FR2804863A1 - Compositions for the depigmentation of skin contain a tyrosinase inhibitor and a hydrogen peroxide releasing agent in two distinct formulations stored as parallel or concentric layers which only mix upon release - Google Patents

Abstract

Compositions for the depigmentation of the skin in which the active depigmenting agent is reinforced by the addition of a compound releasing hydrogen peroxide.

Description

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NEW DEPIGMENTING COMPOSITIONS
AND THEIR PROCESS FOR OBTAINING The present invention relates to the field of the necessities of life and more particularly to the field of cosmetology / dermatology and more precisely of cosmeceuticals.

The invention relates more particularly to compositions intended for depigmentation of the skin in which the depigmenting active principle is reinforced in a synergistic manner by the addition of another active principle, with bleaching action.

The invention relates specifically to cosmetic compositions with depigmenting action, in which a tyrosinase inhibitor active ingredient is separately selected from the group consisting of kojic acid, 3-methyl kojic acid, fusaric acid, 5 -hydroxy 2-hydroxy methyl y-pyridone, maltol, isomaltol and 5-ethyl maltol, and a compound releasing hydrogen peroxide, in an excipient or a vehicle suitable for application to the skin, mucous membranes or the integuments.

The present invention also relates to a substantially simpler product making it possible to deliver a cosmetic preparation with two constituents without the viscous fluid phases mixing or at least that they only mix when leaving a container such as a flexible tube or bottle, by pressure.

The present invention has been achieved by forming two separate, consistent gels, placed one above the other in the container and having similar rheological properties so as to achieve a simultaneous fluid flow.

This device is particularly applicable to the depigmenting compositions which are the subject of the invention.

In the depigmenting compositions used so far, the technical problem to be solved was to obtain a long-lasting and prolonged action of the tyrosinase inhibitor.

The usual phenolic and especially polyphenolic derivatives (hydroquinone, caffeic acid, chlorogenic acid, arbutoside) are easily oxidizable and therefore their

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 action is fleeting. An increase in the concentration of active ingredient does not solve this problem and can lead to toxicity phenomena.

It was therefore important to find a compound which exhibits a depigmenting action by inhibiting tyrosinase in a prolonged manner, and at the same time a compound which reinforces this depigmenting action in a synergistic manner without altering the properties of the depigmenting molecule.

This problem was solved according to the invention by adding to a cosmetic composition a tyrosinase inhibitor of the type mentioned above, of a derivative releasing hydrogen peroxide, said composition being presented in the form of two separate preparations which do not mix at the time of use and thus retaining each of the constituents in conditions of complete stability.

A large number of literature references are already known which describe devices for dispensing a two-component medicinal or cosmetic preparation, formed from two separate containers and the overall content of which comes to the dispensing orifice by pressure or by actuation of the device. '' a piston or a worm, to mix.

There has been described in particular (EP377.287) a double dispensing device formed of a sachet containing a composition with two components which are separated by a partition placed in a cylindrical part and compressed against the end wall comprising an outlet and a cutting blade, so that the bag is torn and the composition is expelled entirely through the outlet.

We have also described (EP331.617) the production of toothpaste compositions formed from a combination of two components, one being a pigmented gel with a high water content, and the other being a white toothpaste, the formulations of which are different. , in a device which prevents the migration of the colored gel at the interface of the two components.

This separation is obtained by very different gel consistencies.

A process has also been described in document (EP256.012) for intimately mixing two hardly miscible components arranged in two separate storage compartments. By exerting external pressure on the packaging, the

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 components flow into a common container while being thoroughly mixed.

Also described in French patent 2,705,088 is a cartridge system comprising at least two chambers arranged concentrically with respect to each other, each chamber comprising a socket having an outlet orifice, each of these being embedded one inside the other and separated from each other by a wall in the form of a rope.

There are also known metering and mixing devices for at least two pasty components, the distribution means of which are constituted by gear pumps.

In all these devices, it is necessary to use pastes of different viscosities to prevent the different layers from mixing and above all so that the biphasic appearance is preserved despite the pressure exerted on the container.

The process used for producing the compositions according to the invention is substantially simpler and more effective.

As depigmenting active principle, preference is given to Maltol, isomaltol or 5-ethyl Maltol.

As peroxidized compound releasing hydrogen peroxide, we will first name hydrogen peroxide in free form or combined with an inert support, like the combinations hydrogen peroxide / acetanilide or / urea, organic peroxides like benzoyl peroxide , thenoyl peroxide, cumene peroxide; organic persalts like, performiates, peracetates or perbenzoates, mineral peroxide derivatives like percarbonates, perborates, persilicates or perphosphates. Tertiary amine peroxide can also be used. Preferably, hydrogen peroxide and especially hydrogen peroxide at 20 to 100 volumes are used, and particularly preferably hydrogen peroxide at 30 volumes.

