Cosmetic use of a combination of honeys and royal jelly

Abstract

The present invention relates to a cosmetic composition comprising: a) at least two honeys selected from the group consisting of Norwegian honey, Irish Connemara honey and Ouessant honey; and b) optionally royal jelly.

Description

Title of the invention: Cosmetic use of a combination of honeys and royal jelly. FIELD OF THE INVENTION

[0001] The present invention relates to the field of care for keratinous materials. STATE OF THE ART

[0002] The skin is the body's first line of defense against the environment. Our skin is thus subjected daily to stresses of exogenous or endogenous origin that can induce non-pathological skin reactions that are unsightly and / or uncomfortable. Exogenous stressors are numerous: they are notably of chemical origin, for example xenobiotics, antigens, allergens, emotional stress, cosmetic products; or of environmental origin (temperature, climate, air pollution, cigarette smoke, etc.) or even of mechanical origin (friction, shaving, cleaning, etc.).

[0003] The skin possesses a stress adaptation system to cope with the various internal and external aggressions that affect it daily. Different cellular stress response mechanisms are continuously activated to induce a temporary adaptive response that allows cells to maintain their biological functions in the face of their environment and thus ensure skin homeostasis.

[0004] However, the progressive exhaustion of protective adaptation mechanisms by daily, intense, or repeated stress leads to the gradual decline of cellular functions and the disruption of homeostasis. The inability of cells to respond and adapt to their environment then results in skin aging.

[0005] yH2AX is a key factor in epidermal cellular stress, which is also known to appear to persist with age (Siddiqui et al. (2015) Mutât Res Rev Mutât Res 766:1-19). This marker has also been identified as a marker associated with cell senescence within a tissue (Suryadevara et al. (2024-) Nat Rev Mol Cell Biol; doi: 10.1038 / s41580-024-00738-8). Description of the invention

[0006] Unexpectedly, the Applicant has shown that an association of at least two honeys chosen from the group consisting of Norwegian honey, Irish Connemara honey and Ouessant honey; and possibly royal jelly, makes it possible to decrease the expression of the stress marker yH2AX in primary keratinocytes after exposure to UVB stress, representative of exogenous stress.

[0007] By reducing the effect of environmental stresses on the basal cells of the epidermis, this particular combination of active ingredients therefore makes it possible to improve skin renewal and / or regeneration.

[0008] The present invention thus relates to a cosmetic composition comprising at least two honeys chosen from the group consisting of Norwegian honey, Irish Connemara honey and Ouessant honey.

[0009] In a preferred embodiment, the cosmetic composition according to the invention further comprises royal jelly.

[0010] By "cosmetic composition" we mean any composition with a cosmetic purpose, that is to say aesthetic, which may be brought into contact with the superficial parts of the human body and more particularly with keratinous materials, in particular the skin and / or lips, in particular the skin of the face and / or neck.

[0011] By "physiologically acceptable medium" is meant any excipient suitable for topical use, in contact with keratinous materials, without risk of toxicity, incompatibility, instability and / or allergic response.

[0012] The physiologically acceptable medium generally represents from 1 to 99% by weight, relative to the total weight of said composition.

[0013] The term "keratinous material" refers to the skin and / or its appendages, and the lips, in particular the skin of the face and / or body and the lips. The keratinous materials according to the invention include, in particular, healthy keratinous materials (from "healthy" subjects), that is to say, those not exhibiting any disorders or abnormalities indicative of a pathological condition (from "unhealthy" subjects, those suffering from a pathology). The terms "healthy skin" and / or "lips" will be used interchangeably throughout the rest of this description.

[0014] Another object of the invention relates to a cosmetic process for the care and / or removal of keratinous materials, intended in particular to promote and / or stimulate the renewal and / or regeneration of skin, in particular of the skin and / or lips, in particular intended to stimulate the regeneration of basal cells of the epidermis, in particular of the skin and / or lips, comprising the topical application on keratinous materials, in particular the skin and / or lips, of a cosmetic composition according to the invention.

[0015] The present invention also relates to the cosmetic use of an association comprising; a) at least two honeys chosen from the group consisting of Norwegian honey, Irish Connemara honey, and Ouessant honey; and b) possibly royal jelly; for topical application on keratinous materials, particularly the skin and / or lips, as a cosmetic active ingredient intended to promote and / or stimulate the skin renewal and / or regeneration, particularly of the skin and / or lips, specifically intended to stimulate the regeneration of basal cells of the epidermis, particularly of the skin and / or lips. DESCRIPTION OF THE FIGURES

[0016] [Fig. 1] represents a graph showing the intensity of nuclear yH2AX labeling by cell number after UVB treatment under different conditions. PCR5 = Norwegian Honey 0.09% + Connemara Honey 0.09% + Ouessant Honey 0.009% + Royal Jelly 0.0036%; PCR5 at Uz = Norwegian Honey 0.045% + Connemara Honey 0.045% + Ouessant Honey 0.0045% + Royal Jelly 0.0018%. DETAILED DESCRIPTION OF THE INVENTION

[0017] A first object of the invention relates to a cosmetic composition comprising: a) at least two honeys chosen from the group consisting of Norwegian honey, Irish Connemara honey and Ouessant honey; and b) optionally royal jelly.

