1 - Cosmetic treatment method for reducing or preventing skin redness, characterized in that an effective amount of at least one compound of formula I is applied to the skin:
R1 -CHOH-CH(NH-COR2)(CH2OH) (I)
in which R-| denotes a C-| 3 to C-17 alkoyl or alkenyl radical, R2 denotes a linear C-| 3-
C-| 9 hydrocarbon-based radical which may comprise one or more ethylenically unsaturated groups, especially one or two ethylenically unsaturated groups,
or a composition containing the compound of formula I in a physiologically acceptable medium.
2- Cosmetic method according to Claim 1 , characterized in that it is intended to prevent or reduce skin redness induced by at least one condition chosen from rosacea, irritable or irritated skin, the action of UV radiation, chemical peels, dermabrasion and laser treatments.
3- Cosmetic method according to at least one of the preceding claims, characterized in that the compound of formula I is chosen from N-oleoyl dihydrosphingosine and derivatives thereof.
4- Cosmetic method according to at least one of the preceding claims, characterized in that the compound of formula (I) is 2-oleoylaminooctadecane-1 ,3-diol.
5- Cosmetic treatment method according to at least one of the preceding claims, characterized in that the compound of formula I is used at a concentration from 0.001 % to 10% by weight relative to the total weight of the composition containing it.
6- Cosmetic method according to at least one of the preceding claims, characterized in that the compound of formula I or the composition containing it is applied to the skin after exposure to UV radiation.
7- Cosmetic use of at least one compound of formula I or of a composition containing it as defined in any one of Claims 1 to 5, as a calmative, said compound being present in a cosmetic composition.
8- Cosmetic use of at least one compound of formula I or of a composition containing it according to Claim 7, in the absence of an additional antimicrobial agent, for the treatment or prevention of dandruff conditions.
9- Cosmetic use of at least one compound of formula I according to at least one of Claims 7 or 8, characterized in that the cosmetic composition also contains at least one compound chosen from desquamating agents, antidandruff agents and antipruritic agents. 10- Compound of formula I, as defined in Claims 1 or 4, for its use for the treatment of the signs of skin irritation reactions.
1 1 - Compound of formula I for its use according to Claim 10, characterized in that the signs of skin irritation reactions are chosen from solar erythemas, redness of skin having acne lesions or following an insect sting, seborrhoeic dermatitis and rosacea.
12- Cosmetic treatment method according to at least one of Claims 1 to 6, or cosmetic use according to any one of Claims 7 to 9, characterized in that the compound of formula I is applied in combination with at least one compound chosen from wound- healing agents, depigmenting agents and hydroxy acids.
The present invention relates to the cosmetic treatment and the prevention of redness of the skin or of the scalp, in particular redness associated with exposure to solar radiation, or that occurs especially during procedures that have an aesthetic purpose such as peels. It also relates to the use of compounds from the group of ceramides, as a calmative. These compounds will also be of use for treating the signs of skin irritations.
The present invention additionally relates to a composition comprising a ceramide derivative and optionally at least one compound capable of causing irritation of the skin, mucous membranes and/or scalp, and also to a cosmetic or dermatological assembly.
The field of the invention thus relates to protecting the skin and/or its integuments against skin irritation or skin inflammation induced by a stress.
The term "stress" is understood to mean any stress of exogenous origin, such as a stress of chemical origin (e.g.: xenobiotics, irritant chemicals, etc.), of environmental origin (e.g.: temperature, climate, UV radiation, atmospheric pollution, especially heavy metals, gaseous pollutants such as sulphur dioxide, ozone and nitrogen oxides, oxidative stress, cigarette smoke, etc.), of mecanical origin (e.g.: friction on contact with a razor, etc.), of infectious origin (e.g.: allergen, antigen, etc.), and/or any stress of endogenous origin, such as disorders involving an irritation mechanism and/or hormonal mechanism adversely affecting the skin.
The skin reacts via several combined signs, including redness, temperature rise of the area in question, and a local feeling of discomfort. In the case of an inflammation, the combination of 4 signs is observed, namely swelling (oedema), feeling of heat, pain that appears to pulse and an erythema (local vasodilation). However, some of these signs may be present in other situations, independently of any inflammatory phenomenon.
