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Application of fxr agonists in the treatment of hepatic encephalopathy

A hepatic encephalopathy and drug technology, applied in the field of biomedicine, can solve the problems of OCA application that has not been reported yet, achieve significant liver protection function, reduce the content of blood ammonia, and reduce the effect of injury

Active Publication Date: 2021-09-28
HENAN UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] OCA was successfully developed by Intercept Pharmaceutical Company of the United States. It is the first drug developed for the treatment of cholestatic liver disease in the past two decades. As a bile acid mimic, it can activate FXR. However, there is no information about the application of OCA in hepatic encephalopathy. see the report

Method used

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  • Application of fxr agonists in the treatment of hepatic encephalopathy
  • Application of fxr agonists in the treatment of hepatic encephalopathy
  • Application of fxr agonists in the treatment of hepatic encephalopathy

Examples

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Embodiment 1

[0021] The materials and reagents used in the following examples can be obtained from commercial sources unless otherwise specified.

[0022] 12-week-old wild-type C57BL / 6N male mice: purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., C57BL / 6N FXR-deficient mice: purchased from the City of Hope Medical Center Laboratory in the United States; obeticholic acid ( OCA): purchased from Taosu, catalog number 459789-99-2; methylcellulose: purchased from Taosu, catalog number 9004-67-5; thioacetamide (TAA): purchased from Taosu , catalog number 62-55-5; NH 3 , ALB, ALT, AST, TBA, ALP, BUN and other detection kits: purchased from Fuji, Japan; GFPA antibody: purchased from abcam, catalog number is ab183735; immunohistochemical secondary antibody kit: purchased from Zhongshan Jinqiao, PV -9001.

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Abstract

The invention belongs to the technical field of biomedicine, and in particular relates to the application of FXR agonists in the treatment of hepatic encephalopathy, specifically the application of obeticholic acid in the treatment of hepatic encephalopathy. The present invention also provides the application of the nuclear receptor FXR in the treatment of hepatic encephalopathy, specifically targeting the nuclear receptor FXR to obtain a drug for treating hepatic encephalopathy or protecting the liver. Using the FXR agonist obeticholic acid (OCA) to activate FXR, we found that in the liver injury model, the activation of FXR can induce the expression of key enzymes in the ammonia metabolism pathway such as NAGS, SLC1A4, AL, and reduce the blood ammonia content. Reduce the damage of brain astrocytes; in addition, the activation of FXR can play a significant role in liver protection.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of FXR agonists in the treatment of hepatic encephalopathy. Background technique [0002] Hepatic encephalopathy (hepatic encephalopathy, HE) is a reversible metabolic disease caused by central nervous system dysfunction in patients with acute or chronic liver disease. The pathogenesis of hepatic encephalopathy is relatively complicated, and the theory of ammonia poisoning has been dominant in its pathogenesis hypothesis for a long time. Intestinal-derived toxins such as blood ammonia are metabolized and eliminated by the liver under normal circumstances, but in the case of liver failure and abnormal portosystemic shunt, ammonia and other toxins cannot be eliminated by liver metabolism and directly enter the systemic circulation, and then penetrate the blood -The brain barrier enters the brain, leading to the occurrence of neuropsychiatric symptom...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6883G01N33/68A61K31/575A61K45/06A61K48/00A61P1/16A61P25/00
CPCA61K31/575A61K45/06A61K48/0025A61P1/16A61P25/00C12Q1/6883C12Q2600/158G01N33/6893G01N2800/085
Inventor 陈卫东叶文凌王艳东周云赵世振白校杰赵阳
Owner HENAN UNIVERSITY
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