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Use of long-acting human recombined soluble TNF alpha receptor in preparation of medicament for treating liver failure

A tumor necrosis factor and alpha receptor technology, applied in the field of gene function application and genetic engineering technology, can solve the problems of unsatisfactory effect and the application of soluble TNFα receptor in clinical treatment, etc.

Active Publication Date: 2007-04-25
李海
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But, and those skilled in the art can't know the reason of its unsatisfactory effect so far
Therefore, it is still difficult to practically apply soluble TNFα receptors to clinical treatment.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0105] Example 1: Experiment of preventing acute (burst) liver failure in mice by long-acting human recombinant soluble type I tumor necrosis factor (TNF) alpha receptor (type I LHusTNFR) represented by type I HusTNFR-IgG1: Fc

[0106] D-galactosamine / endotoxin (GaIN / LPS) or Con-A (T cell mitogensconcanavalin A) were injected subcutaneously to make mouse models of fulminant liver failure, and the 48-hour mortality rates were 80% and 50%, respectively. The gross specimen of the liver showed severe congestion and enlargement of the liver; the pathological sections stained with HE showed extensive and severe hepatocyte necrosis.

[0107] Type I LHusTNFR prepared above (type I LHusTNFR-IgG1 prepared by method (1): Fc is a preventive drug) was subcutaneously injected into C57BL / 6 mice (GaIN / LPS group) or BALB / c mice (Con-A group) , the dose is 12.5mg / kg, which is the long-acting type I receptor prevention group; conventional HusTNFR subcutaneous injection of C57BL / 6 mice (GaIN / LPS ...

Embodiment 3II

[0111] Example 3 Experiment of preventing acute (burst) liver failure in mice by long-acting human recombinant soluble type II tumor necrosis factor (TNF) alpha receptor (type II LHusTNFR) represented by type II HusTNFR-human serum albumin

[0112] D-galactosamine / endotoxin (GaIN / LPS) or Con-A (T cell mitogensconcanavalin A) were injected subcutaneously to make mouse models of fulminant liver failure, and the 48-hour mortality rates were 80% and 50%, respectively. The gross specimen of the liver showed severe congestion and enlargement of the liver; the pathological sections stained with HE showed extensive and severe hepatocyte necrosis.

[0113] Type II LHusTNFR prepared by the present invention (type II LHusTNFR-human serum albumin prepared by method (6) is a preventive drug) subcutaneously injected into C57BL / 6 mice (GaIN / LPS group) or BALB / c mice (Con-A group), the dose is between 5-30mg / kg, which is the long-acting type II receptor prevention group; routine HusTNFR subcu...

Embodiment 4

[0114] Example 4: Experiment of preventing subacute liver failure in rats with long-acting human recombinant soluble type I tumor necrosis factor (TNF) alpha receptor (type I LHusTNFR) represented by type I HusTNFR-IgG1: Fc

[0115] D-galactosamine / endotoxin (GaIN / LPS) was injected subcutaneously to make rat subacute liver failure model, and the mortality rate was 60% within one week. The gross specimen of the liver showed severe congestion and enlargement of the liver; the pathological sections stained with HE showed extensive and severe hepatocyte necrosis.

[0116] Type I LHusTNFR prepared by the present invention (type I LHusTNFR-IgG1 prepared by method (1): Fc is a preventive drug) was subcutaneously injected into Spraque-Dawley rats with a dose of 12.5 mg / kg, which was the long-acting type I receptor prevention group; Conventional HusTNFR was subcutaneously injected into Spraque-Dawley rats at a dose of 12.5 mg / kg, which was the conventional type I receptor prevention gr...

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PUM

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Abstract

The invention relates to a method for preparing recombine soluble cancer necrotic factor alpha acceptor (Hus TNFR) gene drug. Wherein, the invention uses I or II type long-effect recombine soluble cancer necrotic factor alpha acceptor, via acute, sub acute liver exhaustion animal mode, to predict the liver exhaustion of mouse, and the result proves that it can prolong 10 times of semi-exhaustion period, with better treatment effect, then non-long-effect HusTNFR.

Description

technical field [0001] The invention belongs to the field of genetic engineering technology and gene function application, and relates to the new medicinal application of recombinant soluble tumor necrosis factor alpha receptor (HusTNFR) gene, in particular to the effect of long-acting human recombinant soluble tumor necrosis factor alpha receptor (LHusTNFR) on acute and Prophylactic and therapeutic uses of the liver in acute liver failure. Background technique [0002] Fulminant hepatic failure (fulminant hepatic failure, FHF) refers to patients without liver disease before the disease, a large number of liver cell necrosis or severe damage to liver function in a short period of time, and hepatic hepatic failure occurs within 8 weeks after the first symptoms appear or within 10 days after the appearance of jaundice. A syndrome of encephalopathy. It is characterized by acute onset, critical condition before illness, lack of effective treatment, and high mortality. [0003]...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61K38/19A61P1/16A61K38/18A61K38/06A61K31/4375
Inventor 李海
Owner 李海
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