Evaluation of percutaneous absorption promoters by means of solid fractal analysis of skin stratum corneum

皮肤角质层固体分形分析评价经皮吸收促进剂

• 批准号: 07672329
• 负责人: TAKAYAMA Kozo
• 金额: $ 1.15万
• 依托单位: Hoshi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672329/
• 关键词: fractal analysis; solid fractal dimension; confocal laser microscope; percutaneous absorption; stratum corneum; skin damage; hairless rat; absorption promoter

Solid fractal dimension of skin stratum corneum was determined in order to evaluate the pathological damages evoked by percutaneous absorption promoters such as d-limonene and Azone in the hairless rat. As a model dermatological system, alcoholic hydrogels containing each of these promoters were applied to the hairless rat abdominal skin. The application site of the skin was excised, fixed with glutaraldehyde and osmic acid, and then lyophilized. The skin surface was scanned with a confocal laser microscope and the image data of skin surface were fed into a computer. The skin surface structure was reconstructed as a contour mapping image on the display. The solid fractal dimension was then estimated based on the extended box-counting algorithm.The solid fractal dimension of untreated skin surface was estimated to be 2.17. The fractal dimension markedly decreased when the skin was treated with hydrogels containing d-limonene. On the other hand, the degree of decrease in fractal dimension was poor when Azone was applied to the skin. The decrease of fractal dimension may be attributed to the smoothing of the skin structure, which will be caused by the hydration and/or edema formation in the shallow part of the skin.The structure change of skin surface evoked by the promoters can be quantified as a nonintegral solid fractal dimension as well as the surface fractal dimension of skin cross section. This suggests the usefulness and reliability of the fractal analysis as a novel method for evaluating the skin damage.

通过测定无毛大鼠皮肤角质层的立体分形维数，研究了右旋柠檬烯和月桂氮卓酮对无毛大鼠皮肤角质层的病理损伤。作为模型皮肤病学系统，将含有这些促进剂中的每一种的醇水凝胶施加到无毛大鼠腹部皮肤。切除皮肤的应用部位，用戊二醛和锇酸固定，然后冻干。用共聚焦激光显微镜对皮肤表面进行扫描，并将皮肤表面的图像数据输入计算机。皮肤表面结构被重建为显示器上的轮廓映射图像。基于扩展的盒计数算法估计了皮肤表面的立体分形维数，得到未经处理的皮肤表面的立体分形维数为2.17。分形维数显着下降时，皮肤处理含有d-柠檬烯的水凝胶。另一方面，当Azone应用于皮肤时，分形维数的降低程度较差。分形维数的降低可能是由于皮肤浅层的水化和/或水肿形成导致皮肤结构的平滑化，促进剂引起的皮肤表面结构变化可以量化为非整数的固体分形维数和皮肤横截面的表面分形维数。这表明分形分析作为一种新的方法来评估皮肤损伤的有效性和可靠性。

项目成果

M.Iwata, Y.Takahashi, S.Shirotake, K.Takayama, Y.Machida, F.Hirahara, H.Minaguchi and T.Nagai: "Effect of sodium caprate on the absorption of progesterone from mixed suppositories administered to the vagina of rabbits" Drug Dev.Ind.Pharm.23. 167-172 (1997

M.Iwata、Y.Takahashi、S.Shirotake、K.Takayama、Y.Machida、F.Hirahara、H.Minaguchi 和 T.Nagai：“癸酸钠对阴道给药混合栓剂中黄体酮吸收的影响”

N.Ohara, K.Takayama, K.Isowa and T.Nagai: "Combined effect of penetration enhancer and temperature on skin irritation in rats" S.T.P.Pharma Sci.6. 142-147 (1996)

N.Ohara、K.Takayama、K.Isowa 和 T.Nagai：“渗透促进剂和温度对大鼠皮肤刺激的综合作用”S.T.P.Pharma Sci.6。

N. Ohara: "Combined effect of d-limonene pretreatment and temperature on the rat skin penetration of lipophilic and hydrophilic drugs" Biol. Pharm. Bull.18. 439-442 (1995)

N. Ohara：“d-柠檬烯预处理和温度对亲脂性和亲水性药物在大鼠皮肤渗透的综合影响”Biol。

Y.Nakamura, K.Takayama, K.Higashiyama, T.Suzuki and T.Nagai: "Promoting effect of O-ethylmenthol on the percutaneous absorption of ketoprofen" Int.J.Pharm.(accepted).

Y.Nakamura、K.Takayama、K.Higashiyama、T.Suzuki 和 T.Nagai：“O-乙基薄荷醇对酮洛芬经皮吸收的促进作用”Int.J.Pharm.（已接受）。

J.Akimoto, K.Takayama, K.Isowa and T.Nagai: "Evaluation of skin irritation of percutaneous absorption promoters by means of fractal dimension of rat skin structure" Int.J.Pharm.128. 251-260 (1996)

J.Akimoto、K.Takayama、K.Isowa 和 T.Nagai：“通过大鼠皮肤结构的分形维数评估经皮吸收促进剂的皮肤刺激性”Int.J.Pharm.128。