Application of pre-clinical pharmacokinetics key technology and research system to pemetrexed

A pemetrexed and key technology technology, which is applied in the preclinical pharmacokinetic key technology and research system in the application field of pemetrexed, can solve the problem that the structural design cannot be fully utilized, and it cannot adapt to the development and transformation of new drug research and development models, etc. problem, to achieve the effect of improving sensitivity

Inactive Publication Date: 2016-04-06
刘晓东 +1
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  • Application Information

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Problems solved by technology

With the transformation of my country's new drug R&D model from "imitation-based" to "combination of imitation and innovation" and "innovation-based", the original pharmacokinetic research and evaluation system in my country can no longer meet the needs of the development and transformation of new drug R&D models. Cannot give full play to the guiding role of pharmacokinetic research in the structural design and optimization of lead compounds, the design and modification of new dosage forms, the prediction of drug interactions, and the clinical safety and rational use of drugs, etc.

Method used

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Embodiment Construction

[0019] The present invention provides the application of the key technology and research system of preclinical pharmacokinetics in pemetrexed, which includes:

[0020] (1) After administering a certain concentration of pemetrexed to the experimental animals for a certain period of time, collect one or more biological samples in blood, urine and feces;

[0021] (2) Process the biological sample obtained in step (1) by liquid-liquid extraction, protein precipitation, and solid-phase extraction techniques to prepare a corresponding solution;

[0022] (3) Analyze the solution prepared in step (2) by liquid chromatography-mass spectrometry (LC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS / MS).

[0023] The experimental animals of the present invention may be rats, mice, guinea pigs, rabbits or dogs.

[0024] The certain concentration and certain time are determined according to the experimental animals.

[0025] In a preferred embodiment, in step (2), the liquid-li...

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Abstract

The invention provides application of a pre-clinical pharmacokinetics key technology and a research system to pemetrexed. The application comprises the steps that 1, after pemetrexed with certain concentration is given to an experimental animal for a certain period of time, one or more biological samples in blood, urine and excrement are collected; 2, the biological samples obtained in the step 1 are treated through liquid-liquid extraction, protein precipitation and solid-phase extraction technologies to be prepared into corresponding solutions; 3, liquid chromatography-mass spectrum (LC-MS) and liquid chromatography-tandem mass spectrum (LC-MS/MS) are adopted for analyzing the solutions prepared in the step 2. According to the application, Caco-2 cells can be adopted for detecting membrane permeating performance and the cell absorbing ability of pemetrexed; or pemetrexed with the certain concentration treats primary culture cerebral microvascular endothelial cells so as to detect blood-brain barrier permeability of pemetrexed; or the overall animal, the overall animal, S9, intestine and liver particle bodies and monoclonal purification enzymes are adopted for detecting the in-vitro metabolism stability of pemetrexed and identifying metabolite.

Description

technical field [0001] The invention relates to the application of the key technology and research system of preclinical pharmacokinetics to pemetrexed. Background technique [0002] In my country, the incidence of cancer is close to the world level, but the mortality rate is higher than the world level. According to relevant data estimates, the outpatient and hospitalization expenses caused by tumors are tens of billions of yuan each year, which is much higher than the medical expenses of other chronic diseases, and it is one of the important factors for the rise of total health expenses. [0003] Pemetrexed is an antifolate preparation with a pyrrolic pyrimidine group in its structure. It can inhibit the growth of tumors by destroying the normal metabolic process dependent on folic acid in cells and inhibiting cell replication. [0004] Pharmacokinetics is a discipline that studies the absorption, distribution, metabolism and excretion process and laws of drugs in organis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/00G01N24/08G01N33/50
CPCG01N30/00G01N24/08G01N33/50
Inventor 卢婷刘晓东
Owner 刘晓东
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