FR2772611A1 - Cosmetic compositions containing auxin, preferably beta-naphthoxyacetic acid, to stimulate collagen synthesis, useful e.g. for combating cutaneous aging - Google Patents

Abstract

Collagen synthesis stimulating cosmetic compositions contain at least one auxin (I).

Description

The invention relates to the use of at least one auxin in a firming cosmetic composition. In particular, the compositions of the invention are intended to stimulate the restructuring of the skin and / or mucous membranes by stimulating the synthesis of collagen.

The subject of the invention is also a firming composition comprising at least one auxin.

The human skin consists of two compartments namely a superficial compartment, the epidermis, and a deep compartment, the dermis.

The natural human epidermis is composed mainly of three types of cells, which are the keratinocytes, a very large majority, melanocytes and 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 a solid support. It is also its nurturing element. It consists mainly of fibroblasts and an extracellular matrix composed mainly of collagen, elastin and a substance called the fundamental substance, components synthesized by the fibroblast. There are also leucocytes, mast cells or tissue macrophages. It is also made up of blood vessels and nerve fibers. In normal skin, ie non-pathological or scarring, the fibroblast is in the quiescent state, ie non-proliferative, not very active from a metabolic and non-mobile point of view.

It is the collagen fibers that ensure the solidity of the dermis. They are very resistant but sensitive to certain enzymes called collagenases. In the dermis, the collagen fibers consist of fibrils sealed to each other, thus forming more than ten different types of structures. The strength of the dermis is largely due to the entanglement of collagen fibers packed against each other in all directions. Collagen fibers contribute to the elasticity and tone of the skin and / or mucous membranes.

The collagen fibers are constantly renewed but this renewal decreases with age which causes a thinning of the dermis. But this thinning of the dermis is also due to pathological causes such as hypersecretion of corticosteroid hormones, certain diseases (Marfan syndrome, Ehlers-Danlos syndrome) or vitamin deficiencies (scurvy). It is also accepted that extrinsic factors such as ultraviolet rays, tobacco or certain treatments (retinoic acid and derivatives, glucocorticoids, vitamin D and derivatives for example) also have an effect on the skin and on its collagen level.

A breakdown of collagen fibers causes the appearance of mole and wrinkled skin that the human being, preferring the appearance of a smooth and tense skin, has always sought to fight.

In addition, at menopause, the main changes in the dermis are a decrease in collagen level and dermal thickness. This leads to a thinning of the skin and / or mucous membranes in the menopausal woman. The woman feels a sensation of "dry skin" or skin that pulls and there is an accentuation of fine lines and wrinkles surface. The skin has a rough appearance on palpation. Finally the skin has a reduced flexibility.

 It is shown that women lose 2.1% of their collagen level a year after menopause and that 30% are lost in the first five postmenopausal years.

We understand the importance of the presence of collagen fibers in the skin and the importance of maintaining or strengthening their presence.

 It is therefore important to have products whose effects aim to maintain the collagen level in the skin and maintain a smooth and tense appearance.

In this respect the Applicant has surprisingly and unexpectedly discovered that certain plant hormones, particularly auxins, have the property of stimulating collagen synthesis.

Auxins are phytohormones, ie plant hormones in the same way as gibberellins, cytokinins, ethylene or abscisic acid.

Plant hormones are chemical messengers that mediate intercellular communications in higher plants. These are usually relatively small molecules that act in very small amounts. Plant hormones are involved in the regulation of plant development processes.

Auxins are plant hormones involved in the regulation of plant cell elongation and plant growth in response to a unidirectional stimulus, a phenomenon known as tropism (see "Plant propagation by tissue culture", George EF and Sherrington
PD, 1984, Exegetics Limited or "Dictionnary of Natural Products" of
Chapman and Hall, 1997).

In the prior art, auxins are known to be used as calcium flux regulators on both sides of cellular membranes (EP 240 257), or as part of antitumor compositions (FR 2 597 39), for the treatment injuries to the surface of the skin and / or mucous membranes (EP 60 553) or for the treatment of burns or ulcers (EP 103 878).

