Evaluation of a hydroquinone-free skin brightening product using in vitro inhibition of melanogenesis and clinical reduction of ultraviolet-induced hyperpigmentation

J Drugs Dermatol. 2013 Mar;12(3):s16-20.

Abstract

Background and objective: Skin lightening preparations are used by people all over the world for a diverse range of dermatologic indications. Hydroquinone (HQ) is the gold 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 for concern. Therefore, there has been a constant search for new treatment alternatives. Understanding the molecular mechanisms involved in pigmentation has resulted in the development of a series of formulations that utilize a multimodal treatment approach. These proprietary formulas combine skin lightening agents that act via different mechanisms of action. The actives included 4-ethoxybenzaldehyde (anti-inflammatory and prostaglandin E2 suppressor), licorice extract (tyrosinase inhibitor), tetrahexyldecyl ascorbate (antioxidant), niacinamide (melanosome transport inhibitor), ethyl linoleate (tyrosinase inhibitor; enhances turnover of epidermis), hexylresorcinol (tyrosinase inhibitor), and retinol (tyrosinase transcription inhibitor; enhances turnover of epidermis).

Methods: Select formulations were tested in several studies using the MelanoDerm™ Skin Model (MatTek Corporation, Ashland, MA) to assess the ability of the product to reduce melanin production and distribution. A single-center, double-blind comparison clinical study of 18 subjects was conducted to evaluate the efficacy of the product in reducing ultraviolet-induced hyperpigmentation. Test sites were irradiated with 1.0, 1.5, 2.0, and 2.5 minimal erythema doses. After 5 days, to allow for pigmentation development, the product or 4% HQ cream was applied to the respective test sites, once daily for 4 weeks. Chroma Meter measurements (L* brightness) and standardized digital photographs were taken of the test sites twice a week.

Results: The test product resulted in greater reduction in melanin as measured by melanin content and histological staining compared with the positive control in the MelanoDerm Skin Model. The product also demonstrated statistically significant reductions in pigmentation compared with baseline (all P ≤.0001) at the end of the clinical study, and produced greater increases in L*, compared with 4% HQ. Results from these studies indicate that a product designed to affect multiple pathways of melanogenesis and melanin distribution may provide an additional treatment option beyond HQ for hyperpigmentation.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Dermatologic Agents / administration & dosage
  • Dermatologic Agents / adverse effects
  • Dermatologic Agents / therapeutic use*
  • Dose-Response Relationship, Radiation
  • Double-Blind Method
  • Erythema / drug therapy
  • Erythema / etiology
  • Female
  • Humans
  • Hydroquinones / administration & dosage
  • Hydroquinones / therapeutic use
  • Hyperpigmentation / drug therapy*
  • Hyperpigmentation / etiology
  • Male
  • Melanins / antagonists & inhibitors*
  • Melanins / biosynthesis
  • Melanins / metabolism
  • Middle Aged
  • Radiation Injuries / prevention & control
  • Skin / radiation effects
  • Treatment Outcome
  • Ultraviolet Rays / adverse effects*
  • Young Adult

Substances

  • Dermatologic Agents
  • Hydroquinones
  • Melanins
  • hydroquinone