WO2003059314A1

WO2003059314A1 - Use of methyl glycine diacetic acid or the derivatives thereof as an exfoliant

Info

Publication number: WO2003059314A1
Application number: PCT/FR2002/004462
Authority: WO
Inventors: Elisabeth Picard-Lesboueyries; Dominique Bernard
Original assignee: L'oreal
Priority date: 2002-01-17
Filing date: 2002-12-19
Publication date: 2003-07-24
Also published as: FR2834635A1; AU2002364471A1

Abstract

The invention relates to the cosmetic use of at least one compound of formula (I) in a cosmetic composition comprising an acceptable physiological environment, which is used to favor exfoliation of the skin and/or stimulate renewal of the epidermis. The compound of said formula (I) can therefore be used for cosmetic purposes to prevent or treat dry skin and/or signs of skin aging and/or skin pigmentation.

Description

Use of methyl glycinediacetic acid or its derivatives as desquamating agent

The invention relates to the cosmetic use of methylglycine diacetic acid or its derivatives, as agents intended to promote the peeling of the skin and / or to stimulate epidermal renewal.

It relates in particular to the use of these compounds for cosmetic purposes, to prevent or treat dry skin and / or cutaneous signs of aging and / or pigmentation of the skin.

Exfoliation is a natural phenomenon linked to the fact that the epidermis, which constitutes the upper layer of the skin, is constantly regenerating.

The human epidermis is made up of several layers of cells in which there are mainly four types of cells: keratinocytes, the vast majority, melanocytes, Langerhans cells and erkel cells. The distribution of these cells in several superimposed layers explains the stratified nature of the epidermis.

The epidermis is conventionally divided into a basal layer of keratinocytes which constitutes the germinal layer of the epidermis, a so-called thorny layer consisting of several layers of polyhedral cells arranged on the germ cells, a so-called granular layer consisting of flattened cells containing inclusions distinct cytoplasmic, keratohyaline grains, and finally an upper layer called the stratum corneum (or stratum corneum), consisting of keratinocytes at the terminal stage of their differentiation called corneocytes. Corneocytes are mummified, anucleated cells which are derived from keratinocytes and are eliminated by peeling. This surface loss is compensated for by the migration of cells from the basal base to the surface of the epidermis. It is the perpetual renewal of the epidermis. Forced elimination of the stratum corneum accelerates renewal and helps fight skin aging.

The corneocytes are mainly composed of a fibrous matrix containing cytokeratins, surrounded by a very resistant structure 15 nm thick, called the horny or comified envelope. The stack of these corneocytes constitutes the stratum corneum which is responsible for the barrier function of the epidermis. During the normal process the most superficial corneocytes detach from the surface of the epidermis.

Intercellular structures derived from desmosomes, called corneosomes or corneodesmosomes, have been described in the stratum corneum. Recent studies have shown their major importance in intercorneocyte cohesion as well as in the scaling process.

Comeodesmosine, further characterized in patent application EP-A-0 972 042, is a protein of the stratum corneum of the epidermis, involved in intercorneocyte cohesion and constitutive of corneodesmosomes.

In the stratum corneum, there is a close correlation between cell dissociation and the proteolysis of certain corneodesmosomal components such as desmoglein I and comeodesmosine. Several serine proteases of the trypsin or chymotrypsin type seem to be involved in the proteolysis of corneodesmosomes, such as in particular proteases of the Chymotrypsin-like or Trypsin-like type (Lundstrδm A., Egelrud T., The Journal of Investigative Dermatology; 1988, 91 : 340-343 and 1990, 84: 216-220).

Various agents are known in the prior art intended to combat skin aging, in particular by promoting flaking, that is to say the elimination of "dead" cells located on the surface of the stratum corneum of the epidermis. . This "desquamating" property is also called, often wrongly, keratolytic property.

Thus, US Pat. No. 4,603,146 describes the use of retinoic acid and its derivatives in cosmetic compositions, with a view to combating skin aging.

