EP1401390A1

EP1401390A1 - Use of at least one 10-hydroxy-2-decenoic acid derivative in compositions for treating the cutaneous signs of ageing

Info

Publication number: EP1401390A1
Application number: EP02751245A
Authority: EP
Inventors: Nathalie Pineau; Dominique Fagot; Emile Benechie; Martine Li; Françoise PICOT; Pierre Potier
Original assignee: LOreal SA
Current assignee: LOreal SA
Priority date: 2001-06-14
Filing date: 2002-06-14
Publication date: 2004-03-31
Also published as: US20050065212A1; FR2825919A1; JP2004534070A; WO2002102346A1; FR2825919B1

Abstract

The invention relates to the use of at least one 10-hydroxy-2-decenoic acid derivative in a composition or for the preparation of a composition, said derivative or composition being designed to inhibit the degradation of the skin and/or mucosa by inhibiting collagenases.

Description

Use of at least one derivative of 10-hydroxy-2-decenoic acid in compositions intended to treat the cutaneous signs of aging

The invention relates to the use in a composition or for the preparation of a composition of at least one derivative of 10-hydroxy-2-decenoic acid, the derivative or the composition being intended to inhibit the degradation of the skin and / or mucous membranes by inhibiting collagenases. The invention also relates to a method of cosmetic treatment of the skin and / or mucous membranes.

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

The natural human epidermis is mainly composed of three types of cells which are the keratinocytes, very majority, the melanocytes and the Langerhans cells. Each of these cell types contributes by its own functions to the essential role played in the body by the skin.

The dermis provides the epidermis with solid support. It is also its nourishing element. It mainly consists of fibroblasts and an extracellular matrix itself composed mainly of collagen, elastin and a substance, known as the fundamental substance, components synthesized by the fibroblast.

There are also leukocytes, mast cells or tissue macrophages. It is also crossed by blood vessels and nerve fibers. In normal skin, that is to say non-pathological or scarring, the fibroblast is in a quiescent state, that is to say non-proliferative, not very active from a metabolic point of view and not mobile.

It is the collagen fibers which ensure the solidity of the dermis. Collagen fibers are made up of fibrils sealed to each other, thus forming more than ten different types of structures. The solidity of the dermis is largely due to the entanglement of collagen fibers packed against each other in all directions. Collagen fibers participate in the elasticity and tone of the skin and or mucous membranes. The collagen fibers are constantly renewed, but this renewal decreases with age, which leads to thinning of the dermis. This thinning of the dermis is also due to pathological causes such as for example the hypersecretion of corticoid hormones, certain pathologies or vitamin deficiencies (case of vitamin C in scurvy). he is also admitted that extrinsic factors such as ultraviolet rays, tobacco or certain treatments (glucocorticoids, vitamin D and derivatives for example) also have an effect on the skin and its collagen level.

However, various factors lead to the degradation of collagen, with all the consequences that can be envisaged on the structure or the firmness of the skin and / or mucous membranes.

Although very resistant, collagen fibers are sensitive to certain enzymes called collagenases. Degradation of collagen fibers results in the appearance of soft, wrinkled skin that humans, preferring the appearance of smooth and taut skin, have always sought to combat.

Collagenases are part of a family of enzymes called metalloproteinases (MMPs) which are themselves members of a family of proteolytic enzymes (endoproteases or endopeptidases) which have a zinc atom coordinated to 3 cysteine residues and a methionine. in their active site and which degrade the macromolecular components of the extracellular matrix and basal membranes at neutral pH (collagen, elastin, etc.). Very widespread in the living world, these enzymes are present, but weakly expressed, in normal physiological situations such as organ growth and tissue renewal.

Their overexpression in humans and their activation are however linked to many processes, sometimes pathological, which involve the destruction and reshaping of the matrix. This either leads to an uncontrolled resorption of the extracellular matrix, or conversely the establishment of a state of fibrosis.

