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Novel nerve protective agent

A neuroprotective agent and dosage technology, which is applied in cardiovascular system diseases, medical preparations containing active ingredients, drug combinations, etc., can solve the problems of inseparable signal pathways, side effects of normal physiological functions, etc., achieve strong protective effects, reduce Cerebral infarct volume and effect of reducing neurological damage

Inactive Publication Date: 2013-09-04
张东才
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it has been clinically proven that there are very few effective neuroprotective agents for stroke. One of the reasons is that any damage is not independent. Oxygen free radical damage is often associated with excitatory amino acid toxicity, apoptosis and inflammatory response. Signaling pathways are inseparable
However, the existing protective agents mainly act on a single target, and have no direct effect on the downstream signal of the target or other cascade reactions; moreover, excessive blocking of a single target often affects the normal physiological function of the target intolerable side effects

Method used

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Examples

Experimental program
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Effect test

Embodiment 1

[0025] The protective effect of antioxidant PG, calcium chelator BAPTA-AM and PARP inhibitor DPQ on hydrogen peroxide-induced apoptosis.

[0026] Human neuroblastoma SK-N-SH cells were cultured in MEM medium and incubated with hydrogen peroxide (final concentration 0.5mmol / L) for 1 hour, then fresh MEM medium was used to replace the hydrogen peroxide-containing medium, and then washed away hydrogen peroxide. Antioxidant PG, calcium ion chelating agent BAPTA-AM and PARP inhibitor DPQ were pre-administered 1 hour before hydrogen peroxide injury, and the administration was continued after the hydrogen peroxide was removed until the experiment was measured. In the experiment, Hoechst 33342 staining was used to calculate cell occurrence The number of apoptosis.

[0027] (1) The changes of calcium ion and PARP during the apoptosis of human neuroblastoma SK-N-SH cells induced by hydrogen peroxide.

[0028] Such as figure 1 Shown: (A) Schematic diagram of changes in calcium ion concentrati...

Embodiment 2

[0031] Antioxidant PG, calcium ion chelator BAPTA-AM and PARP inhibitor DPQ have a dose-dependent protective effect on hydrogen peroxide-induced apoptosis.

[0032] Such as figure 2 Shown: Calcium ion chelating agent BAPTA-AM( figure 2 A), antioxidant PG ( figure 2 B) and PARP inhibitor DPQ ( figure 2 C) Respectively showed a dose-dependent protective effect on hydrogen peroxide-induced apoptosis. The drugs were incubated 1 hour before hydrogen peroxide damage, and then incubated for 8 hours after removing the hydrogen peroxide damage. The number of apoptosis of the cells was counted by Hoechst 33342 staining. The values ​​of each group were divided by the apoptosis value of the hydrogen peroxide group to obtain the standardized apoptosis rate. The displayed value is expressed as the mean ± standard deviation of three independent experiments.

[0033] The drugs were incubated 1 hour before the hydrogen peroxide damage, and then incubated for 8 hours after removing the hydrogen...

Embodiment 3

[0035] Antioxidant PG, calcium ion chelator BAPTA-AM (abbreviated as BA in the figure) and PARP inhibitor DPQ have a protective effect on hydrogen peroxide-induced apoptosis of human neuroblastoma SK-N-SH cells.

[0036] Such as image 3 Shown: after 1 hour incubation with 0.5mmol / L hydrogen peroxide, MEM fresh medium replaces the culture medium containing hydrogen peroxide. The apoptosis rate was detected by Hoechst 33342 staining 8 hours after the hydrogen peroxide was washed away. The values ​​of each group were divided by the apoptosis value of the hydrogen peroxide group to obtain the standardized apoptosis rate. ( image 3 A) The protective effect of the combination of calcium chelator BAPTA-AM and PARP inhibitor DPQ on hydrogen peroxide-induced apoptosis. ( image 3 B) The protective effect of the combination of calcium ion chelator BAPTA-AM and antioxidant PG on apoptosis caused by hydrogen peroxide. ( image 3 C) The protective effect of the combination of antioxidant ...

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Abstract

The invention discloses a novel nerve protective agent, which belongs to the technical field of nerve protective medicine. The novel nerve protective agent comprises one kind or two kinds or three kinds of the following ingredients and contents: (1) antioxidants (with the dosage between 2.0 and 200 mg / kg); and (2) calcium ion antagonists (with the dosage between 1.0 and 400 mg / kg); and (3) adenosine diphosphate RNA polymerase inhibitors (with the dosage between 2.0 and 300 mg / kg). The invention carries out multi-blockage on the neurotrosis induced by free radicals in an acute phase of hypoxic-ischemic brain damage. Particularly, when three kinds of anti-oxygen free radicals-anti-inter-cell calcium ion overloading-PARP inhibitors are in combined use, the invention provides the protective effect on the acute phase damage of the ishemic stroke from multiple levels and multiple target points. Compared with a single protective agent, the compounded protective agent has stronger protective effect on both the in-vivo oxidative stress damage and the in-vitro oxidative stress damage of the ishemic stroke, and has good treatment effect on the hemorrhagic stroke.

Description

Technical field [0001] The invention belongs to the technical field of neuroprotective drugs, and particularly relates to a novel compound neuroprotective agent against ischemic stroke injury. Background technique [0002] With the increase in average life expectancy and changes in lifestyle, the incidence of stroke has shown an upward trend in recent years, especially ischemic stroke; at present, ischemic stroke is one of the most fatal diseases in China. Among them, 80% of strokes are caused by embolism or thrombus obstruction of cerebral blood vessels, resulting in temporary or permanent reduction of cerebral blood flow, which in turn leads to the formation of cerebral infarction. Among the survivors, 30% of patients have severe sequelae due to cerebral infarction, such as vascular dementia and corresponding limb disorders. [0003] Studies have found that in the acute phase of cerebral ischemia (within 72 hours), effective intervention in the pathological process of cerebral i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61P9/10
Inventor 张东才郭静肇玉明韩怡凡李文明
Owner 张东才
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