Application of SAG in preparation of drug for treating diseases of hypoxic-ischemic brain damage during development

A technology for hypoxia-ischemia and developmental stage, which is applied in the fields of cardiovascular system diseases, drug combinations, and pharmaceutical formulas. It can solve the problems of incompletely clear pathogenesis of HIE, limited treatment methods, lack of effective treatment methods, etc., and achieve obvious social benefits. and economical effects

A technology for hypoxia-ischemia and developmental stage, which is applied in the fields of cardiovascular system diseases, drug combinations, and pharmaceutical formulas. It can solve the problems of incompletely clear pathogenesis of HIE, limited treatment methods, lack of effective treatment methods, etc., and achieve obvious social benefits. and economical effects

CN108938631AActive Publication Date: 2018-12-07THE WEST CHINA SECOND UNIV HOSPITAL OF SICHUAN
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  • Application of SAG in preparation of drug for treating diseases of hypoxic-ischemic brain damage during development
  • Application of SAG in preparation of drug for treating diseases of hypoxic-ischemic brain damage during development
  • Application of SAG in preparation of drug for treating diseases of hypoxic-ischemic brain damage during development

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Experimental program
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Effect test

Embodiment Construction

[0018] 1. Experimental materials and reagents

[0019] 1.1. Experimental animals

[0020] Healthy and clean 7-day-old newborn SD rats, male or female, weighing 14-22 grams, were purchased from Chengdu Dashuo Experimental Animal Co., Ltd. The experiment is divided into two parts, the first part is to determine the appropriate SAG concentration. Randomly divided into sham operation group, solvent control group, SAG high-dose experimental group (25mg / kg), SAG medium-dose experimental group (15mg / kg), SAG low-dose experimental group (5mg / kg), each group of 12 SD large mouse. Solvent control group, SAG high-dose experimental group, SAG medium-dose experimental group, and SAG low-dose experimental group were intraperitoneally injected with solvent (double distilled water) or corresponding concentration of SAG 2 hours after modeling. According to the results of TTC and H&E staining, the suitable dose group of SAG was determined. The second part will be randomly divided into sham ...

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Abstract

The invention discloses an application of SAG in preparation of a drug for treating diseases of hypoxic-ischemic brain damage during development. Experiments show that intraperitoneal injection of 5-25mg / kg of SAG after 2 hours after hypoxic-ischemia in neonatal rats can reduce cerebral infarction. Further study on the neonatal rats applied with 15mg / kg of SAG shows that SAG can significantly improve brain damage and reduce nerve cell disintegration and necrosis after anoxia and ischemia. The Morris water maze experiments prove that 15mg / kg of SAG can effectively improve the learning ability of hypoxic-ischemic rats. Further study shows that 2, 3, 5-cholo-triphenyltetrazolium-positive cells of the rats in the SAG medium-dose experimental group rat (15mg / kg SAG) are significantly reduced, the IL-1 beta and TNF-alpha mRNA in the cerebral cortex are decreased and the expression of a glial fibrillary acidic protein is reduced.

Description

technical field [0001] The present invention relates to the application of Smoothened Agonist (SAG for short), especially the application in pharmacy. Background technique [0002] Hypoxic-ischemic encephalopathy (HIE) is a common neurological disease in newborns, which can lead to epilepsy, cerebral palsy, growth retardation, etc., and brings a heavy burden to society and families. Despite decades of research, the pathogenesis of HIE is still not completely clear, and clinically effective treatments are lacking. Therefore, it is of great and positive significance to actively explore the intervention and treatment of HIE. The existing clinical treatment methods are very limited, mainly mild hypothermia and symptomatic and supportive treatment. [0003] Smoothened Agonist (SAG for short) is a small molecular synthetic substance with the molecular formula C 28 h 29 C l2 N 3 OS, molecular weight 526.52, chemical structure as follows: [0004] [0005] SAG is now mainly...

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Application Information

Patent Timeline
07 Dec 2018
Publication
CN108938631A
IPC
A61K31/4436; A61P9/10
CPC
A61K31/4436; A61P9/10
Inventors
母得志; ι»„ε…°