The family of metalloproteinases is made up of several well-defined groups based on their similarities in terms of structure and substrate specificity (see Woessner JF, Faseb Journal, vol. 5, 1991, 2145). Among these groups, mention may be made of collagenases intended for degrading fibrillar collagens (MMP-1 or interstitial collagenase, MMP-8 or neutrophil collagenase, MMP-13 or collagenase 3), gelatinases which degrade collagen type IV or any denatured form of collagen (MMP-2 or gelatinase A (72 kDa), MMP-9 or gelatinase B (92 kDa)), stromelysins (MMP-3) whose broad spectrum of activity is aimed at proteins in the matrix extracellular such as glycoproteins (fibronectin, laminin), proteoglycans, etc., or even membrane metalloproteinases. Prolonged exposure to ultraviolet radiation, particularly type A and / or B ultraviolet radiation, stimulates the expression of collagenases, particularly MMP-1. This is one of the components of photo-induced skin aging.

In addition to the menopause, the main modifications concerning the dermis are a reduction in the collagen level and the dermal thickness. This results in menopausal women thinning of the skin and or mucous membranes. The woman then feels a feeling of "dry skin" or of skin that pulls and there is an accentuation of fine wrinkles and fine lines on the surface. The skin has a rough appearance on palpation. Finally, the skin has reduced flexibility.

We then understand from reading the above the importance of collagen in the structure of tissues, particularly of the skin and / or mucous membranes, and the importance of combating its degradation so as to fight against aging whether chronobiological or photo-induced and its consequences, thinning of the dermis and / or degradation of collagen fibers which cause the appearance of soft and wrinkled skin.

One of the aims of the present invention is therefore to be able to have a new product which has a collagenase inhibiting effect and if possible no significant side effects.

Now, surprisingly and unexpectedly, the applicant has now discovered that certain specific derivatives of 10-hydroxy-2-decenoic acid exhibit an activity which inhibits the activity of collagenases, through the inhibition of the production and / or collagenase synthesis. By inhibition of production is meant inhibition of the signaling pathways leading to expression of collagenase messenger RNA and or inhibition of the translation of collagenase messenger RNA into proteins and / or inhibition of the secretion of collagenases outside the collagenase-producing cell.

In the publications of the prior art, derivatives of 10-hydroxy-2-decenoic acid are known for their property as activators of the immune system.

To the knowledge of the applicant, it has never been described in the prior art that derivatives of 10-hydroxy-2-decenoic acid exhibit an activity that inhibits the activity of collagenases. Consequently, the Applicant proposes the use of certain specific derivatives of 10-hydroxy-2-decenoic acid to inhibit the activity of collagenases and thus combat the degradation of collagen thus making it possible to treat the cutaneous signs of aging linked to the collagen breakdown.

By cutaneous signs of aging linked to the degradation of collagen, we mean all modifications of the external appearance of the skin due to the degradation of collagen, such as for example wrinkles and fine lines, withered skin, thinned skin, lack of elasticity and / or tone of the skin, but also all internal modifications of the skin which do not systematically result in a modified external appearance.

The first object of the invention is therefore the use in a composition of an effective amount of 10-hydroxy-2-decenoic acid derivatives of formula described below, the derivative or composition being intended to inhibit the expression of proteases of the extracellular matrix, particularly of metalloproteinases and even more particularly of matrix metalloproteinase type 1 (MMP-1). The invention therefore relates to compounds derived from 10-hydroxy-2-decenoic acid of the following formulas:

2-dimethylaminoethyl 10-hydroxy-dec-2-enoate of formula:

2,3-dihydroxypropyl 10-hydroxy-dec-2-enoate of formula:

1, 3-di- (10-hydroxy-dec-2-enoate) of 2-hydroxypropyl of formula:

Propyl 1,2,3-tri- (10-hydroxy-dec-2-enoate) of formula

1, 2-di- (10-hydroxy-dec-2-enoate) of 3 - [(2-methoxy) -ethoxy-methoxy] -propyl of formula:

Subsequently in the text, the term "derivatives of 10-hydroxy-2-decenoic acid" is understood to strictly denote the compounds described above, of natural or synthetic origin, purified or any preparation containing them. By natural origin is meant a compound extracted from natural material in which it is found. By synthetic origin is meant a compound prepared by chemical synthesis or by biotechnology.

