CH706226B1 - Preparation for skin lightening. - Google Patents

Abstract

L-cysteine, L-cysteamine, dithiotreitol and glutathione are very effective in lightening the skin. These molecules are unstable in aqueous solution and develop an unpleasant odor and brown discolouration during prolonged storage. To stabilize and ensure good behavior regarding the color and odor of these molecules during storage in cosmetic and pharmaceutical products, a combination with derivatives of ascorbic acid is proposed. This allows the manufacture of effective creams and lotions to lighten the natural color of the skin or to lighten stains due to hyperpigmentation.

Description

Melanogenesis

[0001] The coloration of human skin is very variable. It comes from melanin, a macromolecule with radicular properties. Melanin is synthesized from tyrosine, a cyclic amino acid, by melanocytes located in the basal stratum, the innermost layer of the epidermis. This synthesis begins with an enzymatic phase (tyrosinase) and continues with non-enzymatic reactions, especially oxidations with phenolic intermediates. The production of melanin is stimulated mainly by UV rays and hormones (MSH, Melanocyte Stimulator Hormone). Once synthesized, melanin is accumulated in melanosomes. They are vesicles whose plasma membrane surrounds melanin. The melanosomes are finally transported by means of the fine tubes (dendrites) which bind the melanocytes to the keratinocytes towards the surface of the skin. The melanosomes cluster like a hat above the nucleus of the keratinocyte and thus protect the genetic base of the cell against UV rays.

In principle we can divide the preparations to lighten the skin in 2 categories: cosmetics, especially creams to lighten black skin or healthy skin. They are widespread in Africa and Asia; cosmetic / medical preparations for lightening dark spots on the skin or for homogenizing irregularities in the coloring of the skin. The hyperpigmentation is manifested in most cases as irregular and dark spots on the skin. Melasma or chloasma are spots that appear during or after pregnancy or are caused by mostly hormonal medications, scars after acne, burns, insect bites and other injuries. The spontaneous formation of "liver spots" on parts of the skin exposed to the sun is widespread among the elderly population.

The most used molecule for lightening the skin is hydroquinone 0.5-10% in creams or lotions. It inhibits melanogenesis by inactivating tyrosinase and in addition it releases the free radical of semi quinone which is toxic to melanosomes (Jimbow K., Obata H., Pathak MA., Et al., Mechanism of depigmentation by hydroquinone; Dermatol, 1974, 62 (49): 436-49 and Denton CR, Lermer AB, Fitzpatrick TB, Inhibition of melanin formation by chemical agents, J. Invest Dermatol 1952, 18 (2): 119-7. 35). Due to its irritating effect, the use of hydroquinone is regulated in most countries.

Many manufacturers of cosmetics offer molecules or combinations less irritating to lighten the skin. Their action is not always satisfactory and requires a long treatment. Their action is directed to the different biochemical stages of melanogenesis (Barry Ladizinski, Nisha Mistry, Roopal V. Kundu: Widespread Use of Toxic Skin Lightening Compounds: Medical and Psychosocial Aspects, Dermatol Clinic 29 (2011), 111-123). .

[0005] Among the best known, mention may be made of: Tyrosinase inhibitor: hydroquinone, kojic acid, acelaic acid, arbutin, 4-hydroxyanisole, glabridin (hydrophobic fraction of licorice extract), methimazole, alpha lipoic acid. Melanogenesis inhibitor: ascorbic acid, 4-butylresorcinol, L-cysteamine, niacinamide, retinoines, dithiotreitol, methylsulfonylmethane (USP Application No. US 2005/0226627 A1). Inhibitor of glycosylation of tyrosinase: N-acetylglucosamine. Melanosome transfer inhibitor: extracts from plants such as soybean and waltheria indica, other plants containing polyphenols.

The ideal preparation for lightening the skin or balancing hyperpigmentation must have a rapid and selective action on the pigmentation of melanocytes, without killing them and without any short or long term side effect. If possible the action must touch several phases of melanogenesis.

[0007] The sulfur-containing molecules such as L-cysteamine having a strong reducing action are among the most effective. However, they have two major disadvantages that hitherto prevented their use in cosmetics. Due to their instability in aqueous solution in cosmetic preparations, they develop an unpleasant smell and a brown coloring.

The invention described below indicates combinations that stabilize these molecules. These combinations allow the industrial manufacture of cosmetic and medical preparations acceptable from the point of view of lightening activity, pleasant odor and light coloring, and which are stable during the storage time under commercial conditions.

