Construction method of tree shrew model for evaluating pharmacokinetics and pharmacodynamics of anti-influenza drugs

A technology of anti-influenza virus and pharmacokinetics, applied in the field of medicine

Inactive Publication Date: 2019-03-12
THE FIRST AFFILIATED HOSPITAL OF GUANGZHOU MEDICAL UNIV (GUANGZHOU RESPIRATORY CENT) +3
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Tree shrews (Tupaia belangeri, family Tupaiidae) are small mammals that look like squirrels. They are mainly distributed in Yunnan, Guizhou, Guangxi and other regions in China. In 2013, scientists from the Kunming Institute of Zoology, Chinese Academy of Sciences discovered that tree shrews have a smaller relationship with primates. Commonly used animal models such as mice are closer, and in many respects have the genetic basis that can be used to replace large primate experimental animals such as rhesus monkeys (Fan Y, Huang ZY, Cao CC et al., Genome of the Chinese treeshrew. Nature communications. 2013, 4:1426.), has been widely used in various disease models such as viral infectious diseases (Zheng Yongtang, Yao Yonggang, Xu Lin, etc., Basic biology and disease models of tree shrews, October 2014, Yunnan Science and Technology Press; Wang Xiaojuan , Yang Chun, Su Jianjia, New progress of tree shrews in medical experimental research, Chinese Journal of Comparative Medicine, 2010; 20(2): 67-70), tree shrews have been used in influenza virus research in the 1980s, this topic The group further confirmed that compared with the characteristics of human influenza disease, tree shrews are more simulated than other common influenza animal models in terms of influenza symptoms, virus replication, and respiratory receptor distribution. Kinetics and pharmacodynamics studies have not been reported. Whether the tree shrew can become an animal model of influenza with good drug treatment predictability and provide an effective detection platform for the development of effective treatment methods for human (avian) influenza diseases is still unknown.

Method used

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  • Construction method of tree shrew model for evaluating pharmacokinetics and pharmacodynamics of anti-influenza drugs
  • Construction method of tree shrew model for evaluating pharmacokinetics and pharmacodynamics of anti-influenza drugs
  • Construction method of tree shrew model for evaluating pharmacokinetics and pharmacodynamics of anti-influenza drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1: Pharmacokinetics and antiviral efficacy of oseltamivir in tree shrews

[0023] 1. Pharmacokinetic study of oseltamivir

[0024] After 40 adult healthy Chinese Burmese tree shrews (male and female) fasted for 12 hours (free drinking water), 4 tree shrews in each group were given oseltamivir 10mg / kg by oral gavage, and recorded to At the time of drug administration, 0.5ml of blood was collected through the tail vein or femoral vein at 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours after administration, and the collected blood was placed in a centrifuge tube containing heparin. Centrifuge at 1500g at 4°C for 10 minutes, then transfer the plasma to an EP tube and store it in a deep-low temperature freezer at -80°C.

[0025]Accurately weigh an appropriate amount of oseltamivir phosphate, oseltamivir carboxylate and internal standard peramivir, and use 90% v / v methanol aqueous solution to make a stock solution of about 1 mg / mL, in which oseltamivir phosphate needs to...

Embodiment 2

[0030] Example 2: Pharmacokinetics and antiviral pharmacodynamics results of oseltamivir in tree shrews

[0031] 1. Comparison of pharmacokinetic parameters between tree shrews and several other animal models of influenza

[0032] Tree shrews were orally administered oseltamivir phosphate 10mg / kg / d, and the drug-time curve after administration was as follows figure 1 and figure 2 (The four different curves in the figure represent the respective C-t drug-time curves of the four tree shrews) As shown: the main pharmacokinetic parameters in the tree shrews were calculated by detecting the blood drug concentration of oseltamivir after oral administration, and the peak blood drug Concentration (C max ) is 1.34μg / ml, peak time (T max ) is 0.75h, serum clearance half-life (T 1 / 2 ) is 2.03h, the area under the plasma concentration-time curve (AUC 0-12 ) is 1.76mg*h / liter.

[0033] 2. Pharmacodynamic study of oseltamivir on tree shrews infected with H9N2 and H1N1 influenza virus...

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Abstract

The invention provides a construction method of a tree shrew model for evaluating pharmacokinetics and pharmacodynamics of anti-infuenza drugs. The method adopts tree shrew as a platform to evaluate the drug effect of oseltamivir for treating the tree shrew infected by different influenza viruses. The drug plasma clearance half-time period and time to peak of the tree shrew after taking the oseltamivir are similar to that of mice, and the detoxification and corresponding inflammation response of H9N2 influenza viruses in the tree shrew body can be reduced by virtue of the treatment with the oseltamivir, so that the tree shrew can be used as an influenza animal model with the drug treatment foreseeability.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a method for constructing a tree shrew model for evaluating pharmacokinetics and pharmacodynamics of anti-influenza virus drugs. Background technique [0002] Influenza disease seriously threatens human health (Fischer WA 2nd, Gong M, Bhagwanjee S et al., Global burden of influenza as a cause of cardiopulmonary mortality and mortality. Glob Heart. 2014; 9 (3): 325-336.), prepare a Animal models that can effectively replicate the characteristics of human influenza disease and good drug predictability are of great value for the development and screening of new anti-influenza virus drugs or vaccines, and the evaluation of antiviral treatment options. Currently commonly used influenza animal models such as mice and ferrets are too different from human species, and the predictability of drugs is often poor. For example, the pathogenic mechanism of mouse influenza is quite...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/215A61P31/16A01K67/02G01N33/569
CPCA01K67/02A61K31/215A61P31/16G01N33/56983
Inventor 杨子峰袁兵李润峰杨春光夏雪山张荣平张云辉冯悦钟南山
Owner THE FIRST AFFILIATED HOSPITAL OF GUANGZHOU MEDICAL UNIV (GUANGZHOU RESPIRATORY CENT)
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