Of course, it is possible to use according to the invention the derivatives of 10-hydroxy-2-decenoic acid alone or as a mixture.

Likewise, the derivatives of 10-hydroxy-2-decenoic acid can be used in their Cis and / or Trans form. Finally, the use according to the invention can be envisaged in a curative and / or preventive manner.

By inhibition is meant according to the invention, totally or partially reducing the level of production, expression and / or translation and / or secretion of proteases of the extracellular matrix.

Preferably according to the invention, the use of at least one derivative of 10-hydroxy-2-decenoic acid aims to combat the degradation of collagen, very preferably to treat the cutaneous signs of aging linked to the degradation of collagen , especially during menopause.

Among the skin lesions linked to the degradation of collagen, the invention is particularly aimed at treating wrinkles and fine lines, withered skin, soft skin, thinned skin or even the lack of elasticity and / or tone of the skin.

The 10-hydroxy-2-decenoic acid derivative can alone constitute the active principle of the compositions of the invention.

The amount of 10-hydroxy-2-decenoic acid derivatives which can be used according to the invention obviously depends on the desired effect and must be in an amount effective to inhibit expression and / or translation and / or secretion of proteases from the extracellular matrix.

By way of example, the amount of 10-hydroxy-2-decenoic acid derivatives which can be used according to the invention can range, for example, from 0.001% to 10% and preferably from 0.01% to 1% of the total weight of the composition.

The composition of the invention may be in any conceivable dosage form, suitable for topical application to the skin and / or the mucous membranes and / or the hair.

Preferably, the composition of the invention is intended for administration by the topical route.

The composition of the invention can be a cosmetic or dermatological composition. Preferably according to the invention, the composition is a cosmetic composition. The composition is a cosmetic composition because it is intended to improve the general skin appearance of the individual who uses it.

Very preferably, the composition of the invention is a cosmetic composition intended for administration by the topical route.

For administration by topical application to the ^* skin, hair and / or mucous membranes, the composition according to the invention obviously comprises a cosmetically acceptable medium, i.e. a medium compatible with the skin, mucous membranes, nails , the hair and can be in all dosage 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 or multiple emulsion, an aqueous or oily gel, a liquid, pasty or solid anhydrous product, an oil dispersion in an aqueous phase using spherules, these spherules possibly being polymeric nanoparticles such as nanospheres and nanocapsules or better lipid vesicles of ionic and or nonionic type.

This composition 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. It can also be in solid form, and for example in the form of a stick. It can be used as a care product, as a cleaning product, as a makeup product or even as a simple deodorant product.

In a known manner, the composition of the invention may contain the adjuvants usual in the cosmetic and dermatological fields, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, antioxidants, solvents, perfumes, fillers , filters, pigments, chelating agents, odor absorbers and coloring materials. The amounts of these various adjuvants are those conventionally used in the fields considered, 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, into the aqueous phase, into the lipid vesicles and / or into the nanoparticles.

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% of the total weight of the composition. 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 the coemulsifier are present in the composition in a proportion ranging from 0.3% to 30% by weight, and preferably from 0.5% to 20% of the total weight of the composition.

As oils which can be used in the invention, mention may be made of mineral oils, oils of vegetable origin (apricot oil, sunflower oil), oils of animal origin, synthetic oils, silicone oils and oils. fluorinated (perfluoropolyethers). Fatty alcohols (cetyl alcohol), fatty acids, waxes (beeswax) can also be used as fats.

As emulsifiers and coemulsifiers which can be used in the invention, mention may, for example, be made of fatty acid and polyethylene glycol esters such as PEG-40 stearate, PEG-100 stearate, fatty acid and polyol esters such as glyceryl stearate and sorbitan tristearate.

As hydrophilic gelling agents, mention may in particular be made 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.

The present invention further relates to a cosmetic treatment process intended to treat cutaneous signs of aging linked to the degradation of collagen, that is to say all modifications of the external appearance of the skin due to the degradation of collagen, such as for example wrinkles and fine lines, withered skin, mole skin, thinned skin, lack of elasticity and / or tone of the skin, but also all internal modifications of the skin which do not systematically result in an appearance modified exterior, such as for example all internal degradations of the skin, particularly of collagen, following exposure to ultraviolet radiation, characterized in that it is applied to the skin, to the hair, and / or to the mucous membranes , or that a cosmetic composition is ingested comprising at least at least one derivative of 10-hydroxy-2-decenoic acid.

