5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine for use in improving the appearance of scars and / or reducing scars

Abstract

The present invention relates to 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine or a composition comprising same for use in improving the appearance of skin scars or scar-like marks and / or for reducing scar-like marks, in particular for alleviating the redness of skin scars or scar-like marks.

Description

[0001] 5,6,5',6'-TETRAPHENYL-3,3'-(1,4-PHENYLENE)-BIS[1,2,4]TRIAZINE FOR USE IN IMPROVING THE APPEARANCE OF SCARS AND / OR REDUCING SCARRING

[0002] TECHNICAL FIELD OF THE INVENTION

[0003] The invention relates to 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine (also called phenylene bis-diphenyltriazine), as well as a composition comprising it, for its use in improving the appearance of skin scars or scar marks and / or reducing scar marks, and in particular in reducing the redness of skin scars or scar marks.

[0004] STATE OF THE ART

[0005] The skin is made up of different tissues that form a vital barrier for the body against the external environment. This barrier protects the body against external aggressions, particularly chemical or mechanical.

[0006] The skin is made up of three main parts: the superficial one, the epidermis, the internal part, the dermis, and a deeper layer, the hypodermis, which interact with each other.

[0007] The human epidermis is composed of four to five distinct layers (depending on the anatomical site) and four types of cells: keratinocytes, which are the vast majority, melanocytes, Langerhans cells and Merkel cells. Each of these cell types contributes through its own functions to the essential role played in the body by the skin, in particular the role of protecting the body from external aggressions. Epidermal cells proliferate at the level of the deepest layer, the basal layer, and differentiate during their migration towards the upper layers to successively form the spinous layer, the granular layer and finally the horny layer (or stratum corneum) which is the most superficial layer of the epidermis.

[0008] Healing is a set of local defense phenomena occurring after an attack: injury, burn, dermatological procedure, surgical intervention. Wound healing is a complex and dynamic biological process that involves the interaction of numerous local and systemic factors in normal tissue repair.

[0009] The progression of wound healing involves several interdependent phases: hemostasis and inflammation, proliferation, and remodeling. Proliferation involves three clearly observable processes: granulation, contraction, and re-epithelialization. During granulation, cells that will be involved in the rest of the repair process proliferate and migrate to the wound bed. These cells include macrophages, fibroblasts, and endothelial cells. Macrophages constantly release chemotactic factors and growth factors. Fibroblasts build the new cellular matrix necessary for cell growth at the bottom of the wound. This scaffolding promotes cell migration.Finally, endothelial cells trigger the formation of vascular buds that will form new capillaries, which will restore perfusion and ensure the supply of oxygen and nutrients essential to the metabolic activity of the cells in the wound.

[0010] Wound contraction is a mechanism for reducing wound size and fibroblasts play a prominent role in this contraction.

[0011] Re-epithelialization involves the regeneration of the epidermis covering a wound to reform an effective barrier against the external environment, capable of pigmentation and regaining its sensory and immune functions. It therefore involves the cellular processes of keratinocyte migration and proliferation, and the restoration of a basement membrane that covers the dermis and epidermis. When the migration of basal cells toward the center of the wound allows the two edges of the wound to join, a wave of cell mitosis occurs to fill the spaces left by the migration and provide cells for the epithelial tissue in three-dimensional regeneration.

[0012] The stages of proliferation of keratinocytes, fibroblasts or endothelial cells can be considered as one of the functional phenomena testifying to the healing activity of an active ingredient.

[0013] An increase in fibroblast proliferation would participate in the healing of a deep wound (damage to the dermis), while an increase in the proliferation and / or migration of keratinocytes would participate in re-epithelialization.

[0014] Healing also poses aesthetic problems when healing defects, or poor healing, can occur, for example with age. The healing and recovery process of skin lesions thus becomes less efficient, and unsightly and almost permanent visible marks may remain.

[0015] All surgical, aesthetic medicine, dermatology and non-medical traumatic lesions such as scrapes, cuts, scratches, burns, but also pathological lesions such as acne, involve a healing process and result in scars, which are more or less marked depending on the quality of this healing.

[0016] There are several types of skin scars depending on their shape, size, or thickness: Atrophic or depressed scar: This type of scar is generally characterized by small, circular, hollow, and sunken marks. These are often marks caused by severe acne or chickenpox. They are often the result of a lack of subcutaneous support or vascularization at the wound site.

[0017] Flat or white scar: This is the most common scar. It is supple, smooth, and white in color. This is considered the "normal" appearance of a well-formed scar, the result of a non-pathological healing process.

[0018] Hypertrophic scar: red and swollen, it can also itch and be itchy (an unpleasant sensation that causes the need to scratch). This scar appears in particular in cases of burns, but also following surgery. This is called a "postoperative scar." Its size can increase for several months before fading. However, it remains red, bulky and generally takes on the appearance of a cord.