The term "redness" is understood to mean a pink to red, or even dark red, coloration of all or part of the skin of the body, scalp, mucous membranes or semi-mucous membranes. This manifestation, also referred to as erythema, may be a sign of a healthy complexion (pink cheeks), but it is sometimes undesirable. This is in particular the case when it is associated with other symptoms of a skin disorder such as rosacea, or couperose.
UV radiation with wavelengths between 280 nm and 400 nm enable tanning of the human epidermis. But it is also known that rays with wavelengths between 280 nm and 320 nm, known by the name UV-B rays, cause erythemas and skin burns. Furthermore, UV-A rays, having wavelengths between 320 nm and 400 nm, are also capable of inducing a detrimental change in the skin: in particular they cause a loss of elasticity of the skin and the appearance of wrinkles leading to premature ageing, and also promote the onset of the erythematous reaction or amplify this reaction in certain individuals and may even be the cause of phototoxic or photoallergy reactions.
Faced with these stresses, the skin reacts via a cutaneous reaction that aims to restore the disrupted homeostatic balance or to repair the damage caused. It implements a cascade of reactions that may give rise to the persistent irritant process, which is characterized mainly by irritation of the skin or an involution of the hair bulb and its matrix environment.
The term "treating", unless otherwise indicated, is understood to mean any action that aims to improve the comfort or the well-being of an individual; this term therefore covers preventing, attenuating or relieving and also curative treatment.
Nowadays, a very large number of treatments exist, possibly involving cosmetic surgery, for enhancing the appearance of human beings. These treatments, which will be referred to hereinbelow as treatments for aesthetic purposes, may act in many ways, and may consist, for example, in erasing or masking certain skin imperfections, in refining the silhouette, or alternatively in attenuating or even erasing the signs of ageing.
Peels are skin treatments intended to bring about signs of skin rejuvenation, such as reduction of wrinkles and increase in the radiance of the skin. These treatments are used in particular to treat facial skin, the decolletage and the back of the hands when these areas exhibit signs of photoageing such as pigmentary spots, wrinkles, loss of radiance, loss of texture, or loss of skin elasticity.
For the purposes of the present invention, the term "treatment for aesthetic purposes" means any treatment for remedying an imperfection deemed as being unsightly, and more generally any treatment for beautifying, i.e. for enhancing the appearance of, the individual undergoing such a treatment.
The treatments for aesthetic purposes under consideration according to the invention may more particularly be surface skin treatments or invasive treatments for aesthetic purposes. For the purposes of the invention, the term "surface skin treatment for aesthetic purposes" means treatments liable to have an aggressive nature with regard to the epidermis and especially liable to cause skin irritation. They may especially be chemical peels and laser treatments.
As surface skin treatment for aesthetic purposes, mention may be made, for example, of chemical peels and laser treatments.
The latest generation of lasers uses a system for transforming the laser beam into a multitude of spaced-out beams in order to produce on the skin spaced-out impacts, thus maintaining areas of unimpaired healthy skin between the affected areas.
For the purposes of the invention, the term "laser treatment" means any treatment for aesthetic purposes using a laser, including the physical peels described previously.
Examples of laser treatments that may thus also be mentioned include laser depilation; laser treatment of angiomas; laser treatment of redness, especially of erythrosis or couperose; laser treatment of lentigo, especially actinic lentigo; laser treatment of tattoos; or laser treatment of wrinkles. Peel procedures, in particular medico-surgical procedures, are quite harsh treatments for the skin. Generally, the harsher they are, the better the final aesthetic result.
Therefore, there is still a need to find novel active agents capable of combating these cutaneous manifestations.
Ceramides are important epidermal lipids, in particular in the stratum corneum. They play a key role in restoring the barrier function.
Application EP 1 962 788 describes the use of ceramides as depigmenting agents, after UV irradiation. The compounds N-oleoyl dihydrosphingosine and N-2-hydroxypalmitoyl dihydrosphingosine have a similar action in a predictive test of incorporation of thiouracil.
Combined use of some sphingolipids with some beta-hydroxy-acids has also been disclosed in the field of dermatological treatments to fight against skin affections, and notably against acne. Such a combined application of sphingolipids and beta-hydroxy-acids in which a good use of the active principles combination anti-bacterial effect is made, is disclosed in the PCT application n° WO 01/70235.
