WO2004012697A1

WO2004012697A1 - Cosmetic use of lignans

Info

Publication number: WO2004012697A1
Application number: PCT/EP2003/007882
Authority: WO
Inventors: Béatrice Renault; Philippe Catroux
Original assignee: L'oréal
Priority date: 2002-07-25
Filing date: 2003-07-18
Publication date: 2004-02-12
Also published as: AU2003250999A1; EP1526832A1

Abstract

The invention relates to the cosmetic use of at least one lignan of given formula, or of a plant extract containing it (such as an extract of flax seeds), in a composition suitable for topical application to the skin and containing a cosmetically acceptable medium, for preventing or treating dryness of the skin, rough skin and/or a dull complexion, and/or for moisturizing or softening the skin. The invention also relates to a cosmetic process for treating dry skin, comprising the topical application to the said skin of a composition containing at least one such lignan or a plant extract containing it, in a cosmetically acceptable medium.

Description

Cosmetic use of lignans

The invention relates to the cosmetic use of at least one lignan of given formula, derived in particular from flax seeds, in a composition suitable for topical application to the skin and containing a cosmetically acceptable medium, for preventing or treating dryness of the skin, rough skin and/or a dull complexion.

Human skin consists of two compartments, namely a surface compartment, the epidermis, and a deep compartment, the dermis .

Natural human epidermis is composed mainly of three types of cells: keratinocytes, which form the vast majority, melanocytes and Langerhans cells. Each of these cell types contributes, by virtue of its intrinsic functions, towards the essential role played in the body by the skin.

In particular, keratinocytes undergo a process of continuous oriented maturation which, for the keratinocytes located in the basal layer of the epidermis, results in the formation of corneocytes, which are totally keratinized dead cells consisting of keratinocytes in the final stage of their differentiation.

This differentiation process makes it possible to result in the formation of epidermal lipids organized as a bilayer in the stratum corneum, which is thus responsible for the barrier function of the epidermis .

It also allows the production of the constituent elements of the NMF (Natural Moisturizing Factor) composed of small molecules with high hygroscopic power playing a moisturizing role. The NMFs also act as plasticizers, and thus contribute towards the suppleness of the skin.

The stratum corneum thus plays a fundamental role in the barrier function and moisturization. The importance of ensuring good differentiation of the keratinocytes to maintain the integrity of the skin barrier and thus to prevent dryness of the skin may therefore be appreciated on reading the text hereinabove.

In addition, an impairment in the differentiation of the keratinocytes will have the effect of accumulating squamae at the surface of the skin, which will modify the interaction between the surface of the skin and the light and will be responsible for a dull, coarse appearance of the skin. The discomfort caused by the phenomenon of dry skin will thus often be accompanied by unaesthetic sensations that it is also sought to combat. However, the Applicant has now discovered, surprisingly and unexpectedly, that certain lignans, extracted in particular from flax seeds, increase the differentiation of keratinocytes and are thus useful in particular for combating dryness of the skin.

Lignans constitute a vast group of natural products characterized by the coupling of two propylbenzene units via a β-β' bond. In other words, they thus have a 2,3-dibenzylbutane structure. These compounds are present especially in a number of cereals, fruit and vegetables and in particular in plants such as flax (especially secoisolariciresinol and isolariciresinol) , chaparral (nordihydroguaiaretic acid) or sesame (sesaminol, sesamolinol and pinoresinol) , in the form of glycosides. These are the main sources of lignans. However, lignans are also found in schisandra, arborvitae, birthwort, orina, nutmeg, magnolia, forsythia and nettle.

The lignan that is most commonly known is nordihydroguaiaretic acid, which is an antioxidant used especially in retinol-based anti-ageing compositions, to prevent oxidation of the latter (EP-0 440 398) . Glycosylated lignans derived from sesame have moreover been described as being useful for firming the skin and preventing the formation of wrinkles and slackening of the skin by scavenging OH° radicals (JP-09 095 417) . They are also well known as antioxidants and may be used in moisturizing and protective creams (US-5 993 795) .. For their part, the glycosylated lignans derived from flax seeds are known to inhibit the production of melanin and thus bleach the skin (JP2001-261 570) , as agents for increasing the activity of catalase and fibroblasts and the synthesis of hyaluronic acid, for preventing or treating UV-induced wrinkles and for reinforcing the elasticity of the skin (JP2001-114 636 and JP2001-122 733) .

