Melaleuca alternifolia extract and its cosmetic uses

Abstract

The present invention relates to the cosmetic field. In particular, the present invention relates to a specific oily extract of Melaleuca alternifolia, a cosmetic composition comprising it, and its use as a cosmetic agent for regenerating, repairing, or anti-fatigue of healthy skin.

Description

Title of the invention: Extract of Melaleuca alternifolia and its cosmetic uses technical field

[0001] The present invention relates to the cosmetic field, in particular to cosmetic agents to combat the effects of fatigue on the skin. TECHNOLOGICAL BACKGROUND

[0002] The skin is the first barrier protecting the body from external aggressions. This organ is composed of several layers of tissue. We distinguish the epidermis, which is the outermost part of the skin, the dermis, a connective tissue made up of fibroblasts and an extracellular matrix, which ensures the cohesion and nutrition of the skin, and the hypodermis made up of adipocytes.

[0003] The epidermis is made up of several cellular layers of keratinocytes. Among others, we distinguish the germinative layer of the epidermis, called the basal layer, containing, in particular, the cutaneous stem cells, the spinous layer, Stratum spinosum, made up of several layers of polygonal cells, the granular layer, Stratum granulosum, comprising one to three layers of flattened cells containing cytoplasmic inclusions, the keratohyalin granules, and finally, the stratum corneum, Stratum corneum which is composed of anucleate cells rich in keratin called corneocytes which correspond to the terminal stage of keratinocyte differentiation.

[0004] The outermost cells of the stratum corneum are continually shed and replaced by cells from a lower layer, according to a process called desquamation. Cellular regeneration of the stratum corneum is based on a process of cell maturation in which cells of the basal layer of the epidermis differentiate and gradually migrate through the different strata of the epidermis until they reach the stratum corneum in the form of corneocytes.

[0005] The skin is generally the first to show signs of fatigue. Fatigue can be caused by many factors, such as lack of sleep, poor or unbalanced diet, overwork, intense or inappropriate work activity, or disruptions in the family sphere. Women juggling family life and work, and young working adults in urban areas are particularly susceptible to chronic fatigue.

[0006] Individuals exposed to such fatigue may exhibit drawn features, a loss of radiance in their complexion or even a dull complexion, dark circles and bags under the eyes. In other words, their face appears tired and marked, even unhealthy. Now, sending back The image of a fit person can be a major concern for active working individuals, especially in a competitive environment and / or in contact with customers.

[0007] Nevertheless, there remains, at present, a need for new cosmetic active ingredients to prevent or treat the visible effects of fatigue on the skin. Summary of the invention

[0008] The invention relates to the cosmetic use of an oily extract of Melaleuca altemifolia, as a cosmetic agent for regenerating, repairing or anti-fatigue of healthy skin, wherein said extract comprises:

[0009] - more than 20% of compounds selected from sesquiterpenes and sesquiterpenoids, and

[0010] - less than 6% of terpinene-4-ol,

[0011] the percentages corresponding to the percentage of peak area corresponding to the chemical compounds of interest relative to the total peak area of ​​the chromatogram obtained by GC / FID analysis on a nonpolar column.

[0012] Preferably, said extract of Melaleuca altemifolia comprises less than 15%, preferably less than 10%, and even better less than 2.0%, of terpineols. In particular, the extract of Melaleuca altemifolia according to the invention may comprise:

[0013] - less than 5.0%, preferably less than 2.0%, better less than 1.0%, of terpinene- 4-ol, and / or

[0014] - less than 5.0%, preferably less than 2.0%, better less than 1.5%, of alpha-terpineol.

[0015] In certain embodiments, said Melaleuca altemifolia extract comprises more than 30%, preferably more than 40%, of compounds selected from sesquiterpenes and sesquiterpenoids. In particular, said Melaleuca altemifolia extract may comprise:

[0016] - 5 to 15% aromadendrene,

[0017] - 10 to 25% ledene,

[0018] - from 10 to 25% delta-cadinene,

[0019] - 1 to 5% globulol, and

[0020] - 1 to 5% viridifloral.

[0021] In a particular embodiment, the extract of Melaleuca altemifolia is obtained by fractional distillation of an essential oil from leaves and / or terminal branches of Melaleuca altemifolia.

[0022] In certain embodiments, said extract of Melaleuca altemifolia is used to treat or prevent one or more signs of skin fatigue selected from loss of skin radiance, dull complexion, uneven complexion, drawn facial features, dark circles under the eyes, bags under the eyes, swollen eyelids, altered skin smoothness, increased skin roughness, loss of elasticity, loss of density, loss of firmness, loss of hydration, appearance of wrinkles, appearance of redness, and combinations thereof.

[0023] In other embodiments, said extract of Melaleuca alternifolia is used as a cosmetic agent to promote or improve skin recovery during sleep and / or as a cosmetic agent to potentiate the natural skin repair and regeneration mechanisms controlled by melatonin.

[0024] Said extract of Melaleuca alternifolia according to the invention can further be used to increase the total duration of sleep, and / or that of deep sleep.

[0025] Typically, said extract of Melaleuca alternifolia is present as a cosmetic active agent in a cosmetic composition, preferably a cream, balm, mask, serum or lotion.

[0026] The invention also relates to an extract of Melaleuca alternifolia as described above.