To the knowledge of the applicant has never been described in the state of the art the use of at least one auxin to stimulate collagen synthesis.

The subject of the invention is therefore the use in a cosmetic composition of an effective amount of at least one auxin, the auxin or the composition being intended to stimulate the synthesis of collagen.

The term auxin is used to describe natural and / or synthetic substances that stimulate the elongation of coleoptiles and stems.

Thus, according to the invention, the auxins can be of natural or synthetic origin. By natural auxin, we mean any auxin, or any preparation containing it, present in a natural state in at least one plant. Synthetic auxin means any compound having an activity similar or identical to natural auxins, but which has been obtained by chemical synthesis or by biotechnology.

Thus, subsequently in the text the term auxin means as a purified natural or synthetic auxin or any preparation containing a natural or synthetic auxin.

The auxins that can be used according to the invention are those described in the two reference works cited earlier in the text. Among these, mention may be made, for example, of 3-indoleacetic acid (IAA), 4-chloroindole-3-acetic acid (4-Cl-lAA), phenylacetic acid (PAA) and indole acid. 3-butyric acid (IBA), 2,4-dichlorophenoxyacetic acid (2,4-D), oc-naphthaleneacetic acid (oc-NAA), p-naphthoxyacetic acid, indole ethanol,
Indole acetaldehyde and indole acetonitrile.

Preferably, according to the invention is used ss-naphthoxyacetic acid.

Of course, it is possible to use according to the invention auxins alone or in mixture.

Especially auxin or the composition containing it are used according to the invention for topical application to the skin and / or the mucous membranes.

We have seen previously that collagen is involved in the solidity of the dermis, therefore in the firmness of the skin and / or mucous membranes.

Thus, one of the aspects of the invention is therefore to propose the use in a cosmetic composition of an effective amount of at least one auxin, the auxin or the composition being intended to reduce the cutaneous signs of aging, more particularly decrease the appearance of soft and / or wrinkled skin.

Another aspect of the invention is to propose the use in a cosmetic composition of an effective amount of at least one auxin, the auxin or the composition being intended to stimulate the firming of the skin and / or mucous membranes.

According to another aspect, the subject of the invention is the use in a cosmetic composition of an effective amount of at least one auxin, the auxin or the composition being intended to promote the smoothing of the skin and / or stretch the skin.

According to another aspect, the subject of the invention is the use in a cosmetic composition of an effective amount of at least one auxin, the auxin or the composition being intended to combat the cutaneous effects of menopause, more particularly the effects of menopause on collagen.

The amount of auxin that can be used according to the invention obviously depends on the desired effect and must be in an amount effective to stimulate collagen synthesis.

By way of example, the amount of auxin that may be used according to the invention may range, for example, from 10.6% to 10% and preferably from 10% to 5% of the total weight of the composition.

The invention further relates to a firming cosmetic composition comprising, in a cosmetically acceptable medium, an effective amount of at least one auxin.

The invention also relates to a cosmetic composition for smoothing the skin or for stretching the skin, comprising in a cosmetically acceptable medium an effective amount of at least one auxin.

The invention also relates to a cosmetic composition for stimulating collagen synthesis comprising in an cosmetically acceptable medium an effective amount of at least one auxin.

The invention finally relates to a cosmetic composition for combating the effects of menopause on collagen comprising in a cosmetically acceptable medium an effective amount of at least one auxin.

By cosmetically acceptable medium is meant a medium compatible with the skin, the mucous membranes, the nails, the hair.

In these compositions, the auxin is preferentially β-naphthoxyacetic acid.

The composition according to the invention obviously comprises a cosmetically acceptable carrier and may be in any of the galenical forms normally used for topical application, especially in the form of an aqueous, hydroalcoholic or oily solution, an oil-in-oil emulsion or water or water-in-oil or multiple, an aqueous or oily gel, a liquid anhydrous product, pasty or solid, an oil dispersion in an aqueous phase using spherules, these spherules may be polymeric nanoparticles such as nanospheres and nanocapsules or better lipid vesicles of ionic and / or nonionic type.

