EP1284715A1

EP1284715A1 - Use of ergothioneine and/or its derivatives as anti-pollution agent

Info

Publication number: EP1284715A1
Application number: EP01934112A
Authority: EP
Inventors: Philippe Catroux; José Cotovio; Daniel Duche
Original assignee: LOreal SA
Current assignee: LOreal SA
Priority date: 2000-05-18
Filing date: 2001-05-14
Publication date: 2003-02-26
Also published as: JP2003533462A; FR2809000B1; FR2809000A1; WO2001087260A1; AU2001260418A1; US20040047823A1

Abstract

The invention concerns the use of ergothioneine and/or its derivatives for topical application as anti-pollution agent, preferably as cosmetic anti-pollution agent, and a cosmetic treatment method using ergothioneine and/or its derivatives.

Description

Use of ¹ ergothioneine and / or its derivatives as an anti-pollution agent.

The subject of the present invention is the use in topical application of ergothionein and / or its derivatives as an anti-pollution agent, as is a cosmetic treatment process using erg othionein and / or its derivatives. Urban areas are regularly subject to pollution peaks. Air pollutants which are widely represented by the primary and secondary products of combustion represent an important source of environmental oxidative stress. Different types of chemicals, xenobiotics and particles make up urban pollution. Three main categories of pollutants can exert deleterious effects on the skin and hair: gases, heavy metals and particles which are combustion residues on which very many organic compounds are absorbed.

It is the outermost tissues that are initially and directly exposed to environmental toxins. The skin is directly and frequently exposed to the pro-oxidant environment. Sources of environmental oxidants include oxygen, UV solar irradiation as well as in polluted air, ozone and oxides of nitrogen and sulfur. Air pollutants represented by the primary and secondary products of domestic and industrial combustion such as mono- and polycyclic aromatic hydrocarbons are also an important source of oxidative stress. The skin is particularly sensitive to the action of oxidative stress and the outermost layer acts as a barrier against oxidative damage. In most circumstances, the oxidant is likely to be neutralized after reaction with keratin materials, but the reaction products formed can be responsible for cellular and tissue damage.

The stratum corneum, the skin barrier, is the contact site between air and skin tissue. The biphasic lipid / protein structure is a crucial determinant of this barrier function of the skin. These elements can react with oxidants and be altered which will favor the phenomena of scaling.

The lipid peroxidation induced by ozone can alter the skin in two ways: 1 / the oxidation and degradation of lipids in the stratum corneum can alter the barrier function of the stratum corneum. The disruption of external lipids and the architecture of proteins seem to be triggering factors in many dermatoses (psoriais, atopic dermatitis, irritant dermatitis). 2 / the increased formation of lipid oxidation products in the upper skin layers can trigger damage in the adjacent skin layers. The reaction of ozone (0 ₃ ) with unsaturated lipids involves addition reactions on the double bonds. This process leads in a second time to the breaking of the lipid chains and to the formation of aldehyde hydroperoxides and hydrogen peroxide.

It is a specific mechanism different from the conventionally described lipoperoxidation mechanism, which is mediated by a radical. Secondary or tertiary ozone-induced lipid oxidation products, which have a lower reactivity to ozone but a longer lifespan, can propagate the effect of ozone. Due to their relative stability, lipid oxidation and peroxidation products, i.e. aldehyde and cholesterol oxides, have the potential to alter cells at distant sites not directly exposed to 0. Significant oxidative damage to the surface layers of the stratum can initiate underlying localized inflammatory processes, leading to the recruitment of phagocytes which, by generating oxidants, will amplify the initial oxidative processes.

In urban pollution, concomitant exposure to 0 ₃ and to ultraviolet (UV) radiation of type A, B and / or C can cause stress synergistic oxidative.

Similarly, we can think that there is a synergy of action between ozone and organic compounds resulting from combustion.

Among the pollutants which can exert deleterious effects on keratin materials, toxic gases such as ozone, carbon monoxide, nitrogen oxides or sulfur oxides, are one of the major constituents.

It has been found that these toxic gases and more particularly ozone promote the desquamation of keratin materials which make said keratin materials dirty and dull. Similarly, these gases are likely to cause cellular asphyxia at the epidermal level.