[0027] An additional object is a precursor composition for the preparation of a cosmetic composition comprising 0.1% to 1% by weight, preferably 0.1% to 0.5% by weight, of an extract of Melaleuca alternifolia according to the invention, in a cosmetically acceptable vehicle, preferably pentylene glycol or tri-heptanoin.

[0028] The invention also relates to a cosmetic composition comprising Melaleuca alternifolia extract or the precursor composition according to the invention, in combination with at least one cosmetically acceptable excipient.

[0029] The cosmetic composition according to the invention may comprise from 0.0005 to 0.01%, preferably from 0.001% to 0.005% by weight of said extract of Melaleuca alternifolia.

[0030] Alternatively, the cosmetic composition according to the invention may comprise from 0.5% to 5% by weight, preferably from 1% to 3% by weight, of the precursor composition.

[0031] The cosmetic composition according to the invention can be chosen from the group consisting of aqueous solutions, hydroalcoholic solutions, oil-in-water (O / W) or water-in-oil (W / O) or multiple (triple: W / O / W or W / O / O) emulsions, nanoemulsions, in particular W / O nanoemulsions, aqueous gels, or dispersions of a fatty phase in an aqueous phase using spherules, suspensions, preferably in aqueous or hydroalcoholic media, liposome suspensions, powders, lotions, milks, creams, ointments, gels, foams, and salves.

[0032] The cosmetic composition according to the invention may be a treatment for treating or prevent skin fatigue, for example with a serum, cream, mask or balm, preferably at night.

[0033] Finally, the invention relates to a cosmetic process for preventing or treating signs of skin fatigue in an individual, said process comprising the application of a cosmetically effective amount of an extract of Melaleuca alternifolia or of a cosmetic composition according to the invention on the skin. FIGURES

[0034] [Fig. 1] represents the modulation of different genes associated with skin repair and the melatonin signaling pathway in the presence of the extract according to the invention in skin expiants subjected to UV stress compared to placebo expiants (subjected to UV stress, in the absence of the extract according to the invention).

[0035] [Fig.2] shows the effect of cutaneous application of the extract according to the invention on the face on the total duration of sleep.

[0036] [Fig.3] shows the effect of cutaneous application of the extract according to the invention on the face on the duration of deep sleep. DESCRIPTION DETAILLEE

[0037] Melatonin is a hormone produced by the pineal gland (also called the epiphysis). Melatonin secretion is inhibited in the presence of light and stimulated in the dark. Through melatonin, the pineal gland informs the brain about the relative durations of light and darkness over a 24-hour period (daily cycle), as well as throughout the year (seasonal cycle). Melatonin is known as the "sleep hormone" and plays a central role in regulating chronobiological rhythms. This hormone is produced in various tissues. The process begins with tryptophan, which is converted into serotonin via different enzymes, and finally into melatonin through the successive action of arylalkylamine N-acetyltransferase and hydroxyindole-O-methyltransferase. Melatonin can act on the skin via two different pathways: independently and in a receptor-dependent manner.Melatonin is capable of acting as a cellular antioxidant, notably by directly scavenging free radicals, but also indirectly by increasing the activity of antioxidant enzymes. This molecule, which has the potential to cross cell membranes, also acts to maintain and protect mitochondrial activity.

[0038] Melatonin also has beneficial effects by activating melatonin receptors. Melatonin receptors are G protein-coupled receptors that exist in two subtypes in humans, namely MT1 and MT2. These two receptors create a biological rhythm that induces sleep. Melatonin receptors are expressed in the brain as well as in peripheral tissues. The MT1 receptor is expressed particularly in the skin. The MT1 receptor is involved in the skin's protective mechanisms against environmental stress, as well as in pigmentation and skin aging.

[0039] Finally, melatonin interacts with the nuclear receptor RORa which acts as an important transcription factor involved in many biological mechanisms, including antioxidant.

[0040] The Applicant has developed a specific extract of Melaleuca alternifolia characterized by an original composition, namely a low terpine-4-ol content and a high content of sesquiterpene and sesquiterpenoid compounds. This extract is obtained by fractional distillation of a traditional Melaleuca alternifolia essential oil. Surprisingly, the Applicant has shown that this extract possesses biological activities that act on the melatonin signaling pathway to mimic and enhance its activity. In particular, the Applicant has shown that the extract according to the invention is capable of activating specific genes of the melatonin signaling pathway in skin expiants exposed to UV radiation, such as ASMTL, RORA, SIRT3, and SLC15A1.Since ASMTL is an enzyme that enables melatonin synthesis and SLC15A1 is a melatonin transporter at the mitochondrial level, the extract has the ability to potentiate the effect of melatonin. Furthermore, like melatonin, the extract is capable of activating RORA and SIRT3, which play a key role in combating cellular damage by limiting oxidative stress.

[0041] The extract according to the invention was also able to induce genes involved in collagen synthesis (COL3A1 and COL1A2) and DNA repair (OGG1) to promote natural skin regeneration and repair mechanisms controlled by melatonin.

[0042] Finally, and quite surprisingly, the Applicant has shown that applying the extract according to the invention in a very low concentration on the skin improves sleep quality in individuals with mild sleep disorders due to their lifestyle, in particular by increasing the total duration of sleep but also the duration of deep sleep, thus promoting the natural repair mechanisms that occur in particular during this phase of sleep.

