中药复方缓释制剂的研究.pdf.pdf

中国协和医科大学硕士学位论文中药复方缓释制剂的研究姓名:司成桃申请学位级别:硕士专业:生药学指导教师:朱春燕 20040601 药用植物研究所硕士论文摘要摘要本文以三七总皂苷和葛根黄酮为模型药物,制备了口服一次,释药可持续 12h的复方缓释片剂。首先建立了一阶导数光谱法及紫外分光光度法,分别用于三七总皂苷和葛根黄酮的制刘含量、释放度及基本性质的测定。上述两种方法简便、准确,完全能够满足试验的要求。对与处方设计密切相关的原料药的一些性质进行了考察。建立了高效液相色谱法检测犬体内葛根素血药浓度,此法灵敏度高、专属性强、绝对回收率较高。在单因素考察的基础上,应用u5(54)均匀设计试验优化了处方,筛选出以 HPMC为凝胶骨架的复方缓释制剂。释药动力学研究结果表明,其体外释放行为符合Peppas过程,释药机制是药物扩散和曹架溶蚀的协同作用。体外释放度测定结果为:在2h释药约30%,4h释药约50%,在6h释药约70%,在12h释药 95%以上。室温放置6个月后,缓释制剂的外观、含量及释放度均没有明显变化。本文以复方普通片为对照,利用HPLC法分别测定了三只比格犬121服单方普通片与复方缓释片的体内葛根素药时曲线,并计算了药动学参数和相对生物利用度。单方普通片的MRT和Tm。没有明显变化,而缓释片的MRT明显延长和Tm。明显滞后,具有比较理想的缓释效果。体内外相关性结果表明,缓释片的体外释放百分率与体内吸l|5疆分率具有较好的相关性“-=),可通过体外释放数据预测体内吸收情况。关键词;三七总皂苷,葛根黄酮,羟丙甲基纤维素,复方缓释制剂,生物利用度体内外相关性垫里焦塑里塞堕堡主篓壅———————垒壁翌!兰!三 ABSTRACT Usin2 PNS and Pueraria Flavones as themodel drug,we prepared ailorally pound sustained—release tabletwhich could release drug for 12hours while being administeredonly once. Firstorder derivativespectrophotometry method andUltravioletspectrophotometry method were developed forassay during thestudy ofphysicochemical properties, content anddrug release on PNS and Pueraria methods were simple andreliable,and fittherequirements physicochemical properties ofPNS andPueraria Flavones were investigated,which were connected closely with pharmaceutic and reliable HPLC method was developed for in vivoassay. We studied some factors which affected the release of thedrug from pound sustain—released tablets,mad uniform testwas used to obtain optimal formulation which contained HPMC as hydrophilic matrix release profile ofsustained—release plied withPeppas equation,and the resultinfer from Peppas model showed thatthemechanism ofrelease forsustained·release tablet was framework corrosion and ofseveral trialsshowed that in thefirsttwo hours,approximate 30%of thedrug was released,in thefirstfourhours approximate 50%of thedrug wasreleased,in thefirstsixhours approximate 70%of thedrug was rel