Furthermore, numerous patents and publications (see for example application EP-A-413,528) as well as numerous commercial cosmetic compositions teach the use of α-hydroxy acids such as lactic acid, glycolic acid or else citric acid to treat skin aging. Finally, β-hydroxy acids and more especially salicylic acid and its derivatives are known for their flaking properties (see documents WO-A-93/10756 and US 4,767,750).

The fact remains that the desire to maintain a youthful appearance always leads to the constant search for new compounds and / or new compositions making it possible to maintain or improve the appearance of the skin.

Certain cosmetic active agents are capable of stimulating the degradation of the proteins of the corneodesmosome and therefore the desquamation, no doubt, as we have seen previously, by promoting the activity of proteases involved in this process.

Along these lines, it has been described in patent application EP-A2-0 852 949 (Shiseido) that derivatives of alpha-amino acids of glycine type promote the degradation of desmogleine (protein of the corneodesmosome).

However, the Applicant has discovered that sodium methyl glycinediacetate is capable of degrading corneodesmosines and therefore finds various applications in cosmetics and dermatology.

Until now, to the knowledge of the Applicant, this compound is in particular marketed as a metal chelating agent intended to be introduced into detergent compositions (detergents), as well as in cosmetic products in order to avoid the phenomena rancidity, color change and precipitation due to heavy metals. Document JP-10 279 987 thus discloses a bactericidal detergent composition comprising derivatives of methyl glycine diacetic acid.

However, it has never been described in the prior art that sodium methyl glycinediacetate can promote desquamation and or stimulate epidermal renewal, in particular by degrading the corneodesmosines, and consequently find applications in the treatment of skin signs of the skin. aging of the skin, dry skin or hyperpigmentation. It is, of course, known to WANG et al., Medical Hypotheses, Vol. 53, n ° 5, pp. 380-382 (1999) that calcium chelators have utility as flaking agents. However, the Applicant has shown that not all chelators have this property, so it was not obvious that the derivatives of methyl glycine diacetic acid, known as calcium chelators (US Pat. No. 5,481,018) , are effective for peeling the skin.

The present invention therefore relates to the cosmetic use of at least one compound corresponding to the following formula (I):

(I) in which:

Ri. R ₂ , R ₃ represent, independently of each other, a hydrogen atom; an alkyl group comprising from 1 to 6 carbon atoms, optionally substituted by a radical -COOR ₄ where R ₄ is an alkyl group comprising from 1 to 4 carbon atoms, or by an amino group, a hydroxy group, an alkoxy group and / or an alkylamino group; or a residue of sugar, or of a salt of such a compound when F ^ and or R ₂ and / or R ₃ represent a hydrogen atom, in a cosmetic composition comprising a physiologically acceptable medium, as agent intended to favor the peeling of the skin and / or to stimulate the epidermal renewal.

The compound of formula (I) above, or at least one of its salts, can thus be used for cosmetic purposes, in a cosmetic composition, as an agent for preventing or treating dry skin, and or cutaneous signs of aging and / or pigmentation of the skin. The invention therefore also relates to these cosmetic uses of the compound of formula (I). Another subject of the invention is a cosmetic treatment process for dry skin and / or cutaneous signs of aging and / or pigmentation of the skin, comprising the topical application to the skin of a composition comprising, in a physiologically medium acceptable, the compound of formula (I) described above or at least one of its salts.

The desquamating compound according to the invention comprises both the individual enantiomers of the compound of formula (I) and the mixtures of these enantiomers.

In formula (I) above, examples of alkyl groups that may be mentioned include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl and hexyl groups.

