PARTICLES CONTAINING RETINOL

Abstract

The present invention relates to the non-therapeutic cosmetic and dermatological field, and more particularly concerns new particles comprising retinol, cetyl palmitate, glyceryl stearate, ceteareth-12, cetearyl alcohol, ceteareth-20, tocopherol and pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, as well as their uses in topical application, particularly cosmetic or dermatological, and their manufacturing processes.

Description

Title of the invention: PARTICLES COMPRISING RETINOL technical field

[0001] The present invention relates to the non-therapeutic cosmetic and dermatological field, and more particularly concerns new particles comprising retinol, cetyl palmitate, tocopherol and pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, as well as their uses in topical application, in particular cosmetic or dermatological and their manufacturing processes. Previous technique

[0002] Retinol is a well-known molecule in the field of cosmetics for stimulating collagen production, increasing the rate of skin cell renewal, thickening the epidermis and unifying the complexion by fading brown spots (Quan, T. Human Skin Aging and the Anti-Aging Properties of Retinol. Biomolecules 2023, 13, 1614).

[0003] Unfortunately, retinol is a fragile, extremely labile molecule that degrades rapidly if certain conditions are not met. In particular, light and oxygen have detrimental effects on the structure of retinol, rapidly transforming it into retinal and a mixture of different epoxides (5,6-epoxyretinol, 5,8-epoxyretinol and 13,14-epoxyretinol) (Crank and Pardijento, Journal of Photochemistry and Photobiology 85 (1995) 93-100).

[0004] Formulators then use different strategies to protect retinol in formulation, whether by adding antioxidants or using airless packaging that limits contact with oxygen in particular.

[0005] Unfortunately, despite these strategies, retinol remains highly unstable once formulated and one study showed that out of 12 commercially available cosmetic formulations containing retinol or one of its derivatives, more than 40% of the products showed a significant decrease in the content of retinol or derivatives after 6 months at 40°C (Rakusa et al, Cosmet Dermatol. 2020;00:1-9.).

[0006] Encapsulation has been one of the solutions found by the cosmetics industry, allowing retinol to be trapped within particles, thus enabling retinol to retain its properties. Patent application WO 2023 / 169963 describes a lipid capsule with an oily core comprising retinol, tocopherol, and soybean oil, the core surrounded by a wax layer comprising cetyl palmitate, lecithin, and sorbitan stearate, the capsule having a hydrophilic surface composed of lauryl glucoside.

[0007] The preservation of retinol over time, in order to maintain its stability, is therefore a major challenge in the cosmetics field. There is a constant need for new formulations that achieve this preservation. Description of the invention

[0008] The Applicant has discovered that particles comprising retinol, cetyl palmitate, glyceryl stearate, ceteareth-20, ceteareth-12, cetearyl alcohol, tocopherol, and pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate are more stable than solutions found in the prior art, thus better protecting the retinol so that it retains its activity over time and / or under heat. The particles according to the invention also allow for better transcutaneous penetration of the retinol.

[0009] The Applicant has also discovered that said particles are particularly interesting for their uses in cosmetics and / or dermatology to prevent and / or reduce aging and / or maintain and / or improve the barrier effect and / or biomechanical properties of healthy skin and / or healthy mucous membranes, in particular to maintain and / or increase the firmness and / or elasticity and / or density of healthy skin and / or healthy mucous membranes.

[0010] A first object relates to particles comprising retinol, cetyl palmitate, glyceryl stearate, ceteareth-20, ceteareth-12, cetearyl alcohol, tocopherol and pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate.

[0011] Advantageously, said particles comprise between 1% and 25% by weight of retinol, preferably between 5% and 20% by weight of retinol, more preferably between 10% and 14% by weight of retinol, relative to the total weight of particles.

[0012] Advantageously, the particles according to the invention comprise between 5% and 60% by weight of cetyl palmitate, preferably between 15% and 50% by weight of cetyl palmitate, more preferably between 25% and 45% by weight of cetyl palmitate, advantageously between 30% and 40% by weight of cetyl palmitate, relative to the total weight of the particles.

[0013] Advantageously, the particles according to the invention comprise between 0.001% and 8% by weight of tocopherol, preferably between 0.01% and 4% by weight of tocopherol, more preferably between 0.1% and 2% by weight of tocopherol, relative to the total weight of the particles.

[0014] Advantageously, the particles according to the invention have an average size between 100 and 900 nm, preferably between 150 and 750 nm, more preferably between 300 nm and 500 nm.

[0015] Advantageously, the particles according to the invention are obtained by phase inversion temperature technology.

[0016] A second object of the invention relates to an aqueous suspension comprising the particles according to the invention in an aqueous solution, advantageously the aqueous solution comprises water and glycerin.

[0017] A third object of the invention relates to a cosmetic composition intended for topical application, comprising particles according to the invention or an aqueous suspension according to the invention, preferably with a content of between 1x10⁴% and 15% (w / w), preferably between 1x10⁻²% and 10% (w / w), advantageously between 0.01% and 6% (w / w), more preferably between 0.1% and 4% (w / w), and even more preferably between 1% and 3% (w / w), relative to the total weight of the composition, and at least one cosmetically acceptable excipient.

[0018] A fourth object of the invention relates to the cosmetic use of the particles according to the invention or of an aqueous suspension according to the invention or of a cosmetic composition according to the invention, to prevent and / or reduce aging, and / or maintain and / or increase the biomechanical properties, and / or maintain and / or increase the barrier effect, of healthy skin and / or healthy mucous membranes.

[0019] Advantageously, the cosmetic use according to the invention makes it possible to maintain and / or increase the firmness, and / or elasticity, and / or thickness, and / or density, of healthy skin and / or healthy mucous membranes.

[0020] Advantageously, the cosmetic use according to the invention is characterized in that the particles are intended to be applied to all or part of the body and / or face and / or scalp, preferably the legs, thighs, arms, stomach, décolleté, neck, armpits, lips, more preferably all or part of the face, and preferably the cheeks, forehead, chin, lips, eye contour, in particular at the level of the cheeks and / or the angular area of ​​the face, more preferably on an area of ​​skin exhibiting a loss of biomechanical properties, in particular a sagging and / or a sagging area of ​​skin and / or an area of ​​skin lacking tone.

[0021] A fifth object of the invention relates to a dermatological composition intended for topical application, comprising particles according to the invention or an aqueous suspension according to the invention, and at least one dermatologically acceptable excipient.

[0022] Advantageously, the dermatological composition according to the invention is characterized in that said particles or aqueous suspension are present in the dermatological composition at a concentration between 1 x 0.4% and 15% by weight, preferably between 1 x 10.2% and 10% by weight, advantageously between 0.01% at 6% by weight, more preferably between 0.1% and 4% by weight, and even more preferably between 1% and 3% by weight, relative to the total weight of the dermatological composition.

[0023] The present invention also relates to the particles according to the invention or the aqueous suspension according to the invention or the dermatological composition comprising them according to the invention for preventing and / or treating pathological skin and / or pathological mucous membranes linked to a loss of elasticity, and / or firmness, and / or density, due to pathologies such as candidiasis, impetigo, eczema, acne, telangiectasias, dermatoporosis, Ehlers-Danlos syndrome, osteogenesis imperfecta, solar elastosis, senile xerosis, diabetes, tetraplegia, Peeling Skin Syndrome, psoriasis, atopic dermatitis and / or cutis laxa pathology.

[0024] A sixth object of the invention relates to a method for producing the particles according to the invention or the aqueous suspension according to the invention, characterized in that the particles are obtained by phase inversion temperature technology.

[0025] Advantageously, the production process according to the invention is characterized in that it comprises the following steps: a) Cetyl palmitate, glycerol stearate, ceteareth-20, ceteareth-12, cetearyl alcohol, sodium stearoyl glutamate and pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate are mixed and heated at a temperature between 60°C and 100°C, protected from light, forming phase A; b) A phase B is prepared by mixing retinol and tocopherol at room temperature; c) Phases A and B are mixed at a temperature between 60°C and 100°C, to obtain a homogeneous product; d) A phase C comprising water and glycerin is heated to a temperature between 60°C and 100°C; e) Phase C is mixed with the product obtained at the end of step c), to obtain an emulsion; f) The emulsion obtained at the end of step e) is cooled to a temperature between 35°C and 55°C; (g) A phase D comprising sodium stearoyl glutamate is added to the cooled emulsion obtained at the end of step (f), the whole is mixed at a temperature between 35°C and 55°C, to obtain a homogeneous solution comprising said particles corresponding to the aqueous suspension.

[0026] Advantageously, the production process according to the invention is characterized in that the solution obtained at the end of step g) has a pH between 7 and 11, preferably between 7 and 10.

[0027] A seventh object of the invention relates to a cosmetic care method for healthy skin and / or healthy mucous membranes characterized in that it comprises the topical application on at least one area of ​​healthy skin and / or healthy mucous membrane, of the particles according to the invention, of the aqueous suspension according to the invention, or of a cosmetic composition according to the invention.

[0028] Advantageously, the cosmetic care process according to the invention makes it possible to prevent and / or reduce aging, and / or maintain and / or increase the biomechanical properties, and / or maintain and / or increase the barrier effect, of healthy skin and / or healthy mucous membranes.

[0029] Advantageously, the cosmetic care process according to the invention makes it possible to maintain and / or increase the firmness, and / or density, and / or thickness, and / or elasticity of healthy skin and / or healthy mucous membranes.

[0030] Advantageously, the cosmetic care process according to the invention is characterized in that the application is carried out on all or part of the body and / or face and / or scalp, preferably the legs, feet, armpits, hands, neck, décolleté, stomach, arms, thighs, hips, buttocks, waist, again preferably all or part of the face, and preferably the cheeks, forehead, chin, lips, eye contour.

[0031] Advantageously, the cosmetic care process according to the invention comprises the following steps:

[0032] - The identification on the individual of an area of ​​healthy skin and / or healthy mucous membrane, for which we wish to prevent and / or reduce aging, and / or maintain and / or increase biomechanical properties, and / or maintain and / or increase the barrier effect,

[0033] - The topical application to this area of ​​healthy skin and / or healthy mucous membrane, of a effective quantity of particles according to the invention, or of the aqueous suspension according to the invention, or of the composition according to the invention, in the form of an active ingredient or a cosmetic composition comprising them. Detailed description

[0034] A first object thus relates to particles comprising retinol, cetyl palmitate, glyceryl stearate, ceteareth-20, ceteareth-12, cetearyl alcohol, tocopherol and pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate.

[0035] The term "retinol" means retinol, its lipophilic derivatives, retinal, retinoic acid and / or mixtures thereof. Preferably, the term "retinol" refers to retinol.

[0036] The term “cetyl palmitate” means the ester derived from palmitic acid and cetyl alcohol, notably marketed under the brand name Cutina® CP by BASF.

[0037] Ceteareth-12 means polyoxyethylene cetostearyl ether comprising 12 moles of ethylene oxide. The global CAS identification number for Ceteareth-12 is 68439-49-6.

[0038] Ceteareth-20 means polyoxyethylene cetostearyl ether comprising 20 moles of ethylene oxide. The global CAS identification number for Ceteareth-20 is 68439-49-6.

[0039] The term “Emulgade® SE-PF” refers to the mixture comprising:

[0040] - between 40 and 70% glycerol stearate,

[0041] - between 10 and 20% ceteareth-20,

[0042] - between 5 and 10% ceteareth-12,

[0043] - between 5 and 10% cetearyl alcohol, and

[0044] - between 5 and 10% cetyl palmitate.

[0045] “Eumulgin® B1” means ceteareth-12.

[0046] “Eumulgin® SG” means sodium stearoyl glutamate, also called Sodium;(4S)-4-amino-5-octadecanoyloxy-5-oxopentanoate (IUP AC name).

[0047] The term “Neutrol® TE” means Tetrahydroxypropyl Ethylenediamine, preferably 2-Propanol, l,l',l",l"'-(l,2-ethanediyldinitrilo)tetrakis-.

[0048] The term "tocopherol" means natural tocopherol (also called vitamin E), synthetic tocopherol, their lipophilic derivatives and / or mixtures thereof, preferably alpha-tocopherol.

[0049] “Tinogard® TT” means pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, also known as PTTH, preferably benzenepropanoic acid, 3,5-bis(l,l-dimethylethyl)-4-hydroxy-, 2,2-bis[[3-[3,5-bis(l,l-dimethylethyl)-4-hydroxyphenyl]-l-oxopropoxy]methyl]-l,3-propanediyl ester.

[0050] In the context of the invention, the term "particle" means a spherical vesicle with a solid core, i.e., solid at a temperature between 0 and 50°C, preferably between 10 and 40°C, more preferably at room temperature. Preferably, the solid core is surrounded by a semi-solid lamellar layer at a temperature between 0 and 50°C, preferably between 20 and 50°C, more preferably at room temperature.

[0051] In one embodiment, the lamellar layer comprises at least one surfactant, such as glycerol stearate, sodium stearoyl glutamate, ceteareth-20 and ceteareth-12 and / or mixtures thereof, preferably the lamellar layer comprises glycerol stearate, ceteareth-20 and ceteareth-12, more preferably the lamellar layer comprises glycerol stearate, sodium stearoyl glutamate, ceteareth-20 and ceteareth-12.

[0052] According to one embodiment, the solid core of the particles according to the invention comprises a single lipid compound, preferably said lipid compound having a melting temperature between 35 and 65°C, preferably between 40 and 60°C, more preferably between 45 and 55°C. Advantageously, the lipid compound is cetyl palmitate.

[0053] By "stable" particles, we mean particles capable of maintaining the retinol content they contain at least 70%, preferably at least 75%, more preferably at least 80%, relative to the initial retinol content in said particles, when stored for 6 months at a storage temperature of 40°C. Advantageously, the "stable" particles are capable of maintaining the retinol content they contain at least 80%, advantageously at least 85%, more advantageously at least 88%, relative to the initial retinol content in said particles, when stored for 6 months at a storage temperature of 25°C.More advantageously, the "stable" particles are capable of maintaining the retinol content they contain, at least 85%, advantageously at least 90%, more advantageously at least 95% compared to the initial retinol content in said particles, when stored for 6 months, at a storage temperature of 4°C.

[0054] According to the invention, the particles preferably comprise between 1% and 25% by weight of retinol, preferably between 5% and 20% by weight of retinol, more preferably between 10% and 14% by weight of retinol, relative to the total weight of the particles.

[0055] According to the invention, the particles comprise between 5% and 60% by weight of cetyl palmitate, preferably between 15% and 50% by weight of cetyl palmitate, more preferably between 25% and 45% by weight of cetyl palmitate, advantageously between 30% and 40% by weight of cetyl palmitate, relative to the total weight of the particles.

[0056] According to one embodiment, the particles according to the invention do not comprise ceramides, and / or lecithin, and / or sphingolipids, or mixtures thereof.

[0057] According to another embodiment, the particles according to the invention do not comprise butylated hydroxytoluene, 2,6-di-tert-butyl-4-methylphenol (BHT) and / or butylated hydroxyanisole (BHA), or mixtures thereof.

[0058] According to another embodiment, retinol, glyceryl stearate, ceteareth-20, ceteareth-12, cetearyl alcohol, pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, tocopherol and cetyl palmitate are miscible with each other during the manufacturing process of the particles according to the invention described below.

[0059] According to the invention, the particles comprise between 10% and 75% by weight of emulsifiers, preferably between 25% and 45% by weight of emulsifiers, plus preferably between 30% and 40% by weight of emulsifiers, relative to the total weight of particles.

[0060] According to the invention, the particles advantageously comprise between 1% and 24% by weight, preferably between 2% and 18% by weight, more preferably between 5% and 14% by weight of glycerol stearate, relative to the total weight of the particles.

[0061] According to the invention, the particles advantageously comprise between 0.01% and 15% by weight, preferably between 0.1% and 10% by weight, more preferably between 0.1% and 5% by weight of ceteareth-20 relative to the total weight of the particles.

[0062] According to the invention, the particles advantageously comprise between 0.001% and 6% by weight, preferably between 0.05% and 4% by weight, more preferably between 0.1% and 3% by weight of cetearyl alcohol relative to the total weight of the particles.

[0063] According to the invention, the particles advantageously comprise between 1% and 30% by weight of ceteareth-12, preferably between 10% and 25% by weight of ceteareth-12, more preferably between 15% and 20% by weight of ceteareth-12, relative to the total weight of the particles.

[0064] In a particular embodiment, the particles comprise:

[0065] - between 1% and 24% by weight, preferably between 2% and 18% by weight, plus preferably between 5% and 14% by weight of glycerol stearate relative to the total weight of particles;

[0066] - between 0.01% and 15% by weight, preferably between 0.1% and 10% by weight, more preferably between 0.1% and 5% by weight of ceteareth-20 relative to the total weight of particles;

[0067] - between 0.001% and 6% by weight, preferably between 0.05% and 4% by weight, more preferably between 0.1% and 3% by weight of cetearyl alcohol relative to the total weight of the particles;

[0068] - between 1% and 30% by weight of ceteareth-12, preferably between 10% and 25% % by weight of ceteareth-12, more preferably between 15% and 20% by weight of ceteareth-12, relative to the total weight of the particles.

[0069] According to the invention, the particles comprise between 0.01% and 10% by weight of antioxidants, preferably between 0.1% and 6% by weight of antioxidants, more preferably between 0.1% and 4% by weight of antioxidants, relative to the total weight of the particles.

[0070] In one embodiment, the particles comprise between 0.001% and 8% by weight of tocopherol, preferably between 0.01% and 4% by weight of tocopherol, more preferably between 0.1% and 2% by weight of tocopherol, relative to the total weight of the particles.

[0071] The particles comprise between 0.005% and 10% by weight of pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, preferably between 0.01% and 6% by weight of pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, more preferably between 0.1% and 3% by weight of pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, relative to the total weight of the particles.

[0072] According to the invention, the particles have an average size between 100 and 900 nm, preferably between 150 and 750 nm, more preferably between 300 nm and 500 nm.

[0073] Preferably, 90% of the particles have an average size greater than 150 nm, preferably greater than 300 nm.

[0074] Advantageously, 90% of the particles have an average size of less than 750 nm, preferably less than 500 nm.

[0075] Preferably, the measurement of the average particle size is carried out by the dynamic light scattering method as described in Example 2 of the present invention.

[0076] "Ambient temperature" is understood to mean a temperature between 18 and 30°C.

[0077] Preferably, the particles according to the invention are contained in an aqueous solution. In this context, the present invention further relates to an aqueous suspension comprising the particles according to the invention in an aqueous solution.

[0078] In one embodiment, the aqueous solution comprises water and glycerin. Thus, the aqueous suspension according to the invention preferably comprises the particles according to the invention and an aqueous solution comprising water and glycerin.

[0079] According to one embodiment, other compounds well known to those skilled in the art may be added to the aqueous solution, such as, for example, emulsifiers, humectants, neutralizing agents, bacteriostatic agents, antioxidants, preservatives, and / or mixtures thereof.

[0080] According to one embodiment, the aqueous suspension comprises between 5% and 25% by weight, preferably between 8% and 20% by weight, preferably between 10% and 20% by weight, more preferably between 10% and 15% by weight of glycerin, relative to the total weight of the aqueous suspension according to the invention.

[0081] According to one embodiment, the aqueous suspension comprises between 1x103% and 4% by weight of sodium stearoyl glutamate, preferably between 0.01% and 2% by weight of sodium stearoyl glutamate, more preferably between 0.1% and 1% by weight of sodium stearoyl glutamate, relative to the total weight of the aqueous suspension according to the invention.

[0082] According to one embodiment, the aqueous suspension comprises between 1 x 103% and 2% by weight, preferably between 0.01% and 1.5% by weight, more preferably between 0.1% and 1% by weight of tetrahydroxypropyl ethylenediamine, relative to the total weight of the aqueous suspension according to the invention.

[0083] According to one embodiment, the aqueous suspension comprises between 0.01% and 6% by weight, preferably between 0.1% and 3% by weight, more preferably between 0.5% and 2.5% by weight of pentylene glycol, relative to the total weight of the aqueous suspension according to the invention.

[0084] The particles according to the invention or the aqueous suspension according to the present invention can be applied topically.

[0085] For the purposes of the present invention, "topical route" means the direct local application and / or vaporization of the particles or the composition comprising them according to the invention on the surface of the area of ​​skin and / or mucous membrane to be treated.

[0086] The particles or aqueous suspension according to the invention can be applied topically to all or part of the skin surface, or to all or part of the mucous membranes, with or without skin appendages.

[0087] The term “skin” means any part of the body and / or face, including the scalp.

[0088] The term “mucous membrane” means the ocular and / or nasal and / or auricular and / or urogenital and / or vaginal and / or oral and / or labial and / or gingival and / or anal mucous membrane.

[0089] The particles according to the present invention can be used for cosmetic purposes in particular, to prevent and / or reduce aging, and / or maintain and / or increase biomechanical properties, and / or maintain and / or increase the barrier effect of healthy skin and / or healthy mucous membranes.

[0090] “Cosmetic use” means a non-therapeutic, non-pharmaceutical or non-dermatological use, that is to say, one which does not require and does not involve therapeutic treatment and is intended to be applied to a part of the body which is said to be healthy, in particular to an area of ​​the skin and / or mucous membrane which is said to be healthy.

[0091] The terms "healthy skin", "healthy mucous membranes" or "healthy tissue" mean an area of ​​skin or mucous membrane on which the particles according to the present invention or the composition according to the invention are applied and which is said to be "non-pathological" by a dermatologist, that is to say, not showing any infection, scar, disease or skin condition such as candidiasis, impetigo, psoriasis, eczema, acne, telangiectasias, dermatitis in particular seborrheic, solar elastosis and / or cutis laxa pathology, not showing any wounds or injuries or dandruff and / or other dermatoses and / or alopecia and / or baldness and / or alopecia areata.

[0092] Advantageously, the particles and optionally the cosmetic composition comprising said particles according to the invention are used topically for the treatment of thin and / or thin healthy skin and / or sensitive healthy skin and / or sensitized and / or reactive healthy skin and / or damaged healthy skin and / or healthy skin.

[0093] The term "thin and / or thin skin" refers to skin that is fragile or has become fragile due to age, such as infant skin or mature skin (i.e., the skin of people over 40), or due to the nature of the skin, for example, the skin of the décolleté, armpits, elbow and / or knee creases, or due to the area, particularly skin on body areas exposed to friction and / or aggression, especially mechanical, for example, the skin of the face and / or hands. Thin and / or thin skin includes skin prone to atopic dermatitis. Thin and / or thin skin is not intended for the prevention and / or treatment of any pathology.

[0094] The term “sensitive and / or sensitized skin” means skin which, by nature or temporarily, tolerates very little external aggressive agents, in particular environmental agents such as pollutants, chemical agents (heavy metals, detergents, compounds contained in cosmetic treatments such as perfumes, preservatives, alcohols, pH, AHAs or in dermatological treatments such as vitamin A, acids), allergens, tobacco, climatic factors (wind, cold, heat), UV, hard water and / or non-pathological physiological variations including stress, changes in diet, hormones (during puberty, pregnancy, menopause and / or andropause), perspiration and / or repeated mechanical aggressions such as hair removal, shaving, washing, friction (repeated hand washing).Sensitive and / or sensitized skin is not pathological, unlike allergic skin. However, it can react to aggressive agents and / or conditions, becoming thinner, particularly in the epidermis. Therefore, the "sensitive skin" characteristic can be assessed by the individual themselves through subjective skin sensations or by a dermatologist through objective skin reactions. Sensitive and / or sensitized skin does not constitute the prevention or treatment of a pathology.

[0095] The particles or aqueous suspension according to the present invention can be included in a cosmetic and / or dermatological composition comprising at least one acceptable cosmetic and / or dermatological excipient, intended for topical application.

[0096] The particles or aqueous suspension according to the present invention can be obtained by any method classically known to those skilled in the art, such as high-pressure homogenization ("Synthesis of lipid nanocarrier loaded with retinol via vacuum emulsification to improve topical delivery", Seung-Hyun Jun et al., Polymers 2021, 13, 826.), phase inversion temperature technology (PIT - Phase Inversion Temperature).

[0097] Preferably, the particles or aqueous suspension according to the invention can be obtained using phase inversion temperature (PIT) technology. This method is simple for the user to implement and less expensive than other methods available on the market.

[0098] In a preferred embodiment, the particles or aqueous suspension according to the invention are obtained by phase inversion temperature technology.

[0099] According to one embodiment, the particles represent between 20 and 60% by weight, preferably between 30% and 50% by weight and more preferably between 35% and 45% by weight, of the total weight of the aqueous suspension according to the invention, i.e. of the aqueous solution comprising said particles.

[0100] According to a particular embodiment, the aqueous suspension according to the invention comprises: - between 20 and 60%, preferably between 30% and 50% and more preferably between 35% and 45%, of particles according to the invention; - between 5% and 25%, preferably between 8% and 20%, preferably between 10% and 20%, more preferably between 10% and 15%, of glycerin; and - water in sufficient quantity to reach 100%, expressed by weight relative to the total weight of the aqueous suspension according to the invention.

[0101] The present invention also relates to the topical cosmetic use of said particles or of said aqueous suspension, as a cosmetic active ingredient or of a cosmetic composition comprising them, for the cosmetic care of healthy skin and / or healthy mucous membranes, in particular to prevent and / or reduce aging, and / or maintain and / or increase the biomechanical properties, and / or maintain and / or increase the barrier effect, of healthy skin and / or healthy mucous membranes.

[0102] The term "cosmetic active ingredient" means a component which has cosmetic properties on the skin and / or mucous membranes, in particular by topical application, more particularly for the care of the skin and / or mucous membranes, advantageously which has cosmetic properties which in particular allow to prevent and / or reduce aging, and / or maintain and / or increase the biomechanical properties, and / or maintain and / or increase the barrier effect, of the skin and / or mucous membranes.

[0103] “Preventing and / or reducing the aging of the skin and mucous membranes” means preventing and / or reducing the appearance of signs of aging, in particular the increase in free radicals and toxins, and the decrease in firmness, elasticity, and / or density. Aging of the skin and / or mucous membranes includes chrono-induced aging and aging induced by extrinsic factors. in particular photo-induced aging. Prevention and / or reduction of skin and / or mucous membrane aging can result in maintaining and / or increasing free radical scavenging activity, cellular oxygenation, firmness, density and / or elasticity.

[0104] Extrinsic factors can be aggressive agents in the environment such as pollution, UV radiation, fumes, tobacco, toxins, or climatic and / or mechanical aggressions.

[0105] For the purposes of this invention, "maintaining biomechanical properties" means preventing and / or avoiding the degradation of the biomechanical properties of the skin and / or mucous membranes, in particular when exposed to environmental, chemical, biological and / or mechanical aggressions, in particular by preventing the skin and / or mucous membranes from becoming damaged and / or by preventing the skin and / or mucous membranes from becoming further damaged.

[0106] For the purposes of this invention, "increasing biomechanical properties" means improving the biomechanical properties of the skin and / or mucous membranes, in particular damaged skin and / or mucous membranes due to exposure to environmental, chemical, biological and / or mechanical aggressions, but also undamaged skin and / or undamaged mucous membranes.

[0107] For the purposes of this invention, "biomechanical properties" means the firmness and / or density and / or elasticity and / or resistance to compression and / or resistance to stretching and / or flexibility and / or extensibility and / or resistance to deformation of the skin and / or mucous membranes. Preferably, this refers to the firmness and / or elasticity and / or density of the skin and / or mucous membranes, in particular the dermis.

[0108] More preferably, firmness and / or density and / or elasticity are defined as the properties limiting and / or reducing sagging, drooping and / or lack of tone in healthy skin and / or healthy mucous membranes, particularly in the cheeks and / or angular area of ​​the face (commonly referred to as the rounded face or V of the face).

[0109] For the purposes of the present invention, "maintaining and / or increasing firmness" means preventing the decrease and / or increasing, for aesthetic purposes, the firmness of skin and / or mucous membranes, in particular those which have lost firmness, particularly under the effect of intrinsic and / or extrinsic factors.

[0110] Intrinsic factors may include the aging of the skin and / or mucous membranes, i.e., chrono-induced aging, which is found, for example, in so-called mature skin, i.e., the skin of people over 40 years of age. These factors may include cellular stress, non-pathological physiological variations such as than a change in diet, hormonal variations, particularly during puberty, pregnancy, perimenopause, menopause and / or andropause.

[0111] Preferably, this involves maintaining and / or increasing the firmness and / or elasticity and / or radiance of the complexion and / or reducing fine lines at the tissue level, compared to the firmness and / or elasticity and / or radiance of the complexion and / or fine lines of a tissue measured in the absence of the particles.

[0112] In an advantageous embodiment of the invention, this refers to an increase measured in vivo, preferably on human facial skin.

[0113] For the purposes of the present invention, from a cosmetic point of view, "maintaining and / or increasing elasticity" means preventing the decrease and / or causing the increase, for aesthetic purposes, of the elasticity of skin and / or mucous membranes which have lost elasticity, in particular under the effect of intrinsic factors, such as the aging of the skin and / or mucous membranes, i.e. chrono-induced aging, which is found for example in so-called mature skin, i.e. the skin of people over 40 years of age, cellular stress, non-pathological physiological variations such as a change in diet, hormonal variations, in particular during puberty, pregnancy, premenopause, menopause and / or andropause.This decrease in elasticity can also occur under the effect of extrinsic factors, such as aggressive environmental agents, such as pollution, fumes, UV radiation, tobacco, toxins, or climatic and / or mechanical stresses.

[0114] Preferably, this refers to an increase in elasticity of the skin and / or mucous membranes, measured in vivo, in the presence of the particles according to the invention, compared to the elasticity of the skin and / or mucous membranes measured in the absence of said particles. In a preferred embodiment of the invention, this refers to an increase measured in vivo, advantageously on human facial skin.

[0115] According to a preferred mode, the particles according to the present invention make it possible to maintain and / or increase the expression of collagen, in particular of type I and / or type III and / or type XVIII, preferably of type I and / or type III.

[0116] For the purposes of the present invention, the term “type I collagen” means type I collagen proteins present in the skin, cornea, tendons, ligaments, bones, and preferably in the skin.

[0117] For the purposes of the present invention, the term “type III collagen” means type III collagen proteins present in the skin, muscles, organs, cardiovascular system, and preferably in the skin.

[0118] The term “maintaining and / or increasing type I collagen expression” means preventing a decrease and / or increasing the level of gene expression, i.e., the expression of mRNAs (messenger RNAs), and / or protein synthesis of collagens of tissues treated by the particles according to the invention or the aqueous suspension according to the invention or the cosmetic composition according to the invention, compared to gene expression and / or protein synthesis measured in the absence of treatment by the particles according to the invention or the aqueous suspension according to the invention or the cosmetic composition according to the invention.

[0119] In a particular embodiment, the aim is to increase collagen I expression by at least 20%, more preferably by at least 35%, advantageously by at least 40%, on skin treated with the particles or aqueous suspension according to the invention, compared to collagen I expression measured on skin treated with an excipient alone. In an advantageous embodiment, this will involve an increase in collagen I expression measured in vivo, and even more advantageously, this increase in collagen I expression will be measured on biopsies of so-called "healthy" skin, i.e., non-pathological skin.

[0120] According to another embodiment, the aim is to increase collagen III expression by at least 15%, more preferably by at least 25%, advantageously by at least 30%, on skin treated with the particles or aqueous suspension according to the invention, compared to collagen III expression measured on skin treated with an excipient alone. In an advantageous embodiment, this will involve an increase in collagen III expression measured in vivo, and even more advantageously, this increase in collagen III expression will be measured on biopsies of so-called "healthy" skin, i.e., non-pathological skin.

[0121] According to an advantageous embodiment of the invention, this is an increase in the level of protein expression of collagen I and / or collagen III measured on biopsies maintained in survival, treated or untreated with the particles according to the invention or with the aqueous suspension according to the invention or with the cosmetic composition according to the invention.

[0122] Advantageously, the measurement of the increase in protein expression of collagen, preferably of collagen I and III, is carried out by ex vivo measurement, preferably after assay by immunolabeling and / or ELISA, under the conditions described in examples 10 and 11.

[0123] The biomechanical properties of the skin and / or mucous membranes can be studied by measurement techniques known to those skilled in the art, in particular by traction, torsion, suction, indentation, ballistometry, high-resolution ultrasound scanning or elastography, preferably by indentation, by high-resolution ultrasound scanning.

[0124] The term "maintaining and / or increasing the barrier effect" of the skin and / or mucous membranes means preventing the decrease and / or increasing the thickness of tissues, particularly the epidermis and / or mucous membranes, and / or preventing the decrease and / or promoting their cohesion at the level of the stratum corneum and / or mucous membranes and / or limit and / or reduce water loss at the level of the skin and / or mucous membranes.

[0125] Advantageously, "maintaining and / or increasing the barrier effect" means maintaining and / or increasing the thickness of the epidermis, preferably increasing the average thickness of the epidermis by at least 20%, more preferably by at least 35%, advantageously by at least 45%, when treated with the particles or aqueous suspension according to the invention, compared to the average thickness of the epidermis treated with an excipient alone. In an advantageous embodiment, this will involve an increase in the average thickness of the epidermis in vivo, and even more advantageously, this increase will be measured on biopsies of skin described as "healthy," that is, non-pathological.

[0126] The measurement of the increase in epidermal thickness can be carried out by any means well known to those skilled in the art, such as by measuring the average thickness of the epidermis by optical microscopy, under the conditions described in Example 9.

[0127] In an advantageous embodiment of the invention, this will involve an increase in the epidermis measured in vivo on subjects with healthy, i.e., non-pathological skin and / or mucous membranes.According to one embodiment, the particles according to the present invention and / or a composition comprising them according to the invention and / or the aqueous suspension according to the present invention are intended to be applied to all or part of the body and / or face and / or scalp, preferably the legs, thighs, arms, stomach, décolleté, neck, armpits, lips, more preferably all or part of the face, and preferably the cheeks, forehead, chin, lips, eye contour, in particular on the cheeks and / or the angular area of ​​the face (commonly called the rounded face or V-shape of the face), more preferably on an area of ​​skin exhibiting a loss of biomechanical properties, in particular sagging and / or a sagging area of ​​skin and / or an area of ​​skin lacking tone.

[0128] According to the invention, the particles or aqueous suspension according to the present invention can be used alone, as a cosmetic active ingredient and / or can be in the form of a cosmetic composition, intended for topical application, comprising said particles or aqueous suspension and at least one cosmetically acceptable excipient, in particular to prevent and / or reduce skin and / or mucosal aging, and / or maintain and / or increase the biomechanical properties, and / or maintain and / or increase the barrier effect, of healthy skin and / or healthy mucous membranes.

[0129] The present invention therefore also relates to a cosmetic composition intended for topical application, comprising the particles or aqueous suspension according to the invention, and at least one cosmetically acceptable excipient.

[0130] The term "cosmetic composition" means a non-therapeutic composition, that is to say, one which is not intended for therapeutic use and which is applied to a part of the body which is said to be healthy, in particular to an area of ​​the skin and / or mucous membrane which is said to be healthy.

[0131] Advantageously, the cosmetic composition according to the invention comprises the aqueous suspension according to the invention, at a concentration between 1x10 4% and 15% (w / w), preferably between 1x10 2% and 10% (w / w), advantageously between 0.01% and 6% (w / w), more preferably between 0.1% and 4% (w / w), and even more preferably between 1% and 3% (w / w), relative to the total weight of the cosmetic composition, said cosmetic composition further comprising at least one cosmetically acceptable excipient.

[0132] For the purposes of the present invention, a "cosmetically acceptable" excipient means a compound and / or solvent that is topically acceptable, i.e. an ingredient suitable for topical application, non-toxic, non-irritating, not inducing an allergic response, not chemically unstable, for healthy skin and / or healthy mucous membranes, in particular the scalp.

[0133] The cosmetic composition according to the invention can be chosen from a solution, aqueous or oily, an aqueous cream or gel or an oily gel, in particular a shower gel, a shampoo; a milk; an emulsion, a microemulsion or a nanoemulsion, in particular oil-in-water or water-in-oil or multiple or silicone; a mask; a serum; a lotion; a liquid soap; a dermatological bar; an ointment; a balm; a butter; a mousse; a patch.

[0134] It may also be a makeup product or a makeup removal product.

[0135] The compositions according to the invention may contain any suitable solvent and / or any suitable vehicle and / or any suitable excipient, possibly in combination with other compounds of interest.

[0136] Therefore, for these compositions, the excipient contains, for example, at least one compound chosen from the group including preservatives, emollients, emulsifiers, surfactants, moisturizers, thickeners, conditioners, mattifying agents, stabilizers, antioxidants, texturizing agents, gloss enhancers, film-forming agents, solubilizers, pigments, colorants, perfumes and sunscreens.

[0137] These excipients are preferably chosen from the group consisting of amino acids and their derivatives, polyglycerols, esters, polymers and cellulose derivatives, lanolin derivatives, phospholipids, lactoferrins, lactoperoxidases, sucrose-based stabilizers, vitamin E and its derivatives, natural and synthetic waxes, vegetable oils, triglycerides, unsaponifiables, phytosterols, plant esters, silicones and their derivatives, protein hydrolysates, jojoba oil and its derivatives, fat / water-soluble esters, betaines, aminoxides, plant extracts, sucrose esters, titanium dioxide, glycines, and parabens, and preferably from the group consisting of butylene glycol, steareth-2, steareth-21, glycol-15 stearyl ether, cetearyl alcohol, phenoxyethanol, methylparaben, ethylparaben, the propylparaben, butylparaben, butylene glycol, natural tocopherols, glycerin, dihydroxycetyl sodium phosphate, isopropyl hydroxycetyl ether, glycol stearate, triisononanoin,octyl cocoate, polyacrylamide, isoparaffin, laureth-7, a carbomer, propylene glycol, glycerol, bisabolol, a dimethicone, sodium hydroxide, PEG-30 dipolyhydroxysterate, caprylic / capric triglycerides, cetearyl octanoate, dibutyl adipate, grapeseed oil, jojoba oil, magnesium sulfate, EDTA, a cyclomethicone, xanthan gum, citric acid, sodium lauryl sulfate, mineral waxes and oils, isostearyl isostearate, propylene glycol dipelargonate, propylene glycol isostearate, PEG-8, beeswax, hydrogenated palm kernel oil glycerides, palm oil glycerides hydrogenated lanolin oil, sesame oil, cetyl lactate, lanolin alcohol, castor oil, titanium dioxide, lactose, sucrose, low-density polyethylene, isotonic saline solution, and mixtures thereof.

[0138] The cosmetic composition may further include active ingredients to strengthen the skin barrier effect, inducing a complementary or synergistic effect with the particles according to the invention, chosen from those which strengthen the barrier effect and reduce insensible water loss and / or those which increase the water content of the skin and / or mucous membranes and / or stimulate the synthesis of aquaporin to improve water circulation in cells.Examples include serine, urea and its derivatives, products such as marine collagen microspheres and chondroitin sulfate as a glycosaminoglycan, a formulation comprising a hyaluronic acid salt, urea, trehalose, glycerol triacetate and polyquaternium 51 marketed under the names Marine Filling Spheres™ and Advanced Moisturizing Complex™ respectively; hyaluronic acid microspheres marketed under the name Hyaluronic Filling Spheres™; a red algae extract or a mixture of acacia polysaccharide, alginate and serine marketed under the names Osmogelline™ and Micropatch™ Serine respectively; or a combination of pullulan, hyaluronic acid or a . salts or one of its derivatives and alginic acid, one of salts or one of its derivatives, marketed under the name Patch2O™.

[0139] Other compounds that may be used include alkylcelluloses, lecithins, sphingoid-based compounds, ceramides, phospholipids, cholesterol and its derivatives, glycosphingolipids, phytosterols (stigmasterol and beta-sitosterol, campesterol), essential fatty acids, 1,2-diacylglycerol, 4-chromanone, pentacyclic triterpenes such as ursolic acid, petrolatum, lanolin, sugars, in particular trehalose and its derivatives, rhamnose, fructose, maltose, lactose, erythritol, mannitol, D-xylose and glucose, adenosine and its derivatives, sorbitol, polyhydric alcohols, advantageously in C2-C6, and even more advantageously in C3-C6, such as glycerin, propylene glycol, 1,3-butylene glycol, dipropylene glycol, diglycerin, polyglycerin and their mixtures, glycerol and its derivatives, glyceryl polyacrylate, sodium lactate, pentanediol, serine, lactic acids, AHAs,BHA, sodium pidolate, xylitol, sodium lactate, ectoine and its derivatives, chitosan and its derivatives, collagen, plankton, steroid derivatives (including DHEA, its 7-oxidized and / or 17-alkylated derivatives and sapogenins), methyl dihydrojasmonate, vitamin D and its derivatives, Malva sylvestre extract or Centella asiatica extract, acrylic acid homopolymers, beta-glucan and in particular sodium carboxymethyl beta-glucan, a C-glycoside derivative such as those described in application WO2002051828, rosehip oil, a zinc-enriched Prophyridium cruentum microalgae extract marketed by Vincience under the name Algualane Zinc™, arginine, acetyl hexapeptide marketed by Lipotech under the name Diffuporine™, the Viola tricolor hydrolysate marketed by Silab under the name Aquaphyline™,or a polysaccharide extracted from Cassia angustifolia seeds marketed under the name Hyalurosmooth™ by the applicant, a fermented hydrolysate of Saccharomyces cerevisiae marketed under the name Relipidium™, or one or more of the compounds of the Natural Moisturizing Factor or a natural honey extract marketed by the applicant under the name Melhydran™.

[0140] The cosmetic composition may also include other cosmetic and / or dermatological agents having the same properties and inducing a synergistic or non-synergistic effect with the particles according to the invention, or cosmetic agents with complementary effects.

[0141] These may include, for example, moisturizing, anti-free radical, anti-aging, soothing, anti-inflammatory, whitening, mattifying ingredients and / or thermal waters.

[0142] Preferably, the composition comprising the particles according to the invention further comprises one or more cosmetic active ingredients having properties identical to the particles according to the invention and inducing an effect synergistic or not with said particles, or contain cosmetic agents with complementary effects.

[0143] These may also include anti-aging active ingredients such as an extract of Nephelium lappaceum leaves marketed under the name Nephoria™ or an extract of Cichorium intybus marketed under the name Lox-Age™ by BASF Beauty Care Solutions and / or an extract of the aerial parts of Cistus monspeliensis marketed under the name Cist'M™ and / or an extract of Hibiscus abelmoschus seeds under the name Linefactor™ by BASF Beauty Care Solutions and / or the peptides Replexium™, Revitofirm™, Dermagenist™ and / or Lys'lastine™ also marketed by BASF Beauty Care Solutions as well as Matrixyl™, Matrixyl 3000T and / or bakuchiol.

[0144] These may be tightening agents and / or moisturizing active ingredients such as an extract of Nephelium lappaceum bark marketed under the name Nephydrat™ by BASF Beauty Care Solutions and / or active agents increasing the barrier effect of the epidermis such as, for example, an extract of hydrolyzed linseed marketed under the name Oligolin™ by BASF Beauty Care Solutions.

[0145] The tensor agents usable in the invention can be chosen from synthetic polymers, such as polyurethane latex or acrylic latex, polymers of natural origin, in particular polyholosides in the form of starch or in the form of carrageenans, alginates, agars, gellans, cellulosic polymers and pectins; plant proteins and protein hydrolysates; mixed silicates; wax microparticles; colloidal particles of inorganic filler chosen for example from silica, silica-alumina composites; as well as mixtures thereof.

[0146] Finally, these may be cosmetic ingredients such as antimicrobial agents, free radical scavengers, soothing, calming or relaxing agents, agents acting on microcirculation to improve skin radiance, particularly on the face, healing agents or slimming agents. Advantageously, the cosmetic and / or dermatological composition of the present invention also contains one or more tightening agents and / or one or more antimicrobial agents and / or one or more free radical scavengers and / or one or more soothing agents and / or one or more slimming agents and / or one or more agents active on microcirculation.

[0147] Among the antimicrobial agents associated with the particles according to the invention in a preferred embodiment of the present invention, mention may be made of 2,4,4'-trichloro-2'-hydroxy diphenyl ether (or triclosan), 3,4,4'-trichlorobanilide, phenoxyethanol, phenoxypropanol, phenoxyisopropanol, hexamidine isethionate, metronidazole and its salts, miconazole and its salts, itraconazole, terconazole, econazole, the ketoconazole, saperconazole, fluconazole, clotrimazole, butoconazole, oxiconazole, sulfaconazole, sulconazole, terbinafine, undecylenic acid and its salts, benzoyl peroxide, 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, phytic acid, N-acetyl-L-cysteine, lipoic acid, azelaic acid and its salts, arachidonic acid, resorcinol, octoxyglycerin, octanoylglycine, caprylyl glycol, 10-hydroxy-2-decanoic acid, farnesol, phytosphingosines and mixtures thereof.

[0148] Antiradical agents may be vitamin C and its derivatives including ascorbyl glucoside, phenols and polyphenols, in particular tannins, ellagic acid and tannic acid; epigallocatechin and natural extracts containing it, in particular green tea extracts; anthocyanins; phenolic acids, stilbenes; actives that scavenge mono- or polycyclic aromatic compounds, tannins such as ellagic acid and indole derivatives and / or actives that scavenge heavy metals such as EDTA, antiradical actives such as vitamin E and its derivatives such as tocopheryl acetate; bioflavonoids; coenzyme Q10 or ubiquinone.

[0149] As soothing agents included in the composition of the invention, pentacyclic triterpenes, ursolic acid and its salts, oleanolic acid and its salts, betulinic acid and its salts, salts of salicylic acid and in particular zinc salicylate, bisabolol, allantoin, omega-3 unsaturated oils, cortisone, hydrocortisone, indomethacin and beta methasone, anti-inflammatory agents, and in particular those described in application FR2847267, in particular Pueraria lobata root extract marketed under the name Inhipase™ by the applicant, Theobroma cacao extracts may be used.

[0150] The active ingredients acting on microcirculation, vasoprotectors or vasodilators, can be chosen from flavonoids, ruscogenins, nicotinates, essential oils.

[0151] The present invention further relates to a method for producing the particles according to the present invention or the aqueous suspension according to the present invention, by phase-inversion temperature technology, in particular comprising the following steps:

[0152] a) Cetyl palmitate, glycerol stearate, ceteareth-20, ceteareth-12, cetearyl alcohol and pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate are mixed and heated at a temperature between 60°C and 100°C, protected from light, forming phase A;

[0153] b) A phase B is prepared by mixing retinol and tocopherol at room temperature;

[0154] c) Phases A and B are mixed at a temperature between 60°C and 100°C, to obtain a homogeneous product;

[0155] d) A phase C comprising water and glycerin is heated to a temperature between 60°C and 100°C;

[0156] e) Phase C is mixed with the product obtained at the end of step c), to obtain an emulsion;

[0157] f) The emulsion obtained at the end of step e) is cooled to a temperature between 35°C and 55°C;

[0158] g) A phase D comprising sodium stearoyl glutamate is added to the cooled emulsion obtained at the end of step f), the whole is mixed at a temperature between 35°C and 55°C, to obtain a homogeneous solution comprising the particles according to the invention, i.e. the aqueous suspension according to the invention;

[0159] h) Optionally, said particles are recovered (isolated).

[0160] The solution obtained at the end of step g) has a pH between 7 and 11, preferably between 7 and 10.

[0161] Preferably, step a) is carried out at a temperature between 70°C and 90°C, more preferably between 75°C and 85°C, advantageously at 80°C.

[0162] Preferably, step c) is carried out at a temperature between 70°C and 90°C, more preferably between 75°C and 85°C, advantageously at 80°C.

[0163] Preferably, step d) is carried out at a temperature between 70°C and 90°C, more preferably between 75°C and 85°C, advantageously at 80°C.

[0164] Preferably, the emulsion is cooled in step f) to a temperature between 40°C and 55°C, more preferably between 45°C and 55°C, advantageously at 50°C.

[0165] Preferably, it is introduced at step a), between 5% and 25% by weight, more preferably between 10% and 20% by weight of cetyl palmitate relative to the total weight of the aqueous suspension obtained.

[0166] Preferably, it is introduced at step a), between 0.1% and 10% by weight, more preferably between 1% and 6% by weight of glycerol stearate relative to the total weight of the aqueous suspension obtained.

[0167] Preferably, it is introduced at step a), between 1% and 20% by weight, more preferably between 3% and 10% by weight of ceteareth-12 relative to the total weight of the aqueous suspension obtained.

[0168] Preferably, it is introduced at step a), between 0.01% and 5% by weight, more preferably between 0.1% and 2% by weight of ceteareth-20 relative to the total weight of the aqueous suspension obtained.

[0169] Preferably, it is introduced at step a), between 0.005% and 5% by weight, more preferably between 0.05% and 2% by weight of cetearyl alcohol relative to the total weight of the aqueous suspension obtained.

[0170] Preferably, it is introduced at step a), between 0.01% and 5% by weight, more preferably between 0.1% and 2% by weight of pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate relative to the total weight of the aqueous suspension obtained.

[0171] Preferably, it is introduced in step b), between 1% and 10% by weight, more preferably between 2% and 8% by weight of retinol relative to the total weight of the aqueous suspension obtained.

[0172] Preferably, it is introduced in step b), between 0.005% and 5% by weight, more preferably between 0.05% and 2% by weight of tocopherol relative to the total weight of the aqueous suspension obtained.

[0173] Preferably, it is introduced at step d), between 5% and 25% by weight, preferably between 8% and 20%, more preferably between 10% and 20%, more preferably between 10% and 15%, by weight of glycerin relative to the total weight of the aqueous suspension obtained.

[0174] Preferably, it is introduced at step d), between 30% and 60% by weight, more preferably between 40% and 50% by weight of water relative to the total weight of the aqueous suspension obtained.

[0175] Preferably, it is introduced at step g), between 1x103% and 4% by weight, more preferably between 0.01% and 2% by weight, advantageously between 0.1% and 1% by weight of sodium stearoyl glutamate relative to the total weight of the aqueous suspension obtained.

[0176] According to one embodiment, other compounds well known to those skilled in the art may be added at any stage of the process, preferably at stage a) in phase A, at stage b) in phase B, at stage d) in phase C and / or during stage g) in phase D, such as, for example, emulsifiers, humectants, neutralizing agents, bacteriostatic agents, antioxidants...

[0177] The emulsifier can be chosen from among all those well known to those skilled in the art, such as, for example, glyceryl stearate, ceteareth-20, ceteareth-12, cetearyl alcohol, sodium stearoyl glutamate and mixtures thereof.

[0178] The humectant can be chosen from among all those well known to a person skilled in the art, in particular glycerin.

[0179] The neutralizing agent can be chosen from among all those well known to those skilled in the art, such as pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate.

[0180] The antioxidant can be chosen from among all those well known to those skilled in the art, such as tocopherol, pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate ... and mixtures thereof.

[0181] The bacteriostatic agent can be chosen from among all those well known to those skilled in the art, such as benzyl alcohol, pentylene glycol, and mixtures thereof.

[0182] The present invention also relates to a cosmetic care method for healthy skin and / or healthy mucous membranes characterized in that it comprises the topical application to at least one area of ​​healthy skin and / or healthy mucous membrane of the particles according to the invention or of an aqueous suspension according to the invention, in particular as described above, or of a cosmetic composition comprising them, in particular to prevent and / or reduce aging, and / or maintain and / or increase the biomechanical properties, and / or maintain and / or increase the barrier effect, of healthy skin and / or healthy mucous membranes.

[0183] Advantageously, the particles or aqueous suspension according to the invention, preferably in the form of a cosmetic composition comprising them, is used in regular topical application and preferably at least once a day, advantageously twice a day, for at least 1 month, preferably for at least 2 months, more preferably for at least 3 months.

[0184] The cosmetic care process according to the invention for preventing and / or reducing aging, and / or maintaining and / or increasing and / or biomechanical properties, and / or maintaining and / or increasing the barrier effect of the skin and / or mucous membranes, advantageously comprises the following steps:

[0185] - The identification on the individual of an area of ​​healthy skin and / or healthy mucous membrane, for which we wish to prevent and / or reduce aging and / or maintain and / or increase biomechanical properties and / or maintain and / or increase the barrier effect,

[0186] - Topical application to this area of ​​healthy skin and / or healthy mucous membrane, of an effective quantity of particles according to the invention or the aqueous suspension according to the invention, in the form of an active ingredient or a cosmetic composition comprising said particles or said suspension.

[0187] In another embodiment, the particles according to the invention can be incorporated into a cosmetic composition.

[0188] According to one embodiment, the cosmetic care process according to the invention is characterized in that it comprises the topical application to at least one area of ​​healthy skin and / or healthy mucous membrane of the particles or of a cosmetic composition comprising them, to maintain and / or increase the firmness and / or density and / or thickness and / or elasticity of healthy skin and / or healthy mucous membranes.

[0189] Advantageously, the particles or the composition comprising them according to the invention are intended to be applied to all or part of the body and / or face and / or scalp, preferably the legs, feet, armpits, hands, neck, décolletage, stomach, arms, thighs, hips, buttocks, waist, preferably all or part of the face, and preferably the cheeks, forehead, chin, lips, and eye contour.

[0190] Advantageously, the particles and / or the composition comprising them and / or the aqueous suspension are intended to be applied to an area of ​​healthy tissue exhibiting sagging and / or drooping and / or an area of ​​healthy tissue lacking tone.

[0191] Thus, advantageously the cosmetic composition is intended for topical application on healthy skin and / or healthy mucous membranes.

[0192] Alternatively, the particles according to the invention can be presented in all the galenic forms classically used for topical application.

[0193] According to one embodiment, the cosmetic care process according to the invention is such that the particles are in the form of an aqueous suspension according to the invention integrated into a cosmetic composition, said aqueous suspension is present in the composition at a concentration of 1x10 4% and 15% (w / w), preferably between 1x10 2% and 10% (w / w), advantageously between 0.01% and 6% (w / w), more preferably between 0.1% and 4% (w / w), and even more preferably between 1% and 3% (w / w), relative to the total weight of the composition, said composition further comprising at least one cosmetically acceptable excipient.

[0194] The invention further relates to particles or an aqueous suspension according to the invention or to a dermatological composition comprising them, for its use by topical route for the treatment and / or prevention and / or reduction of the occurrence of pathologies related to pathological skin and / or pathological mucous membranes, such as candidiasis, impetigo, eczema, acne, telangiectasias, dermatoporosis, Ehlers-Danlos syndrome, osteogenesis imperfecta, solar elastosis, senile xerosis, diabetes, tetraplegia, Peeling Skin Syndrome, psoriasis, atopic dermatitis and / or cutis laxa pathology.

[0195] For the purposes of the present invention, "dermatological composition" means a composition intended to prevent the occurrence of pathologies and / or to treat pathological skin and / or pathological mucous membranes related to a loss of elasticity and / or firmness and / or density due to pathologies.

[0196] According to one embodiment, the particles or aqueous suspension according to the invention are characterized in that they are in the form of a dermatological composition comprising at least one dermatologically acceptable excipient.

[0197] In particular, the particles are particles according to the invention, more particularly as described and / or defined above in the present description. Similarly, the aqueous suspension is, in particular, the aqueous solution according to the invention, more particularly as described and / or defined above in this description.

[0198] According to one embodiment, the dermatological composition comprises the particles according to the invention in the form of an aqueous solution according to the invention, said aqueous suspension is present in the composition at a concentration between 1x103% to 15% by weight, preferably between 1x102% to 10% by weight, advantageously between 0.01% to 6% by weight, more preferably between 0.1% to 4% by weight, and even more preferably between 1% to 3% by weight, relative to the total weight of the composition.

[0199] The invention will be better understood upon reading the description of the figures and examples that follow.

[0200] Examples referring to the description of the invention are given below. These examples are provided by way of illustration and shall in no way limit the scope of the invention. Each example is general in scope.

[0201] The examples form an integral part of the present invention and any feature which appears new in relation to any prior art from the description taken as a whole, including the examples, forms an integral part of the invention.

[0202] On the other hand, in the examples, all percentages are given by weight unless otherwise indicated, and the temperature is expressed in degrees Celsius unless otherwise indicated. EXAMPLES

[0203] Example 1: A process for manufacturing particles according to the invention comprising vitamin E, Tinogard® TT and cetyl palmitate

[0204] a) Preparation of phase A:

[0205] 7.5 g of Emulgade® SE-PF in pellet form, 7.5 g of Eumulgin® B1 wax solid, 0.62 g of Tinogard® TT in powder form and 15 g of cetyl palmitate in pellet form are heated to 80°C + / - 2°C protected from light and mixed.

[0206] The mixture is left under agitation for 1 hour at a temperature of 80°C, in order to allow the waxes to melt completely and obtain a homogeneous mixture.

[0207] b) Preparation of phase B:

[0208] 10.16 g of Retinol 50 (50% retinol and 50% polysorbate 20) in the form of a crystalline liquid and 0.34 g of DL alpha tocopherol in liquid form are mixed at room temperature.

[0209] c) Phases A and B are mixed for a maximum of 5 minutes, at a temperature of 80°C + / - 2°C and under Rayneri stirring of 500 rpm.

[0210] d) Preparation of phase C:

[0211] 43.78 g of water and 12.5 g of glycerin in liquid form are mixed and then heated to 80°C + / - 2°C.

[0212] e) Phase C is then added to the mixture obtained in c) and the whole is mixed under Rayneri stirring at 500 rpm, in order to obtain an emulsion.

[0213] f) The emulsion obtained in step e) is cooled naturally, under Rayneri stirring. Said mixture is in the form of a translucent gel when it reaches a temperature between 65-70°C. When said gel reaches a temperature of 60°C, a pale yellow emulsion forms;

[0214] g) 0.6 g of Eumulgin® SG are added to the emulsion obtained in step f) when said emulsion reaches a temperature of 50°C+ / -5°C;

[0215] h) 1.5 g of pentylene glycol are added to the mixture obtained in step g) when said mixture reaches a temperature of 40°C + / -5°C;

[0216] i) 0.5 g of Neutrol TE are added to the mixture obtained in step h), when said mixture reaches a temperature below 40°C.

[0217] The pH of the product obtained in i) is 9 + / -0.1.

[0218] The product obtained in i) is an aqueous solution comprising the particles according to the present invention.

[0219] [Tables 1] Trade names INCI names Suppliers Functions Weight ( g) Emulgade® SE -PF 40-70% Glyceryl Stearate 10-20% Ceteareth-20 5-10% Ceteareth-12 5-10% Cetearyl Alcohol 5-10% cetyl palmitate BASF Emulsifier 7.5 Eumulgin® B 1 Ceteareth-12 BASF Emulsifier 7.5 Cutina® CP Cetyl palmitate BASF Wax 15 Eumulgin® SG Sodium Stearoyl Glutamate BASF Emulsifier 0.6 Glycerin Glycerin AMI Humectant 12.5 Pentylene Glyc ol Pentylene Glycol Minasolve SAS U Preservative 1.5 Neutrol TE Tetrahydroxypropyl Ethylenedi amine BASF Neutralizing agent 0.5 Retinol 50 50% Retinol, 50% polysorbate-20 BASF Active 10.16 DL Alpha tocopherol Tocopherol BASF Antioxidant 0.34 Tinogard® TT Pentaerythrityl Tetra-di-t-butyl Hydroxyhydrocinnamate BASF Antioxidant 0.62 Water / / / 43.78 Total 100

[0220] Example 2: Measurement of the particle size according to the invention obtained according to Example 1

[0221] i) 1 g of the product obtained according to Example 1 is diluted in 50 ml of reverse osmosis water. The mixture is maintained for 5h30 under magnetic stirring and at room temperature.

[0222] ii) 100 pL taken from the mixture obtained in i) are mixed with 10 ml of osmosis water to perform the particle size reading.

[0223] The particle size is measured using the Malvern DLS ZS90. The particle size obtained is 295 nm with a polydispersity of 0.255.

[0224] [Tables2] Average size (nm) Polydispersity Test 1 444 0.338 Test 2 373 0.243 Test 3 393 0.249 Average 403 0.277

[0225] Example 3: Measurement of the quantity of retinol in the particles according to the invention obtained according to Example 1

[0226] Sample preparation:

[0227] 200 mg of the product obtained according to example 1 and 5 ml of water are mixed for 2 minutes by sonication, then top up to 25mL with tetrahydrofuran.