[0019] Stretched scar: This is a long, hollow scar. It appears when the skin around the scar is stretched. Stretch marks are one of these types of scars.

[0020] However, at the beginning of healing, all scars tend to be red, a normal phenomenon linked to inflammation. The shades are also very variable depending on the color of the skin. The lesion will also remain red throughout the healing process, which will last more or less time depending on the size of the wound.

[0021] Exposure to the sun may further discolor the scar. The epidermis, which is thinner and more fragile at the scar, will then be very sensitive to UV rays throughout the skin's repair process.

[0022] The field of photoprotection remains a major public health issue to prevent skin damage from overexposure to the sun. Skin damage is mainly induced by ultraviolet radiation (UVA and / or UVB), but also by visible light, particularly high-energy visible blue light, and infrared via damage to macromolecules leading to DNA lesions, oxidative stress, lipid peroxidation and degradation of the dermal matrix.

[0023] Therefore, irritated skin exposed to UV rays is even more fragile and therefore requires more attention for proper healing.

[0024] There is always a need to propose new compositions to promote and improve the healing of damaged or irritated skin, and to enable rapid repair of skin lesions and, above all, to obtain the most aesthetic scars possible. SUMMARY OF THE INVENTION

[0025] The Applicant observed that a composition comprising phenylene bis-diphenyltriazine made it possible to reduce scar marks and to reduce the red coloration of said marks.

[0026] The present invention thus relates to 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine for its use in improving the appearance of skin scars or scar marks and / or reducing scar marks.

[0027] The present invention also relates to the use of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine for improving the appearance of skin scars or scar marks and / or reducing scar marks.

[0028] The present invention also relates to the use of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine for the preparation of a cosmetic or pharmaceutical (e.g. dermatological) composition intended to improve the appearance of skin scars or scar marks and / or reduce scar marks.

[0029] The present invention also relates to a method for improving the appearance of skin scars or scar marks and / or reducing scar marks comprising administering, preferably by topical application, to a person in need thereof an effective amount of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine.

[0030] The present invention also relates to a composition comprising 5, 6, 5', 6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine, and at least one cosmetically or pharmaceutically acceptable excipient for improving the appearance of skin scars or scar marks and / or reducing scar marks.

[0031] The present invention also relates to the use of a composition comprising 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine, and at least one cosmetically or pharmaceutically acceptable excipient for improving the appearance of skin scars or scar marks and / or reducing scar marks.

[0032] The present invention also relates to the use of a composition comprising 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine, and at least one cosmetically or pharmaceutically acceptable excipient for the preparation of a cosmetic or pharmaceutical (e.g. dermatological) composition for improving the appearance of cutaneous scars or scar marks and / or reducing scar marks. The present invention also relates to a method for improving the appearance of cutaneous scars or scar marks and / or reducing scar marks comprising administering, preferably by topical application to the skin, to a person in need thereof an effective amount of a composition comprising 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine, and at least one cosmetically or pharmaceutically acceptable excipient.

[0033] Advantageously, 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine may be used in combination with at least one healing agent.

[0034] The present application therefore also relates to a combination of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine with a healing agent, and in particular with zinc sulfate, copper sulfate, panthenol or madecassoside.

[0035] The present application also relates to a composition, more particularly a cosmetic or pharmaceutical (e.g. dermatological) composition, comprising 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine, a healing agent (e.g. zinc sulfate, copper sulfate, panthenol or madecassoside) and at least one cosmetically or pharmaceutically acceptable excipient.

[0036] DETAILED DESCRIPTION OF THE INVENTION tetraphenyl-3,3'-(L4-phenylene)-bis[L2,4]triazine

[0037] 5,6,5',6'-Tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine, (CAS No.: 55514-22-2, Trade Name: Triasorb™) also known as phenylene bis-diphenyltriazine, is a sunscreen, more specifically an ultra-broad spectrum sunscreen capable of filtering the harmful part of the solar spectrum, which includes UV radiation (UVB and UVA), but also high-energy visible blue light. In the remainder of the description, the terms 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine and phenylene bis-diphenyltriazine are used interchangeably.

[0038] The term "sunscreen" refers to a substance capable of filtering solar radiation to protect a surface, typically skin or hair, from the harmful effects of this radiation.

[0039] A sunscreen is called a "UVA filter" or "UVB filter" depending on whether it filters mainly UVA or UVB rays. A so-called "broadband" or "broad spectrum" sunscreen filters both UVA and UVB rays.

[0040] An "ultra-broadband" or "ultra-broad spectrum" sunscreen is a broadband sunscreen as defined above that also filters out high-energy visible blue light. The term "ultraviolet radiation" or "UV radiation," commonly abbreviated "UV," refers to solar ultraviolet radiation but also to artificial ultraviolet radiation, generated by tanning lamps, for example. It includes, in particular, UVA and UVB radiation.

