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Remedy for acute hepatitis or preventive/remedy for fulminant hepatitis

A technology for acute hepatitis, therapeutic agent, applied in antiviral agents, digestive system, peptide/protein components, etc., can solve problems such as decreased platelet count and poor prognosis

Inactive Publication Date: 2010-03-10
CHUGAI PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Liver transplantation has also been attempted recently, but the prognosis is poor, with a survival rate of about 30%
When the virus is the pathogen, some people are trying to use interferon therapy as an antiviral therapy, but this therapy will cause fever, joint pain, myalgia, decreased white blood cell and platelet count, decreased appetite, weight loss, hair loss, thyroid Dysfunction, myocardial dysfunction, diabetes exacerbation, proteinuria and other side effects, so it is not very effective

Method used

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  • Remedy for acute hepatitis or preventive/remedy for fulminant hepatitis
  • Remedy for acute hepatitis or preventive/remedy for fulminant hepatitis
  • Remedy for acute hepatitis or preventive/remedy for fulminant hepatitis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] [0023] Preparation of preparations containing apolipoprotein A-II

[0047] Human plasma from which hepatitis virus and other pathogenic microorganisms have been substantially removed was used as a raw material, and the IV-1 fraction was obtained by Cohn's low-temperature ethanol fractionation of human plasma. 1.2 kg of the fraction IV-1 was dissolved in 2.4 L of a solution containing 100 mM tris(hydroxymethyl)aminomethane and 6 M urea, pH adjusted to 7.8-8.2, in a low temperature room at 2-8°C. Then, an ethanol / chloroform solution (1:1) equal to that of the solution was added and mixed, and centrifuged at 12,000 g for 10 minutes at 4° C. to recover the supernatant protein component. 4.1 L (1.2 times the amount) of ethanol was added to the recovered 3.4 L supernatant, and centrifuged at 12,000 g at 4° C. for 10 minutes to recover 6.8 L of the supernatant. Further, 5.4 L (0.8 times the amount) of ethanol was added to the recovered supernatant, and centrifuged at 12000 g ...

Embodiment 2

[0054] [0025] (1) Construction of recombinant human apolipoprotein A-II expression vector

[0055] The human apolipoprotein A-II gene was cloned by PCR using a human liver cDNA library (manufactured by Takara Biotech Co., Ltd., product code 9505) as a template. Wherein, the sequence shown in SEQ ID NO: 1 in the sequence listing is used as a forward primer, and the sequence shown in SEQ ID NO: 2 in the sequence listing is used as a reverse primer. The obtained PCR fragment was cloned into pCR2.1 vector (manufactured by Invitrogen) according to the TA cloning method using TOPO TA Cloning Kit (manufactured by Invitrogen).

[0056] (2) Preparation of human apolipoprotein A-II expression strain with short bacillus (Bacillus brevis)

[0057] Expression strains were constructed by transforming Bacillus brevis with a vector containing the resulting human apolipoprotein A-II gene. The method for constructing an expression strain was carried out according to the method described in Pa...

example 5

[0058] First construct the plasmid vector according to the method of the patent example 1, and then construct the plasmid vector inserted with the human apolipoprotein A-II gene. Then, according to the method described in Patent Example 5, the brevibacillus H102 (FERM BP-1087) was transformed by electroporation.

[0059] (3) After the transformant was cultured in TMN medium at 30° C. for 3 days, the culture solution was centrifuged to separate the supernatant to obtain the culture supernatant.

[0060] In order to confirm the amino acid sequence of the gained human apolipoprotein A-II, analyze the base sequence of the pCR2.1 carrier with a 3100 type DNA sequencer (manufactured by ABI company), when it is converted into amino acid, obtain the SEQ ID NO in the sequence listing :3 sequence shown.

[0061] This amino acid sequence is the same sequence as the mature protein part of human apolipoprotein A-II (initial accession number: P02652) described in Swiss-Prot Protein Knowled...

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Abstract

In the case where acute hepatitis progresses to fulminant hepatitis, a large amount of hepatocytes are rapidly broken and, in its turn, the prognosis is seriously worsened. Thus, it is meaningful to predict the progress of acute hepatitis into fulminant hepatitis at the early stage and quickly start an appropriate treatment therefor. Although the prediction of fulminant hepatitis becomes possibleowing to the recent advances in test methods and diagnostic techniques, there has been no appropriate preventive / remedy for fulminant hepatitis. Under these circumstances, it is intended to provide aremedy for acute hepatitis or a preventive / remedy for fulminant hepatitis with little side effect. ¢MEANS FOR SOLVING PROBLEMS! A medicinal composition for solving the above problem which contains apolipoprotein A-II.

Description

technical field [0001] [0001] The present invention relates to a therapeutic agent for acute hepatitis or a preventive and therapeutic agent for fulminant hepatitis containing apolipoprotein A-II as an active ingredient. Background technique [0002] [0002] The liver plays an important role in life activities such as synthesizing essential substances and excreting waste. Hepatitis is a disease that causes inflammation of the liver and decreased liver function when the liver cells that have the above-mentioned functions are destroyed by viruses, alcohol, drugs, etc. [0003] The symptoms of hepatitis are malaise, loss of appetite, vomiting, fever, jaundice and so on. Hepatitis that manifests symptoms within 6 months is called acute hepatitis. Hepatic coma grade II or higher encephalopathy and prothrombin time of 40% or less due to high degree of liver cell dysfunction within 8 weeks after the onset of acute hepatitis symptoms are called fulminant hepatitis. [0004] In ful...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61P1/16
CPCA61K38/1709A61P1/16A61P31/14
Inventor 佐佐木哲也原尚子石川诚
Owner CHUGAI PHARMA CO LTD
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