[0228] The mixture obtained is eluted in a column with a linear elution gradient of 0.6 mL / min using acetonitrile alone or in a mixture with water as the mobile phase. Elution is started at t0 with a mixture of 70% acetonitrile and 30% water, gradually reaching a 100% acetonitrile mobile phase at 12 minutes. This mobile phase composition is maintained for 8 minutes, after which the initial mobile phase conditions, namely the 70% acetonitrile and 30% water mixture, are returned at 32 minutes. Finally, this mobile phase composition is maintained for 5 minutes.

[0229] The retinol content within the particles was determined by HPLC with an Agilent 1260 Infinity diode array detector (Agilent Technologies Inc., USA) using an Agilent Thermo C30 column, 150*3mm (1-49#), at a temperature of 35°C.

[0230] The injection volume is 2 pl and retinol detection takes place at 325 nm (retinol retention time between 5 and 6 minutes).

[0231] The assay was carried out on the product obtained according to example 1. A quantity of retinol of 4.89% was found within the particles according to the invention.

[0232] Example 4: Study of the stability of retinol in particles according to the present invention and in particles devoid of Tinogard® TT, obtained according to example 1

[0233] The particles according to the invention were obtained according to example 1.

[0234] Particles without Tinogard® TT were manufactured according to the method of the example 1, in which the 0.62 g of Tinogard® TT have been replaced by 0.62 g of tocopherol. The process and the rest of the ingredients are identical.

[0235] Each of the products obtained, the particles according to the invention and the particles without Tinogard® TT, was divided into 3 batches, stored in aluminum-covered plastic (PET) bottles, without the use of inert gas, and stored at 4°, 25°, and 40°C, respectively. The bottles were opened at each stability point measurement, at t0, t = 1 month, t = 2 months, t = 3 months, and t = 6 months. The stability study was conducted over 6 months. The retinol content was determined according to the procedure described in Example 3.

[0236] [Tables3] Evolution of retinol content of particles without Tinogard® TT, as a function of time and temperature: 1 month 2 months 3 months 6 months 4°C -98% 98% 95% 93% 25°C 100% 97% 99% 93% 86% 40°C -92% -88% 79%

[0237] [Tables4] Evolution of the retinol content of the particles according to the invention as a function of time and temperature: 1 month 2 months 3 months 6 months 4°C - 94% 95% 92% 95% 25°C 100% 94% 96% 89% 88% 40°C - 91% 93% 91% 80%

[0238] The particles according to the present invention have a higher retinol content over time when stored at 40°C, after 3 months and 6 months. The particles according to the present invention also have a higher retinol content after 6 months when stored at 4°C, 25°C and 40°C respectively.

[0239] The presence of Tinoguard TT in the particles according to the invention therefore makes it possible to increase the stability over time of the retinol contained in the particles according to the invention, preferably from 6 months and regardless of the storage temperature.

[0240] Example 5: Study of the stability of retinol in particles according to the present invention and in particles devoid of Tinogard® TT, obtained according to Example 1 and incorporated into a cosmetic formulation

[0241] The particles according to the invention were obtained according to Example 1 and were introduced into a cosmetic composition at a concentration of 2% by weight relative to the total weight of the cosmetic composition.

[0242] The T-free antioxidant particles, Tinogard® TT, were manufactured according to Example 4 and were introduced into a cosmetic composition at a concentration of 2% by weight relative to the total weight of the cosmetic composition.

[0243] Two unencapsulated (free) retinol compositions are used as controls:

[0244] - An unencapsulated (free) retinol composition, formulated with the same anti oxidants that in the particles according to the invention (Tinogard® TT and tocopherol), was introduced into a cosmetic composition with a concentration of 0.21% by weight of retinol (as retinol supplied by BASF, formulated with 49.11% polysorbate 20 by weight, 47.6% retinol by weight and 3.29% tocopherol by weight relative to the total weight of the retinol composition supplied by BASF), and a concentration of 0.0124% by weight of Tinogard TT, relative to the total weight of the cosmetic composition,

[0245] - A non-encapsulated (free) retinol composition, formulated solely with of tocopherol (therefore without Tinogard® TT), was introduced into a cosmetic composition with a concentration of 0.21% by weight of retinol (as retinol supplied by BASF, formulated with 49.11% polysorbate 20 by weight, 47.6% retinol by weight and 3.29% tocopherol by weight relative to the total weight of the retinol composition supplied by BASF), and a concentration of 0.0124% by weight of tocopherol, relative to the total weight of the cosmetic composition.

[0246] The cosmetic compositions were formulated at a temperature below 30°C.

[0247] [Tables 5] Phase Ingredient Composition with particles without Tinogard TT® (% by weight) Composition free retinol + tocopherol (% by weight) Composition free retinol + tocopherol + Tinogard® TT (% by weight) Composition particles according to the invention (% by weight) A Myritol 318 8 8 8 8 Emulgade® PL 68 / 50 1 1 1 1 Tinogard TT / / 0.0124 / Tocopherol / 0.0124 / / Retinol (BASF) * polysorbate 20: Retinol: Tocopherol = 49.11%: 47.6% : 3.29% / 0.21 0.21 / Lanette O 3.5 3.5 3.5 3.5 B Water 71 72.7776 72.7776 71 Glycerin 5 5 5 5 Rheocare

[0248] Each of the products was stored in plastic (PET) bottles covered with aluminum foil, without the use of inert gas, and stored at 25°C and 40°C, respectively. The stability study was conducted over 3 months, and the bottles were opened at each stability point measurement: t0, t=1 month, t=2 months, and t=3 months. The retinol content was determined according to the procedure described in Example 3.

[0249] The results representing the evolution of the retinol content in the different compositions are presented below.

[0250] [Tableauxô] Compositions for 1 month, 2 months, 3 months 25°C 40°C 25°C 40°C 25°C 40°C Composition without particles without Tinogard® TT 100% 100% 80% 90% 60% 80% 50% Composition of free retinol + tocopherol 100% 100% 67% 78% 33% 67% 22% Composition of free retinol + tocopherol + Tinogard® TT 100% 100% 73% 91% 55% 82% 45% Composition with particles as per invention 100% 100% 88% 100% 75% 100% 63%

[0251] After one month of storage at 40°C, better results are obtained for the cosmetic composition comprising the particles according to the invention (88% of the initial retinol content is found in the composition comprising the particles according to the invention) compared to other cosmetic compositions with free retinol or with particles without Tinogard TT (67%, 80% and 73% of the initial retinol content in the cosmetic composition comprising respectively free retinol and tocopherol, particles without Tinogard® TT and free retinol with tocopherol and Tinogard® TT).

[0252] After 2 months of storage at 25°C, better results are obtained for the cosmetic composition comprising the particles according to the invention (100% of the initial retinol content is recovered in the composition comprising the particles according to the invention) compared to other cosmetic compositions with free retinol or with particles lacking Tinogard TT (78%, 90%, and 91% of the initial retinol content in the cosmetic composition comprising, respectively, free retinol and tocopherol, particles without Tinogard® TT, and free retinol with tocopherol and Tinogard® TT). The same trend is observed after 2 months of storage at 40°C.

[0253] After 3 months of storage at 25°C, better results are also obtained for the cosmetic composition comprising the particles according to the invention (100% of the initial retinol content is recovered in the composition comprising the particles according to the invention) compared to other cosmetic compositions with free retinol or with particles lacking Tinogard TT (67%, 80%, and 82% of the initial retinol content in the cosmetic composition comprising, respectively, free retinol and tocopherol, particles without Tinogard® TT, and free retinol with tocopherol and Tinogard® TT). The same trend is observed after 3 months of storage at 40°C.

[0254] The particles according to the invention therefore allow for better preservation of the initial retinol content in a cosmetic composition over time than particles without Tinogard TT or free (non-encapsulated) retinol compositions formulated with 1 or 2 antioxidants.

[0255] Example 6: Inflammation / irritation tests of free retinol and retinol in particles according to the present invention 1. Materials and methods:

[0256] Retinol has been shown to induce an increase in the expression of IL-8 (a pro-inflammatory mediator responsible for retinol-induced skin irritation (B.-H. Kim et al. / Toxicology Letters 146 (2003) 65-73)) in epidermal cells and fibroblasts,

[0257] 1.1 Cell culture and sample processing

[0258] Normal human dermal fibroblasts (NHDF) were cultured in DMEM culture medium supplemented with 10% heat-inactivated fetal calf serum and 1% penicillin / streptomycin / amphotericin B at 37°C under a controlled atmosphere (95% air and 5% CO2).

[0259] When they reached 80-90% confluence, the NHDF cells were hydrolyzed and seeded onto several 96-well plates at a density of 5,000 cells per well. The cells were treated for 48 hours with the following samples to be evaluated (n=3):

[0260] - The NT witness, untreated

[0261] - A mixture of 0.005% particles comprising encapsulated Tinogard® TT at 0.62% and 0.00025% by weight of free retinol, in the form of retinol supplied by BASF and pre-formulated with 49.11% polysorbate 20, 47.6% retinol and 3.29% tocopherol by weight.

[0262] - 0.005% of particles according to the invention corresponding to 0.00025% of pure retinol, manufactured according to example 1.

[0263] [Tables7] Samples Concentration (%) Preparation of the stock solution Free retinol + particles comprising Tinogard® TT 0.005% particles + 0.00025% retinol (corresponding to 5% of the stock solution) Dilution of the particles in the culture medium to 0.1%. Dissolution of the retinol in DM SO₂ (5%). Dilution in a culture medium containing 0.005% pure retinol. Mixing of the two media and dilution to the intended concentration. Particles according to the invention: 0.005% particles encapsulating 5% retinol (i.e., ultimately 0.00025% retinol) (Corresponds to a 5% dilution of the stock solution). Dilution of the retinol particles in the culture medium to 0.1% and dilution to the intended concentration.

[0264] 1.2 Analysis of pro-inflammatory proteins by ELIS A

[0265] After 48 hours of treatment, the cellular supernatant was collected and the concentration of IL-8 was measured using an ELISA kit in accordance with the manufacturer's instructions (IL-8 ELISA Kit (R&D Systems).

[0266] The amount of IL-8 was quantified by reading the absorbance at 450 nm using a microplate reader.

[0267] 1.3 Statistics

[0268] Data are presented as mean ± SD and analyzed with a Student's t-test *, ** p < 0.01.

[0269] 2. Results:

[0270] The results are presented in the table. The level of interleukin-8 secreted by NHDFs, a marker of inflammation, is equivalent between the untreated NT control sample and the sample treated with the particles according to the invention (100% versus 102.7%), whereas the sample treated with free retinol shows a significant increase in the level of interleukin-8 secreted by NHDFs (147.4%).

[0271] The particles according to the invention make it possible to inhibit inflammation and / or irritation induced by retinol on the skin and / or mucous membranes.

[0272] Effect of test samples on the expression of 1TL-8 in NHDFs.