[0041] By "UVA radiation" or simply "UVA" is meant ultraviolet rays with an X-ray wavelength between 320 and 400 nm.

[0042] By "UVB radiation" or simply "UVB" is meant ultraviolet rays with an X-ray wavelength between 290 and 320 nm.

[0043] By "high energy visible blue light" or "HEV" is meant rays with an X-ray wavelength between 400 and 450 nm, in particular between 400 and 450 nm. Depending on the radiation filtration mechanism, i.e. whether the radiation is absorbed and / or reflected, or even diffused by the solar filter, a distinction is made, strictly speaking: filters in the strict sense, which mainly absorb the radiation, and screens, which absorb and reflect the radiation.

[0044] However, in the remainder of the description, the term "solar filter", sometimes abbreviated "filter", will be used interchangeably, whether it is a filter or a screen. The term "UV filter" can also be used instead of "solar filter".

[0045] A sunscreen can be "lipo-soluble" or "water-soluble", depending on whether it dissolves more easily in lipids or in water, or "insoluble". A non-soluble sunscreen is typically in particulate form, and can nevertheless be incorporated into a sunscreen composition, in particular in a dispersed form, in particular water-dispersed when it is dispersed in an aqueous phase.

[0046] Phenylenese bis-diphenyltriazine is a non-soluble type filter. In particular, it is a water-dispersible filter, which is typically in the form of an aqueous dispersion, comprising between 20% and 50%, in particular between 40% and 50% by weight of active material relative to the total weight of the dispersion.

[0047] Advantageously, the process for preparing the aqueous dispersion consists of grinding the insoluble organic filter in the form of particles, using a grinding apparatus and in the presence of a grinding aid. Conventionally, wet grinding processes are used (wet grinding, wet mixing) and the grinding aid allows better dispersion of the particles. These techniques are well known to those skilled in the art. The grinding apparatus may be, for example, a microbead mill, a vibrating mill or a ball mill. Depending on the grinding process, the grinding aid is chosen from the group consisting of anionic, non-ionic or amphoteric surfactants, emulsifiers and dispersants such as PPG-1-PEG-9 Lauryl Glycol Ether (Eumulgin® L, marketed by BASF).

[0048] In a particular embodiment, the size D50 of the phenylene bis-diphenyltriazine particles is between 100 and 1000 nm, more particularly between 100 and 500 nm, even more particularly between 120 and 400 nm, in particular between 120 and 250 nm, in particular between 120 and 200 nm, typically between 150 and 200 nm.

[0049] By "D50" or "median" particle size is meant the size for which the cumulative function F(D) is equal to 50%, F(D) being defined according to the following relation: in which: f(D) is the particle size distribution in number, and Di is a size class.

[0050] The value of the D50 size can be determined by laser diffraction, in particular using a Mastersizer 3000 laser diffraction granulometer, especially in liquid form.

[0051] Healing agent

[0052] Phenylenese bis-diphenyltriazine can be used in combination with at least one healing agent.

[0053] For the purposes of this description, the term “healing agent” means an agent capable of improving and / or accelerating the healing process.

[0054] The healing agent may be, for example, zinc sulfate, copper sulfate, zinc gluconate, allantoin, panthenol, madecassoside, a lysate or secretome of a fermentation medium of a non-pathogenic bacterium, in particular lactic acid bacteria, proteobacteria and more particularly the secretome of Aquaphilus dolomiae (also called LMB64 bacteria), zinc oxide, aloe vera (in particular aloe vera gel), honey or a mixture thereof.

[0055] The healing agent may be, in particular, zinc sulfate, copper sulfate, panthenol, madecassoside, a secretome of Aquaphilus dolomiae, or a mixture of these. It may also be zinc sulfate, copper sulfate, panthenol, madecassoside, or a mixture of these.

[0056] The bacterium LMB64, also called Aquaphilus dolomiae, is described in international application WO2012 / 085182 and filed in the name of the applicant at the National Collection of Cultures of Microorganisms (CNCM), Institut Pasteur, Paris, on April 8, 2010 under reference 1-4290.

[0057] The secretome of Aquaphilus dolomiae or of the LMB64 bacterium may be a bacterial secretome as defined in international application WO2018 / 185324, said secretome being capable of being obtained, or obtained, by a method comprising the steps of: a) culturing the LMB64 bacterium in a culture medium and conditions adapted to its growth, b) liquid / solid separation, in particular by centrifugation, and recovery of the liquid phase, c) obtaining the secretome comprising the biomolecules secreted by the LMB64 bacterium in the liquid phase, advantageously with the addition of a basic buffer (so as to have a pH advantageously between 8 and 12, in particular between 9 and 11), for example a Tris-arginine buffer.

[0058] According to a preferred embodiment, the method for preparing the bacterial secretome may comprise the following steps:

[0059] • a first inoculum of LMB64 bacteria is prepared in a first suitable culture medium containing mineral, protein and carbohydrate substances suitable for this preculture, for example in an Erlenmeyer flask;

[0060] • a second pre-fermentation culture in batch mode in a second culture medium close to or identical to the first culture medium (or any equivalent medium) is then carried out;

[0061] • fed-batch fermentation in a medium identical or close to the second culture medium is then carried out, in order to obtain a high cell density;

[0062] • a centrifugation step then allows the elimination of cells and cellular debris and the recovery of the culture supernatant (liquid phase);

[0063] • a basic buffer (so as to have a pH advantageously between 8 and 12, in particular between 9 and 11), for example a Tris-arginine buffer, is added to the culture supernatant to give a buffered supernatant which is left in contact with the buffer for 1 to 7 hours, at a temperature between 1 and 6°C;

[0064] • the buffered supernatant is then clarified by filtration, for example on a filter or filter cartridge with a threshold of 0.4 pm, preferably 0.2 pm, so as to eliminate suspended particles which would not have been eliminated during the centrifugation step.

[0065] The bacterial secretome can be prepared more particularly according to examples 1-2 of international application WO2018 / 185324.

[0066] The secretome of Aquaphilus dolomiae will more specifically be aquaphilus dolomiae ferment filtrate (INCI name).

[0067] For the purposes of the present invention, the term "secretome" means all the biomolecules secreted and externalized by a bacterium, and more particularly the bacterium LMB64 or Aquaphilus dolomiae, without modification, alteration or lysis of the bacterial cell. These biomolecules more particularly comprise proteins, peptides and secondary metabolites secreted and externalized by the bacterium. These biomolecules will therefore be present in the culture medium.

[0068] By "culture medium" is meant any medium comprising at least the nutrients necessary for the growth and multiplication of bacteria. The culture medium is more particularly a liquid medium allowing the recovery of the culture supernatant containing the secretome. The culture medium may include in particular water, a carbon source, a nitrogen source and salts.

[0069] Composition

[0070] The composition according to the present invention comprises 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine, as defined above, and at least one cosmetically or pharmaceutically acceptable excipient. It is more particularly a cosmetic or pharmaceutical (e.g. dermatological) composition. This composition may further comprise at least one healing agent as defined above.

[0071] In the present invention, "cosmetically or pharmaceutically acceptable" is intended to mean that which is useful in the preparation of a composition which may have a cosmetic or pharmaceutical application, and which is generally safe, non-toxic and neither biologically nor otherwise undesirable and which is acceptable for human cosmetic or pharmaceutical use. "Cosmetically or pharmaceutically acceptable excipient" means any cosmetically or pharmaceutically acceptable adjuvant enabling the manufacture, preservation or administration of the composition.

[0072] In a particular embodiment, the composition according to the invention is in the form of an emulsion, preferably oil-in-water.

[0073] For the purposes of the present invention, the term "emulsion" means any type of emulsion obtained by dispersing a discontinuous internal phase in a continuous external phase, one of these phases being an aqueous phase and the other being an oily phase. This is, for example, an oil-in-water or water-in-oil or multiple emulsion, preferably an oil-in-water emulsion.

[0074] The emulsion can be more or less fluid and can be presented in particular in the form of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste, or possibly an aerosol, a mousse or a spray, and can also be water resistant.

[0075] The composition according to the invention is intended more particularly for topical application to the skin.

[0076] In a particular embodiment, the phenylene bis-diphenyltriazine represents between 1% and 5%, in particular between 2% and 5%, in particular between 2% and 4%, typically between 3% and 4% by weight relative to the total weight of the composition.

[0077] When the composition also comprises at least one healing agent, the healing agent represents 0.1 to 10% and preferably 0.5 to 5% by weight relative to the total weight of the composition.

[0078] It is understood that these mass percentages, as well as all those indicated in the description, are expressed as a percentage of mass of active material relative to the total mass of the composition.

[0079] In the composition according to the present invention, phenylene bis-diphenyltriazine may be combined with one or more other sunscreens, to constitute a photoprotective system which makes it possible, after application to a surface (skin, hair, etc.), by mechanisms of absorption and / or reflection and / or diffusion of UVA and / or UVB radiation, to prevent, or at least limit, the contact of said radiation with said surface. The photoprotective system constituting a composition according to the invention preferably comprises one or more liposoluble UV filters chosen from the following filters (i) to (v): (i) 2-[4-(diethylamino)-2-hydroxybenzoyl]hexyl benzoate (CAS No.: 302776-68-7), also called diethylamino hydroxybenzoyl hexyl benzoate or DHHB, marketed by BASF under the name Uvinul APlus®.

[0080] It is a liposoluble UVA filter, with a maximum absorption wavelength Àmax equal to 354 nm.

[0081] In a particular embodiment, the DHHB represents between 1% and 10%, for example between 3% and 10%, in particular between 4% and 9%, typically between 5% and 8%, in particular between 5% and 7%, in particular between 6% and 7% or advantageously between 5% and 6% by weight, relative to the total weight of the composition.

[0082] (ii) 2,4-bis[4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-(4-methoxyphenyl)-l,3,5-triazine (CAS No. 187393-00-6), also known as bis-ethylhexyloxyphenol methoxyphenyl triazine or BEMT, marketed by BASF under the name Tinosorb S®.

[0083] It is a liposoluble broadband filter, having two absorption peaks at 310 nm and 340 nm. In a particular embodiment, the BEMT represents between 1% and 4%, in particular between 2% and 4%, in particular between 2% and 3% by weight relative to the total weight of the composition.

[0084] (iii) 4-tert-butyl-4-methoxydibenzoylmethane or butyl methoxydibenzoylmethane (chemical name: l,4-(l,l-dimethylethyl)phenyl-3-(4-methoxyphenyl)-l,3-propanedione; CAS No.: 70356-09-1), also known as avobenzone or BMDBM, marketed in particular by DSM under the name Parsol 1789®.

[0085] It is a liposoluble UVA filter, with a maximum absorption wavelength Àmax equal to 357 nm.

[0086] In a particular embodiment, the BMDBM represents between 1% and 10%, for example between 1% and 8%, in particular between 1% and 5%, typically between 2% and 4% by weight, relative to the total weight of the composition.

[0087] (iv) ethylhexyl triazone or EHT (chemical name: 4-[[4,6-bis[[4-(2-ethylhexoxy-oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid, 2-ethylhexyl ester; CAS No.: 88122-99-00), marketed by BASF under the name Uvinul T 150®.

[0088] It is a liposoluble UVB filter, with a maximum absorption wavelength λmax equal to 314 nm.

[0089] In a particular embodiment, the EHT represents between 1% and 6%, typically between 2% and 5%, in particular between 3% and 5%, in particular between 3.5% and 4.5% by weight relative to the total weight of the composition. (v) diethylhexyl butamido triazone or DBT (chemical name: 4,4'-[[6-[[4-[[(l,1- dimethylethyl)amino]carbonyl]phenyl]amino]-l,3,5-triazine-2,4-diyl]diimino]bis-,bis(2- ethylhexyl)benzoate; CAS No.: 154702-15-5), marketed by 3V Sigma under the name Uvasorb HEB®.

[0090] It is a liposoluble UVB filter, with a maximum absorption wavelength λmax equal to 310 nm.

[0091] In a particular embodiment, the DBT represents between 1% and 6%, typically between 2% and 5%, in particular between 3% and 5%, in particular between 3.5% and 4.5% by weight relative to the total weight of the composition.

[0092] The photoprotective system constituting a composition according to the invention may further comprise one or more additional particulate organic UV filters, in addition to phenylene bis-diphenyltriazine, chosen from the following filters (vi) and (vii):

[0093] (vi) methylene bis-benzotriazolyl tetramethylbutylphenol (chemical name: 2,2'-methylene- bis-(6-(2H-benzotriazol-2-yl)-4-(l,l,3,3-tetramethylbutyl)phenol; CAS No.: 103597-45-1) also known as MBBT, marketed by BASF under the name Tinosorb M®.

[0094] It is a broadband filter, having two absorption peaks at 306 nm and 348 nm, of the non-soluble type. MBBT is typically in the form of an aqueous dispersion, comprising between 40% and 60%, typically 50% by weight of active material relative to the total weight of the dispersion.

[0095] In a particular embodiment, the MBBT represents between 1% and 7%, typically between 2% and 6%, in particular between 2% and 5%, in particular between 3% and 4% by weight relative to the total weight of the composition.

[0096] In a particular embodiment, the size D50 of the MBBT particles is between 50 nm and 250 nm, in particular between 60 nm and 150 nm.

[0097] (vii) 2,4,6-tris(biphenyl-4-yl)-l,3,5-triazine (CAS No. 31274-51-8) also trisbiphenyl triazine or TBPT, marketed by BASF under the name Tinosorb A2B®.

[0098] It is a UVB filter, with a maximum absorption wavelength Àmax equal to 310 nm, of the non-soluble type.

[0099] TBPT is typically in the form of an aqueous dispersion, comprising between 40% and 60%, typically 50% by weight of active ingredient relative to the total weight of the dispersion.

[0100] In a particular embodiment, the TBPT represents between 1% and 7%, in particular between 2% and 7%, in particular between 2% and 6% by weight relative to the total weight of the composition. In a particular embodiment, the size D50 of the TBPT particles is between 50 nm and 250 nm, in particular between 80 nm and 150 nm.

[0101] In a particular embodiment, the photoprotective system constituting a composition according to the invention may further comprise one or more particulate inorganic filters (also called mineral filters), such as titanium dioxide (TiCh) or zinc oxide (ZnO). The particulate inorganic filter(s) optionally present in the composition according to the invention typically have a particle size D50 of between 15 nm and 150 nm. In another particular embodiment, the photoprotective system constituting a composition according to the invention does not comprise a particulate inorganic filter.

[0102] In a particular embodiment, the photoprotective system constituting a composition according to the invention may further comprise at least one water-soluble filter, such as phenyl benzymidazole sulfonic acid. In another particular embodiment, the photoprotective system constituting a composition according to the invention does not comprise a water-soluble filter.

[0103] In a particular embodiment, the composition according to the invention does not comprise ethylhexyl salicylate, octocrylene, ethylhexyl methoxy cinnamate, isoamyl methoxy cinnamate, homosalate, para-aminobenzoic acid (PABA), octyl dimethyl PABA, 3-methylbenzylidene camphor, 4-methylbenzylidene camphor, benzophenone-3 and / or benzophenone-4.

[0104] In a particular embodiment, the total number of UV filters present in the composition is less than or equal to 5, preferably less than or equal to 4, and / or all of the UV filters present in the composition represent between 4% and 25% by weight, in particular between 6% and 20% by weight, in particular between 7% and 18% by weight, typically between 8% and 17% by weight, relative to the total weight of the composition.

[0105] In an advantageous embodiment, the photoprotective system of the composition according to the invention consists of:

[0106] (a) 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine,

[0107] (b) 2,4-bis[4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-(4-methoxyphenyl)-1,3,5-triazine (BEMT),

[0108] (c) hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate (DHHB), and

[0109] (d) a sunscreen (d) chosen from ethylhexyl triazone (EHT) and diethylhexyl butamido triazone (DBT). In particular, the sunscreen (d) corresponds to ethylhexyl triazone. In this particular embodiment, 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine advantageously represents between 1% and 5%, in particular between 2% and 5%, in particular between 2% and 4%, typically between 3% and 4% by weight relative to the total weight of the composition.

[0110] In this particular embodiment, the DHHB advantageously represents between 1% and 10%, for example between 3% and 10%, in particular between 4% and 9%, typically between 5% and 8%, for example between 5% and 7%, in particular between 6% and 7% or advantageously between 5% and 6% by weight, relative to the total weight of the composition.

[0111] In this particular embodiment, the BEMT advantageously represents between 1% and 4%, in particular between 2% and 4%, in particular between 2% and 3% by weight of the composition relative to the total weight of the composition.

[0112] In this particular embodiment, the sunscreen (d), i.e. the EHT or the DBT, advantageously represents between 1% and 6%, typically between 2% and 5%, in particular between 3% and 5%, in particular between 3.5% and 4.5% by weight relative to the total weight of the composition.

[0113] The composition according to the invention comprises at least one cosmetically or pharmaceutically (e.g. dermatologically) acceptable excipient, which are in particular conventionally used in the art, for example chosen from liquid lipophilic compounds, water-miscible polyols, emulsifiers, consistency agents, water-retentive agents, texturizing agents, opacifiers, coloring pigments, antifoaming agents, perfumes, preservatives, polymers, fillers, sequestrants, bactericides, odor absorbers, alkalizing or acidifying agents, surfactants, free radical scavengers, vitamins, alpha-hydroxy acids, active agents (in particular moisturizing agents, antioxidants, etc., for example hyaluronic acid or a salt thereof such as the sodium salt), thermal waters (e.g. Avène water), etc.

[0114] Applications

[0115] Phenylenese bis-diphenyltriazine or a composition according to the invention comprising it makes it possible to improve skin scars or scar marks, more particularly makes it possible to improve the appearance of skin scars or scar marks, and / or to reduce scar marks.

[0116] A scar or skin scar is a mark left on the skin by an injury during and after the repair of the skin tissue. A scar mark is a mark left on the skin by an injury after the repair of the skin tissue.

[0117] Thus, phenylene bis-diphenyltriazine or a composition according to the invention comprising it makes it possible to reduce the redness of scars or scar marks. Since the scars or scar marks are less red, they are less visible and their appearance is improved. In particular, the redness of the scars or scar marks is reduced more strongly (i.e. in color intensity) and / or more quickly (i.e. in duration).

[0118] The skin will be more particularly damaged or irritated skin, particularly exposed to UV rays, such as solar radiation. The damaged skin will preferably be re-epithelialized skin, that is to say that the lesion is epithelialized, namely that it is already covered by an epithelium (even if this may still be thin).