The invention

After a large number of tests, we surprisingly found that sulfur molecules are stable in combination with certain derivatives of ascorbic acid. These combinations are stable in aqueous solution in cosmetic or medical preparations, without diminishing their lightening action on the skin. This allows the industrial manufacture of creams and other preparations having a good smell and a clear coloring.

Ascorbic acid is rapidly oxidized in aqueous solution, causing a strong brown coloration. Sodium ascorbyl phosphate, magnesium ascorbyl phosphate and ascorbyl palmitate, on the other hand, are stable and can stabilize L-cysteamine.

Example 1: Cream for lightening the skin <tb> Oil-in-water emulsion base <SEP> 95.45% <Tb> L-cysteamine <September> 3% <tb> Sodium ascorbyl phosphate <SEP> 1% <tb> Citric acid <SEP> 0.5% <Tb> Perfume <September> 0.05% <Tb> <September> 100%

Example 2: cream for lightening dark spots on the skin <tb> Oil-in-water emulsion base <SEP> 90.92% <Tb> L-cysteamine <September> 4.8% <tb> Sodium ascorbyl phosphate <SEP> 0.5% <tb> Ascorbyl palmitate <SEP> 0.5% <Tb> o-niacinamide <September> 3% <tb> Glycolic acid <SEP> 0.2% <Tb> Perfume <September> 0.08% <Tb> <September> 100%

Example 3: super active cream against skin blemishes for dermatologists <tb> Oil-in-water emulsion base <SEP> 83.9% <Tb> L-cysteamine <September> 8% <tb> Sodium ascorbyl phosphate <SEP> 1% <tb> Ascorbyl palmitate <SEP> 1.5% <Tb> p-niacinamide <September> 5% <tb> Lactic acid <SEP> 0.5% <Tb> Perfume <September> 0.1% <Tb> <September> 100%

[0014] Remarks: by replacing the o-niacinamide with p-niacinamide, discoloration of the spots becomes stronger. The acid pH (between 5.5-6.2) emulsions accelerates the metabolism of the skin. In addition L-cysteamine is more stable at this pH.

Example of in vivo treatment to lighten healthy skin

Mr. BK, a 37-year-old man, phototype IV (swarthy), applied the cream of Example 2, once a day in the evening on the face and neck, for 2 months. The color of the skin was measured before the beginning and after 2 months.

Chromameter used: mexameter MX-18 (Khazaka electronic GmbH, Germany).

Pre-treatment value: Melanin 320

Value after 2 months of treatment: Melanin 210

Similarly photos of the skin surface before and after treatment were taken with a dermatoscope type Hnadyscope (FotoFinder GmbH, Germany). This treatment cleared the skin color evenly without any side effects and in addition the surface of the skin seemed fresher and younger, indicating a rejuvenating effect.

Example of in vivo treatment to lighten uneven skin pigmentation

Ms. MH, a 36-year-old woman, prototype III, had an excess of pigmentation on the dorsal side of her legs, due to excessive exposure to the sun. She applied the cream of Example 3 every night for 2 months on the left leg leaving the untreated right leg for comparison. The color of the skin was measured before and after this treatment and at the same time photographed.

Value before treatment: Melanin 370

Value after 2 months of treatment: Melanin 230

This treatment cleared the hyperpigmentation of the skin homogeneously without any side effects.

Claims (7)

1. Cosmetic and pharmaceutical preparation for lightening human skin or reducing dark spots on the skin, which combine derivatives of ascorbic acid with the following sulfur-containing molecules: L-cysteine, L-cysteamine, dithiotreitol and glutathione . 2. Preparation according to claim 1, the ascorbic acid derivatives are sodium ascorbyl phosphate, magnesium ascorbyl phosphate and ascorbyl palmitate. 3. Preparation according to claims 1 and 2 characterized in that the concentration of sulfur molecules is 0.2-20%. 4. Preparation according to claims 1-3 characterized in that the concentration of ascorbic acid derivatives is 0.2-10%. 5. Preparation according to claims 1-4 characterized in that they contain ortho or para niacinamide to increase the effectiveness and cosmetic action of said preparations. 6. Preparation according to claims 1-5 characterized in that they contain 0.05% -1% of an organic acid, preferably citric acid, glycolic or lactic acid. 7. Preparation according to claims 1-6 characterized in that they are in topical form such as cream, lotion, gel, spray, foam or patch.