雷公藤甲素阿魏酸醇质体的制备与评价
|
摘要
目的研究雷公藤甲素阿魏酸醇质体最佳制备工艺,并考察其制剂性能和体外透皮特性。方法 MTT法确定雷公藤甲素与阿魏酸的配伍比例。采用注入法制备雷公藤甲素阿魏酸醇质体,在单因素实验结果的基础上,采用Box-Behnken设计优化处方,并对其粒径、包封率、电位、分析方法学及体外释放行为进行研究。采用改良的Franz扩散池进行醇质体的体外透皮实验。结果雷公藤甲素与阿魏酸的配伍比例为1∶100。醇质体优化处方为乙醇体积分数为20%,磷脂质量分数为2.2%,超声时间为90 s,制备出的醇质体外观为澄清液体,微有蓝色乳光,平均粒径为(46.75±2.39)nm,Zeta电位为(-46.32±3.76)m V,包封率为(67.72±1.10)%。醇质体中阿魏酸、雷公藤甲素的体外透皮行为均符合Higuchi方程。结论醇质体粒径小、分布均匀、稳定性良好,有良好透皮吸收特性,可为雷公藤有效成分的局部透皮制剂开发提供一定依据。
Objective In order to optimize the preparation technology of triptolide and ferulic acid ethosomes and evaluate its characteristics of the in vitro transdermal penetration and the preparations performance using ethosome as carrier. Methods The compatibility ratio between triptolide and ferulic acid was determined by MTT. The triptolide and ferulic acid ethosomes were prepared with injection method based on the results of single factor experiments, Box-Behnken design was used to optimize the particle size, electric potential, and encapsulation efficiency(EE) of the ethosomes, and the in vitro release behavior prepared by the optimal formulation were studied. The in vitro transdermal absorption experiment was carried out in optimized Franz diffusion cells. Results The ratio of triptolide to ferulic acid was 1∶100. The optimized prescription of the ethosomes was 20% ethanol, 2.2% phospholipid, 90 s ultrasonic time. The results showed that the appearance of the triptolide and ferulic acid ethosomes was clear liquid with blue opalescence in an average diameter of(46.75 ± 2.39) nm at potential of(-46.32 ± 3.76) m V, and the EE was(67.72 ± 1.10)%. The in vitro transdermal behaviors of ferulic acid and triptolide in the ethosomes were in line with the Higuchi equation. Conclusion The ethosomes has the advantages of small particle size, uniform distribution, good stability, and good transdermal absorption property, so as to provide the basis for the development of the transdermal preparation of the effective components of Tripterygium wilfordii.
Objective In order to optimize the preparation technology of triptolide and ferulic acid ethosomes and evaluate its characteristics of the in vitro transdermal penetration and the preparations performance using ethosome as carrier. Methods The compatibility ratio between triptolide and ferulic acid was determined by MTT. The triptolide and ferulic acid ethosomes were prepared with injection method based on the results of single factor experiments, Box-Behnken design was used to optimize the particle size, electric potential, and encapsulation efficiency(EE) of the ethosomes, and the in vitro release behavior prepared by the optimal formulation were studied. The in vitro transdermal absorption experiment was carried out in optimized Franz diffusion cells. Results The ratio of triptolide to ferulic acid was 1∶100. The optimized prescription of the ethosomes was 20% ethanol, 2.2% phospholipid, 90 s ultrasonic time. The results showed that the appearance of the triptolide and ferulic acid ethosomes was clear liquid with blue opalescence in an average diameter of(46.75 ± 2.39) nm at potential of(-46.32 ± 3.76) m V, and the EE was(67.72 ± 1.10)%. The in vitro transdermal behaviors of ferulic acid and triptolide in the ethosomes were in line with the Higuchi equation. Conclusion The ethosomes has the advantages of small particle size, uniform distribution, good stability, and good transdermal absorption property, so as to provide the basis for the development of the transdermal preparation of the effective components of Tripterygium wilfordii.
引文
[1]杨坤,吴东方,程虹.雷公藤提取物治疗类风湿关节炎的Meta分析[J].药物流行病学杂志,2016,25(11):677-682.
