公开(公告)号：US20210378995A1

公开(公告)日：2021-12-09

申请号：US17282428

申请日：2019-10-09

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ DE ROUEN NORMANDIE ,  CENTRE HOSPITALIER UNIVERSITAIRE DE ROUEN ,  UNIVERSITÉ GRENOBLE ALPES ,  CENTRE HOSPITALIER UNIVERSITAIRE DE GRENOBLE

发明人： Jérémy BELLIEN ,  Frédéric BOUNOURE ,  Mohamed SKIBA ,  Yann SAVINA ,  Matthieu ROUSTIT ,  Jean-Luc CRACOWSKI

IPC分类号： A61K31/17 ,  A61K31/197 ,  A61K31/4468 ,  A61K31/53 ,  A61P17/00 ,  A61P9/14 ,  A61P3/10

摘要： Microvascular dysfunction remains a major contributor to the development of skin complications. The inventors assessed the impact of the local inhibition of soluble epoxide hydrolase (sEH), which metabolizes vasodilator and anti-inflammatory epoxyeicosanoids, on the diabetic skin microvascular dysfunction. The inventors have therefore developed some formulations of sEH inhibitors (GSK2256294 and t-AUCB) for topical administration. In particular, they show that an aqueous gel containing 400 mg/L t-AUCB dissolved in 50% dimethy lsulfo xide (DMSO) allowed a stable and continuous diffusion of t-AUCB from 2 hours after application on skin pig ears to over a period of 24 h. Compared to a control gel, the gel with t-AUCB did not significantly modify the basal skin blood flow but improved the altered hyperemic response of db/db mice 2 hours after application. The results show that the topical administration of a sEH inhibitor improves the skin microcirculatory function, representing a promising pharmacological approach to prevent the development of skin complications especially in diabetic patients.