In particular, cellular asphyxia of keratin materials has been observed in the presence of ozone. This gas in high doses can also induce direct cytotoxicity, capable of leading to cell necrosis, alkylation of cellular nucleophiles, mechanisms which can be at the origin of sensitization u of skin carcinogenesis.

Thus, there is a need for compositions making it possible to avoid the harmful effects due to these pollutants such as ozone, so as to protect the keratin materials.

It has now been found, quite surprisingly, that the use of ergothioneine and / or its derivatives makes it possible to protect keratin materials from the effects of pollutants.

Thus, the main object of the invention is the use in topical application of ergothionein and / or its derivatives, as an anti-pollution agent, and preferably as an anti-pollution cosmetic agent.

Cosmetic anti-pollution agent is understood to mean an agent which protects the skin and keratin materials so as to prevent, attenuate and / or eliminate the deleterious effects of toxic gases such as ozone.

Ergothionein and / or its derivatives can in particular correspond to those of formula (I):

H (I)

in which :

X represents a group -O-R 'or -NRR';

R, R 'and R "represent simultaneously or independently of one another, a hydrogen atom, an alkyl group, an alkenyl group or an acyl group C _j -C _j g, or to one of the salts of compounds of formula (I).

By alkyl, alkenyl, acyl group C _j -C _j g means the alkyl, alkenyl or acyl groups having from 1 to 18 carbon atoms, linear or branched, optionally substituted by a hydroxyl group (itself can be esterified ), a halogen atom, a carboxylic group and its derivatives, an amino group and its derivatives, and which may contain in the chain heteroatoms such as O or S.

Preferably, R, R 'and R "denote, independently of one another, a hydrogen atom, an ethyl, acetyl or acyl group and X denotes NH ₂ .

Even more preferably, the compound of formula (I) is ergothionein and in particular L - (+) - ergothionein, L - (-) - ergothioneine, D - (+) - ergothionein and D - (-) - ergothioneein. The preferred compound according to the invention is L - (+) - ergothionein.

Ergothionein and / or its derivatives, as defined above, are used in particular to protect keratin materials from the effects of toxic gases and more particularly ozone.

In the context of the present invention, the term “keratinous material” in particular means the skin, the scalp, the hair, the eyelashes, the eyebrows, the nails and the mucous membranes.

Ergothionein and / or its derivatives can also be used as an anti-pollution agent, preferably as an anti-pollution cosmetic agent, to improve cellular respiration and / or reduce flaking and / or to avoid tarnishing or dirtying keratin materials. .

The invention also relates to the use of ergothioneine and / or its derivatives in or for the preparation of a composition, preferably cosmetic, with topical anti-pollutant application.

It has also been found that these compositions have good stability properties, both in an acid medium and in a basic medium.

Finally, since ergothionein has the advantage of being odorless, the compositions used in the invention will be easily accepted by consumers.

This composition may in particular contain from 0.005% to 10%, and preferably from 0.01 to 5% by weight of active material of ergothionein and / or its derivatives relative to the total weight of the composition.

This composition can also contain at least one other anti-pollution compound. This can in particular be chosen from anthocyanins and / or its derivatives, compounds containing a thioether, sulfoxide or sulfone function, heavy metal chelators such as, for example, N, N'-dibenzyl ethylene acid derivatives diamine N, N'- diacetic, antioxidants, ellagic acid or plant extracts such as those of the Pontederiaceae family.

The cosmetic compositions used according to the invention also comprise a cosmetically acceptable medium which more particularly consists of water and / or optionally a solvent cosmetically acceptable organic.

The organic solvents can represent from 5 to 98% of the total weight of the composition. They can be chosen from the group consisting of hydrophilic organic solvents, lipophilic organic solvents, amphiphilic solvents or their mixtures.

Among the hydrophilic organic solvents, mention may be made, for example, of lower, linear or branched mono-alcohols having from 1 to 8 carbon atoms such as ethanol, propanol, butanol, isopropanol, isobutanol, polyethylene glycols having from 6 to 80 ethylene oxides, polyols such as propylene glycol, isoprene glycol, butylene glycol, glycerol, sorbitol, mono- or dialkyls of isosorbide in which the alkyl groups have from 1 to 5 atoms carbon like dimethyl isosorbide, glycol ethers like diethylene glycol mono-methyl or mono-ethyl ether and propylene glycol ethers like dipropylene glycol methyl ether.