Lignans, for example those derived from flax, have moreover been described as being useful in preventing osteoporosis and certain cancers, but also as anti -viral agents and fungicides. It has thus been proposed to use them to treat the symptoms of the menopause (EP-0 906 761) . However, to the Applicant's knowledge, it has never before been suggested that certain lignans in aglycone form, derived in particular from flax seeds, can be useful in compositions applied topically to the skin in particular for combating dryness of the skin. Thus, one subject of the invention is the cosmetic use of at least one lignan corresponding to formula (I) :

in which:

Ri and R each represent a -CH₂-OH group or, taken together, form a furanone ring, R₃ and R₄ independently represent a hydroxyl group or an

-0-CH₃ group,

R₅, R₆ and R₇ independently represent a hydroxyl group or an -0-CH₃ group or a hydrogen atom, it being understood that at least one of the groups R₃ and R₄ and at least one of the groups R₅, R₆ and R₇ represents an -0-CH₃ group,

R₈ and R₉ each represent a hydrogen atom or together form a bond, or of a plant extract containing it, in a composition suitable for topical application to the skin and containing a cosmetically acceptable medium, for preventing or treating dryness of the skin, rough skin and/or a dull complexion, and/or for moisturizing or softening the skin. A subject of the invention is also a cosmetic process for treating dry skin, comprising the topical application to the said skin of a composition containing, in a cosmetically acceptable medium, at least one lignan such as defined above.

For the purposes of the present invention, the term "cosmetically acceptable" means an inert medium that is compatible with the skin, its integuments and/or mucous membranes, which does not result in itching, stinging, tautness or redness liable to put the user off using the composition, and which has a pleasant appearance, odour and feel. The lignans corresponding to formula (I) above are advantageously chosen from: secoisolariciresinol, isolariciresinol and matairesinol .

Secoisolariciresinol is available, for example, from the company Apin Chemicals in powder form.

Rather than making use of purified lignans, it is possible in the present invention to use lignan- rich plant extracts. The plant , extract used according to the invention may be obtained from any plant material cultivated in vivo or in vitro. The expression "in vivo cultivation" means any cultivation of conventional type, i.e. in the soil in the open air or in a greenhouse, or alternatively out of the soil. The expression "in vitro cultivation" means all the techniques known to those skilled in the art for artificially obtaining a plant or part of a plant . The selection pressure imposed by the physicochemical conditions during the growth of plant cells in vitro makes it possible to obtain standardized plant material available throughout the year, in contrast with plants cultivated in vivo.

The lignans may especially be extracted from flax seeds, in particular from the species Linum usitatissinum, which thus constitutes the preferred source for supplying lignans of formula (I) or a plant extract according to the invention.

The extraction process used for extracting the lignans according to the invention in aglycone form usually comprises the following steps: a) the enzymatic hydrolysis of flax seeds in aqueous medium, or the extraction of flax seeds with an aqueous, alcoholic or aqueous-alcoholic solvent, and b) the acidic hydrolysis of the extract obtained.

The acidic hydrolysis step allows the lignans to be isolated in aglycone form.

The solvent used in step (a) is generally chosen from water, ethanol and methanol, and mixtures thereof .

According to one preferred embodiment of the invention, the above process also comprises a preliminary step of defatting the flax seeds using an organic solvent such as n-hexane. An example of such an extraction process is given in the publication by L. P. Meagher et al . , Isolation and Characterization of the Lignans, Isolariciresinol and Pinoresinol, in Flaxseed Meal, J. Agric. Food Chem. , 1999, 47, 3173-3180.

As a variant, the lignans according to the invention may be obtained by acidic hydrolysis of glycosylated lignans obtained according to the process described in US-5 705 618. This process comprises the extraction of a commercially available defatted flax seed meal, using an aqueous-alcoholic mixture, followed by the removal of the residual solids and the removal of the lignan-rich alcoholic solvent, to obtain a concentrate that is subjected to a basic hydrolysis intended to decomplex the lignans. This hydrolysed concentrate is then subjected to a liquid/liquid fractionation, for example using an ethyl acetate/water mixture, or is passed through an ion-exchange resin to concentrate the lignans, which are then separated out by chromatography.

