皮肤生理指标检测优选特应性皮炎润肤剂的实验研究
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摘要
目的探讨以神经酰胺、透明质酸钠、丹皮酚、山茶籽油为主要成分研制润肤剂用于治疗特应性皮炎(AD)动物模型,并证实其有效性和安全性。方法按L9(34)正交实验表设计4种主要成分的配比,采用四因素三水平安排实验,将4~6周BALB/c小鼠制备的AD动物模型分为9组,分别涂抹9种主要成分浓度不一的润肤剂,通过检测治疗前及治疗后的皮肤含水量、经皮水分丢失(TEWL)筛选最优处方,并进行药效学及皮肤刺激性实验。结果通过正交表的极差分析以及方差分析得出神经酰胺对皮肤含水量影响最大,山茶籽油对TEWL影响最大,最优的处方为1号,主要成分的配比为D1E1F1G1;药效学实验显示高、中、低剂量组与空白对照组相比治疗后的皮肤含水量、pH值、TEWL值均明显改善,且P值均<0.05,与阳性对照组相比无统计学差异,P值均>0.05;皮肤刺激性试验结果为0分,无刺激性。结论该润肤剂能明显改善AD小鼠皮肤含水量、pH、TEWL,可用于修复AD小鼠的皮肤屏障,且无刺激性。
Objective To optimize the formulation of an emollient for treatment of atopic dermatitis prepared using ceramide,sodium hyaluronate, paeonol, and camellia-seed oil. Methods The emollients with different ratios of the 4 components were designed according to the L9(34)orthogonal table with 4 factors and 3 levels. The efficacy of the prepared emollients was tested in 4-6 week-old BALB/c mouse models of atopic dermatitis to determine the optimal formulation of the emollient by evaluating skin water content, transepidermal water loss(TEWL), pharmacodynamics and skin irritation. Results Range analysis of the orthogonal table and analysis of variance showed that ceramide and camellia seed oil contents had the greatest impact on the skin water content and TEWL, respectively, and the optimal composition of the emollient contained the 4components at the ratios of D1E1F1G1. Pharmacodynamic experiments showed that at high, medium and low doses, the emollient with the optimal formulation significantly improved the skin water content, pH and TEWL in the mice(P<0.05) with similar effects in the positive control group(P>0.05) and a skin irritation test score of 0. Conclusion The emollient we prepared can significantly improve skin water content, pH and TEWL in the mouse model of atopic dermatitis without skin irritations.
Objective To optimize the formulation of an emollient for treatment of atopic dermatitis prepared using ceramide,sodium hyaluronate, paeonol, and camellia-seed oil. Methods The emollients with different ratios of the 4 components were designed according to the L9(34)orthogonal table with 4 factors and 3 levels. The efficacy of the prepared emollients was tested in 4-6 week-old BALB/c mouse models of atopic dermatitis to determine the optimal formulation of the emollient by evaluating skin water content, transepidermal water loss(TEWL), pharmacodynamics and skin irritation. Results Range analysis of the orthogonal table and analysis of variance showed that ceramide and camellia seed oil contents had the greatest impact on the skin water content and TEWL, respectively, and the optimal composition of the emollient contained the 4components at the ratios of D1E1F1G1. Pharmacodynamic experiments showed that at high, medium and low doses, the emollient with the optimal formulation significantly improved the skin water content, pH and TEWL in the mice(P<0.05) with similar effects in the positive control group(P>0.05) and a skin irritation test score of 0. Conclusion The emollient we prepared can significantly improve skin water content, pH and TEWL in the mouse model of atopic dermatitis without skin irritations.
引文
[1]瞿旻晔,袁晓琳,马健.特应性皮炎发病过程及其机制研究现状探讨[J].中国皮肤性病学杂志,2015,29(10):1085-7.
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[3]唐萍,谭琦,王华.皮肤屏障关键结构与特应性皮炎的相关性[J].激光杂志,2013,34(5):118-9.
[4]Yoshida S,Yasutomo K,Watanabe T.Treatment with DHA/EPA ameliorates atopic dermatitis-like skin disease by blocking LTB4production[J].J Med Invest,2016,63(3-4):187-91.
[5]杨扬,马慧军,胡蓉.皮肤角质层的相关屏障结构和功能的研究进展[J].中国美容医学,2012,21(1):158-61.
[6]任发亮,顾恒.中外特应性皮炎诊疗指南比较[J].中国皮肤性病学杂志,2013,27(2):210-3.
[7]杨雪源,徐丽敏,周爱民,等.含马齿苋及牛油果树提取物的医学护肤品辅助治疗特应性皮炎的临床观察[J].临床皮肤科杂志,2010,39(7):460-2.
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[11]陈祥娥,凌沛学.透明质酸与化妆品[J].食品与药品,2010,20(7):278-80.
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[14]陈軻,刘振香,罗小会.野生山茶籽油润肤霜的研制[J].金华职业技术学院学报,2015,15(3):80-5.
[15]蒋玲艳,王林果,欧熳熳.茶油抑菌效果的研究[J].安徽农业科学,2008,36(14):5913-4.
[16]王爱萍,袁丹,孙考祥,等.山茶油对非甾体抗炎药经皮渗透的促进作用[J].沈阳药科大学学报,2006,50(10):621-4.
[17]Choi J H,Park B H,Kim H G,et al.Inhibitory effect of Psidium guajava water extract in the development of 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice[J].Food Chem Toxicol,2012,50(8):2923-9.
[18]纪玉青,贾强,赵雪铮,等.2,4-二硝基氯苯诱导超敏反应性皮炎小鼠淋巴细胞增殖与活化研究[J].中国职业医学,2014,41(5):489-95.
[19]张丽霞,王倩,陈金,等.特应性皮炎小鼠模型建立方法的研究[J].实用医院临床杂志,2014,11(2):16-8.
