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Application of AZD1480 in preparing drug for treating influenza virus infection

A technology of 1.AZD1480, 6.AZD1480, applied in the application field of medicine, can solve the problem of undiscovered AZD1480 anti-therapy influenza, etc., achieve great clinical treatment potential, save cost, improve survival time and ultimate survival rate

Inactive Publication Date: 2019-08-23
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

AZD1480 inhibits tumor angiogenesis and local metastasis by affecting the tumor microenvironment. However, there is no report about AZD1480 anti-therapeutic influenza

Method used

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  • Application of AZD1480 in preparing drug for treating influenza virus infection
  • Application of AZD1480 in preparing drug for treating influenza virus infection
  • Application of AZD1480 in preparing drug for treating influenza virus infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1: Evaluation of the anti-inflammation activity of AZD1480 in U937 cell line induced by influenza virus

[0049] 1 cell culture

[0050] After 2 passages, the frozen and revived cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum and double antibodies (penicillin 100U / ml, streptomycin 100μg / 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 AZD1480

[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. Afte...

Embodiment 2

[0064] Example 2: Evaluation of AZD1480's anti-inflammatory activity against other influenza viruses in U937 cell lines

[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 AZD1480 significantly inhibited the secretion of these three inflammatory factors in a dose-dependent manner, and was a broad-spectrum anti-inflammation drug caused by influenza virus.

Embodiment 3

[0067] Example 3: Evaluation of the effect of AZD1480 on anti-inflammation caused by influenza virus 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 0.1ml of anesthetic per gram of body weight), and then infected with 2LD50 H1N1 mouse lung-adapted strain virus solution of 2LD50 by intranasal drip 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, the dose is 15mg / kg once a day, with an interval of 24h. The body weight of each group of ani...

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Abstract

The invention discloses application of AZD1480 in preparing a drug for treating influenza virus infection. The applicant detects toxicity of the AZD1480 on cells in a human monocyte cell line U937, and measures the secretion inhibition effect of the AZD1480 on the three important inflammatory factors of IL-8, IP-10 and MCP-1 in the U937 cell line in a concentration range of no toxicity or low toxicity, and results show that the small molecule compound has significant anti-inflammatory activity and has a dose-dependent effect. In a lethal mouse influenza infection model, the AZD1480 is used fortreating an infected mouse, which can effectively reduce the concentration of inflammatory factors in a lung lavage fluid of the infected mouse, delay the rate of weight loss of the mouse and increase the survival rate of the mouse. Therefore, the AZD1480 is a novel anti-inflammatory drug against influenza, has the advantages of good safety, high selection index, effective animal model experimentand the like, can be used for developing the drugs for treating the influenza virus infection, and has broad application prospects.

Description

technical field [0001] The invention belongs to the technical field of medicine, and mainly relates to the application of AZD1480 in the preparation of medicine 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 glycop...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/506A61P31/16
CPCA61K31/506A61P31/16
Inventor 陈绪林陈思
Owner 武汉威立得生物医药有限公司
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