Application of combination of Farnesoid XReceptor (FXR) agonist and apoptotic inhibitor in preparation of superior anti-hepatic fibrosis drugs

An apoptosis inhibitor and anti-hepatic fibrosis technology, applied in the field of medicine, can solve the problems of reduced drug efficacy, increased cholesterol level, decreased high-density lipoprotein level, etc., and achieves the effect of avoiding side effects and excellent anti-fibrosis.

Inactive Publication Date: 2018-06-05
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, clinical studies have found that long-term use of large doses of obeticholic acid can cause various adverse reactions such as increased cholesterol levels and decreased high-density lipoprotein levels.
Therefore, in order to avoid these adverse reactions, the dose of obeticholic acid needs to be reduced in clinical application, but it also faces the risk of reduced efficacy

Method used

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  • Application of combination of Farnesoid XReceptor (FXR) agonist and apoptotic inhibitor in preparation of superior anti-hepatic fibrosis drugs
  • Application of combination of Farnesoid XReceptor (FXR) agonist and apoptotic inhibitor in preparation of superior anti-hepatic fibrosis drugs
  • Application of combination of Farnesoid XReceptor (FXR) agonist and apoptotic inhibitor in preparation of superior anti-hepatic fibrosis drugs

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0020] Experimental example 1 Obeticholic acid relieves CCl 4 Liver fibrosis induced by intraperitoneal injection

[0021] 1 Experimental materials

[0022] The C57BL / 6 species mice used in the present invention were purchased from the Comparative Medicine Center of Yangzhou University;

[0023] Obeticholic acid used in the present invention is purchased from MedChem Company, CCl 4 Purchased from Shanghai Lingfeng Chemical Reagent Company, mineral oil (Mineral Oil) purchased from Sigma-Aldrich Company; reverse transcription kit was purchased from Applied Biosystems Company, Trizol RNAiso plus was purchased from TAKARA Company.

[0024] 2 Experimental methods

[0025] 2.1 Establishment of animal model and administration method

[0026] 30 male C57BL / 6 mice (6-8 weeks old, body weight 20-24g) were randomly divided into blank group after adaptive feeding for 1 week, CCl 4 Model group, low-dose obeticholic acid group, and high-dose obeticholic acid group. Before the experime...

Embodiment 2

[0057] Example 2 The combination of obeticholic acid and IDN-6556 can significantly relieve CCl 4 Liver fibrosis induced by intraperitoneal injection

[0058] 1 Experimental materials

[0059] The IDN-6556 used in the present invention was purchased from MedChem, and other biological materials and chemical materials were the same as in Example 1.

[0060] 2 Experimental methods

[0061] 2.1 Establishment of animal model and administration method

[0062] 48 male C57BL / 6 mice (6 to 8 weeks, body weight 20g to 24g) were randomly divided into blank group after adaptive feeding for 1 week, CCl 4 The model group, the obeticholic acid single administration group, the IDN-6556 single administration group, and the obeticholic acid combined with IDN-6556 administration group consisted of 5 groups. Before the experiment, the animals had free access to food and maintained a circadian rhythm of 12 hours of light and 12 hours of darkness. Laboratory temperature: 20-25°C, humidity 50±5...

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Abstract

The invention belongs to the field of biomedicines, and provides a scheme of combination of an apoptotic inhibitor and Farnesoid XReceptor (FXR) agonist for exerting the synergetic liver protection anti-fibrosis effect. Particularly, the invention relates to therapeutic medication measure for liver fibrosis at an important stage according to chronic liver disease. The invention provides application of combination of FXR agonist and the apoptotic inhibitor in preparation of superior anti-hepatic fibrosis drugs, and particularly the FXR agonist, namely obeticholic acid and the apoptotic inhibitor IDN6556 are selected for use, when the FXR agonist and the apoptotic inhibitor are subjected to low-dosage combination, the glutamic-pyruvic transaminase level in serum can be obviously reduced, thestructural forms and functions of liver cells can be improved, and the fibrotic symptoms is reduced, and due to drug combination, the liver protection effect is obviously superior to that of the single use of the FXR agonist and the apoptotic inhibitor. The invention provides a preparation method of a new superior liver protection anti-fibrosis drug.

Description

technical field [0001] The present invention relates to the field of medicine. The invention relates to the application of a farnesoid X receptor (FXR) agonist in combination with an apoptosis inhibitor in the preparation of an effective anti-fibrosis drug. Specifically, this project uses the FXR agonist obeticholic acid and the apoptosis inhibitor IDN-6556. in CCl 4 In the induced mouse liver fibrosis model, the combination of the two has significantly enhanced anti-fibrosis efficacy. technical background [0002] Liver fibrosis (Liver Fibrosis) refers to a damage repair reaction mainly caused by the deposition of extracellular matrix mainly composed of collagen. Liver fibrosis is the basic stage of the formation of many complex liver diseases in the body. It is an early reversible stage of liver cirrhosis. If it is not treated in time, it will lead to decompensated liver cirrhosis, various terminal liver diseases and related complications. However, there is no specific...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/575A61P1/16A61K31/216
CPCA61K45/06A61K31/216A61K31/575A61K2300/00
Inventor 郝海平王洪周济宇王广基郭怡彤黄宁宁
Owner CHINA PHARM UNIV
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