The Japanese patent application n° JP 2005 187398, in which the combined use of some sphingolipids with antimicrobial agents for scalp care is disclosed, in particular for the treatment of dandruff states of scalp, may also be cited. Unexpectedly, it has now been found, within the context of the present invention, that specific ceramides make it possible to combat skin redness, in particular redness induced by UV irradiation. It has also been found that these ceramides, by favouring re-epithelialization, stimulate the healing and the recovery of a normal barrier function.
This is why one subject of the present invention is a cosmetic treatment method for reducing or preventing skin redness and/or the signs of cutaneous microcirculation, characterized in that an effective amount of at least one compound of formula I is applied to the skin:
R1 -CHOH-CH(NH-COR2)(CH2OH) (I)
in which R-| denotes a C-| 3 to C-\ j alkoyl or alkenyl radical, R2 denotes a linear C13-C-19 hydrocarbon-based radical which may comprise one or more ethylenically unsaturated groups, especially one or two ethylenically unsaturated groups; the method may also be carried out by applying a composition containing the compound of formula I in a physiologically acceptable medium.
As further mentioned in the present specification, in some embodiments, a compound of formula (I) may be used in combination with one or more other active agents, such as compounds chosen from wound-healing agents, depigmenting agents and hydroxylated acids.
Another subject of the invention is the cosmetic use of at least one compound of formula I as a calmative. Preferably, said compound, when used as a calmative, is present in a cosmetic and/or dermatological composition.
According to the invention, the term "calmative" is understood to mean an agent which helps to reduce the skin and/or scalp inconvenience, for example by calming feelings of inconvenience, feelings of itching or by attenuating redness. Another subject of the invention is a compound of formula I , in particular chosen from N- oleoyl dihydrosphingosine and phosphoryl derivatives thereof, for its use for the treatment of the signs of skin irritation reactions.
The invention also relates to the use of at least one compound of formula I for the preparation of compositions intended for the treatment of solar erythemas, redness accompanying a burn, and erythemas associated with the use of peels or lasers. The invention also relates to compositions comprising at least said compound of formula I, combined with at least one other calmative or compositions comprising at least said compound combined with at least one agent having a particular irritant side effect (e.g.: cosmetic active agents, dermatological active agents).
Unless otherwise indicated, within the context of the invention, the term "skin" means any cutaneous surface of the body, including the skin and broadened to the scalp and to the mucous and semi-mucous membranes and the term "integuments" means the eyelashes, body hair, head hair and nails.
One subject of the invention also relates to compositions combining at least one compound of formula I with one or more other active agents, especially chosen from agents that act on the microcirculation. Active agents that act on the microcirculation (vasoprotective agent, vasoconstrictor agent) may be chosen from flavonoids, ruscogenins, esculosides, escin extracted from horse chestnut, nicotinates, hesperidin methyl chalcone, lavender or rosemary essential oils, extracts of Ammi visnaga.
The amount of these active agents may vary to a large extent. Generally, these active agents are present at a concentration ranging from 0.01 % to 15% and preferably from 0.05% to 10% by weight relative to the total weight of the composition.
Indeed, it has surprisingly been found that the compounds of formula I according to the invention may prevent or reduce the appearance of skin redness, whether or not it is caused by UV irradiation. Skin redness may especially be induced by at least one condition chosen from rosacea, irritable or irritated skin, the action of UV radiation, chemical peels, dermabrasion and laser treatments, but also the redness associated with acne lesions or following insect stings.
Moreover, the compounds of formula I according to the invention favour the reconstruction of a good quality epidermis after a lesion, especially after an injury or an excoriation. This is an improvement and an acceleration of the re-epithelialization on skin for which the physical integrity is interrupted; this effect is different from a barrier effect observed during the application of ceramides by re-establishing the lipid content at the skin surface. The ceramides of formula I bring about a faster healing (re-epithelization) (estimated by measuring the transepidermal water loss, or TEWL). Ceramides are known for being constituents of the skin barrier, but not for directly stimulating the proliferation of epidermal cells. The healing rate exhibits a significant difference compared to the placebo (same excipient without ceramide).
The method and the uses according to the invention will in particular be suitable for the treatment of redness caused by UV irradiation, in particular skin irradiation at an erythematous dose.
It has been found, within the context of the present invention, that ceramides of class II such as the compounds of formula I, and in particular 2-OLEOYLAMINOOCTADECANE-1 ,3-DIOL
. .. · . .^. · . ,^„.,-.Q „u
are particularly effective for preventing such redness or erythemas.
