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Application of vitamin D analogue for treating or preventing viral hepatitis

A technology for viral hepatitis and derivatives, applied in antiviral agents, drug combinations, organic active ingredients, etc., to achieve excellent clinical safety, excellent pharmacokinetic properties, and good druggability

Pending Publication Date: 2022-03-22
HOLY HAID LAB CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The point is that there is still no drug that can completely clear the virus and achieve a functional cure for hepatitis B

Method used

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  • Application of vitamin D analogue for treating or preventing viral hepatitis
  • Application of vitamin D analogue for treating or preventing viral hepatitis
  • Application of vitamin D analogue for treating or preventing viral hepatitis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0109] Example 1 - Application of HepG2-NTCP cells to evaluate the in vitro anti-HBV activity of paricalcitol (HD009, compound 9), alfacalcitol (HD125, compound 18) and calcifediol (HD135, compound 3)

[0110] Compound preparation method is as follows:

[0111] Take the preparation of 20mM concentration as an example, the volume of solvent DMSO (μl) = sample mass (mg) × purity ÷ molecular weight ÷ 20 × 10 6

[0112] Control compounds include ETV (Entecavir) (batch number: P1214012; 99.0% purity), purchased from Shanghai Titan Technology Co., Ltd.; HD131 (vitamin D2), HD132 (vitamin D3), HD134 (docalcitol), purchased from Shanghai Tao Su Biochemical Technology Co., Ltd. The concentration of the stock solutions of the above control compounds was 20 mM and stored at -20°C.

[0113] Table 1. Major Reagents and Cell Viruses

[0114]

[0115] Experimental program

[0116] Plating Cells and Compound Treatment

[0117] On day 0, HepG2-NTCP was plated into 48-well plates (7....

Embodiment 2-A

[0153] Embodiment 2-AAV HBV mouse model experiment

[0154]Administration was carried out according to the following table 7, and the content of HBV DNA, HBeAg and HBsAg in the cell culture supernatant was detected with reference to the same method as above, and the results are shown in Table 8:

[0155] Table 7

[0156] way of administration time blank 0, once a day 7 days HD125 2ug / kg, once a day 7 days

[0157] Table 8

[0158] HD125 Log HBV DNA Log HBsAg Log HBeAg 0day 6.56 3.41 2.66 7day 4.61 2.96 2.61 Variation -1.95 -0.45 -0.05

[0159] Animal experiment results also show that HD125 (alfacalcidol) can effectively reduce HBV DNA, HBsAg and HBeAg, showing good antiviral effect in vivo.

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PUM

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Abstract

The present invention relates to the use of vitamin D analogs for the treatment or prevention of viral hepatitis. Specifically, the invention provides a compound as shown in a general formula 1 or pharmaceutically acceptable salt thereof, and application of the compound or the pharmaceutically acceptable salt in treating or preventing viral hepatitis. Preferably, the viral hepatitis is hepatitis B. The invention also provides a pharmaceutical composition for treating or preventing viral hepatitis, which comprises the compound as shown in the general formula 1 or pharmaceutically acceptable salt thereof, one or more optional additional therapeutic or prophylactic agents, and a pharmaceutically acceptable carrier.

Description

[0001] This application claims priority to the prior application filed with the State Intellectual Property Office of China on January 10, 2021, with patent application number 202110027380.8, entitled "Application of Vitamin D Analogues for the Treatment or Prevention of Viral Hepatitis" . The entirety of this prior application is incorporated by reference into the present application. technical field [0002] The invention relates to the technical field of antiviral drugs, in particular to a pharmaceutical composition for treating or preventing viral hepatitis and its application. Background technique [0003] Human hepatitis B virus (HBV) infection is an important public health problem worldwide. After acute hepatitis B virus infection, about 8% still develop into chronic hepatitis B infection, and persistent HBV infection will lead to liver cirrhosis and even liver cancer. Although the new hepatitis B infection rate has been effectively controlled with the widespread po...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/592A61P1/16A61P31/20
CPCA61K31/592A61P1/16A61P31/20
Inventor 李瑛颖陈明键仇思念
Owner HOLY HAID LAB CORP
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