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The compositions according to the invention are in the form of two separate fluid preparations of high viscosity which do not mix until the product is delivered.

 The compositions according to the invention are in particular in the form of two gels of equivalent rheology, aqueous or non-aqueous, not or little miscible during or after their preparation and arranged in two parallel or concentric layers, at least one of which has a high viscosity.

 The viscous excipient will be a cetyl alcohol derivative or a carbomer, preferably a pharmaceutical quality such as the acrylic polymer sold under the brand Carbopol 941 or Carbopol 1322 (Goodrich). It can also be a natural gelling product such as Xanthan gum, Guar gum, Gellan gum, chemical derivatives of natural gum such as cationic Guar gum, or cellulose derivatives such as methylcellulose, ethylcellulose, (p -hydroxy ethyl) cellulose, (hydroxy propyl) cellulose, hydroxypropyl methyl cellulose and other similar derivatives.

It is preferable to use Lanette wax and in particular that marketed under the name Lanette C16. The gel also contains emulsifying agents of the surfactant type, stabilizing agents, emollient agents and pH regulating agents.

Suitably the gel containing the tyrosinase inhibitor compound has a lower viscosity of between 400 and 4,000 m Pas. On the contrary, the gel containing the compound releasing the hydrogen peroxide will be of higher consistency.

The preparation can also contain plant extracts, in particular those rich in phenols, polyphenols or tannins, such as for example an extract of scutellaria root or mulberry root, an extract of Aloe ferox or of Reglisse (Glycirrhizha glabra ) or tannic acid itself.

The preparation can also contain one or more hydroxyl acids such as glycolic acid, glucinic acid, muconic acid, malic acid or lactic acid.

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 The preparation can also contain photoprotective agents in particular against UV A and UV B rays. Organic agents such as p-amino benzoic acid, carotenoids or tea extracts, or mineral agents such as micronized titanium dioxide suspended in dimethicone.

The hydrogen peroxide is preferably used in the form of hydrogen peroxide of concentration ranging from 10 to 100 volumes, such as for example hydrogen peroxide at 20 volumes or 30 volumes. It is obviously possible to use hydrogen peroxide in a less concentrated form (at 5 volumes for example), or in a more concentrated form (at 45 volumes for example), on the sole condition that the final preparation is not irritating.

The antibacterial agent used to preserve and prevent bacterial attack is a paraben or a quaternary ammonium salt (cetyl pyridinium or benzododecinium salt). A diazolidinylurea sold under the names Germaben II or III can also be advantageously used.

The preparation can also contain one or more pH regulating agents such as a buffer agent pH 6 - 6.5, or a neutralizing agent such as an alkali metal carbonate or an alkali metal hydroxide. Preferably the pH of the composition is between 5.0 and 6.5 and preferably between 5.10 and 6.0.

The preparation also contains silicone derivatives which improve the texture of the preparation, the smoothness to the touch and spreading, the fluidity of the preparation, such as dimethicone, dimethiconol, simethicone and similar silicones.

The preparation also contains one or more emulsifying agents such as sorbitan stearate or sucrose cocoate. It may also contain one or more co-emulsifying agents, that is to say compounds present in too small doses to be emulsifying but whose weak surfactant action is sufficient to be effective. An example is cetyl phosphate, potassium salt marketed under the name Amphisol K.

The compositions according to the invention can also be added with a dye, a pigment, a perfume or a product giving a pearly appearance.

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 The compositions according to the invention find use in cosmetics to ensure depigmentation of the skin and the integuments as well as in the case of hyperpigmentation or irregular pigmentation.

The compositions according to the invention also find use in dermatology for the treatment of melanocytic hyperactivity and of hyperpigmentation linked to the proliferation of melanocytes. In this regard, mention may be made of the treatment of ephelids or sound spots, solar lentigo and lentigo of old age. Mention will be made in particular of the treatment of pigment spots which appear on the upper face of the hands, in particular in the elderly, on the forearms, and on the face. This manifestation results in hyperpigmentation of the lower layer of the epidermis and in an increase in the number of melanocytes.

To this end, the composition according to the invention will be applied from 1 to 4 times a day on the part concerned for 30 days to 90 days consecutively.

The compositions according to the invention do not show any local toxicity or intolerance. They are not allergenic.

EXAMPLE 1 Preparation of a bilayer cream based on Maltol.

