基于粉体学表征技术的浙贝母配方颗粒处方和工艺研究
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摘要
目的研究浙贝母配方颗粒处方和工艺。方法采用煎煮法对浙贝母进行提取;采用喷雾干燥法制备浙贝母浸膏粉;采用湿法挤压制粒、挤出-滚圆制粒、流化床制粒3种方法制备浙贝母配方颗粒,设定以粉体流动性参数休止角、最终体积减少度(a)、充填速度常数(b、k)及颗粒一次收得率为指标的综合评价方法,优选颗粒的最佳制备工艺、处方辅料及其配比;采用HPLC法测定颗粒中有效成分贝母素甲和贝母素乙含量,色谱柱为Agilent Zorbax Eclipse XDB-C18(150 mm×4.6mm,5μm);流动相为乙腈-水-二乙胺(70∶30∶0.03);检测器为蒸发光散射;体积流量为1.0 m L/min;柱温为30℃。结果流化床制粒法制得的浙贝母配方颗粒综合评分最高,最佳处方为浸膏粉-糊精-95%乙醇(100∶100∶160),颗粒一次收得率为91.3%,休止角为30.73°,a值为0.109 1,b值为0.025 5,k值为0.030 1,流动性好,得率高;高效液相色谱法测得颗粒中贝母素甲含量为0.305%,贝母素乙含量为0.098%。结论优化的浙贝母配方颗粒处方和工艺均达到设计要求,可用于工艺化大生产。
Objective To study the prescription and process of Fritillariae Thunbergii Bulbus(FTB) formula granules. Methods FTB was extracted by decocting method. FTB extract powder was prepared by spray drying method. Wet-extruding granulating, extruded-rolling granulating, and one-step granulating were adopted for preparing the formula granules. A comprehensive evaluation method was based on the powder fluidity parameters such as the rest angle, the final volume reduction degree(a), the filling velocity constant(b, k), and the yield of the particles, to optimize the optimum preparation process, prescription excipients and their proportion. An HPLC method was used to determine the contents of peimine and peiminine. The chromatographic column was the Agilent Zorbax Eclipse XDB-C18 column(150 mm × 4.6 mm, 5 μm), and the flow phase was Acetonitrile-water-diethylamine(70∶30∶0.03); The volume flow was 1.0 m L/min; The column temperature was 30 ℃. Results The synthesis score of the FTB formula granules prepared by one-step granulating method was the highest. The best prescription was the extract powder-dextrin-95% ethanol solution(100∶100∶160). The particle yield was 91.3%, the rest angle was 30.73°, the value of a was 0.109 1, the value of b was 0.025 5 and the value of k was 0.030 1, the fluidity of the granules was good and the yield was high. The content of peimine was 0.305% and the content of peiminine was 0.098% in the particles by HPLC. Conclusion In this experiment, the formulation and process of FTB formula granules were designed to met the design requirements, which could be used in the production of the technology.
Objective To study the prescription and process of Fritillariae Thunbergii Bulbus(FTB) formula granules. Methods FTB was extracted by decocting method. FTB extract powder was prepared by spray drying method. Wet-extruding granulating, extruded-rolling granulating, and one-step granulating were adopted for preparing the formula granules. A comprehensive evaluation method was based on the powder fluidity parameters such as the rest angle, the final volume reduction degree(a), the filling velocity constant(b, k), and the yield of the particles, to optimize the optimum preparation process, prescription excipients and their proportion. An HPLC method was used to determine the contents of peimine and peiminine. The chromatographic column was the Agilent Zorbax Eclipse XDB-C18 column(150 mm × 4.6 mm, 5 μm), and the flow phase was Acetonitrile-water-diethylamine(70∶30∶0.03); The volume flow was 1.0 m L/min; The column temperature was 30 ℃. Results The synthesis score of the FTB formula granules prepared by one-step granulating method was the highest. The best prescription was the extract powder-dextrin-95% ethanol solution(100∶100∶160). The particle yield was 91.3%, the rest angle was 30.73°, the value of a was 0.109 1, the value of b was 0.025 5 and the value of k was 0.030 1, the fluidity of the granules was good and the yield was high. The content of peimine was 0.305% and the content of peiminine was 0.098% in the particles by HPLC. Conclusion In this experiment, the formulation and process of FTB formula granules were designed to met the design requirements, which could be used in the production of the technology.
