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大鼠静脉注射三种不同制剂后槲寄生共存成分药代动力学相互作用的研究。

A study of pharmacokinetic interactions among co-existing ingredients in Viscum coloratum after intravenous administration of three different preparations to rats.

作者信息

Ma Yuying, Fan Ronghua, Duan Mengmeng, Yu Zhiguo, Zhao Yunli

机构信息

Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.

出版信息

Pharmacogn Mag. 2015 Jul-Sep;11(43):455-62. doi: 10.4103/0973-1296.160448.

Abstract

BACKGROUND

Viscum coloratum (Komar) Nakai, known as Hujisheng in china, has been widely used as a herb medicine to treat a variety of diseases, including cardiovascular diseases, cancer, hypertension, hepatitis and hemorrhage.

OBJECTIVE

The aim was to investigate pharmacokinetic interactions among co-existing ingredients in V. coloratum after intravenous administration of three different preparations (four monomer solutions, the mixture of them and Viscum coloratum extracts) to rats.

MATERIALS AND METHODS

After protein precipitation pretreatment with plasma samples, high performance liquid chromatographic methods were developed and applied to quantitatively determinate the four components [syringin (Syri), homoeriodictyol-7-O-β-D-glycoside (Hedt-III), homoeriodictyol-7-O-β-D-apiose (1 → 2)-β-D-glycoside (Hedt-II) and homoeriodictyol-7-O-β-D-apiosiyl-(1 → 5)-β-D-apiosyl-(1 → 2)-β-D-glycoside (Hedt-I)]. The pharmacokinetic parameters (Area under the curve [AUC(0-t)], AUC(0-∞), t 1/2) were calculated using DAS 2.1 software (Chinese Pharmacological Society, Shanghai, China) and compared statistically by One-way analysis of variance using SPSS software (18.0, Chicago, IL, USA) with P < 0.05 considered statistically significant.

RESULTS

Good linearities were achieved in the measured concentration range with R (2) it0.9920. Precision, accuracy and extraction recovery were all within the acceptable range. For Syri, there was a significant difference only on t 1/2 among three treatment groups. For Hedt-I, Hedt II and Hedt-III, three flavonoid glycosides, the change of AUC(0-t), AUC(0-∞) and t 1/2 were markedly distinctive and even converse.

CONCLUSION

Complex, extensive pharmacokinetic interactions were observed among these components in V. coloratum. They were mutually influenced by the in vivo absorption, distribution, metabolism and elimination. The result suggested traditional Chinese medicine was a complicated system, and we should take a scientific and dialectic view in the research and development processes.

摘要

背景

槲寄生在中国被称为胡寄生,作为一种草药已被广泛用于治疗多种疾病,包括心血管疾病、癌症、高血压、肝炎和出血。

目的

研究给大鼠静脉注射三种不同制剂(四种单体溶液、它们的混合物以及槲寄生提取物)后,槲寄生中共存成分之间的药代动力学相互作用。

材料与方法

用血浆样本进行蛋白沉淀预处理后,建立高效液相色谱法并用于定量测定四种成分[紫丁香苷(Syri)、高圣草素 - 7 - O - β - D - 糖苷(Hedt - III)、高圣草素 - 7 - O - β - D - 芹糖基(1→2)-β - D - 糖苷(Hedt - II)和高圣草素 - 7 - O - β - D - 芹糖基 -(1→5)-β - D - 芹糖基 -(1→2)-β - D - 糖苷(Hedt - I)]。使用DAS 2.1软件(中国药理学会,中国上海)计算药代动力学参数[曲线下面积[AUC(0 - t)]、AUC(0 - ∞)、t1/2],并使用SPSS软件(18.0,美国伊利诺伊州芝加哥)通过单因素方差分析进行统计学比较,P < 0.05被认为具有统计学意义。

结果

在所测浓度范围内具有良好的线性关系,R(2)≥0.9920。精密度、准确度和提取回收率均在可接受范围内。对于Syri,三个治疗组之间仅在t1/2上存在显著差异。对于三种黄酮苷Hedt - I、Hedt II和Hedt - III,AUC(0 - t)、AUC(0 - ∞)和t1/2的变化明显不同甚至相反。

结论

在槲寄生的这些成分之间观察到复杂、广泛的药代动力学相互作用。它们在体内的吸收、分布、代谢和消除方面相互影响。结果表明中药是一个复杂的系统,我们在研发过程中应持科学辩证的观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/4522830/038bcb641a5e/PM-11-455-g001.jpg

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