As lipophilic organic solvents, mention may, for example, be made of fatty esters such as diisopropyl adipate, dioctyl adipate, alkyl benzoates.

As amphiphilic organic solvents, mention may be made of polyols such as propylene glycol derivatives (PPG), such as esters of polypropylene glycol and of fatty acids, of PPG and of fatty alcohols such as PPG-23 oleyl ether and PPG-36 oleate.

So that the compositions of the invention are more pleasant to use (softer on application, more nourishing, more emollient), it is possible to add a fatty phase to the medium of these compositions.

The fatty phase preferably represents from 0 to 50% by total weight of the composition.

This fatty phase can comprise one or more oils preferably chosen from the group consisting of:

- volatile or non-volatile, linear, branched or cyclic silicones, organo-modified or not, water-soluble or liposoluble,

- mineral oils such as paraffin and petrolatum oil, - oils of animal origin such as perhydrosqualene, - oils of vegetable origin such as sweet almond oil, avocado oil, castor oil, olive oil, jojoba oil, sesame oil, l peanut oil, macadamia oil, grape seed oil, rapeseed oil, coconut oil, - synthetic oils such as Purcellin oil, isoparaffins,

- fluorinated and perfluorinated oils,

- fatty acid esters such as Purcellin oil.

It can also contain as fat (one) or more fatty alcohols, fatty acids or waxes (paraffin, polyethylene wax, Carnauba, beeswax).

In a known manner, the compositions used in the invention may also contain adjuvants customary in the cosmetic field chosen from the group consisting of conventional aqueous or lipophilic gelling agents and / or thickeners, hydrophilic or lipophilic active agents, preservatives, antioxidants , perfumes, emulsifiers, hydrating agents, pigmenting agents, depigmenting agents, keratolytic agents, vitamins, emollients, - sequestrants, surfactants, polymers, alkalizing or acidifying agents, fillers, anti-free radical agents, ceramides, sun filters, especially ultraviolet filters, insect repellents, slimming agents, coloring matters, bactericides, anti-dandruff agents.

The quantities of these various adjuvants are those conventionally used in the fields considered.

Of course, those skilled in the art will take care to choose the optional compound (s) to be added to the composition according to the invention, so that the advantageous properties intrinsically attached to the composition according to the invention are not, or substantially not, altered by the proposed addition.

The compositions used according to the invention can be in all the gallenic forms normally used for topical application, in particular in the form of an aqueous, hydroalcoholic or oily solution, of an oil-in-water or water-in-oil emulsion or multiple, of an aqueous or oily gel, of an anhydrous product liquid, pasty or solid or of an oil dispersion in an aqueous phase using spherules, these spherules possibly being polymeric nanoparticles such as nanospheres and nanocapsules, or better, hpidic vesicles of ionic type and / or non-ionic.

The compositions used in the present invention 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. , of a foam. They can optionally be applied to the skin in the form of an aerosol.

They can also be in solid form, and for example in the form of a stick.

They can be used as a care product and / or as a makeup product.

The compositions according to the invention can have a pH of between 3 and 8, preferably between 5 and 7.

Another object of the invention consists in a cosmetic treatment process intended to obtain protection of the organism against the effects of pollution, consisting in applying to the keratinous material a cosmetically effective amount of ergothionein and / or its derivatives as defined above.

Another cosmetic treatment method according to the invention, intended to obtain protection of the body against the effects of pollution, consists in applying to the keratin material a cosmetic composition according to the invention as defined above.

The examples which follow are intended to illustrate the invention, without however being limiting in nature. EXAMPLE I

Demonstration of the protective effect of ergothioneine

I. Protocol

First, human keratinocytes from surgical plasties, previously seeded on D-3 in a 48-well dish at a rate of 25,000 cells / cm ² , are pretreated with ergothionein solubilized in the culture medium for 24 hours, at a concentration of 0.5 mM final.

We then incorporate a marker, 2,7-dichlorofluorescin diacetate: after eliminating the ergothionein solution and rinsed with PBS, the human keratinocytes are contacted for 30 minutes with a solution of 2,7-dichlorofluorescin diacetate (320 μM in phosphate buffered saline PBS) at a rate of 500 μl per well, then rinsed again with PBS.

