COSMETIC OR PHARMACEUTICAL COMPOSITION FOR REDUCING IMMUNOSUPPRESSION INDUCED BY EXPOSURE TO ULTRAVIOLET RADIATION

Abstract

COSMETIC OR PHARMACEUTICAL COMPOSITION FOR REDUCING IMMUNOSUPPRESSION INDUCED BY EXPOSURE TO ULTRAVIOLET RADIATION The present invention relates to a composition, advantageously dermocosmetic, for topical application, comprising γ-oryzanol and / or tamanu oil for use as an immunoprotective agent and for reducing the isomerization of trans urocanic acid into cis form.

Description

Title of the invention: COSMETIC OR PHARMACEUTICAL COMPOSITION FOR REDUCING IMMUNOSUPPRESSION INDUCED BY EXPOSURE TO ULTRAVIOLET RADIATION FIELD OF THE INVENTION

[0001] The present invention relates to a composition, advantageously cosmetic or dermatological, intended for the protection of urocanic acid, an endogenous chromophore present in the horny layer of human skin. The invention also relates to the use of said composition for reducing immunosuppression, in particular induced by exposure to ultraviolet radiation. STATE OF THE ART

[0002] Ultraviolet (UV) radiation consists of light with wavelengths between 100 nm and 400 nm, traditionally divided into 3 subgroups: UV-A (400-315 nm), UV-B (315-280 nm) and UV-C (280-100 nm). UV-C, with its short wavelength, is the most energetic and most harmful UV. It is filtered by the ozone layer of the atmosphere and most of it does not reach the Earth's surface. UV-A and UV-B are necessary for the proper functioning of the human body. However, these radiations are the cause of most damage to the skin.

[0003] UV-B rays are particularly responsible for stimulating the production of the skin's natural pigment called melanin. The production of melanin is the cause of the phenomenon commonly known as tanning. UV-B rays also stimulate cells to produce a thicker epidermis. The reactions described above constitute a defense mechanism of the body against UV rays.

[0004] UV-B rays, which are more energetic than UV-A rays, are also responsible for solar erythema or sunburn, which reaches its maximum intensity 24 hours after exposure.

[0005] The high energy of UV-B generates molecular disorders (DNA alteration and protein damage, particularly their carbonylation) which, in the long term, saturate and block the nuclear DNA repair system. This leads to permanent mutations in the genome of the affected cells, which are the cause of skin cancers. This is then a direct toxicity of UV-B.

[0006] Traditionally, UV-A rays, which have no visible harmful effects in the short term, have been considered harmless. However, it is now recognized that UV- They penetrate into the deeper layers of the skin, where they produce harmful effects, particularly within the connective tissue and on the blood vessels. They are notably at the origin of the phenomenon called heliodermia, that is to say the premature actinic aging of the skin.

[0007] Furthermore, although UV-B rays are the main cause of skin cancer, UV-A rays also have an indirect contribution to this type of damage. Indeed, UV-A and UV-B rays are responsible for the production of free radicals, in particular ROS (Reactive Oxygen Species). These are unstable molecules with a very short half-life, ranging from nanoseconds to milliseconds. ROS are capable of damaging intracellular structures (DNA, membranes, intracellular proteins, etc.) as well as extracellular structures (components of the extracellular matrix such as collagen fibers, etc.).

[0008] When UV rays penetrate the skin, depending on their wavelengths, the photons will be absorbed by molecules present in the skin called chromophores. Chromophores, due to the existence of conjugated double bonds in their atomic configuration, are capable of absorbing or diffusing radiation characteristic of UV.

[0009] Urocanic acid, or (E)-imidazole-4-acylic acid, is a major epidermal chromophore (Kaneko et al., 2009). It occurs in the skin in two isoforms: trans and cis. The trans form of urocanic acid has a high absorption coefficient at wavelengths between 260 and 310 nm. Due to its significant presence in the stratum corneum and its ability to absorb UV-B radiation, it contributes to the natural photoprotection of the skin (Barresi et al., 2011). It complements the action of other natural chromophores in the skin, such as melanin, present in the layers of the epidermis.

[0010] The photoprotective ability of trans-urocanic acid has been confirmed by topical application to human skin. The application of a cream containing 5% trans-urocanic acid provides a sun protection factor (SPF) of 1.58 (de Fine Olivarius et al., 1996).

[0011] The high concentration of urocanic acid in the epidermis results from the degradation of filaggrin, a histidine-rich protein. Free histidine undergoes non-oxidative deamination catalyzed by an enzyme, histidase, also called histidine ammonia-lyase, allowing the formation of urocanic acid which is accompanied by a release of ammonia (Barresi et al., 2011). In humans, the Hal gene encoding histidase is expressed in the liver and epidermis. In vitro, the expression of this enzyme is highly regulated in differentiating keratinocytes.

[0012] Mutations in the Hal gene have been identified as causing a benign metabolic disorder, histidinemia. These mutations lead to higher histidine concentration and decreased urocanic acid concentration in the epidermis (Barresi et al., 2011).

[0013] A study was carried out on mice in which histidase activity was suppressed (His mice) corresponding to an animal model of histidinemia. These mice therefore have a deficiency in trans-urocanic acid. The decrease in trans-urocanic acid in His mice is associated with a reduction in the UV-B absorption capacity of the stratum corneum and an increased sensitivity to cell apoptosis and DNA damage compared to healthy wild-type mice. These results highlight the participation of endogenous trans-urocanic acid in the protection of the skin against the harmful effects of UV radiation (Barresi et al., 2011).

[0014] In this same study, an application of 50 μg of exogenous trans-urocanic acid reduced UV-B-induced DNA damage by 48% in mice with histidinemia and by 31% in the normal mouse population. These data show that topical application of trans-urocanic acid improves protection against UV-B-induced DNA damage.

[0015] In addition to a photoprotective effect by absorbing UV-B radiation, trans-urocanic acid also protects the skin by eliminating hydroxyl radicals generated by UV irradiation (Barresi et al., 2011). These data therefore suggest preserving the urocanic acid content of the skin layer. Thus, patent application EP 0 701 814 describes hydrophobic inorganic pigments used in cosmetic compositions capable of reducing the elimination of urocanic acid from the skin during swimming.

[0016] As mentioned previously, urocanic acid is found in two isomeric forms: trans and cis. In the epidermis, it is initially present in the trans form. Exposure to UV radiation, especially UV-B, induces isomerization of trans-urocanic acid into the cis form (Kaneko et al., 2009). Photoisomerization of trans-urocanic acid to cA-urocanic acid occurs in a dose-dependent manner (Walterscheid et al., 2006). Following exposure to UV radiation, high amounts of cA-urocanic acid are detected in the skin for several weeks (Beissert et al., 2001).

[0017] Furthermore, it has been observed that UV radiation induces photoimmunosuppression which alters immune functions and disrupts tumor surveillance mechanisms. Therefore, photoimmunosuppression is involved in photocarcinogenesis (Coelho et al., 2016). Immunosuppression induced by exposure to UV radiation is initiated by a multitude of processes such as DNA damage, induction of cytoplasmic transcription factors, activation of macrophages, disruption of antigen presentation, modulation of cytokines or isomerization of urocanic acid (Coelho et al., 2016).

[0018] Thus, it has been demonstrated that cA-urocanic acid is an important mediator of immunosuppression induced by exposure to UV radiation (de Fabo and Noonan, 1983) and is responsible for a decrease in cutaneous tumor immunity. cA-urocanic acid inhibits the ability of Langerhans cells to present tumor antigens allowing immune tumor responses (Beissert et al., 2001).

[0019] More specifically, immunosuppression affects antigen-presenting epidermal Langerhans cells (LCs), which undergo morphological and functional alterations. Under the influence of, for example, UV rays, they migrate into the peripheral lymph nodes where they induce the proliferation of suppressor T lymphocytes (natural killer and regulatory) producing immunoregulatory cytokines, respectively interleukin-4 (IL-4) or interleukin-10 (IL-10). Keratinocytes are also the target of UV rays and secrete multiple soluble mediators with immunosuppressive activities, in particular IL-10.

