WO2014132217A1

WO2014132217A1 - Composition comprising rebaudioside a and a substituted cellulose

Info

Publication number: WO2014132217A1
Application number: PCT/IB2014/059301
Authority: WO
Inventors: Jérémy BERTHELOT; Chantal JOUY; Véronique Chevalier
Original assignee: L'oreal
Priority date: 2013-02-28
Filing date: 2014-02-27
Publication date: 2014-09-04

Abstract

The present invention relates to a composition, preferably a cosmetic composition, comprising, in a cosmetically acceptable medium, rebaudioside A and at least one substituted cellulose selected from hydroxyalkylcelluloses and alkylcelluloses. The invention also relates to a process for stabilizing rebaudioside A in aqueous phase in a composition, to a kit and also to cosmetic treatment processes for stimulating, restoring or regulating the metabolism of skin melanocytes, for preventing, reducing and/or treating a skin complexion impairment, for lightening the skin, for stimulating, restoring or regulating the metabolism of skin cells or semi-mucous membrane cells, and for preventing and/or treating the signs of ageing of the skin or semi-mucous membranes.

Description

"Composition comprising rebaudioside A and a substituted cellulose"

The present invention relates to the cosmetic field, and more particularly to a process for stabilizing a cosmetic active agent, rebaudioside A, in aqueous phase.

The present invention also relates to novel compositions, preferably cosmetic compositions, comprising the said active agent, and also to cosmetic treatment processes.

The stabilization of cosmetic active agents that are soluble in cosmetic solvents and especially in water is a recurrent problem.

The reason for this is that, in the case of instability of the active agents, the cosmetic qualities of the composition are generally modified. This may be reflected by cloudiness of the composition, by yellowing of the composition, especially if its preparation process comprises a heating phase, by the development of odour, or by a less smooth appearance of the composition if it is intended for topical application, or even phase separation. The composition may also show a loss of efficacy.

In addition, it is essential for cosmetic compositions of this type to be stable over a broad temperature range. Specifically, in the course of its duration of use, the product may be exposed to temperatures ranging from -20°C to +45°C minimum depending on the climatic, storage and/or transportation conditions.

For example, active agents which exist in several polymorphic forms, i.e. in the form of several crystalline states having different arrangements and/or conformations of molecules in the crystal lattice, may be particularly unstable in aqueous media.

More precisely, the active agent rebaudioside A (also known as Reb A), which is a steviol glycoside derivative, extracted from Stevia, is a polymorphic molecule existing in several commercial forms as indicated below.

Document US 2011/01 11115 describes certain polymorphic forms of rebaudioside A and also processes for preparing them.

Rebaudioside A is an active agent derived from the agrifood industry where it is especially used for its strong sweetening power and its anti-hyperglycaemiant properties.

Furthermore, it has been shown that this active agent has cosmetic applications as regards antiageing, antioxidant and bleaching and/or lightening of the skin.

Now, it turns out that the thermodynamically stable form of Reb A generally has low solubility in cosmetic solvents. In order to improve the formulation of Reb A, a process for transforming this active agent into a water-soluble form was proposed, starting from a pre-existing process which consists essentially in heating to a temperature of about 90°C or more, in the presence of water and under a sufficient pressure so as to prevent boiling, as described in patent application WO 2010/118218.

However, this form is very sparingly stable since it recrystallizes.

There is thus a need to prepare novel cosmetic compositions comprising rebaudioside A that is water-soluble while at the same time remaining stable over time and at temperatures above room temperature, for example up to at least 45°C, and which, of course, conserves its cosmetic properties.

There is also a need to provide a process for stabilizing rebaudioside A in aqueous phase in a cosmetic composition.

The aim of the present invention is to satisfy these needs.

The Applicant has found, unexpectedly and advantageously, that the introduction of a substituted cellulose into a composition comprising rebaudioside A dissolved in aqueous phase can prevent or limit its recrystallization over time.

Thus, according to a first of its aspects, a subject of the invention is a composition, preferably a cosmetic composition, comprising, in a cosmetically acceptable medium, rebaudioside A and at least one substituted cellulose.

Namely, a subject of the invention is a composition, preferably a cosmetic composition, comprising, in a cosmetically acceptable medium, rebaudioside A which is present in an amount of from 0.5% to 20% by weight relative to the total weight of the composition and at least one substituted cellulose which is chosen from hydroxyalkylcelluloses and alkylcelluloses.

Advantageously, this composition is applied topically.

According to another of its aspects, a subject of the invention is a composition, preferably a cosmetic composition, comprising, in a cosmetically acceptable medium, rebaudioside A and at least one polymer of polyvinyl alcohol type comprising at least units of formula (I):

(I) and optionally units of formul

OCOCH, preferably in which the units of formula (II) are present in a maximum amount of 5 mol% relative to the final polymer.

The Applicant has found, unexpectedly and advantageously, that the introduction of a polymer of polyvinyl alcohol type into a composition comprising rebaudioside A dissolved in aqueous phase can prevent or limit its recrystallization over time.