[0018] In a particular embodiment, the cosmetic composition according to the invention comprises: a) at least two honeys selected from the group consisting of Norwegian honey, Irish Connemara honey and Ouessant honey; and b) royal jelly.

[0019] In a particular embodiment, the cosmetic composition according to the invention comprises: a) Norwegian honey, Connemara Irish honey and optionally Ouessant honey; and b) optionally royal jelly.

[0020] In a particular embodiment, the cosmetic composition according to the invention comprises: a) Norwegian honey, Connemara Irish honey and optionally Ouessant honey; and b) royal jelly.

[0021] In a particular embodiment, the cosmetic composition according to the invention comprises: a) Norwegian honey, Ouessant honey and optionally Connemara Irish honey; and b) optionally royal jelly.

[0022] In a particular embodiment, the cosmetic composition according to the invention comprises: a) Norwegian honey, Ouessant honey and optionally Connemara Irish honey; and b) royal jelly.

[0023] In a particular embodiment, the cosmetic composition according to the invention comprises: a) Irish Connemara honey, Ouessant honey and optionally Norwegian honey; and b) optionally royal jelly.

[0024] In a particular embodiment, the cosmetic composition according to the invention comprises: a) Connemara Irish honey, Ouessant honey and optionally Norwegian honey; and b) royal jelly.

[0025] In a preferred embodiment, the cosmetic composition according to the invention comprises: a) Norwegian honey, Connemara Irish honey and Ouessant honey; and b) optionally royal jelly.

[0026] In a particularly preferred embodiment, the cosmetic composition according to the invention comprises: a) Norwegian honey, Connemara Irish honey and Ouessant honey; and b) royal jelly. Honey

[0027] Honey is one of the products derived from beekeeping, along with royal jelly, propolis, pollen, and beeswax. However, these products are distinct from one another, both in their method of production and / or harvesting within the hive and in their composition and properties.

[0028] Honey and pollen are substances that constitute the bees' diet throughout the year, the former providing sugars, the latter proteins. Honey and pollen can be stored for long periods in the hive.

[0029] Honey is produced by foraging bees, which collect nectar from flowers and process it through successive digestions and regurgitations. The acidic pH of the bees' stomachs, along with the enzymatic activities of invertase, diastase, and amylase, results in a supersaturated aqueous solution composed of more than 80% sugars, primarily fructose (approximately 38%) and glucose (approximately 31%), with smaller amounts of sucrose, maltose, and other complex sugars. Honey is also low in fats, fiber, and proteins. Depending on the bee variety and the environment in which they live, different honeys can exhibit considerable variability.

[0030] There are thus different types of honey, distinguished according to the type of flower or its geographical area of ​​origin, each with a characteristic flavor and appearance. Nectar honey is made by bees from the nectar of the flowers they forage, and monofloral honey is defined as honey that comes largely from a single variety of flower, while other honeys are classified as multifloral. Norwegian Honey

[0031] The "Norwegian honey" or "Norwegian Kjartans honey" used in the context of the invention is a honey originating in Norway produced by the black bee (Apis mellifera mellifera) in a preserved and wild environment surrounded by natural parks.

[0032] The Norwegian honey used in the context of the invention exhibits a high degree of molecular diversity, including, for example, terpenes and vitamin derivatives, as well as a similar proportion of polyphenols and organic acids.

[0033] Physicochemical analyses of this honey have thus shown that, in addition to sugars, it comprised, in a particular way: - between 20% and 25% fatty acids and derivatives; - between 8% and 12% of terpenes and terpenoids; - between 30% and 35% polyphenols, - between 29% and 33% organic acids; and - between 1% and 5% vitamins and derivatives.

[0034] In a preferred embodiment, Norwegian honey, when present in the cosmetic composition according to the invention, is present in a content ranging from 0.0001% to 5%, preferably from 0.001% to 1%, more preferably from 0.01% to 0.1% by weight relative to the total weight of the composition. Connemara Irish Honey

[0035] The "Irish Connemara honey" or "Irish honey" used in the context of the invention is a honey originating from the Connemara region of Ireland produced by the black bee (Apis mellifera mellifera) in a preserved and wild environment.

[0036] The Connemara Irish honey used in the context of the invention has a wide variety of fatty acids and polyphenols.

[0037] Physicochemical analyses of this honey have thus shown that, in addition to sugars, it comprised, in a particular way: - between 25% and 35% fatty acids and derivatives; - between 40% and 45% polyphenols; and - between 20% and 25% organic acids.

[0038] In a preferred embodiment, Irish Connemara honey, when present in the composition, is present in a content ranging from 0.0001% to 5%, preferably from 0.001% to 1%, preferably still from 0.01% to 0.1% by weight relative to the total weight of the composition. Ouessant Honey

[0039] The "Ouessant honey" or "Ouessant black bee honey" used in the context of the invention is a honey originating from the island of Ouessant, which is made by the Ouessant black bee, or black bee endemic to the island.

[0040] The Ouessant black bee is a pure breed of a local ecotype of the Western European Black Bee (Apis mellifera mellifera). The island of Ouessant, a protected ecosystem listed by UNESCO, offers the bees a rare and preserved environment, composed in particular of brambles and heather. Ouessant honey is brown and contains amino acids, collagen activators, calcium, magnesium, and trace elements beneficial to the skin.

[0041] Physicochemical analyses of this honey have thus shown that, in addition to sugars, it contained, in a particular way: - between 80% and 90% polyphenols; - between 1% and 5% minerals; and - between 10% and 15% amino acids.

[0042] In a preferred embodiment, Ouessant honey, when present in the composition, is present in a content ranging from 0.00001% to 0.5%, preferably from 0.0001% to 0.1%, preferably still from 0.001% to 0.01% by weight relative to the total weight of the composition. Royal jelly

[0043] Royal jelly is another product derived from beekeeping.

[0044] While honey is produced by foraging bees, it is the worker bees that produce royal jelly from pollen and nectar collected by the bees from flowers. Royal jelly results from the secretion of their mandibular and hypopharyngeal salivary glands. Worker bees are a category of bees that perform multiple tasks essential to the maintenance and survival of the colony, with the queen and drones ensuring the colony's reproduction.

[0045] Royal jelly constitutes the food of all larvae in the hive, without exception, during the first three days of their lives, and the exclusive food of the queen throughout her entire life. Due to its very complete composition, royal jelly provides all the nutrients necessary for the growth of the larvae and the queen's well-being: a large quantity of water (between 60 and 70%), sugars (between 9 and 23%), proteins (between 10 and 18%), a large proportion of which are amino acids, and lipids (between 4 and 8%). It is in the form of an acidic, gelatinous, white-yellow colloid and contains a specific fatty acid: 10-HDA (10-hydroxy-2-decenoic acid), identified as responsible for an important activity related to colony development strategies.

[0046] Royal jelly exhibits great variability depending on the variety of bees and the environment in which they live.

[0047] The royal jelly used in the context of the invention can be any type of royal jelly, produced by any variety of bee of the species Apis mellifera.

[0048] In a preferred embodiment, royal jelly, when present in the composition, is present in a content ranging from 0.0001% to 0.5%, preferably from 0.0001% to 0.1%, more preferably from 0.0010% to 0.01% by weight relative to the total weight of the composition. Use

[0049] Another object of the invention relates to the cosmetic use of an association comprising; a) at least two honeys chosen from the group consisting of Norwegian honey, Irish Connemara honey, and Ouessant honey; and b) possibly royal jelly; for topical application on keratinous materials, in particular the skin and / or lips, as a cosmetic active ingredient intended to promote and / or stimulate skin renewal and / or regeneration, in particular of the skin and / or lips, in particular intended to stimulate the regeneration of basal cells of the epidermis, in particular of the skin and / or lips.

[0050] In a particular embodiment, the association according to the invention comprises: a) at least two honeys selected from the group consisting of Norwegian honey, Irish Connemara honey and Ouessant honey; and b) royal jelly.

[0051] In a particular embodiment, the association according to the invention comprises: a) Norwegian honey, Connemara Irish honey and optionally Ouessant honey; and b) optionally royal jelly.

[0052] In a particular embodiment, the association according to the invention comprises: a) Norwegian honey, Irish Connemara honey and optionally Ouessant honey; and b) royal jelly.

[0053] In a particular embodiment, the association according to the invention comprises: a) Norwegian honey, Ouessant honey and optionally Connemara Irish honey; and b) optionally royal jelly.

[0054] In a particular embodiment, the association according to the invention comprises: a) Norwegian honey, Ouessant honey and optionally Connemara Irish honey; and b) royal jelly.

[0055] In a particular embodiment, the association according to the invention comprises: a) Connemara Irish honey, Ouessant honey and optionally Norwegian honey; and b) optionally royal jelly.

[0056] In a particular embodiment, the association according to the invention comprises: a) Connemara Irish honey, Ouessant honey and optionally Norwegian honey; and b) royal jelly.

[0057] In a preferred embodiment, the combination according to the invention comprises: a) Norwegian honey, Connemara Irish honey and Ouessant honey; and b) optionally royal jelly.

[0058] In a particularly preferred embodiment, the combination according to the invention comprises: a) Norwegian honey, Connemara Irish honey and Ouessant honey; and b) royal jelly.

[0059] In a particular embodiment, the association according to the invention is used in the form of a cosmetic composition as defined above. cosmetic process

[0060] Another object of the invention relates to a cosmetic process for the care and / or makeup of keratinous materials, intended in particular to promote and / or stimulate the renewal and / or regeneration of skin, in particular of the skin and / or lips, in particular intended to stimulate the regeneration of basal cells of the epidermis, in particular of the skin and / or lips, comprising the topical application on keratinous materials, in particular the skin and / or lips, of a cosmetic composition according to the invention.

[0061] By "promoting and / or stimulating skin renewal and / or regeneration" according to the invention, it is understood in particular that the combination of honeys and possibly royal jelly described above is intended to promote the renewal and development of skin cells and tissues, particularly of the skin and / or lips. In particular, this refers to epidermal renewal.

[0062] By "basal cells of the epidermis", we mean here the cells of the basal layers of the epidermis which ensure the formation and renewal of the cells of the epidermis, and are themselves derived from the division of "epidermal stem cells".

[0063] The inventors have shown in particular that the combination of honeys and possibly royal jelly described above makes it possible to reduce the effect of environmental stress on primary keratinocytes, confirming its ability to promote the regeneration of basal cells of the epidermis.

[0064] In a preferred embodiment, the composition is applied to fragile, stressed and / or aged skin and / or lips, in particular skin subjected to certain environmental factors (oxidative stress, irritant stress...).