[0020] At the molecular level, deoxyribonucleic acid (DNA) is the main UV chromophore in the skin, and the formation of pyrimidine dimers is directly involved in UV-induced immunosuppression. As already mentioned, UV also induces photoisomerization of trans-urocanic acid to cis-urocanic acid capable of exerting immunosuppressive properties. UV also interacts with cytoplasmic and membrane targets capable of modifying signal transduction, or the transcription of genes involved in the immune response.

[0021] In human keratinocytes, cA-urocanic acid stimulates the expression of UV-inducible genes including the cyclooxygenase-2 (COX-2) gene, leading to an increase in the production of immunomodulatory mediators such as prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6) (Kaneko et al., 2009).

[0022] The cis isomer of urocanic acid may also promote the formation of skin cancers generated by exposure to UV radiation. A study on mice reveals that the photocarcinogenic activity of cA-urocanic acid can be reduced by application of interleukin-12 (IL-12) (Beissert et al., 2001). This cytokine can be produced by a variety of immunocompetent cells such as dendritic cells, macrophages or keratinocytes. LTL-12, considered immunoprotective, is able to antagonize immunosuppression induced by exposure to UV radiation.

[0023] The discovery of the immunosuppressive and, indirectly, carcinogenic role of cis-urocanic acid marked the end of the cosmetic use of the molecule. Indeed, the application of an exogenous source of urocanic acid, even in the trans form, could lead to photoisomerization of trans-urocanic acid and therefore to the presence of high epidermal levels of cis isomer. Under these conditions, cis-urocanic acid could exert its harmful effects on the immune defenses of the skin.

[0024] Other studies have implicated the cis-form of urocanic acid in the etiopathology of inflammatory skin conditions, including benign summer light eruption (BLE) (Schornagel, 2007) and chronic urticaria (Ye et al., 2016). These data suggest disruption of human mast cell activity via œ-urocanic acid (Walterscheid et al., 2006).

[0025] In summary, trans-urocanic acid is naturally present in the skin. The chromophore role of this acid represents a natural, biomimetic and endogenous pathway to protect skin cells from the sun, but only to the extent that its transformation into the cis isomer can be controlled. The isomerization of urocanic acid in the stratum corneum can be at least partially blocked by applying UV filters, in particular UV-B filters, to the skin surface, capable of "blocking" UV rays.

[0026] Over the last few decades, increasingly efficient chemical and mineral filters have been developed, exhibiting increased photostability and broad absorption spectra with respect to UV-A and / or UV-B. These filters provide good photoprotection and can prevent the isomerization of urocanic acid.

[0027] However, their massive use in cosmetic products is increasingly criticized. Indeed, sunscreens often have allergenic properties and can be toxic or harmful if they penetrate through the epidermal barrier. This risk is particularly pronounced in the case of "nano" filters, that is, made up of particles with an average size of less than 100 nanometers. In addition, several chemical filters are suspected of being endocrine disruptors.

[0028] The impact of filters, however, goes beyond their consequences on humans: filters are often poorly biodegradable and become environmental pollutants. Among other examples of ecotoxic effects, several sunscreens are said to have a negative impact on the viability of marine reefs and are notably responsible for the phenomenon of coral bleaching (Danovaro et al., 2008).

[0029] There therefore remains a clear need to develop alternatives to cosmetic sunscreens capable of preventing the isomerization of cutaneous trans-urocanic acid and thus protecting the skin against the phenomenon of immunosuppression induced by an ex- position to UV radiation.

[0030] DESCRIPTION OF THE INVENTION

[0031] Surprisingly, the Applicant has demonstrated that two active ingredients of plant origin, having very limited ecotoxicity and suitable for use in human cosmetics, make it possible to meet these needs.

[0032] Thus, the present invention relates to a composition comprising y-oryzanol and / or tamanu oil, namely y-oryzanol or tamanu oil or a mixture thereof.

[0033] According to a first aspect, a composition comprising γ-oryzanol and / or tamanu oil is used as an immunoprotective agent, i.e. for reducing, diminishing or inhibiting immunosuppression.

[0034] Advantageously, it is a cosmetic composition, preferably dermo-cosmetic.

[0035] According to a particular embodiment, immunosuppression is induced by exposure to ultraviolet radiation, also called photoimmunosuppression.

[0036] Preferably, protection against immunosuppression is achieved by topical application of a composition comprising y-oryzanol or tamanu oil, used alone.

[0037] Alternatively, protection against immunosuppression is achieved by topical application of a composition comprising y-oryzanol and tamanu oil used in combination.

[0038] Advantageously, immunosuppression is induced by the isomerization of trans-urocanic acid leading to an increase in the concentration of trans-urocanic acid in the skin. A protocol for measuring this isomerization is described in the embodiment examples.

[0039] Note that as mentioned above, the cytokine IL-12 is considered to be such an agent capable of reducing or inhibiting immunosuppression induced by exposure to UV radiation. Accordingly, IL-12 can be used as a positive control to evaluate the immunoprotective potential of a compound or composition according to the invention.

[0040] For the purposes of the invention, "immunoprotection" means the phenomenon of protecting, preserving or guaranteeing the activity of the body's immune system. This effect involves the conservation or maintenance of immune surveillance, a rapid response after immune activation and rapid and effective elimination of immune system activating agents or antigens such as viruses, bacteria or fungal microorganisms.

[0041] For the purposes of the invention, the term “immunoprotective agent” means a product, a compound or a composition conferring immunoprotection.

[0042] For the purposes of the invention, "immunosuppression" means the phenomenon of decrease, reduction or inhibition of the activity of the body's immune system, in particular the body's specific immunological reactions against an antigen, i.e. a foreign body entering the body.

[0043] For the purposes of the invention, “photoimmunosuppression” or “immunosuppression induced by exposure to ultraviolet radiation” means the phenomenon of immunosuppression originating from exposure of the skin to ultraviolet radiation.

[0044] According to a particular embodiment, photoimmunosuppression is induced by exposure to UV-B.

[0045] The invention therefore relates to a cosmetic composition for topical application containing y-oryzanol and / or tamanu oil for its use as a protective agent for the trans form of cutaneous urocanic acid.

[0046] According to the invention, the term “cutaneous urocanic acid” means urocanic acid present in the human horny layer.

[0047] The invention also relates to a method for protecting the trans form of cutaneous urocanic acid comprising the application to the skin of a cosmetic composition comprising y-oryzanol and / or tamanu oil.

[0048] For the purposes of the invention, the term "protection of the trans form of urocanic acid" means blocking the isomerization of at least 40%, advantageously at least 50%, advantageously at least 60%, even more advantageously 70%, or even 80% or even more advantageously 90%, of trans-urocanic acid into cis-urocanic acid, in particular following irradiation with a UV-A dose of 9 J / cm2 and a UV-B dose of 300 mJ / cm2.

[0049] Alternatively, the term "protection of the trans form of urocanic acid" means the isomerization of at most 60%, advantageously at most 50%, advantageously at most 40%, even more advantageously at most 30%, or even 20% or 10% of the trans-urocanic acid into czs-urocanic acid, in particular following irradiation with a UV-A dose of 9 J / cm2 and a UV-B dose of 300 mJ / cm2.

[0050] For the purposes of the invention, the term "protective agent for the trans form of urocanic acid" means a cosmetic composition capable of preventing the isomerization of at least 40%, advantageously at least 50%, advantageously at least 60%, even more advantageously 70%, or even 80% or even more advantageously 90% of the / / wM-urocanic acid into czs-urocanic acid, in particular following irradiation with a UV-A dose of 9 J / cm2 and a UV-B dose of 300 mJ / cm2.

[0051] Alternatively, the term “protective agent for the trans form of urocanic acid” means a cosmetic composition capable of limiting isomerization by at most 60%, advantageously at most 50%, advantageously at most 40%, even more typically at most 30%, or even 20% or 10% of trans-urocanic acid into cis-urocanic acid following irradiation with a UV-A dose of 9 J / cm2 and a UV-B dose of 300 mJ / cm2.

[0052] According to a particular embodiment, the protection of urocanic acid is obtained by topical application of a composition comprising y-oryzanol and / or tamanu oil as well as at least one mineral and / or organic sunscreen.