In addition, by “sugar residue” or sugar residue is meant the fraction of the sugar molecule to which a hydroxyl function is linked, by a covalent bond, when the sugar is in free form. In formula (I) above, an ester-type bond with the sugar is thus obtained. The latter can in particular be chosen from: glucose, galactose, xylose, fucose, mannose or even from polysaccharides. The bond of the type -CO- O- [sugar residue], will be, for example in the case of glucose:

Preferred compounds for use in the present invention are those for which Ri = R ₂ = R ₃ = H and their physiologically acceptable salts, in particular inorganic salts. The particularly preferred compound is sodium methyl glycinediacetate, which is the trisodium salt of the compound of formula (I) corresponding to the above definition. Such a compound is for example available from BASF under the trade name Trilon M ^®. The compound of formula (I) will be present, in the composition containing it, in an amount effective to obtain the desired effect. By way of example, the composition will contain from 0.01 to 40% by weight and, better still, from 0.1 to 10% by weight of compound of formula (I), relative to the total weight of the composition.

The composition according to the invention is generally suitable for topical application to the skin and therefore comprises a physiologically acceptable medium, that is to say compatible with the skin and optionally with the mucous membranes and / or the integuments.

It can be more or less fluid and have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste, a foam. It can optionally be applied to the skin in the form of an aerosol or patch. It can also be in solid form, in particular in the form of a lip stick. It can be used as a care product and / or as a make-up product for the skin or the lips.

In a known manner, the composition according to the invention can also contain the adjuvants usual in the cosmetic field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, antioxidants, solvents, perfumes, fillers, filters, pigments, odor absorbers and coloring matters. The amounts of these various adjuvants are those conventionally used in the field under consideration, and for example from 0.01 to 20% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase or into the aqueous phase. In any event, these adjuvants, as well as their proportions, will be chosen so as not to harm the desired properties of the compound according to the invention.

When the composition of the invention is an emulsion, the proportion of the fatty phase can range from 5 to 80% by weight, and preferably from 5 to 50% by weight relative to the total weight of the composition. The oils, emulsifiers and coemulsifiers used in the composition in the form of an emulsion are chosen from those conventionally used in the field under consideration. The emulsifier and co-emulsifier are generally present in the composition in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition . As oils which can be used in the composition of the invention, there may be mentioned for example:

- hydrocarbon oils of animal origin, such as perhydrosqualene;

- hydrocarbon oils of vegetable origin, such as liquid triglycerides of fatty acids containing from 4 to 10 carbon atoms and the liquid fraction of shea butter;

- synthetic esters and ethers, in particular of fatty acids, such as oils of formulas R ¹ COOR ² and R ¹ OR ² in which R ¹ represents the remainder of a fatty acid containing from 8 to 29 carbon atoms, and R ² represents a branched or unbranched hydrocarbon chain containing from 3 to 30 carbon atoms, such as for example Purcellin oil, isononyl isononanoate, isopropyl myristate, 2-ethyl palmitate -hexyl, octyl-2-dodecyl stearate, octyl-2-dodecyl erucate, isostearyl isostearate; hydroxylated esters such as isostearyl lactate, octylhydroxystearate, octyldodecyl hydroxystearate, diisostearyl malate, triisocetyl citrate, heptanoates, octanoates, decanoates of fatty alcohols; polyol esters, such as propylene glycol dioctanoate, neopentylglycol diheptanoate and diethyleneglycol diisononanoate; and pentaerythritol esters such as pentaerythrityl tetraisostearate;

- linear or branched hydrocarbons, of mineral or synthetic origin, such as paraffin oils, volatile or not, and their derivatives, petrolatum, polydecenes, hydrogenated polyisobutene such as parlamam oil; - fatty alcohols having from 8 to 26 carbon atoms, such as cetyl alcohol, stearyl alcohol and their mixture (cetylstearyl alcohol), octyldodecanol, 2-butyloctanol, 2-hexyldecanol, 2-undecylpentadecanol, oleic alcohol or linoleic alcohol;

