甘草总黄酮微海绵的制备及体外释放度评价
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摘要
目的:优选甘草总黄酮微海绵的制备工艺并考察其体外释放度。方法:利用类乳剂溶媒扩散法制备甘草总黄酮微海绵,以微海绵得率、包封率及分散系数为指标,通过星点设计-效应面法考察聚乙烯醇用量、药物与乙基纤维素的比例、搅拌速度对甘草总黄酮微海绵制备工艺的影响。利用紫外分光光度法测定甘草总黄酮微海绵的包封率,检测波长335 nm;建立HPLC同时测定甘草总黄酮中甘草苷、异甘草苷、甘草素、异甘草素、甘草查尔酮A和光甘草定的含量,检测波长300 nm,流动相乙腈-甲醇-0.2%磷酸水溶液梯度洗脱;利用透析法比较甘草总黄酮及甘草总黄酮微海绵中6个成分的体外释放度。结果:甘草总黄酮微海绵的最佳制备工艺为聚乙烯醇用量2.69%,药物-乙基纤维素(6∶1),搅拌速度1 100 r·min~(-1),搅拌时间4 h。8 h内甘草总黄酮中甘草苷、异甘草苷、甘草素、异甘草素、甘草查尔酮A和光甘草定的累积释放度分别为87.47%,86.83%,76.98%,78.48%,86.58%和56.58%,24 h内甘草总黄酮微海绵中这6个成分的累积释放度分别为91.45%,89.74%,77.57%,82.64%,87.74%和67.74%。结论:利用类乳剂溶媒扩散法制备的甘草总黄酮微海绵粒径大小均匀、工艺稳定且操作简便。甘草总黄酮微海绵具有明显的缓释作用。
Objective:To optimize preparation technology of Glycyrrhizae Radix et Rhizoma flavonoids microsponges and investigate its in vitro release. Method:Glycyrrhizae Radix et Rhizoma flavonoids microsponges were prepared by quasi-emulsion solvent diffusion method,taking yield of microsponges,encapsulation efficiency and dispersion coefficient as indexes,central composite design-response surface methodology was adopted to investigate effect of dosage of polyvinyl alcohol(PVA),ratio of drug and ethyl-cellulose,stirring speed on preparation procedure of the microsponges. Encapsulation efficiency of the microsponges was determined by UV spectrophotometry. The content of six major ingredients in Glycyrrhizae Radix et Rhizoma flavonoids were investigated simultaneously by HPLC,detection wavelength was 300 nm,mobile phase was acetonitrile-methanol-0. 2% phosphoric acid aqueous solution for gradient elution. Difference of in vitro release between Glycyrrhizae Radix et Rhizoma flavonoids and the microsponges was compared by dialysis method. Result:Optimum preparation technology of the microsponges were as follows:PVA amount of 2. 69%,drug-ethyl-cellulose(6 ∶ 1),stirring speed of 1 100 r·min~(-1),stirring time of 4 h. Within 8 h,cumulative release rates of liquiritin,isoliquiritin,liquiritigenin,isoliquiritigenin,licochalcone A and glabridin in Glycyrrhizae Radix et Rhizoma flavonoids were87. 47%,86. 83%,76. 98%,78. 48%,86. 58% and 56. 58%; within 24 h,cumulative release rates of these components were 91. 45%,89. 74%,77. 57%,82. 64%,87. 74% and 67. 74%,respectively. Conclusion:Glycyrrhizae Radix et Rhizoma flavonoids microsponges are homogeneous with an obvious sustained release property,and the optimum preparation technology is stable and simple.