The amount of lignan (s) that may be used according to the invention obviously depends on the desired effect and may thus vary within a wide range. To give an order of magnitude, an amount of lignan (s) representing from 0.001% to 10% of the total weight of the composition and preferably from 0.01% to 2% of the total weight of the composition may be used. The composition according to the invention may be in any presentation form normally used in cosmetics and dermatology, and it may especially be in the form of an optionally gelled solution, a dispersion of the lotion type, optionally a two-phase lotion, an emulsion obtained by dispersing a fatty phase in an aqueous phase (O/W emulsion) or conversely ( /O emulsion) , or a triple emulsion ( /O/ or 0/ /O emulsion) or a vesicular dispersion of ionic and/or nonionic type. These compositions are prepared according to the usual methods .

This composition may be more or less fluid and may have the appearance of a white or coloured cream, an ointment, a milk, a lotion, a serum, a paste or a mousse. It may optionally be applied in the form of an aerosol. It may also be in solid form, in particular in the form of a stick or a patch. It may be used as a care product and/or as a makeup product for the skin. In a known manner, the composition of the invention may also contain adjuvants that are common in cosmetics, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preserving agents, antioxidants, solvents, fragrances, fillers, screening agents, pigments, odour absorbers and dyestuffs. The amounts of these various adjuvants are those conventionally used in the field under consideration, for example from 0.01% to 20% relative to the total weight of the composition. Depending on their nature, these adjuvants may be introduced into the fatty phase, into the aqueous phase, or into lipid vesicles. In any case, these adjuvants, and also the proportions thereof, will be chosen so as not to harm the desired properties of the lignans according to the invention.

When the composition of the invention is an emulsion, the proportion of the fatty phase may 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 co-emulsifiers used in the composition in emulsion form are chosen from those conventionally used in the field under consideration. The emulsifier and co-emulsifier are 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 that may be used in the invention, mention may be made of mineral oils (liquid petroleum jelly) , oils of plant origin (avocado oil or soybean oil) , oils of animal origin (lanolin) , synthetic oils (perhydrosqualene) , silicone oils (cyclomethicone) and fluoro oils (perfluoropolyethers) . Fatty alcohols (cetyl alcohol) , fatty acids and waxes (carnauba wax or ozokerite) may also be used as fatty substances.

As examples of emulsifiers and co-emulsifiers that may be used in the invention, mention may be made of fatty acid esters of polyethylene glycol such as

PEG-20 stearate, and fatty acid esters of glycerol such as glyceryl stearate.

Hydrophilic gelling agents that may be mentioned in particular include carboxyvinyl polymers (carbomer) , acrylic copolymers such as acrylate/alkylacrylate copolymers, polyacrylamides, polysaccharides, natural gums and clays, and lipophilic gelling agents that may be mentioned include modified clays, for instance bentones, metal salts of fatty acids, hydrophobic silica and polyethylenes .

According to one preferred embodiment of the invention, the composition also contains at least one compound chosen from desquamating agents.

The term "desquamating agent" means any compound capable of acting: either directly on desquamation by promoting exfoliation, such as β-hydroxy acids, in particular salicylic acid and its derivatives (including 5-n- octanoylsalicylic acid) ; α-hydroxy acids, such as glycolic acid, citric acid, lactic acid, tartaric acid, malic acid or mandelic acid; urea; gentisic acid; oligofucoses; cinnamic acid; extract of Saphora japonica; resveratrol; or on the enzymes involved in the desquamation or degradation of corneodesmosomes, glycosidases, stratum corneum chymotryptic enzyme (SCCE) , or even other proteases (trypsin, chymotrypsin-like) . Mention may be made of agents for chelating mineral salts: EDTA; N-acyl-N,N' ,N' -ethylenediaminetriacetic acid; amino- sulphonic compounds and in particular (N-2-hydroxy- ethylpiperazine-N-2-ethane) sulphonic acid (HEPES) ; 2-oxothiazolidine-4-carbόxylic acid (procysteine) ; α-amino acid derivatives of the type such as glycine (as described in EP-0 852 949, and sodium methyl glycine diacetate sold by BASF under the trade name Trilon M) ; honey; sugar derivatives such as 0-octanoyl- 6-D-maltose and N-acetylglucosamine.

The concentration of these optional additional agents in the composition according to the invention may range from 0.0001% to 20% by weight and is preferably between 0.001% and 5% by weight relative to the total weight of the composition.