This composition may 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 mousse . 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 as a simple deodorant product.

In a known manner, the composition of the invention may also contain the usual adjuvants 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 dyestuffs. The amounts of these various adjuvants are those conventionally used in the fields 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, 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. The oils, emulsifiers and coemulsifiers used in the composition in emulsion form 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 that 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). It is also possible to use fatty alcohols (cetyl alcohol), fatty acids and waxes (beeswax) as fatty substances.

As emulsifiers and coemulsifiers that can be used in the invention, mention may be made, for example, 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 (carbomer), acrylic copolymers such as copolymers of acrylates / alkylacrylates, polyacrylamides, polysaccharides, natural gums and clays, and, as lipophilic gelling agents, it is possible to mention mention modified clays such as bentones, metal salts of fatty acids, hydrophobic silica and polyethylenes.

The composition may contain other hydrophilic active agents such as proteins or protein hydrolysates, amino acids, polyols, urea,
Allantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts and hydroxy acids.

As lipophilic active agents, it is possible to use retinol (vitamin A) and its derivatives, tocopherol (vitamin E) and its derivatives, essential fatty acids, ceramides, essential oils, salicylic acid and its derivatives.

It is also possible to use, in combination with the auxin used according to the invention, compounds chosen from vegetable hormones; antibacterial agents such as macrolides, pyranosides and
tetracyclines, and especially erythromycin; calcium antagonists, such as verapamil and diltiazem; OH radical scavengers, such as dimethylsulfoxide; - extracts of plants such as lridaceae or soy
whether or not to contain isoflavones; extracts of micro-organisms, in particular bacterial extracts
like those of non-photosynthetic filamentous bacteria;
To the above list, other compounds can also be added, namely for example potassium channel openers such as diazoxide and minoxidil, spiroxazone, phospholipids such as lecithin, linoleic and linolenic acids, salicylic acid and its derivatives described in French Patent FR 2,581,542, such as salicylic acid derivatives bearing an alkanoyl group having from 2 to 12 carbon atoms at the 5-position of the benzene ring, hydroxycarboxylic or ketocarboxylic acids and their esters, lactones and their corresponding salts, anthralin, carotenoids, eicosatetraenoic and eicosatrienoic acids or their esters and amides, vitamin D and its derivatives.

According to the invention, it is possible, inter alia, to associate at least one auxin with other active agents intended in particular for the prevention and / or treatment of cutaneous affections. Among these active agents, there may be mentioned by way of example -the agents modulating the differentiation and / or the proliferation and / or the
skin pigmentation such as retinoic acid and its isomers, retinol and
its esters, vitamin D and its derivatives, estrogens such as estradiol,
Kojic acid or hydroquinone; antibacterials such as clindamycin phosphate, erythromycin or
antibiotics of the class of tetracyclines - agents modulating bacterial adhesion on the skin and / or mucous membranes
such as honey, especially the mile of acacias and some sugar derivatives - antiparasitics, especially metronidazole, crotamiton or
pyrethroids; antifungals, in particular compounds belonging to the class of
imidazoles such as econazole, ketoconazole or miconazole or their
salts, polyene compounds, such as amphotericin B, the compounds of the
family of allylamines, such as terbinafine, or octopirox; antiviral agents such as acyclovir; steroidal anti-inflammatory agents, such as hydrocortisone,
betamethasone valerate or clobetasol propionate, or anti-inflammatory agents
non-steroidal inflammatory drugs such as ibuprofen and its salts, diclofenac
and its salts, acetylsalicylic acid, acetaminophen or acid
glycyrrhetinic - anesthetic agents such as lidocaine hydrochloride and its derivatives - antipruritic agents such as thenaldine, trimeprazine or cyproheptadine; keratolytic agents such as alpha and beta acids
hydroxycarboxylic or beta-keto carboxylic acid, their salts, amides or esters
and more particularly hydroxy acids such as glycolic acid, acid
lactic acid, salicylic acid, citric acid and, in general, acids
fruit, and n-octanoyl-5-salicylic acid - anti-free radical agents, such as alpha-tocopherol or its esters,
su peroxide dismutases, some metal chelators or ascorbic acid
and its esters - antiseborrhoeics such as progesterone; anti-dandruff such as octopirox or zinc pyrithione; - anti-acne drugs such as retinoic acid or benzoyl peroxide.