Objective:To optimize preparation technology of Glycyrrhizae Radix et Rhizoma flavonoids microsponges and investigate its in vitro release. Method:Glycyrrhizae Radix et Rhizoma flavonoids microsponges were prepared by quasi-emulsion solvent diffusion method,taking yield of microsponges,encapsulation efficiency and dispersion coefficient as indexes,central composite design-response surface methodology was adopted to investigate effect of dosage of polyvinyl alcohol(PVA),ratio of drug and ethyl-cellulose,stirring speed on preparation procedure of the microsponges. Encapsulation efficiency of the microsponges was determined by UV spectrophotometry. The content of six major ingredients in Glycyrrhizae Radix et Rhizoma flavonoids were investigated simultaneously by HPLC,detection wavelength was 300 nm,mobile phase was acetonitrile-methanol-0. 2% phosphoric acid aqueous solution for gradient elution. Difference of in vitro release between Glycyrrhizae Radix et Rhizoma flavonoids and the microsponges was compared by dialysis method. Result:Optimum preparation technology of the microsponges were as follows:PVA amount of 2. 69%,drug-ethyl-cellulose(6 ∶ 1),stirring speed of 1 100 r·min~(-1),stirring time of 4 h. Within 8 h,cumulative release rates of liquiritin,isoliquiritin,liquiritigenin,isoliquiritigenin,licochalcone A and glabridin in Glycyrrhizae Radix et Rhizoma flavonoids were87. 47%,86. 83%,76. 98%,78. 48%,86. 58% and 56. 58%; within 24 h,cumulative release rates of these components were 91. 45%,89. 74%,77. 57%,82. 64%,87. 74% and 67. 74%,respectively. Conclusion:Glycyrrhizae Radix et Rhizoma flavonoids microsponges are homogeneous with an obvious sustained release property,and the optimum preparation technology is stable and simple.
引文
[1]景晶,赵金英,华冰,等.甘草总黄酮抑制硫代乙酰胺诱导肝纤维化大鼠肝组织中TGF-β1及Caspase-3的表达[J].中国中药杂志,2015,40(15):3034-3040.
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[5]赵世元,农智新,钟振国.甘草总黄酮体内抗肿瘤作用的实验研究[J].广西医学,2006,28(9):1348-1350.
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[10]余琳,李小芳,冉茂莲,等.星点设计-效应面法优化甘草总黄酮骨架缓释片处方[J].中药与临床,2014,5(6):16-18.
[11]陈丽华,冯怡,徐德生,等.含甘草总黄酮效应组分微丸的制备及性质考察[J].中药材,2008,31(3):434-438.
[12]Embil K,Nacht S.The Microsponge Delivery System(MDS):a topical delivery system with reduced irritancy incorporating multiple triggering mechanisms for the release of actives[J].J Microencapsul,1996,13(5):575-588.
[13]Chadawar V,Shaji J.Microsponge delivery system[J].Curr Drug Deliv,2007,4(2):123-129.
[14]LI S S,LI G F,LIU L,et al.Evaluation of paeonol skintarget delivery from its microsponge formulation:in vitro skin permeation and in vivo microdialysis[J].PLo S One,2013,8(11):e79881.
[15]Amrutiya N,Bajaj A,Madan M.Development of microsponges for topical delivery of mupirocin[J].AAPS Pharm Sci Tech,2009,10(2):402-409.
[16]臧巧真,唐涛,龙凯花,等.星点设计-效应面法优化α-细辛脑纳米粒原位凝胶的处方及其体外释放性能考察[J].中国实验方剂学杂志,2016,22(13):7-10.
[17]伍蔚萍,孙文基,阎宏涛,等.分光光度法测定甘草中总黄酮的含量[J].药物分析杂志,2005,25(4):469-472.
[18]周斌,常军,刘可越,等.紫外分光光度法测定甘草中总黄酮的含量[J].安徽农业科学,2009,37(31):15246-15247.
[19]左婷,翁立冬,刘莉,等.HPLC同时测定甘蒲祛斑凝胶中甘草素、异甘草素、甘草查尔酮A的含量[J].中国实验方剂学杂志,2015,21(8):73-76.
[20]任明,许真真.HPLC-UV切换波长法同时测定复方甘草合剂中甘草苷,异甘草苷,甘草素和甘草酸[J].山东医药,2016,56(11):35-37.
[21]闫鑫,吕邵娃,郭玉岩,等.槲皮素-PLGA嵌段共聚物纳米粒冻干粉的制备及体外释放性能考察[J].中国实验方剂学杂志,2016,22(14):10-13.
