当归配方颗粒质量标准规范化研究

【作者】 王万；

【导师】 吴纯洁；

【作者基本信息】 成都中医药大学 ， 药剂学， 2006， 硕士

【摘要】 当归配方颗粒质量标准规范化研究系“十五”国家重大科技专项“创新药物和中药现代化”课题。本研究在中医药理论指导下，按照《中药配方颗粒注册管理办法（试行）》要求，对当归配方颗粒进行了系统研究。 当归配方颗粒由当归单味中药加工制成。根据临床用药需要，结合当归所含成分理化性质，拟定出制备工艺路线，采用正交试验等法进行多指标综合评价，筛选出了最佳制备工艺条件为：加10倍量水提取挥发油4小时，挥发油用倍他环糊精包合，备用；药渣加8倍量水煎煮1小时，滤过，滤液与蒸馏后的水液合并，减压浓缩成相对密度约1.06（80℃）的清膏，喷雾干燥成细粉，加入上述用倍他环糊精包合的挥发油及糊精适量，混匀，干压制粒，即得。 质量标准方面，重点对鉴别、浸出物及阿魏酸含量进行了研究，建立了薄层色谱鉴别方法；通过对多批样品进行测定，暂定70％乙醇浸出物含量不得少于65％（热浸法）；采用HPLC法测定阿魏酸含量并进行了系统方法学研究，根据测定多批样品结果暂定本品每袋含当归以阿魏酸(C₁₀H₁₀O₄)计，不得少于1.5mg。 按照质量标准（草案）及相关技术要求进行了稳定性研究，三批样品用市售包装铝塑袋分装，经三个月常温留样考察，结果三批样品各项指标均符合规定。 指纹图谱研究，确定了以0.5％磷酸-甲醇梯度洗脱的色谱条件，基本确定色谱图中11个共有峰为当归配方颗粒的指纹特征，方法学验证表明其整体性、特征性、稳定性基本符合要求；此外，还分别以当归对照药材和正十八烷内标物质作对照对挥发油的气相鉴别进行了探索研究。 通过采用血虚、血瘀及痛经扭体模型进行药效对比研究，结果当归配方颗粒与当归饮片作用无显著性差异；急性毒性研究结果显示，与当归饮片比较，当归配方颗粒毒性无差异。 以上试验表明：制备工艺合理可行，质量标准可控，成品安全、有效、稳定。更多还原

【Abstract】 The study on standardization of quality standard for Danggui Concen--trated Granule is one of the State level important items. Under the guidance of theories of Traditional Chinese Medicine and Pharmacy, according to the related law, this thesis has made a comprehensive and systematic study on this project.Danggui concentrated granule is made from Danggui Slice. By adopting different experiment methods including orthogonal experiment, the optimal preparation process have been obtained as follows: Isolate volatile oil from Danggui Slice by distillation for 3 hours with 10 portions water, collect the volatile oil and coat it by B-CD, store the coated volatile oil and the aqueous solution for further use. Decoct the residue with 8 portions water for 1 hour, filter, and combine the filtrate with the above aqueous solution, concentrate to a thin extract with a relative density of 1.06（80℃）, spray drying. Add the above coated volatile oil and a quantity of dextrin, mix well, dry granulation.Efforts on quality standard have mainly been put into identification and determination. Methods for TLC identification have been established, meanwhile, the content of 70% ethanol-soluble estractives and ferulic acid have been determined. It contains 70% ethanol-soluble estractives not less than 65%, and ferulic acid (C₁₀H₁₀O₄) not less than 1.5 mg per bag.The preliminary stability test has been fulfilled according to the quality standard and the guidance of related rules, which indicates that the packed granule was stable in 3 months. Furthermore, HPLC fingerprint and GC identification methods are studied to a certain extent.Results of pharmacodynamics and acute toxicity indicate that Danggui concentrated granule is safe and effective compared with Danggui slice.All the experiments mentioned above prove that the preparation technique is reasonable and practicable, the standard is controllable, and the finished product is safe and effective as well as stable.更多还原