On the contrary, a ceramide such as hydroxy palmitoyl sphinganine, has no anti- erythematous activity after irradiation by UV radiation.
The compounds of formula I or the compositions containing them are thus of use for preventing or reducing skin redness following exposure to UV radiation, or for preventing or reducing the cutaneous signs associated with a cutaneous surface treatment chosen from chemical peels, dermabrasion and laser treatments.
The method according to the invention is cosmetic, as it aims to improve the appearance of an individual in good health; it has a purely aesthetic purpose, especially when it is combined with a cutaneous surface treatment for reducing the cutaneous signs of ageing, which corresponds to a physiological modification.
According to one of the embodiments of the method according to the invention, the compound of formula I or the composition containing it is applied to the skin after exposure to UV radiation. One subject of the invention is especially a cosmetic method for improving the appearance of the skin of a subject in which, after a first step of invasive treatment for aesthetic purposes, a compound of formula I or a composition containing it is applied to the skin that has undergone the treatment. The invasive treatment for aesthetic purposes will especially be chosen from chemical peels, dermabrasion and laser treatments. The cosmetic method will especially be intended to prevent or reduce skin redness.
Compound I will be able to be applied to the skin immediately after the exposure of the skin to the condition capable of inducing skin redness, or after a period of between 2 minutes and 6 hours after this exposure. This application will then be able to be repeated for several days, especially for 1 to 15 days, and in particular for 1 to 8 days. It could be a daily application or a multiple daily application, especially in the evening before going to bed.
According to another embodiment, the compound of formula I - or the composition containing it - will be applied to skin after healing.
This embodiment will be especially advantageous for the treatment of acne marks, which may persist in subjects even though the acnes spots have disappeared, but that leave redness remaining for several months or several years.
These various embodiments may of course be combined.
The concentrations of compounds I applied will be adapted by a person skilled in the art as a function of the formulation and of the desired effect. Compositions suitable for the implementation of the invention contain, for example, the compound of formula I at a concentration of from 0.001 % to 10% by weight relative to the total weight of the composition, especially from 0.1 % to 5%, or even less than or equal to 2% by weight relative to the total weight of the composition.
In particular, use will be made of a compound of formula I chosen from N-oleoyl dihydrosphingosine and derivatives thereof.
The invention also relates to the cosmetic use of at least one compound of formula I as a calmative; the compound of formula I will preferably be in a cosmetic composition containing a physiologically acceptable medium.
The compounds of formula I are more particularly of use for preventing or reducing a skin reaction induced by the action of chemicals, of compounds capable of causing a skin irritation or itch, or of a peel, the action of temperature, of climate, of UV radiation, of atmospheric pollution, or else the action of friction on the skin, mucous membrane or scalp.
According to one of its aspects, the invention relates to the use of at least one compound of formula I, or of a composition containing it, for the treatment or prevention of dandruff conditions. The compound(s) of formula I will advantageously be applied to the scalp, in order to prevent or reduce the cutaneous signs associated with dandruff conditions, and especially redness or irritation. According to the invention, the compound of formula I will be able to be applied in combination with at least one compound chosen from wound-healing agents, antidandruff agents, depigmenting agents, desquamating agents such as hydroxy acids, and antipruritic agents such as crotamiton.
Other additional active agents will be able to be present in the compositions according to the invention, in particular calmatives.
In some particular embodiments of the use of at least one compound of formula (I), or of a composition containing it, for treating or preventing dandruff states, said compound of formula (I) is used in the absence of an additional antimicrobial agent. In these particular embodiments, said compound of formula (I) is not combined with an additional antimicrobial agent.
The invention also relates to a combination product for simultaneous use, separate use or sequential use over time, comprising:
(i) at least one compound of formula I or hydroxy palmitoyl sphinganine,
(ii) at least one compound chosen from wound-healing agents, antidandruff agents and desquamating agents, in particular alpha or beta hydroxy acids.
The invention also relates to a combination product for simultaneous use, separate use or sequential use over time, comprising:
(i) at least one compound of formula I or hydroxy palmitoyl sphinganine,
(ii) at least one compound chosen from wound-healing agents and antidandruff agents. In the above embodiment, said combination product may be exempt from desquamating agent. In the above embodiment, said combination product may comprise a desquamating agent with the exception of a beta-hydroxy-acid compound. In the above embodiment, said combination product may be exempt from beta-hydroxy-acid compound, or alternatively, may be exempt from beta-hydroxy-acid compound and alpha-hydroxy-acid compound. Beta- hydroxy-acid compounds encompass compounds of formulae (A) and/or (B) disclosed somewhere else in the present specification.
