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Application of neuraminidase and inhibitor to preparation of medicines for treating hypertension

A technology of neuraminidase and high blood pressure, which is applied in the field of biomedicine and can solve problems such as the undiscovered correlation of neuraminidase

Active Publication Date: 2018-02-23
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] In subsequent studies, the applicant also found that neuraminidase is related to various diseases. After searching, no prior art has been found to disclose the relationship between neuraminidase and these diseases

Method used

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  • Application of neuraminidase and inhibitor to preparation of medicines for treating hypertension
  • Application of neuraminidase and inhibitor to preparation of medicines for treating hypertension
  • Application of neuraminidase and inhibitor to preparation of medicines for treating hypertension

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] 1. Experimental method

[0019] SPF grade 9-week-old SHR male rats (body weight 180-200g) were fed freely for 3 days, and their blood pressure was measured 5 times adaptively. Divided into 5 groups, 10 rats in each group: model group and zanamivir, oseltamivir phosphate, coptisine, salvianolic acid B administration group. Another 9-week-old normotensive WKY male rats were used as the control group. Rats in the administration group were given 0.2mg / kg / d zanamivir (i.v.), 5mg / kg / d oseltamivir phosphate (p.o.), 40mg / kg / d coptisine (p.o.), 40mg / kg / d salvianolic acid B (p.o.), the model group and the control group were administered intragastrically with an equal volume of 0.5% CMC-Na, and the administration continued for 4 weeks.

[0020] After 4 weeks of administration, operate according to the requirements of the automatic non-invasive blood pressure measurement system (Chengdu Taimeng; model BP-600A), and measure the blood pressure of each group of rats 1 hour after th...

Embodiment 2

[0027] The human umbilical vein endothelial cell line (HUVEC-c) was cultured in high-glucose DMEM medium with 10% fetal bovine serum and 1% double antibody at 37°C and 5% CO 2 . The medium was changed every other day, after being digested and passaged with 0.25% trypsin, they were replanted in culture dishes according to different conditional media, and were divided into blank control group (control group), hypertension model group (hypertension group), zanami Zanamivir intervention group (zanamivir group), oseltamivir phosphate intervention group (oseltamivir phosphate group), coptisine intervention group (coptisine group), salvianolic acid B intervention group (salvianolic acid B group) .

[0028] The conditioned medium was prepared according to the experimental groups as follows:

[0029] ①Blank control group: normal medium containing 10% serum; ②Hypertensive model group: normal medium containing 10% serum and angiotensin II at a concentration of 1 μg / ml; ③Zanamivir inter...

Embodiment 3

[0036] The commercially available neuraminidase inhibitor screening kit P0309 (Beyotime, Beyotime) was used to test the inhibitory activity of salvianolic acid B in vitro, and the positive control drug was oseltamivir phosphate. Add 70 μL of buffer solution and 10 μL of neuraminidase solution to each well of a 96-well plate, then add 10 μL of different concentrations of the test solution, shake and mix, incubate at 37°C for 5 minutes, add 10 μL of the solution containing the fluorescent substrate, shake and mix Homogenize, incubate at 37°C for 30min, and perform fluorescence measurement, wherein the excitation wavelength is 322nm and the emission wavelength is 450nm. The inhibition rates of different test solutions were calculated according to the fluorescence readings, and the IC50 values ​​of the positive control drugs oseltamivir phosphate and salvianolic acid B were further obtained. The results are shown in Table 3.

[0037] Table 3 IC50 values ​​of positive control drug...

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Abstract

The invention discloses the application of neuraminidase and an inhibitor to preparation of medicines for treating hypertension. The known zanamivir and oseltamivir phosphate are effective inhibitorsof the neuraminidase, the inhibition effect of coptisine on the neuraminidase is disclosed in the previous patent application of an applicant, and the applicant finds that danshinolic acid B can inhibit the activity of the neuraminidase in vitro and is the inhibitor of the neuraminidase; in-vivo experiments prove that the neuraminidase inhibitors can effectively inhibit the activity of the neuraminidase of vascular endothelial cells so as to reduce blood pressure. Therefore, the neuraminidase and the inhibitor thereof can be applied to preparation of the medicines for treating hypertension.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to the application of enzymes and enzyme inhibitors, in particular to the application of neuraminidase and its inhibitors in the preparation of medicines for treating hypertension. Background technique [0002] Neuraminic acid is a class of natural sugar and acid compounds widely present in organisms. It is now confirmed that there are more than 50 natural derivatives of neuraminic acid, and N-acetylneuraminic acid and N-glycolylneuraminic acid are the more common ones. Neuraminic acid is usually linked to the end of glycoconjugates such as glycoproteins and glycolipids in the form of short chain residues. Neuraminic acid is an important biological information transfer molecule, and the neuraminidative modification of cell surface glycoproteins and glycolipids plays a vital role in many biological processes, including cell adhesion, antigen recognition and signal transduction. [0003] In ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/47A61K31/343A61K31/4375A61K31/351A61K31/215A61P9/12
CPCA61K31/215A61K31/343A61K31/351A61K31/4375A61K38/47C12Y302/01018
Inventor 齐炼文张蕾魏婷婷
Owner CHINA PHARM UNIV
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