【作者】 张良；

【导师】 许沛虎； 熊富良；

【作者基本信息】 武汉理工大学 ， 药剂学， 2007， 硕士

【摘要】 水飞蓟是菊科水飞蓟属植物，原产南欧、北非，以民间草药用于治疗肝胆疾病，具有抗肝胆病毒，保护肝细胞膜，改善肝功能的生理活性。水飞蓟素是水飞蓟的干燥果实中提取分离得到的有效成分，为黄酮类化合物，其中水飞蓟宾为其主要活性成分。临床上主要用于急慢性肝炎，肝硬变等疾病，具有疗效好、副作用小的特点。本课题根据药材性质和临床用药特点，设计和研制护肝康分散片。以总黄酮和水飞蓟宾的含量为考察指标，采用正交设计法优选药物有效部位水飞蓟素的最佳提取和纯化工艺条件。水飞蓟素最佳提取工艺为水飞蓟药材粉碎用5倍量石油醚脱脂后，采用10倍量90％的乙醇提取3次，每次1小时，合并滤液，收集浓缩。水飞蓟总黄酮最佳纯化工艺为采用8％浓缩液，3倍量体积乙酸乙酯萃取2次，每次静置10分钟。纯化后水飞蓟总黄酮的含量达到提取物的70％，水飞蓟宾的含量达到27％。通过比较考察实验、多指标综合评分的正交设计法优选分散片的最佳处方，并通过单因素多水平实验优化制剂工艺。确定护肝康分散片处方为水飞蓟素提取物117g，微晶纤维素75g，糊精30g，羧甲基淀粉钠10g，低取代羟丙基纤维素16.5g，硬脂酸镁1.5g。规格0.25g／片，每片含水飞蓟宾30mg。制剂成品各项指标均符合分散片制剂标准要求。质量标准研究中，采用TLC法对提取物和制剂中水飞蓟素进行定性鉴别，采用紫外分光光度法测定水飞蓟总黄酮含量，采用高效液相色谱法测定水飞蓟宾的含量，高效液相色谱条件：以Kromasil C₁₈（250 mm×4.6mm，5μm）为分析柱，以甲醇：乙腈：0.5％冰醋酸（40：5：55，体积比）为流动相，检测波长为287nm，柱温为30℃，进样量为5μl，流速为1ml／min。建立分散片溶出度方法：中国药典2005版附录溶出度测定第一法，0.5％吐温80溶液900ml为溶出介质，温度37士0.5℃，转速为100 r／min，45min取样，水飞蓟素溶出度不低于70％。研究表明，优选的水飞蓟总黄酮提取纯化工艺稳定可行。护肝康分散片的制剂工艺处方科学，工艺稳定。建立水飞蓟总黄酮和水飞蓟宾的含量测定方法准确可靠，方便快捷，能有效控制产品质量。本研究达到了课题预期目的。更多还原

【Abstract】 Silybum marianum L. Gaertn is Compositae silymafin genus, Originating in southern Europe, North Africa, it is a civil herbs for the treatment of liver and gallbladder diseases, have a anti-virus hepatolithiasis and protection of liver cell membrane effect. Silymarin, a polyphenolic flavonoid isolated from the seeds of milk thistle Silybum marianum, is composed mainly of silibinin with small amounts of other silibinin. Silibinin is the principal component and main active substance of silymarin. Silymarin or silibinin is used clinically for the treatment of liver diseases, which has the advantage of good therapy and little side-effect. This study dosage form was chosen considering the herbs’s nature and clinical needs, designed on the basis of dispersible tablets’ making process. the Hu gankang dispersible tablets was designed and developed.On the premise of the best abstraction solvent, Orthogonal test was used for studying the effect of silymarin extraction and purifiction as total flavonoids and silybin contentcontent index. The best extracting technical conditions of silymarin were as follows: 5times Petroleum ether impregate the comminute silymarin used to excluding oil, 10 times of amount of 90% alcohol extracted for 3 times each time for 1 hours. The best purifying technical conditions were as follows: 3 times amount of ethyl acetate extracted 8% concentrated solution for 2 times each time for 10 minutes. Purified silymarin total flavonoids extract of the content is as high as the 70 percent, silybin content to 27%.Comparing experimental study and more indicators orthogonal test was optimized by multi-level single-factor experiment.The prescription of Hu gangkang desperside tablet as fellow: the extraction product of silymarin 117g, Microcrystalline cellulose 75g, Dextrin 30g, Sodium carboxymethyl starch 10g, Low replace hydroxypropyl cellulose 16.5g. Magnesium stearate 1.5g. The specifications of prcparations is 1.5 g per tablet, which contain 30mg silybin. All targets are in line with the standard requirements of dispersible tablet formulations. HPLC conditions is: The Kromasil C18 column was used, The mobile phase consisted of methanol-acetonitrile-0.5% glacial acetic acid Solution (40:5:55). The detection wavelength was 287nm., Column tempcrature is 30℃, flow ratc is 1ml/min. injection size is 5μl. The soluble point experiment is follow China Pharmacopoeia (2005) Dissolution of the first methods. 0.5%tween80 solution 900 ml for dissolution media, the temperature is 37±0.5℃, the rotation speed is 100 r/min, put out samples when it have past 45 minutes. Dissolution point of Silymarin must not be lower than 70%.Research shows that, The optimum extraction and purifition technology of total flavonoids from Silybum marianum is stable and feasible. Preparation Process of Hu gankang dispersible tablets is scientific, stable, specific. UV spectrophotometry and HPLC spectrophotometry which was used to determinate the silymarin is accurate and reliable.更多还原