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Use of Talazoparib in preparation of drugs for treating or preventing diseases related with hepatitis virus

A technology of hepatitis virus and hepatitis B virus, which is applied in the field of medicine, can solve the problems of enhanced radiation toxicity effect, inapplicability, enhanced cytotoxicity of radiotherapy and chemotherapy, etc., and achieve the effect of improving the therapeutic effect

Active Publication Date: 2019-02-22
THE WEST CHINA SECOND UNIV HOSPITAL OF SICHUAN +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, inhibition of PARP-1 can sensitize tumor cells to chemotherapeutic drugs that induce DNA damage, such as platinum, cyclophosphamide, camptothecin, etc., leading to enhanced cytotoxicity of radiochemotherapy
The first-generation PARP inhibitors (3-AB) and their derivatives can enhance radiation toxicity, but they are not clinically applicable due to lack of specificity

Method used

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  • Use of Talazoparib in preparation of drugs for treating or preventing diseases related with hepatitis virus
  • Use of Talazoparib in preparation of drugs for treating or preventing diseases related with hepatitis virus
  • Use of Talazoparib in preparation of drugs for treating or preventing diseases related with hepatitis virus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Example 1 Taraparib induces the expression of HBx and the chromosomal aberration of the liver cells carrying hepatitis B virus. experimental method:

[0058] 1. HBx protein expression and construction of HBV genome integrated cell line.

[0059]HL02-H1 is a human liver cell line that stably expresses the entire HBV genome. HL02-H1 was deposited in China Center for Type Culture Collection (CCTCC, accession number: C201554). The HBx protein expression cell HL-7702 / HBx and its control cell HL-7702 / pLV were constructed by a lentivirus infection system. The specific methods of lentivirus packaging and infection are conventional techniques and will not be repeated here.

[0060] 2. Taraparib induces chromosomal aberrations in HBx protein expressing cells and hepatitis B virus host cells.

[0061] HL-7702, HL02-H1, HL-7702 / pLV and HL-7702 / HBx cells were respectively inoculated into two 6cm diameter culture dishes, and after overnight culture, each cell was added with tarapa...

Embodiment 2

[0066] Example 2 Low-dose tarapanib specifically inhibits the expression of HBx and the proliferation of hepatitis B virus host liver cells

[0067] experimental method:

[0068] Colony formation experiments were used to further verify the specific inhibitory effect of taraparib on hepatocytes expressing HBx and hepatitis B virus host.

[0069] HL-7702, HL02-H1, HL-7702 / pLV and HL-7702 / HBx cells were seeded in 10 cm diameter culture dishes respectively, and 800 cells were added to each culture dish. After culturing overnight, add tarapanib or the same volume of DMSO (control group) the next day. After 10 days of continuous treatment with tarapanib, the cells were fixed with methanol, stained with Giemsa stain, and the number of clones was counted. All experiments were repeated 3 times.

[0070] Drug management includes taraparib monotherapy and its combination with platinum compounds (cisplatin). The concentration of taraparib single drug treatment is 0, 5, 10, 20, 50nM; t...

Embodiment 3

[0081] The curative effect of embodiment 3 taraparib to hepatitis B virus positive liver cancer

[0082] experimental method

[0083] Twenty-seven 6-week-old athymic female nude mice were randomly divided into 9 groups, each mouse was inoculated with HL02-H1 in the armpit and groin, and the inoculation quantity was 4x10 6 . The tumor volume is about 70-100mm 3 start injecting the drug. The drug injection regimen was a combination of taraparib and platinum drugs (cisplatin), and a solvent control group (DMSO) and a cisplatin single drug control group were set up. The specific dosages are as follows: the combined dosage of taraparib is 2.5mg / kg / day, and the dosages of other inhibitors are: BGB-290: 10mg / kg / day, BGP-15: 10mg / kg / day, E7449: 4mg / kg / day, Lukaparib: 10mg / kg / day, cisplatin dosage 3mg / kg, twice a week. The drug injection time was 12 days, and the tumor surface volume was measured on days 2, 5, 7, 8, 9, and 12. Tumor volume was calculated according to the followin...

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Abstract

The invention discloses use of a PAPP inhibitor Talazoparib or salt and solvate thereof in the preparation of drugs for treating or preventing diseases related with hepatitis virus. The diseases are infected by hepatitis B virus, are related with the infection of the hepatitis B virus and include acute hepatitis, chronic hepatitis, hepatic fibrosis, liver cirrhosis, liver cancer or cholangiocellular carcinoma and the like; by utilizing a Talazoparib single drug or combining the Talazoparib single drug with other anticancer drugs, host cells of the hepatitis B virus can be effectively eliminated, and the growth of positive cancer cells of the hepatitis B virus can be effectively inhibited; and compared with other types of PARP inhibitors such as Olaparib, Talazoparib has obvious advantageson the dosage and the treatment effect that: Talazoparib can be used for relatively effectively controlling the infection of the hepatitis B virus, inhibiting the development of positive cancers of the hepatitis B virus and relatively effectively controlling the proliferation of the positive cancers, with relatively large volume (not smaller than 400mm<3>) of the hepatitis B virus in a relativelylater period in a relatively low dosage range (0.015mg / kg / d-0.275mg / kg / d and is a unique anti-cancer drug for healing the type of tumors at present.

Description

technical field [0001] The invention belongs to the field of medicine, in particular to the use of the PARP inhibitor taraparib in the preparation of medicines for treating or preventing hepatitis B virus infection and related diseases caused by it. Background technique [0002] Acute hepatitis B virus (Hepatitis virus B, HBV) infection often transforms into chronic infection, long-term hepatitis B virus activity causes liver cell damage and necrosis, stimulates regeneration and proliferation of liver cells, local immune response, and causes liver lesions, Including liver fibrosis, cirrhosis and liver cancer. [0003] Primary liver cancer is currently the fourth most common malignant tumor and the third leading cause of cancer death. Hepatocellular carcinoma caused by hepatitis B virus accounts for more than 90% of primary liver cancer. According to its clinical and pathological staging, surgical resection, local ablation, interventional therapy (TACE), radiotherapy and che...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/5025A61P31/20A61P1/16A61P35/00
CPCA61K31/5025A61P1/16A61P31/20A61P35/00
Inventor 刘聪孔道春纪建国姜长安唐子执曾鸣张臣良王小军
Owner THE WEST CHINA SECOND UNIV HOSPITAL OF SICHUAN
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