The cells are then exposed to ozone: After putting the cells in contact with a new solution of ergothionein in

PBS at a concentration of 1 mM, at a rate of 100 μl per well, the cells are exposed to ozone in an incubator (37 ° C., humid atmosphere) with an ozone concentration of 10 ppm.

The effects induced by ozone are then measured by measuring the appearance of 2,7-dichlorofluorescine (DCF: excitation at 485 nm and emission at 530 nm) after different exposure times: 0, 5, 10 and 20 minutes.

IT Results:

4 independent experiments were carried out and each measurement was repeated 6 times.

The results are given in the table below: Toxicity of ozone to human keratinocytes in culture, in the absence or presence of ergothioneine at the concentration of ImM, as a function of the time of exposure (n = 4).

The appearance of peroxides generated by ozone at the cellular level results in an increase in fluorescence. For each time, the fluorescence values of the unprotected controls are reduced to 100%. The results, in the presence of ergothionein, are then expressed relative to this control value. A decrease in this value indicates a protective effect of the extract.

m. conclusions

In the presence of a high concentration of ozone, ergothionein significantly reduces the effects induced by ozone. This protection is maximum from 5 minutes and 10 minutes of exposure (81.1% and 74.1% drop in induced stress). It is still significant after 20 minutes of exposure (48.6% drop in induced stress). FORMULATION EXAMPLES

Example 1: According to the usual preparation techniques, the constituents below are mixed to prepare an emulsion.

L (+) ergothioneine where R = H, R '= Ethyl 1 g R "= H and X = NH ₂

oxyethylenated polyethylene glycol 3 g per 50 moles of ethylene oxide

monodiglyceryl stearate 3 g

vaseline oil 24 g

cetyl alcohol 5 g

water qs 100 g

Example 2: In the same way, an emulsion is prepared according to a conventional technique, from the following compounds: ergothioneine where R = H, R '= Ethyl, 0.1 g R "= H and X = OH

octylpalmitate 10 g

glyceryl isostearate 4 g

vaseline oil 24 g

vitamin E 1 g

glycerol 3 g

water qs 100 g Example 3: From the constituents below, the following composition is formulated.

L (+) ergothioneine where R = H, R '= Ethyl, 0.02 g R "= methyl and X = NH ₂

jojoba oil 13 g

parabenzoxy benzoate 0.05 g of methyl and isopropyl

potassium sorbate 0.3 g

cyclopentadimethylsiloxane 10 g

stearyl alcohol 1 g

stearic acid 4 g

polyethylene glycol stearate 3 g

vitamin E 1 g

glycerol 3 g

water qs 100 g

Example 4:

From the constituents below, the following composition is formulated:

L (+) ergothioneine where R = H, R '= Ethyl, 2 g R "= H and X = NH ₂

paraffin oil 15 g

parabenzoxy benzoate 0.05 g of methyl and isopropyl

potassium sorbate 0.3 g

cyclopentadimethylsiloxane 10 g

sorbitol 5 g

ellagic acid 0.1 g

stearyl alcohol 1 g

stearic acid 4 g

polyethylene glycol stearate 3 g

vitamin E 1 g

glycerol 3 g

water qs 100 g

Claims

1. Use in topical application of ergothionein and / or its derivatives as an anti-pollution agent, preferably as an anti-pollution cosmetic agent.

2. Use according to claim 1, characterized in that the ergothionein and / or its derivatives correspond to formula (I):

H (I)

in which :

X represents a group -OR 'or -NRR'; R, R 'and R "represent simultaneously or independently of one another, a hydrogen atom, an alkyl group, an alkenyl group or an acyl group C _j -C _j g, or to one of the salts of compounds of formula (I), the alkyl, alkenyl or acyl groups having from 1 to 18 carbon atoms, linear or branched, optionally substituted by a hydroxyl group, which can be esterified, a halogen atom, a carboxylic group and its derivatives, an amino group and its derivatives, and which may contain in the chain heteroatoms such as O or S.

3. Use according to claim 2, in which the groups R, R ′ and R "of the compound of formula (I) denote, simultaneously or independently of one another, a hydrogen atom, an ethyl or acetyl group or acyl and X denotes NH ₂ .