The cosmetic treatment process of the invention can be implemented in particular by applying the cosmetic compositions as defined above, according to the usual technique for using these compositions. For example: application of creams, gels, serums, lotions, milks, shampoos or anti-sun compositions, on the skin, or on the hair or application of toothpaste on the gums.

The following examples and compositions illustrate the invention without limiting it in any way. In the compositions the proportions indicated are percentages by weight.

Example 1 Effect of 2-dimethylaminoethyl 10-hydroxy-dec-2-enoate on the production of collagenases.

The effect of 2-dimethylaminoethyl 10-hydroxy-dec-2-enoate on the production of interstitial collagenase was evaluated in a culture model of A2058 cells (derived from human melanomas: Templeton NS et al. 1990; Cancer Res ., 50: 5431-5431) and in a culture model of HT1080 cells derived from human fibrosarcoma (American Type Culture Collection: reference CCL 121). A2058 cells express and constitutively secrete type 1 metalloproteinase. HT1080 cells express little type 1 metalloproteinase in the basal state, but this expression is increased in the presence of TPA.

The cells are incubated in a MEM medium without phenol red containing amino acids at a concentration of 2 mM, sodium pyruvate at a concentration of 1 mM and 10% carbon-containing calf serum. They are then cultured at a density of 20,000 cells per well in the 24 wells of multiwell plate.

Twenty four hours after the cultivation, the cells are brought into contact with 2-dimethylaminoethyl 10-hydroxy-dec-2-enoate at a concentration of 25 μg ml. The production of interstitial collagenase is evaluated 96 hours later in the culture medium. This is carried out using an Elisa kit (Biotrack human MMP1; Amersham)

The results are expressed as a percentage decrease in the production of interstitial collagenase relative to the control, that is to say relative to a culture carried out under the same conditions in the absence of derivative.

The results show that the derivative at a dose of 25 μg / ml of decreases the production of interstitial collagenase by the A 2058 cells and by the HT61080 cells.

Example 2: Examples of formulations illustrating the invention and particularly the compositions according to the invention. These compositions were obtained according to the techniques conventionally used in the cosmetic industry.

Composition 1: Face care cream (oil-in-water emulsion) 10-Hydroxy-dec-2-enoate of 2-dimethylaminooethyl 1%

Glycerol stearate 2.00%

Polysorbate 60 (Tween 60 ^® sold by the company ICI) 1.00%

Stearic acid 1.40%

Triethanolamine 0.70% Carbomer 0.40%

Liquid fraction of shea butter 12.00%

Perhydrosqualene 12.00%

Antioxidant 0.05%

Perfume 0.50% Preservative 0.30%

Water qs 100.00%

Composition 2: Gel for the skin

10-Hydroxy-dec-2-enoine 2,3-dihydroxypropyl 2% All trans retinoic acid 0.05%

Hydroxypropylcellulose (Klucel H ^® sold by the company Hercules) 1.00%

Antioxidant 0.05%

Isopropanol 40.00%

Preservative 0.30% Water qs 100.00%

Composition 3: Gel for facial care

10-Hydroxy-dec-2-enoate of 2-dimethylaminoethyl 2,5%

Hydroxypropylcellulose (Klucel H ^® sold by the company Hercules) 1.00% Antioxidant 0.05%

Isopropanol 40.00%

Preservative 0.30%

Water qs 100.00% Composition 4: Gel

10-2,3-Dihydroxypropyl 1,5-Hydroxy-dec-2-enoate 1,5%

Hydroxypropylcellulose (Klucel H ^® sold by the company Hercules) 1.00%

Antioxidant 0.05% Lidocaine hydrochloride 2.00%

Isopropanol 40.00%

Preservative 0.30%

Water qs 100.00%

Composition 5: Sun erythema care cream (oil-in-water emulsion)

