Research for establishment of evaluation method for the skin irritation using a Three-Dimensional Cultured Human Skin Model instead of in vivo results.

研究建立利用三维培养人体皮肤模型代替体内结果的皮肤刺激评价方法。

• 批准号: 15590137
• 负责人: SUGIBAYASHI Kenji
• 金额: $ 1.98万
• 依托单位: Josai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590137/
• 关键词: Skin irritation; MTT assay; Kinetic analysis; サイトカイン; 皮膚刺激性評価法; 速度論的解析; 三次元培養ヒト皮膚モデル; 皮膚刺激性; 塩化セチルピリジニウム; Hill式; ヘアレスマウス; モルモット

In the present report, time course of skin irritation determined by MTT assay and the relationship between skin irritation and the irritant concentration in the three-dimensional cultured human skin model as well as hairless mouse skin were analyzed using cetylpyridinium chloride (CPC) as a model test compound.1)Reaction site of the skin irritationAlthough different numbers of dead cell were found between the dorsal and abdominal skins after in vivo application of the same dose of CPC, a similar value was obtained against the skin concentration of CPC, suggesting that skin irritation is directly related to the CPC concentration where skin irritation takes place. When evaluating the in vitro data by Sigmoid Emax model, form factor, Y and the maximal value, Emax, were very similar to those in the in vivo study. Thus, the cultured cells can be used as a tool for prediction of skin irritation.2)Evaluation of CPC irritation for keratinocytes and fibroblastsSkin irritation study showed number of dead human keratiocytes was 10 times higher than that of dead human fibroblasts. This result suggests that keratinocytes, constituting the outmost layer of the skin, play an important role to protect body from the outside irritation compared to fibroblasts which were existed in deep site of the skin.

本文以氯化十六烷基吡啶(CPC)为模型试验化合物，用四甲基偶氮唑盐比色法测定了皮肤刺激性的时程，并分析了皮肤刺激性与皮肤刺激物浓度的关系。1)皮肤刺激性的反应部位相同剂量的CPC在背部和腹部皮肤中发现不同数量的死亡细胞，但与CPC的皮肤浓度相近，提示皮肤刺激性与发生皮肤刺激的部位的CPC浓度直接相关。当用Sigmoid Emax模型评估体外数据时，形状因子Y和最大值Emax与体内研究中的结果非常相似。2)评价CPC对角质形成细胞和成纤维细胞的刺激性皮肤刺激性研究表明，死人角质形成细胞的数量是死人成纤维细胞的10倍。这一结果表明，与存在于皮肤深层的成纤维细胞相比，构成皮肤最外层的角质形成细胞在保护身体免受外界刺激方面发挥着重要作用。

项目成果

Kinetic Analysis on the Skin Disposition of Cytootoxicity as an Index of Skin Irritation Produced by Cetylpyridinium Chloride : Comparison of In Vitro Data using a Three-Dimensional Cultured Human Skin Model with In Vivo Results in Hairless Mice.

作为氯化十六烷基吡啶产生的皮肤刺激指标的细胞毒性皮肤处置的动力学分析：使用三维培养人类皮肤模型的体外数据与无毛小鼠的体内结果的比较。

• 发表时间: 2006
• 期刊: Pharmaceutical Research 23・2
• 作者: Kano S;Sugibayashi K.;Kano S
• 通讯作者: Kano S

Kinetic analysis on the skin disposition of cytotoxicity as an index of skin irritation produced by cetylpyridinium chloride:: Comparison of in vitro data using a three-dimensional cultured human skin model with in vivo results in hairless mice

• DOI: 10.1007/s11095-006-9141-z
• 发表时间: 2006-02-01
• 期刊: PHARMACEUTICAL RESEARCH
• 影响因子: 3.7
• 作者: Kano, S;Sugibayashi, K
• 通讯作者: Sugibayashi, K