薄荷素油鼻黏膜保湿微乳的制备及其黏膜黏附性和纤毛毒性研究
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摘要
目的:制备薄荷素油鼻黏膜保湿微乳,并对其黏膜黏附性和纤毛毒性进行考察。方法:以聚氧乙烯氢化蓖麻油为乳化剂制备薄荷素油鼻黏膜保湿微乳,基于综合评分以正交设计法优化微乳的制备工艺;对所制微乳进行表征并采用气相色谱法测定薄荷醇含量;通过测定蟾蜍在体纤毛传输速率评价其黏膜黏附性,测定蟾蜍离体纤毛持续运动时间以评价其纤毛毒性。结果:自制微乳的优化制备工艺为先将薄荷素油与乳化剂分散,再加入无水乙醇、食用甘油、蒸馏水混合后,于1 200 r/min的转速下搅拌2h。3批自制微乳中薄荷醇的平均含量为2.682、2.507、2.496 mg/mL,RSD为2.89%(n=3)。自制微乳高、中、低剂量组(以薄荷醇计2.561、0.256、0.128 mg/mL)蟾蜍在体上颚纤毛传输速率分别为(0.65±0.01)、(0.78±0.03)、(0.92±0.04)cm/min,显著低于生理盐水组和复方薄荷脑滴鼻液组(P<0.05);蟾蜍离体上颚纤毛运动时间分别为(206.7±4.9)、(226.0±13.5)、(269.3±12.9)min,显著长于去氧胆酸钠组(P<0.05)。结论:自制微乳的制备工艺可行、质量可控,其黏膜黏附性较好,无纤毛毒性。
OBJECTIVE:To prepare the Peppermint oil moisturizing microemulsion for nasal mucosa and survey its mucosal adhesion and cilia toxicity. METHODS:The polyoxyethylene hydrogenated castor oil was used as emulsifier to prepare the Peppermint oil moisturizing microemulsion for nasal mucosa,and the preparation technology was optimized on the basis of comprehensive score by orthogonal design. The microemulsion was characterized and the menthol content was determined by GC.The mucosal adhesion was evaluated by measuring the transport rate by cilia in vivo,and the cilia toxicity of microemulsion was evaluated by measuring the sustained movement time of cilia in vitro. RESULTS:The optimal preparation technology of self-made microemulsion was to firstly disperse the peppermint oil and the emulsifier,then add anhydrous ethanol,edible glycerin and distilled water,and stir at 1 200 r/min for 2 h. The average contents of menthol in the three batches of the microemulsion were 2.682,2.507 and 2.496 mg/mL(RSD=2.89%,n=3),respectively. The cilia transport rates in vivo were(0.65±0.01),(0.78±0.03)and(0.92 ± 0.04) cm/min in high-dose,medium-dose,and low-dose groups of self-made microemulsion(2.561,0.256,0.128 mg/mL of menthol) respectively,which were significantly lower than normal saline group and compound menthol nasal droups(P<0.05). The cilia movement time in vitro were(206.7 ± 4.9),(226.0 ± 13.5),(269.3 ± 12.9)min,which were significantly longer than sodium deoxycholate group(P<0.05). CONCLUSIONS: The preparation technology of self-made microemulsion is easy-to-handle and controllable in quality. The prepared microemulsion shows good mucosal adhesion without cilia toxicity.
