Glycosaminoglycan derivative and method for producing same

Abstract

The present invention provides a glycosaminoglycan derivative in which a group derived from glycosaminoglycan and a group derived from a physiologically active substance having at least one of a carboxy group and a hydroxy group are coupled by covalent bond with a spacer therebetween, in which the spacer is selected in accordance with the decomposition rate of the covalent bond to the group derived from the physiologically active substance.

1 . A method for suppressing pain, the method comprising administering a pharmaceutical composition to a living body,
 wherein the pharmaceutical composition comprises:   a group derived from glycosaminoglycan,   a group derived from a physiologically active substance, and   a spacer which couples the group derived from glycosaminoglycan to the group derived from the physiologically active substance by a covalent bond,   wherein the glycosaminoglycan is at least one selected from the group consisting of a chondroitin sulfate, and a derivative thereof,   wherein the physiologically active substance is selected from a group consisting of a nonsteroidal anti-inflammatory drug and a steroid, and the group derived from the physiologically active substance and the spacer are covalently bonded through an ester bond,   wherein the glycosaminoglycan has a carboxy group, a molecule for forming the spacer has an amino group corresponding to the carboxy group of the glycosaminoglycan, and the group derived from glycosaminoglycan and the spacer are covalently bonded through an amide bond,   wherein the molecule for forming the spacer has a coupling group which may have one or more substituent and couples the carboxy group and the amino group and the length of the coupling group between the carboxy group and the amino group is 2 to 12 atoms, and   wherein a dissociation rate of the physiologically active substance from the glycosaminoglycan derivative is 0.1 to 20%/day in a phosphate buffered saline with pH of 7.5 at 36° C.   
     
     
         2 . The method according to  claim 1 , wherein the dissociation rate of the physiologically active substance from the glycosaminoglycan derivative is 0.1 to 10%/day in a phosphate buffered saline with pH of 7.5 at 36° C. 
     
     
         3 . A method for obtaining anti-inflammatory effect, the method comprising:
 administering a pharmaceutical composition to a living body,   wherein the pharmaceutical composition comprises:   a group derived from glycosaminoglycan,   a group derived from a physiologically active substance, and   a spacer which couples the group derived from glycosaminoglycan to the group derived from the physiologically active substance by a covalent bond,   wherein the glycosaminoglycan is at least one selected from the group consisting of a chondroitin sulfate, and a derivative thereof,   wherein the physiologically active substance is selected from a group consisting of a nonsteroidal anti-inflammatory drug and a steroid, and the group derived from the physiologically active substance and the spacer are covalently bonded through an ester bond,   wherein the glycosaminoglycan has a carboxy group, a molecule for forming the spacer has an amino group corresponding to the carboxy group of the glycosaminoglycan, and the group derived from glycosaminoglycan and the spacer are covalently bonded through an amide bond,   wherein the molecule for forming the spacer has a coupling group which may have one or more substituent and couples the carboxy group and the amino group and the length of the coupling group between the carboxy group and the amino group is 2 to 12 atoms, and   wherein a dissociation rate of the physiologically active substance from the glycosaminoglycan derivative is 0.1 to 20%/day in a phosphate buffered saline with pH of 7.5 at 36° C.   
     
     
         4 . The method according to  claim 3 , wherein the dissociation rate of the physiologically active substance from the glycosaminoglycan derivative is 0.1 to 10%/day in a phosphate buffered saline with pH of 7.5 at 36° C.