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Application of NADPH in preparing medicaments for preventing and treating ischemic cerebral stroke

A drug and aspect technology, applied in the field of new drug use, to achieve the effect of small dosage and wide use

Active Publication Date: 2013-10-09
山东蓝康药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, there is currently no literature reporting whether TIGAR and NADPH play a protective role in cerebral ischemia

Method used

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  • Application of NADPH in preparing medicaments for preventing and treating ischemic cerebral stroke
  • Application of NADPH in preparing medicaments for preventing and treating ischemic cerebral stroke
  • Application of NADPH in preparing medicaments for preventing and treating ischemic cerebral stroke

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0047] Example TIGAR reduces cerebral ischemia-reperfusion injury by increasing the production of NADPH

[0048] (1) Experimental materials

[0049] Clean-grade male ICR mice, weighing 23-28 g, were provided by the Experimental Animal Center of Soochow University, experimental animal production license number: XCYK (Su) 2002-2008, experimental animal use license number: SYXK (Su) 2002-0037. Room temperature 22°C, humidity 50-60%, well ventilated, artificial day and night (12h / 12h), free to eat and drink. Before the experiment, the male mice were acclimatized in the breeding environment for 2 days. Divided into 5 groups: overexpression TIGAR mice group (LV-TIGAR mice), silent TIGAR mice group (LV-sh_TIGAR or knockdown mice), LV-GFP group was the negative control group of overexpression TIGAR mice, LV-sh_TIGAR group was Negative control group of silenced TIGAR mice. NADPH reagent was purchased from Jiangsu Biyuntian Biological Reagent Company; the source of exogenous NADPH dr...

Embodiment 2

[0089] Example 2 The protective effect of exogenous NADPH on primary cortical neuron injury in mice lacking glucose and hypoxia

[0090] (1) Experimental materials and grouping are the same as in Example 1. Refer also to Example 1 for the relevant experimental conditions.

[0091] (2) Experimental plan:

[0092] Culture of primary cortical neurons: Take 17-day-pregnant ICR mouse fetuses under sterile conditions, peel off the cerebral hemispheres, peel off the pia mater and blood vessels under a dissecting microscope, separate the cerebral cortex tissue, and rinse with pre-cooled PBS for 2- 3 times, then digested with 1.25% trypsin at 37°C for 15-30min, stopped the trypsin with DMEM / F12 culture medium containing 10% serum, then treated the cells with DNase I for 3min, and finally separated the tissue into a single cell suspension by blowing with a pipette Cells were counted with a counting plate in Neurobasal Medium containing 10% B27, 5% Pen / Strep, and 25 μM Glutamate, and s...

Embodiment 3

[0103] Example 3 Therapeutic Administration of NADPH to Reduce Cerebral Ischemia Damage

[0104] Experimental material, grouping are with embodiment 1. Refer also to Example 1 for the relevant experimental conditions.

[0105] Experimental program:

[0106] ICR mice, weighing 23-28 g, were randomly divided into 6 groups, 20 in each group, respectively saline (vehicle) group, 0h group, 2h group, 4h group, 6h group, and 8h group. NADPH (2.5mg / kg) was injected into the body through the tail vein at 0h, 2h, 4h, 6h, and 8h after reperfusion.

[0107] The experimental results are as follows:

[0108] Figure 21 The effect of NADPH given therapeutically on cerebral infarct volume in mice with cerebral ischemic stroke. The results of TTC staining showed that compared with the vehicle group, after reperfusion 0h, 2h, 4h tail vein administration of NADPH significantly reduced the volume of cerebral infarction in mice (p<0.05, p<0.01). There was no significant difference between 6h...

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Abstract

The invention discloses an application of NADPH in preparing medicaments for preventing and treating ischemic cerebral stroke. Research proves that by increasing NADPH generation and reducing ROS level in cells, TIGAR helps to protect neutrons from cerebral ischemia-reperfusion injury mediated by oxidative stress. Therefore, the giving of exogenous NADPH helps to reduce cerebral infarction volume, substantially improve behavior obstacle of cerebral ischemia mice, mitigate cerebral edema, improve mouse long-term survive capability and enhance neurobehavioral function rehabilitation.

Description

technical field [0001] The invention belongs to the technical field of new uses of medicines, and specifically relates to the application of NADPH as a medicine for preventing and treating cerebral ischemic stroke. Background technique [0002] Stroke, also known as cerebral apoplexy or cerebrovascular accident, is a sudden-onset cerebral blood circulation disorder and one of the three major diseases that threaten human health. The characteristics of high residual rate and high recurrence rate. Stroke refers to patients with cerebrovascular disease, due to various predisposing factors causing cerebral artery stenosis, occlusion or rupture, resulting in acute cerebral blood circulation disorder, clinically manifested as symptoms of transient or permanent brain dysfunction and signs. Stroke is divided into ischemic stroke and hemorrhagic stroke. In recent years, the number of patients with cerebrovascular diseases in my country has increased year by year, and ischemic cereb...

Claims

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Application Information

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IPC IPC(8): A61K31/7084A61P9/10
CPCA61K31/7084A61P9/10
Inventor 秦正红李梅
Owner 山东蓝康药业有限公司
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