基于液质联用技术的瑞香狼毒化学成分及药代动力学研究

发布时间：2018-05-29 03:38

本文选题：瑞香狼毒 + 液质联用　；参考：《河北大学》2017年硕士论文

【摘要】：瑞香狼毒为瑞香科植物Stellera chamaejasme L.的干燥根,又名断肠草,始载于《神农本草经》,瑞香狼毒性味苦平,有逐水祛痰,破疾杀虫之功效。现代药理学和临床研究表明瑞香狼毒具有抗HIV病毒、抗肿瘤、抗菌、抗结核、抗白血病、抗惊厥、抗癫痫等作用。目前,对于瑞香狼毒的研究主要集中于某一类或几种化学成分的提取、分离,而对其药材中多组分的同时分析,炮制对各化学成分的影响及体内代谢研究报道较少。本论文根据目前的研究不足进行了以下研究:1、采用MIM-IDA-EPI扫描方式为主,LTQ/Orbitrap mass分析方法为辅的分析方法对瑞香狼毒水提液进行分析、鉴定。结果显示共鉴定出瑞香狼毒中61种化合物(其中黄酮类23种,香豆素类14种,萜类2种,木脂素6种,苯丙素3种,其它类13种),并对其可能的裂解途径进行推测,总结质谱裂解规律。该方法简便、快速,为全面研究瑞香狼毒的化学组成和质量控制奠定了基础,为中药材的定性鉴别提供有效手段。2、采用正负离子模式相结合的MIM-IDA-EPI检测方式,对炮制前后瑞香狼毒中的特征峰运用代谢组学技术对瑞香狼毒中的特征峰进行比较,采用多元统计法和药理相结合的方法对特征峰进行筛选、并根据信息鉴定特征峰。通过分析发现瑞香狼毒生品和各炮制品间化学成分具有明显差异,并发现炮制后有大量峰存在显著性差异,其中29个差异变量的结构已得到鉴定。3、建立可同时测定大鼠血浆中新狼毒素A、新狼毒素B、异狼毒素、西瑞香素含量的液质联用方法,并用于大鼠灌胃给药瑞香狼毒水提液后该4种成分的药代动力学研究。结果表明血浆中新狼毒素A、B、异狼毒素、西瑞香素在大鼠血浆中的定量下限均可达0.274 ng/mL,在0.274~200 ng/mL浓度范围内线性关系良好(r0.99),批内和批间精密度(RSD)均小于10%。新狼毒素A在0.5 h(tmax)达到最大浓度(Cmax)5.24ng/mL,西瑞香素在0.083 h(tmax)达到最大浓度(Cmax)1.48 ng/mL,表明这两种物质吸收迅速,可快速进入血液循环系统。新狼毒素B和异狼毒素在大鼠血浆中均没有暴露。
[Abstract]:Stellera chamaejasme is Stellera chamaejasme L. Dry root, also known as amputation grass, first contained in "Shennong Herbal Medicine", daphrophon wolf toxic taste bitter, water dispelling phlegm, killing the efficacy of disease. Modern pharmacological and clinical studies have shown that Daphne chamaejasme has antiviral, antitumor, antimicrobial, antituberculosis, antileukemia, anticonvulsant and antiepileptic effects. At present, the research of chamaeanthus chamaejasme venom is mainly focused on the extraction and separation of one or more chemical constituents, but there are few reports on the effects of processing on each chemical component and metabolism in vivo by simultaneous analysis of multicomponent in its medicinal materials. In this paper, the following research was carried out according to the deficiency of current research: 1. The MIM-IDA-EPI scanning method was used to analyze and identify the aqueous extract of Stellera chamaejasme venom by using the LTQ / Orbitrap mass analysis method. The results showed that 61 compounds (23 flavonoids, 14 coumarins, 2 terpenoids, 6 lignins, 3 phenylpropionins and 13 other species) were identified and their possible cleavage pathways were deduced. The cracking law of mass spectrometry was summarized. The method is simple and rapid, which lays a foundation for the overall study of chemical composition and quality control of Rubus chamaejasme venom, and provides an effective method for the qualitative identification of Chinese medicinal materials. The method of MIM-IDA-EPI combined with positive and negative ion mode is adopted. The characteristic peaks of chamaejus chamaejasme venom before and after processing were compared by metabolic technique. The characteristic peaks were screened by multivariate statistics and pharmacology, and the characteristic peaks were identified according to the information. It was found that there were significant differences in chemical constituents between raw and processed products of chamaejasma chamaejasme and a large number of peaks after processing. The structure of 29 different variables has been identified. A method for simultaneous determination of the contents of neophaliphin A, neopyclotoxin B, isocatoxin, and siderin in plasma of rats was established. The pharmacokinetics of the four components was studied after the rats were given water extract of Daphne chamaejasme. The results showed that the lower limit of plasma quantification of new wolf toxin, isopyclotoxin and ciprofloxacin in plasma of rats was 0.274 ng / mL, the linear relationship was good in the range of 0.274 ~ 200 ng/mL, and the intra and inter-assay precision was less than 10%. The maximum concentration of new wolf toxin A was 5.24ng / mL at 0.5 h / t max, and the maximum concentration of sirosin was 1.48ng / mL at 0.083 h / t _ (max), indicating that the two substances were absorbed rapidly and could enter the blood circulation system quickly. Neither new wolf toxin B nor iso-wolf toxin was exposed to plasma in rats.
【学位授予单位】：河北大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R284;R285;O657.63

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