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Application of fingolimod hydrochloride in preparation of medicine for treating drug-induced liver injury

A fingolimod hydrochloride injury technology, applied in the application field of fingolimod hydrochloride, preparation of drugs for the treatment of drug-induced liver injury, can solve problems such as large side effects

Inactive Publication Date: 2019-05-14
THE SECOND AFFILIATED HOSPITAL OF NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Technical problem to be solved: The present invention aims at the problem of large side effects in the use of existing liver-protecting and enzyme-lowering drugs, and provides an application of fingolimod hydrochloride in the preparation of drugs for treating drug-induced liver injury

Method used

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  • Application of fingolimod hydrochloride in preparation of medicine for treating drug-induced liver injury
  • Application of fingolimod hydrochloride in preparation of medicine for treating drug-induced liver injury
  • Application of fingolimod hydrochloride in preparation of medicine for treating drug-induced liver injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] FTY720 attenuates APAP-induced liver injury

[0017] 1. Method: Source of kits required for the experiment: AST and ALT kits were purchased from Nanjing Jiancheng Bioengineering Institute, and FTY720 was purchased from Cayman Chemical Company. The experiment was divided into 4 groups: C57BL / 6 normal control group, FTY720 single treatment group, APAP single treatment group, FTY720 and APAP co-treatment group. The mice were starved overnight, and after 0.5 hour intraperitoneal injection of phosphate buffer solution or APAP (250 mg / kg ), FTY720 (5 mg / kg ) was injected intraperitoneally, the mice were anesthetized and sacrificed 6 hours and 24 hours later, and blood was collected.

[0018] 2. Results: see figure 1 , give mice intraperitoneal injection of APAP (250 mg / kg), at 6 hours and 24 hours can be observed in serum AST and ALT expression levels significantly increased; while FTY720 (5 mg / kg) and APAP co-treatment group, serum AST and ALT levels were significantly red...

Embodiment 2

[0020] FTY720 can reduce liver tissue necrosis induced by APAP

[0021] 1. Method: The mice were grouped as described in Example 1. The mice were starved overnight, and after 0.5 hours of intraperitoneal injection of phosphate buffered saline or APAP (250 mg / kg), FTY720 (5 mg / kg ) was injected intraperitoneally, respectively. After 6 hours and 24 hours, the mice were sacrificed under anesthesia, and the liver tissues were taken for H&E staining and TUNEL staining.

[0022] 2. Results: see figure 2 , After APAP treatment, the area of ​​diffuse apoptotic necrosis in the center of the hepatic lobule of the mouse was significantly increased, and after 6 hours and 24 hours of treatment with FTY720, the area of ​​necrosis in the mouse liver tissue was significantly reduced.

Embodiment 3

[0024] FTY720 can reduce the infiltration of inflammatory cells in liver tissue induced by APAP

[0025] 1. Method: The mice were grouped as described in Example 1, starved overnight, intraperitoneally injected with phosphate buffer saline or APAP (250 mg / kg) for 0.5 hours, and intraperitoneally injected with FTY720 (5 mg / kg), respectively, at 6 hours And 24 hours later, the mice were anesthetized, and the liver was removed. The liver tissue was fixed with 4% formaldehyde solution at 4 degrees for 72 hours and then sectioned. Histochemistry was stained with MPO and CD68.

[0026] 2. Results: see image 3 , After APAP treatment, the number of neutrophils and macrophages in the diffuse necrosis area of ​​the mouse hepatic lobule increased significantly. Cell and macrophage numbers were significantly reduced.

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Abstract

The invention relates to application of Fingolimod hydrochloride in preparation of drugs for treating drug-induced liver injury. The Fingolimod hydrochloride (FTY720) can be used for remarkably lowering the level of alanine transaminase and aspartate transaminase in APAP-induced liver injury, reducing the area of necrosis of liver tissue, lowering the mouse death rate induced by fatal dose of APAP and reducing the expression level of inflammatory factors and chemotactic factors during the drug-induced liver injury.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to the application of fingolimod hydrochloride in the preparation of medicines for treating drug-induced liver injury. Background technique [0002] As an important detoxification organ of the human body, the liver is easily damaged by toxic substances. In my country, liver disease is a disease with a high incidence rate and is difficult to cure, and it is also one of the common refractory diseases in the world today. The carrier rate of hepatitis B virus in my country is about 10%, which is very harmful to human health. Liver injury is generally susceptible in the population, the incubation period is short, and the course of the disease is directly related to the dose of infection, which can cause different degrees of liver cell necrosis, fatty deformation, liver cirrhosis, and liver cancer. A variety of drugs can cause liver damage, such as anti-tumor chemotherapy drugs, anti...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/137A61P1/16
CPCA61K31/137
Inventor 周洪廖翔张俊尤强朱星星温爽
Owner THE SECOND AFFILIATED HOSPITAL OF NANJING MEDICAL UNIV