【作者】 戚秋鹏；

【导师】 莫凤奎； 王中彦；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2003， 硕士

【摘要】 本文选用万氏牛黄清心丸作为模型药物，研究了方中诸药有效部位的提取工艺，建立了检测内在质量的定性定量方法，在此基础上研究制备了万氏牛黄清心缓释微丸。 采用TLC方法，对万氏牛黄清心缓释微丸中有效成分盐酸小檗碱、黄芩苷、栀子苷进行了定性鉴别；采用HPLC法对样品中盐酸小檗碱、黄芩苷、栀子苷进行了含量测定，并测定了肠液中盐酸小檗碱和酚红的浓度，建立了测定家兔血浆中盐酸小檗碱浓度的方法。 通过单因素考察实验和正交实验设计法分别确定了黄连、黄芩、栀子、郁金的最佳提取工艺；采用β-CD对提取的挥发油进行了包合研究，并通过均匀实验设计法进行了工艺的优化。 对壳聚糖的脱乙酰度和分子量进行了测定；以壳聚糖为原料制备了羟丙基壳聚糖。通过单因素实验，考察了碱化、反应温度、反应时间、反应介质对产物取代度的影响，并对产物进行了定性鉴别，考察了产物的水溶性和特性粘度。 采用大鼠在体灌流方案，通过不同肠段的结扎对盐酸小檗碱的吸收部位和吸收动力学进行实验研究。实验结果表明：盐酸小檗碱在肠道的吸收较差，主要集中在小肠的上部吸收，按十二指肠、空肠、回肠和结肠的顺序，吸收百分率和吸收速率常数K_a依次降低。各肠段间吸收百分率和吸收速率常数有显著差异。药物在肠道内的吸收机制是被动扩散的方式。 以MCC为稀释剂，3％HPMC水溶液为粘合剂，采用离心造粒法，在优化条件下可制得表面较为光滑、圆整度较高的万氏牛黄清心微丸。体外沈阳药科大学硕士学位论文 摘要溶出实验表明，微丸中盐酸小梁碱的溶出度符合制剂要求。 以自制的羟丙基壳聚糖和pH依赖型辅料丙烯酸树脂的水分散体作为包衣材料制备了3种包衣微丸，体外模拟人体胃肠道pH条件下测定盐酸小巢碱的释放度，结果表明释药呈现出一种pH依赖型梯度释药特征。 家兔口服自制的万氏牛黄清心缓释胶囊后盐酸小凳碱的血药浓度测定结果表明，盐酸小梁碱的峰值血药浓度Cm。明显降低，作用时间显著延长，体内也呈现了预期的梯度脉冲释药特征。更多还原

【Abstract】 Wanshi Niuhuang Qingxin pills(WSNHQXP) was selected as model drug and the preparation techniques of active fraction of medicinal materials in prescription were investigated. The qualitative and quantitative analysis methods were developed to control the inherent quality of formulation. Based on these results, Wanshi Niuhuang Qingxin sustained-release pellets(WSNHQX SRP) were investigated.TLC methods were used to identify Berberine Hydrochloride, Baicalin, Geniposide in WSNHQX SRP; the method of HPLC for Berberine Hydrochloride, Baicalin, Geniposide were developed to determine their contents in preparation. The concentration of Berberine Hydrochloride and phenolsulfonphthalein in intestine solution and concentration of Berberine Hydrochloride in rabbit plasma were also assayed by HPLC method.The extraction techniques of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Gardenia jasminoides Ellis, Curcuma wenyujinY.H.Chen et C.Ling were optimized by orthogonal experiment design method and single-factor test method, respectively. The b-CD inclusion complex of Zedoary Turmeric oil was formulated by the method of uniform experiment design.Deacetylation degree and molecular weight of chitosan were determined. Chitosan was selected as a material to synthesize hydropropylated chitosan and the effects of alkalization, reaction temperature, time, solvent on degrees ofsubstitution were studied. Hydropropylated chitosan was identified, solubility and intrinsic viscosity were investigated, too.The absorption sites and the absorption kinetics were studied from various intestinal segments ligation using in situ perfusion method in rats. The research demonstrated that Berberine Hydrochloride was poorly absorbed in intestine in general and mostly absorbed in the upper small intestine. The absorption fraction and absorption rate constant were gradually decreased from Duodenum to Colon. The mechanism of gastrointestinal absorption of Berberine Hydrochloride is that the drug transfers to cell via passive diffusion.Wanshi Niuhuang Qingxin pellets with perfect shape and surface characteristics were prepared in a centrifugal granulator by using MCC as filler and 3% HPMC solution as adhesive agent under optimum condition. The dissolution rate of Berberine Hydrochloride meets the demands of preparation.A pH-dependent gradient-release pellet system was investigated by using hydropropylated chitosan and the dispersion system of various methacrylic acid copolymers in water as coater. In vitro experiment makes it clear that various components with different properties are released synchronously.The plasma concentration of Berberine Hydrochloride in three rabbits after a single oral administration of WSNHQX SRP was studied with WSNHQXP as a reference preparation. The results showed that the plasma concentration of Berberine Hydrochloride was steadier and its Cmax decreased significantly, A characteristic of gradient-release was observed in the concentration-time curves of Berberine Hydrochloride of WSNHQX SRP.更多还原