[0053] γ-oryzanol is a mixture of ferulic acid esters of sterols and triterpene alcohols that is found naturally in rice bran and germ. γ-oryzanol is a known antioxidant used in cosmetics as an anti-wrinkle, anti-aging and antioxidant agent. However, to the Applicant's knowledge, its properties of stabilizing the trans form of urocanic acid in response to exposure to UV-B radiation have never been described.

[0054] According to a particular embodiment, y-oryzanol corresponds to the substance having the CAS number 11042-64-1.

[0055] In a preferred embodiment, the γ-oryzanol is derived from rice, advantageously from rice bran, extracted using an organic solvent, then concentrated, recrystallized and dried.

[0056] Advantageously, the purified y-oryzanol represents at least 60%, advantageously at least 80%, preferably at least 90%, or even 95% or 99% of the total dry mass of the rice bran extract.

[0057] Alternatively, the y-oryzanol may be contained in a rice plant extract titrated in y-oryzanol.

[0058] Advantageously, the y-oryzanol contained in the plant extract represents between 1% and 100% by weight relative to the total weight of the extract, preferably between 10% and 100%, advantageously between 50% and 100%.

[0059] In a particular embodiment, the y-oryzanol corresponds to the raw material available under the name Oryzanol and marketed by the company TSUNO, RICE FINE CHEMICALS, or the Gamma Oryzanol marketed by the company IKEDA. These raw materials correspond to the INCI designation oryzanol.

[0060] According to a particular embodiment, the γ-oryzanol represents between 0.001% and 20% by weight of the composition, preferably between 0.01% and 10%, even more advantageously between 0.1% and 5%.

[0061] Tamanu oil, also called nyamplung oil, is derived from the berry of the plant Calophyllum inophyllum (C. inophyllum) or a related species, Ca-lophyllum tacamahaca (C. tacamahaca). C. inophyllum is an evergreen tree, native to Melanesia, which has gradually colonized the shores of the Pacific and is mainly located on the Scattered Islands south of the Celebes archipelago. C. tacamahaca, for its part, is a species endemic to the Mascarene Islands (Mauritius and Reunion). Tamanu oil has been known for centuries for its soothing, healing, and antioxidant properties. However, to the Applicant's knowledge, its properties of stabilizing the trans form of urocanic acid in response to exposure to UV-B radiation have never been described.

[0062] Advantageously, tamanu oil is obtained by hulling the berries, drying the almonds, cold mechanical pressing and filtration.

[0063] In a particular embodiment, the tamanu oil contains unsaponifiable oils, tocotrienols, as well as phytosterols. Advantageously, the tamanu oil comprises between 1 and 4% of unsaponifiable oils.

[0064] Thus, the cosmetic raw material NYAMPLUNG OIL, marketed by the company SOLIANCE and corresponding to the INCI designation Calophyllum inophyllum seed oil, can be used in the context of the present invention. According to an alternative embodiment, tamanu oil corresponds to the INCI designation Calophyllum ta-camahaca seed oil. Thus, the raw material PERROTOL marketed by the company Promedica and which corresponds to an extract of C. tacamahaca, can be used in the context of the present invention.

[0065] According to a particular embodiment, the tamanu oil represents between 0.001% and 20% by weight of the composition, preferably between 0.01% and 10%, even more advantageously between 0.1% and 5% by weight of the composition.

[0066] In a particular embodiment, the composition for its use according to the invention comprises y-oryzanol and tamanu oil. This combination of the two active ingredients makes it possible to benefit from a reinforced effect in the protection of the trans form of urocanic acid and makes it possible to reduce the concentrations used of each of the two active ingredients.

[0067] In a particular embodiment, the composition comprising y-oryzanol and / or tamanu oil is free of organic (or chemical) or mineral sunscreens.

[0068] According to another embodiment, the composition according to the invention comprises y-oryzanol and / or tamanu oil and at least one organic or mineral, lipophilic or hydrophilic sunscreen.

[0069] For the purposes of the invention, the term "sun filter" refers to organic compounds, and the term "sunscreen" refers to mineral compounds, respectively, capable of filtering UV-A, UV-B and / or UV-C.

[0070] Advantageously, the composition according to the invention comprises one or more broad-spectrum organic sunscreens, i.e. compounds or mixtures of compounds which absorb UV-A, UV-B, UV-C and possibly visible light.

[0071] Among the broad spectrum organic filters, the filters corresponding to the designations The following INCI names may be used in the context of the invention: tris biphenyl triazine, bis ethylhexyloxyphenol methoxyphenyl triazine, methylene bis-benzotriazolyl tetra-methylbutylphenol. For example, these are marketed by the company BASF respectively under the names TINOSORB S® / TINOSORB AQUA®, TINOSORB A2B®, TINOSORB M®. Two other examples of broad-spectrum filters suitable for the composition according to the invention correspond to the INCI designation diethylhexyl butamido triazone, for example marketed by the company SIGMA 3V under the name UVASORB HEB®, and phenylene bis-diphenyltriazine marketed by the company PLANTES & INDUSTRIE under the name TRIASORB®.

[0072] Thus and according to a particular embodiment, the composition according to the invention comprises at least one organic filter chosen from the following compounds, identified by their INCI designation: tris biphenyl triazine, bis ethylhexyloxyphenol methoxyphenyl triazine, methylene bis-benzotriazolyl tetramethylbutylphenol, diethylhexyl butamido triazone, phenylene bis-diphenyltriazine and their mixtures, advantageously, bis ethylhexyloxyphenol methoxyphenyl triazine.

[0073] According to another particular embodiment, the composition contains at least one organic filter and / or one additional mineral screen, each of which can be in aqueous (hydrophilic) and / or oily (lipophilic) phase.

[0074] Thus and by way of example, the composition according to the invention may contain UV-B filters capable of contributing to the stabilization or solubilization of the other filters or even of stabilizing each other and increasing the sun protection factor (SPF).

[0075] In a particular embodiment, the composition according to the invention further comprises the liposoluble UV-B filter α-(trimethylsilyl)-co-(trimethylsilyloxy)poly[oxy(dimethyl)silylene]-co-[oxy(methyl)(2-{4-[2,2-bis(ethoxycarbonyl)vinyl]phenoxy}-1-methyleneethyl)silylene]-co-[oxy(methyl)(2-(4-[2,2-bis(ethoxycarbonyl)vinyl]phenoxy)prop-1-enyl)silylene], a silicone polymer capable of filtering UV-B radiation. This filter corresponds for example to the cosmetic raw material Parsol SLX®, marketed by the company DSM according to the INCI designation polysilicone-15. Another advantageous liposoluble UV-B filter is the raw material corresponding to the INCI designation ethylhexyl salicylate. This filter is, for example, marketed by the company DSM under the name PARSOL® EHS. Another example of a liposoluble UV-B filter suitable according to the invention is the filter corresponding to the INCI designation ethylhexyl triazone.This filter is available from BASF under the trade name UVINUL® T150.

[0076] Thus and in another particular embodiment, the composition according to the invention comprises at least one UV-B filter chosen from the following group of compounds identified by their INCI designation: polysilicone-15, ethylhexyl salicylate, ethylhexyl triazone and mixtures thereof.

[0077] In a particular embodiment, the composition is free from the following filters: 4-methylbenzylidene camphor, benzophenone-2, benzophenone-3, ethylhexyl methoxycinnamate, octocrylene and homosalate.

[0078] In an advantageous embodiment, the composition according to the invention comprises at least one UV-A filter, in order to ensure complete filtration of the harmful part of the solar spectrum.

[0079] Advantageous UV-A filters within the meaning of the present invention are the following compounds, identified by their INCI designation: butyl methoxydibenzoylmethane and diethylamino hydroxybenzoyl hexyl benzoate, corresponding respectively to the raw materials Parsol 1789® marketed by the company DSM and UVINUL® A+ marketed by the company BASF.

[0080] In a particular embodiment, the UV-A filter is bis-(diethylaminohydroxybenzoyl benzoyl) piperazine (INCI) (CAS number 919803-06-8), corresponding for example to the raw material C1332® marketed by the company BASF.

