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Application of nicotinamide mononucleotide in the preparation of drugs for promoting nerve regeneration after cerebral ischemia

A single nucleotide, nerve regeneration technology, applied in the field of medicine, to achieve the effect of rich variety, wide therapeutic window, and improvement of nerve function damage

Active Publication Date: 2018-06-29
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Whether nicotinamide mononucleotide can promote the differentiation and migration of neural stem cells to neurons, improve neurological function, and improve the survival rate and quality of life of patients has not been reported in the literature.

Method used

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  • Application of nicotinamide mononucleotide in the preparation of drugs for promoting nerve regeneration after cerebral ischemia
  • Application of nicotinamide mononucleotide in the preparation of drugs for promoting nerve regeneration after cerebral ischemia
  • Application of nicotinamide mononucleotide in the preparation of drugs for promoting nerve regeneration after cerebral ischemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] The brain injury model was prepared by occluding the midvein of the mouse brain. The model preparation process was as follows: the mouse (C57BL / 6J, purchased from Shanghai Sleike Experimental Animal Co., Ltd.) was anesthetized (4% chloral hydrate, 0.1ml / 10g, intraperitoneally After the injection), stroke surgery was performed (①The mouse was selected with 5-0 monofilament nylon suture, and the final diameter of the top was 0.150-0.200 mm. A median incision was made in the ventral neck, and the sternohyoid muscle and sternomastoid were further bluntly separated. The right common carotid artery (CCA) and the right external carotid artery (ECA) were exposed. ②The proximal end of the CCA and the beginning of the external carotid artery were ligated with 3-0 suture. ③The internal carotid artery (ICA) Use a 3-0 suture to loosely ligate, and make sure that no branch is tied.④ 3mm below the common carotid artery bifurcation, use a 6-0 suture to loosely ligate to mark the positio...

Embodiment 2

[0039] The brain injury model was prepared by blocking the midvein of the mouse brain, and the preparation process of the model was the same as in Example 1.

[0040] The administration group was injected intraperitoneally with nicotinamide mononucleotide (NMN) (purchased from Sigma, USA) at 500 mg / kg / day (prepared in normal saline) for 9 consecutive days; the control group was injected with the same amount of normal saline for 9 consecutive days.

[0041] After 14 days, the Morris water maze test was used to evaluate the learning and memory functions of the two groups of mice. The steps of the Morris water maze experiment are as follows: (1) put the mouse into the water facing the pool wall, and randomly put it into the four directions of east, west, south and north as the starting position. The time (seconds) and the path length (meters) for the mouse to find the underwater platform were recorded. In the first few training sessions, if the mouse finds the underwater platfor...

Embodiment 3

[0044] The neural stem cells cultured in vitro were used, and the control group was given physiological saline and nicotinamide mononucleotide (NMN, purchased from Sigma Company) at a dose of 300 μM.

[0045] The process of culturing neural stem cells in vitro is as follows: Pregnant mice (gestational age 14-15 days) were sacrificed by cervical dislocation. After washing, the fetal mice were taken out and the brain tissue was separated. Use microsurgical scissors to cut up the brain tissue, add 2ml of Accutase digestive enzyme dropwise, put it into the cell culture incubator, and digest it for 15-20 minutes. After digestion, an equal volume of neural stem cell culture medium was added to terminate the digestion. After filtering through a 200-mesh nylon mesh, centrifuge at 1000 rpm for 10 minutes, discard the supernatant, and collect the cells. After the cells were resuspended, they were inoculated in neural stem cell medium. Put them in a 37°C, 5% carbon dioxide incubator an...

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Abstract

The invention relates to the technical field of medicines. The present invention provides application of nicotinamide mononucleotide in preparation of medicines for promotion of nerve regeneration after cerebral ischemia, and the nicotinamide mononucleotide can be used as an active pharmaceutical ingredient and a pharmaceutically acceptable supplementary material for preparation of medicine compositions. The nicotinamide mononucleotide compound itself is an endogenous protective substance, and the available data do not report the adverse reaction, so that the nicotinamide mononucleotide as a medicine or a health product is high in safety and wide in therapeutic window.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of nicotinamide mononucleotide in the preparation of medicines for promoting nerve regeneration or health food. Background technique [0002] Ischemic stroke is a common disease that seriously endangers human health, and its disability rate is very high. Stroke survivors often have different degrees of dysfunction, which seriously affects the quality of life of patients and brings heavy burdens to society and families. Studies have found that scientific and reasonable intervention on factors related to the acute phase of stroke can effectively reduce the mortality and disability rates. The traditional view is that after cerebral ischemia occurs, [0003] Neurons necrotic due to ischemia cannot recover or regenerate because neurogenesis occurs only during embryonic and early birth. However, in recent years, studies have found that there are a large number of ne...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/706A61P25/00A23L33/00
CPCA61K31/706
Inventor 缪朝玉王培赵衍管云枫刘昕竹
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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