解郁安神方中4种混合挥发油脂质体的制备与评价
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摘要
为增加解郁安神方中挥发油的稳定性和溶解度,该研究拟将其制成脂质体制剂。采用紫外分光光度法和葡聚糖凝胶柱法建立了测定脂质体包封率的方法,以包封率和粒径为评价指标,进行单因素考察,采用Box-Behnken效应面法优化设计,并对最优处方的挥发油脂质体制剂进行表征,以甲基丁香酚、榄香素、β-细辛醚、α-细辛醚为指标性成分,采用改良的Franz扩散池对挥发油脂质体制剂的体外透皮性能进行评价。结果显示,卵磷脂浓度、卵磷脂与挥发油质量比、搅拌速度为影响脂质体制剂最显著的3个因素;挥发油脂质体制剂的最优处方为卵磷脂质量浓度为7 g·L~(-1),卵磷脂与挥发油的质量比5∶1,搅拌速度330 r·min~(-1);所制备的脂质体带蓝色乳光,且流动性好、均一半透明,粒径为(102.6±0.35) nm,Zeta电位为(-17.8±0.306) mV,渗透率为(1.67±1.01)%,脂质体在4℃下储存较稳定;经皮给药24 h,甲基丁香酚、榄香素、β-细辛醚、α-细辛醚体单位时间累积渗透量分别为(30.485 2±1.238 9),(34.794 8±0.928 3),(26.677 1±1.171 7),(3.066 2±0.175 3)μg·cm~(-2),脂质体中甲基丁香酚、榄香素、β-细辛醚、α-细辛醚的体外透皮行为均符合Higuchi方程。该研究制得的挥发油脂质体符合相关的质量要求,为多组分中药挥发油脂质体的制剂研究提供了一定的参考。
In order to increase the stability and solubility of essential oil in Jieyu Anshen Formula, this study was to prepare the essential oil into liposomes. In this experiment, the method for the determination of encapsulation efficiency of liposomes was established by ultraviolet spectrophotometer and dextran gel column. The encapsulation efficiency and particle size of liposomes were used as evaluation indexes for single factor investigation and Box-Behnken design-response surface method was used to optimize the design. Then the optimal formulation of volatile oil liposome was characterized using methyleugenol, elemin, β-asarone and α-asarone as index components. Finally, the in vitro transdermal properties of liposomes were studied by modified Franz diffusion cell. The results showed that the concentration of lecithin, the mass ratio of lecithin to volatile oil, and the stirring speed were the three most significant factors affecting the liposome preparation. The optimum formulation of volatile oil liposome was as follows: the concentration of lecithin was 7 g·L~(-1); mass ratio of lecithin to volatile oil was 5∶1; and the stirring speed was 330 r·min~(-1). Under such conditions, the prepared liposomes had blue emulsion light, good fluidity, half translucent, with particle size of(102.6±0.35) nm, Zeta potential of(-17.8±0.306) mV, permeability of(1.67±1.01)%, and stable property if liposome was stored at 4 ℃. 24 h after percutaneous administration, the cumulative osmotic capacity per unit time was(30.485 2±1.238 9),(34.794 8±0.928 3),(26.677 1±1.171 7),(3.066 2±0.175 3) μg·cm~(-2)respectively for methyleugenol, elemin, β-asarone and α-asarone. In vitro transdermal behaviors of methyleugenol, elemin, β-asarone and α-asarone in liposomes were all consistent with Higuchi equation. The prepared volatile oil liposomes met the relevant quality requirements, providing a reference for further research on preparation of multi-component Chinese medicine essential oil liposomes.