substances such as substance P, CGRP or
bradykinin or NO synthase inhibitors, compounds described as
being active in the treatment of sensitive skin and as having
anti-irritant effects, especially with regard to irritating compounds
possibly present in the compositions.

As actives, it is possible to use, in particular, moisturizers such as polyols (for example glycerine), vitamins (for example D-panthenol), anti-inflammatory agents, soothing agents (allantoin, cornflower water), filters UVA and UVB, the matting agents (eg partially crosslinked polydimethylorganosiloxanes sold under the name KSGCR by Shin Etsu), and mixtures thereof.

It is also possible to add anti-wrinkle active agents, and especially tensor products such as vegetable proteins and their hydrolysates, in particular the soy protein extract sold under the name EleseryltE) by the company LSN or the oat derivative sold under the name Reductine (IX) by the company Silab.

Of course, auxins can be used in the preparation of cosmetic and / or pharmaceutical, particularly dermatological, compositions intended to stimulate the synthesis of collagen.

Other characteristics and advantages of the invention will emerge more clearly from the examples which follow, given by way of illustration and not limitation. In the foregoing or the foregoing, the proportions are given in weight percent unless otherwise indicated.

EXAMPLE 1 Study of the Effect of SS-Naphthoxy Acetic Acid on the Synthesis of Collagen

The study is done by measuring the incorporation of radioactive proline into normal human dermal fibroblast cultures.

The fibroblast cultures are carried out according to the standard cell culture methods, namely in MEM / M199 medium sold by Gibco, in the presence of sodium bicarbonate (1.87 mg / ml) of L-glutamine (2 mM). penicillin (50 IU / ml) and 10% fetal calf serum (Gibco).

The test is performed on cell cultures at 80% confluency in 24-hole plate. The α-naphthoxyacetic acid, at a concentration of 10 -4 M, is contacted with the cells for 48 hours. Labeling with tritiated proline (L- [2,3-3H] -proline sold by Amersham, 33 μCi / ml) is carried out for 24 hours.

The level of incorporated tritiated proline is measured at the end of the test by acid precipitation of the proteins on filters and counting by liquid scintillation.

The results are evaluated with respect to a control consisting of cells that have not been treated with β-naphthoxyacetic acid.

A positive control (vitamin C at 201 μg / ml) known to stimulate collagen synthesis and a negative control (10-6 M retinoic acid) known to inhibit collagen synthesis are introduced into the assay as a reference.

The results of this test are presented in the following table.

<Tb>

Treatment <SEP> cpm <SEP>% <SEP> p
<tb><SEP> Cells <SEP> No <SEP> Processed <SEP> 19261 <SEP> 100 <SEP>
<tb><SEP><SEP> ss-naphthoxyacetic acid <SEP> 34683 <SEP> 180 <SEP><0.01
<tb><SEP><SEP> Retinoic acid <SEP> 13160 <SEP> 68 <SEP><0.01
<tb><SEP> Vitamin <SEP> C <SEP> 40344 <SEP> 209 <SEP><0.01
<tb> cpm: shots per minute. p: confidence interval calculated according to the Dunett method.

These results show that p-naphthoxyacetic acid significantly stimulates the incorporation of proline in collagen and therefore has an effect on the neosynthesis of collagen.

Example 2: Examples of compositions according to the invention. These compositions are obtained by the usual techniques commonly used in cosmetics or pharmacy.