[0081] Thus and in a particular embodiment, the composition according to the invention comprises at least one UV-A filter chosen from the following group of compounds identified by their INCI designation: butyl methoxydibenzoylmethane, diethylamino hydroxybenzoyl hexyl benzoate, bis-(diethylaminohydroxybenzoyl benzoyl) piperazine and mixtures thereof.

[0082] Other advantageous UV filters within the meaning of the present invention are water-soluble filters, such as for example:

[0083] - the filter corresponding to the INCI designation disodium phenyl dibenzimidazole te- trasulfonate, notably available under the name Neo Heliopan® AP marketed by the company SYMRISE;

[0084] - the filter corresponding to the INCI designation phenylbenzimidazole sulfonic acid, in particular available under the name Neo Heliopan® hydro marketed by the company SYMRISE, preferably in combination with a basic amino acid, advantageously arginine. In practice, the basic amino acid represents between 0.5 and 2% by weight of the composition, preferably between 1 and 1.5%.

[0085] In a particular embodiment, the composition according to the invention comprises at least one water-soluble filter chosen from the following group of compounds identified by their INCI designation: disodium phenyl dibenzimidazole tetrasulfonate, phenylbenzimidazole sulfonic acid and mixtures thereof.

[0086] Advantageously, the inorganic mineral filters, or mineral screens, are metal oxides and / or other compounds which are difficult to dissolve or insoluble in water, in particular oxides of titanium (TiO2), zinc (ZnO), iron (Fe2O3), zirconium (ZrO2), silicon (SiO2), manganese (e.g. MnO), aluminum (A12O3), or cerium (Ce2O3).

[0087] According to a particular embodiment, the inorganic mineral filters can be used in the form of an oily or aqueous predispersion available on the market. These predispersions can advantageously be supplemented with dispersion auxiliaries and / or solubilization mediators.

[0088] The inorganic mineral filters can also be surface-treated or encapsulated, in order to give them a hydrophilic, amphiphilic or hydrophobic character. This surface treatment can consist of the mineral filters being provided with a thin inorganic and / or organic, hydrophilic and / or hydrophobic film.

[0089] In a particular embodiment, the composition according to the invention comprises at least one mineral screen chosen from the following group of compounds identified by their INCI designation: zinc oxide, titanium dioxide and mixtures thereof. By way of example, these screens are marketed by the company BASF, under the trade names Z-COTE® LSA and T-Lite®, respectively.

[0090] The lists of UV filters cited above which can be implemented within the meaning of the present invention are of course given for information purposes and are not limiting.

[0091] Advantageously, the organic filters and / or mineral screens represent between 0.1% and 30% by weight of the composition, advantageously between 0.5% and 20%, even more advantageously between 1% and 15%.

[0092] According to a particular embodiment, the composition according to the invention has a sun protection factor ("SPF" or FPS) greater than or equal to 10, preferably greater than or equal to 20, advantageously greater than or equal to 30, even more advantageously greater than or equal to 50, or even equal to or greater than 100.

[0093] According to a preferred embodiment, the composition according to the invention comprises a UV-A / UV-B protection ratio equal to or greater than 1 / 3.

[0094] Advantageously, the composition according to the invention has a critical wavelength (Xc) greater than 370 nm. This value, which is determined by in vitro methods known to those skilled in the art, corresponds to the wavelength for which the integral of the absorption spectrum curve, starting at 290 nm, reaches 90% of the integral between 290 and 400 nm.

[0095] The composition according to the invention may further comprise an SPF “booster”, i.e. an agent that enhances the sun protection factor, and / or a photostabilizer, i.e. an ingredient that makes it possible to increase the SPF or to photostabilize the filters, such an ingredient not being considered itself as a sun filter. Examples include:

[0096] - buytloctyl salicylate (INCI), a photostabilizer advantageously representing between 0.01% and 10% by weight of the composition, even more advantageously between 0.1% and 2%. This raw material is, for example, marketed by the company HALLSTAR under the name Hallbrite® BHB;

[0097] - benzotriazolyl dodecyl p-cresol (INCI), a photostabilizer representing advantageously preferably between 0.01% and 10% by weight of the composition, even more advantageously between 0.1% and 2%. This raw material is for example marketed by the company BASF under the name TINOGARD® TL;

[0098] - pongamol (INCI), a plant molecule absorbing UV-A rays, representing advantageously between 0.5 and 2% by weight of the composition, even more advantageously of the order of 1%. By way of example, the raw material Pongamia Extract marketed by the company GIVAUDAN can be used in the context of the present invention;

[0099] - ethylhexyl methoxycrylene (INCI), photostabilizer, solubilizer and “booster” of SPF advantageously representing between 1% and 5% by weight of the composition. The raw material SolaStay® SI marketed by the company HALLSTAR can be used in the context of the present invention;

[0100] - a styrene acrylate copolymer (INCI: styrene / acrylate copolymer), representing preferably between 1% and 10% by weight of the composition. The raw materials SunSpheres® H53 and SunSpheres® PGL Polymer, marketed by the company DOW CHEMICALS, can be used in the context of the present invention;

[0101] - diethylhexyl syringylidene malonate (INCI), advantageously representing between 1% and 10% by weight of the composition. The raw material OXYNET® ST, marketed by the company MERCK, can be used in the context of the present invention;

[0102] - a water-dispersible polyester, corresponding to the INCI designations polyester-5 (and) Sodium silicoaluminate, advantageously representing between 1% and 10% by weight of the composition, in particular EASTMANN AQ™38S Polymer marketed by the company SAFIC-ALCAN;

[0103] - an acrylate copolymer having a glass transition temperature of -5°C to - 15°C as measured by differential scanning calorimetry, said copolymer advantageously representing between 1% and 10% by weight of the composition. For example, a polymer corresponding to the INCI designation Acrylate copolymer, such as the raw material EPITEX 66, marketed by the company DOW CHEMICALS, can be used in the context of the present invention.

[0104] In a particular embodiment, the composition according to the invention also comprises one or more substances capable of filtering visible light, in particular blue light. By way of example, the compounds described in document EP 1 484 051 can be used to ensure filtration of blue light.

[0105] According to another embodiment, the composition according to the invention may comprise furthermore an extract of the bacterium Arthrobacter agilis, in particular an extract rich in carotenes, as described in document WO 2014 / 167247. Advantageously, the composition according to the invention comprises from 0.00001% to 0.1% by weight of the composition, even more advantageously from 0.0001% to 0.001% of such a dry extract.

[0106] In a preferred embodiment, the composition according to the invention further comprises other components which can contribute to internal protection by an action which can consist of DNA protection, an anti-radical action or a combined effect of these actions.

[0107] The protective action of a composition according to the invention against oxidative stress or against the effect of free radicals can be further improved if it also comprises one or more antioxidants, easily selected by a person skilled in the art, for example, from the following list: totarol, magnolol, honokiol, amino acids and their derivatives, peptides (D and / or L-camosine) and their derivatives (for example anserine, hypotaurine, taurine), carotenoids, carotenes (α-carotene, [3-carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and its derivatives (dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosylated esters, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, y-linoleic, cholesteryl and glyceryl) as well as salts thereof, dilauryl thiodipropionate,distearyl thiodipropionate, thiodipropionic acid and its derivatives, sulfoximine compounds (buthionine sulfoximine, homocysteine ​​sul-foximine, buthionine sulfones, penta-, hexa- and heptathionine sulfoximine), chelating agents (such as α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (such as citric, lactic, or malic acid), humic acid, bile acid, bile extracts, bilirubin, bi-liverdin, EDTA, EGTA, pentasodium ethylenediamine tetramethylene phosphonate and its derivatives, unsaturated fatty acids and their derivatives, vitamin A and its derivatives (vitamin A palmitate), coniferyl benzoate from the resin of benzoin, rutinic acid and its derivatives, a-glycosyl rutin, ferulic acid and its derivatives, furfurylideneglucitol, camosine, butylhydroxytoluene, butylhy-droxyanisole, nordihydroguaiaretic acid, trihydroxybutyrophenone, quercetin,uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (ZnO, ZnSO4), selenium and its derivatives (selenomethionine), stilbenes and their derivatives (stilbene oxide, trans-stilbene oxide).

