Excerpt de articulo sobre despigmentantes....

Discussion:
Inhibition of tyrosinase activity is the most effective way to reduce hyperpigmentation. However, most topical products with tyrosinase
inhibitors lack clinical efficacy. This is no surprise, as most screenings for inhibitors have been performed with the only commercially
available enzyme, tyrosinase from the mushroom Agaricus bisporus.9,10 This is mainly due to considerable difficulties to
extract sufficient amounts of human tyrosinase from biological sources. In fact, many substances described as inhibitors of tyrosinase
were only tested on mushroom tyrosinase and are, thus, very effective inhibitors of mushroom tyrosinase, but rather poor
inhibitors of human tyrosinase. The objective of this study, therefore, was to compare the inhibitory capacity of arbutin, hydroquinone,
kojic acid and 4-butylresorcinol on melanin production using human in vitro test systems and to select the best active
ingredient for further in vivo studies. All four substances are known as tyrosinase inhibitors,11 however, the published range of
inhibitory activity is extremely broad and divergent. In the medical literature, hydroquinone is considered the gold
standard for the treatment of hyperpigmentation. However, there are severe concerns regarding the safety of hydroquinone. Banned
in the EU from the use in cosmetics, it is still sold in the USA as over-the-counter drug in formulations with up to 2% hydroquinone.
Recently, the FDA also expressed concerns12; however, a final ruling is still pending. The published IC50 values for hydroquinone
in the mushroom tyrosinase inhibition cover a wide range from 1.113 to 680 lmol ⁄ L.14 In our human assay, hydroquinone was
remarkably ineffective and only marginally inhibited human tyrosinase, barely reaching 50% inhibition at 4400 lmol ⁄ L. Since Palumbo
published his results in 199115 hydroquinone is considered a tyrosinase inhibitor; however, the cytotoxic effects seem to be more
important for the efficacy of the molecule,2 not only for the adverse effects. This view is substantiated by our results with the Melano-
Derm skin models. Here, hydroquinone (IC50 < 40 lmol ⁄ L) is almost as effective as the potent tyrosinase inhibitor 4-butylresorcinol.
Although arbutin is considered a potent tyrosinase inhibitor, the published IC50 values for mushroom tyrosinase range from
40 lmol ⁄ L16 to more than 30,000 lmol ⁄ L.17 On human tyrosinase, we found an IC50 in the millimolar range (6500 lmol ⁄ L),
and also on MelanoDerm models we measured an IC50 in the same range (>5000 lmol ⁄ L). According to the literature, alphaarbutin
seems to be slightly more effective than beta-arbutin, but both are hydroquinone prodrugs and the activity depends on the
release of hydroquinone from the molecule.2 The European Union Scientific Committee on Consumer Products published a critical
opinion on arbutin. The release of hydroquinone from the molecule raised their concern, and consequently the SCCP regards the
use of arbutin in cosmetic products as unsafe.18
…
Therefore, 4-butylresorcinol was selected for several clinical studies to prove in vivo efficacy. In comparison with 4-
hexylresorcinol and 4-phenylethylresorcinol, 4-butylresorcinol treated age spots showed a faster onset of improvement and also a
higher degree of lightening after 12 weeks of treatment. A study with a spot applicator showed continuous improvement over the
entire treatment period and even after ceasing treatment, the age spots remained for 4 weeks significantly lighter than control spots.
Even 13 weeks later, some of the spots still showed some improvement. Based on these results, a skin care line was developed and
tested under dermatological supervision on Asian women with pigmentary disorders like melasma, age spots or postinflammatory
hyperpigmentation.27 The results of the studies demonstrate a significant pigment-reducing efficacy of the test products and a clear
clinical benefit of the tested product line in the management of facial hyperpigmentation.
In conclusion, the present data show that 4-butylresorcinol is a powerful human tyrosinase inhibitor with remarkable in vivo effectiveness.
Topical products containing 4-butylresorcinol show strong efficacy on age spots, melasma28 and other facial hyperpigmentation.

JEADV 2013, 27 (Suppl.1), 19–23