[20]中华人民共和国卫生部.化妆品卫生规范-2007(皮肤刺激性/腐蚀性试验)[J].北京:中华人民共和国卫生部,2007:102-9.
[21]Hattori K,Nishikawa M,Watcharanurak K,et al.Sustained exogenous expression of therapeutic levels of IFN-gamma ameliorates atopic dermatitis in NC/Nga mice via Th1 polarization[J].J Immunol,2010,184(5):2729-35.
[22]Matsuda H,Watanabe N,Geba G P,et al.Development of atopic dermatitis-like skin lesion with Ig E hyperproduction in NC/Nga mice[J].Int Immunol,1997,9(3):461-6.
[23]云晴,杨高云,乌日娜.小鼠模型在特应性皮炎方面的研究进展[J].临床和实验医学杂志,2012,11(22):1827-9.
[24]蔄茂强,Peter ME.特应性皮炎患者皮肤的水通透屏障功能改变及其临床意义[J].临床皮肤科杂志,2007,36(10):671-3.
[25]张怀亮.皮肤生理量化指标研究新进展[J].中国中西医结合皮肤性病学杂志,2003,2(1):59-62.
[26]魏静,张伟敏,钟耕.神经酰胺对皮肤生理作用及其在化妆品中应用[J].粮食与油脂,2007,21(1):21-4.
[2]彭星,刘玉梅.特应性皮炎发病机制的研究进展[J].中国实验诊断学,2014,18(10):1734-7.
[3]唐萍,谭琦,王华.皮肤屏障关键结构与特应性皮炎的相关性[J].激光杂志,2013,34(5):118-9.
[4]Yoshida S,Yasutomo K,Watanabe T.Treatment with DHA/EPA ameliorates atopic dermatitis-like skin disease by blocking LTB4production[J].J Med Invest,2016,63(3-4):187-91.
[5]杨扬,马慧军,胡蓉.皮肤角质层的相关屏障结构和功能的研究进展[J].中国美容医学,2012,21(1):158-61.
[6]任发亮,顾恒.中外特应性皮炎诊疗指南比较[J].中国皮肤性病学杂志,2013,27(2):210-3.
[7]杨雪源,徐丽敏,周爱民,等.含马齿苋及牛油果树提取物的医学护肤品辅助治疗特应性皮炎的临床观察[J].临床皮肤科杂志,2010,39(7):460-2.
[8]Novotny J,Janusova B,Novotny M,et al.Short-chain ceramides decrease skin barrier properties[J].Skin Pharmacol Physiol,2009,22(1):22-30.
[9]Na JI,Hwang JS,Park HJ,et al.A new moisturizer containing physiologic lipid granules alleviates atopic dermatitis[J].J Dermatolog Treat,2010,21(1):23-7.
[10]崔媛,段潜,李艳辉.透明质酸的研究进展[J].长春理工大学学报(自然科学版),2011,34(3):101-6.
[11]陈祥娥,凌沛学.透明质酸与化妆品[J].食品与药品,2010,20(7):278-80.
[12]杨正生,彭振辉,姚青海,等.丹皮酚的药理作用研究进展[J].中国药物与临床,2011,11(5):545-7.
[13]高健,相海鹰,许同桃,等.丹皮酚及其席夫碱衍生物的抑菌性研究[J].化学试剂,2007,29(1):59-60.
[14]陈軻,刘振香,罗小会.野生山茶籽油润肤霜的研制[J].金华职业技术学院学报,2015,15(3):80-5.
[15]蒋玲艳,王林果,欧熳熳.茶油抑菌效果的研究[J].安徽农业科学,2008,36(14):5913-4.
[16]王爱萍,袁丹,孙考祥,等.山茶油对非甾体抗炎药经皮渗透的促进作用[J].沈阳药科大学学报,2006,50(10):621-4.
[17]Choi J H,Park B H,Kim H G,et al.Inhibitory effect of Psidium guajava water extract in the development of 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice[J].Food Chem Toxicol,2012,50(8):2923-9.
[18]纪玉青,贾强,赵雪铮,等.2,4-二硝基氯苯诱导超敏反应性皮炎小鼠淋巴细胞增殖与活化研究[J].中国职业医学,2014,41(5):489-95.
[19]张丽霞,王倩,陈金,等.特应性皮炎小鼠模型建立方法的研究[J].实用医院临床杂志,2014,11(2):16-8.
[20]中华人民共和国卫生部.化妆品卫生规范-2007(皮肤刺激性/腐蚀性试验)[J].北京:中华人民共和国卫生部,2007:102-9.
[21]Hattori K,Nishikawa M,Watcharanurak K,et al.Sustained exogenous expression of therapeutic levels of IFN-gamma ameliorates atopic dermatitis in NC/Nga mice via Th1 polarization[J].J Immunol,2010,184(5):2729-35.
[22]Matsuda H,Watanabe N,Geba G P,et al.Development of atopic dermatitis-like skin lesion with Ig E hyperproduction in NC/Nga mice[J].Int Immunol,1997,9(3):461-6.
[23]云晴,杨高云,乌日娜.小鼠模型在特应性皮炎方面的研究进展[J].临床和实验医学杂志,2012,11(22):1827-9.
[24]蔄茂强,Peter ME.特应性皮炎患者皮肤的水通透屏障功能改变及其临床意义[J].临床皮肤科杂志,2007,36(10):671-3.
[25]张怀亮.皮肤生理量化指标研究新进展[J].中国中西医结合皮肤性病学杂志,2003,2(1):59-62.
[26]魏静,张伟敏,钟耕.神经酰胺对皮肤生理作用及其在化妆品中应用[J].粮食与油脂,2007,21(1):21-4.