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Application of panatinib in preparation of medicament for treating influenza virus infection

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

Inactive Publication Date: 2019-07-16
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, so far, no relevant reports have been found on ponatinib for anti-treatment of influenza.

Method used

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  • Application of panatinib in preparation of medicament for treating influenza virus infection
  • Application of panatinib in preparation of medicament for treating influenza virus infection
  • Application of panatinib in preparation of medicament for treating influenza virus infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1: Evaluation of anti-influenza virus-induced inflammatory activity of ponatinib in U937 cell line

[0050] 1 cell culture

[0051] 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.

[0052] 2 Cytotoxicity detection of ponatinib

[0053] 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, and the final concentrations were 0.002 μM, 0.005 μM, 0.014 μM, 0.041 μM, 0.123 μM, 0.37 μM, 1.111 μM, 3.333 μM and 1...

Embodiment 2

[0065] Example 2: Evaluation of ponatinib's anti-inflammatory activity against other influenza viruses in U937 cell line

[0066] In this example, the U937 cell line was infected with the H3N2 subtype (A / Human / Hubei / 3 / 2005), and the specific method was the same as that in Example 1.

[0067] The results confirmed that ponatinib 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

[0068] Example 3: Evaluation of the effect of Ponatinib on anti-influenza virus-induced inflammation in a lethal influenza infection model in mice

[0069] 1 Experimental process:

[0070] 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.

[0071] 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. .

[0072] 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 gro...

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Abstract

The invention discloses an application of panatinib in the preparation of a medicament for treating influenza virus infection. The applicant tests the toxicity of panatinib to cells on human monocyteseries U937 and tests the secretion inhibitory effect of panatinib on the three important inflammatory factors IL-8, IP-10 and MCP-1 in U937 cell line in a non-toxic or low-toxic concentration range.The result shows that the small-molecular compound has significant anti-inflammatory activity and dose-dependent effect. In a lethal mouse influenza infection model, panatinib is used for treating infected mice, and can effectively reduce the concentration of inflammatory factors in lung lavage fluid of the infected mice, delay the reduction speed of the weight of the mice, and improve the survival rate of the mice. Therefore, the panatinib disclosed by the invention is a novel anti-inflammatory drug aiming at influenza, has the advantages of good safety, high selection index and effective animal model experiments, can be used for developing drugs for treating influenza virus infection, and has wide application prospect.

Description

technical field [0001] The invention belongs to the technical field of medicine, and mainly relates to the application of ponatinib 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 glyc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/5025A61P31/16
CPCA61K31/5025A61P31/16
Inventor 陈绪林陈思
Owner 武汉威立得生物医药有限公司
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