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Application of gemfibrozil and derivatives thereof for treating and/or preventing neurodegenerative diseases

A neurodegenerative, gemfibrozil technology, applied in the field of gemfibrozil and its derivatives in the preparation of drugs for the treatment and/or prevention of neurodegenerative diseases, which can solve the problems of drugs that do not completely cure the disease

Pending Publication Date: 2020-05-01
KUNMING INST OF ZOOLOGY CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] At present, the treatment of AD is mainly adjuvant therapy. These drugs can only improve the symptoms of patients to a certain extent, and there is no drug that can completely cure the disease.

Method used

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  • Application of gemfibrozil and derivatives thereof for treating and/or preventing neurodegenerative diseases
  • Application of gemfibrozil and derivatives thereof for treating and/or preventing neurodegenerative diseases
  • Application of gemfibrozil and derivatives thereof for treating and/or preventing neurodegenerative diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0185] Example 1 Study on Gemfibrozil Alleviating Symptoms of AD Cognitive Impairment

[0186] In order to study whether gemfibrozil can alleviate the symptoms of AD cognitive impairment, 8-month-old APP / PS1ΔE9 mice were selected to conduct water maze test after administration of gemfibrozil. Briefly, gemfibrozil was dissolved in DMSO to 50 mg / mL, and then diluted with drinking water of mice to a liquid medicine with a final concentration of 50 μg / mL, wherein the final concentration of DMSO in the liquid medicine was 0.1%. Allow the mice to drink the potion ad libitum. Mice in the control group drank drinking water containing 0.1% DMSO freely. After continuous administration for two to two months, a water maze experiment was performed on the APP / PS1ΔE9 mice in the gemfibrozil-administered group and the control group to detect the learning and memory abilities of the mice in different groups. The results showed that after 7 days of training, all APP / PS1ΔE9 mice could find the...

Embodiment 2

[0189] Example 2 Gemfibrozil relieves anxiety symptoms in APP / PS1ΔE9 mice

[0190] Progressive cognitive decline and increased anxiety are two important clinical features of AD patients. In order to study whether gemfibrozil can alleviate the anxiety symptoms of APP / PS1ΔE9 mice, an open field experiment was used for further testing. The results of the study showed that there was no significant difference in the exercise capacity of APP / PS1ΔE9 mice with or without administration of gemfibrozil ( figure 2 in A and 2 in B). However, after gemfibrozil administration, the anxiety symptoms of APP / PS1ΔE9 mice were significantly improved; compared with the control group, APP / PS1ΔE9 mice after gemfibrozil administration stayed in the central area of ​​the open field The time is significantly increased ( figure 2 A in A and C in 2).

[0191] It can be seen that gemfibrozil can really relieve the anxiety symptoms of AD mice.

Embodiment 3

[0192] Example 3 Gemfibrozil improves neuroplasticity in APP / PS1ΔE9 mice

[0193] Based on the fact that gemfibrozil can improve cognitive dysfunction and relieve anxiety behaviors in AD mice, in order to study whether gemfibrozil can improve neuroplasticity in APP / PS1ΔE9 mice, AD mice were administered with gemfibrozil for 2 months. Brain tissue was harvested from mice, followed by immunohistochemistry and Golgi staining. The results of immunohistochemical experiments showed that after administration of gemfibrozil, the immunogenicity of PSD-95 protein in the hippocampal tissue of APP / PS1ΔE9 mice was significantly up-regulated ( image 3 Middle A-B), suggesting that gemfibrozil can improve postsynaptic integrity in AD mice. The results of Golgi staining also showed that after administration of gemfibrozil, the density of dendritic spines in the hippocampal neurons of APP / PS1ΔE9 mice was significantly up-regulated ( image 3 Middle C-D).

[0194] In summary, gemfibrozil can...

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Abstract

The invention provides application of gemfibrozil and pharmaceutically acceptable salt, ester or stereoisomer thereof in preparation of medicines for treating and / or preventing neurodegenerative diseases. The neurodegenerative disease are selected from Alzheimer's disease, Parkinson's disease, Huntington's disease or amyotrophic lateral sclerosis. The invention also provides a pharmaceutical composition for treating and / or preventing the neurodegenerative diseases, wherein the pharmaceutical composition comprises the gemfibrozil, and the pharmaceutically acceptable salt, ester or stereoisomerthereof; and preferably, the pharmaceutical composition further comprises one or more pharmaceutical carriers. The invention also provides application of the pharmaceutical composition containing thegemfibrozil and the pharmaceutically acceptable salt, ester or stereoisomer thereof in preparation of medicines for treating and / or preventing the neurodegenerative diseases.

Description

technical field [0001] The invention relates to the technical field of new uses of medicines, in particular to the use of gemfibrozil and derivatives thereof in the preparation of medicines for treating and / or preventing neurodegenerative diseases. Background technique [0002] Gemfibrozil (Gemfibrozil), chemical name: 2,2-dimethyl-5-(2,5-dimethylphenoxy)valeric acid, structural formula is as follows: [0003] [0004] Gemfibrozil is known as a blood lipid regulating drug of clofibrate derivatives, used for the treatment of hyperlipidemia, suitable for severe type IV or type V hyperlipoproteinemia, coronary heart disease, type IIb hyperlipoproteinemia and Other blood lipid regulating drugs are ineffective. [0005] Neurodegenerative diseases (NDD), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), are serious brain lesions, Has gradually become a worldwide health care problem. Unfortunately,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/192A61P25/28A61P25/16A61P25/14A61K31/216A61K31/196
CPCA61K31/192A61P25/28A61P25/16A61P25/14A61K31/216A61K31/196A61K31/13A61K31/702A61K31/24A61K31/55A61K31/445
Inventor 姚永刚罗荣灿李桂瑜苏凌燕阳静张登峰
Owner KUNMING INST OF ZOOLOGY CHINESE ACAD OF SCI
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