引文
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[2]徐孝琦,徐孝玮.贝母的研究综述[J].求医问药,2013,11(2):319-320.
[3]卓诗勤,张浩,丁弋娜,等.硫熏和鲜切浙贝母的化学成分及其药理作用的比较研究[J].中华中医药学刊,2016,34(3):618-621.
[4]祝兴伟,张少华,王治维,等.一株来自于伊犁贝母的内生尖孢镰孢菌Y1的抑菌活性初步研究[J].菌物学报,2009,15(3):332-334.
[5]张明发,沈雅琴.浙贝母药理研究进展[J].上海医药,2007,28(10):459-461.
[6]黄丽晶,高文远,李霞,等.平贝母水提物抗炎作用研究[J].天津中医药,2009,26(6):495-496.
[7]王云飞,顾政一,何承辉.贝母属植物化学成分与药理活性研究进展[J].西北药学杂志,2015,30(4):436-440.
[8]陈梅花,王慧春,朱艳媚,等.贝母的药理研究[J].安徽农业学报,2007,13(1):103-105.
[9]Pae H O,Oh H,Choi B M,et al.Differentiation-inducing effects of verticinone,an isosteroidal alkaloids isolated from the bulbus of Fritillaria ussuriensis,on human promyelocytic leukemia HL-60 cells[J].Biol Pharm Bull,2002,25(11):1409-1411.
[10]张莹,王蕾.中药逆转肺癌多药耐药的研究新进展[J].药物评价研究,2015,38(6):686-689.
[11]李萍,季晖.贝母类中药的镇咳祛痰作用研究[J].中国药科大学学报,1993,24(6):360-362.
[12]陈泽乃,陆阳.中药贝母中水溶性成分的研究[J].中国中药杂志,1996,21(7):420-422.
[13]Li H J,Jiang Y,Li P.Characterizing distribution of steroidal alkaloids in Fritillaria spp.and related compound formulas by liquid chromatography-mass spectrometry combined with hierarchial cluster analysis[J].J Chromatogr A,2009,1216:2142-2149.
[14]童志远,颜晓燕.贝母化学成分及质量控制方法研究进展[J].西南军医,2009,11(2):260-261.
[15]李伟,胡凯文,苏伟,等.浙贝母散剂逆转急性白血病多药耐药的临床研究[J].北京中医药大学学报,2004,27(1):63-65.
[16]李冬云,叶霈智,田劭丹,等.浙贝及其配方颗粒治疗难治性急性白血病临床疗效观察[J].中医药学刊,2006,24(8):1449-1450.
[17]肖志杰,黄华,曾春华,等.附子配伍贝母对大鼠心功能的影响[J].上海医药,2007,28(10):459-461.
[18]傅凌鸥,吴春暖,孙丽,等.2013—2015年天津市肿瘤医院中药配方颗粒的使用情况分析[J].现代药物与临床,2016,31(12):2057-2063.
[19]郝云芳,倪艳,李先荣.中药配方颗粒的质量控制方法研究进展[J].药物评价研究,2013,36(4):307-310.
[20]鹿岩,李妮,段梦雅,等.2010—2013年357种中药配方颗粒的临床使用分析[J].现代药物与临床,2014,29(9):1050-1053.
[21]李远辉,李慧婷,李延年,等.高品质中药配方颗粒与关键制造要素[J].中草药,2017,48(16):3259-3266.
[22]徐亚运,孔铭,李松林.硫熏白芍配方颗粒检控指标的探讨[J].中草药,2017,48(18):3728-3733.