OBJECTIVE:To prepare the Peppermint oil moisturizing microemulsion for nasal mucosa and survey its mucosal adhesion and cilia toxicity. METHODS:The polyoxyethylene hydrogenated castor oil was used as emulsifier to prepare the Peppermint oil moisturizing microemulsion for nasal mucosa,and the preparation technology was optimized on the basis of comprehensive score by orthogonal design. The microemulsion was characterized and the menthol content was determined by GC.The mucosal adhesion was evaluated by measuring the transport rate by cilia in vivo,and the cilia toxicity of microemulsion was evaluated by measuring the sustained movement time of cilia in vitro. RESULTS:The optimal preparation technology of self-made microemulsion was to firstly disperse the peppermint oil and the emulsifier,then add anhydrous ethanol,edible glycerin and distilled water,and stir at 1 200 r/min for 2 h. The average contents of menthol in the three batches of the microemulsion were 2.682,2.507 and 2.496 mg/mL(RSD=2.89%,n=3),respectively. The cilia transport rates in vivo were(0.65±0.01),(0.78±0.03)and(0.92 ± 0.04) cm/min in high-dose,medium-dose,and low-dose groups of self-made microemulsion(2.561,0.256,0.128 mg/mL of menthol) respectively,which were significantly lower than normal saline group and compound menthol nasal droups(P<0.05). The cilia movement time in vitro were(206.7 ± 4.9),(226.0 ± 13.5),(269.3 ± 12.9)min,which were significantly longer than sodium deoxycholate group(P<0.05). CONCLUSIONS: The preparation technology of self-made microemulsion is easy-to-handle and controllable in quality. The prepared microemulsion shows good mucosal adhesion without cilia toxicity.
引文
[1]孔雪,赵华,唐颖.皮肤模型在化妆品功效评价中的应用研究进展[J].日用化学工业,2017,47(4):228-231、236.
[2]张晓彤,李宝树,孙斌,等.干燥性与萎缩性鼻炎鼻黏液纤毛传输功能的比较[J].临床耳鼻咽喉科杂志,2003,17(11):646-647、649.
[3]曾卫东,骆文龙.鼻腔鼻窦黏膜黏液纤毛系统研究进展[J].重庆医学,2004,33(12):1886-1888.
[4]哈宝君.鼻腔护理的临床意义[J].中国煤炭工业医学杂志,2009,12(9):1447-1449.
[5]LANDIS BN,BEGHETTI M,MOREL DR,et al.Somatosympathetic vasoconstriction to intranasal fluid administration with consecutive decrease in nasal nitric oxide[J].Acta Physiologica Scandinavica,2003,177(4):507-515.
[6]TANJA H,RAINER KW,DETLEF B.Rhinitis sicca,dry nose and atrophic rhinitis:a review of the literature[J].Eur Arch Otorhinolaryngol,2011,268(1):17-26.
[7]杨贺,李巍.慢性干燥性鼻炎的诊治[J].中国实用乡村医生杂志,2008,15(12):4-5.
[8]张荣发,杨宗发,江尚飞.薄荷油的药理毒理作用研究进展[J].中国药业,2012,21(19):1-3.
[9]ELITEZ Y,EKINCI M,ILEM-OZDEMIR D,et al.Tc-99m radiolabeled alendronate sodium microemulsion:characterization and permeability studies across caco-2 cells[J].Curr Drug Deliv,2018,15(3):342-350.
[10]杨晓艳,易蕾.佐米曲普坦-双氯芬酸微乳的制备及体外透皮研究[J].中国药房,2017,28(13):1841-1844.
[11]谢明华,蔡鑫君,封玲,等.利多卡因微乳凝胶剂的制备及初步药效学研究[J].中国现代应用药学,2015,32(4):442-446.
[12]王玮,肖颖.头孢丙烯掩味微丸的制备及其丸芯的处方工艺优化[J].中国药房,2018,29(19):2622-2625.
[13]马聪,包永睿,孟宪生,等.基于层次分析和量效对比法优选荆芥总黄酮提取工艺[J].中药材,2015,38(2):381-385.
[14]曹东,金风丽,方芳,等.润燥护鼻乳膏部分药效学及安全性实验研究[J].成都中医药大学学报,2010,33(3):51-53.
[15]王爱娟,李昕,王晖.复方川芎嗪对动物鼻黏膜及纤毛的毒性研究[J].中药药理与临床,2016,32(1):141-145.
[16]王晓丹,王晖,吴江锋,等.复方地西泮对蟾蜍鼻黏膜纤毛毒性作用的研究[J].中药新药与临床药理,2012,23(3):255-258.
[17]刘剑云,史亚军,施俊辉,等.贝加灵喷雾剂的纤毛毒性作用及黏膜刺激性实验研究[J].时珍国医国药,2012,23(4):881-882.