[2]吴少辉,刘光明.雷公藤内酯的提取、分析和药理作用研究进展[J].现代药物与临床,2011,26(1):36-39.
[3]Fan D,He X,Bian Y,et al.Triptolide modulates TREM-1signal pathway to inhibit the inflammatory response in rheumatoid arthritis[J].Int J Mol Sci,2016,17(4):498-???.
[4]黄郑隽,阙慧卿,朱惠,等.雷公藤甲素对生殖系统毒性的研究进展[J].药物评价研究,2013,36(3):224-227.
[5]Lu Y,Xie T,Zhang Y,et al.Triptolide Induces hepatotoxicity via inhibition of CYP450s in rat liver microsomes[J].BMC Complement Altern Med,2017,doi:10.1186/s12906-016-1504-3.
[6]Yang J,Sun L,Wang L,et al.Activation of Sirt1/FXR signaling pathway attenuates triptolide-induced hepatotoxicity in rats[J].Front Pharmacol,2017,doi:10.3389/fphar.2017.00260.
[7]Li X,Jiang Z,Zhang L.Triptolide:Progress on research in pharmacodynamics and toxicology[J].J Ethnopharmacol,2014,155(1):67-79.
[8]王贝,江振洲,张陆勇.雷公藤甲素毒性及减毒的研究进展[J].药物评价研究,2012,35(3):211-215.
[9]赵小梅,宫嫚,董捷鸣,等.甘草炮制雷公藤降低其肝毒性作用的初步研究[J].中国中药杂志,2017,42(1):119-124.
[10]张静,江莹,王芳,等.基于“异类相制”理论探讨雷公藤肝毒性配伍减毒的作用[J].中草药,2014,45(18):2711-2715.
[11]郜丹,李晓菲,尹萍,等.基于炮制减毒思想的何首乌肝毒性物质基础初步研究[J].中草药,2017,48(10):2044-2050.
[12]韩菁婕,柳芳,张相林,等.雷公藤主要活性成分的结构修饰及药理活性研究进展[J].中国药房,2016,27(4):560-562.
[13]陶玲,肖芳,朱卫丰,等.雷公藤减毒研究进展[J].中国实验方剂学杂志,2017,23(5):229-234.
[14]施晓琴,赵继会,王志东,等.醇质体在经皮给药方面的应用[J].中国实验方剂学杂志,2013,19(12):352-355.
[15]吴艳丽,危红华,张朵朵,等.辛夷挥发油鼻腔醇质体喷雾剂的制备及其质量评价[J].中草药,2014,45(10):1393-1397.
[16]Abdulbaqi I M,Darwis Y,Khan N A K,et al.Ethosomal nanocarriers:The impact of constituents and formulation techniques on ethosomal properties,in vivo studies,and clinical trials[J].Int J Nanomed,2016,11:2279-2304.
[17]叶菲,许东航.肉桂提取物醇质体透皮吸收研究[J].药物评价研究,2013,36(2):119-122.
[18]朱亚楠,王满,王璐璐,等.含聚乙二醇1000维生素E琥珀酸酯的秋水仙碱醇质体的制备及其体外透皮效果研究[J].中草药,2015,46(24):3655-3660.
[19]阮浩澜,陈琪,黎旸,等.基于狗肾小管上皮细胞的雷公藤甲素体外肾毒性研究[J].中国药师,2015,18(1):1-4.
[20]刘涛,郭辰,赵晓红.毒理学研究中的体外细胞毒性评价[J].生命科学,2014,26(3):319-324.
[21]朱希聪,张为,林兰英,等.雷公藤甲素醇质体体外透皮性能和在体抗炎活性的研究[J].中国麻风皮肤病杂志,2012,28(4):277-279.
[22]李海霞,杨耀,路春波,等.醋酸钙梯度主动载药法制备芦丁纳米脂质体[J].郑州大学学报:医学版,2015,50(5):682-686.
[23]张越,瞿叶清,陈军,等.阿魏酸脂质体的体外释放度考察[J].中国实验方剂学杂志,2016,22(19):1-5.
