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Application of mitiglinide in preparation of medicine for treating cerebral arterial thrombosis

A technology for ischemic stroke and ischemic stroke, applied in the field of application of mitiglinide in the preparation of drugs for the treatment of ischemic stroke, achieving huge market value and social benefits

Inactive Publication Date: 2013-08-14
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, studies have found that mitiglinide can maintain and prolong the protective effect of ischemic preconditioning on myocardial ischemia, but its protective effect on neurological injury diseases such as cerebral ischemic nerve injury and neurodegenerative diseases has not been reported yet. It has extremely high potential value and social significance to develop it into a drug for the treatment of ischemic stroke

Method used

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  • Application of mitiglinide in preparation of medicine for treating cerebral arterial thrombosis
  • Application of mitiglinide in preparation of medicine for treating cerebral arterial thrombosis
  • Application of mitiglinide in preparation of medicine for treating cerebral arterial thrombosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1 Neuroprotective effect of mitiglinide on transient middle cerebral artery embolism model (tMCAo) mice

[0024] 1.1 Experimental materials

[0025] 1.1.12-3 months old, male C57BL / 6J mice, 24-28g. Purchased from the Experimental Animal Center of Nanjing Medical University, animal production license number: SCXK (Su) 2008-0004. Feeding conditions include standard feed, tap water, room temperature maintained at (24±2)°C, humidity 50-60%, and daily light and dark times of 12 hours each. Before the experiment, the animals were placed in the experimental environment for 3 days to adapt.

[0026] 1.1.2 Miglinide calcium (Lianyungang Runzhong Pharmaceutical Co., Ltd., batch number 1612001), prepared with normal saline, the concentration of the mother solution is 1.2mg / ml, and stored at -20°C. 2,3,5-triphenyltetrazolium chloride (2,3,5-triphenyltetrazoliumchloride, TTC, purchased from sigma company), and others are commercially available.

[0027] 1.2 Method

[00...

Embodiment 2

[0037] Example 2 Study on the neuroprotective effect of mitiglinide on rats with permanent middle cerebral artery embolism (pMCAo)

[0038] 2.1 Experimental materials

[0039] 2.1.1 Animals: 2-3 months old, male SD rats, 230-270g. Purchased from the Experimental Animal Center of Nanjing Medical University, animal production license number: SCXK (Su) 2008-0004. Feeding conditions include standard feed, tap water, room temperature maintained at (24±2)°C, humidity 50-60%, and daily light and dark times of 12 hours each. Before the experiment, the animals were placed in the experimental environment for 3 days to adapt.

[0040] 2.1.2 Same as 1.1.2.

[0041] 2.2 Method

[0042] pMCAo rat model: Rats were fasted for 12 hours before operation, and the rats were anesthetized by intraperitoneal injection of chloral hydrate (350mg / kg), so that the rats stopped their voluntary activities and their muscles relaxed. Referring to the tMCAo mouse model, the right middle cerebral artery ...

Embodiment 3

[0047] Implementation Example 3 The protective effect of mitiglinide on oxygen-glucose deprivation SH-SY5Y cell injury

[0048] 3.1 Experimental materials

[0049] SH-SY5Y cell line: neuron cell line, purchased from Union Cell Institute, Chinese Academy of Medical Sciences. Methazolium Blue (MTT) was purchased from Guangzhou Chemical Reagent Factory; microplate reader was purchased from Thermo Company.

[0050] LDH assay kit: product of Nanjing Jiancheng Institute of Bioengineering.

[0051] 3.2 Method

[0052] 3.2.1 SH-SY5Y cell oxygen-glucose deprivation model: SH-SY5Y cell line was cultured in DMEM medium containing 10% FBS (37°C, 5% CO 2 ), inoculated on a 96-well plate and cultured for 24 hours before the experiment. On the experimental day, pre-administration was incubated for 30 minutes, and then the drug-containing sugar-free DMEM medium was changed to a three-gas incubator (37°C, 1% O 2 , 94%N 2 , 5%CO 2 ) Oxygen-glucose-deprived culture for 60 minutes, return ...

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Abstract

The invention provides an application of mitiglinide (MGN) in preparation of a medicine for treating the cerebral arterial thrombosis. An experiment shows that under the condition that the dosage of blood sugar is not reduced, the MGN can obviously improve the neurological disorder of a mice model or a rat model suffering from the cerebral arterial thrombosis and reduce the volume of the cerebral infarction; and the MGN inhibits the reduction of the survival rate of SH-SY5Y cells of a neuron cell strain caused by the oxygen-glucose deprivation (OGD), so that release of lactic dehydrogenase (LDH) is reduced, and the neuronal apoptosis caused by the OGD is improved. A result shows that the MGN has pharmacological effects of treating the cerebral arterial thrombosis and reducing the neuron damage caused by the OGD; and the treatment effect is bidirectional. The invention aims to prepare the medicine for treating the cerebral arterial thrombosis by taking the MGN as an active component.

Description

technical field [0001] The invention belongs to the application of mitiglinide, in particular to the application of mitiglinide in the preparation of medicine for treating ischemic stroke. Background technique [0002] Stroke is a group of cerebral blood circulation disorders with sudden onset and characterized by focal neurological loss. Its etiology is mainly caused by various factors that cause stenosis, occlusion or rupture of cerebral arteries, resulting in acute cerebral blood circulation disorder, clinically manifested as symptoms and signs of transient or permanent neurological dysfunction, with high morbidity and high fatality High morbidity rate, high disability rate, high recurrence rate and other characteristics, most of the surviving patients have residual dysfunction such as hemiplegia and aphasia. In European and American countries, stroke is the third leading cause of death after tumors and heart diseases, and it ranks the second leading cause of death in my...

Claims

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Application Information

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IPC IPC(8): A61K31/4035A61P25/00A61P9/10
Inventor 胡刚王林晓丁建花董银凤曹文静
Owner NANJING MEDICAL UNIV
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