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Application of NADPH in positional drug-induced mitochondrial toxicity

A mitochondrial and drug technology, applied in the direction of antidote, drug combination, medical preparations containing active ingredients, etc., can solve the problem of mitochondrial toxicity caused by no NADPH antagonistic drugs, and achieve the effect of reducing mortality and curbing progress

Active Publication Date: 2017-09-29
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

[0007] At present, there are no reports of mitochondrial toxicity caused by NADPH antagonists

Method used

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  • Application of NADPH in positional drug-induced mitochondrial toxicity
  • Application of NADPH in positional drug-induced mitochondrial toxicity
  • Application of NADPH in positional drug-induced mitochondrial toxicity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1 Preparation of NADPH capsules

[0040] The composition of present embodiment NADPH capsule is: NADPH 20g, suspending agent microcrystalline cellulose 60g, preservative tert-butyl-4-hydroxyanisole 0.04g, lubricant magnesium stearate 2g, filler lactose added to 200g.

[0041] The preparation method comprises the following steps: respectively weighing the above prescription amount of NADPH and various pharmaceutical excipients, mixing uniformly, sieving through a 60-mesh sieve for three times, and packing into capsule shells to obtain the product.

experiment example 1

[0042] Experimental example 1 NADPH reduces the in vivo active form of MPTP, MPP + and the injury experiment of rotenone on PC12 cells

[0043] 1. Purpose of the experiment

[0044] Study of NADPH on MPTP's in vivo active form MPP + , rotenone and CCCP on the damage of PC12 cells.

[0045] 2. Experimental method

[0046] 2.1 Experimental materials

[0047] The differentiated PC12 cell line was purchased from Shanghai Institute of Cells, Chinese Academy of Sciences.

[0048] 2.2 Experimental method

[0049] 2.2.1 PC12 cells to MPP + , Establishment of in vitro model of rotenone

[0050] PC12 cells were cultured in DMEM with 10% fetal bovine serum, MPP + 5mM or rotenone 500nM or CCCP10M intervention 24h model.

[0051] 2.2.2 Administration method

[0052] NADPH 10 μM, 30 μM or 100 μM in MPP + Added 1 h before the intervention, and the cell viability was detected by the CCK-8 method. MPP + After 24 hours of intervention, 10 μL of CCK-8 chromogen was added to 100 μ...

experiment example 2

[0068] Experimental example 2 NADPH reduces MPTP-induced mitochondrial damage in mouse midbrain neurons

[0069] 1. Purpose of the experiment

[0070] To study the effect of NADPH on mitochondrial damage of midbrain neurons in MPTP model mice. 2. Experimental method

[0071] 2.1 Experimental materials and experimental environment

[0072] Clean-grade male C57bl / 6 mice, weighing 25-30 g, male, 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.

[0073] The room temperature is 22°C, the humidity is 50-60%, the ventilation is good, artificial day and night (12h / 12h), free to eat and drink. Before the experiment, the mice were acclimatized in the rearing environment for 2 days.

[0074] 2.2 Experimental grouping

[0075] C57bl / 6 mice were randomly divided into 5 groups, namely: normal control group, model control group, and experi...

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Abstract

The invention belongs to the field of drugs or health products and particularly relates to an application of NADPH in positional drug-induced mitochondrial toxicity. The research finds that the NADPH has a protective effect on mitochondria damage caused by MPTP and rotenone, plays a neuroprotective effect through the protective effect, but has no protective effect on CCCP-caused mitochondria damage, so that the NADPH can be applied to control of neurodegenerative diseases, such as ageing, sub-health and huntington's chorea caused by mitochondrial dysfunction, vascular dementia, Lewy body dementia with frontal dementia, amyotrophic lateral sclerosis and multiple sclerosis.

Description

technical field [0001] The invention belongs to the field of medicine or health products, and specifically relates to the application of NADPH in antagonizing the mitochondrial toxicity caused by drugs. Background technique [0002] Mitochondria are indispensable organelles in cell physiological activities. Mitochondria are mainly responsible for the production of ATP, which is equivalent to the "power plant" of human cells, providing energy for all physiological activities of cells. A large number of studies have shown that mitochondria play a very important role in regulating cell growth, proliferation, differentiation and death. Especially under pathological conditions, the functional state of mitochondria largely determines the survival and death of cells. In recent years, more and more studies have shown that mitochondrial damage is an important feature of the toxicity of many drugs, and suggest that mitochondria may be an important target of drug toxicity. [0003] S...

Claims

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Application Information

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IPC IPC(8): A61K31/7084A61P39/02A61P39/06A61P25/28
CPCA61K31/7084
Inventor 秦正红周静思吴锋
Owner 山东蓝康药业有限公司
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