Desquamating agents that are particularly suitable for the invention will be chosen from hydroxy acids, in particular alpha or beta hydroxy acids, especially salicylic acid and derivatives thereof, 5-n-octanoylsalicylic acid, jasmonic acid and derivatives thereof, in particular jasmonic acid (3-hydroxy-2-pentylcyclopentaneacetic acid) and the cosmetically acceptable salts thereof.
Compositions (i) and (ii) may be packaged separately inside two compartments, formed either by two separate containers, or inside a single device. The term "single device" is understood within the present invention to mean a device via which the two compartments are firmly attached to one another.
The present invention finally comprises an assembly, in particular a cosmetic or dermatological assembly, comprising two compositions in two separate containers or two separate parts of one and the same container, one of the compositions comprising at least one compound of formula I or phosphoryl derivatives thereof and the other composition comprising at least one compound chosen from wound-healing agents and depigmenting agents and, in some embodiments, the other composition may comprise desquamating agents, especially hydroxy acids.
Another subject of the invention is a compound of formula I, especially N-oleoyl dihydrosphingosine and/or derivatives thereof, for its use for the treatment of the signs of skin irritation reactions. The invention also relates to the use of at least one compound of formula I, especially N- oleoyl dihydrosphingosine and/or derivatives thereof, for the preparation of a composition intended for the treatment of the signs of skin irritation reactions, in particular chosen from solar erythemas, redness of skin having acne lesions or following an insect sting, seborrhoeic dermatitis and rosacea. Wound-healing agents
As examples of wound-healing agents mention may especially be made of: sugar derivatives such as O-octanoyl-6-D-maltose and N-acetyl glucosamine, allantoine, urea, wheat germ oil, certain amino acids such as hydroxyproline, arginine, serine, glutamic acid, and also extracts of white lily (e.g.: Phytelene Lys 37EG 16295 from Indena), a yeast extract, such as the wound-healing agent LS 7225B from LS (Cognis), tamanu oil, Saccharomyces cerevisiae extract or Biodynes TRF from Arch Chemical, oat extracts, chitosan and derivatives, carrot extracts, Artemia extract or GP4G from Vincience, sodium acexamate, lavandin extracts, honey or propolis extracts, ximeninic acid and salts thereof, such as acido ximeninico from Indena, Rosa rugosa oil, Souci Ami Liposolible from Alban Muller, horsetail extracts, Herbasol lemon from Cosmetochem, Helichrysum extracts, β-glucan and derivatives, shea butter and purified fractions thereof, modified exopolysaccharides and alkylsulphonated polyaminosaccharides. As preferred wound-healing agents according to the invention, use will be made of tamanu oil, sodium acexamate, honey extracts, horsetail extracts and Helichrysum extracts, and mixtures thereof. Advantageously, the compound of formula I or derivatives thereof will be combined with an agent chosen from ascorbic acid and derivatives thereof such as magnesium ascorbyl phosphate and ascorbyl glucoside, and/or madecassoside, and/or a tepescohuite extract, or a C-glycoside derivative, and/or mixtures thereof in any proportion. The term "C-glycoside derivative" is understood in particular to mean the compounds described in application EP 1 345 919 and that favour the synthesis of GAGs.
These compounds correspond to the formula:
R' represents a saturated linear Ci to C2o, preferably Ci to Ci0, alkyl radical, or an unsaturated linear C2 to C2o, preferably C2 to Ci0, alkyl radical, or a saturated or unsaturated, branched or cyclic C3 to C20, preferably C3 to Ci0, alkyl radical, which is optionally substituted as described previously;
S represents a monosaccharide, in particular D-glucose, D-xylose, N-acetyl-D-glucosamine or L-fucose, more particularly D-xylose; and
X represents a group chosen from -CO-, -CH(OH)-, -CH(NR'1R'2)- or -CH(R')-, as described previously.
Among the C-glycoside derivatives that correspond to the preceding formula, use is more preferably made of those for which: R' represents a saturated linear Ci to C4, preferably Ci to C3, alkyl radical, optionally substituted with -OH, -COOH or -COORV, RV being a saturated linear Ci to C4 alkyl radical, especially the ethyl radical;
S represents a monosaccharide, as described previously; and
X represents a group chosen from -CO-, -CH(OH)-, -CH(NH2)-, and more particularly a - CH(OH)- group.
