Application of dexrazoxane in preparation of drug for treating neurodegenerative diseases

A technology of neurodegenerative and dextropropanimine, which is applied in nervous system diseases, drug combinations, pharmaceutical formulations, etc., can solve the problem of no reports of dextropropimine in the treatment of neurodegenerative diseases, etc., and achieve the reduction of α-synuclear Protein deposition, huge market value and social benefits, the effect of improving behavioral disorders

Inactive Publication Date: 2012-02-15
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Dextropropanimine is currently mainly used clinically for the prevention and treatment of cardiotoxicity during doxorubicin treatment, but there is no report on the treatment of neurodegenerative diseases

Method used

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  • Application of dexrazoxane in preparation of drug for treating neurodegenerative diseases
  • Application of dexrazoxane in preparation of drug for treating neurodegenerative diseases
  • Application of dexrazoxane in preparation of drug for treating neurodegenerative diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Dextropropanimine improves the behavioral symptoms of 6-hydroxydopamine-induced Parkinson's disease model rats

[0036] 1.1 Experimental materials

[0037] 7-8 weeks old, 180-220g healthy male SD rats. Feeding conditions included 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.

[0038]Dextropropylimine (DEX) was donated by Jiangsu Aosaikang Pharmaceutical Co., Ltd. 6-Hydroxydopamine (6-OHDA) and apomorphine (apomorphine) were purchased from Sigma (St. Louis, MO, USA), and both were prepared in normal saline. Aliquots of 6-OHDA were stored at -20 °C, and apomorphine was freshly prepared within 30 min before administration. Brain stereotaxic instrument was purchased from Stoelting Company of the United States.

[0039] 1.2 Establishment of animal models

[0040] Anesthe...

Embodiment 2

[0045] Example 2 Neuroprotective Effect of Dextropropanimine on Chronic MPTP / p Nerve Injury Model Mice

[0046] 2.1 Experimental materials

[0047] 3-4 months old, healthy male C57BL / 6J mice. Feeding conditions included 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.

[0048] Dextropropylimine (DEX) was donated by Jiangsu Aosaikang Pharmaceutical Co., Ltd. MPTP was purchased from Sigma (St. Louis, MO, USA), and probenecid was purchased from Jinan Times Pharmaceutical Technology Co., Ltd. DEX was prepared with normal saline, prepared into a stock solution and stored at -20 °C, and the prepared stock solution was diluted with normal saline to the required concentration before use. MPTP was prepared with normal saline within 30 min before administration and kept on ice. Probenecid was pre...

Embodiment 3

[0058] Example 3 Dextropropanimine to MPP + induce Protective effect of SH-SY5Y cell injury

[0059] 3.1 Experimental materials

[0060] SH-SY5Y cell line: dopaminergic neuron cell line, purchased from Union Cell Institute, Chinese Academy of Medical Sciences. Dextropropylimine (DEX) was donated by Jiangsu Aosaikang Pharmaceutical Co., Ltd. MPP + purchased from Sigma (St. Louis, MO, USA); H 2 o 2 and methazolium blue (MTT) were purchased from Guangzhou Chemical Reagent Factory; microplate reader was purchased from Thermo Company.

[0061] 3.2 Experimental method

[0062] Cells were seeded on 96-well plates and cultured for 24 hours, then the culture medium was replaced, and the cells were randomly divided into groups. Pretreatment with different concentrations of DEX for 30 min, followed by H 2 o 2 (300 μM, 2h) or MPP + (500 μM, 48h), 20 μl of 5 mg / ml MTT solution was added to each well, and incubation was continued for 4 h before the culture was terminated. Car...

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Abstract

The invention provides application of dexrazoxane in preparation of drug for treating neurodegenerative diseases. Experiments prove that dexrazoxane can improve the behavior disorder of model rats of Parkinson's disease belonging to neurodegenerative diseases, inhibit the decrease of TH (helper T cell) nerve cells in mouse mesencephalic SNc (substantia nigra compact part) and ventral tegmental area (VTA), which is caused by MPTP / p (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / probenecid) modeling, improve the proliferation and activation of astrocyte and microglia, obviously inhibit the over-expression of alpha-synuclein in substantia nigra compact part and reticular part, and inhibit the reduction of survival rate of dopaminergic neuron cell strain SH-SY5Y cells, which is caused by H2O2 and MPP<+> (1-methyl-4-phenylpyridinium ion). The results show that dexrazoxane has the action of treating neurodegenerative diseases. Through the invention, dexrazoxane can be used as an active ingredient to prepare the drug for treating neurodegenerative diseases.

Description

technical field [0001] The invention belongs to the field of medicines, and relates to the application of dextropropimine in the preparation of medicines for treating neurodegenerative diseases. [0002] Background technique [0003] Neurodegenerative diseases (Neurodegenerative diseases, NDD) are a type of chronic central nervous system diseases based on the progressive degeneration and death of neurons, mainly affecting the cognitive function or motor function of patients, mainly including Alzheimer's disease (Alzheimer's disease, AD), Parkinson's disease (PD), Huntington's disease (Huntington disease), spinocerebellar ataxia (spinal cerebellar ataxias), amyotrophic lateral sclerosis (amyotrophic lateral sclerosis) and spinal cord muscle Atrophy (spinal muscular atrophy), etc. Although the clinical manifestations and lesion characteristics of these diseases are not the same, they all have the common features: progressive degeneration and necrosis of neurons, significant ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/496A61P25/28A61P25/16A61P25/00
Inventor 胡刚鲁明丁建花苏存锦范益柳梦笛赵方方王玲
Owner NANJING MEDICAL UNIV
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