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Application of carbinoxamine maleate in preparation of anti-influenza virus medicine

A carbinoxamine maleate, anti-influenza virus technology, applied in the field of medicine, can solve the problems of limited use, not widely used, etc., and achieve the effect of wide application prospects, safety, high efficiency and side effects

Active Publication Date: 2020-03-10
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, continuous evolution and rapid drug resistance of influenza A viruses, especially to amantadine and oseltamivir, limit the use of these two classes of drugs
Favipiravir is an RNA-dependent RNA polymerase inhibitor. It is a broad-spectrum antiviral drug. It is currently only listed in Japan as an anti-influenza virus drug and has not been widely used.

Method used

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  • Application of carbinoxamine maleate in preparation of anti-influenza virus medicine
  • Application of carbinoxamine maleate in preparation of anti-influenza virus medicine
  • Application of carbinoxamine maleate in preparation of anti-influenza virus medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1 Detection of anti-influenza virus activity of compound CAM in vitro

[0032] The in vitro antiviral experiment of the present invention involves multiple subtypes of influenza A and B viruses, including A / Shanghai / 37T / 2009(H1N1), A / Puerto Rico / 8 / 1934(H1N1), A / Guizhou / 54 / 1989(H3N2) and B / Shanghai / 2017(BY), the specific methods are as follows:

[0033] MDCK cells press 2×10 4 / Well inoculated in 96-well plate at 37℃, 5% CO 2 Culture to a single layer in a constant temperature cell incubator. Add 50μl serially diluted compound and 50μl 100TCID to each well 50 The mixed influenza virus solution infects the cells, and the cells are incubated at 37°C for 8 hours. Discard the mixed solution, add DMEM (containing 2μg / mlTPCK) blank medium 200μl per well, and continue to culture for 48h. Combined with the CCK-8 method, the antiviral activity of the compound is determined by the protective effect of the compound on the cell, and the half effective concentration IC is furth...

Embodiment 2

[0037] Example 2 Detection of Cytotoxicity of Compound CAM

[0038] The CCK-8 method is used to detect the cytotoxicity of compound CAM; the specific method is as follows:

[0039] MDCK cells press 1×10 4 / Well inoculated in 96-well plate at 37℃, 5% CO 2 Cultured to a single layer in a constant temperature cell incubator, add DMEM gradient dilution CAM to a 96-well plate, 100μl per well, continue culturing for 72h, add 20μL of CCK-8 solution to each well, incubate at 37°C for 1h, using multifunctional The microplate reader (Ultra 384, Tecan, NC) detects the absorbance at 450nm, and uses the cell survival rate as an indicator of the toxicity of CAM to MDCK cells; the test results show that the compound CAM has low cytotoxicity and high safety, such as figure 2 As shown, the compound CAM is less toxic to cells and has almost no toxicity to MDCK cells within the concentration range of 250 μM. Its half toxic concentration (CC 50 ) Is 240.52±12.53μM ( image 3 ); The highest drug concen...

Embodiment 3

[0040] Example 3 Detection of anti-influenza virus activity of compound CAM in vivo

[0041] The present invention further evaluates the in vivo inhibitory activity of CAM against influenza virus, using 4 to 8 weeks of C57BL / 6 female mice infected with influenza A virus H7N9 1 hour to intervene in CAM, and detecting the survival rate 14 days after infection, the specific method is as follows:

[0042] A 10LD50 influenza A virus A / Shanghai / 4664T / 2013 (H7N9) was used to inoculate C57BL / 6 female mice aged 4-8 weeks. After 1 hour of infection, CAM was injected intraperitoneally with high dose (10mg / kg / day) and low dose (1mg / kg / day) respectively for continuous intervention for 5 days, and the neuraminidase inhibitor oseltamivir phosphate (OSE ) (1mg / kg / day) was used as the positive control group, and the PBS group was used as the negative control. The survival rate of mice was calculated at 2, 4, 6, 8, 10, 12 and 14 days after influenza virus infection; Mice infected with influenza vir...

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Abstract

The invention belongs to the technical field of medicine, and relates to an application of carbinoxamine maleate in preparation of an anti-influenza virus medicine. Experiments show that the carbinoxamine maleate has significant anti-influenza activity against different types and subtypes of influenza viruses in a completely non-toxic concentration environment, and inhibits the replication of alltested virus strains in a dose-dependent manner, so that the results indicate that the anti-influenza virus activity of the carbinoxamine maleate has a certain broad spectrum; influenza viruses described in the invention include influenza A and B viruses, including H1N1, H3N2, H7N9, H5N1, H7N1, H7N2, H7N3, H7N7, H9N2 or B type; the action mechanism study provided by the invention shows that the carbinoxamine maleate mainly inhibits the viruses from entering host cells by interfering with the endocytosis of the influenza viruses; and the carbinoxamine maleate can be used to prepare the medicinefor preventing and treating influenza, and provides a novel way and means for the prevention and treatment of the influenza.

Description

Technical field [0001] The invention belongs to the technical field of medicine, and relates to the application of carbisamine maleate in the preparation of anti-influenza A virus drugs. Background technique [0002] The prior art discloses that influenza viruses can cause acute respiratory infectious diseases, have extremely high morbidity and high mortality, and pose a major threat to human health. Influenza virus belongs to the single-stranded negative-strand RNA virus of the Orthomyxoviridae family. According to its pathogenicity and host type, it can be divided into four types: A (A), B (B), C (C), and D (D) ; Among them, influenza A virus (IAV) has the widest host range and the strongest pathogenicity. At the same time, studies have found that some influenza B virus strains can also cause human infections. Approximately 5 million people worldwide die from seasonal influenza every year The outbreak. Although most influenza virus infections are self-limiting, they can somet...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4402A61P31/16
CPCA61K31/4402A61P31/16
Inventor 陆路姜世勃徐巍刘腾王茜花晨王聪付玉红李佩玉
Owner FUDAN UNIV
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