Unlock instant, AI-driven research and patent intelligence for your innovation.

Application of targeted complement inhibitor in preparation of medicine for improving cholestatic liver injury

A complement inhibitor and cholestasis technology, applied in the field of biomedicine, can solve the problems of limited clinical prevention and treatment methods, increase the risk of surgery and prognosis, and achieve the effects of strong targeting, reduced polarization, and reduced infiltration.

Pending Publication Date: 2022-03-22
THE FIRST AFFILIATED HOSPITAL OF GUANGXI MEDICAL UNIV
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

CLI can significantly increase the risk of surgery and prognosis, but its clinical prevention and treatment methods are very limited

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of targeted complement inhibitor in preparation of medicine for improving cholestatic liver injury
  • Application of targeted complement inhibitor in preparation of medicine for improving cholestatic liver injury
  • Application of targeted complement inhibitor in preparation of medicine for improving cholestatic liver injury

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0022] Preparation of targeting complement inhibitor CR2-Crry: prepared by linking complement receptor 2 (CR2) to membrane binding regulatory factor (Crry). For specific preparation, please refer to: Atkinson C, Song H, Lu B , etal. Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection. J ClinInvest. 2005; 115(9): 2444-2453 Preparation of CR2-Crry fusion protein in Methods. The prepared amino acid sequence of the targeted complement inhibitor CR2-Crry used in the examples is shown in SEQ ID NO.1, which contains 585 amino acids.

[0023] Complement C3 knockout mice (C3 - / - mice, C3 knockout mice) were B6; 129S4-C3tm1Crr / J strains, purchased from The Jackson Laboratories (Bar Harbor, Maine, USA).

Embodiment 1

[0025] 1. Establishment of the overall model related to the experiment

[0026] Bile duct ligation (BDL) was performed on mice to establish a model of cholestatic liver injury. The steps are as follows: anesthetize the mouse with isoflurane, fix its limbs, and disinfect the abdomen of the mouse. Use scissors to cut the abdominal wall longitudinally along the midline of the mouse abdominal wall, and the length of the incision is about 2 cm. The abdominal incision was expanded to expose the hilum of the liver. The gastric antrum and duodenum were lightly pressed with a cotton swab, and pulled downward slightly. A transparent duct was seen running in front of the hepatic portal vein, which was the common bile duct. Use the tip of forceps to bluntly dissect the common bile duct and the portal vein, and free 2-3mm of the common bile duct. Thread two 9-0 nylon threads for a double ligature, and cut off the ends of the threads. After the abdominal wall was sutured, the mice were t...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses application of a targeted complement inhibitor in preparation of a medicine for improving cholestatic liver injury. The invention relates to application of a targeted complement inhibitor CR2-Crry in preparation of a medicine for improving cholestatic liver injury. The amino acid sequence of the CR2-Crry is as shown in SEQ ID NO. 1. According to the present invention, the complement receptor 2 (CR2) is fused with the C3 activation inhibition factor Crry, the CR2 is combined to the complement activation site in the targeting manner, and the Crry specificity is adopted to inhibit the C3 activation so as to inhibit the complement system activation; by establishing a mouse cholestatic liver injury model and comparing liver injury level changes of a CR2-Cryy treatment group and a control group, results prove that CR2-Crry can significantly improve cholestatic liver injury, inhibit infiltration of inflammatory cells in the liver, inhibit polarization of M1 type macrophages in the liver and reduce expression of proinflammatory factors. The improvement effect of inhibiting the complement system on cholestatic liver injury is further verified through a C3 gene knockout mouse.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and relates to the application of targeted complement inhibitors in the preparation of drugs for improving cholestatic liver damage. Background technique [0002] Cholestatic liver injury (CLI) refers to abnormal bile production, secretion or excretion caused by various etiologies, bile cannot be normally discharged into the intestinal tract through the bile duct, and is caused by stasis in the liver and then back into the blood. The pathological state of a series of organic damage and dysfunction, the main clinical manifestations are jaundice and liver function damage. If the disease progresses further, it can cause liver failure or even death. Among surgical system diseases, biliary obstruction caused by diseases such as liver cancer, bile duct tumors, and space-occupying lesions of the head of the pancreas is a common cause of CLI. The mechanism of CLI is not very clear at present, previou...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/19A61K47/64A61P1/16C07K19/00
CPCA61K38/19A61K47/6425A61P1/16C07K14/70596C07K14/472C07K14/4703C07K2319/00
Inventor 何松青郭振亚袁观斗
Owner THE FIRST AFFILIATED HOSPITAL OF GUANGXI MEDICAL UNIV