[0043] Thus, all of these results support the topical cosmetic use of the extract according to the invention as an anti-fatigue agent, i.e. to treat or prevent the cutaneous signs of fatigue, and more generally as an agent to promote or improve skin recovery during sleep, in particular by potentiating the natural skin repair and regeneration mechanisms controlled by melatonin.

[0044] Without wishing to be bound by any theory, the Applicant is of the opinion that these properties result from the specific composition of the extract prepared by fractional distillation of the essential oil of M. altemifolia.

[0045] To the Applicant's knowledge, the extract according to the invention and its use as a skin anti-fatigue agent have never been described or suggested in the prior art.

[0046] Melaleuca altemifolia is a plant endemic to Australia that Aboriginal people have traditionally used as a medicinal herb and antiseptic. The prior art relates essentially to the essential oil of Melaleuca altemifolia, which has a composition and uses distinct from the extract according to the invention. Indeed, the essential oil of Melaleuca altemifolia is an essential oil typically obtained by steam distillation of the leaves and / or twig tips of Melaleuca altemifolia, i.e., the tea tree.

[0047] The main active component of the essential oil of M. altemifolia is terpinene-4-ol. By way of example, the essential oil of Melaleuca altemifolia as defined according to ISO 4730:2017 comprises, among other things, 35-48% terpinene-4-ol, as well as 14-28% gamma-terpinene, 6-12% alpha-terpinene, and 0.2-5% alpha-terpineol.

[0048] The essential oil of M. altemifolia is traditionally used in dermatology and medicine for its anti-acne, antibacterial, and antifungal properties. M. altemifolia essential oil is thus used on the skin or mucous membranes to treat infections such as fungal infections, skin abscesses, boils, and canker sores. It is also used to treat certain ENT infections and as a repellent in aromatherapy.

[0049] The present invention therefore relates to the said extract of Melaleuca altemifolia and its uses in the cosmetic field.

[0050] a. Extract of Melaleuca altemifolia according to the invention

[0051] Thus, according to a first aspect, the present invention relates to an extract of Melaleuca altemifolia poor in terpinen-4-ol, or more generally in terpineols and monoterpenes, and enriched in sesquiterpenes and / or sesquiterpenoids.

[0052] The Melaleuca altemifolia extract according to the invention is fat-soluble. More precisely, the extract according to the invention is an oily extract, also referred to as oil.

[0053] Preferably, the Melaleuca altemifolia extract according to the invention comprises:

[0054] - more than 20% of compounds selected from sesquiterpenes and sesquiterpenoids, and

[0055] - less than 6% of terpinene-4-ol.

[0056] Unless otherwise stated, in this application, the percentages of compounds included in the extract of Melaleuca altemifolia correspond to the percentages of peak area corresponding to the chemical compounds of interest relative to the total area of ​​the peaks of the chromatogram obtained by GC / FID analysis on a nonpolar column, for example based on dimethylpolysiloxane, preferably carried out under the conditions described in example 1.

[0057] In some embodiments, the Melaleuca altemifolia extract according to the invention comprises less than 5.0%, for example less than 4.5%, 4.0% or 3.5% of terpinen-4-ol.

[0058] In some embodiments, the extract according to the invention comprises less than 3.0%, for example less than 2.0% or 1.0% or even less than 0.5% of terpinen-4-ol.

[0059] Terpinene-4-ol is also called 4-terpineol, para-menth-l-en-4-ol, or 1-isopropyl-4-methyl-3-cyclohexen-1-ol.

[0060] In some embodiments, the Melaleuca altemifolia extract according to the invention comprises less than 5.0%, preferably less than 2.0%, or even less than 1.5%, of alpha-terpineol.

[0061] In some embodiments, the Melaleuca altemifolia extract according to the invention generally comprises less than 15.0%, preferably less than 10.0%, or even less than 8.0%, 6.0%, 5.0%, 4.0%, 3.0% or 2.0% of terpineols.

[0062] Terpineols are unsaturated monocyclic monoterpene alcohols. In the context of the present invention, terpineols include terpinen-4-ol, alpha-terpineol, beta-terpineol, gamma-terpineol, terpinen-1-ol, and terpinen-5-ol.

[0063] In some embodiments, the Melaleuca altemifolia extract according to the invention comprises less than 10%, preferably less than 5% or 2%, or even less than 1%, of monoterpenes.

[0064] Monoterpenes are terpenes formally composed of two isoprene units.

[0065] In the context of the present invention, monoterpenes include, among others, terpinenes such as alpha-terpinene and gamma-terpinene (or "terpinolene"), alpha-phellandrene, alpha-p-dimethylstyrene, alpha-pinene, beta-pinene, limonene, sabinene, para-cymene, alpha-thujene, or myrcene.

[0066] In particular, the Melaleuca altemifolia extract according to the invention may comprise less than 5%, preferably less than 2%, or even less than 1% or 0.5% of terpinenes.

[0067] In some embodiments, the Melaleuca altemifolia extract according to the invention comprises less than 10%, preferably less than 5% or 2%, or even less than 1%, of monoterpenoids other than terpineols, such as eucalyptol, camphor, or trans-piperitol.

[0068] In some embodiments, the Melaleuca altemifolia extract according to the invention comprises more than 30% or 40%, or even more than 50%, 60%, or 70% of compounds selected from sesquiterpenes and sesquiterpenoids.

[0069] Sesquiterpenes are terpenes formally composed of three isoprene units.

