石菖蒲挥发油微乳鼻喷剂的制备及其质量评价
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摘要
目的以具有抗老年痴呆作用的石菖蒲挥发油为模型药物,制备石菖蒲挥发油鼻喷微乳。方法根据石菖蒲挥发油在各溶媒中的溶解度初步确定微乳处方组成,并通过绘制伪三元相图,通过比较微乳区域大小、稳定性、载药量等优选最优处方。结果优选最优处方为石菖蒲挥发油-Cremophor EL-丙三醇-水(6.25∶20.83∶10.42∶62.5),平均粒径为(30.5±0.2)nm,多分散系数(PDI)为0.150±0.002,黏度(2.80±0.21)m Pa·s;以β-细辛醚计,体外透皮速率为(1 288.76±16.20)μg/(cm2·h),比石菖蒲挥发油普通乳透皮速率提高了14倍;蟾蜍纤毛毒性实验显示该制剂无显著毒性。结论所制得的石菖蒲挥发油鼻喷微乳理化性质稳定,透皮性能好,对鼻黏膜纤毛毒性低。
Objective Taking the volatile oil of Acori Tatarinowii Rhizoma with the effect of anti-senile dementia as model drug to prepare Acori Tatarinowii Rhizoma-volatile oil microemulsion(AO-ME). Methods The composition of microemulsion was preliminarily determined according to the solubility of volatile oil from Acori Tatarinowii Rhizoma in various solvents. By drawing pseudo-ternary phase diagram, the optimal microemulsion formulation was selected according to the size of particles and microemulsion region, stability of preparations and drug loading. Results The optimal microemulsion formulation was that volatile oil of Acori Tatarinowii Rhizoma-Cremophor EL-glycerol-water was 6.25∶20.83∶10.42∶62.5. The average particle size of AO-ME was(30.5 ± 0.2) nm with a polydispersity index of 0.150 ± 0.002. The viscosity value of AO-ME was(2.80 ± 0.21) mPa·s. In vitro transdermal rate of AO-ME was(1 288.76 ± 16.20) μg/(cm2·h), measured in β-asarone. Compared with ordinary emulsion, the transdermal rate of AO-ME was increased 14 times. The ciliary toxicity test of toad showed that the preparation had no significant toxicity. Conclusion The preparation of AO-ME was prepared with stable physicochemical properties, good transdermal properties, and low toxicity to nasal mucosa cilia.
Objective Taking the volatile oil of Acori Tatarinowii Rhizoma with the effect of anti-senile dementia as model drug to prepare Acori Tatarinowii Rhizoma-volatile oil microemulsion(AO-ME). Methods The composition of microemulsion was preliminarily determined according to the solubility of volatile oil from Acori Tatarinowii Rhizoma in various solvents. By drawing pseudo-ternary phase diagram, the optimal microemulsion formulation was selected according to the size of particles and microemulsion region, stability of preparations and drug loading. Results The optimal microemulsion formulation was that volatile oil of Acori Tatarinowii Rhizoma-Cremophor EL-glycerol-water was 6.25∶20.83∶10.42∶62.5. The average particle size of AO-ME was(30.5 ± 0.2) nm with a polydispersity index of 0.150 ± 0.002. The viscosity value of AO-ME was(2.80 ± 0.21) mPa·s. In vitro transdermal rate of AO-ME was(1 288.76 ± 16.20) μg/(cm2·h), measured in β-asarone. Compared with ordinary emulsion, the transdermal rate of AO-ME was increased 14 times. The ciliary toxicity test of toad showed that the preparation had no significant toxicity. Conclusion The preparation of AO-ME was prepared with stable physicochemical properties, good transdermal properties, and low toxicity to nasal mucosa cilia.
引文
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[18]刘伟,张莹莹,周文杰,等.复方彻清膏微乳的制备及稳定性研究[J].中草药,2018,49(14):3252-3260.
[19]李绍林,王光明,颜仁梁,等.石菖蒲挥发油SFE-CO2萃取工艺的优化[J].中成药,2017,39(7):1518-1521.