[2]吴少辉,刘光明.雷公藤内酯的提取、分析和药理作用研究进展[J].现代药物与临床,2011,26(1):36-39.
[3]Fan D,He X,Bian Y,et al.Triptolide modulates TREM-1signal pathway to inhibit the inflammatory response in rheumatoid arthritis[J].Int J Mol Sci,2016,17(4):498-???.
[4]黄郑隽,阙慧卿,朱惠,等.雷公藤甲素对生殖系统毒性的研究进展[J].药物评价研究,2013,36(3):224-227.
[5]Lu Y,Xie T,Zhang Y,et al.Triptolide Induces hepatotoxicity via inhibition of CYP450s in rat liver microsomes[J].BMC Complement Altern Med,2017,doi:10.1186/s12906-016-1504-3.
[6]Yang J,Sun L,Wang L,et al.Activation of Sirt1/FXR signaling pathway attenuates triptolide-induced hepatotoxicity in rats[J].Front Pharmacol,2017,doi:10.3389/fphar.2017.00260.
[7]Li X,Jiang Z,Zhang L.Triptolide:Progress on research in pharmacodynamics and toxicology[J].J Ethnopharmacol,2014,155(1):67-79.
[8]王贝,江振洲,张陆勇.雷公藤甲素毒性及减毒的研究进展[J].药物评价研究,2012,35(3):211-215.
[9]赵小梅,宫嫚,董捷鸣,等.甘草炮制雷公藤降低其肝毒性作用的初步研究[J].中国中药杂志,2017,42(1):119-124.
[10]张静,江莹,王芳,等.基于“异类相制”理论探讨雷公藤肝毒性配伍减毒的作用[J].中草药,2014,45(18):2711-2715.
[11]郜丹,李晓菲,尹萍,等.基于炮制减毒思想的何首乌肝毒性物质基础初步研究[J].中草药,2017,48(10):2044-2050.
[12]韩菁婕,柳芳,张相林,等.雷公藤主要活性成分的结构修饰及药理活性研究进展[J].中国药房,2016,27(4):560-562.
[13]陶玲,肖芳,朱卫丰,等.雷公藤减毒研究进展[J].中国实验方剂学杂志,2017,23(5):229-234.
[14]施晓琴,赵继会,王志东,等.醇质体在经皮给药方面的应用[J].中国实验方剂学杂志,2013,19(12):352-355.
[15]吴艳丽,危红华,张朵朵,等.辛夷挥发油鼻腔醇质体喷雾剂的制备及其质量评价[J].中草药,2014,45(10):1393-1397.
[16]Abdulbaqi I M,Darwis Y,Khan N A K,et al.Ethosomal nanocarriers:The impact of constituents and formulation techniques on ethosomal properties,in vivo studies,and clinical trials[J].Int J Nanomed,2016,11:2279-2304.
[17]叶菲,许东航.肉桂提取物醇质体透皮吸收研究[J].药物评价研究,2013,36(2):119-122.
[18]朱亚楠,王满,王璐璐,等.含聚乙二醇1000维生素E琥珀酸酯的秋水仙碱醇质体的制备及其体外透皮效果研究[J].中草药,2015,46(24):3655-3660.
[19]阮浩澜,陈琪,黎旸,等.基于狗肾小管上皮细胞的雷公藤甲素体外肾毒性研究[J].中国药师,2015,18(1):1-4.
[20]刘涛,郭辰,赵晓红.毒理学研究中的体外细胞毒性评价[J].生命科学,2014,26(3):319-324.
[21]朱希聪,张为,林兰英,等.雷公藤甲素醇质体体外透皮性能和在体抗炎活性的研究[J].中国麻风皮肤病杂志,2012,28(4):277-279.
[22]李海霞,杨耀,路春波,等.醋酸钙梯度主动载药法制备芦丁纳米脂质体[J].郑州大学学报:医学版,2015,50(5):682-686.
[23]张越,瞿叶清,陈军,等.阿魏酸脂质体的体外释放度考察[J].中国实验方剂学杂志,2016,22(19):1-5.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |