卡比多巴左旋多巴缓释片的研制及药效学评价  

Preparation and Pharmacodynamic Evaluation of Carbidopa Levodopa Sustained-release Tablets

作　　者：郭辉 寻明金 冯中 张贵民 崔庆艳 GUO Hui;XUN Mingjin;FENG Zhong;ZHANG Guimin;CUI Qingyan(National Engineering and Technology Research Center of Chirality Pharmaceutical,Lunan Pharmaceutical Group Co.,Ltd.,Linyi 276000;International Pharmaceutical Engineering Lab.in Shandong Province,Shandong New Time Pharmaceutical Co.,Ltd.,Linyi 273400)

机构地区：[1]鲁南制药集团股份有限公司,国家手性制药工程技术研究中心,山东临沂276000 [2]山东新时代药业有限公司,山东省药物国际化工程实验室,山东临沂273400

出　　处：《中国医药工业杂志》2022年第6期862-867,共6页Chinese Journal of Pharmaceuticals

摘　　要：采用微晶纤维素(MCC)、羟丙甲纤维素(HPMC)、羟丙纤维素(HPC)的组合替代原研制剂(息宁~?)中的关键辅料乙酸乙烯酯与巴豆酸共聚物,研制了卡比多巴左旋多巴缓释片,并根据0.1 mol/L盐酸中卡比多巴和左旋多巴的释放数据,筛选了MCC、HPMC和HPC的用量。结果显示,MCC用量8%、HPMC用量1.6%和HPC用量6%的自制缓释片与原研制剂中卡比多巴和左旋多巴的释放行为相似;并且本工艺稳定、批间差异小。采用1-甲基-4-苯基-1,2,3,6-四氢吡啶致帕金森病小鼠模型进行药效学评价。结果显示,与模型组相比,自制缓释片组小鼠游泳评分和悬挂评分以及多巴胺含量均显著增加,提示自制缓释片具有治疗帕金森病的潜在效果。The carbidopa levodopa sustained-release tablets were prepared,which contained a combination of microcrystalline cellulose(MCC),hydroxypropyl methyl cellulose(HPMC) and hydroxypropyl cellulose(HPC) instead of the key excipient,poly(vinyl acetate-co-crotonic acid),in the original preparation(Sinemet).The amounts of MCC,HPMC and HPC were optimized with the release data of carbidopa and levodopa from the sustained-release tablets in 0.1 mol/L hydrochloric acid.The results showed that the release behaviors of carbidopa and levodopa from the self-made sustained-release tablets with 8% of MCC,1.6% of HPMC and 6% of HPC and the original preparation were similar.Moreover,this preparation process was robust and had low inter-batch variability.1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson disease(PD) was established to evaluate the pharmacodynamics.The results showed that there were significant differences in scores of mice swimming and suspension tests,and dopamine level between the model group and the self-made sustained-release tablets,suggesting that the self-made tablets had a potential therapeutic effect for PD.

关 键 词：卡比多巴 左旋多巴 缓释片 体外释放 药效学 

分 类 号：R944.9[医药卫生—药剂学]