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Application of hydrolase inhibitor t-TUCB in Alzheimer disease

A technology of inhibitors and hydrolytic enzymes, applied in the field of pharmacology, can solve the problems of complex etiology, lack of a safe and effective drug, and unclear pathogenesis, and achieve easy preparation, good oral bioavailability, and improve AD pathology The effect of features

Inactive Publication Date: 2021-10-19
广州市中西医结合医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The etiology of AD is complex and the pathogenesis is unclear. The main neuropathological features of AD are senile plaques (Amyloidplaques), neurofibrillary tangles (Neuronal tangels), accompanied by gliosis, loss of neurons and synapses, and blood vessels. Although pathological features are clear, and AD biomarkers and clinical imaging studies have brought hope for early diagnosis in recent years, more than 50% of AD patients cannot be diagnosed and rescued. There is no safe and effective drug that can fundamentally reverse the pathological process of AD; the five drug treatments approved by FAD: acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine and trarine) and NMDA receptor blockers (memantine) can only delay AD Therefore, to elucidate the pathogenesis of AD and find drugs that can safely and effectively reverse the pathological process of AD and improve cognitive dysfunction in AD is the key scientific issue in the current AD prevention and treatment research;

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  • Application of hydrolase inhibitor t-TUCB in Alzheimer disease
  • Application of hydrolase inhibitor t-TUCB in Alzheimer disease

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Embodiment Construction

[0019] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Apparently, the described embodiments are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.

[0020] The invention provides a technical solution:

[0021] The application of hydrolase inhibitor t-TUCB in Alzheimer's disease comprises the following steps:

[0022] S1. Gastrointestinal administration of 6-month-old 5XFAD Different doses of t-TUCB (0.5mg / kg, 1mg / kg, 2mg / mg) were administered to mice for a total of 8 weeks, and t-TUCB was dissolved in 40% PEG-400 solution prepared with normal saline;

[0023] S2. Then we killed the mice, took out their heads, and frozen...

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Abstract

The invention discloses an application of a hydrolase inhibitor t-TUCB in Alzheimer's disease, which comprises the following steps: S1, performing intragastric administration on 6-month-old 5XFAD mice with different doses of t-TUCB (0.5 mg / kg, 1mg / kg and 2mg / mg) for 8 weeks, and dissolving the t-TUCB in a 40% PEG-400 solution prepared from normal saline; S2, then killing the mice, taking out the head, freezing and slicing, detecting and analyzing the levels of Abeta in hippocampus and motor cortex in the mice of the administration group and the mice of the solvent group by using immunofluorescence staining (6E10), and result analysis shows that compared with the mice of the solvent group, the percentage of the area fraction of plaques in a 1mg group, a 2mg group, a hippocampus and a motor cortex is remarkably reduced. The modern compound t-TUCB prepared by the invention can show good oral bioavailability and pharmacokinetics, is easier to prepare, and can obviously play a role in improving AD pathological characteristics, thereby further improving learning memory and cognitive competence.

Description

technical field [0001] The invention relates to the technical field of pharmacy, in particular to the application of hydrolase inhibitor t-TUCB in Alzheimer's disease. Background technique [0002] Alzheimer's disease (AD) is a common chronic and progressive senile disease with the highest prevalence rate and loss of cognitive function as the core symptom. Epidemiological surveys have found that people over 65 years old The incidence of moderate and mild dementia is 10%, and the incidence of moderate and severe dementia is 5%. At present, there are about 47.5 million dementia patients in the world, and it is estimated that by 2050, it may exceed 130 million, of which 60-70% are AD patients, causing social and economic burden every year As high as 6,000-1000,000 billion US dollars, at this stage, my country's elderly population ranks first in the world, about 220 million, based on which it is estimated that there are nearly ten million AD patients in my country; it can be seen ...

Claims

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Application Information

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IPC IPC(8): A61K31/196A61P25/28
CPCA61K31/196A61P25/28
Inventor 肖晓丹高峰王帅关燕菲陈庆状
Owner 广州市中西医结合医院
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