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Application of polypeptide AT03 in medicine used for treating primary biliary cholangitis

An AT03, primary technology, applied in the field of biochemistry, can solve problems such as unsatisfactory treatment of PBC, achieve the effects of good biological activity, low cost, and easy to scale up production

Pending Publication Date: 2021-04-16
SHENZHEN TURIER BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it is worth noting that the adverse reaction of pruritus is more likely to occur when OCA treatment is used, and the higher the dose, the higher the incidence rate. In some trials, some PBC patients even stopped treatment because of pruritus (Kowdley K V, Luketic V,Chapman R,et al.A randomized trial of obeticholic acid monotherapy in patients with primary biliarycholangitis[J].Hepatology,2018,67(5):1890-1902.)
[0005] At present, the treatment of PBC is still unsatisfactory, so it is urgent to find better therapeutic drugs

Method used

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  • Application of polypeptide AT03 in medicine used for treating primary biliary cholangitis
  • Application of polypeptide AT03 in medicine used for treating primary biliary cholangitis
  • Application of polypeptide AT03 in medicine used for treating primary biliary cholangitis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1, the preparation of polypeptide AT03

[0031] The amino acid sequence of polypeptide AT03 is: Val-His-Val-Val-R 1 ; where R 1 =-NH 2 . In this example, AT03 was synthesized by the Fmoc solid-phase polypeptide synthesis method from the carboxy-terminus to the amino-terminus, and the amino acids of the polypeptide AT03 were connected sequentially according to the sequence of amino acids mentioned above.

[0032] (1) Polypeptide synthesis

[0033] The preparation condition of the present invention adopts MBHAR (Amide-MBHA-Resin amide-protected MBHA resin) or Wang resin, and synthesizes by removing the Fmoc protecting group with the method of activating lipid.

[0034] The indene detection reagent of the present invention comprises following components:

[0035] Reagent 1: 20g phenol / 5mL ethanol;

[0036] Reagent 2: 0.05 0.001M KCN ​​(water) / 2.5mL pyridine;

[0037] Reagent 3: 0.5g ninhydrin / 10mL ethanol;

[0038] The usage ratio of the indene detection...

Embodiment 2

[0057] Example 2, the improved therapeutic effect of the polypeptide AT03 of the present invention on the common bile duct ligation (BDL) rat model of cholestatic liver cirrhosis

[0058] The specific method of this embodiment is as follows.

[0059] 1. Test drug: polypeptide AT03, positive control drug (ursodeoxycholic acid, UDCA). Storage conditions -20°C.

[0060] Modeling method: before the operation, the experimental animals were anesthetized with 3% pentobarbital sodium at a dose of 60 mg / kg. After routine disinfection of the abdominal skin, an incision was made along the midline of the abdomen to expose the common bile duct. After side suturing and ligation, no active bleeding in the abdominal cavity was detected, the abdomen was routinely closed. In the sham operation group, the abdomen was only opened and the common bile duct was freed, and antibiotics were given for postoperative care according to the animal reaction. Animals in the normal control group were not giv...

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Abstract

The invention discloses application of polypeptide AT03 in a medicine used for treating primary biliary cholangitis. The amino acid sequence of the polypeptide AT03 is Val-His-Val-Val-R1, wherein R1 is -NH2. A large number of experimental studies prove that the polypeptide AT03 has a treatment effect on a common bile duct-ligated rat cholestatic liver cirrhosis model, and the treatment effect is specifically shown in that liver cholestasis, intrahepatic biliary obstruction, liver cell injury and liver tissue fibrosis process can be improved; and the polypeptide AT03 can be used for preparing the medicine used for treating primary biliary cholangitis.

Description

technical field [0001] The invention belongs to the technical field of biochemistry, in particular, the invention relates to a new application of polypeptide AT03, that is, the application of the polypeptide AT03 in the treatment of primary biliary cholangitis. Background technique [0002] Primary biliary cholangitis (PBC) is a relatively rare progressive cholestatic liver disease characterized by intrahepatic cholestasis and damage to bile duct cells, leading to liver fibrosis and cirrhosis. Serial complications, the mortality rate is three times that of ordinary people (Prince M, Chetwynd A, Newman W, et al. Survival and symptom progression in a geographically based cohort of patients with primary biliary pneumonia: follow-up for up to 28years[J]. Gastroenterology, 2002, 123(4):1044-51.). At the beginning, the disease was named primary biliary cirrhosis (PBC), and later in 2015 it was officially renamed as primary biliary cholangitis in order to describe the symptoms mor...

Claims

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Application Information

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IPC IPC(8): A61K38/07A61P1/16A61P29/00
Inventor 张斌智叶淑银
Owner SHENZHEN TURIER BIOTECH CO LTD
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