In order to increase the stability and solubility of essential oil in Jieyu Anshen Formula, this study was to prepare the essential oil into liposomes. In this experiment, the method for the determination of encapsulation efficiency of liposomes was established by ultraviolet spectrophotometer and dextran gel column. The encapsulation efficiency and particle size of liposomes were used as evaluation indexes for single factor investigation and Box-Behnken design-response surface method was used to optimize the design. Then the optimal formulation of volatile oil liposome was characterized using methyleugenol, elemin, β-asarone and α-asarone as index components. Finally, the in vitro transdermal properties of liposomes were studied by modified Franz diffusion cell. The results showed that the concentration of lecithin, the mass ratio of lecithin to volatile oil, and the stirring speed were the three most significant factors affecting the liposome preparation. The optimum formulation of volatile oil liposome was as follows: the concentration of lecithin was 7 g·L~(-1); mass ratio of lecithin to volatile oil was 5∶1; and the stirring speed was 330 r·min~(-1). Under such conditions, the prepared liposomes had blue emulsion light, good fluidity, half translucent, with particle size of(102.6±0.35) nm, Zeta potential of(-17.8±0.306) mV, permeability of(1.67±1.01)%, and stable property if liposome was stored at 4 ℃. 24 h after percutaneous administration, the cumulative osmotic capacity per unit time was(30.485 2±1.238 9),(34.794 8±0.928 3),(26.677 1±1.171 7),(3.066 2±0.175 3) μg·cm~(-2)respectively for methyleugenol, elemin, β-asarone and α-asarone. In vitro transdermal behaviors of methyleugenol, elemin, β-asarone and α-asarone in liposomes were all consistent with Higuchi equation. The prepared volatile oil liposomes met the relevant quality requirements, providing a reference for further research on preparation of multi-component Chinese medicine essential oil liposomes.
引文
[1] 王雅琪,杨园珍,伍振锋,等.中药挥发油传统功效与现代研究进展[J].中草药,2018,49(2):455.
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[4] Lan Y, Wu Q, Mao Y Q, et al. Cytotoxicity and enhancement activity of essential oil from Zanthoxylum bungeanum Maxim.as a natural transdermal penetration enhancer[J]. J Zhejiang Univ Sci B, 2014,15(2): 153.
[5] 张定堃,傅超美,林俊芝,等.中药制剂的“药辅合一”及其应用价值[J].中草药,2017, 48(10): 1920.
[6] 韩亚亮,刘萍,何新荣,等.石菖蒲挥发油的基本成分及其药理作用研究进展[J].中国药物应用与监测,2011,8(2):120.
[7] 王睿,费洪新,李晓明,等.石菖蒲的化学成分及药理作用研究进展[J].中华中医药学刊,2013,31(7):1606.
[8] 冯波,靖慧军,郭敏娟,等.石菖蒲挥发油和水煎液的抗焦虑作用[J].中国实验方剂学杂志,2014,20(9):207.
[9] 李英超,谢小倩,王梦真,等.甲基丁香酚药理及毒理作用的研究进展[J].中南药学,2018,16(9):1249.
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[12] 袁菊,张亚宁,范云鹏,等.响应面分析法优化蜂胶黄酮脂质体制备工艺[J].食品科学,2012,33 (20):1.
[13] Brandl M. Liposomes as drug carriers:a technological approach[J]. Biotechnol Annu Rev,2001,7(1):59.
[14] Kumar G P, Mishra S,Kumar S K,et al. Development of nitrendipine nanoliposome for transdermal drug delivery: preparation,characterization and permeation studies[J].Drug Deliv, 2017,7(1):48.
[15] 张佳佳,朱源,余江南,等.辛香料挥发油类化学成分的新型载体系统研究进展[J].中国中药杂志,2015,40(20):3932.
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[17] 钟芮娜,汪小涵,王欣桐,等.石菖蒲挥发油自纳米乳的制备与质量评价[J].中国中药杂志,2018,43(20):4062.
[18] 何良飞,陶玲,管咏梅,等.雷公藤甲素阿魏酸醇质体的制备与评价[J].中草药,2018,49(12):2817.
[19] 王凤玉,张保献,张广平,等.盐酸常山碱的理化性质及其脂质体包封率的测定方法考察[J].中国实验方剂学杂志,2019,25(1):177.
[19] 张建林,陶玲,管咏梅,等.中药挥发油的促透皮作用及在外用制剂研究中的问题分析[J].中草药,2017,48(24):5263.
[20] 武燕,刘健.藏药柳茶挥发油对小鼠急性心肌缺血损伤的干预作用[J].中国现代应用药学,2017,34(3):315.
[21] 陈海鹰,范正达,朱珊梅,等.一种中药空气消毒剂中挥发油的抑菌活性研究[J].今日药学,2017,27(1):26.
[22] 司奇,吴丹,曹青日,等.缬草挥发油β-环糊精包合物的制备与评价[J].中国中药杂志,2013,38(14):2309.
[23] 李民,孙阳恩,张路,等.肉桂中挥发油提取及β-环糊精包合工艺研究[J].中国现代应用药学,2016,33(9):1124.
[24] Gumí T,Gascón S,Torras C,et al. Vanillin release from macrocapsules[J]. Desalination,2009,245 (1/3):769.