Advantageously, a subject of the invention is a composition, preferably a cosmetic composition, comprising, in a cosmetically acceptable medium, Rebaudioside A, said Rebaudioside A being present in a content of from 0.5% to 20 % by weight relative to the total weight of the composition, and at least one polymer of polyvinyl alcohol type comprising at least units of formula (I):

and optionally units of formul

OCOCH, preferably in which the units of formula (II) are present in a maximum amount of 5 mol% relative to the final polymer, said polymer of polyvinyl alcohol type being present in a content of from 0.001 to 10 % by weight relative to the total weight of the composition.

Advantageously, this composition is applied topically. According to another of its aspects, the present invention relates to the use of the said at least one cellulose for stabilizing rebaudioside A in aqueous phase especially in a composition, preferably a cosmetic composition.

According to another of its aspects, the present invention relates to the use of the said at least one polymer of polyvinyl alcohol type for stabilizing rebaudioside A in aqueous phase especially in a composition, preferably a cosmetic composition.

The aqueous phase may be an aqueous solution, i.e. a solution comprising water, or even consisting of water, or alternatively it may be the aqueous phase of a "direct" emulsion (OAV, oil-in-water emulsion) or an "inverse" emulsion (W/O, water-in- oil emulsion).

According to yet another of its aspects, the present invention relates to a process for stabilizing rebaudioside A in aqueous phase in a composition, preferably a cosmetic composition, comprising at least one step of introducing the said at least one substituted cellulose into a composition comprising rebaudioside A, optionally followed by a step of mixing the composition obtained.

According to yet another of its aspects, the present invention relates to a process for stabilizing rebaudioside A in aqueous phase in a composition, preferably a cosmetic composition, comprising at least one step of introducing the said at least one polymer of polyvinyl alcohol type into a composition comprising rebaudioside A, optionally followed by a step of mixing the composition obtained.

Without wishing to be bound to any theory, it appears that this rebaudioside A- stabilizing property in the cosmetic products helps to prevent crystallization of the said rebaudioside A by inhibiting crystal seeding. The stabilization of rebaudioside A thus ensures its efficacy and especially facilitates its passage through the skin.

According to yet another aspect, the present invention relates to a cosmetic treatment process for stimulating, restoring or regulating the metabolism of skin melanocytes, comprising at least one step of administering, to an individual in need thereof, a composition according to the invention.

According to yet another aspect, the present invention relates to a cosmetic treatment process for preventing, reducing and/or treating a skin complexion impairment, comprising at least one step of administering, to an individual in need thereof, a composition according to the invention. According to yet another aspect, the present invention relates to a cosmetic treatment process for lightening the skin, comprising at least one step of administering, to an individual in need thereof, a composition according to the invention.

According to yet another aspect, the present invention relates to a cosmetic treatment process for stimulating, restoring or regulating the metabolism of skin cells or semi-mucous membrane cells, comprising at least one step of administering, to an individual in need thereof, a composition according to the invention.

According to yet another aspect, the present invention relates to a cosmetic treatment process for preventing and/or treating the signs of ageing of the skin or semi- mucous membranes, comprising at least one step of administering, to an individual in need thereof, a composition according to the invention.

In the context of the present invention, the preferred routes of administration are the topical route or the oral route and advantageously the topical route, i.e. the application of a composition in accordance with the invention directly in contact with the target surface of the skin or of a semi-mucous membrane.

According to yet another of its aspects, the present invention relates to a kit comprising at least one container containing a composition in accordance with the invention, and at least one device arranged to enable the administration of the said composition to an individual, and/or to increase the efficacy of the said composition on an individual, and/or to promote the topical penetration of the said composition on an individual.

Rebaudioside A

The present invention relates to the use of rebaudioside A (Reb A, also known as "RA" or β-D-glucopyranosyl 13-[(2-0-P-D-glucopyranosyl-3-0-P-D-glucopyranosyl-P- D-glucopyranosyl)oxy]kaur-16-en-18-oate) as main active agent. It is a diterpene glycoside that is more particularly found in extracts of Stevia.

Reb A is represented by formula (I):

The present invention naturally employs an effective amount of Reb A so as to obtain the desired effect. This effective amount may vary with regard to various parameters which are in particular the indication targeted, the characteristics of the individual treated, the galenical form adopted, the nature of the formulation excipients or the presence of additional active agent(s).

For the purposes of the present invention, the term "effective amount" means a sufficient and necessary amount of a given active agent to exert the desired effect and in particular the antiageing and/or antioxidant and/or bleaching effect for the cosmetic application.

Such an amount may be determined by any method known to a person skilled in the art, for example by means of in vitro, ex vivo or in vivo trials, such as clinical trials.

Advantageously, the amount of Reb A ranges from 0.01% to 20% by weight, preferably from 0.05% to 10% by weight, especially from 0.1% to 10% by weight and more preferably from 0.5% to 5% by weight relative to the total weight of the composition.

More advantageously, the amount of Reb A ranges from 0.5% to 10% by weight, especially from 0.5% to 5% by weight relative to the total weight of the composition.

According to a preferred embodiment, the main active agent according to the invention, i.e. Reb A, is used in the form of an extract of at least one plant of the Stevia genus.

The use of the main active agent according to the invention in the form of an extract of at least one plant of the Stevia genus is particularly advantageous in that it affords a novel cosmetic active agent of natural origin and thus satisfies an increasing demand from consumers in this direction. The Stevia genus belongs to the family of the Asteraceae, which combines 150 to 240 species of shrubs or aromatic herbs, some of which contain natural sweeteners. The Stevia plants are plants originating from the tropical regions of Latin America.

