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Galactose-pronged polysaccharides in a formulation for antifibrotic therapies

  • US 8,722,645 B2
  • Filed: 07/17/2012
  • Issued: 05/13/2014
  • Est. Priority Date: 05/16/2006
  • Status: Active Grant
First Claim
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1. A composition comprising:

  • a. an effective amount of a galacto-rhamnogalacturonan compound and an acceptable pharmaceutical carrier, wherein the 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,wherein the galacto-rhamnogalacturonan compound is derived from USP pectin;

    wherein the effective amount of the galacto-rhamnogalacturonan, when administered in a subject having at least one of the following;

    chronic liver disease associated with the development of fibrosis, established liver fibrosis, or cirrhosis, is capable of inhibiting or slowing down of the progression of liver fibrosis or cirrhosis or reduction of established liver fibrosis or cirrhosis based on evidence comprising reduction of the level of biochemical markers of liver fibrosis, non invasive testing of liver fibrosis or cirrhosis or liver histologic grading of fibrosis or cirrhosis;

    wherein, when the galacto-rhamnogalacturonan compound is utilized at a concentration of 0.1-0.5 mg/ml to treat LX2 immortalized human hepatic stellate cells in a MTT cell viability assay, the assay treatment results in substantially no decreased viability of activated hepatic stellate cells following administration of the compound, and wherein when the galacto-rhamnogalacturonan compound is utilized at a concentration of 0.1-0.5 mg/ml to treat LX2 immortalized human hepatic stellate cells in a proliferation assay, the assay results in substantially no effect on cell proliferation following administration of the compound; and

    b. a therapeutic agent, wherein the therapeutic agent is a compound selected from the group consisting of antibodies specific to cell-surface and/or intracellular;

    (i) β

    -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-β

    1;

    (xi) endothelin receptor antagonists;

    (xii) collagen synthesis and degradation modulating compounds;

    (xiii) actin synthesis and degradation modulating compounds; and

    (xiv) tyrosine kinases.

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