Clinical efficacy evaluation of the skin lightening effects of multimodality formulations in a UV-induced hyperpigmentation model

Skin lightening preparations are used by people all over the world for a diverse range of dermatologic indications. Hydroquinone is the criterion standard and remains the only prescription product available in the United States for the treatment of generalized facial hyperpigmentation. Irritation and the risk of exogenous ochronosis are the main adverse effects of concern. Therefore, there has been a constant search for developing new treatment alternatives. Understanding the molecular mechanisms involved in pigmentation allows us to develop a novel product that uses a multimodal treatment approach. We developed three proprietary formulas (SM1, SM2, and SM3) combining skin lightening agents that act via different mechanisms of action. The actives included 4-ethoxybenzaldehyde (an antiinflammatory and PGE2 suppressor), licorice extract (tyrosinase inhibitor), THD ascorbate (antioxidant), niacinamide (melanosome transport inhibitor), ethyl linoleate tyrosinase inhbitor (enhances turnover of epidermis), hexyl resorcinol (antioxidant), and retinol (tyrosinase transcription inhibitor; enhances turnover of epidermis). A singlecenter, double-blind comparison study was conducted to compare the efficacy of SM1, SM2, and SM3 in reducing UV-induced hyperpigmentation. Eighteen healthy subjects with Fitzpatrick skin types III completed the study. At baseline, five test areas were marked onto the backs of the subjects: untreated control, positive control (hydroquinone 4%), SM1, SM2, and SM3. Assignments of the test products to test areas were randomized to avoid site bias. Test sites were irradiated with 1.0, 1.5, 2.0, and 2.5 MEDs. After 2 days, to allow for pigmentation development, 30 μL of each test product were applied to the respective test sites by the study staff, once daily for 4 weeks (Monday through Saturday). Chromameter measurements (L∗ brightness) and standardized digital photography were taken twice a week of the test sites. At the end of treatment, all three formulas demonstrated statistically significant reductions in UV-induced hyperpigmentation compared to baseline (all P ≤ .0001). SM1 and SM2 consistently provided greater increases in L∗ compared to the positive control hydroquinone 4%. Results from this study indicate these topical formulas which incorporate a multimodal approach to skin lightening may provide an additional treatment option beyond hydroquinone for hyperpigmentation.