[0065] By "fragile skin" we mean here skin that is more receptive to external aggressions than non-fragile skin.

[0066] By "aged skin" we mean here skin showing signs of aging, such as wrinkles and fine lines.

[0067] By "stressed skin" we mean here skin subjected to stresses of endogenous or exogenous origin.

[0068] By "skin subjected to an environmental factor", we mean that the skin is subjected to stress of exogenous origin, for example emotional or chemical stress, likely to induce unsightly non-pathological skin reactions, the skin is more sensitive to stimuli, the complexion is dull, the skin is visibly tired.

[0069] Advantageously, the compositions used in the context of the cosmetic use and / or the cosmetic process of the invention are those described below. Compositions and galenics

[0070] In a preferred embodiment, the cosmetic composition according to the invention is a care and / or makeup composition for keratinous materials, in particular for the skin and / or lips and especially for the skin of the face and / or neck.

[0071] The cosmetic composition of the invention generally comprises, in addition to the combination of honeys and possibly royal jelly described above, one or more acceptable cosmetic excipients from among those known to the person skilled in the art in order to obtain a composition for topical application for example in the form of a milk, cream, ointment, water-in-oil or oil-in-water emulsion, balm, stick, gel, lotion, serum, oil, or powder.

[0072] The cosmetic composition of the invention may also be in the form of a patch or a mask, in particular a mask in the form of a thick cream, or in the form of a cellulose mask soaked in the combination of honeys and royal jelly, or a composition containing it.

[0073] In a preferred embodiment, said composition is in the form of an emulsion, lotion, gel, cream, oil, milk, serum, balm, stick or powder.

[0074] The cosmetic composition of the invention may be in any galenic form suitable for topical application on keratinous materials in particular of the skin and / or lips and especially of the skin of the face and / or neck, and may further comprise at least one cosmetic ingredient chosen from antioxidants, perfumes, vitamins, thickening agents, emollients, moisturizing agents, anti-aging agents, lifting agents, tightening agents, plumping agents, soothing agents, anti-pollution agents, brightening or depigmenting agents, fillers, mother-of-pearl and mixtures thereof.

[0075] In a preferred embodiment, the cosmetic composition according to the invention comprises: - Norwegian honey in a content ranging from 0.0001% to 5%, preferably from 0.001% to 1%, preferably even more from 0.01% to 0.1% by weight relative to the total weight of the composition, - Connemara honey from Ireland in a content ranging from 0.0001% to 5%, preferably from 0.001% to 1%, preferably even more from 0.01% to 0.1% by weight relative to the total weight of the composition, and - Royal jelly in a content ranging from 0% to 0.5%, preferably from 0.0001% to 0.1%, preferably still from 0.0010% to 0.01% by weight relative to the total weight of the composition.

[0076] In another preferred embodiment, the cosmetic composition according to the invention comprises: - Norwegian honey in a content ranging from 0.0001% to 5%, preferably from 0.001% to 1%, preferably even more from 0.01% to 0.1% by weight relative to the total weight of the composition, - Ouessant honey in a content ranging from 0.00001% to 0.5%, preferably from 0.0001% to 0.1%, preferably even more from 0.001% to 0.01% by weight relative to the total weight of the composition, and - Royal jelly in a content ranging from 0% to 0.5%, preferably from 0.0001% to 0.1%, preferably still from 0.0010% to 0.01% by weight relative to the total weight of the composition.

[0077] In another preferred embodiment, the cosmetic composition according to the invention comprises: - Connemara honey from Ireland in a content ranging from 0.0001% to 5%, preferably from 0.001% to 1%, preferably even more from 0.01% to 0.1% by weight relative to the total weight of the composition, - Ouessant honey in a content ranging from 0.00001% to 0.5%, preferably from 0.0001% to 0.1%, preferably even more from 0.001% to 0.01% by weight relative to the total weight of the composition, and - Royal jelly in a content ranging from 0% to 0.5%, preferably from 0.0001% to 0.1%, preferably still from 0.0010% to 0.01% by weight relative to the total weight of the composition.

[0078] In another preferred embodiment, the cosmetic composition according to the invention comprises: - Norwegian honey in a content ranging from 0.0001% to 5%, preferably from 0.001% to 1%, preferably even more from 0.01% to 0.1% by weight relative to the total weight of the composition, - Connemara honey from Ireland in a content ranging from 0.0001% to 5%, preferably from 0.001% to 1%, preferably even more from 0.01% to 0.1% by weight relative to the total weight of the composition, - Ouessant honey in a content ranging from 0.00001% to 0.5%, preferably from 0.0001% to 0.1%, preferably even more from 0.001% to 0.01% by weight relative to the total weight of the composition, and - Royal jelly in a content ranging from 0% to 0.5%, preferably from 0.0001% to 0.1%, preferably still from 0.0010% to 0.01% by weight relative to the total weight of the composition.

[0079] Thus, in the cosmetic composition according to the invention, preferably - Norwegian honey, when present in the composition, is present in a content ranging from 0.0001% to 5%, preferably from 0.001% to 1%, preferably still from 0.01% to 0.1% by weight relative to the total weight of the composition, - Irish Connemara honey, when present in the composition, is present in a content ranging from 0.0001% to 5%, preferably from 0.001% to 1%, preferably still from 0.01% to 0.1% by weight relative to the total weight of the composition, - Ouessant honey, when present in the composition, is present in a content ranging from 0.00001% to 0.5%, preferably from 0.0001% to 0.1%, preferably even more from 0.001% to 0.01% by weight relative to the total weight of the composition, and / or - Royal jelly, when present in the composition, is present in a content ranging from 0% to 0.5%, preferably from 0.0001% to 0.1%, preferably still from 0.0010% to 0.01% by weight relative to the total weight of the composition.

