**3.6 Investigation of the effect on skin**

The investigation of the effect of Enkorten on skin was conducted using the mouse ear model (according to: Hypersensitivity Test Methods: NTP-National Toxicology Program - Good Science and Good Decisions - NIEHS, USA, 2002).

Adult BALB/c male and female mice, divided into groups of 6 animals (the Institute's own breeding colony) were receiving Enkorten in 2HD (α-MSH 0.028 mg/kg + met-enkephalin 0.143 mg/kg) per day, by i.p. route, during 4 days. As an irritant, croton oil (3%, in acetone) was applied topically, in a volume of 25 μL, once, at the fifth day of the first Enkorten application. By applying the dose of Enkorten in such conditions, the irritation/inflammation process on the mouse skin caused by croton oil was inhibited by 35% compared to the control group that received the physiological solution. Enkorten action was slightly more pronounced in males during the first 24 hours.

The doubled human therapeutic dose of Enkorten, applied topically to skin in a volume of 25 μL, 6 hours prior to the irritant application (3% croton oil in acetone, in the volume of 25 μL, topically), led to the inhibition of the irritation/inflammation processes by 57% to 60%, compared to both male and female control mice.

It can be concluded that Enkorten administered preventively, in a dose equivalent to the doubled human therapeutic dose, by i.p. route, during 4 days, reduced the irritation/inflammation processes for about 35%. Compared to the control, this drug, applied once, topically, reduced irritation/inflammation processes caused on the mouse skin by 60%.