According to the invention, the extract of a plant from the Stevia genus can be chemically modified (it is then semi-synthetic) but it is preferably natural.

An extract of a plant of the Stevia genus, for the purposes of the present invention, can be prepared from any plant material derived from the said plant or from its cells cultivated according to conventional methods or by in vivo biotechnology or derived from in vitro culturing.

The term "in vivo culturing" means any culturing of conventional type, i.e. in soil in the open air or in a greenhouse, or alternatively without soil.

The term "in vitro culturing" means all the techniques known to those skilled in the art which make it possible to artificially obtain a plant or a plant part. The selection pressure imposed by the physicochemical conditions during the growth of plant cells in vitro makes it possible to obtain a standardized plant material which is available throughout the year, in contrast to plants cultivated in vivo.

An extract of a plant of the Stevia genus used in the present invention may be obtained from any plant material derived from this whole plant or from any part of this plant, for instance the leaves, stems, flowers and flowering tops, seeds, buds and roots, undifferentiated cells or plant stem cells.

Preferably, an extract of a plant of the Stevia genus in accordance with the invention is obtained from the leaves.

Even more preferably, an extract of a plant of the Stevia genus in accordance with the invention originates from a plant of the species Stevia rebaudiana (Bertoni), also known as Eupatorium rebaudianum or " weet leaf .

Such a species is today cultivated in many countries and on continents other than Latin America, in particular in Singapore, Taiwan, Malaysia, South Korea, China, Israel or even Australia.

Preferably, the amount of extract of a plant of the Stevia genus ranges from 0.00001% to 50% by weight, preferably from 0.0001% to 10% by weight and better still from 0.01%) to 4% by weight, relative to the total weight of the said composition. As rebaudioside A that may be used in the present invention, mention may be made especially of the Stevia extract containing 99% of rebaudioside A sold by the company Blue California under the name Good'n sweet™ and also the Stevia extract containing 97% of rebaudioside A sold by the company Chengdu Wagott Pharmaceutical under the name ViaSweet™.

It may also be the Stevia extract fermented by a yeast described in document WO 2003/035090.

The intrinsic properties of the main active agent according to the invention, i.e. Reb A, are such that they allow the use, within a composition according to the invention, of compounds or active agents which normally cannot be used because they are difficult to formulate, dissolve, deliver in a controlled manner or vectorize.

Thus, as indicated above, an extract according to the invention can advantageously be combined with at least one additional active agent chosen from polyols and in particular glycerol and propylene glycol, vitamins, keratolytic and/or desquamating agents, and calmatives, and mixtures thereof.

The term "desquamating agent" especially means compounds that are capable of effecting desquamation by promoting exfoliation, such as β-hydroxy acids, in particular salicylic acid and derivatives thereof (including 5-(n-octanoyl)salicylic acid); a-hydroxy acids, such as glycolic, citric, lactic, tartaric, malic or mandelic acid; urea; gentisic acid; oligofucoses; cinnamic acid; Saphora japonica extract and resveratrol.

The choice and the content of these additional active agents depend in particular on the administration route under consideration, which falls within the competence of a person skilled in the art.

These additional active agents may be present in a composition according to the invention in a content ranging from 0.001% to 50% by weight, preferably ranging from 0.01% to 10% by weight and preferentially ranging from 0.01% to 5% by weight relative to the total weight of the composition comprising them.

Celluloses

The substituted celluloses (or cellulose derivatives) that may be used in accordance with the invention are especially chosen from • hydroxyalkylcelluloses such as hydroxyethylcellulose (also known as HEC), hydroxymethylcellulose, hydroxypropylcellulose (also known as HPC), hydroxybutylcellulose, hydroxyethylmethylcellulose and hydroxypropylmethylcellulose (also known as HPMC),

· alkylcelluloses such as methylcellulose, ethylcellulose and ethylhexy 1 cellul o se .

The composition according to the invention may further comprise at least one substituted cellulose chosen from:

• carboxyalkylcelluloses such as carboxymethylcellulose (also known as CMC),

• quaternized celluloses.

More preferably, the substituted cellulose that is suitable for use in the invention is a hydroxyalkylcellulose, preferably a hydroxy(Ci-C6)alkylcellulose and even more preferentially hydroxyethylcellulose and hydroxypropylmethylcellulose.

Hydroxyethylcellulose is especially sold under the name Cellosize™ (QP and

WP) by the company The Dow Chemical Company and more precisely under the names Cellosize™ HEC QP 15000-H, Cellosize™ HEC QP 300, Cellosize™ HEC QP 30000-H, Cellosize™ HEC QP 40, Cellosize™ HEC QP 4400-H and Cellosize™ HEC QP 52000-H, under the name AEC™ Hydroxyethylcellulose by the company A&E Connock (Perfumery&Cosmetics) Ltd, under the name Alcoramnosan™ by the company Vevy Europe SpA, and under the names Cellosize™ HEC QP and Cellosize™ HEC WP by the company Amerchol Corporation.