[0080] In a particularly preferred embodiment, in the cosmetic composition according to the invention: - Norwegian honey is present in the composition at a level ranging from 0.01% to 0.1% by weight relative to the total weight of the composition, - Connemara honey from Ireland is present in the composition at a level ranging from 0.01% to 0.1% by weight relative to the total weight of the composition, - Ouessant honey is present in the composition at a level ranging from 0.001% to 0.01% by weight relative to the total weight of the composition, and - Royal jelly is present in the composition at a content ranging from 0.0010% to 0.01% by weight relative to the total weight of the composition.

[0081] Depending on the nature of the composition, one or more cosmetically acceptable excipients will be selected from among polymers, surfactants, rheology agents, perfumes, electrolytes, pH adjusters, antioxidants, preservatives, colorants, mother-of-pearl, pigments and mixtures thereof.

[0082] By "cosmetically acceptable" is meant that the composition is suitable for topical use, in contact with the skin and / or lips of mammals and more particularly human skin and / or lips.

[0083] The aqueous phase generally represents from 1 to 99% by weight, relative to the total weight of said composition. Aqueous phase

[0084] The aqueous phase of the composition according to the invention comprises water and optionally a water-soluble solvent.

[0085] The term "water-soluble solvent" according to the invention means a compound that is liquid at room temperature and miscible with water (miscibility in water greater than 50% by weight at 25 °C and atmospheric pressure). Examples include: - lower C1-C5 monoalcohols such as ethanol, isopropanol and their mixtures; - C2-C8 glycols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, dipropylene glycol, and their mixtures; - C2-C32 polyols such as polyglycerols, polyethylene glycols, and their mixtures, - and their mixtures.

[0086] It may also include hydrophilic gelling agents, antioxidants, preservatives and mixtures thereof.

[0087] By way of “hydrophilic gelling agents”, one may mention in particular acrylic acid polymers such as those of INCI name Carbomer or commercial reference Carbopol®, copolymers of acrylic and methacrylic acids, carboxyvinyl polymers, associative thickeners of the acrylic or polyurethane type, polysaccharide gelling agents such as alginates, natural or modified gums such as xanthan gum, carrageenan gum, agar gum, guar gum, gellan gum, chitosans, mannans, pullulans, cellulose derivatives, gelatin, pectins, mineral gelling agents such as bentones or modified silicas, and mixtures thereof.

[0088] The term "natural or modified gum" refers to a polysaccharide, possibly modified, that hydrates in an aqueous medium to form a viscous solution or dispersion. Natural gums include seaweed extracts, plant exudates, gums extracted from plant seeds or roots, and those obtained by microbiological fermentation. Modified or semi-synthetic gums include derivatives of cellulose and starch and, generally, derivatives of all natural gums.

[0089] The content of hydrophilic gelling agent(s) in the cosmetic composition of the invention will generally range from 0.01% to 5%, in particular from 0.1% to 4%, preferably from 0.2% to 3% and even more preferably from 0.5% to 2% by weight relative to the total weight of said composition. Additional ingredients

[0090] The composition according to the invention may also include any additive commonly used in cosmetics such as antioxidants, perfumes, vitamins, thickening agents, emollients, moisturizing agents, anti-aging agents, lifting agents, tightening agents, plumping agents, soothing agents, anti-pollution agents, brightening or depigmenting agents, fillers, mother-of-pearl and mixtures thereof.

[0091] The additional ingredients advantageously used in the composition of the invention can be present in a content ranging from 0.0001% to 50%, preferably from 0.001% to 10% by weight (of raw material) relative to the total weight of the composition.

[0092] The present invention will now be illustrated in the following non-limiting examples. Unless otherwise indicated, percentages are expressed as a percentage of the weight of raw material relative to the total weight of the composition. EXAMPLES Example 1

[0093] In this example, the inventors evaluated the protective efficacy of a combination of honeys, and possibly royal jelly, on the nuclear expression of yH2AX in an in vitro model of cultured keratinocytes.

[0094] The phosphorylated form of histone H2AX on serine 139, called yH2AX, is detectable within the first minute following ionizing radiation that induces DNA double-strand breaks (simulating external stress) in a cultured cell population. Its appearance and disappearance kinetics follow those of DNA double-strand breaks in a dose-dependent manner, making yH2AX a good marker of double-strand breaks (Rogakou et al. (1998) J Biol Chem 273(10):5858-68). Materials and Methods Preparation of the tested active ingredients

[0095] • Compounds tested:

[0096] 1 - Royal Jelly (Pyrenean Royal Jelly Common) at 0.0036% 2 - Honey from Norway (COMMUNELLE MIELS NORVEGE KJARTANS) at 0.09% 3 - Honey from Ireland Connemara (CONNERMARA HONEY - MARTIN CURRAN) at 0.09% 4 - Ouessant Honey (Breton Black Bee Conservation Association) at 0.0045% • Associations tested:

