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A kind of onium bromide and its application in neurodegenerative disease medicine

A neurodegenerative, onium bromide technology, applied in nervous system diseases, applications, antipyretics, etc., can solve the problems of patients' discomfort, cranial nerve damage that cannot be repaired, no effective prevention and control of disease progression, etc., and achieve good curative effect , Inhibit neuroinflammation and increase ChAT level

Active Publication Date: 2020-08-14
NINGBO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, these drugs only relieve the symptoms of AD, and cannot repair the damage to the cranial nerves that has been caused, and have no effective prevention and control of the deterioration of the disease. At the same time, these drugs are also accompanied by side effects such as dizziness, nausea, and vomiting, which seriously cause the patient's depression. unwell

Method used

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  • A kind of onium bromide and its application in neurodegenerative disease medicine
  • A kind of onium bromide and its application in neurodegenerative disease medicine
  • A kind of onium bromide and its application in neurodegenerative disease medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] 1. Improving effect of onium bromide on memory ability

[0037] 1.1 Experimental materials

[0038] Onium bromide was dissolved in dimethyl sulfoxide (DMSO, purchased from Sinopharm Chemical Reagent Co., Ltd.), with concentrations of 10 μmol / L and 33 μmol / L, respectively. Scopolamine (Scopolamine, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) was dissolved in normal saline (purchased from Zhejiang Dubang Pharmaceutical Co., Ltd.) at a concentration of 0.5 mg / L (because Scopolamine has a similar chemical structure to ACh, it can compete with ACh ACh receptors on the postsynaptic membrane, leading to cognitive impairment, so it is often used in the establishment of AD models). Donepezil (Donapezil) was dissolved in normal saline (purchased from Zhejiang Dubang Pharmaceutical Co., Ltd.), with a concentration of 0.5 mg / L.

[0039] 1.2 Experimental grouping

[0040] Select 40 mice of similar size and weight, and randomly divide them into 5 groups, with...

Embodiment 2

[0062] 2. Inhibitory effect of onium bromide on acetylcholinesterase (AChE)

[0063] 2.1 Experimental materials

[0064] onium bromide. Acetylthiocholine iodo (AChI, purchased from sigma company) was dissolved in 100mmol / L Na2HPO4 solution with a concentration of 20mmol / L. Dithiobis(2-nitrobenzoic acid) (DTNB, purchased from Life Science Company). Ethylpromazine (BuChE inhibitor, purchased from sigma company) was dissolved in dimethyl sulfoxide (DMSO, purchased from Sinopharm Chemical Reagent Co., Ltd.) at a concentration of 20 mmol / L.

[0065] 2.2 Experimental method

[0066] 2.2.1 Preparation of brain homogenate

[0067] A number of normal mice were taken, and the brains were taken after decapitation. The cerebral cortex was separated on ice and dried with liquid nitrogen. After weighing the cortex, add 10 times of lysis buffer (HEPES 10mmol / L, Triton X-100 0.5%, EDTA 5mmol / L, EGTA5mmol / L, NaCl 1000mmol / L, adjust pH=7.5), homogenate until the destruction stops . After...

Embodiment 3

[0082] 3. Inhibitory effect of onium bromide on neuroinflammation

[0083] 3.1 Experimental materials

[0084] IL-1β (Interleukin-1β) ELISA Kit, IL-6 ELISA Kit, TNF-α (Tumor Necrosis Factor α) ELISA Kit, IL-10 ELISA Kits (the above kits were all purchased from Jiangsu Enzyme Biotechnology Co., Ltd.); BCA working solution (purchased from Beyontian Biotechnology Co., Ltd., configured according to the volume of A solution: the volume of B solution = 50:1); RIPA-PIC-phosphoric acid Enzyme inhibitor lysate (configured according to RIPA volume: PIC volume: phosphatase inhibitor volume = 97:2:1); 1.5M Tris-HCL buffer (PH=8.8, PH=6.8, purchased from Solei Biotechnology Co., Ltd.); 30% PAGE-Pre-Solution 29:1 (purchased from Suo Laibao Biotechnology Co., Ltd.); 10% SDS solution (purchased from Suo Laibao Biotechnology Co., Ltd.); TEMED; anti-IL-17 antibody , HRP-labeled goat anti-mouse secondary antibody (purchased from Santa Cruz Biotechnology), Bio-rad electrophoresis instrument, Bi...

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Abstract

The invention relates to onium chloride which takes acetamide as a raw material, is an indole compound synthesized by an artificial chemical synthesis means, belongs to beta-carboline alkaloid and isa large plane structure molecule comprising five rings. Onium chloride can significantly inhibit AChE noncompetitively, raise a ChAT level and synergically resist a neurodegenerative disease from multiple targets; and onium chloride can influence levels of some important inflammatory factors and effectively inhibit neuroinflammation. Onium chloride has a good treatment effect on the neurodegenerative disease.

Description

technical field [0001] The invention relates to the technical field of drugs for neurodegenerative diseases, in particular to an onium bromide and its application in drugs for neurodegenerative diseases. Background technique [0002] Neurodegenerative diseases include Alzheimer's disease (Alzheimer's disease, AD), Parkinson's disease (Parkinson's disease, PD), amyotrophic lateral sclerosis, ataxia telangiectasia, bovine spongiform encephalopathy, Creutzfeldt-Jacob Multiple sclerosis, Huntington's disease, cerebellar atrophy, multiple sclerosis, primary lateral sclerosis, spinal muscular atrophy, etc., is a disease state in which neurons in the brain and spinal cord are gradually lost Caused by loss of neurons or their myelin sheath. Under normal circumstances, neurons in the brain and spinal cord cannot regenerate, and excessive damage to neurons may be irreversible. Therefore, neurodegenerative diseases can worsen over time and lead to dysfunction of the nervous system, r...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D471/14A61K31/437A61P25/28A61P25/00A61P29/00A23L33/10
CPCA23L33/10A23V2002/00A61P25/00A61P25/28A61P29/00C07D471/14A23V2200/322
Inventor 潘汉博崔巍梁洪泽严小军孙晴镁
Owner NINGBO UNIV
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