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Human sDR5-Fc recombinant fusion protein and its new application

A fusion protein, sdr5-fc technology, applied in the direction of drug combination, peptide/protein composition, hybrid peptide, etc., to achieve the effect of improving survival rate, reducing liver cell apoptosis rate, and reducing liver pathological damage

Active Publication Date: 2019-09-17
SHENZHEN ZHONGKE AMSHENN MEDICINE CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

) At present, whether sDR5 has a therapeutic effect on drug-induced liver injury, there is no report at home and abroad

Method used

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  • Human sDR5-Fc recombinant fusion protein and its new application
  • Human sDR5-Fc recombinant fusion protein and its new application
  • Human sDR5-Fc recombinant fusion protein and its new application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Example 1: Human sDR5-Fc recombinant fusion protein can block TRAIL-induced liver cell apoptosis

[0058] The HepG2 cells in the logarithmic growth phase were plated on a 96-well plate, and the same concentration of actinomycin D was added to each well to inhibit cell division, and 2-fold diluted TRAIL protein was added to each well to induce cell apoptosis. %CO 2 After incubating in the incubator for 18-22 hours, add freshly prepared 20:1 mixed MTS / PMS chromogenic solution 20ul / well, continue culturing in the incubator for 3-4 hours, and detect its A490-A630 with a microplate reader value. Thus, the EC90 value of TRAIL killing activity was calculated.

[0059] HepG2 cells in the logarithmic growth phase were plated on a 96-well plate, the same concentration of actinomycin D was added to each well to inhibit cell division, and the same concentration of TRAIL protein was added to each well to induce 90% cell apoptosis. 2-fold diluted human sDR5-Fc recombinant fusion p...

Embodiment 2

[0061] Example 2: Human sDR5-Fc antibody fusion protein in the treatment of APAP-induced liver injury

[0062] (1) 40 C57BL / 6 male mice were equally divided into 4 groups (normal saline group, 0.1mg / kg sDR5-Fc group, 1mg / kg sDR5-Fc group, 10mg / kg sDR5-Fc group, sDR5-Fc The sequence is SEQ ID NO.1), 10 mice in each group, each mouse was given 400mg / kg APAP by intragastric administration, and after 1 hour, each group of mice was given intraperitoneal injection of normal saline, 0.1mg / kg sDR5-Fc, 1mg / kg sDR5-Fc, 10mg / kg sDR5-Fc, the administration volume is 10ml / kg, 6h, 24h, 32h and 48h after APAP administration, blood was collected from the submandibular vein of each mouse, the serum was separated, and the serum was tested Transaminase levels. The mice were sacrificed at 48 hours, part of the liver was fixed in 4% PFA, embedded in paraffin, sectioned, HE stained, TUNEL stained, and TRAIL immunohistochemical stained.

[0063] The results are displayed (see figure 2 ): 10mg / kg...

Embodiment 3

[0066] Example 3: Synergistic treatment of APAP-induced liver injury by human sDR5-Fc recombinant fusion protein and NAC

[0067] Forty C57BL / 6 male mice were equally divided into 4 groups (normal saline group, 10mg / kg sDR5-Fc group, 100mg / kgNAC group, 10mg / kg sDR5-Fc and 100mg / kg NAC combined administration group, sDR5-Fc The sequence is SEQ ID NO.1), 10 mice in each group, each mouse was given 500mg / kg APAP by intragastric administration, and after 1 hour, each group of mice was given intraperitoneal injection of normal saline, 10mg / kg sDR5-Fc , 100mg / kg NAC, 10mg / kg sDR5-Fc and 100mg / kg NAC were administered in combination, and the administration volume was 10ml / kg. 24 hours after APAP administration, blood was collected from the submandibular vein of each mouse, and the serum was separated and detected. Serum transaminase levels.

[0068] The results are displayed (see image 3 ): 10mg / kg sDR5-Fc recombinant fusion protein and 100mg / kg NAC can act synergistically to sign...

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Abstract

The invention relates to human sDR5-Fc recombinant fusion protein and application of the human sDR5-Fc recombinant fusion protein to preparation of medicine for preventing and treating drug induced liver injury. Through long-time study of the inventor, the protein gene sequence is selected again, and the novel human sDR5-Fc recombinant fusion protein provided by the invention is obtained. Through a great number of experiments, the human sDR5-Fc recombinant fusion protein can obviously reduce the serum transaminase level in various mouse drug induced liver injury models; the liver pathologic damage is reduced; the liver cell apoptosis rate is obviously reduced; the mouse survival ratio is improved. The human sDR5-Fc recombinant fusion protein is used as novel candidate medicine for preventing and treating the drug induced liver injury; the treatment range is wide; targets are specific; the action is special and fast; the curative effect is obvious; the safety is high; great development potential is realized.

Description

technical field [0001] The invention relates to the field of recombinant protein and medicine, in particular to a human sDR5-Fc recombinant fusion protein and its application in the preparation of drugs for preventing and treating drug-induced liver injury. Background technique [0002] Drug-induced liver injury (DILI) refers to liver injury induced by various prescription or non-prescription chemical drugs, biological agents, traditional Chinese medicines, natural medicines, health products, dietary supplements and their metabolites, and even excipients. Drug-induced liver injury may occur in patients with or without underlying liver diseases in the past after taking drugs. DILI is one of the most common and serious adverse drug reactions, which can lead to acute liver failure (ALF) or even death in severe cases. Drug-induced liver injury is the most common reason new drugs are discontinued and withdrawn from the market. In my country, due to the continuous increase of dr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00A61K38/19A61P1/16
Inventor 万晓春陈倩张青梅
Owner SHENZHEN ZHONGKE AMSHENN MEDICINE CO LTD
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