Compound of glycosaminoglycan and its preparation method as well as application

Abstract

The present invention is related to a compound conjugating a drug with a glycosaminoglycan, such as hyaluronic acid (HA), where the drug is useful for the treatment of diseases such as inflammation, auto-immune disease, allergy, infection and preferably cancer. The conjugated compound of the present invention can increase the concentration of drug at the specific site of disease by an interaction of the glycosaminoglycan used as target drug delivery carrier and the CD44 cell surface receptor, then enhancing the therapeutic efficacy and reducing the systemic side effect of the site-delivered drug.

What is claimed is: 
     
         1 . A compound consisting of a conjugate from a glycosaminoglycan and an active compound, wherein the active compound is conjugated by means of a functional group to a carboxylic group of the glycosaminoglycan, its derivative, or a salt thereof to form a covalent conjugation, and wherein the active compound consists of anti-inflammatory drug, anti-allergy drug and steroid. 
     
     
         2 . The compound according to  claim 1 , wherein the anti-inflammatory drug is COX-2 antagonist. 
     
     
         3 . The compound according to  claim 2 , wherein the COX-2 antagonist is Celecoxib. 
     
     
         4 . The compound according to  claim 1 , wherein the anti-allergy drug is Fexofenadine. 
     
     
         5 . The compound according to  claim 1 , wherein the steroid is Budesonide and Prednisolone. 
     
     
         6 . The compound according to  claim 1 , wherein the covalent conjugation is a direct conjugation by means of an amide bond or an ester bond. 
     
     
         7 . The compound according to  claim 1 , wherein the active compound is also indirectly conjugated to the carboxylic group of the glycosaminoglycan through a linker. 
     
     
         8 . The compound according to  claim 7 , wherein the linker is selected from the group consisting of adipic dihydrazide, polypeptide, peptide, lipid, amino acid and linear or branched, aliphatic, aromatic or araliphatic C 2 -C 20  dicarboxylic acids. 
     
     
         9 . The compound according to  claim 1 , wherein the glycosaminoglycan is hyaluronic acid. 
     
     
         10 . The compound according to  claim 9 , wherein the hyaluronic acid has an average molecular weight comprised in the range from 5 kDa to 2000 kDa. 
     
     
         11 . The compound according to  claim 1 , for use in the treatment of acute or chronic inflammation. 
     
     
         12 . The compound according to  claim 11 , wherein the inflammation is induced or caused by infection, injury, autoimmune disease, or allergy. 
     
     
         13 . The compound according to  claim 11 , wherein the autoimmune disease is Rheumatoid arthritis. 
     
     
         14 . A method for treatment of inflammation, comprising a step of administering to a subject in need thereof a therapeutically effective amount of a compound consisting of a conjugate from a glycosaminoglycan and an active compound according to  claim 1 . 
     
     
         15 . The method according to  claim 14 , wherein the inflammation is induced or caused by infection, injury, autoimmune disease, or allergy. 
     
     
         16 . A pharmaceutical composition comprising at least one conjugate from a glycosaminoglycan and an active compound according to  claim 1  in combination with at least one excipient and/or diluent. 
     
     
         17 . The pharmaceutical composition according to  claim 16 , wherein the composition is for treating inflammation. 
     
     
         18 . The pharmaceutical composition according to  claim 17 , wherein the inflammation is induced or caused by infection, injury, autoimmune disease, or allergy. 
     
     
         19 . The pharmaceutical composition according to  claim 16 , wherein the composition is designed for oral or injectable administration.