- partially hydrocarbon and / or silicone fluorinated oils such as those described in document JP-A-2-295912; - silicone oils such as volatile or non-volatile polymethylsiloxanes (PDMS) with a linear or cyclic silicone chain, liquid or pasty at room temperature, in particular cyclopolydimethylsiloxanes (cyclomethicones) such as cyclohexasiloxane; polydimethylsiloxanes comprising alkyl, alkoxy or phenyl groups, during or at the end of the silicone chain, groups having from 2 to 24 carbon atoms; phenylated silicones such ^as' phenyltrimethicones, phenyldimethicones, phenyltrimethylsiloxydiphenylsiloxanes, diphenyl dimethicones, diphenylmethyldiphenyltrisiloxanes, 2-phenylethyl trimethylsiloxysilicates, and polymethylphenylsiloxanes;

- their mixtures. As emulsifiers and co-emulsifiers which can be used in the invention, mention may, for example, be made of O / W emulsifiers such as fatty acid and polyethylene glycol esters, in particular PEG-100 stearate, and fatty acid esters. and glycerin such as glyceryl stearate, as well as W / O emulsifiers such as oxyethylenated poly (methyl ketyl) (dimethyl) methylsiloxane available under the trade name ABIL WE09 from the company Degussa Goldschmidt.

As hydrophilic gelling agents, mention may be made in particular of carboxyvinyl polymers (carbomers), acrylic copolymers such as acrylate / alkyl acrylate copolymers, polyacrylamides, polysaccharides, natural gums and clays, and, as lipophilic gelling agents, cite modified clays such as bentones, metal salts of fatty acids, hydrophobic silica and polyethylenes.

As fillers which can be used in the composition of the invention, mention may, for example, be made, in addition to pigments, of silica powder; talc; starch crosslinked with octenylsuccinic anhydride sold by the company National Starch under the name DRY FLO PLUS (28-1160); polyamide particles and in particular those sold under the name ORGASOL by the company Atochem; polyethylene powders; microspheres based on acrylic copolymers, such as those in ethylene glycol dimethacrylate / lauryl methacrylate sold by the company Dow Corning under the name POLYTRAP; expanded powders such as hollow microspheres and in particular, microspheres sold under the name EXPANCEL by the company Kemanord Plast or under the name MICROPEARL F 80 ED by the company Matsumoto; silicone resin microbeads such as those sold under the name TOSPEARL by the company Toshiba Silicone; and their mixtures. These fillers can be present in amounts ranging from 0 to 20% by weight and preferably from 1 to 10% by weight relative to the total weight of the composition or of the preparation according to the invention.

UVA and / or UVB filters can also be introduced into the composition according to the invention, chosen from organic filters and mineral filters optionally coated to make them hydrophobic. As active agents which can be used in the composition according to the invention, there may be mentioned in particular: depigmenting or propigmenting agents; anti-glycation agents; NO synthase inhibitors; 5α-reductase inhibitors; lysyl and or prolyl hydroxylase inhibitors; agents stimulating the synthesis of dermal or epidermal macromolecules and or preventing their degradation; agents stimulating the proliferation of fibroblasts and or keratinocytes or stimulating the differentiation of keratinocytes; muscle relaxants; anti-microbial agents; tensing agents; anti-pollution and / or anti-radical agents; soothing agents; active lipolytics or having a favorable activity, direct or indirect, on the reduction of adipose tissue; agents acting on the microcirculation; agents acting on the energy metabolism of cells; and their mixtures.

The invention will be better understood, and its advantages will emerge more clearly in the light of the following examples, which are given by way of illustration, and without limitation.

EXAMPLES

Example 1: Exfoliation test by measuring the degradation of corneodesmosines

In this example, the ability of sodium methyl glycinediacetate to promote desquamation by the degradation of corneodesmosines is studied.

