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Application of dasatinib in preparing drugs for treating influenza virus infection

A technology of influenza virus infection and dasatinib, applied in the field of medicine, can solve problems such as undiscovered, and achieve the effects of reducing the degree of weight loss, reducing the time of clinical trials, and saving costs

Inactive Publication Date: 2019-10-11
武汉威立得生物医药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no relevant report on the treatment of influenza with dasatinib

Method used

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  • Application of dasatinib in preparing drugs for treating influenza virus infection
  • Application of dasatinib in preparing drugs for treating influenza virus infection
  • Application of dasatinib in preparing drugs for treating influenza virus infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048]Example 1: Evaluation of dasatinib's anti-inflammation activity induced by influenza virus in U937 cell line

[0049] 1 cell culture

[0050] After two subcultures, the frozen and revived cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum and double antibodies (penicillin 100U / ml, streptomycin 100ug / ml), and the seeding density was not low. at 5x10 5 cell / ml, passage density not higher than 2x10 6 cell / ml.

[0051] 2 Cytotoxicity detection of dasatinib

[0052] U937 cells by 1.5×10 5 Cells / well (volume 100 μL) were seeded in a 96-well cell culture plate; the drug was prepared with 100 μL culture medium (RPMI-1640 medium + 10% serum + double antibody) per well, and added to the corresponding cell wells for mixing. Nine concentration gradients were set for the drug, and two replicate wells were set for each gradient concentration. The final concentrations were 0.02 μM, 0.05 μM, 0.14 μM, 0.41 μM, 1.23 μM, 3.7 μM, 11.11 μM, 33.33 μM and 100 μM. A...

Embodiment 2

[0064] Example 2: Evaluation of dasatinib's anti-inflammatory activity against other influenza viruses in U937 cell line

[0065] In this example, the U937 cell line was infected with the H3N2 subtype (A / Human / Hubei / 3 / 2005), and the method was the same as in Example 1.

[0066] The results confirmed that dasatinib significantly inhibited the secretion of these three inflammatory factors in a dose-dependent manner, and was a broad-spectrum anti-inflammatory drug caused by influenza virus.

Embodiment 3

[0067] Example 3: Evaluation of the effect of dasatinib on anti-influenza virus-induced inflammation in a lethal influenza infection model in mice

[0068] 1 Experimental process:

[0069] 1) BALB / c mice aged 6-8 weeks were randomly divided into a drug evaluation group and a negative control group (PBS), with 8 mice in each group. Before the formal experiment, the mice were acclimated to the environment for 2-3 days.

[0070] 2) On the day of challenge, the mice were lightly anesthetized with 1% pentobarbital sodium (about 0.1 mL of anesthetic per gram of body weight), and then infected with 2LD50 H1N1 mouse lung-adapted strain virus solution of 2LD50 by nasal drop method with a pipette gun. .

[0071] 3) Administration started on the 3rd day after virus infection and continued until the 6th day after infection, for a total of 4 days of administration. Oral administration is adopted, and the dose is 15 mg / kg once a day with an interval of 24 hours. The body weight of each ...

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Abstract

The invention discloses application of dasatinib in preparing drugs for treating influenza virus infection. The toxicity of the dasatinib on cells is detected on a human monocytic line U937, then within the concentration range of nontoicity or low toxicity, the secretion inhibition effect of the dasatinib on three important inflammatory factors of IL-8, IP-10 and MCP-1 in the cell line U937, and results show that the small-molecular compound has significant anti-inflammatory activity and shows a doseage-dependent effect. In a fatal mouse influenza infection model, the dasatinib is utilized fortreating an infected mouse, the concentration of the inflammatory factors in lung washing liquid of the mouse can be effectively lowered, the weight lowering speed of the mouse is lowered, and the survival rate of the mouse is increased. Therefore, the dasatinib is a novel anti-inflammatory drug for influenza, has the advantages that the safety and selection index are high, and animal model experiments are effective, can be used for developing drugs for treating the 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 dasatinib in the preparation of medicines for treating 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 virion surface gly...

Claims

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Application Information

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IPC IPC(8): A61K31/506A61P31/16A61P29/00
CPCA61K31/506A61P31/16A61P29/00
Inventor 陈绪林陈思
Owner 武汉威立得生物医药有限公司
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