[22]纪周新,刘琳琳,李艺养,等.丹参素脂质体的制备及体外释放度研究[J].中国药师,2015,18(10):1649-1651.
[2]Kim Y W,Ki S H,Lee J R,et al.Liquiritigenin,an aglycone of liquiritin in Glycyrrhizae radix,prevents acute liver injuries in rats induced by acetaminophen with or without buthionine sulfoximine[J].Chem Biol Interact,2006,161(2):125-138.
[3]傅乃武,刘朝阳,张如意,等.甘草黄酮类和三萜类化合物抗氧化作用的研究[J].中药药理与临床,1994(5):26-29.
[4]贾国惠,贾世山.甘草中黄酮的药理作用研究进展[J].中国药学杂志,1998,33(9):3-6.
[5]赵世元,农智新,钟振国.甘草总黄酮体内抗肿瘤作用的实验研究[J].广西医学,2006,28(9):1348-1350.
[6]Fukai T,Marumo A,Kaitou K,et al.Anti-helicobacter pylori flavonoids from licorice extract[J].Life Sci,2002,71(12):1449-1463.
[7]王明利,李春明,董萍,等.甘草黄酮治疗黄褐斑临床疗效观察[J].辽宁药物与临床,2003,6(3):128-129.
[8]Tawata M,Aida K,Noguchi T,et al.Anti-platelet action of isoliquiritigenin,an aldose reductase inhibitor in licorice[J].Eur J Pharmacol,1992,212(1):87-92.
[9]刘永,文振催,黄志刚,等.HPLC法同时测定甘草总黄酮分散片中甘草素和甘草查尔酮A的含量[J].今日药学,2016,26(1):19-21.
[10]余琳,李小芳,冉茂莲,等.星点设计-效应面法优化甘草总黄酮骨架缓释片处方[J].中药与临床,2014,5(6):16-18.
[11]陈丽华,冯怡,徐德生,等.含甘草总黄酮效应组分微丸的制备及性质考察[J].中药材,2008,31(3):434-438.
[12]Embil K,Nacht S.The Microsponge Delivery System(MDS):a topical delivery system with reduced irritancy incorporating multiple triggering mechanisms for the release of actives[J].J Microencapsul,1996,13(5):575-588.
[13]Chadawar V,Shaji J.Microsponge delivery system[J].Curr Drug Deliv,2007,4(2):123-129.
[14]LI S S,LI G F,LIU L,et al.Evaluation of paeonol skintarget delivery from its microsponge formulation:in vitro skin permeation and in vivo microdialysis[J].PLo S One,2013,8(11):e79881.
[15]Amrutiya N,Bajaj A,Madan M.Development of microsponges for topical delivery of mupirocin[J].AAPS Pharm Sci Tech,2009,10(2):402-409.
[16]臧巧真,唐涛,龙凯花,等.星点设计-效应面法优化α-细辛脑纳米粒原位凝胶的处方及其体外释放性能考察[J].中国实验方剂学杂志,2016,22(13):7-10.
[17]伍蔚萍,孙文基,阎宏涛,等.分光光度法测定甘草中总黄酮的含量[J].药物分析杂志,2005,25(4):469-472.
[18]周斌,常军,刘可越,等.紫外分光光度法测定甘草中总黄酮的含量[J].安徽农业科学,2009,37(31):15246-15247.
[19]左婷,翁立冬,刘莉,等.HPLC同时测定甘蒲祛斑凝胶中甘草素、异甘草素、甘草查尔酮A的含量[J].中国实验方剂学杂志,2015,21(8):73-76.
[20]任明,许真真.HPLC-UV切换波长法同时测定复方甘草合剂中甘草苷,异甘草苷,甘草素和甘草酸[J].山东医药,2016,56(11):35-37.
[21]闫鑫,吕邵娃,郭玉岩,等.槲皮素-PLGA嵌段共聚物纳米粒冻干粉的制备及体外释放性能考察[J].中国实验方剂学杂志,2016,22(14):10-13.
[22]纪周新,刘琳琳,李艺养,等.丹参素脂质体的制备及体外释放度研究[J].中国药师,2015,18(10):1649-1651.