水溶性甘草次酸冻干粉的制备及理化分析

目的：制备水溶性甘草次酸冻干粉，并进行理化分析。方法：将甘草次酸溶解于三氯甲烷和乙醇的混合溶剂作为油相，甘露醇溶解于三氯甲烷饱和水溶液作为水相，使用高速匀浆器进行乳化形成油包水型（o/w）粗乳，接着转入高压均质机内乳化得到亚微乳。再利用真空旋转蒸发除去有机溶剂，经冷冻干燥获得水溶性甘草次酸冻干粉。形成粗乳的第一步乳化工艺借助单因素法进行优化。结果：甘草次酸粗乳的最佳制备工艺条件是油相和水相体积比为15%，甘草次酸浓度为155 mg·mL^-1，乳化次数为18 次；水溶性甘草次酸冻干粉在水中分散良好呈现乳光，没有肉眼可见颗粒；其平均粒径为241.1 nm，扫描电镜下观察呈规则棒状；在37 ℃水中溶解度为23.08 μg·mL^-1，比甘草次酸原粉（3.84 μg·mL^-1）提高了大约5 倍。结论：乳化法能将甘草次酸粒径减小至纳米范畴，并且提高其水中溶解度。

Objective: To prepare and conduct physicochemical analysis of water-soluble glycyrrhetinic acid freeze-dried powder. Methods: Glycyrrhetinic acid was dissolved in the mixed solvent with chloroform and ethanol,which was used as oil phase. Meanwhile,mannitol was dissolved in water saturated by chloroform,which was used as water phase. High speed homogenizer was utilized to prepare crude emulsion. Next,high pressure homogenization technique was employed to treat the crude emulsion to obtain submicron emulsion. The residual organic solvent was eliminated through vacuum rotary evaporation. Finally,water soluble glycyrrhetinic acid freeze-dried powder was obtained by lyophilization. The emulsification technology used to prepare crude emulsion was optimized by single factor method. Results: The optimized conditions were the volume ratio of oil phase and water phase(15%),glycyrrhetinic acid concentration(155 mg·mL^-1),emulsification times(18). The watersoluble glycyrrhetinic acid freeze-dried powder was dispersed well in water and opalescent and there was no visible particles;its mean particle size was 241.1 nm with regular rod-like structure observed through scanning electron microscope;the water solubility of water-soluble glycyrrhetinic acid freeze-dried powder at 37℃ was 23.08 μg·mL^-1, which increased about 5 times compared with glycyrrhetinic acid(3.84 μg·mL^-1). Conclusion: The particle size of glycyrrhetinic acid can be reduced to nanometer scale by emulsification method and the water solubility of glycyrrhetinic acid can be improved.

[1] 中国药典2015 年版. 一部[S]. 2015:附录86 ChP 2015. Vol Ⅰ[S]. 2015:Appendix 86
[2] 江苏新医学院. 中药大辞典[M]. 上海:上海人民出版社,1977:52 New Medical College of Jiangsu. Dictionary of Medicinal Plant[M]. Shanghai:Shanghai People's Press,1977:52
[3] 胡志厚. 甘草酸类药物的研制及应用[J]. 药学学报,1988,23 (7):553 HU ZH. Development and application of glycyrrhizic acid drugs[J]. Acta Pharm Sin,1988,23(7):553
[4] KU CM,LIN JY. Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1/Th2 cytokine secretion profiles using murine primary splenocytes[J]. Food Chem,2013, 141(2):1104
[5] YANG MH,KIM J,KHAN IA,et al. Nonsteroidal anti-inflammatory drug activated gene-1(Nag^-1)modulators from natural products as anti-cancer agents[J]. Life Sci,2014,100(2):75
[6] SONG J,KO HS,SOHN EJ,et al. Inhibition of protein kinase C alpha/beta li and activation of C-Jun Nh2-terminal kinase mediate glycyrrhetinic acid induced apoptosis in non-small cell lung cancer Nci-H460 cells[J]. Bioorg Med Chem Lett,2014,24(4):1188
[7] BORDBAR N,KARIMI MH,AMIRGHOFRAN Z. Phenotypic and functional maturation of murine dendritic cells induced by 18 alphaand beta-glycyrrhetinic acid[J]. Immunopharm Immunot,2014, 36(1):52
[8] SALOMATINA OV,MARKOV AV,LOGASHENKO EB,et al. Synthesis of novel 2-cyano substituted glycyrrhetinic acid derivatives as inhibitors of cancer cells growth and no production in ipsactivated J-774 cells[J]. Bioorgan Med Chem,2014,22(1):585
[9] ISBRUCKER RA,BURDOCK GA. Risk and safety assessment on the consumption of licorice root(Glycyrrhiza sp.),its extract and powder as a food ingredient,with emphasis on the pharmacology and toxicology of glycyrrhizin[J]. Regul Toxicol Pharm,2006,46(3):167
[10] SHIN YW,BAE EA,LEE B,et al. In vitro and in vivo antiallergic effects of Glycyrrhiza glabra and its components[J]. Planta Med, 2007,73(3):257
[11] PARK HY,PARK SH,YOON HK,et al. Anti-allergic activity of 18 beta-glycyrrhetinic acid-3-O-beta-D-glucuronide[J]. Arch Pharm Res,2004,27(1):57
[12] ZHAO CH,XU J,ZHANG YQ,et al. Inhibition of human enterovirus 71 replication by pentacyclic triterpenes and their novel synthetic derivatives[J]. Chem Pharm Bull,2014,62(8):764
[13] PADUCH R,KANDEFER-SZERSZEN M. Antitumor and antiviral activity of pentacyclic triterpenes[J]. Mini Rev Org Chem,2014, 11(3):262
[14] JIA J,SUN XH,SHAO TF,et al. Synthesis of novel caffeyl triterpenic esters and their hepatic protective effect[J]. Chin J Org Chem,2012,32(4):760
[15] HUANG LR,LUO H,YANG XS,et al. Enhancement of antibacterial and anti-tumor activities of pentacyclic triterpenes by introducing exocyclic alpha,beta-unsaturated ketone moiety in ring A[J]. Med Chem Res,2014,23(11):4631
[16] TIAN JL,WANG L,WANG L,et al. A wogonin-loaded glycyrrhetinic acid-modified liposome for hepatic targeting with anti-tumor effects[J]. Drug Deliv,2014,21(7):553
[17] 杨文远,熊楚明,张金国. 反相高效液相色谱法测定甘草中甘草 次酸含量[J]. 宁夏工程技术,2003,2(3):246 YANG WY,XIONG CM,ZHANG JG. Determination of glycyrrhetic acid in Glycyrrhiza by high performance liquid chromatography[J]. Ningxia Eng Technol,2003,2(3):246