Hydroxypropylmethylcellulose is especially sold under the name Metolose™ by the company Shin-Etsu, and more specifically, for example, under the names Metolose™ 60 SH 4000, Metolose™ 60 SH 50, Metolose™ 90 SH 100, Metolose™ 90 SH 4000, Metolose™ 90 SH 15000, Metolose™ 65 SH 50, Metolose™ 65 SH 4000, Metolose™ 60 SH 4000, and Metolose™ 60 SH 5, under the name Methocel™ by the company The Dow Chemical Company, and more specifically, for example, under the names Methocel™ E-3, Methocel™ E-6, Methocel™ E-50, Methocel™ E4M, Methocel™ F50, Methocel™ F4M, Methocel™ K100, Methocel™ K4M and Methocel™ K100M, and under the name Headcel™ by the company Shandong Head, and more specifically, for example, under the names Headcel™ 60HD3, Headcel™ 60HD15, Headcel™ 60HD4000, Headcel^{1 M} 65HD50, Headcel^1M 75HD 100, Headcel^1M 75HD4000, Headcel^{1 M} 75HD15000 and Headcel^1M 75HD 100000.

The substituted celluloses that are suitable for use in the invention have a mass- average molecular weight of between 1000 and 10 000 000 g/mol, preferably between 20 000 and 5 000 000 g/mol and even more preferentially between 50 000 and 3 000 000 g/mol.

The substituted celluloses used according to the invention are present in an amount of from 0.001% to 30% by weight, preferably from 0.01% to 20% by weight and even more preferentially from 0.1% to 10% by weight, relative to the total weight of the composition.

According to a preferred embodiment, the rebaudioside AJ substituted cellulose(s) weight ratio is from 0.0002 to 50 000, preferably from 0.005 to 3000 and even more preferentially from 0.01 to 50.

Polymer of polyvinyl alcohol type

A polymer of polyvinyl alcohol type may also be used in the compositions according to the invention. This polymer comprises at least units of formula (I):

and optionally units of formula (II):

Advantageously, the units of formula (II) are present in the final polymer in an amount of from 0 to 3 mol% and preferably in an amount of from 0.05 mol% to 2 mol%.

According to a particular embodiment, the polymer has a mass-average molecular weight of between 1000 and 1 000 000 g/mol, preferably between 10 000 and 500 000 g/mol and even more preferentially between 50 000 and 400 000 g/mol. When it is present in the composition according to the invention, the amount of polymer of polyvinyl alcohol type is from 0.001% to 50% by weight, preferably from 0.01% to 10% by weight and even more preferentially from 0.1% to 5% by weight, relative to the total weight of the composition.

According to a preferred embodiment, the rebaudioside A/polymer of polyvinyl alcohol type weight ratio is from 0.0002 to 50 000, preferably from 0.005 to 3000 and even more preferentially from 0.01 to 50.

Among the polymers of vinyl alcohol type, mention may be made especially of:

- the products sold under the name Alcohol Polivinilico® and more specifically the product Alcohol Polivinilico® 72000 by the company Merck;

- the products sold under the name Celvol® or Selvol® by the company Sekisui Specialty Chemicals, and in particular:

o Celvol 205 PV Alcohol®, and

o Selvol 540 Polyvinyl Alcohol®;

- the products sold under the name Elvanol® by the company Dupont, and in particular:

o Elvanol® 50-42, and

o Elvanol® 71-30;

- the products sold under the name Rhodoviol® by the company Rhodia Chimie, and in particular:

o Rhodoviol® 25/140, and

o Rhodoviol® 4/125.

Uses

Imbalances in the metabolism of the melanocytes, in particular related to age, can be the cause of various aesthetic disorders of the skin. These disorders can affect the complexion and/or the pigmentation of the skin and furthermore occur in an exacerbated fashion in elderly skin.

The defects of pigmentation of the skin can be marked by the presence of more or less extensive surface skin blemishes, having a darker or lighter colour than the normal colour of the skin of the individual which surrounds the said skin blemishes. The skin pigmentation defects especially encompass melasma (pregnancy mask) and lentigines, including liver spots and actinic lentigo.

In particular, the melasma or chloasma under consideration in the invention can be triggered by exposure to UV rays, or can occur on photosensitive skin, photoallergic skin or skin subject to a phototoxicity reaction.

Lentigines arise in the form of hyperpigmented skin blemishes which can appear at any age and are usually darker and more extensive than freckles. Lentigines encompass in particular (i) solar lentigines, which appear in light-skinned individuals on skin regions exposed for a long time to the sun, (ii) lentiginous pigmentations resulting from skin therapies involving UV-A radiation (320-400 nanometres - also known as PUVA therapy), (iii) multiple lentigines, especially on the palms, soles of the feet, mucous membranes or unexposed skin, or also (iv) lentigines affecting the lips, vulva or penis.

The skin pigmentation defects also encompass hyperpigmentation conditions resulting from thermal burns or acne-type hyperpigmentation, or resulting from insect stings, cuts and other mechanical skin trauma, in particular during shaving, and pseudofolliculitis due to bodily hairs becoming ingrown resulting from shaving or depilation.

A skin pigmentation defect that is more particularly under consideration in the invention may be chosen from melasma, chloasma, lentigines, senile lentigo, hyperpigmentations caused by an abrasion and/or a burn and/or a scar, hyperpigmentations or any other pigmentary lesions.

