Methods and topical pharmaceutical compositions for the treatment of skin microvascular dysfunction

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% dimethylsulfoxide (DMSO) allowed a stable and continuous diffusion of t-AUCB from 2 hours after application on skin pig ears to over a period of 24h. 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.

Keywords: Skin complications, skin ulcers, diabetes, systemic sclerosis, soluble epoxide hydrolase, sEH
Patent Application number: EP18 306 336.1
Publications:
Diab Vasc Dis Res. 2019 Nov;16(6):523-529. doi: 10.1177/1479164119860215. Epub 2019 Jul 3.

Reference:

BIO17360-T1

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Aymeric Empereur
Aymeric Empereur
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Patent filling date: 2018-10-10

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