[23]张爱丽,章晨峰,邵杰.基于Minitab软件优化天舒胶囊一步制粒工艺[J].中草药,2013,44(22):3131-3135.
[2]徐孝琦,徐孝玮.贝母的研究综述[J].求医问药,2013,11(2):319-320.
[3]卓诗勤,张浩,丁弋娜,等.硫熏和鲜切浙贝母的化学成分及其药理作用的比较研究[J].中华中医药学刊,2016,34(3):618-621.
[4]祝兴伟,张少华,王治维,等.一株来自于伊犁贝母的内生尖孢镰孢菌Y1的抑菌活性初步研究[J].菌物学报,2009,15(3):332-334.
[5]张明发,沈雅琴.浙贝母药理研究进展[J].上海医药,2007,28(10):459-461.
[6]黄丽晶,高文远,李霞,等.平贝母水提物抗炎作用研究[J].天津中医药,2009,26(6):495-496.
[7]王云飞,顾政一,何承辉.贝母属植物化学成分与药理活性研究进展[J].西北药学杂志,2015,30(4):436-440.
[8]陈梅花,王慧春,朱艳媚,等.贝母的药理研究[J].安徽农业学报,2007,13(1):103-105.
[9]Pae H O,Oh H,Choi B M,et al.Differentiation-inducing effects of verticinone,an isosteroidal alkaloids isolated from the bulbus of Fritillaria ussuriensis,on human promyelocytic leukemia HL-60 cells[J].Biol Pharm Bull,2002,25(11):1409-1411.
[10]张莹,王蕾.中药逆转肺癌多药耐药的研究新进展[J].药物评价研究,2015,38(6):686-689.
[11]李萍,季晖.贝母类中药的镇咳祛痰作用研究[J].中国药科大学学报,1993,24(6):360-362.
[12]陈泽乃,陆阳.中药贝母中水溶性成分的研究[J].中国中药杂志,1996,21(7):420-422.
[13]Li H J,Jiang Y,Li P.Characterizing distribution of steroidal alkaloids in Fritillaria spp.and related compound formulas by liquid chromatography-mass spectrometry combined with hierarchial cluster analysis[J].J Chromatogr A,2009,1216:2142-2149.
[14]童志远,颜晓燕.贝母化学成分及质量控制方法研究进展[J].西南军医,2009,11(2):260-261.
[15]李伟,胡凯文,苏伟,等.浙贝母散剂逆转急性白血病多药耐药的临床研究[J].北京中医药大学学报,2004,27(1):63-65.
[16]李冬云,叶霈智,田劭丹,等.浙贝及其配方颗粒治疗难治性急性白血病临床疗效观察[J].中医药学刊,2006,24(8):1449-1450.
[17]肖志杰,黄华,曾春华,等.附子配伍贝母对大鼠心功能的影响[J].上海医药,2007,28(10):459-461.
[18]傅凌鸥,吴春暖,孙丽,等.2013—2015年天津市肿瘤医院中药配方颗粒的使用情况分析[J].现代药物与临床,2016,31(12):2057-2063.
[19]郝云芳,倪艳,李先荣.中药配方颗粒的质量控制方法研究进展[J].药物评价研究,2013,36(4):307-310.
[20]鹿岩,李妮,段梦雅,等.2010—2013年357种中药配方颗粒的临床使用分析[J].现代药物与临床,2014,29(9):1050-1053.
[21]李远辉,李慧婷,李延年,等.高品质中药配方颗粒与关键制造要素[J].中草药,2017,48(16):3259-3266.
[22]徐亚运,孔铭,李松林.硫熏白芍配方颗粒检控指标的探讨[J].中草药,2017,48(18):3728-3733.
[23]张爱丽,章晨峰,邵杰.基于Minitab软件优化天舒胶囊一步制粒工艺[J].中草药,2013,44(22):3131-3135.