Coméodesmosine is one of the major markers of desquamation in the corneodesmosome. It is studied on immunoblot after separation by electrophoresis and transfer to the membrane. After specific labeling with the monoclonal antibody G36-19, it is revealed by chemiluminescence. The murine monoclonal antibody G36-19 is specific to comesodesmosine, it is part of a series of antibodies directed against epidermal differentiation antigens, produced after immunization of a mouse with a homogenate of the human plantar stratum corneum, then characterized (Serre G. et al., J. invest. Dermatol. 1991; 97 (6): 1061-72).

Varnished strippings are carried out on the lower legs of volunteers (modification of the procedure of Lundstrôm A. and Egelrud T. Acta Derm. Venereol. (Stockh) 71, 471 -474, 1991). The nylon-varnish sheets associated with the corneocytes are immersed in acetone 1 ml / cm ^{2 in} order to detach the corneocytes. The mixture is filtered and then rinsed three times with the same volume of acetone in order to remove all traces of varnish. Finally the mixture is dried under vacuum: acetone powders of stratum corneum are then obtained.

The acetone powders are aliquoted by 1 mg. 100 μl of aqueous solutions containing 2% of active ingredient adjusted to a pH 8.0 are added. Cookies without assets are produced under the same conditions. Two incubation times are studied: t = 0 and t = 8h. In the latter case the incubation takes place at 34 ° C with shaking.

After incubation, the mixtures are centrifuged for 10 min at 10,000 g. The supernatant is removed and replaced with 100 μl of Laemmli buffer 0.0625 M Tris / HCl pH 6.8, 2% SDS, 200 mM DTT, 10% glycerol which allows the extraction of proteins. The mixture is brought to the boil for 10 min at 100 ° C. and then ground in a Potter. The mixture is centrifuged for 10 min at 10000 g then the supernatant is collected. It contains proteins from the corneodesmosome.

The total proteins are dosed according to the Bradford method (Biorad kit). This allows an adjustment to 0.6 mg / ml of the samples and an actual comparison of the treatments. The samples and a 1/3 rainbow low molecular weight standard (Amersham Pharmacia Biotech) are separated by electrophoresis on a 12% acrylamide gel for V h at 100 V, then 1 h at 200 V. After electrophoresis, the proteins are transferred to the Immobilon-P membrane (Millipore) for 3 h at 60V. The membrane is then incubated 2 times 15 min in TBS-TL buffer: 25mM Tris, 0.15M NaCl pH 7.2, 0.05% Tween 20, 0.5% Skimmed milk powder in order to block non-specific sites . Incubation with the G36-19 antibody at 1/12500 is carried out overnight at 4 ° C. After two rinses of 5 min in TBS-TL the membrane is incubated with a goat anti-mouse IG antibody (H + L) peroxidase conjugate (Biorad) at 1/4000 1h30 at room temperature. After several rinses of 5 min in TBS-TL then TBS (without milk or Tween), the membrane is incubated for 1 min in 10 ml of ECL reagent (Amersham Pharmacia Biotech). The chemiluminescence of the coméodesmosine bands is measured with the FluorS Multimager (Biorad). The 46 kDa band is quantified with the Quantity-one software (Biorad).

The results of this study are summarized in Table 1 below. Glycine is used as the reference compound in this study; patent application EP-A2-0 852 949 (Shiseido) having shown that glycine promotes the degradation of desmogleine (protein of the corneodesmosome). It has been tested according to a protocol similar to that described above.

Table 1 Effect of sodium methyl glycinediacetate on the degradation of corneodesmosines

The control is carried out with the solubilization buffer, without active, under the conditions of the test. This control takes into account the natural degradation of the corneodesmosines which takes place during the incubation.

It is clear that sodium methyl glycinediacetate promotes the degradation of corneodesmosines and that it is better than the glycine used as a positive control in this test.

Example 2: comparative test

Two other chelators were tested in the same manner as described in Example 1 sodium iminosuccinate and triacetic acid lauroyl ethylene diamine.

These compounds did not have a favorable activity on the degradation of coméodesmosine as shown in Table 2 below. Table 2 Effect of two chelating agents on the degradation of corneodesmosines

EXAMPLE 3 Prodesquamant Hydrating Cream

The following composition is prepared in a conventional manner for a person skilled in the art.

