Application of alanyl-glutamine (Ala-Gln) in preparation of medicine for preventing and treating acute liver failure

A technology for acute liver failure and glutamate dipeptide, which is applied in the field of biomedicine to achieve the effects of inhibiting the relevant inflammatory response in the liver, reducing the liver function index, and reducing congestion and edema.

Active Publication Date: 2021-08-06
NINGBO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above studies show that dipipeptide has a good protective effect in various cell and tissue injury models, bu...

Method used

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  • Application of alanyl-glutamine (Ala-Gln) in preparation of medicine for preventing and treating acute liver failure
  • Application of alanyl-glutamine (Ala-Gln) in preparation of medicine for preventing and treating acute liver failure
  • Application of alanyl-glutamine (Ala-Gln) in preparation of medicine for preventing and treating acute liver failure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1 The protective effect of CG dipeptide on acute liver failure induced by LPS combined with D-Gal

[0027] 1. Experimental materials:

[0028] In this example, the dosage form of dipeptide injection is adopted, including dipeptide main body and drug carrier.

[0029] Among them, the main body of dipeptide is a composition containing one or more of dipeptide and its pharmaceutically acceptable salts, esters, and solvates. The main compound of dipeptide is synthesized by the laboratory itself.

[0030] Wherein, the drug carrier includes water, physiological saline, phosphate buffer saline, bacteriostatic water, ethanol, polyhydric alcohol and mixture thereof, as well as liposome and polymer nanoparticle. These compositions must be sterile and liquid injectables.

[0031] 2. Experimental method:

[0032] (1) Construction of mouse model of acute liver failure and treatment with dipeptide administration:

[0033] This experiment was carried out in an SPF level ex...

Embodiment 2

[0049] Example 2 The effect of gludipeptide on the hepatocyte apoptosis pathway induced by LPS combined with D-Gal

[0050] 1. Experimental method:

[0051] (1) Construction of mouse model of acute liver failure and administration of CG dipeptide: the same as in Example 1

[0052] (2) Protein extraction and Western blot analysis:

[0053] Add the cut liver tissue into RIPA lysate (Biyuntian) containing protease inhibitor (Roche), put it into a tissue vibrating grinder (Shanghai Jingxin) for full shaking and lysing, centrifuge at 12000g for 5 minutes, and take the protein on the The supernatant was boiled for 10 minutes, quantified by the BCA protein quantification kit (Thermo), and then subjected to SDS-PAGE gel electrophoresis, and then the protein was transferred to a PVDF membrane, blocked with 5% BSA for 1 h, using anti-Bax primary antibody (CST) and Anti-caspase-3 primary antibody (CST) was incubated overnight at 4°C. After washing 3 times, they were incubated with enz...

Embodiment 3

[0056] Example 3 Effect of CG dipeptide on redox balance in acute liver failure induced by LPS combined with D-Gal

[0057] 1. Experimental method:

[0058] (1) Construction of mouse model of acute liver failure and administration of CG dipeptide: the same as in Example 1

[0059] (2) Protein extraction and Western blot analysis:

[0060] The primary antibody used in Western blot is an anti-Nrf-2 antibody (Wuhan Sanying), and the other parts are the same as in Example 2.

[0061] 2. Experimental results:

[0062] Under normal circumstances, the liver can maintain its own redox balance, but when acute liver failure occurs, the redox balance in the liver is disrupted, resulting in oxidative stress. Under stress, the liver tissue is more vulnerable to excessive free radicals, leading to liver damage. Therefore, the state of oxidative stress is one of the important indicators to measure liver damage. Experimental results such as image 3 As shown, the results showed that in ...

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Abstract

The invention discloses application of alanyl-glutamine (Ala-Gln) in preparation of a medicine for preventing and treating acute liver failure. The application is characterized in that the alanyl-glutamine or pharmaceutically acceptable salt, ester and solvate thereof is applied to prevention and treatment of an acute immune mouse liver failure model induced by Lipopolysaccharide (LPS) combined with D-galactosamine (D-Gal). Pharmacological experiments find that the alanyl-glutamine administration can obviously improve the liver tissue structure disorder, reduce extravasated blood and edema of liver tissues, reduce glutamic-pyruvic transaminase, glutamic oxalacetic transaminase and other liver function indexes and inhibit inflammatory reactions in the liver. The application has the advantage that the alanyl-glutamine provides a new method for preventing and treating LPS/D-Gal induced acute liver failure and liver injury.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of a dipeptide in the preparation of medicines for preventing and treating acute liver failure. Background technique [0002] Acute liver failure (ALF) is a kind of severe clinical syndrome caused by various factors in a short period of time, a large number of hepatic cell necrosis and severe liver function damage, and hepatic encephalopathy. The incidence of acute liver failure is increasing year by year, and it has become a public health problem that seriously affects human health. At present, the commonly used treatment methods include eliminating the cause, improving immune function, preventing complications, artificial liver treatment, liver transplantation, etc. Among them, liver transplantation is the most effective method for the treatment of liver failure, but due to the scarcity of liver sources and high cost, it is relatively expensive. It is diffi...

Claims

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Application Information

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IPC IPC(8): A61K38/05A61P1/16
CPCA61K38/05A61P1/16
Inventor 李龙赵玉芬胡嘉继
Owner NINGBO UNIV
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