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[麻黄汤有效配伍成分在发热大鼠体内的药代动力学研究]

[Pharmacokinetics of compatible effective components of Mahuang Decoction in febrile rats].

作者信息

Wan Jia-Yang, Tian Yan-Fang, Wan Hai-Tong, Yu Li, Zhou Hui-Fen, Li Chang, He Yu

机构信息

Zhejiang Chinese Medical University Hangzhou 310053,China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2019 May;44(10):2149-2155. doi: 10.19540/j.cnki.cjcmm.20190125.002.

Abstract

In the present paper,after the febrile rat model was prepared by injecting yeast,orthogonally compatible effective components from prescription drugs of Mahuang Decoction( Ephedra sinica total alkaloids,Cinnamomum cassia essential oil,amygdalin,Glycyrrhiza uralensis total flavonoids+G. uralensis total saponins) with nine different dosage ratios were given by gavage administration.The plasma concentrations of main active ingredients including ephedrine hydrochloride,pseudoephedrine hydrochloride,methylephedrine hydrochloride,cinnamic acid,amygdalin,liquritin and glycyrrhizin at different time points were analyzed by liquid chromatograph mass spectrometer( LC-MS). Based on the pharmacokinetic parameters of non-compartmental model,the area under curve of total quantum( AUCt) and the mean chromatographic retention time of total quantum( MRTt) were further calculated,in order to evaluate the effect of compatibility on the total statistical moment parameters. The results showed that the pharmacokinetic characteristics of main active components in febrile rats were significantly different after treatment with orthogonally compatibility of E. sinica total alkaloids,C.cassia essential oil,amygdalin,G. uralensis total flavonoids and G. uralensis total saponins. Orthogonal analysis confirmed that different compatibility components had different effects on the total statistical moment parameters. The contribution of effective components of Mahuang Decoction to AUCtwas as follows in a descending order: E. sinica total alkaloids>C. cassia essential oil>amygdalin>G. uralensis total flavonoids+G. uralensis total saponin,while the contribution to MRTtwas: E. sinica total alkaloids >G. uralensis total flavonoids+G. uralensis total saponin>amygdalin>C. cassia essential oil. The E. sinica total alkaloid had the greatest effects on both of the above parameters,and the optimal combination was A_3B_3C_2D_1 for AUCt,and A_1B_1C_1D_1 for MRTt.

摘要

在本研究中,通过注射酵母制备发热大鼠模型后,将麻黄汤(麻黄总生物碱、肉桂挥发油、苦杏仁苷、甘草总黄酮+甘草总皂苷)中9种不同剂量配比的正交配伍有效成分进行灌胃给药。采用液相色谱-质谱联用仪(LC-MS)分析不同时间点盐酸麻黄碱、盐酸伪麻黄碱、甲基麻黄碱、肉桂酸、苦杏仁苷、甘草苷和甘草酸等主要活性成分的血药浓度。基于非房室模型的药代动力学参数,进一步计算总量曲线下面积(AUCt)和总量平均色谱保留时间(MRTt),以评价配伍对总统计矩参数的影响。结果表明,发热大鼠经麻黄总生物碱、肉桂挥发油、苦杏仁苷、甘草总黄酮和甘草总皂苷正交配伍处理后,主要活性成分的药代动力学特征有显著差异。正交分析证实,不同配伍成分对总统计矩参数有不同影响。麻黄汤有效成分对AUCt的贡献由大到小依次为:麻黄总生物碱>肉桂挥发油>苦杏仁苷>甘草总黄酮+甘草总皂苷;对MRTt的贡献依次为:麻黄总生物碱>甘草总黄酮+甘草总皂苷>苦杏仁苷>肉桂挥发油。麻黄总生物碱对上述两个参数的影响最大,AUCt的最佳组合为A_3B_3C_2D_1,MRTt的最佳组合为A_1B_1C_1D_1。

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