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A small molecule drug and its use in the treatment of intermittent hypoxia

A drug and seed technology, applied in the field of medicine, to achieve the effect of enhancing drug efficacy, improving hippocampal synaptic plasticity, and alleviating the decline

Active Publication Date: 2022-03-29
ZHEJIANG MEDICAL COLLEGE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Various pharmaceutical agents have been tried for the treatment of OSA, but none were considered sufficiently effective

Method used

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  • A small molecule drug and its use in the treatment of intermittent hypoxia
  • A small molecule drug and its use in the treatment of intermittent hypoxia
  • A small molecule drug and its use in the treatment of intermittent hypoxia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Intermittent hypoxic animal model preparation

[0038] Clean grade male C57BL / 6 mice, Zhou Ling 7 weeks, with a weight of 20 to 22g, provided by the China University of Chinese University. This experiment uses chronic intermittent hypoxia (IH) to simulate obstructive sleep apnea (OSA) disease. Put the C57 male mouse in a special low oxygen chamber (46 × 20 × 22 cm), and control nitrogen and oxygen into the amount through the oxygen concentration of the container and the computer program setting (Oxycycler Model A48XOV; Reming Bioinstruments ), The oxygen concentration in the low oxygen chamber decreases from 21% to 10%, and then recovered from 10% to 21% as a cycle, each cycle of 90s, and continuously cycle a week, a total of 2 weeks. At the same time, the remote sensor inside the low oxygen can also detect temperature, humidity, carbon dioxide (CO). 2 )concentration. The temperature in the cabin is maintained at 22 to 24 ° C, and the water is placed in the low oxygen cha...

Embodiment 2

[0104] 1. Preparation of the extract of water fly:

[0105] Water thistle seeds are cryorated to 24 h, and it is pulverized with a multi-function soymilk, and it has been removed from the extract to extract, dried to extract the extract with petroleum ether (30 ~ 60 ° C). After adding ethanol in an oil ratio of 1: 15, after immersion for 6 h, it is placed in an ultrasonic cleaner, a temperature of 60 ° C, ultrasonic power 100%, ultrasonic treatment, ultrasonic treatment, filtration, decompression distillation (44 ° C), obtained Yellow powdered substance. Dissolve, centrifugal, filtration, repeating twice, and extract it. The total flavonoid content was 62.31 mg / g of the total flavonoid content of 62.31 mg / g, and the water flying belly content was 39.62 mg / g.

[0106] 1.1 Determination of total flavonoids:

[0107] Accurately, 0.3 g of sample was dissolved in 40 ml of methanol, and then diluted with the same solvent to 50.0 mL, shake well; evaporate 1.0 mL of this solution to...

Embodiment 3

[0126] 1. Preparation of the water thistle extract is the same as in Example 2

[0127] 2, intermittent hypoxia animal model

[0128] 2.1 Model Establishment and Example 1

[0129] 2.2 Drug configuration and grouping

[0130] The GSK2606414 was dissolved in a dual vapor containing 0.5% hydroxypropylmethylcellulose, and the concentration was 5 mg / ml; the water thistle extract was dissolved in a dual steam containing 0.5% hydroxypropyl methylcellulose, and the configured concentration was 5 mg / ml; dissolved the tandem glycoside in dual vapor containing 0.5% hydroxypropylmethylcellulose, the concentration was 5 mg / ml. The mice were randomly divided into 6 groups using a random digital table: Intermittent hypoxic group (IH): 0.5% hydroxypropylmethylcellulose 0.2mL; IH + GSK2606414 group (IH + GSK2606414) (Experimental Group 2): Gas GSK2606414 0.2ml (50mg / kg / day); IH + Waterfill Extract Group (Experimental Group 3): Gas Gas Extract 0.168ml (42 mg / kg / day); IH + GSK2606414 ...

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Abstract

The invention discloses a small molecule drug and its application in treating intermittent hypoxia, and relates to the technical field of medicine. The drug includes GSK2606414 and milk thistle extract, which can significantly improve hippocampus-dependent cognitive function decline; it has a certain effect on the improvement of hippocampal synaptic plasticity, and can inhibit the activation of the PERK pathway. The drug is administered in the amount of 45-55 mg / kg of GSK2606414 and 32.4-50 mg / kg of milk thistle extract per day, administered once a day or divided into 2-4 times, taking 12-14 days or longer.

Description

Technical field [0001] The invention belongs to the field of medical technology, and more particularly to a small molecule drug and its use in the treatment of intermittent hypoxia. Background technique [0002] Oxygen is essential in maintaining body energy metabolism and steady-state balance, which is an indispensable life element of normal development and growing growth. The oxygen required by the human metabolism is transported by the blood circulation system to each tissue organ. The study found that various organs and tissue inhibitors are generally lower than those in the external atmosphere, organs and tissues, are called "physiological hypoxic". During the development of the embryo formation of vascular systems, the oxygen partial pressure in the embryonic neurovascus region was less than 7.6 mmHg. Therefore, physiological hypoxia has an important role in embryonic development and maintenance of brain. The study found that: chronic and moderate intermittent hypoxic expos...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/519A61K36/28A61P25/28A61P11/00
CPCA61K31/519A61K36/28A61P25/28A61P11/00A61K2300/00
Inventor 陈健徐麟皓王征
Owner ZHEJIANG MEDICAL COLLEGE
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