4. Use according to any one of claims 1 to 3, in which the compound of formula (I) is ergothionein.

5. Use according to any one of claims 1 to 4, in which the compound of formula (I) is L - (+) -ergothioneine.

6. Use in topical application of ergothioneine and / or its derivatives as defined in any one of claims 1 to 5 as an anti-pollution agent, preferably as an anti-pollution cosmetic agent, making it possible to protect keratin materials from the effects toxic gases.

7. Use according to claim 6, characterized in that ergothionein and / or its derivatives as defined in any one of claims 1 to 5 make it possible to protect keratin materials from the effects of ozone.

8. Use in topical application of ergothionein and / or its derivatives as defined in any one of claims 1 to 5, as anti-pollution agent, preferably as anti-pollution cosmetic agent, making it possible to improve cellular respiration and / or reduce flaking and / or avoid tarnishing or dirtying keratin materials.

9. Use of ergothionein and / or its derivatives in or for the preparation of a composition, preferably cosmetic, with topical anti-pollutant application.

10. Use according to claim 9, characterized in that said anti-polluting composition contains from 0.005% to 10% and preferably from 0.01 to 5% by weight of ergothioneine and / or its derivatives relative to the total weight of composition.

11. Use according to any one of claims 9 to 10, characterized in that said composition also contains at least one other anti-pollution compound.

12. Use according to claim 11, characterized in that said anti-pollution compound is chosen from anthocyanins and / or its derivatives, compounds containing a thioether, sulfoxide or sulfone function, heavy metal chelators such as, for example, N, N'-dibenzyl ethylene diamine N, N'-diacetic acid, antioxidants, acid ellagic or plant extracts such as those of the Pontederiaceae family.

13. Use according to any one of claims 9 to 12, characterized in that the composition also contains a cosmetically acceptable medium consisting of water and / or at least one organic solvent chosen from the group consisting of organic solvents hydrophilic, lipophilic organic solvents, amphiphilic solvents or mixtures thereof.

14. Use according to claim 13, characterized in that the organic solvents are chosen from the group consisting of mono- or poly-functional alcohols, optionally oxyethylenated polyethylene glycols, polypropylene glycol esters, sorbitol and its derivatives, dialkyls isosorbid, glycol ethers and polypropylene glycol ethers, fatty esters.

15. Use according to claim 13 or 14, characterized in that the organic solvent (s) represent from 5 to 98% of the total weight of the composition.

16. Use according to any one of claims l i to 15, characterized in that it further comprises at least one fatty phase.

17. Use according to claim 16, characterized in that the fatty phase represents from 0 to 50% of the total weight of the composition.

18. Use according to any one of claims 9 to 17, characterized in that it also contains at least one additive chosen from the group consisting of conventional aqueous or lipophilic gelling agents and / or thickeners, hydrophilic or lipophilic active agents , preservatives, antioxidants, perfumes, emulsifiers, hydrating agents, pigmenting agents, depigmentants, keratolytic agents, vitamins, emollients, sequestrants, surfactants, polymers, alkalizing or acidifying agents , fillers, anti-free radical agents, ceramides, sun filters, in particular ultraviolet, insect repellents, agents slimming, coloring matters, bactericides, dandruff.

19. Composition as defined according to any one of Claims 9 to 18, characterized in that it is in the form of an aqueous, hydroalcoholic or oily solution, of an oil-in-water or water-in emulsion -oil or multiple, of an aqueous or oily gel, of a liquid, pasty or solid anhydrous product or of an oil dispersion in an aqueous phase using spherules.

20. Composition as defined according to any one of Claims 9 to 19, characterized in that the composition has the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste, a foam or a solid.

21. Composition as defined according to any one of claims 9 to 20, characterized in that it has a pH of between 3 and 8, preferably between 5 and 7.

22. Cosmetic treatment method intended to obtain protection of the organism against the effects of pollution, characterized in that it consists in applying to the keratinous material a cosmetically effective amount of ergothionein and / or its derivatives such as defined in any one of claims 1 to 8.

23. Cosmetic treatment method intended to obtain protection of the organism against the effects of pollution, characterized in that it consists in applying to the keratinous material a cosmetic composition as defined in any one of claims 9 to 21.