Development of novel percutaneous absorption promoters

新型经皮吸收促进剂的研制

• 批准号: 06452378
• 负责人: NAGAI Tsuneji
• 金额: $ 3.71万
• 依托单位: Hoshi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06452378/
• 关键词: Percutaneous absorption; Absorption promoter; omicron-Ethylmenthol; Menthol; Ketoprofen; Skin irritation; Pharmacological activity; Stratum corneum; 経皮吸; ケトプロ; 促進機構; 経皮吸収促進剤; エチルエーテル誘導体; フルルビプロフェン; イソニアジド; ラット

The promoting effect of menthol ethylether derivative (MET) on the percutaneous absorption of ketoprofen from alcoholic hydrogels was evaluated in rats. The skin permeation of ketoprofen was analyzed by a membrane diffusion model, and the diffusion and partition parameters of ketoprofen were estimated. The diffusion parameter was remarkably enhanced when the hydrogel containing 0.5% MET was applied, while further increase of MET (1-3%)resulted in a little enhancement of skin permeation of ketoprofen. On the other hand, the partition parameter was hardly changed with an increase of MET concentration in the hydrogels.To evaluate in vivo percutaneous absorption of ketoprofen from hydrogels containing MET (0-3%), a pharmacokinetic model was derived on the assumption of a constant penetration rate (Rp). Similar to the results obtained with the in vitro experiment, Rp values increased significantly by the administration of hydrogels containing a littel amount of MET (-0.5%). Such promoting action was also observed with menthol, however, the degreeof enhancement with menthol was poor, compared with MET.At least 2% of menthol was required so as obtain an equal activity observed with 0.5% MET.The anti-inflammatory action of ketoprofen hydrogels containing MET was investigated with a rat paw edema test. When a little amount of MET (0.5%) was formulated in the hydrogel, a significant inhibition to the edema was observed. More than 2% of menthol was required so as to obtain the equal activity recognized in the hydrogel with 0.5% MET, indicating that the pharmacological activity of ketoprofen absorbed percutaneously correlated well with pharmacokinetic results.

研究了薄荷醇乙醚衍生物(MET)对醇性凝胶中酮洛芬透皮吸收的促进作用。用膜扩散模型分析了酮洛芬的皮肤渗透行为，估算了酮洛芬的扩散参数和分配参数。加入0.5%MET水凝胶后，扩散参数显著增加，而进一步增加MET(1~3%)，对酮洛芬的皮肤渗透有一定的促进作用。另一方面，分配参数几乎不随MET浓度的增加而变化。为了评价含MET(0-3%)水凝胶中酮洛芬的体内透皮吸收，在恒定渗透速率(Rp)的假设下，建立了药物动力学模型。与体外实验结果相似，加入少量MET(-0.5%)的水凝胶使Rp值显著增加。薄荷脑也有这种促进作用，但薄荷醇的促进作用不如甲硫氨酸。至少需要2%的薄荷醇才能获得与0.5%甲硫氨酸相同的活性。用大鼠足肿胀实验考察了含有甲硫氨酸的酮洛芬水凝胶的抗炎作用。当水凝胶中加入少量MET(0.5%)时，可明显抑制水凝胶中的水肿。超过2%的薄荷脑才能获得与0.5%甲硫氨酸水凝胶相同的活性，表明经皮吸收的酮洛芬的药理活性与药代动力学结果有很好的相关性。

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