[0273] [Tables8] IL-8 Expression (%) Standard Deviation (%) pvs NT pvs Sample 1 NT (untreated) 100.0% 7.5% / / Free Retinol 147.4% 6.8% 0.00808** / Particles according to the invention 102.7% 7.8% 0.77664 0.00382**

[0274] Example 7: Cosmetic active ingredients comprising the particles according to the invention

[0275] Active ingredient no. 1

[0276] [Tables9] INCI CAS No. Quantity (% by weight) Water 7732-18-5 45.78 Cetyl palmitate 95912-87-1 15.37 - 15.75 Glycerin 56-81-5 12.50 Ceteareth-12 68439-49-6 7.87 - 8.2 Polysorbate 20 9005-64-5 5.13-5.82 Retinol 68-26-8 4.34 - 5.03 Glyceryl Stearate 67701-33-1 3.00 - 5.25 Pentylene Glycol 5343-92-0 1.50 Ceteareth-20 68439-49-6 0.75 - 1.5 Pentaerythrityl Tetra-di-t-butyl Hydroxyhydrocinn amate 6683-19-8 0.62 Sodium Stearoyl Glutamate 38517-23-6 0.60 Cetearyl Alcohol 67762-27-0 0.37 - 0.75 Tetrahydroxypropyl Ethylenediamine 102-60-3 0.50 Tocopherol 10191-41-0 0.34

[0277] Active ingredient no. 2

[0278] [TableauxlO] INCI CAS No. Quantity (% by weight) Water 7732-18-5 45.33 Cetyl Palmitate 95912-87-1 15.37 - 15.7 Glycerin 56-81-5 12.50 Ceteareth-12 68439-49-6 7.87 - 8.2 Polysorbate 20 9005-64-5 5.13-5.82 Retinol 68-26-8 4.34 - 5.03 Glyceryl Stearate 67701-33-1 3.00 - 5.25 Ceteareth-20 68439-49-6 0.75 - 1.5 Pentaerythrityl Tetra-di-t-butyl Hydroxyhydrocinnamate 6683-19-8 0.62 Sodium Stearoyl Glutamate 38517-23-6 0.60 Cetearyl Alcohol 67762-27-0 0.37 - 0.75 Benzyl Alcohol 100-51-6 1 Tocopherol 10191-41-0 0.34

[0279] Example 8: Cosmetic composition formulated with the cosmetic active ingredient comprising the particles according to the invention

[0280] [Tableauxll] Phase Ingredient Concentration (% by weight) Names INCI A Myritol 318 RC 8 Caprylic / Capric Triglyceride Emulgade® PL 6 8 / 50 1 Cetearyl Glucoside, Cetearyl Alcohol Lanette O 3.5 Cetearyl Alcohol B Water 77 Water Glycerin 5 Glycerin Rheocare XGN (5%) 2 Xanthan Gum (5%) PE9010 (0.2%) Water (94.8%) Eumulgin® SG 1 Sodium Stearoyl Glutamate C PE9010 0.5 Phenoxyethanol (90%) Ethylhexylglycerin (10%) D Encapsulated Reti nol (BASF) CNW -TV (5% Retinol) 2 Glycerin, Cetyl palmitate, Ceteareth-12, Gly ceryl Stearate,Pentylene Glycol,Sodium Stear oyl Glutamate, Ceteareth-20, Tetrahydroxypro pyl Ethylenediamine, Cetearyl Alcohol, Aqua / Water, Retinol, Polysorbate 20, Tinogard® TT, Tocopherol Total 100

[0281] Example 9: Study of the thickness of the epidermis on paraffin blocks of skin explants treated with the particles according to the invention and free retinol at different concentrations.

[0282] The aim of this study is to show that the particles according to the invention are at least as effective as an unencapsulated retinol solution at the same concentration and on 3 targets classically stimulated by retinol: the increase in epidermal thickness, the stimulation of collagen I and collagen III. • Preparation of the expiatory tokens

[0283] Expenditures of 11+1 mm in diameter were prepared from an abdominal plasty of a 52-year-old woman with a phototype II according to the Fitzpatrick classification.

[0284] At Jl, the expiants were placed in survival mode in BEM (BIO-EC's Expiants Medium) at 37°C in a humid atmosphere, enriched with 5% CO2.

[0285] 3 expiants at each time (J4, J7) and for each condition were realized. • Preparation of products to be applied

[0286] Since retinol is available as a fat-soluble powder, it was diluted in ethanol (4% final concentration) and then in a 1.5% carboxymethylcellulose (CMC) gel to prepare the 0.1% and 0.3% retinol controls. The retinol used was supplied by Sigma (R7632).

[0287] For the condition "Particles according to the invention", the tested product was diluted directly in 1.5% CMC gel containing 4% ethanol.

[0288] The condition "Excipient alone" corresponds to the 1.5% CMC gel containing 4% ethanol (=CMC gel).

[0289] Summary of tested conditions:

[0290] [Tables 12] Composition of the tested formula Untreated control - Excipient only CMC gel (1.5% with 4% ethanol) Retinol 0.1% Retinol at 0.1% in CMC gel Retinol 0.3% Retinol at 0.3% in CMC gel Particles according to the invention 2% Particles according to the invention at 2% in CMC gel (i.e. -0.1% of pure retinol) Product application

[0291] On days 0, 3, 4, and 6, the tested products were applied topically at a rate of 2 ql per expiant (2 mg / cm²) and spread using a spatula. The expiants in the control groups received no treatment except for the replacement of the culture medium. The culture medium was replaced by half (1 ml per well) on days 0, 3, 4, and 6. • Samples

[0292] On days 4 and 7, the 3 expiants from each batch were taken and cut in half. One part was fixed in a buffered formalin solution, and the other was frozen at -80°C. • Histological treatments and measurements performed

[0293] After 24 hours in buffered formalin, the samples were dehydrated and impregnated with paraffin using a Leica PEARL automated dehydration system. They were block-formed using a Leica EG 1160 embedding station. 5 sq m sections were prepared using a Minot-type microtome, Leica RM 2125, and mounted on histological glass slides.

[0294] The frozen samples were cut into 7 pm thick sections using a Leica CM 3050 cryostat.

[0295] Microscopic observations were carried out using optical microscopy, with the aid of a Leica DMLB type microscope, Olympus BX43 or Olympus BX63.

[0296] The shots were taken with an Olympus DP camera and cellSens software (Olympus). • Measurement of epidermal thickness (on paraffin blocks)

[0297] In this study, there are 3 paraffin blocks for each condition tested. Each skin biopsy was cryo-sectioned and 3 sections were prepared for image analysis and subsequently, 3 image acquisitions were taken for each section (Leica DMLB type microscope, Olympus BX43 or Olympus BX63, NIH Image J-Fiji software).

[0298] For each image, 10 measurements were taken to determine an average thickness of the living layer of the epidermis. In total, 90 measurements were therefore analyzed for each condition.

[0299] The results are expressed as mean thickness in % (percentage) normalized with the condition "Excipient alone", + / - SEM (standard error of the mean) n=90

[0300] Statistical analysis was performed using Student's t-test, following the recommendations of the Sigmaplot® software (Systat Software Inv. USA). The significance level was set at 5% (p<0.05).

[0301] [Tables 13 Epidermal thickness at day 7 (% / Excipient) SEM Significance vs Excipient Significance vs Free Retinol 0.1% Significance vs Free Retinol 0.3% Untreated control 101 2 ns Excipient 100 2 - Free Retinol 0.1% 127 2 *** Free Retinol 0.3% 155 2 *** Particles according to the invention 2% 150 3 *** *** ns

[0302] n=90 ; *** (p<0.001 ) ; Ns = not significant

[0303] The excipient alone (CMC at 1.5% with 4% ethanol) does not cause any effect on the increase in epidermal thickness.

[0304] Compared with the excipient alone, the application of free retinol at 0.1% and 0.3% induces a significant increase in epidermal thickness, of 27% and 55% respectively.

[0305] Treatment with 2% of particles according to the invention causes a significant increase in epidermal thickness of 50% compared to the excipient alone, significantly greater than the increase observed with 0.1% retinol (p<0.001) and equivalent to the increase observed with 0.3% free retinol.

[0306] The particles according to the invention at 2% induce a significant increase in the thickness of the epidermis, in a manner similar to the application of a free retinol treatment at 0.3%.

[0307] The retinol encapsulated in the particles according to the invention is more effective than a 0.1% free retinol solution and is as effective as a 0.3% free retinol solution.

[0308] Example 10: Study of collagen I expression on frozen sections of skin explants treated with the particles according to the invention and free retinol at different concentrations.

[0309] The experimental protocol is identical to that described in Example 9. • Immunostaining of collagen I (on frozen blocks)

[0310] Immunostaining of collagen I was performed on day 4 on frozen sections (3 expiants) with a polyclonal anti-collagen I antibody (Abcam, ref. abl38492-1001) diluted 1:1600 in 0.3% PBS-BSA-Tween 20 (0.05%) for 1 hour at room temperature and visualized in AlexaFluor AF488 (Lifetechnologies, ref. Al 1008). Nuclei were counterstained with propidium iodide.

[0311] Quantification of immunostaining was performed using image software (Olympus cellSens software) coupled to a microscope (Leica type DMLB, Olympus BX43 or Olympus BX63). (3 images / expiant)

[0312] Results are expressed as a percentage of stimulation (%) normalized to the condition "Excipient alone", + / - SD (standard deviation) n=9

[0313] Statistical analysis was performed using Student's t-test with a significance threshold set at 5% (p<0.05).

[0314] [Tables 14] Collagen stimulation I at day 4 (% / Excipient) SD Significance vs Excipient Significance vs Free Retinol 0.1% Significance vs Free Retinol 0.3% Untreated control 34 12 *** Excipient 100 23 - free retinol 0.1% 148 14 *** free retinol 0.3% 152 10 *** Salt particles of the invention 2% 143 18 *** ns ns

[0315] n=9 ; ** (p<0.01); Ns = not significant

[0316] The excipient alone (CMC at 1.5% with 4% ethanol) induces a significant stimulation of collagen I synthesis.

[0317] Compared with the excipient alone, the application of free retinol at 0.1% and 0.3% induces a significant stimulation of collagen I synthesis of 48% and 52% respectively.

[0318] Treatment with 2% of particles according to the invention causes a significant stimulation of collagen I synthesis of 43% compared with the excipient alone, which is equivalent to the application of a retinol solution alone at 0.1 or 0.3%.

[0319] The retinol encapsulated in the particles according to the invention is always bioavailable and as effective as a 0.1% free retinol solution on collagen I synthesis.

[0320] Example 11: Study of collagen III expression on frozen sections of skin explants treated with the particles according to the invention and free retinol at different concentrations.

[0321] The experimental protocol is identical to that described in Example 9. • Immunostaining of collagen III (on frozen blocks)

[0322] Immunostaining of collagen III was carried out on day 7 on frozen sections (3 expiants) with an anti-collagen III antibody (SBD, Ref: 1330-01), diluted 1:200 in 0.3% PBS-BSA for 1h at room temperature, with a biotin / streptavidin amplification system, revealed in VIP (Vector laboratories, Ref. SK-4600), a substrate of peroxidase giving a purple color once oxidized.

[0323] Quantification of immunostaining was performed using image software (Olympus cellSens software) coupled to a microscope (Leica type DMLB, Olympus BX43 or Olympus BX63). (3 images / expiant)

[0324] Results are expressed as a percentage of stimulation (%) normalized to the condition "Excipient alone", + / - SD (standard deviation) n=9

[0325] Statistical analysis was performed using Student's t-test with a significance threshold set at 5% (p<0.05).

[0326] [Tables 15] Collagen III Stimulation at Day 7 (% / Excipient) SD Significance vs Excipient Significance vs Free Retinol 0.1% Significance vs Free Retinol 0.3% Untreated Control 100 14 ** Excipient 100 17 - Free Retinol 0.1% 141 28 ** Free Retinol 0.3% 147 30 ** Particles according to the invention 2% 134 22 ** ns ns

[0327] n=9 ; ** (p<0.01 ) ; Ns = not significant

[0328] The excipient alone (CMC at 1.5% with 4% ethanol) does not induce stimulation of collagen III.

[0329] Compared with the excipient alone, the application of free retinol at 0.1% and 0.3% induces a significant stimulation of collagen III synthesis of 41% and 47% respectively.

[0330] Treatment with 2% of particles according to the invention causes a significant stimulation of collagen I synthesis of 34%, compared with the excipient alone, equivalent to the application of a retinol solution alone at 0.1% or 0.3%.

[0331] The retinol encapsulated in the particles according to the invention is always bioavailable and as effective as a 0.1% free retinol solution on the synthesis of collagen III.

[0332] Example 12: Study of the transcutaneous penetration of the particles according to the invention and of free retinol.

[0333] The aim of this study is to show that the particles according to the invention are capable of penetrating as far as the dermis.

[0334] Retinol was co-encapsulated with an oily fluorescent probe (Nile Red) in the particles according to the invention, and the product was applied to a skin sample. Quantification of the fluorescence detected in the dermis was then performed 24 hours after application of the product. • Preparation of products to be tested

[0335] Unencapsulated Nile Red retinol solution:

[0336] 19.35 g of Retinol 50 were mixed with 0.64 g of DL alpha tocopherol and 0.01 g of Nile Red (N-3013, Merck).

[0337] The retinol-Nile Red solution thus obtained therefore contains 0.05% Nile Red.

[0338] Aqueous solution comprising the particles according to the invention formulated with the Nile Red:

[0339] The solution was prepared according to Example 1, with 0.005 g of Nile Red added in phase B (mixture with retinol and DL alpha tocopherol).

[0340] The aqueous solution thus obtained contains 0.005% by weight of Nile Red after manufacture, relative to the total weight of the aqueous solution.

