METHODS AND TOPICAL PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF SKIN MICROVASCULAR DYSFUNCTION

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.