[0108] In a particular embodiment, the composition according to the invention also contains glycyrrhetinic acid, a derivative or a salt of this acid, used as a soothing agent (anti-inflammatory agent) and advantageously representing between 0.01% and 2% by weight of the composition, preferably between 0.1% and 1%.

[0109] According to another preferred characteristic of the invention, the cosmetic and / or dermatological composition contains at least one, or even all of the following constituents exerting a biological activity in vivo on the cells of the skin, lips, hair and / or mucous membranes subjected to UV-A and / or UV-B radiation, respectively:

[0110] - an antiradical agent preserving cellular structures, such as for example vitamin E and / or its fat-soluble or water-soluble derivatives, in particular tocotrienol and / or tocopherol, advantageously representing between 0.001 and 10% by total weight of the composition, even more advantageously between 0.02 and 2%, preferably of the order of 0.04%;

[0111] - vitamin PP, advantageously representing between 0.001 and 1% by total weight of the composition, even more advantageously from 0.01% to 0.3%;

[0112] - a protective agent of the p53 protein, such as for example epigallocatechin gallate (EGCG), advantageously representing between 0.001 and 0.1% by total weight of the composition, even more advantageously from 0.005% to 0.05%.

[0113] The composition according to the invention may also further comprise peptide extracts of soy and / or wheat, such as those described in EP 2 059 230.

[0114] In practice, the peptide extracts originating from soybean and wheat seeds are derived from an enzymatic hydrolysis of said seeds via peptidases which makes it possible to recover peptides with an average size of 700 Daltons. Preferably, the soybean peptide extract is the extract identified under CAS number 68607-88-5, just as the wheat peptide extract is the extract identified under CAS number 70084-87-6. The wheat and soybean extracts may correspond to the INCI designations Hydrolyzed wheat protein and Hydrolyzed soy protein, respectively.

[0115] In a particular embodiment, the soy and wheat peptide extracts are used together, for example in a weight ratio respectively between 80 / 20 and 20 / 80, advantageously between 70 / 30 and 30 / 70, preferably equal to 60 / 40.

[0116] In an advantageous embodiment, the soybean and / or wheat peptide extracts are free of synthetic tripeptides GHK (glycyl-histidyl-lysine; INCI: Tripeptide-1). In practice, the soybean and / or wheat peptide extracts represent from 0.01 to 20% by total weight of the composition, advantageously from 0.1% to 10%, even more advantageously from 0.2% to 0.7%.

[0117] In an alternative embodiment, the composition according to the invention comprises, in accordance with the teachings of document FR 2 865 398, the combination of at least one amino acid chosen from the group consisting of ectoine, creatine, ergothioneine and / or camosine, or their physiologically acceptable salts, and mannitol or a mannitol derivative.

[0118] Preferably, the composition according to the invention comprises in a physiologically acceptable medium the amino acid or one of its salts, alone or as a mixture in proportions of between 0.001% and 10% by total weight of the composition, and preferably between 0.01% and 5%.

[0119] The composition according to the present invention preferably comprises, in a physiologically acceptable medium, mannitol or one of its derivatives, in proportions of between 0.01% and 30% by total weight of the composition, advantageously between 0.1% and 10%.

[0120] In a preferred embodiment, the composition according to the invention comprises ectoine and mannitol.

[0121] According to a particular embodiment, the composition according to the invention contains one or more other tanning or self-tanning agents. It may be a self-tanner which reacts with the amino acids of the skin according to a Maillard reaction or via a Michael addition, or a melanogenesis promoter or a propigmenting compound which promotes the natural tanning of the skin.

[0122] Such a substance is preferably present in the composition in an amount ranging from 0.01% to 20% by total weight of the composition, advantageously from 0.5% to 15%, even more advantageously from 1% to 8%.

[0123] The self-tanning substances may be 1,3-dihydroxyacetone (DHA), gly-cerolaldehyde, hydroxymethylglyoxal, y-dialdehyde, erythrulose, 6-aldo-D-fructose, ninhydrin, 5-hydroxy-l,4-naphthoquinone (juglone), 2-hydroxy-l,4-naphthoquinone (lawsone), or a combination thereof.

[0124] The propigmenting substances may be melanocyte stimulating hormone (a-MSH), peptide analogues of a-MSH, endothelin-1 receptor agonists, p opiate receptor agonists, cAMP stimulating agents, tyrosinase stimulating agents.

[0125] In a particular embodiment, the composition according to the invention further comprises, as a self-tanner, a combination of dihydroxy methylchromonyl palmitate and / or dimethylmethoxy chromanol as well as a lipophilic form of tyrosine.

[0126] This combination of active ingredients effectively stimulates tanning. Dihydroxy methylchromonyl palmitate (CAS number: 1387636-35-2) corresponds, for example, to the cosmetic ingredient marketed by Merck under the name RonaCare® Bronzyl. Dimethylmethoxy chromanol (CAS number: 83923-51-7) corresponds to the cosmetic ingredient marketed by LIPOTEC SA under the name lipochromone-6.

[0127] According to a particular embodiment, dihydroxy methylchromonyl palmitate or dimethylmethoxy chromanol is present in the composition according to the invention at height of 0.01% to 10% by total weight of the composition, advantageously from 0.05% to 10%, even more advantageously from 0.1% to 5%, more particularly from 0.1% to 0.5%.

[0128] The lipophilic form of tyrosine, within the meaning of the invention, is a tyrosine-based ingredient having a more pronounced lipophilic character than tyrosine. The lipophilic form of tyrosine may in particular correspond to oleoyl tyrosine (CAS No.: 147732-57-8), which is found, for example, in the liquid cosmetic ingredient TYR-OL, marketed by the company SEDERMA, and which comprises approximately 50% by weight of oleoyl tyrosine in butylene glycol (approximately 30% + approximately 20% oleic acid), or in the liquid cosmetic ingredient TYR-EXCEL, marketed by the company SEDERMA, which comprises approximately 50% by weight of oleoyl tyrosine, approximately 20% oleic acid (CAS No.: 112-80-1) and approximately 30% Luffa cy-lindrica oil (sponge gourd seed oil; CAS No.: 1242417-48-6).

[0129] According to another embodiment, the lipophilic form of tyrosine corresponds to a vegetable oil in which tyrosine has been formulated.

[0130] According to a particular embodiment, the vegetable oil is oleic sunflower oil, advantageously deodorized. Thus, the raw material OLEOACTIF TYROSINE BASE HELIANTHUS ANNUS marketed by the company OLEOS, and corresponding to the INCI designations Helianthus annuus seed oil (and) tyrosine (and) glyceryl stearate, can be used in the context of the present invention.

[0131] In practice, the lipophilic form of tyrosine, such as in cosmetic ingredients based on oleoyl-tyrosine (advantageously at 50% by weight) or tyrosine formulated in vegetable oil, represents between 0.1% and 10% by total weight of the composition, advantageously between 1 and 3%, even more advantageously between 1% and 1.5%.

[0132] The composition according to the invention may also contain active ingredients having depigmenting properties, such as for example: - lysine azeilate, or other derivatives or salts of azelaic acid - andrographolide, in particular the extract of Andrographis paniculata corresponding to the INCI designation Andrographis paniculata leaf extract; - native ascorbic acid (vitamin C) or its derivatives, in particular the derivatives corresponding to the INCI Ascorbyl Glucoside Ethyl ascorbic acid, Ascorbyl methylsilanol pectinate, Sodium ascorbyl phosphate and Ascorbyl tetraiso-palmitate; - arbutin or a plant extract containing it, in particular bearberry extract corresponding to the INCI designation Arctostaphylos uva-ursi leaf extract; - glabridin or a plant extract containing it, in particular extracts of licorice corresponding to the INCI designation Glycyrrhiza glabra root extract, Glycyrrhiza inflata root extract, Glycyrrhiza uralensis root extract; - biomimetic peptides corresponding to the INCI designations hexapeptide 2 and / or nonapeptide-1; - an aqueous extract of an algae called Palmaria palmata, in particular the extract corresponding to the INCI designation Palmaria palmata extract; - 4-n-butylresorcinol; - vitamin PP, also called niacinamide or nicotinamide, and its derivatives; - or their mixtures.