[0070] In the context of the present invention, sesquiterpenes include, among others, aromadendrene, ledene (or "viridiflorene"), delta-cadinene, beta-caryophyllene, alloaromadendrene, valencene, beta-selinene, bicycloelemene, alpha-cubebene, beta-guaiene, alpha-copaene, alpha-gurjunene, beta-ylangen, alpha-humulene, or beta-cedrene, beta-maaliene, gamma-murolene, gamma-curcumene, gamma-cadinene, or cadina-l,4-diene.

[0071] Sesquiterpenoids are derivatives of sesquiterpenes, generally formed by synthetic or biological modification of sesquiterpenes (typically, by oxidation and / or rearrangement).

[0072] In particular, sesquiterpenoids include additional functional groups compared to sesquiterpenes, including an oxygen (for example an ester, alcohol, ketone or ether function) and / or fewer alkyl groups (for example one less methyl).

[0073] In the context of the present invention, the sesquiterpenoids include, among others, calamenene, alpha-calacorene, beta-calacorene, delta-cadinol, elema-l,ll-dien-15-al, globulol, vidifloral, cadin-4-en-10-ol, ledol, ro-sifoliol, or spathulenol.

[0074] The extract according to the invention may in particular comprise at least 20% (e.g. at least 25%) of the following sesquiterpene and sesquiterpenoid compounds: aromadendrene, ledene, delta-cadinene, globulol and viridifloral.

[0075] In a particular embodiment, said extract of Melaleuca altemifolia according to the invention comprises:

[0076] - 5 to 15% aromadendrene,

[0077] - 10 to 25% ledene, and

[0078] - from 10 to 25% delta-cadinene.

[0079] In a more particular embodiment, said extract of Melaleuca altemifolia according to the invention comprises:

[0080] - 5 to 15% aromadendrene,

[0081] - 10 to 25% ledene,

[0082] - from 10 to 25% delta-cadinene,

[0083] - from 1.0 to 5.0% globulol, and

[0084] - from 1.0 to 5.0% viridifloral.

[0085] In another additional embodiment, the extract according to the invention comprises:

[0086] - less than 6% (for example less than 5%, 4.5%, 4.0%, 3.5%, 3.0% 2.0%, 1%, 0.5%) of terpinen-4-ol,

[0087] - less than 5%, (for example less than 2.0% or 1.5%) of alpha-terpineol,

[0088] - less than 15.0% (for example, less than 10.0%, 8.0%, 6.0%, 5.0%, 4.0%, 3.0% or 2.0%) of terpineols,

[0089] - less than 10% (for example less than 5%, 2%, or 1%) of monoterpenes,

[0090] - less than 10% (for example less than 5%, 2%, or 1%) of monoterpenoids other than terpineols,

[0091] - at least 25% (for example more than 30%, 40%, 50%, 60%, or 70%) of compounds selected from sesquiterpenes and sesquiterpenoids.

[0092] Preferably, the extract according to the invention comprises at least 25% of compounds selected from aromadendrene, ledene and delta-cadinene.

[0093] In particular, the extract according to the invention may include:

[0094] - from 5 to 15% aromamadendrene,

[0095] - 10 to 25% ledene, and

[0096] - from 10 to 25% delta-cadinene.

[0097] In another additional embodiment, the extract according to the invention comprises:

[0098] - less than 6% (for example less than 5%, 4.5%, 4.0%, 3.5%, 3.0% 2.0%, 1%, 0.5%) of terpinen-4-ol,

[0099] - less than 5%, (for example less than 2.0% or 1.5%) of alpha-terpineol,

[0100] - less than 15.0% (for example less than 10.0%, 8.0%, 6.0%, 5.0%, 4.0%, 3.0% or 2.0%) of terpineols,

[0101] - less than 10% (for example less than 5%, 2%, or 1%) of monoterpenes,

[0102] - less than 10% (for example less than 5%, 2%, or 1%) of monoterpenoids other than terpineols,

[0103] - at least 27% (for example, more than 30%, 40%, 50%, 60%, or 70%) of compounds selected from sesquiterpenes and sesquiterpenoids.

[0104] Preferably, the extract according to the invention comprises at least 27% of compounds selected from aromadendrene, ledene, delta-cadinene, globulol and viri-difloral.

[0105] In particular, the extract according to the invention may include:

[0106] - 5 to 15% aromadendrene,

[0107] - 10 to 25% ledene,

[0108] - from 10 to 25% delta-cadinene,

[0109] - from 1.0 to 5.0% globulol, and

[0110] - from 1.0 to 5.0% viridifloral.

[0111] The extract according to the invention can be obtained from an essential oil of Melaleuca alternifolia (hereinafter referred to as "first essential oil" or "starting essential oil") by fractional distillation.

[0112] The starting essential oil is typically rich in terpinene-4-ol and is gen- rarally obtained by steam distillation or hydrodistillation of all or part of Melaleuca alternifolia, preferably leaves and / or twigs.

[0113] In some embodiments, the starting essential oil of Melaleuca al-ternifolia may comprise:

[0114] - 35 to 48% (for example, 37 to 45%) of terpinen-4-ol,

[0115] -from 10 to 28% (for example from 14 to 28%) of gamma-terpinene,

[0116] -from 5.0 to 13% (for example from 6 to 12%) of alpha-terpinene,

[0117] - from 0.2 to 8.0% (for example from 0.2 to 5.0% or from 1.5 to 8.0%) of alpha-terpineol, and

[0118] Preferably, it comprises less than 3.0% of aromadendrene, less than 3.0% of ledene, less than 3.0% of delta-cadinene, less than 1.0% of globulol, and less than 1.0% of viridifloral.