The present invention may also be used to prevent, reduce and/or treat a pregnancy mask.

An active agent of the invention may be used more particularly to lighten or whiten the skin.

The present invention also relates to aesthetic disorders of the skin affecting the skin complexion.

Thus, the invention may suitably be used for preventing, reducing and/or treating a lack of uniformity of the skin complexion, or even for improving the skin complexion, in particular of elderly skin.

The invention advantageously promotes and maintains the radiance of the skin complexion and in particular a uniform complexion. According to one embodiment, a use according to the invention makes it possible to treat and/or prevent an impairment in the radiance of the complexion or a loss of radiance of the skin complexion. A use according to the invention can give the skin a uniform, luminous, more radiant, or even more glowing, complexion indicative of skin in good health.

The invention can advantageously prevent, reduce and/or treat a muddy skin complexion, a dull skin complexion, a non-uniform skin complexion or skin imperfections chosen in particular from spots, dry patches, dyschromias or blackheads or also prevent, reduce and/or treat a waxen, sallow, greyish or ashen, or even sickly, complexion.

Rebaudioside A may more preferentially be used for preventing, reducing and/or treating an impairment in the skin complexion chosen from an impairment in the radiance of the skin complexion, a muddy skin complexion, a dull skin complexion, a nonuniform skin complexion, spots, dry patches, dyschromias and/or blackheads.

According to one embodiment, a skin more particularly under consideration in the present invention may be elderly skin.

The present invention relates to the entire surface of an individual's skin. Preferably, the present invention may be used with regard to regions of skin more regularly exposed to the sun, to UV radiation or to external stress factors, such as pollution, irritation due to rubbing, or cigarette smoke. In particular, the present invention may advantageously be used with regard to the skin of the hands, face or neckline.

Composition

Advantageously, the active agent according to the invention, namely Reb A, optionally as a mixture with other additional active agent(s), may be formulated in a cosmetic or dermatological composition.

Preferably, a composition of the invention is a cosmetic composition.

According to a first embodiment variant, the main active agent according to the invention is intended for topical administration.

Thus, the compositions comprising the main active agent according to the invention may be in the form of products for caring for the skin or semi-mucous membranes, such as a protective, treatment or care composition for the face, for the lips, for the hands, for the feet, for the anatomical folds or for the body (for example, day cream, night cream, makeup-removing cream, makeup base, antisun composition, protective or care body milk, aftersun milk, skincare or scalp-care lotion, gel or foam, serum, powder, mask, artificial tanning composition, aftershave composition, hair composition, product for the region of the armpits, or hygiene and cleansing product.

According to a second embodiment variant, the main active agent according to the invention is intended for oral administration.

Thus, the composition of the invention may be in any suitable form, particularly in the form of a drinkable solution, a drink, a tablet, a gel capsule, a wafer capsule, or alternatively a nutritional food or a nutritional supplement.

According to a third embodiment variant, the main active agent according to the invention is intended for intracutaneous administration, such as intradermal or subcutaneous administration. This administration may, for example, be performed by means of a device for intracutaneous injection (syringe, implant or reservoir and microneedles) or alternatively an ultrasound or iontophoresis device, or even a light or thermal device. Such an administration may also be performed by mesotherapy.

The intracutaneous use of a composition of the invention is to be distinguished from a surgical operation and is targeted only at exerting a surface treatment of the skin for aesthetic, protective, repair or comfort purposes. In other words, in the present invention, the intracutaneous administration route is reflected only by superficial penetration of the skin and thus does not come within any medical, surgical or therapeutic context.

It is alternatively possible, intracutaneously, to favour administration using a topical patch.

Preferably, the main active agent according to the invention, namely Reb A, is intended for topical administration, i.e. for administration by application to the surface of the keratin material under consideration.

Preferably, the said main active agent in accordance with the invention, when it is present in a composition, may be formulated in a physiologically acceptable medium.

For the purposes of the present invention, the term "physiologically acceptable medium" is intended to denote a medium that is suitable for the topical, oral or intracutaneous, such as intraepidermal, intradermal or subcutaneous, administration of a composition. A physiologically acceptable medium is preferentially a cosmetically or dermatologically acceptable medium, i.e. a medium that has no unpleasant odour or appearance and that is entirely compatible with the administration route under consideration.

When the composition is intended for topical administration, i.e. for administration by application to the surface of the keratin material under consideration, such a medium is considered to be physiologically acceptable when it does not cause any stinging, tightness or redness unacceptable to the user.

When the composition is intended for oral administration, such a medium is considered to be physiologically acceptable when it does not cause any digestive intolerance.

Moreover, when the composition is intended for intracutaneous administration, such a medium is considered to be physiologically acceptable when it does not cause any reaction experienced as unpleasant by the user, for example stinging, tightness or redness, or even does not cause any inflammatory, allergic, oedematous or pruritic reactions.

The composition according to the invention may be in any galenical form normally used in cosmetics and dermatology.

