain hetero atoms, a substituted or unsubstituted bisarylalkyl or bisaryl radical, a substituted or unsubstituted radical or a condensed aromatic compound, and a substituted or unsubstituted radical of a heterocyclic compound;

X is identical to or different from X'"'"' and Y is identical to or different from Y'"'"'.

2. A dialysis membrane as claimed in claim 1, wherein n=0.003-2.6.

3. A dialysis membrane as claimed in claim 2, wherein n =0.005 to 0.95.

4. A dialysis membrane as claimed in claim 1, where s =0 to 0.5 n.

5. A dialysis membrane as claimed in claim 1, wherein Z is a nitrogen or a sulfur atom.

6. A dialysis membrane as claimed in claim 1, wherein X or X'"'"' is substituted with the molecular radicals Y or Y'"'"'.

7. A dialysis membrane as claimed in claim 1, wherein the modified cellulose contains at least one member selected from the group consisting of secondary, tertiary and quaternary amino groups, carboxy groups, sulfo groups, phosphonato groups and silicato groups.

8. A dialysis membrane as claimed in claim 7, wherein X-Y is at least one member selected from the group consisting of dialkylaminoalkylene, carboxyalkylene, carboxyarylalkylene, sulfurfoalkylene, sulfoarylalkylene, phosphonatoalkylene and phosphonatoarylalkylene.

9. A dialysis membrane as claimed in claim 1, wherein X-Y is silicatopropylene.

10. A dialysis membrane as claimed in claim 1, wherein said alkyl group is at least one member selected from the group consisting of ethyl, methyl and propyl.

11. A dialysis membrane as claimed in claim 1, wherein said hetero atoms are at least one number selected from the group consisting of O, S, N, P and Si.