【作者】 黄玉新；

【导师】 李廷利；

【作者基本信息】 黑龙江中医药大学 ， 中药学， 2006， 硕士

【摘要】 中药复方四逆散水煎物在改善睡眠、提高睡眠质量方面具有独特的疗效,为阐明其改善睡眠作用药效物质基础,本课题以四逆散水煎物为研究对象,以中药指纹图谱技术和血清药物化学方法为主要研究手段,首先在240nm、210nm波长下建立了四逆散水煎物的HPLC指纹图谱,采用相关系数法评价了指纹图谱的相似度,在同条件下建立了四逆散水煎物中芍药苷、柚皮苷、橙皮苷、甘草酸、甘草次酸的含量测定方法,以此为四逆散水煎物的制备提供质控标准;在此基础上,进行了四逆散拆方煎煮化学成分变化分析,以说明四逆散在拆方煎煮过程中的成分变化,经过对比发现,四逆散在全方煎煮过程中产生了各单味药中所不含有的新成分,不同煎煮物中主要成分的含量测定结果表明,四逆散中各单味药中成分之间存在明显的相互增溶作用。在确定了甲醇法制备血清样品和给药5h为最佳采血时间后,建立了四逆散血清指纹图谱,确定了8个共有峰;同时对血中移行成分来源进行了认定,其中1号、2号成分均来源于枳实,属枳实及四逆散水煎物中可直接入血成分,3号成分为白芍的体内代谢转化物,4号成分为甘草的体内代谢转化物,5号成分为枳实体内代谢转化物,6号成分属甘草及四逆散水煎物可直接入血成分,7号成分为柴胡经配伍后入血的成分,8号成分为枳实与其它药物配伍经体内代谢所产生的新物质;研究中分析了连续给药7天与单次给药后血中移行成分的动态变化,对比后发现,四逆散水煎物经过连续给药7d后血清中成分比一次给药5h血清中多出现α、β、γ、δ、ε、θ6个成分,其中γ成分为芍药苷,θ成分为甘草次酸。最后比较了给药前后脑脊液中成分的变化,分析发现,脑脊液中除戊巴比妥钠成分外,并无血中移行成分的进入,给药后大鼠脑脊液中的内源性物质分泌显著增多。上述研究结果,为四逆散改善睡眠作用机制的阐明及深层次的开发研究奠定了基础。更多还原

【Abstract】 Chinese medicine prescription sinisan has an unique curative effect on improving sleep. In order to clarify active constituents of sedation function, decoction of sinisan was pilot studied by the method of fingerprint spectrum and serum pharmacochemistry. Firstly, HPLC fingerprint spectrum of decoction of sinisan was established at 210nm、 240nm wave length, the similarity of fingerprints were estimated by correlation coefficient method. Under the established HPLC condition, compounds containing mensurations of Paeoniflorin 、 Naringin> Hesperidin、 Glycyrrhizin、 Glycyrrhetinic acid were established. These methods were Sinisan quality controlling standerdization. On base of these results, the changes of compounds of decocted prescription units were analyzed. The study on compounds in extra-somatic discovered that a new compound was generated during the decoction of sinisan. Furthermore, every compound had an obvious solubilization. The serum fingerprint spectrum of sinisan was established after confirming methanol methods to prepare serum samples and the time of gathering blood samples after oral administration of Sinisan five hours as optimal time. There were eight peaks in the serum fingerprint spectrum. Meanwhile, the origins of these compounds were analyzed. Both compounds land 2 were found rooted in FRUCTUS AURANTII IMMATURUS by the study of the adscription of serum compound. They belong to the constituents of FRUCTUS AURANTII IMMATURUS and decoction of sinisan which can be absorbed into blood directly. Compound 3 is the metabolite of RADIX PAEONIAE ALBA in vivo. Compound 4 is the metabolite of RADIX ET RHIZOMA GLYCYRRHIZAE in vivo. Compound 5 is the metabolite of FRUCTUS AURANTII IMMATURUS in vivo. Compound 6 is constituent which belongs to the constituent absorbed into blood directly. Compound 7 is the constituents absorbed into blood after adding RADIX BUPLEURI. Compound 8 is a new substance which generated by the internal metabolizing after adding FRUCTUS AURANTII IMMATURUS and other medications. Compared the changes between the compounds of seven days oral continued administration of decoction of sinisan with that of five hours singleadministration in serum, a > J3 > y ? 5 x e N 9 , the six more compounds were found ,among which compound Y is Paeoniflorin and compound 9 is Glycyrrhetic acid. Finally, by the analysis of the compound in cerebrospinal fluid, we found that there was no other compound absorbed into blood except for the Pentobarbitalum Natricum. Moreover, the endogenous substance of cerebrospinal fluid was increased obviously. All the results provided a basic data for the further studies on effective constituents and the effecting mechanism of Sinisan.更多还原