基于体内时空规律的胆木制剂物质基础研究

The basic research of ethnic drug Nauclea Officinalis and its preparations are still rather weak, Clarification of the material basis for ethnic drug is critical research and breakthrough point, We suggest the core of material basis for component composition of danmu preparations are alkaloids and phenols based on preliminary studies..In this project we will take the main phenolic compounds and alkaloids in the danmu preparations for active ingredients, from the perspective of metabolism in vivo in-depth study of the material basis of danmu preparations. To reveal the effect of composition in the body composition, prototype and metabolites of danmu preparations in the blood will be analyzed and identification by UPLC-QTOF-MS; To Clarify the main way of action and metabolic pathways of the active ingredient, Pharmacokinetic will be studied by plasma concentration method; To clear effective ingredients, metabolites of bile, urine and fecal will be analyzed and identification and law of excretion of active ingredient will be studied. Eventually the differences of active ingredient in the vivo process, as well as the metabolic characteristics will be revealed. vivo rules of time and space of active ingredient of danmu preparations will be studied by qualitative and quantitative means, and thus the material basis in vivo biliary of danmu preparations will be clarifyied

民族药胆木及其制剂的基础研究还比较薄弱，而物质基础的阐明是民族药研究的关键与突破口，基于前期研究我们提出构成胆木制剂抗炎作用物质基础组分的核心是：生物碱与酚类物质。.本项目聚焦于胆木制剂中主要酚类和生物碱类物质，从体内时空变化规律深入地研究胆木制剂的物质基础：采用UPLC-QTOF-MS分析并鉴定胆木制剂入血成分的原型和代谢产物，揭示其体内效应成分组成；以血药浓度法研究其活性成分的药动学，明确活性成分的主要作用方式和代谢途径；分析并鉴定给药后胆汁、尿和粪便中代谢产物和活性成分的排泄规律；最终得出活性成分的体内代谢特征，并揭示多种给药方式（口服胆木浸膏片和肌注胆木注射液）活性成分在体内过程的差异性。本项目采用定性与定量相结合的手段，研究胆木制剂活性成分在体内的时空变化规律，进而阐明其抗炎物质基础。

胆木 (Nauclea officinalis)，又名乌檀，为茜草科乌檀属植物，其主要以茎皮入药，是我国少数民族黎族民间常用药，具有清热解毒、消肿止痛、抗菌消炎之功效。国内目前主要有胆木注射液和胆木浸膏片等中药剂型，临床上用于治疗急性扁桃体炎、咽炎、结膜炎以及上呼吸道感染等症状。胆木注射液和胆木浸膏片使用比较广泛，疗效确切，然而发挥疗效的体内物质基础并不清楚。.本项目首先制备了胆木中的9个生物碱（苷）类单体化合物，采用UPLC-PDA-QTOF/MS技术鉴定出了胆木注射液中22个成分，进而采用UPLC-PDA法同时测定胆木注射液和胆木浸膏片中12个成分含量，为其进一步体内物质基础研究的开展奠定坚实基础。此外，采用UPLC-PDA-QTOF/MS分析技术，鉴定大鼠给予胆木制剂后的入血成分，初步阐明其体内效应物质基础；建立了灵敏而可靠的UFLC-MS/MS多反应监测（MRM）模式，测定大鼠血浆中6种生物碱的浓度，研究了胆木制剂在大鼠体内的药代动力学特征；采用UPLC-QTOF/MS技术鉴定了胆木提取物和胆木注射液在大鼠体内血、尿液、粪便和胆汁中的代谢产物。.本项目从体外和体内角度系统的研究了胆木制剂化学成分群的组成和含量测定。揭示了胆木制剂体外化学成分群组成，鉴定了体内化学成分群，进一步鉴定了体内代谢产物。同时定量分析了体外化学成分群的含量，并研究了活性成分的药代动力学特征，阐明了胆木制剂的体内外物质基础组成。