[0119] Skin lesions can appear following trauma or following medical or surgical procedures, invasive or non-invasive, curative or for aesthetic purposes.

[0120] Injured or irritated skin will preferably be skin with abrasions, scratches, cuts, scrapes, bites (e.g., insect bites), grazes, burns, abrasions (e.g., from rubbing), sutures, excoriated acne lesions, post-traumatic lesions, post-surgical lesions, lesions following a dermatological procedure, lesions following a cosmetic procedure, lesions following a cosmetic medical procedure, a tattoo (e.g., less than six weeks old) or a combination of these.

[0121] Lesions following a dermatology, aesthetic or aesthetic medicine procedure may follow cryotherapy, mesotherapy, waxing, treatment with intense pulsed light (hair removal) or laser (hair removal, ablative laser, vascular laser, particularly for the treatment of rosacea, etc.), peeling, etc.

[0122] EXAMPLES

[0123] Example 1: Evaluation of the anti-red mark effect of a composition comprising phenylene bis-diphenyltriazine

[0124] A composition comprising phenylene bis-diphenyltriazine (composition 1) was evaluated after epidermal alteration obtained with an Erbium-YAG laser.

[0125] The objective of this study is to evaluate a reference composition comprising healing agents and a composition according to the invention comprising phenylene bis-diphenyltriazine on erythema present during healing, after alteration of the skin with an Erbium-YAG laser. This is a monocentric study, compared with a commercial reference product (composition 2) and an untreated area, randomized for the area of ​​application of the products.

[0126] The measurements are taken on 3 areas of the anterior surfaces of the 2 forearms (1 untreated area, 1 area on which composition 1 is applied, 1 area on which composition 2 is applied).

[0127] The study lasts 19 days in total and includes 10 visits excluding the pre-inclusion visit. The 10 visits allow for regular measurements throughout the study. The study includes 18 subjects.

[0128] Composition 1 is presented in Table 1 below: [Table 11

[0129] Composition 2 is detailed below. It is a skin repair balm.

[0130] Composition 2 (INCI Names): Aqua, Hydrogenated Polyisobutene, Dimethicone, Glycerin, Butyrospermum Parkii Butter / Shea Butter, Butylene Glycol, Aluminum Starch Octenyl Succinate, Propanediol, Panthenol, Cetyl PPG / PEG-10 / 1 Dimethicone, Tristearin, Zinc Gluconate, Madecassoside, Manganese Gluconate, Magnesium Sulfate, Disodium EDTA, Copper Gluconate, Acetylated Glycol Stearate, Polyglyceryl-4 Isostearate, Sodium Benzoate, Phenoxyethanol, Chlorhexidine Digluconate, CI 77891 / Titanium Dioxide.

[0131] The epidermis of each subject is altered on D1 with an Erbium-YAG laser in 3 areas of a few square centimeters on the anterior surface of the forearms. One area is not treated, while compositions 1 and 2 are applied respectively to the other 2 areas.

[0132] Compositions 1 and 2 are applied twice a day, at a dose of approximately 2 mg / cm 2 , for 18 days following laser ablation of the epidermis.

[0133] Skin erythema and pigmentation were assessed on the study areas at each visit using standardized photographs of the study areas taken at each visit up to day 19 with a C-Cube camera. Skin erythema and pigmentation were objectively assessed using software for processing standardized photographs of the study areas using a C Cube camera. When subjects were included, photographs were taken before the alteration of the epidermis with the Erbium-YAG laser and then within 10 minutes afterward. At subsequent visits, photographs were taken before the application of the products.

[0134] The results on the color of erythema (measurement of the parameter "a" which accounts for the red color) over time are summarized in Table 2 below.

[0135] [Table 2]

[0136] At the inclusion visit, the laser procedure induced a very significant increase in the parameter "a" measuring the red color of the erythema. This erythema was most marked on day 2 in all groups. A significant reduction in erythema was then observed compared to the values ​​obtained after laser.

[0137] It is important to note that at the end of the study, residual erythema was found in the untreated group (p=0.0044 vs. value before laser), as with the reference composition 2 (p=0.0048). On the other hand, at the end of the study, after application of composition 1 according to the invention comprising phenylene bis-diphenyltriazine, the erythema was statistically no longer visualized (p=0.08).

[0138] Example 2: Clinical study on the efficacy and tolerance of a composition comprising phenylene bis-diphenyltriazine

[0139] The study was conducted on 87 subjects. They applied composition 1 according to the invention twice a day for 3 weeks.

[0140] All subjects had irritated skin following: a specific KTP vascular laser (14% of subjects), cryotherapy (13% of subjects), tattooing (13% of subjects), cuts and grazes (14% of subjects), insect bites (7% of subjects), friction abrasions (11% of subjects), excoriated acne (6% of subjects), glycolic acid peeling (11% of subjects), or intense pulsed light laser (11% of subjects).