Composition 1: care cream
Beeswax 1.5
Apricot almond oil 13.0%
Perfume
0.01% s-naphthoxyacetic acid
Xanthan 0.5%
Cyclopentadimethylsiloxane 5.0%
Demineralized water sterilized 69,29
Sucrose mono-di-palmitostearate 3.0
Methylglucose sesquistearate 3.0%
Stearic acid 1.0%
Cetyl alcohol 3.0%
Conservatives 0.3%
Composition 2: body oil
Vaseline oil 47.99%
Apricot almond oil 6.0%
Perfume 1.0
0.01% s-naphthoxyacetic acid
Cyclopenta dimethylsiloxane 45.0%
Composition 3: cleansing milk
2-ethylhexyl palmitate 10.5%
Liquid fraction of shea butter 16.5%
Conservatives 0.3%
Perfume 0, 15%
0.01% s-naphthoxyacetic acid
Sodium hydroxide 0.04%
Carboxyvinyl polymer 0.2
Demineralized water sterilized 69.8
Mixture of cetylstearylglucoside
and cetyl and stearyl alcohols 2,5
Composition 4: care cream
Beeswax 1.5
Apricot almond oil 13.0%
Conservatives 0.3%
Perfume 0.4%
Triethanolamine 0.17%
Acetic beta-naphthoxy acid 0.01%
2,4-dichlorophenoxyacetic acid 0.01
Xanthan 0.5%
Cyclopenta dimethylsiloxane 5.0%
Demineralized water sterilized 69,28
Sucrose Mono-di-palmitostearate 3.0%
Methylglucose sesquistearate 3.0%
Stearic acid 1.0%
Cetyl alcohol 3.0%

Claims (17)

 1. Use in a cosmetic composition of an effective amount of at least one auxin Auxin or the composition is intended to reduce the cutaneous signs of aging. 2. Use in a cosmetic composition of an effective amount of at least one auxin auxin or the composition being intended to stimulate the firming of the skin and / or mucous membranes. 3. Use in a cosmetic composition of an effective amount of at least one auxin auxin or the composition being intended to promote the smoothing of the skin and / or to stretch the skin. 4. Use in a cosmetic composition of an effective amount of at least one auxin, the auxin or the composition being intended to stimulate collagen synthesis. 5. Use in a cosmetic composition of an effective amount of at least one auxin Auxin or the composition being intended to combat the cutaneous effects of menopause. 6. Use in a cosmetic composition of an effective amount of at least one auxin Auxin or the composition being intended to combat the effects of menopause on collagen. 7. Use according to any one of the preceding claims, characterized in that the composition is used topically on the skin and / or mucous membranes. 8. Use according to any one of the preceding claims, characterized in that the auxin is chosen from indolacetic acid (IAA), 4-Chloroindole-3-acetic acid (4-Cl-lAA), Phenylacetic acid (PAA), Indole-3-butyric acid (IAB), 2,4-dichlorophenoxyacetic acid (2,4-D), Α-naphthaleneacetic acid (α-NAA), p-naphthoxyacetic acid, indole ethanol, indole acetaldehyde and indole acetonitrile. 9. Use according to the preceding claim, characterized in that the auxin is ss-naphthoxyacetic acid. 10. Use according to any one of the preceding claims, characterized in that the auxin is present in an amount ranging from 10-6% to 10% of the total weight of the composition 11. Use according to the preceding claim, characterized in that auxin is present in an amount ranging from 10-3% to 5% of the total weight of the composition. 12. A firming cosmetic composition comprising, in a cosmetically acceptable medium, an effective amount of at least one auxin. 13. Cosmetic composition for smoothing the skin comprising in a cosmetically acceptable medium an effective amount of at least one auxin. 14. A cosmetic composition for stretching the skin comprising, in a cosmetically acceptable medium, an effective amount of at least one auxin. 15. Cosmetic composition for stimulating collagen synthesis comprising in a cosmetically acceptable medium an effective amount of at least one auxin. 16. Cosmetic composition for combating the effects of menopause on collagen comprising in a cosmetically acceptable medium an effective amount of at least one auxin. 17. Composition according to any one of claims 12 to 16, characterized in that the auxin is ss-naphthoxyacetic acid.