Design of an Ante-enhancer with an Azone-Mimic Structure using Ionic Liquid
Design of an Ante-enhancer with an Azone-Mimic Structure using Ionic Liquid
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使用离子液体设计具有类氮酮结构的抗增强剂
DOI：
10.1007/s11095-023-03515-y
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发表时间：
2023
影响因子：
3.7
通讯作者：
Sugibayashi Kenji
中科院分区：
文献类型：
--
作者：
Oshizaka Takeshi;Hayakawa Mao;Uesaka Mayu;Yoshizawa Kota;Kamei Tomoyo;Takeuchi Issei;Mori Kenji;Itakura Shoko;Todo Hiroaki;Sugibayashi Kenji
目的月桂氮卓酮（Azone）是20世纪80年代被广泛研究的代表性皮肤渗透促进剂。然而，它没有被批准用于治疗，因为它通过角质层渗透到表皮后引起皮肤刺激。在本研究中，一个所谓的ante-enhancer与Azone模拟结构的基础上设计的ante-enhancer与Azone模拟结构的药物，其通过皮肤渗透后，全身毒性作用可以忽略不计。方法ante-enhancer是利用离子液体技术设计的：离子液体型ante-enhancer（IL-Azone）与Azone模拟结构的离子液体型ante-enhancer（IL-Azone），分别作为阳离子和阴离子物质的ε-己内酰胺和肉豆蔻酸。研究了白细胞介素-氮酮对5-单硝酸异山梨酯（ISMN）、安替比林（ANP）和异硫氰酸荧光素葡聚糖（FD-4）等模型药物透皮渗透的促进作用。采用Draize法评价白细胞介素-氮酮对皮肤的刺激性。Draize法测得的IL-1-Azone对小鼠的抗肿瘤作用显著低于Azone（6.9）。虽然IL-Azone的能力，以提高皮肤渗透不高的Azone，IL-Azone适度增加皮肤渗透的模型化合物测试（ISMN：4.7倍，ANP：4.5倍，FD-4：4.0倍）。使用其他阳离子和阴离子对具有Azone模拟结构的离子液体设计的进一步试验可能会导致更好的前增强剂的开发。图形摘要
PurposeLaurocapram (Azone) was broadly examined as a representative enhancer of skin penetration in the 1980s. However, it was not approved for treatment because it caused skin irritation following its penetration into the epidermis through the stratum corneum. In the present study, a so-called ante-enhancer with an Azone-mimic structure was designed based on an ante-drug with negligible systemic toxic effects following its permeation through the skin.MethodsThe ante-enhancer was designed using ionic liquid technology: an ionic liquid-type ante-enhancer (IL-Azone) with an Azone-mimic structure was prepared from ε-caprolactam and myristic acid as cationic and anionic substances, respectively. The enhancing effects of IL-Azone on the permeation by the following model drugs through pig skin were examined: isosorbide 5-mononitrate (ISMN), antipyrine (ANP), and fluorescein isothiocyanate dextran (FD-4). Skin irritation by IL-Azone was assessed using the Draize method.ResultsThe primary irritation index (P.I.I.) of IL-Azone by the Draize method was markedly lower than that of Azone (6.9). Although the ability of IL-Azone to enhance skin penetration was not as high as Azone, IL-Azone moderately increased skin permeation by the model compounds tested (ISMN: 4.7 fold, ANP: 4.5 fold, FD-4: 4.0 fold).ConclusionsThese results suggest the usefulness of designing a skin penetration enhancer using ionic liquid technology. Further trials on the ionic liquid design with an Azone-mimic structure using other cations and anions may lead to the development of better ante-enhancers.Graphical Abstract
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皮肤毒性
DOI：
--
发表时间：
2020
期刊：
An Introduction to Interdisciplinary Toxicology
影响因子：
--
作者：
M. Hughes
通讯作者：
M. Hughes
影响因子：
5.8
作者：
B. Michniak;M. Player;L. Fuhrman;C. Christensen;J. Chapman;J. Sowell
通讯作者：
B. Michniak;M. Player;L. Fuhrman;C. Christensen;J. Chapman;J. Sowell
[贝纶和尼龙基体的敏化性能问题]。
DOI：
--
发表时间：
1959
期刊：
Zeitschrift fur Haut- und Geschlechtskrankheiten
影响因子：
--
作者：
H. Jansson
通讯作者：
H. Jansson
己内酰胺
DOI：
10.4324/9780429447341-20
发表时间：
2018
期刊：
Handbook of Petrochemicals and Processes
影响因子：
--
作者：
G. Wells
通讯作者：
G. Wells
氮酮对 5-氟尿嘧啶穿过无毛大鼠皮肤转运的渗透增强作用
影响因子：
5.8
作者：
Morimoto Yasunori;Sugibayashi Kenji;Hosoya Ken;W. Higuchi
通讯作者：
W. Higuchi