[0133] The composition according to the invention may also contain active ingredients having healing properties such as, for example, an antimicrobial agent chosen from the active ingredients corresponding to the following INCI designations: copper sulfate, zinc sulfate, sodium hyaluronate, Vitis vinifera (grape) vine extract, or mixtures thereof.

[0134] The composition according to the invention may also contain active ingredients having sebocorrective, keratolytic, sebum-regulating properties and / or anti-acne activity, in order to allow the formulation of sun products treating acne.

[0135] For example, the composition according to the invention may comprise an antimicrobial agent chosen from the active ingredients corresponding to the INCI designations propyl gallate, dodecyl gallate, Ginkgo biloba leaf extract, bakuchiol, dihydromyricetin, zinc gluconate, salicylic acid, or mixtures thereof.

[0136] The composition according to the invention can therefore also comprise at least one ingredient chosen from the following list: - a sun protection factor enhancing agent; - a photostabilizing agent; - an agent capable of filtering visible light, in particular blue light; - an extract of the bacterium Arthrobacter agilis, advantageously rich in caro- tenoids; - at least one polyol chosen from xylitol, rhamnose, sorbitol and mannitol; - an extract of the algae Laminaria ochroleuca, Blidingia minima or Laminaria saccharina; - an extract of the plant Zanthoxylum alatum; - panthenol; - vitamin E or one of its hydrophilic or lipophilic derivatives, or one of their salts, advantageously tocotrienol or tocopherol; - salicylic acid or one of its derivatives; - an extract of cade wood; - an extract from Boldo; - an extract from Meadowsweet; - glycyrrhetinic acid or one of its derivatives or salts; - vitamin PP; - a protective agent of the p53 protein, advantageously epigallocatechin gallate (EGCG); - an extract of karanja oil from Pongamia glabra; - linear paraffins; - ATP (adenosine-5 triphosphate), Gp4G (diguanosine tetraphosphate) or Ap4A (diadenosine tetraphosphate), - an agent limiting the action of iron ions involved in the formation of free radicals, advantageously EDTA; - a peptide extract of soy and / or wheat; - an amino acid selected from the group consisting of ectoine, creatine, ergothioneine, carnosine, tyrosine, decarboxycarnosine, glutamine and their salts; - a tanning or self-tanning agent; - a depigmenting agent; - a healing agent; - a sebocorrective, keratolytic, sebum-regulating and / or anti-acne agent.

[0137] According to a particular embodiment, the composition according to the invention further comprises mannitol and ectoine.

[0138] According to a particular embodiment, the composition according to the invention comprises at least one ingredient chosen from the group comprising the following INCI designations: Homosalate, Ethylhexyl methoxycrylene, Ethylhexyl salicylate, Butyl methoxydibenzoylmethane, advantageously all of these ingredients.

[0139] According to another particular embodiment, the composition according to the invention comprises at least one ingredient chosen from the group comprising the following INCI designations: Octocrylene, Methylene bis-benzotriazolyl tetramethylbutylphenol [nano], Butyl methoxydibenzoylmethane, Bis-ethylhexyloxyphenol methoxyphenyl triazine, advantageously all of these ingredients.

[0140] The composition according to the invention may also contain adjuvants such as those usually used in the field of cosmetics, such as active ingredients, preservatives, antioxidants, complexing agents, solvents, perfumes, fillers, bactericides, electrolytes, odor absorbers, coloring materials or even lipid vesicles. The choice of these adjuvants, as well as their concentrations, must be determined in such a way that they do not modify the properties and advantages sought for the composition of the present invention.

[0141] The composition of the invention is intended for topical application and more particularly for application to the skin, lips, hair and / or mucous membranes. Thus and within the scope of the invention, such a composition is in particular intended for the protection of the skin and / or appendages, in particular the mucous membranes, lips and hair.

[0142] The composition of the invention may be presented in all the galenic forms normally used in the cosmetic and dermatological fields, such as, for example, but in a non-limiting manner, in the form of an aqueous solution, optionally gelled, a dispersion of the lotion type, an oil-in-water (O / W) or conversely water-in-oil (W / O) emulsion, more or less fluid, or a multiple emulsion such as, for example, a triple emulsion (W / O / W or O / W / O), or in the form of a vesicular dispersion of the ionic (liposomes) and / or non-ionic type, a two-phase composition free of emulsifiers and gelling agents whose immiscible phases separate during storage, foam, stick, anhydrous oil, spray or mist.

[0143] In a particular embodiment, the composition according to the invention is an anhydrous oil. This type of formulation makes it possible to prepare minimalist formulas containing a very limited number of ingredients, since emulsifiers, thickeners and gelling agents can be excluded.

[0144] In an advantageous embodiment, the composition according to the invention is a W / O emulsion. Advantageously, the W / O emulsions according to the invention comprise the following compounds identified by their INCI designation: PEG-30 dipolyhydroxystearate or polyglyceryl-4 diisostearate / polyhydroxystearate / sebacate, as emulsifiers. These raw materials are available from the company CRODA under the trade name Cithrol DPHS and from the company EVONIK under the name Isolan GPS, respectively.

[0145] In another embodiment, the composition according to the invention is an O / W emulsion. Advantageously, the O / W emulsions according to the invention comprise an emulsifier chosen from the following group of compounds identified by their INCI designation: sodium stearoyl glutamate, potassium cetyl phosphate, glyceryl stearate / PEG-100 stearate and C20-22 alkyl phosphate / C20-C22 alkyl alcohols, tribehenin PEG-20 esters, C14-C22 alcohols / C12-20 alkyl glucoside, cetearyl alcohol / coco-glucoside and mixtures thereof. For example, the raw material EMULGIN SG corresponding to the INCI designation sodium stearoyl glutamate and marketed by BASF, the raw material EMULIUM 22 corresponding to the INCI designation tribehenin PEG-20 esters and marketed by GATTEFOSSE, the raw material SENSANOV WR corresponding to the INCI designation C20-22 alkyl phosphate / C20-C22 alkyl alcohols and marketed by SEPPIC, the raw material MONTANOV L corresponding to the INCI designation C14-C22 alcohols / C12-20 alkyl glucoside and the raw material AMPHISOL K corresponding to the INCI designation potassium cetyl phosphate and marketed by DSM, the raw material MONTANOV 82 corresponding to the INCI designation cetearyl alcohol / coco-glucoside and marketed by SEPPIC, can be used in the compositions according to the invention.

[0146] The composition according to the invention may also comprise preservatives. Any preservative suitable for use in cosmetic or dermatological compositions may be used in the formulation of a composition according to the invention.

[0147] Advantageously, the preservatives used are alkanediols, even more advantageously 1,2-alkanediols or 1,3-alkanediols, and mixtures thereof.

[0148] In a preferred embodiment, the preservative is a 1,2-diol selected from 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, 1,2-octanediol and 1,2-decanediol, or mixtures thereof.

[0149] In an alternative embodiment, the preservative is a 1,3-diol chosen from 1,3-propanediol and 1,3-butanediol, or mixtures thereof. In practice, these alkanediols are marketed by several companies, in particular the company SYMRISE or MINACARE.

[0150] Preferably, the composition according to the invention comprises between 0.01% and 2% by weight of the composition of diols, advantageously between 0.1% and 1%, for example 0.5%.

[0151] The invention also relates to a method for protecting the trans form of cutaneous urocanic acid, in particular from UV-B-induced isomerization, comprising the application to the skin of a composition as defined above.

[0152] Alternatively, the invention relates to a method for reducing or decreasing the quantity of the cis form of cutaneous urocanic acid, in particular resulting from the isomerization of the trans form induced by UV-B, comprising the application to the skin of a composition as defined above.

[0153] Another aspect of the invention relates to the in vitro use of y-oryzanol and / or tamanu oil, or even a composition as defined above, to protect the trans form of urocanic acid, in particular to reduce, diminish or inhibit its isomerization into the cis form.

[0154] By way of example and in a non-limiting manner, trans-form urocanic acid may be used in a culture medium or be present constitutively in a cell culture, for example of fibroblasts or keratinocytes.

