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Application of tazarotene to preparation of drugs used for treating hepatitis B virus infection

A technology of tazarotene and hepatitis B virus, applied in the field of medicine, can solve problems such as the inhibition of hepatitis B virus by tazarotene which has not been seen

Inactive Publication Date: 2019-02-26
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there is no report about tazarotene inhibiting hepatitis B virus

Method used

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  • Application of tazarotene to preparation of drugs used for treating hepatitis B virus infection
  • Application of tazarotene to preparation of drugs used for treating hepatitis B virus infection
  • Application of tazarotene to preparation of drugs used for treating hepatitis B virus infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1HB

[0022] Embodiment 1 HBV infection system embodiment

[0023] Treating PHH or HepaRG cells infected with hepatitis B virus particles with tazarotene inhibited the production of hepatitis B virus e antigen (HBeAg), hepatitis B surface antigen (HBsAg) and HBV DNA to varying degrees.

[0024] (1) HepaRG cell culture: HepaRG cell line is derived from terminally differentiated cells of human liver precursor cell line, which retains many characteristics of primary human hepatocytes, and can support HBV infection after differentiation; 1) Growth medium: 15 % fetal bovine serum, 100U / L penicillin, 0.1mg / L streptomycin, glutamine, 0.023IU / ml insulin, 4.7μg / ml hydrocortisone, 80μl / ml gentamicin; 2) Differentiation medium : Growth medium + 2% DMSO, need to continue to differentiate for more than two weeks for HBV infection;

[0025] (2) Cultivation of PHH cells: purchased from Shanghai Ruide Biology and cultured in a special commercial medium; it should be pointed out that in the researc...

Embodiment 2

[0031] Embodiment 2.HBV replicative cell line model embodiment

[0032] Test the inhibitory effect of tazarotene on HBV cell lines:

[0033] (1) Cultivation of the liver cell line Hep2.215: use DMEM / F12 culture medium (Gibco company, add 10% fetal bovine serum, 100U / ml penicillin, 100mg / ml streptomycin and 400mg / ml G418) in 5% CO 2 Constant temperature cultivation at 37°C under saturated water vapor environment;

[0034] (2) Cultivation of the liver cell line HepDES19: use DMEM / F12 culture medium (Gibco company, add 10% fetal bovine serum, 100U / ml penicillin, 100mg / ml streptomycin and 400mg / ml G418) in 5% CO 2Incubate at a constant temperature of 37°C in a saturated water vapor environment;

[0035] (3) In Hep2.215 cells and HepDES19 cells, different concentrations of tazarotene were added to the cells, and the cell supernatants were collected after 5 days of treatment to detect HBV antigen markers HBeAg or HBsAg by ELISA; the results showed that tazarotene was Ting was not...

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Abstract

The invention relates to the application of tazarotene to preparation of drugs used for treating hepatitis B virus infection, belonging to the technical field of medicine. The identification results of virus transfection and infection cell model tests prove that tazarotene, a tretinoin drug, has strong anti-hepatitis B virus activity, presents long-lasting virus inhibition ability after withdrawal, and is free of cytotoxic effect at corresponding antiviral working concentrations. The invention also discloses that tazarotene has relatively specific activity in interfering with the stability ofcccDNA and inhibiting the transcription of cccDNA, and discloses the anti-hepatitis B virus activity of adapalene which also belongs to tretinoin drugs and is an analogue of tazarotene. The inventionprovides a technical and theoretical foundation for the application of tazarotene and its analogues to clinical anti-hepatitis B virus intervention and for the preparation of novel anti-hepatitis B virus drugs based on tazarotene and its analogues and derivatives.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a new drug application of tazarotene, in particular to the application of tazarotene and its analogs in the preparation of drugs for treating hepatitis B virus infection, especially in the preparation of drugs that reduce or eliminate hepatitis B virus hepatitis B e Antigens and surface antigens and the use in drugs targeting hepatitis B virus replication template DNA. Background technique [0002] The prior art discloses that hepatitis B virus (HBV) infection is one of the important diseases that seriously endanger human health. According to statistics, although the implementation of hepatitis B vaccination has significantly reduced the risk of HBV infection in newborns in recent years, there are still about 240 million people with chronic hepatitis B virus infection in the world (including more than 90 million in my country), about one million people per year People died of live...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/443A61K45/06A61P31/20
Inventor 袁正宏李保存陈捷亮
Owner FUDAN UNIV
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