Phase A

Demineralized water QSP 100% Preservatives 0.5% Carbomer 0.4% Glycerin 7%

Phase B1

Oxyethylenated sorbitan stearate (200 EO) 0.9%

Phase B2

PEG-100 stearate and 2.1% glyceryl stearate

Apricot oil 10%

Vaseline 2%

Parlam oil 10%

1% UV filter

Ceramides 0.5%

Phase C

Water 2% Hydrochloric acid qs pH 7

Sodium methyl glycinediacetate%

This cream can be used in the care of dry skin.

EXAMPLE 4 Prodesquamant Anti-Aging Cream

PAïase A Acrylate / C copolymer ₁₀ - ₃₀ acrylate 0.5% Water 12%

Phase B

5% hydrogenated polyisobutene

Cyclohexasiloxane 5%

Octyl methoxycinnamate 1%

Phase C

Sodium methyl glycinediacetate 1%

Hydrochloric steel Qsp pH = 7

Glycerin 6%

Preservatives 0.5%

Centelfa Asiatica extract 1%

Water qs 100%

Phase D

Polyacrylamide and C ₁₃ - ₁₄ isoparaffin and laureth-7 1%

This composition can be prepared in the following manner. The polymer of phase A is dispersed in water at 40 ° C. The constituents of phase B are heated to 70 ° C until complete dissolution, then the temperature is reduced to 40 ° C. The constituents of phase C are mixed at 50 ° C. Phase B is then introduced into phase A at 40 ° C with stirring, then phase C is added to them, as well as phase D of geification. EXAMPLE 5 Depigmenting Cream

Phase A

100% QSP demineralized water

Preservatives 0.5%

Carbomer 0.4%

Glycerin 7%

Phase B1

Oxyethylenated sorbitan stearate (200 EO) 0.9%

Phase B2 PEG-100 stearate and glyceryl stearate 2.1%

Cyclohexasiloxane 10%

Parlam oil 5%

2% UV filter

Phase C

Water 2%

Hydrochloric acid qs pH 7

Sodium methyl glycinediacetate 5%

Kojic acid 0.1%

This cream can be used to reduce pigmentation spots on the hands and cleavage.

Claims

1. Cosmetic use of at least one compound corresponding to the following formula (I)

(I)

in which :

Rι _> R _∑ . 3 represent, independently of each other, a hydrogen atom; an alkyl group comprising from 1 to 6 carbon atoms, optionally substituted by a radical -COOR ₄ where R ₄ is an alkyl group comprising from 1 to 4 carbon atoms, or by an amino group, a hydroxy group, an alkoxy group and / or an alkylamino group; or a sugar residue, or a salt of such a compound when R _T and / or R ₂ and / or R ₃ represent a hydrogen atom, in a cosmetic composition comprising a physiologically acceptable medium, as agent intended to promote the peeling of the skin and / or to stimulate epidermal renewal.

2. Use according to claim 1, characterized in that the compound of formula (I) is chosen from those for which R ^ = R ₂ = R = H and their salts, in particular inorganic.

3. Use according to claim 2, characterized in that the compound of formula (I) is sodium methyl glycinediacetate.

4. Cosmetic use of the compound of formula (I) as defined in any one of the preceding claims, or of at least one of its salts, in a cosmetic composition, as an agent for preventing or treating the skin dry and / or skin signs of aging and / or skin pigmentation. 03

16

5. Method for cosmetic treatment of dry skin and / or cutaneous signs of aging and / or pigmentation of the skin, comprising the topical application to the skin of a composition comprising, in a physiologically acceptable medium, the compound of formula (I) described in any one of claims 1 to 3 or at least one of its salts.

6. Method according to claim 5, characterized in that said composition contains 0.1 to 10% by weight of compound of formula (I), relative to the total weight of the composition.