Depigmentation agents

Agents or processes for the cosmetic treatment of the skin, intended to lighten the skin and/or body hair and/or to remove pigmentary irregularities of the skin.

Undesirable pigmentation and hyperpigmentation of the skin (frequent pigmentation disorders occur in women, especially during and after pregnancy, as dark discoloration of the face: melasma). They can be treated medically and cosmetically (not all products allowed for medical use are approved for cosmetics, e.g. hydroquinone).

Physical procedures such as various laser procedures, microdermabrasion and cryotherapeutic procedures are used to lighten the skin. Furthermore, chemical therapy methods are used such as keratolytic, oxidizing and reducing agents (bleaching agents) as well as agents which intervene in the biosynthesis of melanin formation (e.g. tyrosinase-inhibiting preparations).

Physical procedures

• Laser and IPL treatments (ruby laser, alexandrite laser, Nd:YAG laser, erbium YAG laser): Laser treatments use high-energy light. Pigment cells and pigment-bearing keratinocytes in the epidermis are destroyed. Depending on the type of laser, dermal melanocytes can also be destroyed. "Q-switched" lasers with extremely short pulses in the nanosecond range can destroy melanin. These laser systems include the 694-nm ruby laser, the 755-nm alexandrite laser, the 532-nm Nd:YAG laser, and the 1,064-nm Nd:YAG laser. Superficial ablation leading to pigment removal (resurfacing) is possible with 2940-nm erbium YAG and 10,600-nm CO2 lasers.
• Cryopeeling: The ablative superficial cryotherapy is in the hands of the experienced therapist an elegant method to eliminate hyperpigmentation of the skin. Usually a single freezing cycle is sufficient to achieve a sufficient effect.

Chemical procedures

Fruit acid peeling: AHA acids (alpha hydroxy acid) such as glycolic acid remove superficial cellular material containing melanin. Furthermore, stimulation of cell proliferation leads to faster replacement of melanin-containing cells.

Other acid peels: Salicylic acid and highly concentrated free vitamin C (ascorbic acid) also have a keratolytic effect and thus lighten the skin.

Chemical methods: Melanophobic active ingredients

• Liposomal vitamin C: Liposomal vitamin C (ascorbyl phosphate) inhibits tyrosinase and at the same time the subsequent steps of melanogenesis associated with oxidations. Free vitamin C is less suitable because of its instability to atmospheric oxygen and its low penetration capacity.
• Antioxidants: The antioxidant activity of polyphenols is limited. This is especially true for polyphenolic compounds such as catechins, resorcins, flavones, isoflavones and gallates or the extracts of green and black tea, coffee, soy and others.

Tyrosinase inhibitors

• Rucinol: Rucinol (4-butyl-benzene-1,3-diol) is a resorcinol-type tyrosinase inhibitor. Rucinol is used in both topical pharmaceutical and cosmetic preparations.
• Butylresorcinol: B-resorcinol belongs to the tyrosinase inhibitors and is used in cosmetic preparations. Skin irritation rarely occurs and B-resorcinol is effective against the most common forms of hyperpigmentation such as melasma and age spots.
• Azelaic acid: Azelaic acid, a competitive inhibitor of tyrosinase is a naturally occurring, non-toxic dicarboxylic acid. Topical azelaic acid is effective only at high doses, which are possible only in pharmaceutical preparations. However, in cosmetic, liposomal application form, 1% azaleic preparations applied for longer periods show a lightening effect. Azelaic acid has antimicrobial effects in acne and rosacea.
• Arbutin in skin-lightening herbal extracts: Herbal extracts are often used for the preventive application of skin-lightening cosmetic agents. Their mode of action is not always known in detail. They often contain the hydroquinone derivative arbutin as the active ingredient. Examples include the following plant extracts:
• Mallow (Malva sylvestris)
• Peppermint (Mentha piperita)
• Cowslip (Primula veris)
• Lady's mantle (Alchemilla vulgaris)
• Speedwell (Veronica officinalis)
• Lemon balm (Melissa officinalis)
• Yarrow (Achillea millefolium)
• Arbutin (hydroquinone-beta-D-glucoside): Most skin-lightening plant extracts contain arbutin, a naturally occurring glycosidic hydroquinone compound. Arbutin is mainly extracted from Uvae uris folium, the leaves of the bearberry. Compared to hydroquinone, arbutin has the advantage of being less sensitive to atmospheric oxygen. Only small amounts of arbutin are split into its individual components (hydroquinone). Nevertheless, the release of hydroquinone is classified as a concern by the BfR.
• Hydroquinone(not allowed in cosmetics in Europe): Hydroquinone is not allowed in cosmetic lighteners. Hydroquinone is only allowed in hair dyes (max. 0.3%) with the warning "contains hydroquinone". Hydroquinone is freely available in cosmetics in the USA at concentrations < 2%.
• Hydroquinone (allowed in medical preparations): Hydroquinone (2%-4%) is used in medical preparations for hyperpigmentation. The substance inhibits tyrosinase. Accordingly, a preventive effect and lightening of an already existing pigmentation can be observed. In topical lightening pharmaceuticals, hydroquinone is combined with hydrocortisone and retinoids such as vitamin A acid, among others (see Hydroquinone Ointment 3% below). Vitamin A acid provokes an intensive cell renewal process and leads to faster removal of pigments. Hydrocortisone in medical bleaching agents reduces pigment formation of melanocytes.
• Topical retinoids
• Topical tretinoin in concentrations of 0.05-0.1% is also effective. Inflammatory irritation should be avoided if possible (risk of postinflammatory hyperpigmentation). The mechanism of melanin reduction is unknown. Important: Tretinoin treatment must be given consistently over a period of 20 to 40 weeks. Alternatively, 0.1% tazarotene can be used effectively.
• Kojic acid: Like hydroquinone, kojic acid (5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) is a potent reducing agent and inhibits tyrosinase. Kojic acid bleaches very effectively and is widely used in Asia. The substance, which has a mutagenic effect on bacteria, was long suspected of being carcinogenic in Europe. However, studies have not been able to substantiate this assumption. However, kojic acid is banned in cosmetics in Switzerland.
• Licorice root extract (active ingredient: glabridin). Licorice extracts have an effect similar to that of kojic acid. The essential ingredient is glabridin. Glabridin is also an inhibitor of tyrosinase in melanocytes.
• Tranexamic acid: Tranexamic acid is used in Asian countries as a depigmentation agent (in Germany the substance is used as an antifibrinolytic). Tranexamic acid effectively inhibits tyrosinase and results in skin lightening. Liposomal dispersions are particularly effective for melasma.
• Dibenzoyl peroxide: Skin whitening is known to be a side effect of dibenzoyl peroxide, which is included in pharmaceutical creams for acne treatment. Hydrogen peroxide also causes depigmentation (hair bleaching).

Preventive use of sunscreens

The use of physical and chemical sunscreens is the most important accompanying measure when using skin-lightening preparations. Due to the lack of natural protection by melanin, the sensitivity of the skin to UV rays naturally increases.