As mentioned previously, the composition according to the invention may also contain UVA and/or UVB screening agents, in the form of organic or mineral compounds, the latter optionally being coated to make them hydrophobic. The organic screening agents may be chosen especially from: anthranilates, in particular menthyl anthranilate; benzophenones, in particular benzophenone-1, benzophenone-3 , benzophenone-5, benzophenone-6, benzophenone-8 , benzophenone-9, benzophenone-12 and, preferably, benzophenone-2 (oxybenzone) or benzophenone-4 (Uvinul MS40 available from BASF) ; benzylidenecamphors , in particular 3-benzylidenecamphor, benzylidenecamphorsulphonic acid, camphor benzalkonium methosulphate, polyacrylamido- methylbenzylidenecamphor, terephthalylidenedicamphor- sulphonic acid and, preferably, 4-methylbenzylidenecamphor (Eusolex 6300 available from Merck) ; benzimidazoles, in particular benzimidazilate (Neo Heliopan AP available from Haarmann & Reimer) , or phenylbenzimidazolesulphonic acid (Eusolex 232 available from Merck) ; benzotriazoles, in particular drometrizole trisiloxane, or methylenebis-benzo- triazolyltetramethylbutylphenol (Tinosorb M available from Ciba) ; cinnamates, in particular cinoxate, DEA methoxycinnamate, diisopropyl methylcinnamate, glyceryl ethylhexanoate dimethoxycinnamate, isopropyl methoxycinnamate, isoamyl cinnamate and, preferably, ethocrylene (Uvinul N35 available from BASF) , octyl methoxycinnamate (Parsol MCX available from Hoffmann LaRoche) , or octocrylene (Uvinul 539 available from BASF) ; dibenzoylmethanes, in particular butylmethoxy- dibenzoylmethane (Parsol 1789) ; imidazolines, in particular ethylhexyl dimethoxybenzylidene dioxo- imidazoline; PABAs, in particular ethyl dihydroxypropyl PABA, ethylhexyldimethyl PABA, glyceryl PABA, PABA, PEG-25 PABA and, preferably, diethylhexylbutamido- triazone (Uvasorb HEB available from 3V Sigma) , ethylhexyltriazone (Uvinul T150 available from BASF) or ethyl PABA (benzocaine) ; salicylates, in particular dipropylene glycol salicylate, ethylhexyl salicylate, homosalate or TEA salicylate; triazines, in particular anisotriazine (Tinosorb S available from Ciba) ; drometrizole trisiloxane.

The mineral screening agents preferably consist of zinc oxide and/or titanium dioxide, preferably of nanometric size, optionally coated with alumina and/or stearic acid.

The examples that follow are given for purely illustrative purposes and are not intended to limit the scope of this invention. Unless otherwise mentioned, the proportions referred to in the compositions below correspond to weight percentages .

EXAMPLES Example 1: Effect of secoisolariciresinol on keratinocyte differentiation

Principle of the method: The study consists in evaluating the effect of secoisolariciresinol (Apin Chemical) on keratinocyte differentiation, by measuring the transglutaminase (TGk) activity of cultured human epidermal keratinocytes. TGk is a marker of terminal differentiation of the keratinocyte and of the formation of the cornified envelope (corneocyte) .

Human epidermal keratinocytes used at the 3rd passage are inoculated into 96-well plates at a density of 10 000 cells per well and cultured in complete SFM medium (Gibco 170005034, EGF and pituitary extract). After preincubation for 24 hours, the cells are placed in contact with the product (tested at 30 μM) for 48 hours . The cells are subsequently washed and then sonicated on ice in pH 8 Tris/EDTA buffer. The membrane-bound enzyme is extracted in the presence of Triton X100. The TGk activity is assayed by measuring the covalent addition of tritiated putrescine at 2 μCi/ml final to casein. The casein is precipitated with 20% trichloroacetic acid containing 1 mM of putrescine. The precipitates are collected on Skatron filters and collector. The precipitates are washed in 5% TCA medium containing 0.1 mM of putrescine and ethanol. The dry filters are counted by liquid scintillation. The proteins are assayed on each sample using a Dc Protein Assay kit (BioRad) . The TGk activities are given in μg of protein. Retinol (10^-6 M) and a calcium-poor medium were used as references of an anti-differentiating effect .

Inter-group comparisons were performed by analysis- of variance (ANOVA) using Dunnett's multiple comparison test. Results:

The results are collated in Table 1 below.