It may especially be in the form of an aqueous solution, aqueous/alcoholic solution or oily solution, which is optionally gelled, a dispersion of the lotion type, which is optionally a two-phase or three-phase lotion, an oil-in-water or water-in-oil or multiple emulsion, an aqueous gel, a dispersion of oils in an aqueous phase, in particular with the aid of spherules, it being possible for these spherules to be polymer particles or, better still, lipid vesicles of ionic and/or nonionic type, or alternatively in the form of a powder, a serum, a paste, a solid cake which can disintegrate by rubbing an applicator, or a soft or rigid stick which can melt on the skin or semi-mucous membranes. It may be of solid, pasty or more or less fluid liquid consistency.

With regard to the galenical form under consideration, the active agent according to the invention may be formulated with the usual constituents.

As non-limiting illustrations of these usual components, mention may be made in particular of water, solvents, volatile or non-volatile oils, in particular as described in detail below, waxes, pigments, fillers, surfactants, gelling agents, preserving agents, dyestuffs, antioxidants and UV-screening agents, and mixtures thereof. Needless to say, a person skilled in the art will take care to select this or these optional additional compound(s), and/or the amount thereof, such that the advantageous properties of the main active agent according to the invention are not, or are not substantially, adversely affected by the envisaged addition, and such that the properties of the compositions resulting therefrom are compatible with the favoured route of administration.

A composition according to the invention may advantageously be in the form of an emulsion, obtained especially by dispersing an aqueous phase in a fatty phase (W/O) or a fatty phase in an aqueous phase (OAV), of liquid or semi-liquid consistency of the milk type, or of soft, semi-solid or solid consistency of the cream or gel type, or alternatively a multiple emulsion (W/OAV or OAV/O). These compositions are prepared according to the usual methods.

Thus, a composition according to the invention may advantageously comprise from 0.1% to 99.9% by weight and preferably from 30% to 95% by weight of water, relative to the total weight of the said composition.

A composition according to the invention may also advantageously comprise at least one fatty phase that is liquid at room temperature and atmospheric pressure.

The amount of oily phase present in the compositions according to the invention may range, for example, from 0.01% to 90% by weight and preferably from 0.1% to 50% by weight relative to the total weight of the composition.

As examples of oils that may be used in the composition according to the invention, mention may be made of hydrocarbon-based oils of animal origin, hydrocarbon- based oils of plant origin, synthetic esters and ethers, especially of fatty acids, linear or branched hydrocarbons of mineral or synthetic origin, fatty alcohols and silicone oils, and mixtures thereof.

Other fatty substances that may be present in the oily phase are, for example, waxes and fatty acids comprising from 8 to 30 carbon atoms, such as stearic acid, lauric acid, palmitic acid and oleic acid. These fatty substances may be chosen in a varied manner by a person skilled in the art in order to prepare a composition having the desired properties, for example in terms of consistency or texture. Similarly, a composition according to the invention may also comprise at least one dyestuff chosen, for example, from pigments, nacres, dyes and effect materials, and mixtures thereof.

These dyestuffs may be present in a content ranging from 0.01% to 50% by weight and preferably from 0.01% to 10% by weight relative to the total weight of the composition.

A composition according to the invention may also comprise at least one filler, especially in a content ranging from 0.01% to 50% by weight and preferably ranging from 0.01% to 30% by weight, relative to the total weight of the composition. These fillers may be mineral or organic and their choice falls within the competence of a person skilled in the art.

A composition according to the invention, preferably a cosmetic composition, comprising, in a cosmetically acceptable medium, rebaudioside A and at least one substituted cellulose as defined previously, may also comprise at least one polymer of polyvinyl alcohol type as defined previously.

As indicated previously, the administration of the active agent under consideration according to the invention may be performed via the use of a device adjusted to the mode of administration under consideration, i.e. topical, oral or intracutaneous administration. The choice of such devices, made in particular from the viewpoint of the type of administration route favoured, falls within the general knowledge of a person skilled in the art.

Besides the devices already described above, the following may also be considered with regard more particularly to intracutaneous administration:

- devices for direct topical delivery or for delivery by means of a specific applicator, for instance intracutaneous microinjections, or simple or iontophoretic patches;

- electrical, electromagnetic or magnetic devices which enable physical stimulation simultaneously with the application of the said composition at the application site;

- devices for supplying heat and/or cold, thus modifying the electrical signals at certain receptors, for instance the Derm-Ice^® device; and

- devices for supplying light, activating or inhibiting certain enzymatic systems. In the last two alternatives, the device contributes towards stimulating the efficacy of the active agent according to the invention at the administration site under consideration.

Thus, the present invention is also directed towards a kit comprising at least one container containing a composition comprising Reb A in accordance with the invention and at least one device suitable for administering the said composition to an individual and especially as described above.

The present invention relates to a cosmetic treatment process for stimulating, restoring or regulating the metabolism of melanocytes, especially aged melanocytes of the skin or semi-mucous membranes, comprising at least one step of administering, to an individual in need thereof, a composition in accordance with the invention.

According to yet another of its aspects, the present invention is directed towards a cosmetic treatment process for lightening the skin, comprising at least one step of administering, to an individual in need thereof, a composition in accordance with the invention.

According to yet another of its aspects, the present invention relates to a cosmetic treatment process for preventing, reducing and/or treating a skin complexion impairment, comprising at least one step of administering, to an individual in need thereof, a composition in accordance with the invention.