[0097] A - Association Norwegian Honey 0.09% + Connemara Honey 0.09% B - Norwegian Honey 0.09% + Connemara Honey 0.09% + Ouessant Honey 0.009% C - Norwegian Honey 0.09% + Connemara Honey 0.09% + Ouessant Honey 0.009% + Royal Jelly 0.0036% = PCR5 D - Norwegian Honey 0.045% + Connemara Honey 0.045% + Ouessant Honey 0.0045% + Royal Jelly 0.0018% = PCR5 Dose 1 / 2 • Preparation of Royal Jelly

[0098] Preparation of a 10% solution: 110 mg of Royal Jelly is weighed and dissolved in 1100 pL of culture medium. Preparation of 5 mL of 1% solution: 500 pL of 10% Royal Jelly solution is mixed with 4.5 mL of culture medium, then sterilized by filtration (diameter = 0.22 pm). • Preparation of Norwegian Honey

[0099] Preparation of a 10% solution: 104.5 mg of Norwegian Honey is weighed and dissolved in 1045 pL of culture medium. Preparation of 5 mL of 1% solution: 500 pL of 10% Norwegian Honey solution is mixed with 4.5 mL of culture medium, then sterilized by filtration (diameter = 0.22 pm). • Preparation of Connemara Irish Honey

[0100] Preparation of a 10% solution: 112.5 mg of Connemara Irish Honey is weighed and dissolved in 1125 pL of culture medium. Preparation of 5 mL of 1% solution: 500 pL of 10% Connemara Irish Honey solution is mixed with 4.5 mL of culture medium, then sterilized by filtration (diameter = 0.22 pm). • Preparation of Ouessant Honey

[0101] Preparation of a 10% solution: 116 mg of Ouessant Honey is weighed and dissolved in 1160 pL of culture medium. Preparation of 5m L of 1% solution: 500 pL of 10% Ouessant Honey solution is mixed with 4.5 mL of culture medium, then sterilized by filtration (diameter = 0.22 pm). Preparation for 10 ml of each treatment

[0102] [Tables 1] Active (e npL) Treatment MN 0.09% MC 0.09% MO 0.009% GR 0.0036% MN 0.09% MC 0.09% MN 0.09% MC 0.09% MO 0.009% MN 0.09% MC 0.09% MO 0.009% GR 0.0036 % MN 0.045% MC 0.045% MO 0.0045% GR 0.0018% MN 1% 900 900 900 900 450 MC 1% 900 900 900 900 450 MO 1% 90 90 90 45 GR 1% 36 36 18 Qsp 10 mL (middle Epi life™ complete) 9100 9100 9910 9964 8200 8110 8074 9037

[0103] MN: Norwegian Honey

[0104] MC: Connemara Irish Honey

[0105] MO: Ouessant Honey

[0106] GR: Royal Jelly Cell culture and processing

[0107] The study was carried out on Normal Human Keratinocytes (NHK) from an abdominoplasty of a 47-year-old Caucasian woman.

[0108] KHN were seeded in passage 4 in TPP75 flasks in supplemented Epilife™ medium.

[0109] KHN cells were trypsinized pre-confluence (0.05% Trypsin-EDTA, GIBCO-Invitrogen, 25300) and neutralized with serum-containing medium. They were then seeded at passage 5 into 24-well p-plates (ibiTreat, Ibidi) at a density of 35,000 cells per well. This cell density was specifically studied to highlight the expression of the yH2AX marker in the cell nuclei of this culture of normal human keratinocytes rich in proliferative cells corresponding to the cells present in the basal layer of the epidermis.

[0110] After 24 hours of culture, the keratinocyte culture medium was changed to promote consistent cell proliferation. After another 24 hours, the cells were treated with the active ingredients prepared in complete Epilife™ medium. For the untreated (NT) control condition, the medium was replaced with fresh medium. After 24 hours of treatment, the cells were subjected to UVB stress (25 mJ / cm²) in PSB and then retreated with the active ingredients for 4 hours. After 4 hours, the cells were fixed for preparation for immunolabeling. This UVB dose was predetermined and specifically designed for optimal expression of the yH2AX marker. Immunostaining

[0111] The cells were rinsed twice with PBS (PBS Tablets, Invitrogen GIBCO), then fixed with formalin (Formalin Solution 10% Neutral Buffered, Sigma) for 10 min. After two rinses with PBS, the cell membranes were permeabilized with a 0.1% PBS / Triton solution (Triton X-100, Sigma). They were then rinsed twice more with PBS.

[0112] The cells were coated with a 1% PBS / BSA solution (Albumin, from bovine serum, Sigma) for 30 min at room temperature. The PBS / BSA solution was then replaced with a primary antibody solution corresponding to the labeled protein diluted in 1% PBS / BSA.

[0113] The plates were incubated overnight at 4°C. The cells were then rinsed three times with PBS and coated with a secondary antibody solution according to the primary antibody to be targeted (see Table 2) and DAPI at 1 / 500th (4',6'-diamidino-2- Phenylindole dihydrochloride and Invitrogen Molecular Probes were diluted in 1% PBS / BSA. The plates were stored for one hour in the dark at room temperature. The secondary antibody solution was then aspirated, and the cells were rinsed twice with PBS and once with distilled water. The cells were then coated with PBS. The plates were stored at 4°C in the dark until image acquisition.

