Granted Patent B2

US 12,558,371 · App. 17/436,675 · Granted Feb 24, 2026

Inventors: Zhehui Zhao (Beijing, CN); Pingsheng Lei (Beijing, CN); Lianqiu Wu (Beijing, CN); Shuang Yang (Beijing, CN); Wenjie Wang (Beijing, CN); Haijing Zhang (Beijing, CN); Xiang Li (Beijing, CN)

Assignee: Institute of Materia Medica, Chinese Academy of Medical Sciences

A61K31/737A61P19/02C08B37/0069

Abstract

Claims (22)

1 . A metal salt of chondroitin sulfate glycan having formula (I):

which is electrically neutral, and comprises a chondroitin sulfate glycan anion and a metal cation; wherein

the chondroitin sulfate glycan anion has an average molecular weight in a range of from 4,000 Da to 15,000 Da;

the chondroitin sulfate glycan anion has a molar ratio of —SO 3 − to —COO − in a range of from 1.9 to 2.5;

n for the chondroitin sulfate glycan anion is within a range of 6≤n≤45; and

in the formula (I), at least one of the R groups at 2- and 3-positions of glucuronic acid (GlcA) is SO 3 − .

2 . The metal salt of chondroitin sulfate glycan according to claim 1 , wherein the metal cation comprises a sodium ion and/or a calcium ion and/or a potassium ion.

3 . A method for preparation of the metal salt of chondroitin sulfate glycan according to claim 1 , comprising steps of:

mixing a raw material of chondroitin sulfate glycan, a sulfating reagent, and an organic solvent for sulfation to provide a sulfation product system; and

subjecting the sulfation product system successively to a first precipitating treatment, salification treatment, dialysis, a second precipitating treatment, and gel column purification to provide the metal salt of chondroitin sulfate glycan, wherein a salifying reagent used in the salification treatment is an aqueous metal hydroxide solution wherein the raw material of chondroitin sulfate glycan comprises a chondroitin sulfate glycan A and a chondroitin sulfate glycan C; wherein the chondroitin sulfate glycan A has a content in a range of from 70% to 90% by weight, and the chondroitin sulfate glycan C has a content in the range of from 10% to 30% by weight.

4 . The method for preparation according to claim 3 , wherein

the sulfating reagent comprises one or more selected from the group consisting of sulfur trioxide trimethylamine complex, sulfur trioxide pyridine complex, and sulfur trioxide triethylamine complex; and

an equivalent ratio of the sulfating reagent to the repeating disaccharide units in the raw material of chondroitin sulfate glycan is in a range of (1-10):1.

5 . The method for preparation according to claim 4 , wherein the sulfation is performed at a temperature in a range of from 40° C. to 120° C. for a period of time of from 2 h to 36 h; and an equivalent ratio of the sulfating reagent to the repeating disaccharide units in the raw material of chondroitin sulfate glycan is in a range of (3-8):1.

6 . The method for preparation according to claim 3 , wherein the salifying reagent is an aqueous sodium hydroxide solution and/or an aqueous potassium hydroxide solution;

and the salifying reagent has a concentration in a range of from 1 mol/L to 4 mol/L.

7 . The method for preparation according to claim 3 , wherein a first precipitating reagent used in the first precipitating treatment is an aqueous ethanol solution with a volume fraction in a range of from 90% to 95%;

a second precipitating reagent used in the second precipitating treatment is ethanol; and

a dialysis bag used in the dialysis has a molecular weight cut-off in a range of from 3,000 Da to 12,000 Da.

8 . A pharmaceutical composition, wherein the pharmaceutical composition comprises the metal salt of chondroitin sulfate glycan according to claim 1 and a pharmaceutically acceptable carrier or excipient.

9 . A method for treating an inflammatory disease comprising administrating a pharmaceutical composition comprising the metal salt of chondroitin sulfate glycan according to claim 1 to a subject in need thereof.

10 . The method according to claim 9 , wherein the inflammatory disease is ulcerative colitis, osteoarthritis, or rheumatoid arthritis.

Assignments (1)

Priority Claims (1)

Continuity (1)

References Cited (24)