【作者】 李文韬；

【导师】 史国兵；

【作者基本信息】 辽宁医学院 ， 药剂学， 2011， 硕士

【摘要】 目的研究复方参芪五味咀嚼片的提取工艺、制剂成型工艺、中试放大工艺以及相关的质量控制,为新药报批上市提供药学基础,建立复方参芪五味咀嚼片的最佳制备工艺方案以及稳定准确的质量控制方法。方法以五味子醇甲含量、人参皂苷Rg1含量、黄芪甲苷含量为指标,结合醇提取和水提取出膏率,分别进行L9（34）正交试验,筛选最佳提取工艺条件;筛选最佳成型工艺;采用薄层色谱法鉴别了复方参芪五味咀嚼片中的人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1,五味子醇甲,黄芪甲苷和麦冬药材;同时采用高效液相色谱法对片中人参皂苷Rg1、五味子醇甲和黄芪甲苷进行了含量测定,色谱条件分别为:人参皂苷Rg1:Dikma Diamonsil-C18 （200mm×4.6mm, 5μm）,流动相为乙腈-水（20:80）,检测波长为203nm,流速为1.0mL·min^-1 ;五味子醇甲:Dikma Diamonsil-C18 （250mm×4.6mm, 5μm）,流动相为甲醇-水（57.5:42.5）,检测波长为250nm,流速为1.0mL·min^-1;黄芪甲苷:Dikma Diamonsil-C18 （250mm×4.6mm, 5μm）,流动相为乙腈-水（32:68）,蒸发光散射检测器检测,流速为1.0mL·min^-1。结果确定复方参芪五味咀嚼片的最佳制备工艺:处方四味,人参、五味子10倍量90%乙醇加热回流提取三次,每次1.5小时,合并提取液,滤过,滤液回收乙醇并浓缩至相对密度为1.30¹.35（60℃）的稠膏,备用;药渣与麦冬、黄芪10倍量水煎煮三次,每次1.5小时,合并滤液,滤过,滤液浓缩至相对密度为1.10¹.15（60℃）的清膏,加入80%乙醇,搅拌,使药液含醇量达40%,静置24小时,滤过。滤液回收乙醇并浓缩至相对密度为1.30¹.35（60℃）的稠膏,与上述稠膏混匀,喷雾干燥成细粉,加入处方量的蔗糖（15%）、甘露醇（15%）为底粉,将糊精（20%）、蛋白糖（2%）、香精（1%）、硬脂酸镁（1%）用适量水糊化,喷雾制粒,成粒后流化15分钟,加入适量硬脂酸镁,16目筛整粒后,压片,1.8g/片。在选定的薄层色谱条件下,斑点显色清晰,阴性样品无干扰;人参皂苷Rg1、五味子醇甲和黄芪甲苷分别在2.5¹7.5μg·mL^-1、2.4¹2μg·mL^-1、4.6³2.2μg·mL^-1间线性关系良好;人参皂苷Rg1、五味子醇甲和黄芪甲苷平均加标回收率分别为98.1%、RSD=2.0%,97.2%、RSD=1.4%,97.71%、RSD=1.2%。结论对复方参芪五味咀嚼片的醇提取和水提取工艺进行了较为系统的研究,以各指标成分含量为指标,结合醇提取和水提取出膏率所筛选出的最佳工艺条件为新药研制和中试生产提供重要依据;成型工艺结果表明工艺稳定可行;质量控制建立的方法准确、重现性好,可以作为控制其质量的标准。更多还原

【Abstract】 ObjectiveTo investigate the extraction processes, formation technologies, experimental enlargement and related quality control of Compound Shenqi Wuwei chewable Tablets, which provides basic medical to new drug approval in the market, establishes the best extraction process and accurate the quality control standard of Compound Shenqi Wuwei chewable Tablets.MethodsWith content of Schisandrin, ginsenoside Rg1 and AstragalosideⅣfor idex, combining the extraction yield of ethanol extract and water extract, The orthogonal design L9 （34） was used to optimize the extraction process and the optimize formation technologies; Thin layer chromatography （TLC） was used to identify ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, Schizandrin, AstragalosideⅣand ophiopogon japonicus medicinal materials; While high performance liquid chromatography （HPLC） was used to determine the cotent of Ginsenoside Rg1, Schisandrin and AstragalosideⅣintablets. The HPLC conditions for Schisandrin: Dikma Diamonsil-C18 （250mm×4.6mm, 5μm） column was used. The mobile phase consisted of Methanol-water （57.5:42.5）, with a flow rate of 1.0mL·min^-1 and detection wavelength at 250nm under room temperature; For Ginsenoside Rg1: Dikma Diamonsil-C18 （200mm×4.6mm, 5μm） column was used. The mobile phase consisted of acetonitrile-water （20:80）, with a flow rate of 1.0mL·min^-1 and detection wavelength at 203nm under room temperature; For Astragaloside IV: Dikma Diamonsil-C18 （250mm×4.6mm, 5μm） column was used. The mobile phase consisted of Acetonitrile-water （32:68）, with a flow rate of 1.0mL·min^-1 and detection evaporative light-scattering detector （ELSD） under room temperature. ResultsTo determine the best preparation technology of Compound Shenqi Wuwei chewable Tablets: Schisandra chinensis and Ginseng was as follows: 10 fold of 90%ethanol, reflux extracting for 1.5 hours in heating mantles, 3 times. Merging the extract, filtering, filtrate recovery ethanol and the thick paste could be concentrated to relative density 1.30¹.35 （60℃）, reserving it; adding medical slag and shenqi in 10 fold of the boiling water for 1.5 hours, 3 times. merging filtrate, filtering, filtrate could be concentrated to plaster of relative density 1.30¹.35 （60℃） , reserving it; then adding 80% ethanol to 40%, stirring, and leaving for 24 hour and filtering. filtrate recovery ethanol and the thick paste could be concentrated to relative density 1.30¹.35 （60℃）, combining with the above thick paste, spraying dry to fines, adding sucrose （15%）, Mannitol （15%） as bottom fraction, using amylin （20%）, protein sugar （2%）, essence （1%）, magnesium stearate （1%） and an appropriate amount of water into paste and then spray and granulate, fluidifying for 15 min, with the addition of appropriate magnesium stearate, after sieved to 16 meshes, compression 1.8g/ tablet. The dapples in the TLC plate are clean and the result of Separation is good ; The Ginsenoside Rg1, Schizandrin, Astragaloside IV had a linear range of 2.5¹7.5μg·mL^-1, 2.4¹2μg·mL^-1, 4.6³2.2μg·mL^-1, and the average recovery rate of Ginsenoside Rg1, Schizandrin, Astragaloside IV were 98.1%, RSD=2.0%; 97.2%, RSD=1.4%; 97.71%, RSD=1.2%, respectively.ConclusionsThe systematic research on the ethanol extract and water extract process of Shenqi Wuwei chewable Tablets was performed. The quality control indices was chosen to the quality assessment. And the extraction ratio of ethanol extract and water extract were used to screen new drug development and pilot scale production for the best process condition, which is very important for basis; This method is accurate, reproducible and sensitive, and it can be used for the quality control of Compound Shenqi Wuwei chewable Tablets.更多还原