[0114] [Tables2] Target name yH2A.X (Phospho S139) Primary antibody reference 05-636 (Merck Millipore) Primary antibody batch 2739172 Species Mouse Primary antibody dilution 1 / 1000 Permeabilization + Secondary antibody Goat anti-Mouse 568 (Molecular Probes) Secondary antibody reference Al 1004 Secondary antibody dilution 1 / 500 Image acquisition by HCS

[0115] The plates were scanned using the Thermo Cellomics ArrayScan XTi.

[0116] Acquisition conditions: Detection: DAPI: filter XF53_386_23 Alexa Fluor 568: filter XF53_572_15 Resolution: 1104x1104 Objective: 20x dry Number of images: 100 per well (i.e., 4 x 100 = 400 per condition) Image analysis

[0117] The images were then analyzed using Spot Detector image analysis software, a bio-application developed for the ArrayScan system. This program detects the red labeling of the target protein, corresponding to its expression. The measurement area was defined as the entire nucleus of each cell. The number of cells was determined by counting the nuclei using the blue labeling detection method. The results were transferred to a Microsoft Excel file. Statistical analysis

[0118] The statistical analysis of the results was performed using Microsoft Excel software. This analysis consists of calculating the mean, standard deviation, and interval of confidence (a = 0.05) of the ratio of nucleus labeling intensity to the total number of cells per field.

[0119] The significance of the differences in these ratios observed between the control and treatment groups was measured using Student's t-test. Note: Student's t-test is considered significant if its value is less than 0.05. Results

[0120] Fig. 1 shows the expression of the yH2AX marker, quantified by measuring the total intensity of nuclear labeling per cell, under the different conditions tested.

[0121] The results obtained are also presented in Table 3 below.

[0122] [Tables3] Variation in the expression of the marker yH 2AX Treatment MN 0.09% MC 0.09% MO 0.009% GR 0.0036% MN 0.09% MC 0.09% MN 0.09% MC 0.09% MO 0.009% MN 0.09% MC 0.09% MO 0.009% GR 0.0036% MN 0.045% MC 0.045% MO 0.0045% GR 0.0018% vs NT+UV B +3% -14% +11% +8% -21% ** -41%*** -38%*** -42%*** vs MN -23%* -42%*** -40%** 44%*** vs MC -9% -31%* -28% -33%* vs MO -46%*** 44%*** -48%*** vs GR -43%*** -46%***

[0123] NT: untreated; MN: Norwegian Honey; MC: Connemara Irish Honey; MO: Ouessant Honey; GR: Royal Jelly; Student's t-test: ***: p < 0.001; **: p < 0.01; *: p < 0.05.

[0124] We observe in [Fig.1] that the application of UVB stress on keratinocytes, under these culture conditions, is indeed capable of inducing a very significant increase in the nuclear expression of yH2AX (+123%).

[0125] Furthermore, Norwegian honey, Connemara Irish honey, Ouessant honey and royal jelly, used alone, do not have protective activity on the expression of this marker.

[0126] On the other hand, as soon as these ingredients are used in combination with at least two honeys, a decrease in the expression of the marker is observed.

[0127] Particularly advantageously, the combination of the three honeys makes it possible to obtain a significant reduction in the marker (-41%).

[0128] When royal jelly is added to these honeys, a further synergy is observed in the reduction of the marker, since a level of reduction similar to that obtained with the combination of the 3 honeys is observed (-42%) but with half less of each ingredient.

[0129] These results therefore show that an association of at least two honeys chosen from the group consisting of Norwegian honey, Irish Connemara honey and Ouessant honey, and possibly royal jelly, makes it possible to improve or promote skin renewal and / or regeneration, in particular by mitigating the effect of environmental stress on the basal cells of the epidermis. Example 2#: Cosmetic formulations

[0130] 2.1. Composition in the form of an oily-textured composition

[0131] [Tables4] Ingredients % by weight Glycerin 35% Glycols 5% Polyglycerin 2.5% Biosaccharide Gums 0.05% Alcohol 2% Polyglyceryl-10 stearate / Polyglyceryl-10 oleate 1.3% Polyacrylate crosspolymer-6 0.15% Norwegian Honey 0.1% Connemara Honey 0.1% Ouessant Honey 0.01% Royal Jelly 0.004% Perfume, neutralizer, preservative qs Purified water qsp 100%

[0132] The composition was prepared according to the following procedure:

[0133] 1 / Heat the water and the preservative to 65°C. 2 / Using a Rayneri, disperse the Polyacrylate crosspolymer-6 and the Biosaccharide Gums under vigorous stirring for 15 min. 3 / Add the glycols and the rest of the formula until perfectly homogenized under moderate stirring. 4 / Mix the fragrance thoroughly with the Polyglyceryl-10 stearate / Polyglyceryl-10 oleate. Add this phase to the formula. 5 / Using an ultra-turrax, disperse the Royal Jelly in water until completely dispersed. Add this phase to the formula containing the other honeys. 6 / Leave to shake under moderate agitation for 10 min.

[0134] When applied to the skin of the face, the composition of the invention improves or promotes skin renewal and / or regeneration, in particular by mitigating the effect of environmental stress on the basal cells of the epidermis.

