Application of interleukin 21 (IL-21) in preparation of anti-hepatitis B virus (HBV) medicine preparations

A hepatitis B virus, IL-21 technology, applied in the fields of genetic engineering and biomedicine, can solve the problems of large adverse reactions, inability to clear cccDNA of liver cell nucleus, and low patient response rate, so as to improve the conversion rate and reduce hepatitis B. Viral DNA load, effect of durable protection

Inactive Publication Date: 2018-07-27
FUDAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] At present, the drugs for clinical treatment of chronic hepatitis B are limited to α-interferon (interferon, IFN) and nucleoside (acid) analogues, among which α-interferon (2 types) has antiviral and immunomodulatory effects, and is administered by subcutaneous injection. After treatment with alpha interferon, the HBeAg seroconversion rate can reach 29%~32%, but the HBsAg seroconversion rate is lower than 10%; nucleoside (acid) analogs (5 kinds) can inhibit the reverse transcription of HBV , administered orally, afte

Method used

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  • Application of interleukin 21 (IL-21) in preparation of anti-hepatitis B virus (HBV) medicine preparations
  • Application of interleukin 21 (IL-21) in preparation of anti-hepatitis B virus (HBV) medicine preparations

Examples

Experimental program
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Effect test

Embodiment 1

[0031] Example 1: Anti-HBV Intervention Therapy Experiment of IL-21 in Mouse Model

[0032] 10 μg of HBV expression plasmid was dissolved in 2ml of PBS buffer, and injected into 40 male BALB / c mice of 6-8 weeks by tail vein high pressure hydrodynamic method, and 0.2ml of blood was collected through the orbit at 4 w.p.i. The whole blood was treated with anticoagulant, and the separated serum was used for the detection of HBsAg, anti-HBsAg, HBeAg and HBV DNA respectively, among which N mice were all positive for antigen and nucleic acid and negative for antibody in the above three indicators, randomly selected Twelve mice were divided into two groups: IL-21 treatment group (n=6) and control group (n=6), and 25 μg IL-21 was injected by tail vein high pressure hydrodynamic method at two time points of 4 w.p.i and 7 w.p.i. For the overexpression plasmid or the control plasmid (Control), 0.2 ml of blood was collected through the orbit at 8 time points (4.7, 5.4, 6.8, 8.3, 9.7, 11...

Embodiment 2

[0038] Example 2: Mice negative for viral antigens after IL-21 treatment acquire durable protection against HBV

[0039] From the IL-21 intervention group in Example 1, randomly select mice (n=4) that were negative for antigens (HBsAg and HBeAg) after the end of the observation period (> four weeks), and randomly select mice in the control group (n=3) , 10 μg of HBV expression plasmid BPS was dissolved in 2ml of PBS buffer, and injected into the experimental group and the control group mice by tail vein high pressure hydrodynamic method, respectively, at six time points (1 day, 2 days, 3 days, 1 w.p.i, 2 w.p.i and 3 w.p.i) 0.2ml of blood was collected through the orbit. The whole blood was treated with anticoagulant, and the separated serum was used for the detection of HBV-related indicators. The serum separated at the above six time points was used for the detection of HBsAg, Anti-HBsAg and HBeAg, and each serum was tested separately;

[0040] The results are shown in th...

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Abstract

The invention belongs to the fields of genetic engineering and biomedicines and relates to a novel medicinal application of interleukin 21 (IL-21), and particularly relates to an application of the IL-21 in preparation of an anti-HBV preparation. Tests prove that by using the IL-21 for intervening in a HBV chronically infected mouse model, conversion rate of hepatitis B surface antigen (HBsAg) andhepatitis B e antigen (HBeAg) can be significantly increased, and meanwhile, DNA carrying quantity of HBV in serum is significantly reduced. The IL-21 can be used as a medicine precursor for developing a novel anti-hepatitis B virus medicine.

Description

technical field [0001] The invention belongs to the field of genetic engineering and biomedicine, and relates to the new medicinal use of interleukin-21 (Interleukin-21, IL-21), in particular to the use of interleukin-21 in the preparation of anti-hepatitis B virus (Hepatitis B Virus, HBV) pharmaceutical preparations use. Background technique [0002] The prior art discloses that hepatitis B caused by hepatitis B virus (HBV) infection is mainly hepatic inflammatory lesions, and may be complicated by multiple organ damage. Studies have shown that after HBV infection becomes chronic hepatitis B (CHB), it can also lead to liver fibrosis, cirrhosis, primary hepatocellular carcinoma (HCC) and liver failure, eventually leading to death. According to statistics, with the maturity of HBV vaccine and the promotion of vaccination, the rate of new HBV infection has dropped significantly, but there are still about 350 million chronic carriers of HBV in the world, and about 1 million pa...

Claims

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Application Information

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IPC IPC(8): A61K38/20A61P1/16A61P31/20
CPCA61K38/20
Inventor 谢幼华刘晶沈忠良潘少坤
Owner FUDAN UNIV
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