[25] Shah B,Davidson P M,Zhong Q X. Encapsulation of eugenol using Maillardtype conjugates to form transparent and heat stable nanoscale dispersions[J]. LWT-Food Sci Technol,2012,49(1):139.
[2] 陈军,刘培,蒋秋冬,等.中药挥发油作为透皮吸收促进剂的现状与展望[J].中草药,2014, 45(24):3651.
[3] Pang Y X, Fan Z W,Wang D, et al. External application of the volatile oil from Blumea balsamifera may be safe for liver a study on its chemical composition and hepatotoxicity[J].Molecules,2014, 19(11): 18479.
[4] Lan Y, Wu Q, Mao Y Q, et al. Cytotoxicity and enhancement activity of essential oil from Zanthoxylum bungeanum Maxim.as a natural transdermal penetration enhancer[J]. J Zhejiang Univ Sci B, 2014,15(2): 153.
[5] 张定堃,傅超美,林俊芝,等.中药制剂的“药辅合一”及其应用价值[J].中草药,2017, 48(10): 1920.
[6] 韩亚亮,刘萍,何新荣,等.石菖蒲挥发油的基本成分及其药理作用研究进展[J].中国药物应用与监测,2011,8(2):120.
[7] 王睿,费洪新,李晓明,等.石菖蒲的化学成分及药理作用研究进展[J].中华中医药学刊,2013,31(7):1606.
[8] 冯波,靖慧军,郭敏娟,等.石菖蒲挥发油和水煎液的抗焦虑作用[J].中国实验方剂学杂志,2014,20(9):207.
[9] 李英超,谢小倩,王梦真,等.甲基丁香酚药理及毒理作用的研究进展[J].中南药学,2018,16(9):1249.
[10] 姜平川,梁江昌.植物挥发油在外用制剂中的应用[J].内科,2011,6(5):467.
[11] Pierre M B,Dos Santos Miranda Costa I. Liposomal systems as drug delivery vehicles for dermal and transdermal applications[J].Arch Dermatol Res,2011,303(9):607.
[12] 袁菊,张亚宁,范云鹏,等.响应面分析法优化蜂胶黄酮脂质体制备工艺[J].食品科学,2012,33 (20):1.
[13] Brandl M. Liposomes as drug carriers:a technological approach[J]. Biotechnol Annu Rev,2001,7(1):59.
[14] Kumar G P, Mishra S,Kumar S K,et al. Development of nitrendipine nanoliposome for transdermal drug delivery: preparation,characterization and permeation studies[J].Drug Deliv, 2017,7(1):48.
[15] 张佳佳,朱源,余江南,等.辛香料挥发油类化学成分的新型载体系统研究进展[J].中国中药杂志,2015,40(20):3932.
[16] 中国药典.四部[S].2015:203.
[17] 钟芮娜,汪小涵,王欣桐,等.石菖蒲挥发油自纳米乳的制备与质量评价[J].中国中药杂志,2018,43(20):4062.
[18] 何良飞,陶玲,管咏梅,等.雷公藤甲素阿魏酸醇质体的制备与评价[J].中草药,2018,49(12):2817.
[19] 王凤玉,张保献,张广平,等.盐酸常山碱的理化性质及其脂质体包封率的测定方法考察[J].中国实验方剂学杂志,2019,25(1):177.
[19] 张建林,陶玲,管咏梅,等.中药挥发油的促透皮作用及在外用制剂研究中的问题分析[J].中草药,2017,48(24):5263.
[20] 武燕,刘健.藏药柳茶挥发油对小鼠急性心肌缺血损伤的干预作用[J].中国现代应用药学,2017,34(3):315.
[21] 陈海鹰,范正达,朱珊梅,等.一种中药空气消毒剂中挥发油的抑菌活性研究[J].今日药学,2017,27(1):26.
[22] 司奇,吴丹,曹青日,等.缬草挥发油β-环糊精包合物的制备与评价[J].中国中药杂志,2013,38(14):2309.
[23] 李民,孙阳恩,张路,等.肉桂中挥发油提取及β-环糊精包合工艺研究[J].中国现代应用药学,2016,33(9):1124.
[24] Gumí T,Gascón S,Torras C,et al. Vanillin release from macrocapsules[J]. Desalination,2009,245 (1/3):769.
[25] Shah B,Davidson P M,Zhong Q X. Encapsulation of eugenol using Maillardtype conjugates to form transparent and heat stable nanoscale dispersions[J]. LWT-Food Sci Technol,2012,49(1):139.