[0155] The term "culture medium" refers to a support that allows the cultivation of eukaryotic or prokaryotic organisms. This medium provides the essential components for the multiplication of these cells. The term "culture medium" corresponds to any medium of conventionally used culture media, such as minimal, empirical, selective, enriched, differential or discriminatory culture media. It therefore involves cultivating cells on a synthetic medium, under sterile conditions and in a controlled environment.

[0156] In a particular embodiment, the culture medium according to the invention further contains any element necessary for the survival and proliferation of the cells.

[0157] By “cell culture” we mean a set of biological techniques used to enable the survival and growth of cells outside their original environment (in vitro cell culture).

[0158] The manner in which the invention can be implemented and the advantages which result therefrom will become more apparent from the following examples of implementation, given for informational and non-limiting purposes, with the support of the appended figures.

[0159] [Fig. 1]: UCAczs content resulting from UV-induced isomerization of UC Al rans, in the presence of 1%, 0.5% and 0.1% y-oryzanol: used alone (A), in combination with an SPF15 product (B) or an SPF50+ product (C)

[0160] UCAc = cis form of urocanic acid.

[0161] [Fig.2]: UCAczT content resulting from UV-induced FUCA / rans isomerization in the presence of 2%, 1% and 0.5% tamanu oil, used alone (A), in combination with an SPF15 product (B) or an SPF50+ product (C)

[0162] UCAc = cis form of urocanic acid

[0163] [Fig.3]: Absorption spectrum of the product Adaptasun Cream SPF 15 (fie 14E50CMBe) compared to the absorption profiles of the active ingredients tamanu oil and y-oryzanol in the same proportions (l / 2000e).

[0164] EXAMPLES OF IMPLEMENTATION

[0165] The percentages indicated are given by weight of product relative to the total weight of the composition in the tables below. Example I - Day care without filters - H / W emulsion NomlNCI % Aqua / water / eau 55.788 Dicaprylyl carbonate 24.9973 Glycerin 5.00 Dimethicone 3.00 Tribehenin PEG-20 esters 3.00 Cl0-18 triglycerides 2.00 Methylpropanediol 1.40 Calophyllum inophyllum seed oil 1,00 Sucrose stéarate 1,00 Hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer 0,88 Pentylene glycol 0,50 Tocopheryl acetate 0,50 Sodium citrate 0,20 1,2-hexanediol 0,125 Caprylyl glycol 0,125 Mannitol 0,10 Xylitol 0,10 Citric acid 0,09 Polysorbate 60 0,06 Sorbitan isostearate 0,06 Rhamnose 0,05 Ectoin 0,01 Glycyrrhiza glabra (licorice) root extract 0,01 Tocopherol 0,0027 Fructooligosaccharides 0,001 Caprylic / capric triglycéride 0,00095 Laminaria ochroleuca extract 0,00005 Exemple II - émulsion H / E SPF50+

[0167] NomINCI % Aqua / water / eau 49,816 Octocrylene 9,00 Dicaprylyl carbonate 8,4973 Methylene bis-benzotriazolyl tetramethylbutylphenol [nano] 6,00 Glycerin 5,00 Butyl methoxydibenzoylmethane 4,50 Dimethicone 3,00 Tribehenin PEG-20 esters 3,00 Bis-ethylhexyloxyphenol methoxyphenyl triazine 2.50 Cl0-18 triglycerides 2.00 Methylpropanediol 1.40 Sucrose stearate 1.00 Decyl glucoside 0.90 Hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer 0.88 Pentylene glycol 0.50 Oryzanol 0.50 Tocopheryl acetate 0.50 Sodium citrate 0.20 1,2-hexanediol 0.125 Caprylyl glycol 0.125 Mannitol 0.10 Xylitol 0.10 Citric acid 0.09 Polysorbate 60 0.06 Sorbitan isostearate 0.06 Rhamnose 0.05 Propylene glycol 0.048 Xanthan gum 0.024 Ectoin 0.01 Glycyrrhiza glabra (licorice) root extract 0.01 Tocopherol 0.0027 Fructooligosaccharides 0.001 Caprylic / capric triglyceride 0.00095 Laminaria ochroleuca extract 0.00005

[0168] Example III - In tubo evaluation of the protective effect of y-oryzanol or tamanu oil, possibly in combination with a sunscreen, on the isomerization of trans to cis UCA. III-1 Aim of the study

[0169] The aim of this study is to evaluate in tubo the protective effect of y-oryzanol and tamanu oil, possibly in combination with a sunscreen, on the isomerization of urocanic acid (UCA) trans (\JCMrans) to cis (UCAcis). III-2 Materials and methods

[0170] In a first phase, the in tubo test was developed in order to evaluate and measure the protective effect of y-oryzanol and tamanu oil on the isomerization of trans to cis UCA.

[0171] The development took place in 2 stages:

[0172] -Step A: Determination of the experimental conditions allowing the induction of maximum isomerization:

[0173] - Concentration of UCA: lOpg / ml

[0174] - UV dose (UV-A + UV-B) (0.5; 0.8; 1; 2; 4 and 8 DEM or Erythematous Dose Minimum)

[0175] - Solvents: water and water / methanol mixture (MeOH)

[0176] - Presence or absence of aluminum foil around the 6-well plate

[0177] -Step B: Testing of sun products with SPF15 and SPF50+.

[0178] The test was carried out in the presence of sunscreen (1 mg / cm2) deposited on a plate quartz above the UCA solution, according to the conditions determined in step A by adjusting the UV irradiation dose in order to be able to observe isomerization in the presence of solar products.

[0179] The development step made it possible to define the following experimental conditions for the test:

[0180] - Concentration of UCA: lOpg / ml

[0181] - UV dose (UV-A + UV-B): 2 DEM or 9 J / cm2 UV-A + 300 mJ / cm2UV-B. For this irradiation, we observe as much disappearance of UCAtrans as appearance of UCA cis

[0182] - The association of the Water / MeOH mixture and the presence of the aluminum film present the optimal conditions for testing the application of active ingredients in the presence or absence of sunscreen products.

[0183] Once the development was completed, the tests of the 2 active ingredients in association with the sun products were carried out under the conditions determined during the development phase.

[0184] The following conditions were tested: - Negative control (NC) corresponding to the non-irradiated control of the solution containing FUCA / rans; - Positive control (PC) with or without cream, corresponding to the irradiated negative control, protected or not by the products placed on the plate; - Irradiated conditions with or without sunscreen + y-oryzanol or tamanu oil corresponding to the other conditions that measure the effectiveness of y - oryzanol or tamanu oil in solution with UCAtrans, with and without UV filtration.

[0185] The content of UCAtrans and UCAcA was measured by LC-MSMS. Each condition was performed in simplice. The LC-MSMS measurement was performed in duplicate.

[0186] Irradiation was carried out using a Biosun device (Vilber Lourmat); the DEM used correspond to the following irradiations: Doses Correspondence 0.5 DEM 2.25 J / cm2 UV-A + 75 mJ / cm2 UV-B 0.8 DEM 3.6 J / cm2 UV-A +120 mJ / cm2 UV-B 1 DEM 4.5 J / cm2 UV-A + 150 mJ / cm2 UV-B 2 DEM 9 J / cm2 UV-A+ 300 mJ / cm2 UV-B 4 DEM 18 J / cm2 UV-A + 600 mJ / cm2 UV-B 8 DEM 36 J / cm2 UV-A + 1200 mJ / cm2 UV-B

[0187] The following sunscreens were used in the tests: Sun protection Products SPF 15 Institut Esthederm -Adaptasun SPF 15 cream SPF50+ Bioderma - Photodemi Max SP50+

[0188] These products contain a filtration system supplemented by an SPF booster, according to the following tables: Adaptasun Cream SPF15 - Ingredients (INCI) % Homosalate 0.1 to 10 Ethylhexyl methoxycrylene 0.1 to 10 Ethylhexyl salicylate 0.1 to 5 Butyl methoxydibenzoylmethane 0.1 to 5 Photoderm Max SPF50+ - Ingredients (INCI) % Octocrylene 0.1 to 10 Methylene bis-benzotriazolyl tetramethylbutylphenol [nano] 0.1 to 10 Butyl methoxydibenzoylmethane 0.1 to 5 Bis-ethylhexyloxyphenol methoxyphenyl triazine 0.1 to 5

[0189] The active ingredients tested according to the invention are as follows: Code Molecule name Trade name Supplier Batch number Appearance O y-oryzanol ORYZAGAMMA-V Nikko 1780000406 Powder Ny Tamanu oil Nyamplung oil Givaudan J-15 Oily

[0190] The absorption spectra in the UV range of y-oryzanol or tamanu oil were compared to the absorption spectrum of Institut Esthederm -Adaptasun SPF15 cream, according to the following protocol:

[0191] Equipment used:

[0192] - Visible UV spectrophotometer 650S from Perkin Elmer

[0193] - Quartz tank

[0194] - 100mL volumetric flask

[0195] - Propipette

[0196] Dilutions of 1 / 2000 of y-oryzanol, tamanu oil and the system of filtration were carried out. 2 g of y-oryzanol or tamanu oil or the filtration system of Adaptasun SPF15 cream (fie 14E50CMBe) were taken up in 100 g with the diluent Cl2 / 15 alkyl benzoate or ethanol depending on their solubility.