[0135] 2.2. Composition in the form of a serum

[0136] [Tables5] Ingredients % by weight: Cetearyl isononate 7.0000, Steareth-2 0.5000, Steareth-21 0.5000, Jojoba esters 1.5000, Butylene glycol 1.0000, Glycerin 6.0000, Sodium hyaluronate 0.0500, Acrylates / C10-30 alkyl acrylate crosspolymer 0.2500, Xanthan gum 0.1000, Citric acid 0.0200, Trisodium citrate 0.1400, Polymethyl methacrylate 1.8000, Norwegian honey 0.9000, Ouessant honey 0.1000, Royal jelly 0.1000, Tocopheryl acetate 0.2000, Fragrance, neutralizer, preservative qs, Purified water qsp 100%

[0137] The serum is applied to the entire face and in particular to areas where the skin appears stressed.

[0138] In addition to its pleasant texture upon application, it has a remarkable regenerative effect, in particular mitigating the effect of environmental stress on the basal cells of the epidermis.

[0139] 2.3. Composition in the form of a lip balm

[0140] [Tableauxô] Ingredients % by weight: Silica 10%, Nylon powder 7%, Polyethylene wax 17%, Glycerin 14%, Norwegian honey 0.05%, Connemara Irish honey 0.05%, Isopropyl myristate q.s. 100%

[0141] When applied to the lips, this balm improves or promotes skin renewal and / or regeneration, in particular by mitigating the effect of environmental stress on the basal cells of the epidermis. REFERENCES

[0142] • Rogakou et al. (1998) J Biol Chem 273(10):5858-68. • Siddiqui et al. (2015) Mutat Res Rev Mutat Res 766:1-19. • Suryadevara et al. (2024) Nat Rev Mol Cell Biol; doi:10.1038 / s41580-024-00738-8.

Claims

Demands

1. Cosmetic composition comprising at least two honeys selected from the group consisting of Norwegian honey, Irish Connemara honey and Ouessant honey.

2. Cosmetic composition according to claim 1, comprising Norwegian honey, Irish Connemara honey and optionally Ouessant honey; preferably Norwegian honey, Irish Connemara honey and Ouessant honey.

3. Cosmetic composition according to claim 1 or 2, characterized in that it further comprises royal jelly.

4. Cosmetic composition according to claim 3, comprising: a) Norwegian honey, Irish Connemara honey and Ouessant honey; and b) royal jelly.

5. A cosmetic composition according to any one of claims 1 to 4, wherein: - Norwegian honey, when present in the composition, is present in a concentration of 0.0001% to 5%, preferably 0.001% to 1%, preferably a further 0.01% to 0.1% by weight relative to the total weight of the composition, - Irish Connemara honey, when present in the composition, is present in a concentration of 0.0001% to 5%, preferably 0.001% to 1%, preferably a further 0.01% to 0.1% by weight relative to the total weight of the composition, and / or - Ouessant honey, when present in the composition, is present in a concentration of 0.00001% to 0.5%, preferably 0.0001% to 0.1%, preferably even 0.001% to 0.01% by weight relative to the total weight of the composition.

6. A cosmetic composition according to claim 3 or claim 4, wherein: - Norwegian honey is present in the composition in a content ranging from 0.01% to 0.1% by weight relative to the total weight of the composition, - Irish Connemara honey is present in the composition in a content ranging from 0.01% to 0.1% by weight relative to the total weight of the composition, - Ouessant honey is present in the composition at a level ranging from 0.001% to 0.01% by weight relative to the total weight of the composition, and / or - royal jelly is present in the composition at a level ranging from 0.0010% to 0.01% by weight relative to the total weight of the composition.

7. Cosmetic composition according to any one of claims 1 to 6, further comprising at least one cosmetic ingredient selected from antioxidants, perfumes, vitamins, thickening agents, emollients, moisturizing agents, anti-aging agents, lifting agents, tightening agents, plumping agents, soothing agents, anti-pollution agents, brightening or depigmenting agents, fillers, mother-of-pearl and mixtures thereof.

8. A cosmetic process for the care and / or makeup of keratinous materials, intended in particular to promote and / or stimulate skin renewal and / or regeneration, in particular of the skin and / or lips, in particular intended to stimulate the regeneration of basal cells of the epidermis, in particular of the skin and / or lips, comprising the topical application on keratinous materials, in particular the skin and / or lips, of a cosmetic composition as defined in any one of claims 1 to 7.

9. A cosmetic process according to claim 8, wherein the composition is in the form of an emulsion, lotion, gel, cream, oil, milk, serum, balm, stick or powder.

10. Cosmetic process according to claim 8 or claim 9, wherein the composition is applied to fragile, stressed and / or aged skin and / or lips, in particular skin subjected to certain environmental factors (oxidative stress, irritant stress...).

11. Cosmetic use of a combination comprising: a) at least two honeys selected from the group consisting of Norwegian honey, Irish Connemara honey, and Ouessant honey; and b) optionally royal jelly; for topical application to keratinous materials, in particular the skin and / or lips, as a cosmetic active ingredient intended to promote and / or stimulate skin renewal and / or regeneration, in particular of the skin and / or lips, in particular

12. intended to stimulate the regeneration of basal cells of the epidermis, particularly of the skin and / or lips. Cosmetic use according to claim 11, wherein the combination is intended for fragile, stressed and / or aged skin and / or lips, in particular skin subjected to certain environmental factors (oxidative stress, irritant stress...).

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