Use of long-acting human recombined soluble TNF alpha receptor in preparation of medicament for treating liver failure
A tumor necrosis factor and α receptor technology, applied in the fields of genetic engineering technology and gene function application, can solve the problems of unsatisfactory effect and the application of soluble TNFα receptor in clinical treatment, etc.
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Embodiment 1
[0106] 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
[0107] 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.
[0108] 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 2
[0109] Example 2 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-IgG1: Fc
[0110] 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.
[0111]Type II LHusTNFR prepared by the present invention (type II LHusTNFR-IgG1 prepared by method (2): Fc is a preventive drug) was subcutaneously injected into C57BL / 6 mice (GaIN / LPS group) or BALB / c mice (Con-A group) ), the dose was 12.5mg / kg, which was the long-acting type II receptor prevention group; conventional HusTNFR was subcutaneously inje...
Embodiment 3
[0112] 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
[0113] 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.
[0114] 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...
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