人参总皂苷微孔渗透泵控释片的药学初步研究

【作者】 钟玲；

【导师】 尹蓉莉；

【作者基本信息】 成都中医药大学 ， 药剂学， 2006， 硕士

【摘要】 本文以中药人参的有效部位人参总皂苷（gensenosides）为模型药物，进行了渗透泵控释片剂给药系统的研究，制备了人参总皂苷渗微孔透泵控释片剂，目的在于为中药有效组分的口服渗透泵控释制剂提供研究模式，促进新技术新工艺在中药领域中的应用，并为人参总皂苷新型给药系统的老年痴呆疾病治疗药物开发打下良好的基础。 本文采用香草醛—冰醋酸—高氯酸比色法作为人参总皂苷提取物和试验制剂中人参总皂苷含量及其体外释放度的测定方法。对该法进行了方法学考察，人参总皂苷的最大吸收在545nm，辅料在此处无干扰吸收，方法的回收率在95～105％之间，精密度试验的RSD＜3％，重现性试验的RSD＜3％，表明所用含量测定方法专属性、重现性及准确性较好，同时操作简便，具有较强的可操作性。 将人参总皂苷提取物与适宜辅料制成素片，以醋酸纤维素（CA）、邻苯二甲酸二丁酯（DBP）、聚乙二醇400（PEG-400）为包衣材料，丙酮和异丙醇的混合溶液为包衣溶剂，喷雾速度为2ml／min，雾化压力为0.6kg／cm²，包衣锅转速为20r／min，包衣温度为35～40℃，制备了人参总皂苷渗透泵片。采用了相似因子（f₂）法对渗透泵片的体外释药行为进行评价。从制剂成型和体外释放行为的角度，筛选并确定了片心处方，选择氯化钠作为处方中的渗透活性物质，对其用量进行了筛选。对包衣处方中的增塑剂DBP的用量、致孔剂PEG-400的用量及膜的厚度进行了考察，确定了DBP的用量。并以释药曲线的相关系数、前3小时和前10小时的累积释药率为评价指标，对致孔剂PEG-400用量及膜的厚度进行了正交优化考察，结果表明，致孔剂用量对药物释放速率影响程度大于衣膜增重率对药物释放速率的影响，并确定了两者的最佳水平。考察了处方和工艺的重现性，并对其释药曲线进行模型拟合，表明重现性良好，释药曲线符合零级释药方程。 以释放度为指标，对人参总皂苷渗透泵片体外释药的影响因素进行了考察，结果表明溶出方法、转速、释放介质的pH在3.5～7.6范围内，对人参总皂苷渗透泵片体外释药行为无显著影响，而释放介质的pH在1.0时，会对人参总皂苷渗透泵片体外释药有显著影响。更多还原

【Abstract】 In this paper, micro-porous osmotic pump （MPOP） tablets have been prepared, taking the gensenosides, which are the effective fraction of Panax Ginseng, as the model drug. The objectives of the research is to offer a research model of oral osmotic system for the effective fraction of traditional Chinese medicine, advance the application of new technology to traditional Chinese medicine, and lay good foundation of a kind of medicine for Alzheimer disease, which is made of gensenosides by means of the new controlled-dosage form.The colorimetric method was used to determine the contents of total saponins in the extract of gensenosides, its preparation and the samples of the release in vitro of its preparation. The maximal absorption wavelength was 545 nm and the excipients in the preparations didn’t produce any interference at this wavelength. The average recovery was between 95% and 105%. The RSD of the accuracy experiment was less than 3%. The RSD of the repeatability experiment was less than 3%. All the results indicated this method was simple and accurate, with a good reproducibility.Mix gensenosides and proper excipients well, and manufacture them into tablet cores. Cellulose acetate （CA）, dibutylphthalate （DBP） and polyethylene glycol 400 （PEG-400） were selected as the coating materials and acetone-isopropanol co-solvent is employed as coating medium. Tablet cores were coated by pan-spray methods, and the coating process is described as spray rate 2.0ml/min, spray press 0.6kg/cm², air temperature 35～40℃ and pan speed 20rpm. In this way, the gensenosides MPOP tablets were prepared.f₂（similarity factor） was used to evaluate the drug release behavior of gensenosides in this oral osmotic pump system. From two aspects, the dosage form and release in vitro of the gensenosides MPOP tablets, selected the formulation of tablet cores and it was obtained. Sodium chloride was selected as osmotic promoting agents and its dosage was selected. At the same time, the effects of DBP （plasticizers）, PEG-400 （pore former） and coating level were investigated. The results determined the dosage of DBP. The coating level and the dosage of PEG-400 were optimized by orthogonal design, having the linear correlation coefficient of更多还原