Among the C-glycoside derivatives that correspond to the preceding formula, use is very particularly made of those for which R' represents an unsubstituted saturated linear Ci to C4, preferably Ci to C2, alkyl radical, in particular the ethyl radical.
According to one embodiment, use is made of C-p-D-xylopyranoside-2-hydroxypropane or C-a-D-xylopyranoside-2-hydroxypropane; C-p-D-xylopyranoside-2-hydroxypropane is particularly preferred.
According to one particular embodiment, the C-glycoside derivative may be C-a-D- xylopyranoside-2-hydroxypropane that is in the form of a solution containing 30% by weight of active material in a water/propylene glycol (60/40 wt%) mixture.
These compounds act directly on the desquamation by favouring exfoliation, such as alpha hydroxy acids and beta hydroxy acids, polyhydroxy monocarboxylic acids, polyhydroxy bicarboxylic acids, polyhydroxy tricarboxylic acids; and (3-hydroxy-2-pentylcyclopentyl)acetic acid.
As preferred a-hydroxy acids, mention may be made of: glycolic acid, citric acid, lactic acid, tartaric acid, malic acid or mandelic acid.
The preferred β-hydroxy acids are chosen from: salicylic acid and derivatives thereof, in particular 5-n-octanoylsalicylic acid.
In particular, the desquamating agent according to the present invention is chosen from salicylic acid derivatives, jasmonic acid or its derivatives, and gentisic acid or its derivatives, salts thereof and mixtures thereof in any proportion.
According to one particular embodiment of the invention, the desquamating agent likely to be present in the composition according to the invention is chosen from salicylic acid and its derivatives such as 5-n-octanoylsalicylic acid (or capryloylsalicylic acid), 5-n- decanoylsalicylic acid, 5-n-dodecanoylsalicylic acid, 5-n-heptyloxysalicylic acid and their corresponding salts, resulting from a mineral or organic base.
The salicylic acid compound is advantageously chosen from salicylic acid and 5-n- octanoylsalicylic acid and salts thereof. 5-n-Octanoylsalicylic acid will be used more particularly.
The salts of the compounds may be obtained by salification with a mineral or organic base. Examples of mineral bases that may be mentioned include alkali metal or alkaline-earth metal hydroxides, for instance sodium hydroxide or potassium hydroxide, or aqueous ammonia.
Among the organic bases that may be mentioned are amines and alkanolamines. Quaternary salts, for instance those described in patent FR 2 607 498, are particularly advantageous.
The salicylic acid derivatives that can be used according to the invention are described in patents US 6 159 479 and US 5 558 871 , FR 2 581 542, FR 2 607 498, US 4 767 750, EP 378 936, US 5 267 407, US 5 667 789, US 5 580 549 and EP 570 230.
Salicylic acid or the salicylic acid compound as described previously may be present in the composition according to the invention in a content ranging from 0.05% to 10% by weight, preferably ranging from 0.05% to 5% by weight and preferentially ranging from 1 % to 4% by weight relative to the total weight of the composition.
In particular, the desquamating agent is chosen from those described in patent applications FR 2 581 542, WO 98/35973, FR 2 759 370, FR 2 762 839 or EP 0 875 495.
According to another preferred embodiment of the invention, the desquamating agent present in the composition according to the invention is chosen from jasmonic acid and derivatives thereof and especially:
- jasmonic acid,
- 3-hydroxy-2-[(2Z)-2-pentenyl]cyclopentaneacetic acid,
- methyl 3-hydroxy-2-[(2Z)-2-pentenyl]cyclopentaneacetate,
- 3-hydroxy-2-pentylcyclopentaneacetic acid,
- methyl 3-hydroxy-2-pentylcyclopentaneacetate, and
- 2-pentyl-3-hydroxycyclopentaneethanol. Use will in particular be made of 3-hydroxy-2-pentylcyclopentaneacetic acid and/or the sodium salt thereof.
By way of example, the amount of compound of formula (II) that can be used according to the invention may range, for example, from 0.01 % to 30%, preferably from 0.5% to 15% and especially from 1 % to 5% by weight relative to the total weight of the composition.
