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Application of epalrestat in preparation of medicine for preventing and treating cerebral arterial thrombosis

An ischemic stroke and epalrestat technology, applied in the field of medicine, can solve the problem of lack of prevention and treatment drugs for ischemic brain injury, and achieve the effects of reducing endothelial cell apoptosis, reducing infiltration, and reducing inflammatory response.

Active Publication Date: 2022-02-01
HARBIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is still a lack of effective prevention and treatment drugs for ischemic brain injury in patients with ischemic stroke who have missed the treatment time window and cannot use thrombolytic therapy

Method used

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  • Application of epalrestat in preparation of medicine for preventing and treating cerebral arterial thrombosis
  • Application of epalrestat in preparation of medicine for preventing and treating cerebral arterial thrombosis
  • Application of epalrestat in preparation of medicine for preventing and treating cerebral arterial thrombosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] This example investigates the effect of epalrestat on cerebral ischemic injury in the process of cerebral ischemia.

[0056] The experimental animals used in the present invention are all purebred C57BL / 6 male mice with a body weight of 19-21 g, purchased from Liaoning Changsheng Biotechnology Co., Ltd.

[0057] Modeling, grouping, and administration methods: establish the mouse permanent middle cerebral artery occlusion model (pMCAL) and the sham operation group sham, respectively, and divide the pMCAL model and the sham operation (sham) group into normal (ischemic) groups - labeling The normal group, the epalrestat treatment group-Eps group and the sham group were intragastrically administered immediately after the establishment of the model. The dosage of the Eps group was 100 μg / g, and the Normal group was intragastrically administered with the same amount of normal saline.

[0058] Brain tissue sections were taken at the time points of ischemia time of 12h, 1d, 3d ...

Embodiment 2

[0061] This example investigates the effect of epalrestat on the neurobehavioral function of mice during cerebral ischemia.

[0062] This example observes the state and neurobehavioral changes of mice after cerebral ischemia, and reflects the severity of cerebral ischemia in mice. According to the experimental plan, mice are modeled with pMCAL, and the modeling, grouping, and administration methods are the same as in Example 1. same. The neurological score of normal mice is 0, and the more severe the symptoms related to ischemia, the greater the score. The neurobehavioral scoring criteria are shown in Table 1:

[0063] Table 1

[0064] Neurological Svevrity Scores neurobehavioral score Normal neurological function 0 marks Mild neurological deficit (flexion of right forelimb when tail is raised) 1 point Moderate neurological deficit (circles to the right while walking) 2 minutes Moderate neurological deficit (slope to the right) 3 points...

Embodiment 3

[0067] This example investigates the effect of epalrestat on the blood-brain barrier function during cerebral ischemia.

[0068] The modeling, grouping, and administration methods of this embodiment are all the same as in Example 1, and the mice are injected with Evans Blue (EB) dye into the tail vein at the time point when the ischemia time is 12h, 1d, 3d, and 5d, and after 2h The brain tissue was removed by perfusion to observe the penetration of the blue dye in the brain tissue. The result is as Figure 4 As shown, the blue is the damaged area of ​​the blood-brain barrier, and the white is the normal brain tissue; cerebral ischemia damage leads to the destruction of the integrity of the blood-brain barrier, and the EB dye can enter the brain parenchyma through the damaged blood-brain barrier to stain the ischemic area in blue .

[0069] Through trichloroacetic acid extraction, the content of EB in the brain tissue of each group was detected by ultraviolet spectrophotomete...

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Abstract

The invention relates to application of epalrestat in preparation of a medicine for preventing and treating cerebral arterial thrombosis (cerebral infarction), and belongs to the technical field of medicines. The invention provides application of epalrestat in preparation of the medicine for preventing and treating cerebral arterial thrombosis for cerebral arterial thrombosis patients who have missed a treatment time window and cannot be treated by thrombolysis in the early stage of cerebral arterial thrombosis. Epalrestat is used for treatment after cerebral arterial thrombosis, expression of aldose reductase can be inhibited, tight junction protein of cerebral microvascular endothelial cells can be up-regulated, endothelial cell apoptosis can be relieved, neurological dysfunction after cerebral arterial thrombosis can be improved, and integrity of blood-brain barrier after cerebral arterial thrombosis can be maintained; in addition, epalrestat can effectively reduce infiltration of peripheral inflammatory cells and relieve inflammatory response in ischemic brain tissue. The invention provides a new effective way for preventing and treating cerebral arterial thrombosis, and provides a theoretical basis for treating clinical cerebral arterial thrombosis by epalrestat.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to the application of epalrestat in the preparation of medicines for preventing and treating ischemic stroke. Background technique [0002] Stroke, also known as apoplexy, is an acute cerebrovascular disease. It is a disease that causes brain tissue damage due to sudden rupture of blood vessels in the brain or blockage of blood vessels that prevents blood from flowing into the brain, including ischemic and hemorrhagic strokes. The incidence of hemorrhagic stroke is higher than that of hemorrhagic stroke, accounting for 60-70% of the total number of strokes. Ischemic stroke is a complex process involving multiple systems. After ischemia, neurons will be damaged, and the permeability of the blood-brain barrier will increase, causing cerebral edema, resulting in increased intracranial pressure, forming brain herniation, and leading to disease. deterioration. [0003] In ...

Claims

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Application Information

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IPC IPC(8): A61K31/426A61P9/10A61P7/02A61P25/00
CPCA61K31/426A61P9/10A61P7/02A61P25/00
Inventor 王广友张彤帅钟镝汪丹丹张瑶王菁华孔庆飞张海玉孙博穆莉莉吴进荣李玄李晓波赵崴刘玉梅刘希君李呼伦汪嘉麒张思凡郎秀娟
Owner HARBIN MEDICAL UNIVERSITY
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