Biguanide substance and application thereof

A technology of biguanides and metformin, applied in drug combinations, medical preparations containing active ingredients, organic active ingredients, etc., can solve problems such as lack of learning and memory ability of adolescents, and improve the efficiency of brain activity, improve cognitive function, The effect of enhancing cognitive function

Inactive Publication Date: 2019-07-30
UNIVERSITY OF MACAU
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have found that metformin hydrochloride can promote the differentiation and regeneration of nerve cells, but there is no relevant report on metformin hydrochloride and the promotion of learning and memory ability of adolescents

Method used

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  • Biguanide substance and application thereof
  • Biguanide substance and application thereof
  • Biguanide substance and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Normal young male C57 mice aged 3 to 4 weeks (juvenile mice, that is, the age group equivalent to human adolescents) were intraperitoneally injected with different concentrations of metformin hydrochloride for 28 days, and studied learning and memory through the Morris water maze (MWM) test. First, 3-4 week-old C57 male mice with a body weight of 18-20 g were randomly divided into four groups, with 10 animals in each group, divided into a control group and three groups of metformin hydrochloride at different concentrations of 10, 50 and 100 mg / kg. Metformin hydrochloride was purchased from Sigma-Aldrich, dissolved in PBS, and administered to mice by intraperitoneal injection for 4 weeks. From the 29th day of injection, the spatial memory of the four groups of mice was evaluated by MWM experiment.

[0032] Learning and memory behavior assessment experiments were carried out in a black circular pool (160 cm diameter, 60 cm height) filled with water (22±2°C). The pool was...

Embodiment 2

[0037] Example 2: Metformin hydrochloride up-regulates brain-derived neurotrophic factor (BDNF)

[0038] Normal young male C57 mice aged 3 to 4 weeks (juvenile mice, that is, the age group equivalent to human adolescents) were divided into 4 groups with 10 mice in each group, and the experiment was repeated at least three times. The mice were weighed before administration, and the dosage was calculated according to the body weight. The control group was injected with normal saline; the experimental group was injected intraperitoneally with different concentrations of metformin hydrochloride (10 mg / kg, 50 mg / kg, 100 mg / kg) to the mice. After 28 days of administration, the mice were killed by decapitation, and then the brain tissue was quickly dissected and separated on ice, and the olfactory bulbs were removed, and the complete bilateral hemibrains were taken out.

[0039] The mRNA content of three neurotrophic factors BDNF, NFG, and NTF-3 was detected by fluorescent quantitat...

Embodiment 3

[0041] Example 3: The effect of metformin hydrochloride on AMP-dependent protein kinase (AMPK) in mouse brain.

[0042] Normal young male C57 mice aged 3 to 4 weeks (juvenile mice, that is, the age group equivalent to human adolescents) were divided into 4 groups with 10 mice in each group, and the experiment was repeated at least three times. The mice were weighed before administration, and the dosage was calculated according to the body weight. The control group was injected with normal saline; the experimental group was injected intraperitoneally with different concentrations of metformin hydrochloride (10 mg / kg, 50 mg / kg, 100 mg / kg) to the mice. Add 100 μL of PMSF to every 10 mL of RIPA protein lysate at a concentration of 100 mM; add phosphatase inhibitors and protease inhibitors, mix thoroughly, and place on ice for 20 min for later use. The brain tissue of the ischemic side of the mouse was fully cut up on ice, put into the lysate, and fully homogenized with a grinding...

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Abstract

The invention discloses a biguanide substance and application thereof. The biguanide substance, especially metformin hydrochloride can promote the learning and memory ability of adolescents and can promote the learning and memory ability of adolescent mice through an AMPK/PKA-CREB signaling pathway, dentate gyrus newborn neurons are added, the complexity of hippocampal neuron axons is improved, and the number of dendritic spines is increased; a mechanism LTP closely related to learning and memory is adjusted by activating AMPK in the brains of the mice, the PKA signaling pathway is activated,the learning and memory ability of the adolescents is improved, and an experimental basis is provided for research of new nootropic drugs.

Description

technical field [0001] The present invention relates to biguanide substances and applications thereof. Background technique [0002] Nootropics are a new class of central nervous system drugs that can promote learning and enhance memory. Nootropics can selectively act on the cerebral cortex, and have the properties of selectively activating, protecting and promoting the recovery of damaged nerve cells. [0003] Learning and memory ability is one of the most basic and important advanced neural functions of the brain, and it is an important indicator to measure the development of human intelligence. The hippocampus is an essential structure for the formation of memory and spatial navigation. Studies have shown that the hippocampus is related to learning and memory, especially spatial cognition. In particular, the CA3 area is considered to be particularly closely related to spatial discrimination learning and memory activities. Studies have shown that the number of neurons in...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/155A61P25/28
CPCA61K31/155A61P25/28
Inventor 郑文华刘琳琳
Owner UNIVERSITY OF MACAU
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