【作者】 张丽锋；

【导师】 张淑秋；

【作者基本信息】 山西医科大学 ， 药物分析学， 2002， 硕士

【摘要】 盐酸青藤碱临床主要用于治疗风湿性和类风湿性关节炎，本课题通过对原料药鉴别、控释制剂制备、质量标准、稳定性及生物利用度的研究，完成了盐酸青藤碱控释制剂的临床前研究工作，实验结果均符合中国药典(2000版)的规定。 原料药的紫外扫描图谱、质谱图、特异性鉴别反应及薄层层析图谱研究结果表明，本品在264nm处有最大吸收峰，分子量为329，鉴别反应呈阳性，在供试品色谱中，在与对照品相应位置上显相同颜色的斑点。实验结果与文献报道一致，证明供试品为盐酸青藤碱。 根据盐酸青藤碱的紫外吸收特征，建立了其控释微丸制剂的紫外分光光度法(UV)和反相高效液相色谱法(RP-HPLC)的含量测定方法。通过对线性相关性、精密度、重复性、回收率的测定，结果均符合中国药典的要求。 采用膜控技术，离心包衣造粒法制备了盐酸青藤碱控释微丸。首先采用泛丸法制备丸心，通过对粒径分布、平面临界角、休止角、硬度、脆碎度、水分的测定，对丸心质量进行评价。以Eudragit NE30D水分散体为包衣材料，自制小型沸腾流化床包衣设备对丸心的包衣进行处方筛选。离心造粒机进行工艺放大。以药物溶出性能作为控释指标，筛选最山西医科大学 硕士学位论文优控释处方。其次对微丸的体外溶出性能进行了研究，分别考察了港出介质、溶出装置及不同转速对微丸药物溶出的影响，结果满意。 根据中国药典的规定，对盐酸青藤碱控释微丸的稳定性进行考察，包括影响因素试验（高温试验、高湿试验、强光照试验）、加速试验和长期试验。稳定性重点考察项目有微丸外观、特异性鉴别、体外溶出性能。含量。结果表明，微丸包衣膜对热比较敏感，其他考察项目均稳定。 生物利用度实验中，以大为实验动物，正清风痛宁片为参比制剂，反相高效液相色谱法（内标法）对生物样品进行测定。3P87动力学软件拟和动力学参数。结果表明，控释制剂在犬体内血药浓度经时曲线平稳，维持时间长，无明显的峰谷现象，生物利用度较高，达到了预期的目的。更多还原

【Abstract】 Sinomenine hydrochloride is used in treatment of rheumatism and rheumatoid. In this paper, the identify of raw material, preparation of controlled-release pellets, quality standard, stability and bioavailbility were studied. The preclinical studies of sinomenine hydrochloride controlled-release preparation were finished. All the experimental results met Chinese pharmacopoeia (edition 2000) regulations.The material tested was identified as sinomenine hydrochloride according to a maximum absorption peak at 264 nm by ultraviolet scanning pattern, a molecular weight of 299 by mass spectrogram, positive identification reactions, and same Rf and color to reference by TLC.On the base of characteristics ultraviolet absorption of sinomenine hydrochloride, the ultraviolet spectrophotometry (UV) and reverse-phrase high performance liquid chromatography (RP-HPLC) methods were established for analysis of sinomenine. The linearity, specificity, repeatability and recovery met with the requirements of Chinese pharmacopoeia (edition 2000).By using membrane controlled-release technique and centrifugal coating pelletization, sinomenine hydrochloride controlled-release pellets were prepared. The first step is to prepare the core of pellets, The partical size distribution, plane critical angle, angle of repose, brittleness, hardness and moisture were used to evaluate the quality of the core of pellets. Eudragit NE30D was used to coating material. A self-designed minitype boiling fluiding bed equipment was used for screening of the coating prescription. The controlled-release efficacy were assessed according to drug dissolution rate. The equipment of centrifugal coating pelletization was used formagnifying production. The release of pellets were studied with different media, different release equipments and different speeds of revolution.Followed Chinese pharmacopoeia, the stability of sinomenine hydrochloride controlled-release pellets were studied. Influencing factors including high temperature, high humidity and strong light were investigated. Accelerated test and long-term test were conducted. Appearance of pellets, specific identification reactions, dissolutions and content determination were detected for the stability studies. The results showed that the coating membrane of pellets was sensitive to temperature and stable for other factors. In the bioavailbility experiment, the dogs were used as the experimental animals. Zheng qing feng tong ning tablets was used as the reference. Sinomenine in the biologic samples was analyzed by RP-HPLC. Parameters were estimated by 3P87 pharmacokinetics software. The results showed that the concentration-time curve of sinomenine was flatter, the duration was longer, peak and vale was less obvious than that of reference. Bioavailbility was equivalent. The present studies achieved our prospective aims.更多还原