基于生物毒价检测和化学成分分析的毒性中药附子质量评控分析-中药学专业论文.docxVIP

成都中医药大学 成都中医药大学 2013 届博士学位论文 IV IV 效果优于后者，且不会额外引入无机杂质，非常值得推广使用。 无胆炒制附片的毒价和毒效物质含量均显著高于传统胆制附片（P﹤0.01 或 P ﹤0.05），其中毒价约为后者的 2 倍，苯甲酰乌头原碱等三种单酯型生物碱含量约 增加 6 倍。该结果提示，无胆炒制工艺的“减毒存效”效果有待于进一步研究。 5. 初步构建了附子的“毒性效应成分指数” 为了提高安全性评控的便捷性和实用性，本文在毒性成分含量与生物毒价相 关性研究的基础上，提出探索构建基于主要毒性成分含量综合加权的生物毒价预 估值——“毒性效应成分指数”，并初步构建了附子的“毒性效应成分指数”预估 模型。经验证，该模型可用于预估附子的生物毒价。 6. 整合上述研究结果，提出附子质量标准修订建议，并制定质量标准草案 根据附子质量评控方法的对比研究、毒性物质基础和无胆炮制方法的合理性 探讨结果，建议修订商品规格、质量检测方法，即：①规格中增加无胆蒸制附片； ②【检查】项修订双酯型生物碱限量检查法；③【含量测定】项修订单酯型生物 碱含量测定法；④增加【生物毒价测定】项。 综上所述，本文建立了生物毒价测定方法和“毒性效应成分指数”模型，结 合化学成分分析法，提升了评控毒性中药附子安全性的质量标准，丰富和发展毒 性中药质量评价与控制研究模式，为客观评价毒性中药的毒性大小提供研究思路 和手段，为临床用药安全奠定基础。 关键词：毒性中药；附子；质量控制；安全性；生物毒价；毒性效应成分指数； 炮制 V V Abstract Quality control and evaluation of traditional Chinese medicine (TCM) are the important means, which can ensure the safety, effectiveness , stability , controllability and clinical application .Because of the strong toxicity, the quality of toxic TCM will definitely influence its safety and effectiveness in clinical application. However, the current pattern of quality control and evaluation, which is mainly based on the qualitative and quantitative determination of chemical components, is difficult to reflect the safety and efficacy of toxic TCMs. In this paper, we studied the Aconiti Lateralis Radix (Fuzi) in order to enrich and improve the quality control methodology of toxic TCMs in view of bioassay. The toxic-potency assay of Fuzi was established based on the minimum lethal dose to the whole animal. We also established the determination method for the content of 6 kinds of alkaloids by the relative correction factor. The 21 kinds of diterpenoid alkaloids were detected by the HPLC-MS/MS. Based on the toxic-potency assay and chemical composition analysis, we consider the specifications of aconite product and the quality testing method should be modified. The quality standards were revised in draft. Our study also provides a reference for the clinical application of toxic TCMs. The main results are as fol