裸花紫珠药材及相关制剂质量控制方法研究

Study on Quality Control Methods of Callicarpa Nudiflora and Related Preparations

目的:建立裸花紫珠药材及相关制剂质量标准,为临床用药安全提供保障。方法:采用多种柱色谱方法、波谱分析技术、显微法、高效液相色谱法、HPLC-MS/MS法以及现代药理方法对裸花紫珠及相关制剂药效物质基础及作用机理、质量控制方法及药代动力学进行系统研究。结果:从裸花紫珠药材中分离鉴定了76个化合物,发现11个具有止血、活血、抗炎等药效活性成分,并明确了可用于裸花紫珠药材及相关制剂质控定量活性指标成分木犀草苷和毛蕊花糖苷;起草了裸花紫珠药材、干浸膏、裸花紫珠片/胶囊/颗粒5项质量标准;建立了HPLC-MS/MS同时测定大鼠血浆中木犀草苷、毛蕊花糖苷、异毛蕊花糖苷等7种活性成分的血药浓度的方法。结论:通过系统研究,阐明了裸花紫珠药材药效物质基础及作用机理以及主要活性成分药物动力学参数,为临床合理用药提供了科学依据,同时建立了裸花紫珠药材、干浸膏、裸花紫珠片/胶囊/颗粒5项国家药品标准,形成了从裸花紫珠-中间体-系列制剂的完整质量控制体系。

Objective:Establishing quality standards of Callicarpa nudiflora and related preparations,and providing clinical medication safety.Methods:Various methods including column chromatography,spectral analysis,microscopy,HPLC-MS/MS and modern pharmacology were used to systematically study the pharmacodynamic substance basis,mechanism,quality control methods and pharmacokinetics of Callicarpa nudiflora and related preparations.Results:76 compounds were isolated and identified from Callicarpa nudiflora,11 components were considered to be active in stopping bleeding,invigorating the circulation of blood and anti-inflammatory.Luteoloside and acteoside were clarified as quantitative active components for quality control of Callicarpa nudiflora and related preparations.Drafted 5 quality standards of crude materials,dry extract,tablets,capsules,and granules of Callicarpa nudiflora.A HPLC-MS/MS method for analyzing the blood concentration of 7 active components including luteoloside,acteoside and isoacteoside was established.Conclusion:Through systematic research,this paper expounded the pharmacodynamic substance basis,mechanism and pharmacokinetic parameters of the main active ingredients,which provided scientific basis for rational drug use in clinic,and established 5 national drug standards for Callicarpa nudiflora,dry extract,tablets,capsules,and granules,forming a complete quality control system among Callicarpa nudiflora,intermediates,and final series of preparations.