Galactose‑rhamnose galacturonate composition for treating nonalcoholic steatohepatitis and nonalcoholic fatty liver disease

A technology for lactobionate and steatohepatitis, which is applied in the field of chemistry and liver, and can solve the problems of non-existence of specific therapy

Active Publication Date: 2018-04-17
GALECTIN THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

To date, no specific therapy exists for these conditions

Method used

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  • Galactose‑rhamnose galacturonate composition for treating nonalcoholic steatohepatitis and nonalcoholic fatty liver disease
  • Galactose‑rhamnose galacturonate composition for treating nonalcoholic steatohepatitis and nonalcoholic fatty liver disease
  • Galactose‑rhamnose galacturonate composition for treating nonalcoholic steatohepatitis and nonalcoholic fatty liver disease

Examples

Experimental program
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Effect test

Embodiment 1

[0138] Embodiment 1: the method for manufacturing galactose-rhamnose galacturonate compound

[0139] The following are merely illustrative examples of generating therapeutic polysaccharides and are not intended to limit the present invention. In this case, the galactose-rhamnose galacturonate produced has been labeled GR-MD-02 in this application.

[0140] Apple pectin USP HM (50 kg) was dissolved and heated to 35-85°C in water. Add 1M HCl or NaOH to adjust the pH of the solution to pH 5-7 and mix well. Mixing was continued for 2 hours at the 35-85°C set point. 1M NaOH or HCl was added to readjust the pH to between 5 and 7 as needed. The solution was cooled to 30°C. The pH was adjusted to between 5 and 7 at 30°C.

[0141] CuSO 4 Added to pH-adjusted pectin solution to form 1 mM final CuSO 4 concentration. 1mM CuSO 4 The solution was mixed for 30 minutes at a temperature between 10°C and 30°C.

[0142] 1 mM CuSO for 30 min 4 At the end of the mixing step, 50 grams ...

Embodiment 2

[0147] Embodiment 2: the method for treating steatohepatitis mouse model

[0148] The experimental model used in this example was a mouse in which diabetes was induced and a high-fat diet was administered, a model that has been called STAM mouse. Such as figure 1Diabetes was induced with a single injection of streptozocin immediately after birth as shown in , and mice were then fed a high-fat diet 4 weeks later. This is a proven model in which mice consistently develop NASH with hepatocyte fat accumulation, signs of hepatotoxicity, portal and lobular inflammatory infiltrates, perisinusoidal fibrosis, advanced fibrosis with nodular formation, and cirrhosis And eventually hepatocellular carcinoma develops in a certain percentage of animals.

[0149] Disease progression was fatty liver (FL) by 5 weeks of age, steatohepatitis (NASH) by 7 weeks of age, fibrosis (Fib) by 9 weeks of age, nodules (N) by 13 weeks of age , and some animals developed hepatocellular carcinoma (HC) b...

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Abstract

Aspects of the invention provide methods for treating nonalcoholic steatohepatitis and associated liver fibrosis. In particular, aspects of the invention relate to the use of therapeutic formulations comprising galactose-rhamnogalacturonates for the treatment of non-alcoholic steatohepatitis and associated liver fibrosis.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit and priority of U.S. Provisional Application Serial No. 61 / 535,655, filed September 16, 2011, and U.S. Provisional Application Serial No. 61 / 656,288, filed June 6, 2012, the entire disclosure of each through Incorporated herein by reference in its entirety. Background technique [0003] Nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are common liver diseases in the United States. Histopathologically, these conditions resemble alcoholic liver disease, but they occur in people who drink little or no alcohol. Pathological changes in the liver include, but are not limited to, fat accumulation in hepatocytes, signs of hepatocellular degeneration, inflammatory cell infiltration, excessive fibrous tissue deposition, hepatocellular nodule formation, cirrhosis, and hepatocellular carcinoma. To date, no specific therapy exists for these conditions. Therefore, there is a ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/736C08B37/00
CPCA61K31/732A61K31/736A61K45/06A61P1/16A61P35/00A61P43/00A61K2300/00C08B37/0087C08B37/0045C08B37/006
Inventor 彼得·G·特拉伯E·佐默阿纳特尔·A·科尔约瑟夫
Owner GALECTIN THERAPEUTICS
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