Composition of novel carbohydrate drug for treatment of human diseases

Abstract

Aspects of the invention provide compositions for use in the treatment galectin-dependent diseases. In particular, compositions comprising a selectively depolymerized, branched galactoarabino-rhamnogalacturonate whose backbone is predominantly comprised of 1,4-linked galacturonic acid (GalA) moieties, with a lesser backbone composition of alternating 1,4-linked GalA and 1,2-linked rhamnose (Rha), which in-turn is linked to any number of side chains, including predominantly 1,4-b-D-galactose (Gal) and 1,5-a-L-arabinose (Ara) residues.

What is claimed is: 
     
         1 . An arabinogalacto-rhamnogalacturonan compound comprising a 1,4-linked galacturonic acid (GalA) and methyl galacturonate (MeGalA) residues backbone linked to branched heteropolymers of alternating oligomers of α-1,2 linked rhamnose and α-1,4-linked GalA residues, the rhamnose residues carrying a primary branching of oligomers of 1,4-β-D-galactose residues, 1,5-α-L-arabinose residues, or combinations thereof, wherein the arabinogalacto-rhamnogalacturonan compound is capable of reducing the secretion of TNF-alpha cytokine from monocytes stressed with endotoxin. 
     
     
         2 . The compound of  claim 1 , wherein the compound is capable of reducing the secretion of TNF alpha by activated monocytes/macrophages by at least 25%. 
     
     
         3 . The compound of  claim 1 , wherein the 1,4-linked galacturonic acid and methyl galacturonate residues backbone represents between 55 to 85 molar percent of the total carbohydrate molar content, the branched heteropolymer of alternating α-1,2 linked rhamnose and α-1,4-linked GalA residues represents between 1 and 6 molar percent of the total carbohydrate molar content, the oligomer 1,4-β-D-galactose of the primary branching represents between 6 to 15 molar percent of the total carbohydrate molar content and the oligomer 1,5-α-L-arabinose of the primary branching represents between 2 to 8 molar percent of the total carbohydrate molar content, as characterized by gas chromatography/mass spectrometry. 
     
     
         4 . The compound of  claim 1 , further comprising xylose, glucose, fucose residues or combination thereof. 
     
     
         5 . The compound of  claim 1 , wherein the oligomer of 1,4-β-D-galactose residues, 1,5-α-L-arabinose residues or combinations thereof represents at least 8 molar percent of the total carbohydrate molar content. 
     
     
         6 . The compound of  claim 1 , wherein the compound has a 1,4-β-D-galactose to 1,5-α-L-arabinose residues ratio ranging from 2:1 to a 3:1. 
     
     
         7 . The compound of  claim 1 , wherein the compound has an average molecular weight ranging from 2 kDa to 80 kDa. 
     
     
         8 . The compound of  claim 1 , wherein the compound has an average molecular weight ranging from 20 kDa to 70 kDa. 
     
     
         9 . The compound of  claim 1 , wherein the compound has an average molecular weight ranging from 5 kDa to 55 kDa. 
     
     
         10 . The compound of  claim 1 , wherein the compound has a degree of methoxylation ranging from 40% to 70% of the maximum of 87%. 
     
     
         11 . The compound of  claim 1 , wherein the compound has a methyl galacturonate to galacturonic acid ratio ranging from 2:1 to 1:2. 
     
     
         12 . The compound of  claim 1 , wherein the compound has a methyl galacturonate plus galacturonic acid ratio to galactose ranging from 4:1 to 7:1. 
     
     
         13 . The compound of  claim 1 , wherein the compound is substantially free of microbial endotoxin, agricultural pesticides, agricultural herbicides, copper, heavy metals, proteins, nitrogenous compounds or any combination of the foregoing. 
     
     
         14 . The compound of  claim 1 , wherein the compound does not induce decreased viability when used to treat LX2 immortalized human hepatic stellate cells. 
     
     
         15 . The compound of  claim 1 , wherein the compound is capable of reducing expression of galectin-3 or a substantial decrease in secretion of galectin-3 when used to treat stressed LX2 immortalized human hepatic stellate cells producing galectin-3. 
     
     
         16 . A composition comprising a compound according to  claim 1  in an acceptable pharmaceutical carrier, for use in therapeutic formulations. 
     
     
         17 . The composition of  claim 16 , wherein the composition is administered parenterally via an intravenous, subcutaneous, or oral route. 
     
     
         18 . The composition of  claim 16 , further comprising a therapeutic agent. 
     
     
         19 . The composition of  claim 16 , wherein the therapeutic agent is an anti-oxidant compound, an anti-inflammatory agent, vitamins, an immunotherapeutic agent, a neutraceutical supplement or combinations thereof. 
     
     
         20 . The composition of  claim 16 , for use in the treatment of nonalcoholic steatohepatitis, fibrosis, inflammatory disorder, autoimmune disorders, neoplastic conditions or of cancer.