According to yet another of its aspects, the present invention also relates to a cosmetic treatment process for stimulating, restoring or regulating the metabolism of skin cells, in particular of fibroblasts, comprising at least one step of administering, to an individual in need thereof, a composition in accordance with the invention.

According to yet another of its aspects, the present invention also relates to a cosmetic treatment process for preventing and/or treating the signs of ageing of the skin, comprising at least one step of administering, to an individual in need thereof, a composition in accordance with the invention.

A cosmetic process according to the invention may be performed daily, for example at a rate of a single administration per day or of an administration split into two or three times per day, for example once in the morning and once in the evening. Throughout the description, including the claims, the term "comprising a" should be understood as being synonymous with "comprising at least one", unless otherwise mentioned.

The terms "between... and..." and "ranging from... to... " should be understood as being limits inclusive, unless otherwise mentioned.

The examples and figures that follow are presented as non-limiting illustrations of the invention. The percentages are expressed by weight of starting materials. The compounds are, depending on the case, cited as the chemical names or as the CTFA names (International Cosmetic Ingredient Dictionary and Handbook).

Examples

Example 1

Stabilizing effect of hydroxyethylcellulose (HEC) on Reb A

Various test samples in gel form are prepared in 10 ml bottles closed with a leaktight stopper.

Insofar as, when Reb A is conventionally placed at 2% in water, it is not totally dissolved and, furthermore, there is generally total reprecipitation of the Reb A after a few hours, it is preferred to perform the dissolution at 2% with the process of heating at 90°C as described in Example 5 of WO 2010/118218.

Specifically, in this case, Reb A is totally in solution at TO.

A control bottle comprising Reb A sold under the name ViaSweet™ by the company Chengdu Wagott Pharmaceutical at 2% in water is prepared.

A bottle comprising Reb A (identical to that used in the control bottle) at 2% in water into which has been placed hydroxyethylcellulose (HEC) sold under the name Natrosol 250 HHR PC by the company Ashland at 1% is also prepared.

Several comparative tests are then developed, for which each of the bottles comprises Reb A (identical to that used in the control bottle) at 2% and an additive at 1% as indicated in the table below.

The compositions of each bottle are observed with the naked eye in order to determine their limpidity at TO + 24h, TO + 2 weeks (named hereinbelow T + 2W), TO + 2 months (named hereinbelow TO + 2M), TO representing the initial time which corresponds to the moment at which the additive is introduced into the bottle already comprising the Reb A.

It may be estimated that the composition is stable up to a maximum turbidity value of 30.

To facilitate the observation with the naked eye, the bottles are placed before a panel on which are drawn lines in various colours, namely red, white, blue, yellow and black.

The turbidity measurements are taken at room temperature (RT) and/or at 45°C and are collated in the table below.

Additive Additive Macroscopic and microscopic appearance content

TO +24h T0 + 2W T0 + 2M wt%

RT 45°C RT 45°C

Control (water) transparent Crystals Crystals Large crystals precipitate

Low Mw HMPC 1%

transparent - no visible crystals

HEC (720KD) 1% Slight veil - no transparent - no visible crystals visible crystals

HEC (1300KD) 1% transparent - Slight veil

no visible crystals

PVP (1300KD) 1% transparent Crystals veil visible crystals

++ +++

PVP (40KD) 1% transparent Crystals Visible Visible

++ crystals ++ crystals +++

Acrylamido- 1% Crystals + Crystals ++ Crystals + Visible

propanesulfonic crystals ++ acid copolymer

(Hostacerin

AMPS from

Clariant)

It is found that at room temperature the compositions according to the invention are transparent (HEC or HMPC), whereas the comparative compositions are not.

Thus, it is deduced from the visual results (cloudy or clear appearance) that the introduction of HEC or HMPC makes it possible to conserve a gel that is clear or slightly veiled but with no crystals even after a duration of two months, whether at room temperature or at 45°C.

Specifically, the other additives tested and the control (water) have no stabilizing effect on Reb A, or even may bring about its destabilization.

Consequently, it is demonstrated that the substituted celluloses can stabilize Reb A in aqueous phase. This phenomenon is explained by the inhibition of crystallization, i.e. the inhibition of seeding of Reb A crystals.

Example 2 Compositions

The following composition was prepared:

The composition is stable and shows no recrystallization of the Reb A.

Example 3

Stabilizing effect of polyvinyl alcohol (PVA) on Reb A

When Reb A is conventionally placed at 2% in water, it is not totally dissolved and, furthermore, there is generally total reprecipitation of the Reb A after a few hours. So, it is preferred to perform the dissolution at 2% with the process of heating at 90°C as described in Example 5 of WO 2010/1 18218.

Specifically, in this case, the Reb A is totally in solution at TO and has not yet totally reprecipitated after a week. A control bottle comprising Reb A sold under the name ViaSweet™ by the company Chengdu Wagott Pharmaceutical at 2% in water is prepared.

A bottle comprising Reb A (identical to that used in the control bottle) at 2% in water into which has been placed polyvinyl alcohol sold under the name Selvol 540 Polyvinyl Alcohol® by the company Sekisui Specialty Chemicals at 1% is also prepared.

