Skin hyperpigmentation is a common condition that can be the result of a clinical disorder (melasma), trauma, inflammation, or sun exposure. Currently available topical lightening agents for treatment of these conditions have safety concerns and have been pulled from over-the-counter products. Therefore, safe, novel depigmenting agents would have a potentially large consumer market. The present invention relates to methods and compositions for treating hyperpigmentary skin disorders based on the inhibition of a novel regulator of melanogenesis.
Using a genome-wide functional genomics approach designed to identify novel regulators of pigment production in human cells, researchers at UC Irvine determined that the enzyme aldehyde dehydrogenase (ALDH1A1) is novel regulator of pigment production.
Small molecule ALDH inhibitors were found to inhibit melanin accumulation by inhibiting the expression of key genes that are exclusively expressed in pigment cells. This mechanism is distinct from the mechanisms used by currently available pigment inhibitors. The most potent inhibitor found to date is the molecule cyanamide, a generic compound approved in Europe for alcohol aversion therapy. In vitro, cyanamide inhibits pigmentation in human skin cells. Cyanamide can inhibit melanin accumulation both histologically and quantitatively in skin equivalent models which closely mimic human skin.
The above figures demonstrate cyanamide can inhibit pigment accumulation in skin equivalents of darkly pigmented human skin (cyanamide, vehicle control, and kojic acid, a known skin lightener with side effects including skin irritation).
UCI researchers developed and tested 5 formulations, identifying one formulation that performed markedly better than the others. The preferred formulation was tested on healthy human subjects and did not produce any significant irritation.
Future Development Plans
Completion of stability testing is underway. We are currently looking for a commercial partner to further develop this product for skin lightening.
|United States Of America||Issued Patent||9,889,081||02/13/2018||2007-640|
|United States Of America||Issued Patent||8,802,733||08/12/2014||2007-640|