[0119] The Melaleuca alternifolia extract according to the invention is advantageously a fraction obtained from the fractional distillation of a Melaleuca alternifolia essential oil. Fractional distillation is typically carried out under reduced pressure, using a fractional distillation apparatus comprising a boiler, a fractionating column, a condenser, and a collector. The essential oil is heated slowly under reduced pressure so as to collect different successive fractions, each fraction corresponding to a temperature plateau. Fractional distillation is performed in such a way as to initially collect at least one (preferably two, three, or four) distillation fractions enriched in monoterpene and monoterpenoid compounds (in particular terpin-4-ol).Once the fraction(s) enriched in monoterpene and monoterpenoid compounds have been harvested, the fraction corresponding to the extract according to the invention can be harvested. This fraction is typically obtained under reduced temperature and pressure conditions allowing the harvesting of compounds with a boiling point above 200°C at atmospheric pressure.

[0120] Since fractional distillation is a well-known process, a person skilled in the art can determine the heating temperature and pressure to be used to obtain, from a given essential oil, a fraction corresponding to an extract according to the invention, e.g. by implementing routine tests and / or using nomograms.

[0121] In a preferred embodiment, the extract according to the invention is a distillation fraction of an essential oil of Melaleuca alternifolia, preferably obtained by fractional distillation.

[0122] Thus, the extract according to the invention can also be described as "a distillation fraction of an essential oil of Melaleuca alternifolia," said essential oil preferably being obtained by steam distillation or hydrodistillation of leaves and / or twigs of Melaleuca alternifolia. The extract according to the invention is therefore typically an oily extract or an oil of Melaleuca al- ternifolia. Compared to a classic essential oil, the extract according to the invention is depleted in monoterpenes and monoterpinoids.

[0123] In certain embodiments, said extract of Melaleuca altemifolia is obtained by a process comprising:

[0124] i) a hydrodistillation step of all or part of Melaleuca altemifolia, preferably its leaves and / or branch tips, to obtain a first essential oil,

[0125] ii) a fractional distillation step of said first essential oil under conditions of reduced pressure and temperature allowing to collect a fraction corresponding to said extract.

[0126] b. Precursor composition and cosmetic composition comprising the extract according to the invention

[0127] The extract of Melaleuca altemifolia according to the invention has cosmetic effects and can therefore be used as a cosmetic agent.

[0128] In the context of the present invention, "cosmetic agent" means an agent exerting a cosmetic effect on the skin.

[0129] In the context of the present invention, "cosmetic effect" means any non-therapeutic effect intended to modify and / or improve the appearance of the skin or mucous membranes such as the lips, or to protect them from external aggressions (sun, wind, humidity, dryness, chemicals), for example to prevent and / or correct phenomena related to their aging or to prevent or treat the effects caused by fatigue on the skin.

[0130] As will be detailed below, the extract according to the invention can be used as a skin-regenerating, repairing, or anti-fatigue cosmetic agent. For this purpose, the Melaleuca altemifolia extract according to the invention is generally introduced as a cosmetic agent into a cosmetic composition. In other words, said extract is typically applied to the skin of the individual to be treated by means of a cosmetic composition. A precursor composition comprising the Melaleuca altemifolia extract according to the invention can be prepared beforehand and then incorporated into the cosmetic composition.

[0131] Thus, an object of the present invention is a precursor composition for the preparation of a cosmetic composition, said precursor composition comprising from 0.1% to 1% by weight, preferably from 0.1% to 0.5% by weight, of Melaleuca altemifolia extract according to the invention, in a cosmetically acceptable vehicle.

[0132] The cosmetically acceptable vehicle can be of any type. For example, it can be a cosmetically acceptable solvent, in particular lower alcohols, including ethanol, isopropanol, dipropylene glycol, butylene glycol, propanediol, glycerin, sorbitol, propylene glycol, pentylene glycol, tri- heptanoin, an aqueous solution of these, or a mixture of these.

[0133] Preferably, said vehicle is pentylene glycol or triheptanoin.

[0134] Another object of the present invention is a cosmetic composition comprising the extract of Melaleuca alternifolia according to the invention, preferably as a cosmetic agent, or the precursor composition according to the invention, in combination with at least one cosmetically acceptable excipient.

[0135] The cosmetically acceptable excipient(s) present in the composition may be selected from among diluents, dispersing agents, gelling agents, emollients, delivery agents (such as polycationic polymers, phospholipids, unilamellar or multilamellar liposomes, niosomes, ethosomes, lamellar systems, nanosomes, lipid or polymeric vesicles, nanospheres, micro- or nanoparticles of natural or synthetic polymers, hydrogels), gums, resins, solvents, in particular lower alcohols, notably ethanol, isopropanol, dipropylene glycol, butylene glycol, propanediol, glycerin, sorbitol, and propylene glycol, fillers such as modified and polymerized starches, titanium dioxide, or a metallic stearate, preservatives, essential oils, pearlescent agents, colorants, odor absorbers,pH regulators or neutralizers, lubricants, thickeners, hydrotropes such as surfactants (including anionic, cationic, amphoteric, and non-ionic surfactants), humectants, wetting agents, stabilizers, fillers, dispersants, perfumes, organic or mineral pigments such as iron oxides, oily agents such as vegetable oils or fats, animal fats, synthetic oils such as petrolatum, silicone oils (cyclomethicone), fatty alcohol esters, fluorinated oils, waxes, modified clays, bentons, metallic salts of fatty acids, silica, polyethylenes, mica, preservatives, antimicrobial agents, carriers such as mineral, thermal, or floral water, and / or other substances commonly used in cosmetic formulations or pharmaceutical.

[0136] In one embodiment, the cosmetic composition comprises from 0.0005 to 0.01%, preferably from 0.001% to 0.005% by weight of the Melaleuca alternifolia extract according to the invention.

[0137] More specifically, said cosmetic composition may include:

[0138] - from 0.0005% to 0.01% by weight, preferably from 0.001% to 0.005% by weight of said e of Melaleuca alternifolia, and

[0139] - from 99.99% to 99.9995% by weight of one or more acceptable excipients on the cosmetic plan.

[0140] In another embodiment, said cosmetic composition comprises from 0.5% to 5% by weight, preferably from 1% to 3% by weight, of said precursor composition.

[0141] More specifically, said cosmetic composition may comprise:

[0142] - 0.5% to 5% by weight, preferably 1% to 3% by weight of said composition precursor, and

[0143] - from 95% to 99.5% by weight of one or more excipients acceptable in terms of cosmetic.

[0144] In certain embodiments, the cosmetic composition further comprises one or more additional cosmetic active ingredients. The term "cosmetic active ingredient," "cosmetic active ingredient," "cosmetic agent," or "active ingredient with cosmetic effect" refers to a compound capable of exerting at least one cosmetic effect on the skin or its appendages. The term "cosmetic effect" refers to any non-therapeutic effect intended to modify and / or improve the visual appearance and mechanical properties of the skin or mucous membranes such as the lips, to protect them from external aggressions (sun, wind, humidity, dryness, chemicals), to prevent and / or correct phenomena related to their aging, or to prevent or treat the effects of stress or fatigue on the skin.

[0145] Examples of such agents include, among others, anti-wrinkle agents, anti-aging agents, antioxidant agents, moisturizing agents, soothing agents, anti-redness agents, decongestant agents, scrubbing or exfoliating agents, mattifying agents, sebum-regulating agents, brightening agents, anti-spot agents, anti-dark circle or anti-puffiness agents, anti-stress agents, anti-fatigue agents, anti-pollution agents, firming agents, sunscreens and filters, and combinations thereof.

[0146] In particular, the cosmetic composition may include tocopherols, and / or plant extracts such as flaxseed extracts, Vibrio exopolysaccharide extracts, peptides such as trifluoroacetyl tripeptide-2.

[0147] In a particular mode, the cosmetic composition may include an active ingredient selected from an anti-wrinkle agent, an anti-redness agent, an antioxidant agent, a moisturizing active ingredient, a soothing agent, a sebum-regulating agent, an anti-spot or brightening agent, a tightening agent, an anti-pollution active ingredient, an anti-dark circle or anti-puffiness agent, a sun filter or sunscreen, and combinations thereof.

[0148] Examples of anti-pollution agents include extracts of Chrysanthellum Indicum, polysaccharides, particularly marine polysaccharides from an Alteromonas fermentation medium, and Nigari salts.

[0149] Examples of anti-dark circle agents include extracts of Chrysantellum Indicum or extracts and sulfated polysaccharides of algae, particularly Ascophyllum nodosum or Asparagopsis Armata.

[0150] Examples of moisturizing agents include urea, pidolic acid (PCA) and its derivatives, in particular its salts such as arginine PCA, chitosan PCA, its copper (copper PCA), magnesium (magnesium PCA), sodium (sodium PCA) or zinc salts, ethylhexyl PCA, calcium gluconate, hyaluronic acid and its salts and other glycosaminoglycans, fructose, glucose, isomaltose, lactose, trehalose, polydextrose, sucrose, maltitol, mannitol, sorbitol, xylitol and other carbohydrates and derivatives, polyethylene glycols such as PEG-7, PEG-8, PEG-10, PEG-12 or PEG-14, glycerin, propylene glycol, butylene glycol, betaine, citrulline, collagen and its derivatives, histidine, silk, keratin or soy hydrolysates, plant extracts rich in polysaccharides and / or polyphenols, for example extracts of Aloe, cornflower (Centaurea cyanus),Extracts rich in polysaccharides, particularly those derived from fermentation media of marine microorganisms such as Alteromonas and combinations thereof.

[0151] Examples of anti-aging agents include ascorbic acid and its derivatives such as magnesium ascorbyl phosphate, glycosaminoglycans and their derivatives, Cyathea polysaccharides, collagen, linseed extracts (Linum usitatissimum), peptides such as Caprooyl-Tetrapeptide-3 and trifluoroacetyl tripeptide-2, Polygonum aviculare extracts, brown algae extracts, in particular Ascophyllum nodosum, fern extracts, in particular Cyathea cumingii.

[0152] Examples of anti-stress agents include Rosality™ products (a combination of rose water and rose essential oil) and pink-flowered rockrose extract, for example marketed under the brand name IBR-Chill™.

