Compositions Comprising Galactose-Pronged Polysaccharides

Abstract

Methods and compositions for reducing fibrosis and cirrhosis are provided in which an effective dose of an admixture of a polysaccharide compound and, for example, a compound selected from the group consisting of antibodies specific to intracellular or cell-surface: (i) beta-PDGF receptors; (ii) synaptophysin; (iii) zvegf3; (iv) CCR1 receptors; (v) connective tissue growth factor; (vi) alpha 1-smooth muscle actin; (vii) matrix metalloproteinases MMP 2 and MMP9; (viii) matrix metalloproteinase inhibitors TIMP1 and TMP2; (ix) integrins; (x) TFG-β1; (xi) endothelin receptor antagonists; and (xii) collagen synthesis and degradation modulating compounds; (xiii) actin synthesis and degradation modulating compounds; and (xiv) tyrosine kinases is administered to an animal in order to treat fibrosis.

What is claimed is: 
     
         1 . A composition comprising an effective amount of a modified galacto-rhamnogalacturonan compound and an acceptable pharmaceutical carrier,
 wherein the modified galacto-rhamnogalacturonan compound is a branched heteropolymer having a backbone of alternating α-1,2 linked rhamnose and α-1,4-linked GalA residues that carries neutral side-chains of predominantly 1,4-β-D-galactose and/or 1,5-α-L-arabinose residues attached to the rhamnose residues of the backbone, and   wherein the galacto-rhamnogalacturonan compound is modified by demethoxylation, deacetylation or depolymerization.   
     
     
         2 . The composition of  claim 1  wherein the modified galacto-rhamnogalacturonan compound is derived from citrus pectin, apple pectin, soybean hull pectin or sugar beet pectin. 
     
     
         3 . The composition of  claim 1  wherein the modified galacto-rhamnogalacturonan compound is derived from USP pectin. 
     
     
         4 . The composition of  claim 1  wherein the modified galacto-rhamnogalacturonan compound has a molecular weight between 20 kDa and 400 kDa. 
     
     
         5 . The composition of  claim 1  wherein the modified galacto-rhamnogalacturonan compound has a molecular weight between 2 kDa and 200 kDa. 
     
     
         6 . The composition of  claim 1  wherein the modified galacto-rhamnogalacturonan further comprises fucose, xylose, mannose or combinations thereof. 
     
     
         7 . The composition of  claim 1  further comprising an antifibrotic compound 
     
     
         8 . A method comprising the steps of:
 administering parenterally to a subject in need thereof having at least one of the following disease: chronic kidney disease associated with the development of fibrosis, established kidney fibrosis or cirrhosis, chronic lung disease associated with the development of fibrosis, established lung fibrosis or cirrhosis, an effective dose of the galacto-rhamnogalacturonan compound in an acceptable pharmaceutical carrier, wherein the modified galacto-rhamnogalacturonan compound is a branched heteropolymer having a backbone of alternating α-1,2 linked rhamnose and α-1,4-linked GalA residues that carries neutral side-chains of predominantly 1,4-β-D-galactose and/or 1,5-α-L-arabinose residues attached to the rhamnose residues of the backbone and wherein the galacto-rhamnogalacturonan compound is modified by demethoxylation, deacetylation or depolymerization, wherein administration to the subject in need thereof results in inhibition or slowing down of the progression of the fibrosis or cirrhosis or reduction of established fibrosis or cirrhosis; or reduction in the medical consequences of fibrosis or cirrhosis.   
     
     
         9 . The method of  claim 8  wherein the modified galacto-rhamnogalacturonan compound has a molecular weight between 20 kDa and 400 kDa. 
     
     
         10 . The method of  claim 8  wherein the modified galacto-rhamnogalacturonan compound has a molecular weight between 2 kDa and 200 kDa. 
     
     
         11 . The method of  claim 8  wherein the modified galacto-rhamnogalacturonan further comprises fucose, xylose, mannose or combinations thereof. 
     
     
         12 . The method of  claim 8  wherein in the step of administering the modified galacto-rhamnogalacturonan is in an admixture with a therapeutic agent. 
     
     
         13 . The method of  claim 12  wherein the therapeutic agent is an antifibrotic compound.