黄连总生物碱药物树脂骨架型缓释制剂-素材.doc

陕西中医学院 硕士学位论文 黄连总生物碱药物树脂骨架型缓释制剂的研究 姓名:金良 申请学位级别:硕士 专业:中药学 指导教师:唐俊琪 要 本文选用具有多种生理活性的有机碱类药物黄连总生物碱,以药用辅料弱酸性阳 离子交换树脂 IRP88为载体,研究了黄连总生物碱的药物树脂制备工艺和相关机理, 并以此为原料筛选了骨架型缓释片的处方和工艺,并对该制剂体外释药动力学行为及 释药机制等进行了研究。具体内容如下: (1)建立了灵敏、可靠的高效液相色谱法用于分析原料、载药树脂和研究制剂 体外释放,为载药树脂的制备和缓释制剂处方筛选提供理论依据及方法学基础。 (2)采用静态法制备药物树脂复合物,考察了各关键因素对载药速度及程度的影 响,并对离子交换反应的动力学及热力学进行了研究,结果表明该反应符合一级动力 学方程,交换反应为自由能减少,熵增加的过程,可自发进行。并最终确定药物树脂 制备工艺。 (3)运用差示扫描热分析法、红外分析法、X光衍射法证明药物与阳离子交换 树脂之间是通过稳定的离子键结合,而非简单的物理吸附。 (4)考察了药物树脂复合物在体外的释药行为,结果显示药物树脂复合物在人 工胃液可迅速释药;在人工肠液的释药动力学过程可用 Viswanathan方程来描述,属 粒扩散过程控制。 (5)采用全粉末直接压片的方法,通过对释药曲线和释药方程的拟合,筛选了 多种骨架型缓释材料,最终选用 Carbopol 974P NF作为黄连总生物碱药物树脂骨架缓 释片缓释材料,并确定该缓释片释药过程为骨架溶蚀型的近似零级释药过程。 关键词 黄连总生物碱;离子交换树脂;骨架缓释片STUDY ON SUSTAINED-RELEASE MATRIX TABLETS OF THE COMPLEXS OF TOTAL ALKALOIDS FROM COPTIDIS AND ION EXCHANGE RESIN ABSTRACT In this paper, The drug-resin complexes were prepared with organic bases from Rhizoma Coptidis have lots of physiological activity and weak acid cation exchange resin named IRP88 as the carrier, study of the preparation technology and relative mechanismsThe complexes as raw material, to selection the technology and prescription for sustained-release matrix tablets, study the release kinetics and mechanism in vitro. The studies were as follows:1 Established a sensitive and reliable HPLC method for the analysis of raw materials, drug-resins and study the drug release in vitro , in order to provides a theoretical basis and methodological basis for preparation of the drug-resin complexes and sustained-release matrix tablets 2 The drug-resin complexes were prepared by bath process, investigated the critical factor on the drug- exchange speed and extent, and the ion exchange reaction dynamics and thermodynamics have been studied. The exchange reaction between the drug and resin was accorded with first order kinetics reaction, and the free energy reduction, the process of entropy increase can be spontaneous. And ultimately det