枳术颗粒二次开发基础研究

【作者】 尹慧晶；

【导师】 罗惠善； 濮存海；

【作者基本信息】 延边大学 ， 药剂学， 2007， 硕士

【摘要】 枳术颗粒是由炒白术、炒枳实和荷叶三味药材组成的复方制剂，具有健脾消食、行气化湿的功效。处方最初来源于张仲景的《金匮要略.水气病脉证并治》篇中的枳术汤，后经金代张元素变化为枳术丸，记载于《医学启源》中。枳术颗粒是南京中山制药有限公司在生产品种，但生产上得膏率很高，影响制剂的成型工艺完成，影响了该产品产业化规模的实现。本课题对枳术颗粒进行二次开发基础研究，从药物的制备工艺及药效学方面进行研究。选用L₉（3⁴）正交设计表优选超临界CO₂萃取工艺，采用膜分离方法将按原工艺提取的药液按照分子量大小经过膜分成分子量大于20万、20万-2万、小于2万、2万-1万、1万-3000、小于3000六个部位，并考察了各部位的得膏率。建立脾虚和食积小鼠模型，观察超临界萃取部位和膜分离方法分离的各部位对胃排空和小肠推进功能的影响，初步确定有效部位为分子量小于2万的部分和超临界CO₂萃取所得混合萃取物部分。采用GC-MS法对混合萃取物进行结构鉴定，HPLC法对膜分离部位进行指标行成分含量比较，结果共鉴定出42个化学成分，以倍半萜类成分为主，其中γ-榄香烯的含量最高。并且分子量小于2万部位中柚皮苷及橙皮苷含量均大于原工艺，并且该部位的得膏率比原生产工艺的得膏率低10个百分点。选用沸腾喷雾制粒技术建立成型工艺，可获得较好制粒效果。药效筛选出超临界CO₂萃取物部位为有效部位，本文采用CAChe6.1软件计算模拟包合过程，β-环糊精包合技术将超临界萃取物制成包合物，通过DSC，紫外分光光度法，证明萃取物与β-CD已形成包合物。本文采用新型的制剂工艺，选择合适的药理指标药效跟踪筛选有效部位，运用现代统计学方法进行数据分析，为枳术颗粒二次开发提供有力的科学依据。更多还原

【Abstract】 Zhizhu granules are used to treat invigorating the spleen and relieving dyspepsia, regulating vital energy and eliminating dampress, the prescription is made of rhizome atractylodis macrocephalae, Fructus aurantii immaurus and Nelumbo nucifera Gaertn. The original prescription was Zhizhu soup from Zhangzhongjing’s ’Jinkui Yaolue’. And then, the prescription was changed to be Zhizhu pill in Zhangyuansu’s ’Yixue Qiyuan’.Zhizhu granules is a production of producing. The product is according to original technology of water exacting and ethanol precipitation. But the compete power of products are effected by a high rate of exactactives and a large dosge, lt is effect on moulding.In this article, we research Zhizhu granules in the second time. SFE-CO₂,β-cyclodextrin inclusion and Membrane Separation technologles were used in thetask. The study was carried out with orthogonal design and single factor design, and given consideration to the actual situation of produce to optimize the best extract method and optimum inclusion process. The sample was separate in six part by Membrane Separation technologies and the six parts have different molecular weight. We design Stomach model for analyse the different parts. Small molecular weight was good for the stomach. GC-MS was usd to identify compounds in extraction and 42 compounds was identified. We used HPLC to compare content in Membrane Separation parts. Boiling spray granulating is used as molding process.In this article, we use new preparation technology and chose right pharmacology indicator to select effective groups. Also, we use morden statistics to analyse dates and combine Chinese materia medica, analysis chemistry, pharmacology, chemometrics, computer technology as a base of the second development of Zhizhu granules. Through these matters, our research achievements offer credible academic basis for the second exploitation.更多还原