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Pharmacokinetics-pharmacodynamics analysis method for treating chronic heart failure by using astragalus membranaceus and ginseng granules based on metabonomics

A chronic heart failure and pharmacokinetic technology, applied in the field of analysis, can solve the problems of insufficient index components and efficacy indicators, complex chemical components of traditional Chinese medicine compounds, and insufficient correlation between index components and efficacy indicators.

Pending Publication Date: 2021-09-14
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Due to the complex chemical components of traditional Chinese medicines, which have the characteristics of multi-targets, multi-pathways, and multi-levels, compared with single-ingredient western medicines, the PK-PD research of traditional Chinese medicines is more important in selecting typical pharmacokinetic indicators (PK indicators) and The characteristic pharmacodynamic index (PD index) has greater challenges
For the PK-PD research of the compound prescription, the pharmacokinetics (PK index) of the main medicinal components in the prescription is often combined with the change of one or several pharmacological indexes (PD index) to reflect the pharmacodynamic change of the compound prescription, but this However, there are still defects that the index components and drug efficacy indicators are not sufficiently correlated and the index components and drug efficacy indicators are not comprehensive enough.

Method used

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  • Pharmacokinetics-pharmacodynamics analysis method for treating chronic heart failure by using astragalus membranaceus and ginseng granules based on metabonomics
  • Pharmacokinetics-pharmacodynamics analysis method for treating chronic heart failure by using astragalus membranaceus and ginseng granules based on metabonomics
  • Pharmacokinetics-pharmacodynamics analysis method for treating chronic heart failure by using astragalus membranaceus and ginseng granules based on metabonomics

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] 1. Materials and Instruments

[0058] 1.1 Drugs, reagents and instruments

[0059] Tanshinone I (purity>98%, batch number: 170926), dihydrotanshinone I (purity>98%, batch number: 180109), cryptotanshinone (purity>98%, batch number: 171029), formononetin (purity>98% , batch number: 170328), actecoside (purity>98%, batch number: 170730), chlorogenic acid (purity>98%, batch number: 171120), verbascoside (purity>98%, batch number: 170920), glycyrrhizic acid (purity >98%, batch number: 181226), glycyrrhetinic acid (purity>98%, batch number: 170910), liquiritigenin (purity>98%, batch number: 181227), isoliquiritigenin (purity>98%, batch number: 190226), Liquiritin (purity>98%, batch number: 170330), isoliquiritin (purity>98%, batch number: 190317), apiose liquiritin (purity>98%, batch number: 190107) were purchased from Shanghai Ronghe Pharmaceutical Technology Development Co., Ltd. Company; Standards Naringin and Reserpine and Endogenous Standards L-Tryptophan, Xanthine Ac...

Embodiment 2

[0080] Embodiment 2 pharmacokinetic research results and discussion

[0081] 1. Methodology

[0082] 1. Optimization of mass spectrometry conditions

[0083] The prepared mixed standard solution was diluted to a concentration of 1 μg / mL for optimization of mass spectrometry conditions. The MRM parameters of each analyte are shown in Table 1.

[0084] 2. Linearity of the method

[0085] Use concentration of 0.01, 0.025, 0.05, 0.1, 1, 5, 10, 50, 100, 250, 500, 1000, 2500, 5000ng·mL -1 standard solution to draw a standard curve. Taking the peak area ratio (Y) of the analyte and the internal standard in the plasma sample as the ordinate, and the concentration (X) of the analyte as the abscissa, the least squares regression method is used to prepare the calibration curve, and the regression of each compound is obtained. Equation, correlation coefficient (R 2 ) and linear range. The lower limit of quantification (LLOQ) was calculated with the signal-to-noise ratio S / N=3, and S / ...

Embodiment 3

[0107] Example 3 Establishment of PK-PD binding model

[0108] The association analysis results of the 5 active components of Qishen Granules in plasma and the 4 endogenous markers in the metabolic pathways related to CHF and BNP by Phoenix WinNonlin 6.0 software are as follows: image 3 shown. Each endogenous substance can show a clockwise or counterclockwise change with the concentration of the four active ingredients, indicating that the relationship between the active ingredients and the endogenous indicators is not a simple linear relationship, showing complex interrelationships and PK indicators The delayed effect of Qishen Granules indicates that the active ingredients of Qishen Granules play a combined and synergistic effect on the treatment of CHF, which provides a new perspective for elucidating the active substances of Qishen Granules and their mechanism of treating CHF.

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Abstract

The invention relates to a pharmacokinetics-pharmacodynamics analysis method for treating chronic heart failure by using astragalus membranaceus and ginseng granules based on metabonomics, which comprises the following steps: taking 14 main medicinal components in the astragalus membranaceus and ginseng granules as PK indexes, 20 characteristic metabolic markers and clinical common heart failure examination B-type natriuretic peptide as PD indexes, and performing metabonomics-based PK / PD research for treating chronic heart failure by the astragalus membranaceus and ginseng granules. The method can help understand the pharmacodynamic material basis and action mechanism for treating chronic heart failure, and is helpful for guiding the secondary development of the medicine and the clinical reasonable medication of the astragalus membranaceus and ginseng granules.

Description

technical field [0001] The invention relates to an analysis method, in particular to a pharmacokinetic-pharmacodynamic analysis method based on metabolomics for treating chronic heart failure (induced by isoproterenol) with Qishen Granules. Background technique [0002] Qishen granules are derived from clinical experience prescriptions, which are composed of six traditional Chinese medicines of Astragalus, Salvia, Honeysuckle, Scrophulariae, Licorice, and Aconite. Qishen Granules are clinically used to improve and treat myocardial ischemic chronic heart failure, and have a good therapeutic effect. Pharmacological studies have shown that Qishen Granules can inhibit myocarditis damage by regulating the metabolism of arachidonic acid, promote angiogenesis and improve cardiac remodeling by promoting the differentiation of M1 macrophages into M2 macrophages, and it can also regulate Fatty acid and glucose metabolism to improve myocardial energy metabolism. Although Qishen Granu...

Claims

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Application Information

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IPC IPC(8): G16H70/40G01N30/88
CPCG16H70/40G01N30/88G01N2030/8809
Inventor 刘舒刘姝鑫宋凤瑞刘志强郑重邢俊鹏
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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