Table 1

Transglutaminase activity of the keratinocytes

These results show that secoisolariciresinol induces a significant increase in the activity of the TGk present in the keratinocyte cultures and thus pro- differentiating activity with respect to keratinocytes. Moreover, this compound did not exert any cytotoxicity under the test conditions. Example 2 : Fluid containing oleosomes

Phase A

Stearyl heptanoate and stearyl octanoate 5.5 %

Plant oils 11.6 %

UVA-screening agent 1.9 %

Cyclopentasiloxane 3.7 %

Sucrose tristearate 2 %

Oxyethylenated sorbitan monostearate (4 EO) 1.35 %

Stearic acid 1 %

Oxyethylenated hydrogenated castor oil (60 EO) 2.5 %

Tocopheryl acetate 0.5 %

Phase B

Secoisolariciresinol 0.05 %

Preserving agents 0.29 %

Triethanolamine ^' 0.50 %

Disodium EDTA 0.05 %

Glycerol 3 %

Water qs 100 %

This composition may be prepared in the following manner: phases A and B are heated separately to 65°C and are then cooled to room temperature (25°C) . Phase B is then introduced into phase A to obtain an O/W emulsion, which is then subjected to high-pressure homogenization (500b, 1 to 3 times) . This fluid is useful, when applied daily to the face and neck, for improving the radiance of the complexion and making the skin soft .

Example 3: Water-in-oil cream

Phase A

Hydrogenated polyisobutene 5.5 %

Isostearyl neopentanoate 3.5 %

PEG stearate (20 EO) 1 %

PEG glyceryl stearate (100 EO) 2 %

Cetyl alcohol 0.5 %

Stearic acid 1 %

Matairesinol 0.01 %

Phase A '

Cyclomethicone 11 %

Phase B

Preserving agents 0.2 %

Triethanolamine 0.03 %

Water qs 100 %

Phase C

Polyacrylamide and isoparaffin and Laureth-7 1 % (Sepigel 305 from SEPPIC) The above composition may be prepared in the following manner: phase A is heated with stirring until homogeneous. After cooling, phase A' is added and phase B is then heated with stirring, followed by adding phase A, with continued stirring. After cooling to 50°C, phase C is incorporated into the emulsion. A cream that is effective in restoring the skin barrier and thus keeping the skin moisturized is obtained.

Claims

1. Cosmetic use of at least one lignan corresponding to formula (I) :

in which:

R_x and R₂ each represent a -CH₂-OH group or, taken together, form a furanone ring, R₃ and R₄ independently represent a hydroxyl group or an

-0-CH₃ group,

R₅, R_s and R₇ independently represent a hydroxyl group or an -O-CH₃ group or a hydrogen atom, it being understood that at least one of the groups R₃ and R₄ and at least one of the groups R₅, R₆ and R₇ represents an -0-CH₃ group,

R₈ and R₉ each represent a hydrogen atom or together form a bond, or of a plant extract containing it, in a composition suitable for topical application to the skin and containing a physiologically acceptable medium, for preventing or treating dryness of the skin, rough skin and/or a dull complexion, and/or for moisturizing or softening the skin.

2. Use according to Claim 1, characterized in that the said lignan is chosen from: secoisolariciresinol, isolariciresinol and matairesinol .

3. Use according to Claim 1 or 2 , characterized in that the said plant extract is an extract of flax seeds.

4. Use according to Claim 3, characterized in that the said extract of flax seeds is obtainable by a process comprising the following steps: a) the enzymatic hydrolysis of flax seeds in aqueous medium, or the extraction of flax seeds with an aqueous, alcoholic or aqueous-alcoholic solvent, and b) the acidic hydrolysis of the extract obtained.

5. Use according to Claim 4, characterized in that the solvent used in step (a) is chosen from water, ethanol and methanol, and mixtures thereof.

6. Use according to Claim 4 or 5 , characterized in that the said process also comprises a preliminary step of defatting the flax seeds using an organic solvent such as n-hexane .

7. Use according to any one of Claims 1 to 6, characterized in that the said lignan represents from 0.001% to 10% of the total weight of the composition.

8. Use according to Claim 7, characterized in that the said lignan represents from 0.01% to 2% of the total weight of the composition.

9. Use according to any one of Claims 1 to 9, characterized in that the said composition also contains at least one compound chosen from the desquamating agents.

10. Cosmetic process for treating dry skin, comprising the topical application to the said skin of a composition containing, in a cosmetically acceptable medium, at least one lignan of formula (I) as defined in Claim 1, or a plant extract containing it.