[0141] Dermatological checks are carried out on D1 before and after a first application, on D3, D8 and D22.

[0142] The various physical signs (erythema, edema, skin peeling, dry skin, blisters and papules) are assessed during these dermatological checks. Table 3 below summarizes the effect of composition 1 obtained on D3, D8 and D22 compared to D1 before application on the sum of these physical signs (overall score awarded by the dermatologist) [Table 3]

[0143] Furthermore, it should be noted that a significant reduction in erythema and edema is observed after only 2 days of application of composition 1 according to the invention.

[0144] The effectiveness of composition 1 according to the invention on the redness of irritated skin is also evaluated by spectrophotometer measurements. The latter converts the colors perceived by the human eye into a digital code using a camera. It is the parameter "a" which accounts for the red color. The results of this parameter "a" are summarized in Table 4 below.

[0145] [Table 4]

[0146] A significant improvement in red marks is highlighted after only 2 days of application.

[0147] After 21 days of application, the reduction in red marks reached 34% and confirmed the benefit of the composition according to the invention in improving scar marks.

[0148] Subjects also evaluated composition 1 according to different efficacy criteria after 21 days of application:

[0149] Improves the appearance of red marks: 95%

[0150] Helps reduce red marks: 93%

[0151] Helps with skin repair after dermatological or aesthetic procedures or after tattooing: 97%

[0152] Improves skin repair: 98% Example 3: Evaluation of different compositions on the anti-redness effect

[0153] The inflammatory phase (redness, swelling, heat, pain) is essential in the healing process.

[0154] The objective of this study is therefore to induce skin inflammation and to highlight the anti-redness effect of phenylene bis-diphenyltriazine.

[0155] The model used is a pig ear skin model including inflammatory stress (induced by a mixture of an inflammatory mediator selected from TNF-activating agents, an innate immunity mediator selected from TRP receptor activating agents (TRPV1, TRPA1) and a bacterial component which is the LL-37 peptide). The production of cytokines (e.g. IL-8) is then quantified by ELISA (Enzyme-Linked Immunosorbent Assay).

[0156] The following products are tested in this study: a healing agent, a healing agent in combination with phenylene bis-diphenyltriazine,

[0157] Bibliographic references

[0158] WO2012 / 085182

[0159] WO2018 / 185324

[0160] (original in electronic form)

[0161] (This sheet is not part of the international application nor does it count as a sheet thereof)

[0162] RESERVED FOR THE RECEIVING OFFICE

[0163] FOR INTERNATIONAL OFFICE USE ONLY

Claims

CLAIMS 1. Composition comprising 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine and at least one cosmetically or pharmaceutically acceptable excipient for use in improving the appearance of skin scars or scar marks and / or in reducing scar marks.

2. Composition for use according to claim 1, for reducing the redness of skin scars or scar marks.

3. Composition for use according to any one of claims 1 to 2, characterized in that the skin is damaged or irritated skin, in particular exposed to UV rays.

4. Composition for use according to claim 3, characterized in that the injured or irritated skin is skin with abrasions; scratches; cuts; grazes; bites, for example, from insects; grazes; burns; abrasions, for example, from friction; sutures; excoriated acne lesions; post-traumatic lesions; post-surgical lesions; lesions subsequent to a dermatology, aesthetic or aesthetic medicine procedure, for example following cryotherapy, mesotherapy, waxing, treatment with intense pulsed light or laser, or peeling; a tattoo; or a combination thereof.

5. Composition for use according to any one of claims 1 to 4, characterized in that the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine represents between 1% and 5% by weight relative to the total weight of the composition.

6. Composition for use according to any one of claims 1 to 5, characterized in that it further comprises at least one healing agent.

7. Composition for its use according to claim 6, characterized in that the healing agent represents 0.1% to 10% by weight relative to the total weight of the composition.

8. Composition for use according to any one of claims 1 to 7, characterized in that it comprises a photoprotective system consisting of: (a) 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine, (b) 2,4-bis[4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-(4-methoxyphenyl)-l,3,5-triazine, (c) hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate, and (d) a sunscreen (d) chosen from ethylhexyl triazone and diethylhexyl butamido triazone, the photoprotective system representing between 4% and 25% by weight relative to the weight total of the composition, said composition not comprising any sunscreen other than those constituting said photoprotective system.

9. Composition for use according to claim 8, characterized in that 2,4-bis[4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-(4-methoxyphenyl)-1,3,5-triazine represents between 1% and 4% by weight relative to the total weight of the composition, hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate represents between 1% and 10% by weight relative to the total weight of the composition, and the sunscreen (d) represents between 1% and 6% by weight relative to the total weight of the composition.

10. Composition for use according to claim 8 or 9, characterized in that the sunscreen (d) is ethylhexyl triazone.

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