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Application of isoxuling in preparation of medicine for treating or preventing influenza virus infection

A technology of isoxalin and influenza virus, which is applied in the field of medicine, can solve the problem of not finding that isoxalin is anti-influenza virus, and achieve the effect of reducing clinical trial time, saving a lot of cost, and good safety

Inactive Publication Date: 2020-07-10
WUHAN INST OF VIROLOGY CHINESE ACADEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far, no relevant reports about the anti-influenza virus of Iksuling have been found

Method used

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  • Application of isoxuling in preparation of medicine for treating or preventing influenza virus infection
  • Application of isoxuling in preparation of medicine for treating or preventing influenza virus infection
  • Application of isoxuling in preparation of medicine for treating or preventing influenza virus infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1: Evaluation of the anti-influenza virus activity of Ikesuling in U937 cell line

[0060] 1 Cell culture

[0061] After two subcultures, the frozen and revived cells were expanded with RPMI-1640 medium containing 10% fetal bovine serum and double antibodies (penicillin 100U / ml, streptomycin 100ug / ml), and the inoculation density was not lower than 5x10 5 cell / ml, passage density not higher than 2x10 6 cell / ml.

[0062] 2 Cytotoxicity test of isoxuling

[0063] U937 cells by 1.5×10 5 Cells / well (volume 100 μl) were inoculated in a 96-well cell culture plate; the drug was prepared with 100 μl of culture medium (RPMI-1640 medium + 10% serum + double antibody) per well, and added to the corresponding cell wells for mixing. Seven concentration gradients were set for the drug, and two replicate wells were set for each gradient concentration. The final concentrations were 15.6 μM, 31.25 μM, 62.5 μM, 125.0 μM, 250.0 μM, 500.0 μM and 1000 μM. After culturing for 4...

Embodiment 2

[0076] Embodiment 2: Evaluation of the anti-influenza virus activity of Ikesuling in A549 cell line

[0077] In this experiment, a method similar to that of Example 1 was used to evaluate the effect of Ixexulin in human lung epithelial cells A549.

[0078] Since A549 is an adherent cell, when detecting drug toxicity and antiviral activity, the number of cells required in a 96-well plate is 1.5×10 4 cells / well, and the cells need to be plated 24 hours in advance, and the medium should be changed before infection, and the rest of the operations are consistent with Example 1.

[0079] 1 Drug toxicity

[0080] The result is as figure 2 As shown in middle A, after treatment of A549 cells with the highest concentration of 1000 μM for 48 hours, the viability of the cells was still not significantly different from that of the control group, indicating that the concentration of ioxalin had no toxicity to the cells, and its half-toxicity concentration CC 50 Greater than 1000 μM.

...

Embodiment 3

[0085] Example 3: Evaluation of the Anti-Influenza Virus Activity of Ikesuling in U937 Cell Lines

[0086] This embodiment uses H3N2 subtype (A / Human / Hubei / 3 / 2005) and H7N8 subtype (A / Duck / Hubei / 216 / 1983) and type B influenza virus (B / Human / Hubei / 1 / 2007) respectively The method of infecting U937 cell line was the same as that in Example 1. The results confirmed that Ixexulin significantly inhibited the replication of these three influenza viruses in a dose-dependent manner, and belonged to a broad-spectrum anti-influenza virus drug.

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Abstract

The invention discloses an application of isoxsuprine in preparing a drug for preventing or treating influenza virus infection. The applicant tested the toxicity of isoxsuprine to cells on a human lung epithelial cell line A549 and human monocyte cell line U937, and also tested the antiviral activity of isoxsuprine in both cell lines in a completely non-toxic concentration range, and the results showed that this small-molecule compound has significant antiviral activity and the antiviral effect is dose-dependent. In a lethal mouse influenza infection model, the treatment of infected mice withisoxsuprine can effectively reduce the virus titer in the lung lotion of the infected mice, delay the weight loss rate of the mice, prolong the survival time of the mice and improve the survival rateof the mice. Therefore, the isoxsuprine disclosed by the invention is a novel anti-influenza virus drug, has the advantages of good safety, high selection index, effective animal model experiment andthe like, can be used for developing a drug for preventing or treating influenza virus infection, and has a wide application prospect.

Description

technical field [0001] The invention belongs to the technical field of medicine, and mainly relates to the application of isoxuling in the preparation of medicines for treating or preventing influenza virus infection. Background technique [0002] Influenza viruses belong to the family Orthomyxoviridae, the genus Influenzavirus. According to the differences in the antigenic and genetic characteristics of the virion nucleoprotein (NP) and matrix protein (M), influenza viruses are divided into three types: A, B, and C, also known as A, B, and C. The whole genome of influenza A virus consists of eight single-stranded negative-strand RNAs of different sizes, named after segment 1 to segment 8, respectively. The full-length viral genome is about 13.6kb, encoding 10 structural proteins (PB2, PB1, PA, HA, NP, NA, M1, M2, PB1-F2 and NS2 / NEP) and non-structural proteins (NS1). Influenza A viruses can be further divided into 17 H (H1-H17) and 10 N (N1-N10) subtypes based on the viri...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/138A61P31/16
CPCA61K31/138
Inventor 陈绪林刘歌
Owner WUHAN INST OF VIROLOGY CHINESE ACADEMY OF SCI
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