10-Hydroxy-dec-2-enoate of 2-dimethylaminoethyl 1%

Glycerol stearate 2.00% Polysorbate 60 (Tween 60 ^® sold by the company ICI) 1.00%

Stearic acid 1.40% Glycyrrhetinic acid 2.00%

Triethanolamine 0.70%

Carbomer 0.40%

Liquid fraction of shea butter 12.00%

Sunflower oil 10.00% Antioxidant 0.05%

Perfume 0.50%

Preservative 0.30%

Water qs 100.00%

Composition 6: Anti-wrinkle care cream for the face (oil / water emulsion)

10-Hydroxy-dec-2-enoine 2,3-dihydroxypropyle 2,5%

Glycerol stearate 2.00%

Polysorbate 60 (Tween 60 ^® sold by the company ICI) 1.00%

Stearic acid 1.40% n-Octanoyl-5-salicylic acid 0.50%

Triethanolamine 0.70%

Carbomer 0.40%

Liquid fraction of shea butter 12.00%

Perhydrosqualene 12.00% Antioxidant 0.05%

Perfume 0.50%

Preservative 0.30%

Water qs 100.00%

Claims

1. Use in a composition or for the preparation of a composition of at least one derivative of 10-hydroxy-2-decenoic acid, chosen from the following esters: 10-hydroxy-dec-2-enoate of 2- dimethylaminoethyl of formula:

2,3-dihydroxypropyl 10-hydroxy-dec-2-enoate of formula

2,3-di- (10-hydroxy-dec-2-enenoate) of 2-hydroxypropyl of formula

1,2,3-tri- (10-hydroxy-dec-2-enenoate) of propyl of formula:

the derivative or composition being intended to inhibit the expression and / or the translation and / or the secretion of the proteases of the extracellular matrix.

2. Use according to claim 1, characterized in that the derivative or the composition are intended to inhibit the expression and / or the translation and / or the secretion of metalloproteinases.

3. Use according to any one of claims 1 or 2, characterized in that the derivative or the composition are intended to inhibit the expression and or the translation and or the secretion of the type 1 matrix metalloproteinase.

4. Use according to any one of claims 1 to 3, characterized in that the derivative or the composition are intended to combat wrinkles and fine lines.

5. Use according to any one of claims 1 to 3, characterized in that the derivative or the composition are intended to fight against withered skin.

6. Use according to any one of claims 1 to 3, characterized in that the derivative or the composition are intended to fight against thinned skin.

7. Use according to any one of claims 1 to 3, characterized in that the derivative or the composition are intended to combat the lack of elasticity and / or tone of the skin.

8. Use according to any one of claims 1 to 3, characterized in that the derivative or the composition are intended to fight against internal degradations of the skin consecutive to exposure to ultraviolet radiation.

9. Use according to claim 8, the derivative or the composition being intended to combat degradation of collagen.

10. Use in a composition or for ^'preparing a composition of at least one derivative of the acid 10-hydroxy-2-decenoic as described in claim 1, the derivative or the composition being intended to treat skin damage associated with menopause.

11. Use according to any one of the preceding claims, characterized in that the derivative is used in an amount representing from 0.001% to 10% of the total weight of the composition.

12. Use according to the preceding claim, characterized in that the derivative is used in an amount representing from 0.01% to 1% of the total weight of the composition.

13. Use according to any one of the preceding claims, characterized in that the composition is intended for administration by the topical route.

14. A method of cosmetic treatment of the skin intended to treat the cutaneous signs of aging, characterized in that it is applied to the skin, to the hair, and / or to the mucous membranes, or that a composition is ingested cosmetic comprising at least one derivative of 10-hydroxy-2-decenoic acid as described in claim 1 or a composition comprising it.

15. Cosmetic skin treatment method intended to treat fine lines and wrinkles, withered skin, thinned skin, lack of elasticity and / or tone of the skin or any internal modifications of the skin which are not reflected systematically by a modified external appearance, characterized in that one applies to the skin, to the hair, and / or to the mucous membranes, or that one ingests a cosmetic composition comprising at least one acid derivative 10 -hydroxy- 2-decenoic as described in claim 1 or a composition comprising them.