[18]高婷,赵玉娜,何艳萍.复方薄荷脑滴鼻剂的稳定性研究[J].西北药学杂志,2018,33(5):642-645.
[19]赵洺艺,张凯,谢茵,等.微乳碘的抗菌效果及安全性评价[J].中国消毒学杂志,2017,34(4):309-312、315.
[20]王春晓,赵华.化妆品功效评价(Ⅱ):保湿功效宣称的科学支持[J].日用化学工业,2018,48(2):67-72.
[2]张晓彤,李宝树,孙斌,等.干燥性与萎缩性鼻炎鼻黏液纤毛传输功能的比较[J].临床耳鼻咽喉科杂志,2003,17(11):646-647、649.
[3]曾卫东,骆文龙.鼻腔鼻窦黏膜黏液纤毛系统研究进展[J].重庆医学,2004,33(12):1886-1888.
[4]哈宝君.鼻腔护理的临床意义[J].中国煤炭工业医学杂志,2009,12(9):1447-1449.
[5]LANDIS BN,BEGHETTI M,MOREL DR,et al.Somatosympathetic vasoconstriction to intranasal fluid administration with consecutive decrease in nasal nitric oxide[J].Acta Physiologica Scandinavica,2003,177(4):507-515.
[6]TANJA H,RAINER KW,DETLEF B.Rhinitis sicca,dry nose and atrophic rhinitis:a review of the literature[J].Eur Arch Otorhinolaryngol,2011,268(1):17-26.
[7]杨贺,李巍.慢性干燥性鼻炎的诊治[J].中国实用乡村医生杂志,2008,15(12):4-5.
[8]张荣发,杨宗发,江尚飞.薄荷油的药理毒理作用研究进展[J].中国药业,2012,21(19):1-3.
[9]ELITEZ Y,EKINCI M,ILEM-OZDEMIR D,et al.Tc-99m radiolabeled alendronate sodium microemulsion:characterization and permeability studies across caco-2 cells[J].Curr Drug Deliv,2018,15(3):342-350.
[10]杨晓艳,易蕾.佐米曲普坦-双氯芬酸微乳的制备及体外透皮研究[J].中国药房,2017,28(13):1841-1844.
[11]谢明华,蔡鑫君,封玲,等.利多卡因微乳凝胶剂的制备及初步药效学研究[J].中国现代应用药学,2015,32(4):442-446.
[12]王玮,肖颖.头孢丙烯掩味微丸的制备及其丸芯的处方工艺优化[J].中国药房,2018,29(19):2622-2625.
[13]马聪,包永睿,孟宪生,等.基于层次分析和量效对比法优选荆芥总黄酮提取工艺[J].中药材,2015,38(2):381-385.
[14]曹东,金风丽,方芳,等.润燥护鼻乳膏部分药效学及安全性实验研究[J].成都中医药大学学报,2010,33(3):51-53.
[15]王爱娟,李昕,王晖.复方川芎嗪对动物鼻黏膜及纤毛的毒性研究[J].中药药理与临床,2016,32(1):141-145.
[16]王晓丹,王晖,吴江锋,等.复方地西泮对蟾蜍鼻黏膜纤毛毒性作用的研究[J].中药新药与临床药理,2012,23(3):255-258.
[17]刘剑云,史亚军,施俊辉,等.贝加灵喷雾剂的纤毛毒性作用及黏膜刺激性实验研究[J].时珍国医国药,2012,23(4):881-882.
[18]高婷,赵玉娜,何艳萍.复方薄荷脑滴鼻剂的稳定性研究[J].西北药学杂志,2018,33(5):642-645.
[19]赵洺艺,张凯,谢茵,等.微乳碘的抗菌效果及安全性评价[J].中国消毒学杂志,2017,34(4):309-312、315.
[20]王春晓,赵华.化妆品功效评价(Ⅱ):保湿功效宣称的科学支持[J].日用化学工业,2018,48(2):67-72.