[0153] Examples of soothing agents include allantoin, extracts of aloe, birch (e.g., Betula alba), epilobe (Epilobium angustifolium), chestnut (e.g., Castenea saliva), blueberry (for example, centena centa). e.g. Centella asiatica), pear (e.g. Equisetum arvense), fennel (e.g. Foeniculum vulgare), willow (e.g. Hamamelis virginiana), lilac (e.g. Hedera hélix), habiscus sabdariffa, lily (e.g. candidum Empleum malvapare), sylvestris), honeysuckle (e.g. Melissa officinalis), scutellaire (e.g. Scutellaria baicalensis), mimosa (e.g. Mimosa tenuiflora), potentille (e.g. Potentilla erecta ), an oligosaccharide extract or an oligosaccharide, for example, lime peptides, palmiyl tripeptide-8, polysaccharide extracts,in particular, extracts of exopolysaccharides from the Alteromonas fermentation medium and combinations thereof.

[0154] Examples of antioxidant agents include HMR (hydroxymethyl re-sorcinol), ascorbic acid and its derivatives, vitamin B9, histidine hydrochloride, or an extract of willowherb (Epilobium angustifolium). Active ingredients with antioxidant and vitamin-like effects are generally used in a mass percentage of at least 1% relative to the total weight of the cosmetic composition.

[0155] Examples of sebum-regulating agents include flax lignans, rice powder, zinc gluconate, sarcosine, Cinnamomum zeylanicum bark extract, avocado extract, Backhousia citriodora extract and combinations thereof.

[0156] Examples of anti-redness agents include saponins, flavonoids, ruscogenins, esculosides, and extracts containing them, for example Ruscus extracts, as well as certain essential oils, for example lavender or rosemary.

[0157] Examples of anti-stain agents include extracts such as licorice (Glycyrrhyza glabrd), jackfruit extract (Artocarpus heterophyllus), Rumex extract (R. occidentalis), extracts of plants belonging to the genus Citrus, re-sveratrol, peptides such as oligopeptide-68, nonapeptide-1, kojic acid, magnesium ascorbyl phosphate and combinations thereof.

[0158] In a particular embodiment, said cosmetic composition comprises from 0% to 30% by weight, for example from 0% to 15% by weight, of one or more additional cosmetic active agents.

[0159] In a more particular embodiment, said cosmetic composition comprises:

[0160] - from 0.0005% to 0.01% by weight, preferably from 0.001% to 0.005% by weight of said extract of Melaleuca altemifolia according to the invention,

[0161] - from 69.99% to 99.9995% by weight of one or more acceptable excipients on the cosmetic plan, and

[0162] - from 0% to 30% by weight, for example from 0 to 15% by weight, of one or more agents additional cosmetic active ingredients.

[0163] In a more particular embodiment, said cosmetic composition comprises:

[0164] - 0.5% to 5% by weight, preferably 1% to 3% by weight of the composition precursor as described above,

[0165] - from 65% to 99.5% by weight of one or more excipients acceptable in terms of cosmetics, and

[0166] - from 0% to 30% by weight, for example from 0 to 15% by weight, of one or more agents additional cosmetic active ingredients.

[0167] The extract of Melaleuca altemifolia according to the invention, or the precursor composition comprising it, can be incorporated into any type of cosmetic composition. Preferably, this is a cosmetic composition having a form suitable for topical administration, in particular suitable for application to the skin. The cosmetic composition according to the invention can be of any type. In one embodiment, the cosmetic composition is chosen from the group consisting of aqueous solutions, hydroalcoholic solutions, oil-in-water (O / W) or water-in-oil (W / O) or multiple (triple: W / O / W or W / O / O) emulsions, nanoemulsions, in particular O / W nanoemulsions, the droplet size of which is typically less than 100 nm, aqueous gels, or dispersions of an oily phase in an aqueous phase using spherules, suspensions, preferably in aqueous or hydroalcoholic media, liposome suspensions, powders, lotions, milks, creams, ointments, gels, foams, balms, and salves.

[0168] In embodiments, the cosmetic composition according to the invention is a cream, a balm, a mask, a serum or a lotion.

[0169] In a preferred mode, the cosmetic composition according to the invention is a serum, a cream, a mask or a balm, preferably for nighttime use.

[0170] c. Cosmetic Uses and Processes according to the invention

[0171] According to a further aspect, the Invention also relates to the use of Melaleuca alternifolia extract as described above as a cosmetic agent for skin regeneration, repair or anti-fatigue, and more particularly, for treating or preventing one or more signs of skin fatigue.

[0172] The invention also relates to the use of a cosmetic composition according to the invention to treat or prevent one or more signs of skin fatigue.

[0173] For the purposes of this invention, the terms "skin" and "cutaneous" refer to any part of the skin of the human body, in particular the skin of the face, including the lips and eyelids, the neck, and the skin of the hands. Preferably, this refers to the skin on the face, including the area around the eyes and the lips, and on the neck.

[0174] In the context of the present invention, the extract or composition according to the invention is typically applied topically, preferably to skin or mucous membranes. This refers to healthy skin or mucous membranes, that is, skin or mucous membranes free from wounds or skin pathologies. In particular, the extract or composition according to the invention is applied to non-acne-prone skin (that is, skin not suffering from acne), free from wounds, particularly those resulting from insect bites, or from skin infections, e.g., caused by a fungus (mycosis), a bacterium, or a protozoan.