Cream No. 1 Lanette 16 (cetyl alcohol) 2 Incroquat Behenyl TMC (mixture of behenyltrimonium chloride and cetearyl alcohol) 2 Lecinol S-10 (hydrogenated lecithin) 0.30 Amphisol K (potassium cetyl phosphate) 1 Transcutol (ethoxydiglycol) 2.50 Stearyl glycyrrhetinate 0.15 Cetiol OE (dicaprylic ether) 2 Cosmacol ELI (C12-C13 alkyl lactate) 2.50

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DC - 1403 fluid (mixture of dimethiconol and dimethicone) 0.75
Salcare SC96 (mixture of propylene dicaprate
Glycol, polyquaternium-37 and PPG-1 Trideceth-6) 2
Photoprotective complex 5
Propylene Glycol 2 Arlatone 2121 (mixture of sorbitan stearate and Sucrose cocoate) 4 Germaben ## 0.70
Water qs Gluconic Acid 3 Glycolic Acid or Lactic Acid 5 Tannic Acid (Tanlex VB) 2.5 Maltol 2.20 Arbutoside 2 Flower scent 0.30 (Lotus AF3817 scent) Sodium hydroxide qs pH 5.20 Skinone = base depigmenting agent Kojic acid 10 Cream n 2 Hydrogen peroxide at 30 volumes 4 g Water qs 79.38 g EDTA 0.20 g Germaben ## 0.70 g Phosphoric acid 0.015 g Emulsium A (surfactant formed from cetyl alcohol, stearate PEG 75 glyceryl and cetearyl stearate 20 EO) Amphisol K (potassium cetyl phosphate) 0.70 Isononanoyl isononanoate 5 Lanette wax C16 2 Sodium hydroxide at 32% qs pH 5.0

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 EXAMPLE 2 Double-layer cream based on Kojic acid Cream n 1 1 Hydrogen peroxide at 30 volumes 8 Water qs 158.77 g EDTA 0.42 Germaben Il 1.4 Otophosphoric acid 0.03 Emulsium 16 Amphisol K 1.4 Isononanoate isononanoyl 10 Lanette C16 wax 4 33% NaOH 0.147 g The preparation is adjusted to a pH of 5.13 Cream No. 2 Cetyl alcohol 4 Hydrogenated lecithin 0.30 Amphisol K 1 Dicaprylic ether 1 DC - 1401 2 Propylene glycol 2 Kojic acid 10 g EDTA 0.5 g Sodium sulfite 0.3 g Potassium metabisulfite 0.3 g Glycolic Acid 8.5 g Tanlex VB 2 g Grapefruit extract 0.75 g White blackberry extract 3 g Lemon extract in butylene glycol 2.5 g H2O 80.5 g

Claims (16)

 CLAIMS 1. New compositions intended for the depigmentation of the skin in which the depigmenting active principle is reinforced by the addition of another compound releasing hydrogen peroxide. 2. New compositions intended for depigmentation of the skin according to claim 1, in which the depigmenting active principle is chosen from the group consisting of Kojic acid, 3-methyl Kojic acid, fusaric acid, 5- hydroxy 2-hydroxy methyl y-pyridone, maltol, isomaltol and 5-ethylmaltol. 3. New compositions intended for depigmentation of the skin according to claim 1 or claim 2, in which the compound releasing hydrogen peroxide is chosen from the group consisting of hydrogen peroxide, the combinations of hydrogen peroxide an inert support, organic peroxides, organic persalts, mineral peroxide compounds and peroxide of tertiary amine N-oxide. 4. New compositions according to claims 1 to 3, in which the depigmenting active principle is maltol. 5. New compositions according to claims 1 to 3, in which the depigmenting active principle is 5-ethylmaltol. 6. New compositions according to claims 1 to 5, in which the compound releasing hydrogen peroxide is hydrogen peroxide concentrated to 20 to 100 volumes. 7. New compositions according to claims 1 to 6, in which the compound releasing hydrogen peroxide is hydrogen peroxide at 30 volumes. 8. New compositions according to claims 1 to 7, characterized in that they are in the form of two separate fluid preparations, of high viscosity, arranged in two layers which do not mix until the time of delivery. <Desc / Clms Page number 10>  9. New compositions according to claim 8, characterized in that they are in the form of two equivalent rheology gels, aqueous or non-aqueous, not very miscible or immiscible during or after their preparation. 10. New compositions according to claim 8 or claim 9, wherein the fluid preparations are arranged in two parallel or concentric layers. 11. New compositions according to one of claims 8 to 10, in which at least one of the fluid preparations has a high viscosity. 12. New compositions according to one of claims 1 to 11, characterized in that they also contain plant extracts, in particular those rich in phenols, polyphenols or tannins. 13. New compositions according to one of claims 1 to 12, characterized in that they contain one or more pH regulating agents. 14. New compositions according to one of claims 1 to 13, characterized in that they also contain silicone derivatives. 15. New compositions according to one of claims 1 to 14, characterized in that they contain one or more emulsifying agents and optionally one or more co-emulsifying agents. 16. New compositions according to one of claims 1 to 15, characterized in that they also contain an additive chosen from the group formed by dyes, pigments, perfumes and products giving a pearly appearance.