Reference may also be made to the jasmonic acid derivatives as defined in patent applications FR 2 835 526, EP 1 333 022, EP 1 333 021 , EP 1 442 737, EP 1 502 909, FR 2 835 525, FR 2 858 320 or FR 2 850 571.
In particular embodiments of methods and uses of a compound of formula (I), or in particular embodiments of compositions comprising a compound of formula (I), said compound of formula (I) is not combined with a desquamating agent. In other particular embodiments, compound of formula (I) may be combined with at least a desquamating agent with the exception of a beta-hydroxy-acid compound, for example with the exception of a beta- hydroxy-acid compound of formula (A) and/or (B).
In other particular embodiments of methods and uses of a compound of formula (I), or in particular embodiments of compositions comprising a compound of formula (I), said compound of formula (I) is not combined with an hydroxy-acid, or is not associated with a beta-hydroxy-acid.
In still some other particular embodiments, the above compound of formula (I) is used in the absence of a beta-hydroxy-acid compound of formula (A) or of formula (B) below:
R10-C-C-COOR R10— i i COOR
i i I I
OH R20 (A) OH R20 (B)
In which R10 and R20, identicals or differents, represent an hydrogen atom, or a linear or branched alkyl group comprising from 1 to 5 carbon atoms, or a phenyl group, or R10 and R20 form together a 5 or 6-membered cycle, and R is an hydrogen atom, an alkyl group of 1 to 12 carbon atoms, a silyl-alkyl group, an ammonium group or an alkaline or alkaline-earth metal.
The concentration of the various active agents will be adapted by a person skilled in the art but could vary, for example, within proportions ranging from 0.01 % to 15% by weight, preferably ranging from 0.1 % to 10% by weight, relative to the total weight of the composition.
A composition according to the invention may be a composition suitable for a cosmetic or pharmaceutical, particularly dermatological, application. Preferably, this composition according to the invention is intended for a cosmetic application. It is formulated in a physiologically acceptable medium.
The physiologically acceptable medium is preferentially a cosmetically or dermatologically acceptable medium, i.e. a medium that has no unpleasant odour, colour or appearance, and that does not cause the user any unacceptable stinging, tautness or redness.
The term "physiologically acceptable medium" means a medium that is compatible with human keratin materials such as the skin, mucous membranes, scalp and/or hair.
Advantageously, the compositions are in a form suitable for external topical application to the keratin materials.
This composition may be in any galenic form normally used in the cosmetic or pharmaceutical field, and especially in the form of an optionally gelled, aqueous or aqueous- alcoholic solution, of an optionally two-phase lotion-type dispersion, of an oil-in-water or water-in-oil emulsion or multiple (W/O/W or 0/W/O for example) emulsion, of an aqueous gel, of a dispersion of oil in an aqueous phase using spherules, it being possible for these spherules to be polymeric nanoparticles such as nanospheres and nanocapsules or, better still, lipid vesicles of ionic and/or nonionic type; or of an aqueous or oily gel. These compositions are prepared according to the usual methods. According to this invention, a composition in the form of an emulsion, especially an oil-in-water emulsion, is preferably used.
The 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, a gel or a mousse. It may optionally be applied in aerosol form. It may also be in solid form, in particular in stick form. When the composition is an emulsion, the proportion of the fatty phase may range from 5% to 80% by weight and preferably from 8% to 50% by weight relative to the total weight of the composition. The emulsifier and the coemulsifier may be present 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. According to one particular aspect, the invention also relates to a cosmetic assembly comprising: i) a container delimiting at least one compartment, said container being closed by a closing member; and ii) a composition as described previously, placed inside said compartment.
The container may be in any suitable form. It may especially be a bottle, a tube, a jar, a case, a box, a sachet or a casing. The closing member may be in the form of a removable stopper, of a lid, of a seal, of a tear-off strip or of a bottle cap, especially of the type comprising a body attached to the container and a cover cap hinged to the body. It may also be in the form of a member for selectively closing the container, especially a pump, a valve or a flap.
The container may be combined with an applicator. The applicator may be in the form of a fine brush, as described, for example, in patent FR 2 722 380. The product may be contained directly in the container, or indirectly. By way of example, the product may be arranged on an impregnated support, especially in the form of a wipe or a pad, and arranged (individually or in plurality) in a box or in a sachet. Such a support incorporating the product is described, for example, in patent application WO 01/03538.