The compositions of each bottle are observed with the naked eye in order to determine their limpidity at TO + 24h, and TO + 2 weeks (named hereinbelow TO + 2W), TO representing the initial time which corresponds to the moment at which the additive is introduced into the bottle already comprising the Reb A.

Certain turbidity measurements are taken at room temperature (RT) and/or at 45°C and are collated in the table below.

The compositions according to the invention are transparent, whereas the comparative compositions are not always at TO+2 weeks.

Thus, it is deduced from the visual results (cloudy or clear appearance) that the introduction of PVA makes it possible to conserve a gel that is clear after a duration of two weeks, whether at room temperature or at 45°C.

Consequently, it is demonstrated that PVA can stabilize Reb A in aqueous phase. This phenomenon is explained by the inhibition of crystallization, i.e. the inhibition of seeding of Reb A crystals.

Example 4

Compositions

The following composition was prepared:

Phase US INCI Name Concentration

A Glyceryl stearate (and) 2.5

PEG- 100 stearate (Simulsol 165 from

SEPPIC)

A PEG-40 stearate (Tego Acid S40 P 2.5 from Evonik Goldschmidt)

A Cetyl alcohol 1

A Stearyl alcohol 1

A Hydrogenated polyisobutene 5

(Parleam from NOF Corp.)

B Water 50.4

B Caprylyl glycol (199602) 0.5 Hydrolite CG from Symrise

B Polyvinyl alcohol (Selvol 540 1

Polyvinyl Alcohol from Sekisui

Specialty Chemicals)

B Phenoxyethanol 0.5 Phase US INCI Name Concentration

C Isohexadecane (from Ineos) 15

C Carbomer (Carbopol 981 Polymer 0.3

from Lubrizol)

D Triethanolamine 0.3

E Water 18

E Eupatorium rebaudianum Leaf Extract 2

97 % WAV

The composition is stable and shows no recrystallization of the Reb A.

Claims

1. Composition, preferably a cosmetic composition, comprising, in a cosmetically acceptable medium, rebaudioside A which is present in an amount of from 0.5% to 20% by weight relative to the total weight of the composition and at least one substituted cellulose which is chosen from hydroxyalkylcelluloses and alkylcelluloses.

2. Composition according to Claim 1 , in which the substituted cellulose has a mass-average molecular weight of between 1000 and 10 000 000 g/mol, preferably between 20 000 and 5 000 000 g/mol and even more preferentially between 50 000 and 3 000 000 g/mol.

3. Composition according to any one of the preceding claims, in which the said substituted cellulose is a hydroxyalkylcellulose chosen from hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxybutylcellulose, hydroxyethylmethylcellulose and hydroxypropylmethylcellulose.

4. Composition according to any one of the preceding claims, in which the said substituted cellulose is present in an amount of from 0.001% to 30% by weight, preferably from 0.01% to 20% by weight and even more preferentially from 0.1% to 10% by weight relative to the total weight of the composition.

5. Composition according to any one of the preceding claims, in which the rebaudioside A is present in an amount of from 0.5% to 10% by weight and preferably from 0.5% to 5% by weight relative to the total weight of the composition.

6. Composition according to any one of the preceding claims, in which the rebaudioside A/substituted cellulose(s) weight ratio is from 0.0002 to 50 000, preferably from 0.005 to 3000 and even more preferentially from 0.01 to 50.

7. Composition according to any one of the preceding claims, comprising at least one additional active agent chosen from polyols and in particular glycerol and propylene glycol, vitamins, keratolytic and/or desquamating agents, and calmatives, and mixtures thereof

8. Use of at least one substituted cellulose for stabilizing rebaudioside A in aqueous phase in a composition, preferably a cosmetic composition.

9. Process for stabilizing rebaudioside A in aqueous phase in a composition, preferably a cosmetic composition, comprising at least one step of introducing at least one substituted cellulose, into a composition comprising rebaudioside A, optionally followed by a step of mixing the composition obtained.

10. Cosmetic treatment process for stimulating, restoring or regulating the metabolism of skin melanocytes, comprising at least one step of administering, to an individual in need thereof, a composition as defined in Claims 1 to 7.

11. Cosmetic treatment process for preventing, reducing and/or treating a skin complexion impairment, comprising at least one step of administering, to an individual in need thereof, a composition as defined in Claims 1 to 7.

12. Cosmetic treatment process for lightening the skin, comprising at least one step of administering, to an individual in need thereof, a composition as defined in Claims 1 to 7.

13. Cosmetic treatment process for stimulating, restoring or regulating the metabolism of skin cells or semi-mucous membrane cells, comprising at least one step of administering, to an individual in need thereof, a composition as defined in Claims 1 to 7.

14. Cosmetic treatment process for preventing and/or treating the signs of ageing of the skin or semi-mucous membranes, comprising at least one step of administering, to an individual in need thereof, a composition as defined in Claims 1 to 7.

15. Process according to any one of Claims 10 to 14, in which the administration step is a step of topical application or oral administration.

16. Kit comprising at least one container containing a composition as defined in Claims 1 to 7 and at least one device arranged to enable the administration of the said composition to an individual, and/or to increase the efficacy of the said composition on an individual, and/or to promote the topical penetration of the said composition on an individual.