[20]谷福根,张嫒,王毅,等.盐酸文拉法辛鼻喷剂在大鼠体内的药动学研究及对鼻黏膜纤毛毒性的评价[J].华西药学杂志,2018,33(3):287-290.
[21]李新方,李现贵,马志强,等.薄荷脑鼻腔原位凝胶剂的制备及安全性研究[J].药学实践杂志,2017,35(4):321-324.
[22]王章姐,胡容峰,王国凯,等.Box-Behnken设计-效应面法优化柚皮素自微乳给药系统[J].中草药,2014,45(17):2461-2466.
[2]尹芳,宋祯彦,李富周,等.基于网络药理学研究当归芍药散防治阿尔茨海默病的作用机制[J].药物评价研究,2018,41(2):210-215.
[3]柯淑芬,李红.老年痴呆照护机构生活环境评估量表的研究进展[J].中华护理杂志,2014,49(2):211-215.
[4]宋祯彦,陈易璇,余婧萍,等.钩藤散活性成分治疗阿尔茨海默病作用机制的网络药理学分析[J].中草药,2018,49(24):5854-5864.
[5]万素馨,方伟.阿尔茨海默病的治疗药物作用机制研究进展[J].现代药物与临床,2018,33(12):3406-3410.
[6]张璐,李焕娟,朱乃亮,等.基于药物体系质量评价模式的石菖蒲质量表征关联分析研究[J].环球中医药,2015,8(3):274-280.
[7]卢成淑,冯宁,南国,等.石菖蒲及其活性成分防治阿尔茨海默病的研究进展[J].中草药,2016,47(7):1236-1242.
[8]都姣娇,杜安妮.固相微萃取-气相色谱-质谱联用分析石菖蒲中挥发油成分[J].中成药,2014,36(12):2645-2648.
[9]陈小露,袁德俊,吴雪茹,等.两个产地石菖蒲挥发油质量比较研究[J].中药材,2015,38(4):770-773.
[10]王月亮,陈凯,李慧,等.石菖蒲无溶剂微波提取工艺的优化研究及其挥发性成分的GC-MS分析[J].中草药,2016,47(3):414-419.
[11]庞晓丛,王喆,方坚松,等.治疗阿尔茨海默病的中药有效成分的网络药理学研究[J].药学学报,2016,51(5):725-731.
[12]张智华,王秀莲,吴建红,等.石菖蒲-远志药对不同组分对AD模型大鼠学习记忆和海马突触蛋白表达的影响[J].中国实验方剂学杂志,2016,22(7):120-124.
[13]谢红英.石菖蒲杀虫活性、有效成分分离和制剂开发初步研究[D].长沙:湖南农业大学,2004.
[14]吴慧,吴闻哲.经鼻给药增加药物脑靶向的制剂方法[J].世界临床药物,2015,36(1):50-55.
[15]刘建春,杨婉芳,季新燕,等.中药鼻腔给药的脑靶向性探讨[J].中医杂志,2014,55(15):1284-1287.
[16]傅荣萍,刘玉萍,张毕桥,等.大蒜素二烯丙基三硫醚微乳的制备及其对肿瘤细胞增殖与迁移的影响[J].中草药,2018,49(23):5541-5547.
[17]康荣荣,杨苏芳,韩萌,等.微乳在经皮给药系统中的应用[J].中南药学,2014,55(3):253-258.
[18]刘伟,张莹莹,周文杰,等.复方彻清膏微乳的制备及稳定性研究[J].中草药,2018,49(14):3252-3260.
[19]李绍林,王光明,颜仁梁,等.石菖蒲挥发油SFE-CO2萃取工艺的优化[J].中成药,2017,39(7):1518-1521.
[20]谷福根,张嫒,王毅,等.盐酸文拉法辛鼻喷剂在大鼠体内的药动学研究及对鼻黏膜纤毛毒性的评价[J].华西药学杂志,2018,33(3):287-290.
[21]李新方,李现贵,马志强,等.薄荷脑鼻腔原位凝胶剂的制备及安全性研究[J].药学实践杂志,2017,35(4):321-324.
[22]王章姐,胡容峰,王国凯,等.Box-Behnken设计-效应面法优化柚皮素自微乳给药系统[J].中草药,2014,45(17):2461-2466.