The closing member may be coupled to the container by screwing.
Alternatively, the coupling between the closing member and the container is done other than by screwing, especially via a bayonet mechanism, by click-fastening, clamping, welding, adhesive bonding or by magnetic attraction. The term "click-fastening" in particular means any system involving the passing of a rim or bead of material by elastic deformation of a portion, especially of the closing member, followed by return to the elastically unstressed position of said portion after the rim or bead has been passed.
The container may be at least partially made of thermoplastic material, such as polypropylene or polyethylene.
Alternatively, the container is made of non-thermoplastic material, especially glass or metal (or alloy).
The container may have rigid walls or deformable walls, especially in the form of a tube or a tube bottle. The container may comprise means intended to bring about or facilitate the dispensing of the composition. By way of example, the container may have deformable walls so as to cause the composition to exit in response to excess pressurization inside the container, which excess pressurization is brought about by the elastic (or nonelastic) crushing of the walls of the container. Other features and advantages of the invention will emerge more clearly on reading the examples that follow.
In these examples reference will be made to the appended figure, which represents the number of days for normalization (return to the baseline) of the pigmentation (ITA) and the transepidermal water loss (TEWL) of sites treated with the placebo, with various ceramides, or that are untreated.
Example 1 : Effect of oleyl dihydrosphingosine on wound healing
The study was carried out on a panel of 24 volunteers in good health aged from 24 to 27 years old.
The skin blister technique was used to induce standardized skin lesions in the epidermis, with minimum pain. Wound healing generally takes place in 7 to 10 days, corresponding to the covering of the wound by the newly formed epithelium.
The treatments were applied once a day for 15 days after the skin blister had been induced. The volunteers were split into 3 groups, applied to which groups were, respectively, a cream containing 1 % of oleyl dihydrosphingosine (product according to the invention), a cream containing 1 % of hydroxy palmitoyl sphinganine, or the formulation base of identical composition but that contains no ceramide (placebo).
The recovery of the skin integrity was evaluated by measuring the transepidermal water loss, which decreases when the skin is repaired.
The change in this data in damaged areas treated with composition 1 , composition 2, or treated with their common excipient was compared.
- Restoration of the barrier function:
The barrier function was evaluated from the measurement of the TEWL (g/h/m2), measured 3 times a day, every day from D1 to D15, and the average of the 3 measurements was calculated.
The measurement at DO was carried out before the lesion was induced by the skin blister, and constitutes the base value. The D1 measurement was carried out just after the wound was induced.
The transepidermal water loss is significantly different from that of DO from D1 to D7 for the areas treated with oleyl dihydrosphingosine, and returns to normal on D8. For the areas that received no treatment or that received the placebo, the return to a base transepidermal water loss only takes place on D9.
These results show that the topical application of oleyl dihydrosphingosine increases the recovery of the skin integrity after a lesion more rapidly than for untreated skin or for skin receiving a placebo formulation.
Example 2: Effect of oleyl dihydrosphingosine on skin redness The study was conducted on a panel of 19 volunteers in good health aged from 19 to 49 years old. The subjects were all of between phototype III and phototype IV.
The areas of investigation (4 areas of the back) were exposed daily to UV rays for 4 consecutive days with doses of 0.75 MED (minimal erythemal dose).
The oleyl dihydrosphingosine was applied under occlusion, and after tape stripping of the areas of investigation, daily for 7 days before the first UV exposure, then daily on the irradiation days, after the exposures to UV rays. The redness was evaluated by comparative clinical scoring, and by colorimetry
(chromameter, parameter a*).
The erythema is measured just after the UV exposures and up to 24 h after the last irradiation. It is therefore observed that the oleyl dihydrosphingosine has a protective effect against the redness induced by repeated "tape-stripping" operations.
The oleyl dihydrosphingosine has an effect of preventing the appearance of an erythema during exposure to UV radiation, which is not the case for another ceramide, hydroxy palmitoyl sphinganine, or the placebo formulation.
Example 3: Composition for topical application Name Concentration
(% by weight)
Sucrose palmitostearate esters 2
Oxyethylenated sorbitan monostearate 1 .4
Stearic acid 1
Apricot oil 25
Preserving agents 0.65
N-OLEYL DIHYDROSPHINGOSINE 1
CARBOXYVINYL POLYMER 0.5
Deionized water qs 100