[0197] The samples to be measured (dilution to l / 2000e) were placed in a quartz cuvette in the enclosure of the UV-visible spectrophotometer versus a quartz cuvette containing the diluent used to make the dilution (C12 / 15 alkyl benzoate or ethanol). Subsequently, the absorbance from 290 to 400nm (UV-A / UV-B) was measured in 1 nm steps. III-3 Results and conclusions

[0198] The protection index (IP) of y-oryzanol or tamanu oil is determined from the following formula:

[0199] IP(%) = [Positive control - UV stress + active] / [Positive control - negative control] x 100

[0200] The results are presented in the following table: [UCAtrans] in pg / ml (IP) 2 DEM Without filter SPF15 SPF50 CN (non-irradiated) 100 100 100 CP without cream 6.0 / / CP with cream / 24.7 32.6 y-oryzanol 1% 54.7 70.5 89.4 0.5% 44.7 59.9 78.3 0.1% 36.1 53.0 70.7 Tamanu oil 2% 68.9 80.3 94.6 1% 53.6 68.3 84.1 0.5% 37.6 57.3 70.8

[0201] In summary, the protection index gives a measure of the UCAtrans content found in the sample after irradiation compared to CN (non-irradiated).

[0202] As expected, sunscreens alone induce a decrease in FUCAtrans isomerization, with SPF50+ inducing greater protection than SPF15 (32.6% versus 24.7%).

[0203] Surprisingly, y-oryzanol and tamanu oil protect more effectively than the sunscreen (1% y-oryzanol: 54.7%; 2% tamanu oil without filter, i.e. without application of the sunscreen on the quartz plate: 68.9% versus SPF15: 24.7 and SPF50: 32.6).

[0204] The combination of filters and y-oryzanol or tamanu oil allows to obtain almost complete protection of FUCAtrans (2% tamanu oil with SPF50: 94.6%; 1% y-oryzanol with SPF50: 89.4%).

[0205] These results are confirmed in [Fig.l] which shows a decrease in the concentration of cA-urocanic acid after irradiation in the presence of y-oryzanol at 1%, 0.5% and 0.1% by weight of the composition, alone (A), in combination with an SPF15 product (B) or an SPF50+ product (C).

[0206] These results are also confirmed in [Fig.2] which shows a decrease in the concentration of cA-urocanic acid after irradiation in the presence of tamanu oil at 2%, 1% and 0.5% by weight of the composition, alone (A), in combination with an SPF15 product (B) or an SPF50+ product (C).

[0207] [Fig.3] represents the absorption spectrum of the product Adaptasun Cream SPF15 (14E50CMBe) compared to the absorption profiles of y-oryzanol or tamanu oil. The absorption of y-oryzanol and tamanu oil according to the invention in UV is very modest, particularly compared to the absorption profile of the sunscreen product, which is nevertheless incapable of effectively protecting trans UCA.

[0208] The protection conferred on FUCAtrans by y-oryzanol and tamanu oil cannot, therefore, cannot be explained solely by a UV filtration effect.

[0209] BIBLIOGRAPHY

[0210] Barresi, C., Stremnitzer, C., Mlitz, V., Kezic, S. , Kammeyer, A., Ghannadan, M., Posa-Markaryan, K.., Selden, C. Tschachler, E. and Eckhart, L. (2011) Increased sen-sitivity of histidinémie mice to UVB radiation suggests a crucial rôle of endogenous urocanic acid in photoprotection. J. Invest. Dermatol., 131(1) 188-194.

[0211] Beissert, D. Rühlemann, T. Mohammad, S. Grabbe, A, El-Ghorr, M. Norval, H. Morrison, R. D. Granstein, and T. Schwarz, (2001) IL-12 prevents the inhibitory effects of cis-urocanic acid on tumor antigen présentation by Langerhans cells: implications for photocarcinogenesis. J. Immunol., 167(11): 6232-6238.

[0212] Coelho, M. M. V., Matos, T. R. and Apetato, M. (2016) The dark side of the light: mechanisms of photocarcinogenesis. Clin. Dermatol., 34(5) 563-570.

[0213] Danovaro R., Bongiorni L., Corinaldesi C., Giovannelli D., Damiani E., Astolfi P., Greci L. Pusceddu A. (2008) Sunscreens cause coral bleaching by promoting viral infections. Environ Health Perspect., 116(4):441-447.

[0214] De Fabo E.C., Noonan F.P.. (1983) Mechanism of immune suppression by ultraviolet irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its rôle in photoimmunology. JExp Med., 1983 158(1):84-98.

[0215] De Fine Olivarius F., Wulf H.C., Crosby J., Norval M. (1996) The sunscreening effect of urocanic acid. Photodermatol Photoimmunol Photomed., 12:95-9.

[0216] Kaneko, K., Travers, J. B. , Matsui, M. S., Young, A. R., Norval, M. and Walker, S. L. (2009) cA-Urocanic acid stimulâtes primary human kératinocytes independently of serotonin or platelet-activating factor receptors. J. Invest. Dermatol., 129( 11) 2567-2573.

[0217] Schomagel I. (2007) The puzzle of polymorphous light éruption: Patients and pa-thogenesis: Chap. 6, - Doctoral thesis, Utrecht University, the Netherlands.

[0218] Walterscheid, J. P. Nghiem, D. X. Kazimi, N. Nutt, L. K. McConkey, D. J. Norval, M. and Ullrich, S. E. (2006) Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activâtes immune suppression via the 5-HT2A receptor. Proc. Natl. Acad. Sci. U. S. A., 103:17420-17425.

[0219] Ye, Y.-M. Le Pham, D. Park, H.-S. Leung, D. Y. M and Lim, K.-M. (2016) Increased Cis-to-Trans Urocanic Acid Ratio in the Skin of Chronic Urticaria Leads to the Enhancement of Mast Cell Degranulation. J. Allergy Clin. Immunol., 137(2) AB396.

Claims

Claims

1. A combination of y-oryzanol and an organic sunscreen for use against the effects of exposure to ultraviolet radiation via the protection of the trans form of urocanic acid.

2. Combination for use according to claim 1, characterized in that the ultraviolet radiation is UV-B radiation.

3. Combination for its use according to claim 1 or 2, characterized in that it is formulated in a composition and in that the y-oryzanol represents between 0.001% and 20% by weight of the composition, preferably between 0.01% and 10%, advantageously between 0.1% and 5%.

4. Combination for its use according to claim 1, characterized in that the organic filter is chosen from the group consisting of the following INCI designations: tris biphenyl triazine, bis ethylhexyloxyphenol methoxyphenyl triazine, methylene bis-benzotriazolyl tetramethylbu-tylphenol, diethylhexyl butamido triazone, phenylene bis-diphenyltriazine, and mixtures thereof.

5. Combination for use according to claim 3, characterized in that the organic filter represents between 0.1% and 30% by weight of the composition, advantageously between 0.5% and 20%, even more advantageously between 1% and 15%.

6. Combination for use according to one of the preceding claims, characterized in that it is in a form suitable for topical administration.

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