[0341] [Tables 16] Trade names INCI names Suppliers Functions Weight ( g) Emulgade® SE -PF 40-70% Glyceryl Stearate 10-20% Ceteareth-20 5-10% Ceteareth-12 5-10% Cetearyl Alcohol 5-10% cetyl palmitate BASF Emulsifier 7.5 Eumulgin® B 1 Ceteareth-12 BASF Emulsifier 7.5 Cutina® CP Cetyl palmitate BASF Wax 15 Eumulgin® SG Sodium Stearoyl Glutamate BASF Emulsifier 0.6 Glycerin Glycerin AMI Humectant 12.5 Pentylene Glyc ol Pentylene Glycol Minasolve SAS U Preservative 1.5 Neutrol TE Tetrahydroxypropyl Ethylenedi amine BASF Neutralizing agent 0.5 Retinol 50 50% Retinol, 50% Polysorbate-20 BASF Active 10.16 DL Alpha tocopherol Tocopherol BASF Antioxidant 0.34 Tinogard® TT Pentaerythrityl Tetra-di-t-butyl Hydroxyhydrocinnamate BASF Antioxidant 0.62 Nile Red - Merck Fluoride probe center 0.005 Water / / / 43.775 Total 100

[0342] The 2 products were then formulated in a cosmetic cream at a concentration of 10% by weight for the aqueous suspension comprising the particles according to the invention formulated with Nile-Red, relative to the total weight of the cream and 1% by weight for the unencapsulated retinol-Nile Red solution relative to the total weight of the cream, such that the final concentration of the Nile Red probe is 0.0005% by weight in the 2 creams to be tested.

[0343] Cosmetic formulation containing 10% by weight of particles according to the invention + Nile Red

[0344] [Tables 17] Phase Raw materials INCI name % by weight 1 Emulgade SE / PF Glyceryl Stearate, Ceteareth-20, C eteareth-12, Cetearyl alcohol, cety 1 palmitate 5.0 Lanette 22 Behenyl alcohol 2.0 Cegesoft C24 Ethylhexyl palmitate 5.0 Cetiol PGL Hexyldecanol / hexyldecyl laurate 3.0 Cetiol OE Dicapryl ether 3.0 DC 200-100 est Dimethicone 1.0 2 Reverse osmosis water Water 65.6 Euxyl PE9010 Phenoxyethanol, ethylhexylglyce rin 1.0 Glycerin 99-5 Glycerin 3.0 Eumulgin SG Sodium stearoyl glutamate 0.4 3 Rheocare XGN Xanthan gum 0.2 Cosmedia SP Sodium polyacrylate 0.8 4 SLP Retinol - Nile Red 10.0

[0345] Cosmetic formulation containing 1% by weight of free (unencapsulated) Nile Red-Retinol solution

[0346] [Tables 18] Phase Raw materials INCI name % by weight 1 Emulgade SE / PF Glyceryl Stearate, Ceteareth-20, C eteareth-12, Cetearyl alcohol, cety 1 palmitate 5.0 Lanette 22 Behenyl alcohol 2.0 Cegesoft C24 Ethylhexyl palmitate 5.0 Cetiol PGL Hexyldecanol / hexyldecyl laurate 3.0 Cetiol OE Dicapryl ether 3.0 DC 200-100 est Dimethicone 1.0 2 Reverse osmosis water Water 74.6 Euxyl PE9010 Phenoxyethanol, ethylhexylglyce rin 1.0 Glycerin 99-5 Glycerin 3.0 Eumulgin SG Sodium stearoyl glutamate 0.4 3 Rheocare XGN Xanthan gum 0.2 Cosmedia SP Sodium polyacrylate 0.8 4 Free solution Retinol - N Red Island 1.0 Product application and analysis

[0347] Skin expiants (NativeSkin®, Genoskin) from a 42-year-old donor were cultured in a 12-well plate at 37°C for 24 h prior to the application of the 2 creams to be tested.

[0348] 10 ql of each formulation were then added and spread over the surface of the biopsies (n=l per product to be tested) with a sterile glass rod for approximately 20 seconds, then the skin expirys were incubated at 37°C in an incubator humidified with 5% CO2 for 24h (T24h).

[0349] Cryosections 10 µm thick were prepared and treated with DAPI (4',6-diamidino-2-phenylindole) staining. These cryosections were then examined and images were captured using a confocal microscope (Leica SP8). (n=6 images / condition). • Statistical analysis

[0350] Results are expressed as percentage of fluorescence (%) detected in the dermis and normalized to the condition "Retinol+Nile Red unencapsulated", + / - SEM (standard error of the mean) n=6

[0351] Statistical analysis was performed using Student's t-test, following the recommendations of the Sigmaplot® software (Systat Software Inv. USA). The significance level was set at 5% (p<0.05).

[0352] [Tables 19] % fluorescence / Retinol + Nile Red non-encapsulated SEM Statistical analysis vs Retinol + Nile Red non-encapsulated Particles according to invention + Nile Red 160 18 * Retinol + Nile Red non-encapsulated 100 10 -

[0353] n=6

[0354] * (p<0.05)

[0355] The cream containing the particles according to the invention + Nile Red shows an increase in probe penetration into the dermis of 60% compared to the cream containing the unencapsulated form of retinol + Nile Red.

[0356] The particles according to the invention therefore allow better penetration of retinol into the dermis than free retinol.

Claims

Demands

1. Particles comprising retinol, cetyl palmitate, glyceryl stearate, ceteareth-20, ceteareth-12, cetearyl alcohol, tocopherol and pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate.

2. Particles according to claim 1, comprising between 1% and 25% by weight of retinol, preferably between 5% and 20% by weight of retinol, more preferably between 10% and 14% by weight of retinol, relative to the total weight of particles.

3. Particles according to any one of the preceding claims, comprising between 5% and 60% by weight of cetyl palmitate, preferably between 15% and 50% by weight of cetyl palmitate, more preferably between 25% and 45% by weight of cetyl palmitate, advantageously between 30% and 40% by weight of cetyl palmitate, relative to the total weight of the particles.

4. Particles according to any one of the preceding claims, comprising between 0.001% and 8% by weight of tocopherol, preferably between 0.01% and 4% by weight of tocopherol, more preferably between 0.1% and 2% by weight of tocopherol, relative to the total weight of the particles.

5. Particles according to any one of the preceding claims, having an average size between 100 and 900 nm, preferably between 150 and 750 nm, more preferably between 300 nm and 500 nm.

6. Particles according to any one of the preceding claims, characterized in that the particles are obtained by phase inversion temperature inversion technology.

7. Aqueous suspension comprising the particles as defined in any one of claims 1 to 6 in an aqueous solution, advantageously the aqueous solution comprising water and glycerin.

8. A cosmetic composition for topical application, comprising particles as defined in any one of claims 1 to 6 or an aqueous suspension as defined in claim 7, preferably with a content of between 4% and 15% (w / w), preferably between 2% and 10% (w / w), advantageously between 0.01% and 6% (w / w), more preferably between 0.1% and 4% (w / w), and even more preferably between 1% and 3% (w / w), relative to the total weight of the composition, and at least one cosmetically acceptable excipient.

9. Non-therapeutic cosmetic use of the particles as defined in any one of claims 1 to 6, or of an aqueous suspension as defined in claim 7, or of a cosmetic composition as defined in claim 8, to prevent and / or reduce aging, and / or maintain and / or increase the biomechanical properties, and / or maintain and / or increase the barrier effect, of healthy skin and / or healthy mucous membranes.

10. Non-therapeutic cosmetic use according to claim 9, to maintain and / or increase the firmness, and / or elasticity, and / or thickness, and / or density, of healthy skin and / or healthy mucous membranes.

11. Non-therapeutic cosmetic use according to any one of claims 9 or 10, characterized in that the particles are intended to be applied to all or part of the body and / or face and / or scalp, preferably the legs, thighs, arms, stomach, décolleté, neck, armpits, lips, more preferably all or part of the face, and preferably the cheeks, forehead, chin, lips, eye contour, in particular on the cheeks and / or angular area of ​​the face, more preferably on an area of ​​skin exhibiting a loss of biomechanical properties, in particular sagging and / or a sagging area of ​​skin and / or an area of ​​skin lacking tone.

12. Dermatological composition intended for topical application, comprising particles as defined in any one of claims 1 to 6 or an aqueous suspension as defined in claim 7, and at least one dermatologically acceptable excipient.

13. Dermatological composition according to claim 12, characterized in that said particles or aqueous suspension are present in the dermatological composition at a concentration of between 1 x 10⁴% and 15% by weight, preferably between 1 x 10²% and 10% by weight, advantageously between 0.01% and 6% by weight, more preferably between 0.1% and 4% by weight, and even more preferably between 1% and 3% by weight, relative to the total weight of the dermatological composition.

14. Particles as defined in claims 1 to 6, or aqueous suspension as defined in claim 7, or dermatological composition comprising them as defined in claim 12 or 13, for preventing and / or treating pathological skin and / or pathological mucous membranes related to a loss of elasticity, and / or firmness, and / or density, due to pathologies such as candidiasis, impetigo, eczema, acne, telangiectasias, dermatoporosis, Ehlers-Danlos syndrome, osteogenesis imperfecta, solar elastosis, senile xerosis, diabetes, tetraplegia, Peeling Skin Syndrome, psoriasis, atopic dermatitis and / or cutis laxa pathology.

15. A method for producing the particles according to any one of claims 1 to 6 or the aqueous suspension according to claim 7, characterized in that the particles are obtained by phase inversion temperature technology.

16. A production process according to claim 15, characterized in that it comprises the following steps: a) Cetyl palmitate, glycerol stearate, ceteareth-20, ceteareth-12, cetearyl alcohol, sodium stearoyl glutamate, and pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate are mixed and heated at a temperature between 60°C and 100°C, protected from light, forming phase A; b) A phase B is prepared by mixing retinol and tocopherol at room temperature; c) Phases A and B are mixed at a temperature between 60°C and 100°C to obtain a homogeneous product; d) A phase C comprising water and glycerin is heated at a temperature between 60°C and 100°C; e) Phase C is mixed with the product obtained at the end of step c) to obtain an emulsion; f) The emulsion obtained at the end of step e) is cooled to a temperature between 35°C and 55°C;(g) A phase D comprising sodium stearoyl glutamate is added to the cooled emulsion obtained at the end of step (f), the whole is mixed at a temperature between 35°C and 55°C, to; to obtain a homogeneous solution comprising said particles corresponding to the aqueous suspension.

17. Production process according to claim 16, characterized in that the solution obtained at the end of step g) has a pH between 7 and 11, preferably between 7 and 10.

18. A non-therapeutic cosmetic care method for healthy skin and / or healthy mucous membranes characterized in that it comprises the topical application to at least one area of ​​healthy skin and / or healthy mucous membrane of the particles as defined in claims 1 to 6, of the aqueous suspension as defined in claim 7, or of a cosmetic composition comprising them as defined in claim 8.

19. Non-therapeutic cosmetic care method according to claim 18 for preventing and / or reducing aging, and / or maintaining and / or increasing biomechanical properties, and / or maintaining and / or increasing the barrier effect, of healthy skin and / or healthy mucous membranes.

20. A non-therapeutic cosmetic treatment method according to any one of claims 18 or 19, for maintaining and / or increasing the firmness, and / or density, and / or thickness, and / or elasticity of healthy skin and / or healthy mucous membranes.

21. A non-therapeutic cosmetic treatment method according to any one of claims 18 to 20, is characterized in that the application is carried out on all or part of the body and / or face and / or scalp, preferably the legs, feet, armpits, hands, neck, décolletage, belly, arms, thighs, hips, buttocks, waist, again preferably all or part of the face, and preferably the cheeks, forehead, chin, lips, eye contour.

22. A non-therapeutic cosmetic treatment method according to any one of claims 18 to 21, comprising the following steps: - Identifying on the individual an area of ​​healthy skin and / or healthy mucous membrane for which it is desired to prevent and / or reduce aging, and / or maintain and / or increase biomechanical properties, and / or maintain and / or increase the barrier effect, - Applying topically to this area of ​​healthy skin and / or healthy mucous membrane an effective quantity of particles according to one any of claims 1 to 6, or the aqueous suspension according to claim 7, or the composition according to claim 8, in the form of an active ingredient or a cosmetic composition comprising them.