[0175] In other words, the extract or composition according to the invention does not produce a therapeutic effect on the skin when used according to the invention.

[0176] The term "anti-fatigue agent" means a cosmetic agent capable of preventing, treating or alleviating the "skin effects or signs" of fatigue, i.e. the effects of fatigue on the skin.

[0177] In the context of the present invention, "skin signs or effects" shall be understood to mean, any non-pathological alteration or modification of the visual appearance or mechanical properties of the skin. In the context of the present invention, "skin signs or effects" are caused by, or associated with, fatigue.

[0178] “Preventing a sign or effect” means delaying or stopping the appearance of that sign or effect on the skin. “Treating a sign or effect” means reducing, mitigating, diminishing, correcting, or slowing the development of that sign or effect on the skin.

[0179] The sign(s) of skin fatigue may, for example, be a loss of radiance of the skin, a dull complexion, a cloudy complexion, a loss of uniformity of complexion, drawn facial features, dark circles under the eyes, bags under the eyes, swollen eyelids, an alteration of the smooth appearance of the skin, an increase in the roughness of the skin, a loss of elasticity, a loss of density, a loss of firmness, a loss of hydration, the appearance of fine lines or wrinkles, the appearance of redness, and combinations thereof.

[0180] In the context of the present invention, fatigue causing non-pathological changes or alterations to the skin can be of any type. It can be temporary or chronic. It includes fatigue caused by one or more factors, particularly environmental ones. These factors may include, for example, lack of sleep due to work schedules or family circumstances (e.g., the birth of a child), sleep disorders or jet lag, poor or unbalanced diet, alcohol consumption, lack or excess of physical activity, sedentary lifestyle, overwork, intense or unsuitable work activity, night work or shift work, significant screen time, stress, anxiety, or worries related to professional or family life.

[0181] Fatigue can also result from physiological situations such as pregnancy or menopause.

[0182] Preferably, the fatigue is not associated with or caused by a pathological condition in the individual. In certain embodiments, the extract of Melaleuca altemifolia according to the invention can be used for at least one (1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) of the following purposes:

[0183] - To prevent, treat or reduce dark circles and / or puffiness around the eyes,

[0184] - To prevent, treat or reduce eyelid swelling

[0185] - To prevent, treat or reduce skin pigmentation irregularities, including pigment spots induced by fatigue,

[0186] - To homogenize or unify the complexion of the face,

[0187] - To make the complexion of the face brighter and / or more radiant and / or clearer,

[0188] - To prevent or treat a dull complexion, a sallow complexion and / or drawn features,

[0189] - To make the skin, particularly on the face, look fresher and brighter,

[0190] - Soothes facial features,

[0191] - To make the skin look less tired, more relaxed, fresher

[0192] - To make the eyes look less tired, more rested and brighter,

[0193] - To promote or accelerate the recovery of the epidermis, particularly at the level of the face,

[0194] - Revitalize the skin, particularly on the face,

[0195] - To promote a healthy glow,

[0196] - To prevent, treat the alteration of, or restore, the skin's barrier function,

[0197] - To prevent, treat, or mitigate a loss of skin firmness, particularly at the level of the face,

[0198] - To prevent, treat or alleviate skin dehydration (or in a way equivalent to "hydration loss"),

[0199] - To prevent, treat, delay, or reduce the appearance of wrinkles or fine lines, and / or

[0200] - To prevent, treat or reduce the appearance of redness.

[0201] It goes without saying that the non-pathological alterations listed above are associated with or caused by fatigue on the skin.

[0202] In the context of the present invention, a "regenerating or repairing agent" means a cosmetic agent capable of promoting or stimulating skin regeneration or skin repair during sleep so that the skin effects caused by fatigue are reduced, treated, or prevented. This may include chronic fatigue or fatigue caused by one or more factors, including environmental factors. In this regard, the Applicant has observed, in particular, that the extract according to the invention stimulates the genes involved in collagen synthesis in the skin.

[0203] As illustrated in the examples, applying the extract to the skin at a very low concentration, notably imperceptible by smell, improves sleep. It has also been shown that the extract according to the invention is capable of activating melatonin signaling pathways, particularly those involved in DNA repair mechanisms and cellular defense against oxidative stress, as well as in the synthesis and transport of melatonin, for example, induced by exposure to environmental stress such as excessive UV exposure.

[0204] Thus, in a particular embodiment, the extract according to the invention is used as an agent to activate the melatonin signaling pathway and / or potentiate the effect of melatonin at the skin level.

[0205] According to one particular aspect, the extract according to the invention is used to promote or improve skin recovery, particularly during sleep. The extract according The invention is notably used to potentiate the natural skin repair and regeneration mechanisms controlled by melatonin.

[0206] In an additional or alternative aspect, the extract according to the invention is used to improve sleep, in particular to increase the total duration of sleep and / or that of deep sleep.

[0207] According to a further embodiment, the extract according to the invention is used to promote or aid skin recovery during the sleep phase.

[0208] According to a further aspect, the extract according to the invention is used to repair / regenerate the skin in an individual exposed to fatigue, in particular chronic fatigue.

[0209] The extract according to the invention can be used to repair / regenerate skin exposed to stress, in particular environmental stress such as exposure to sun, wind, humidity, dryness or to chemicals or processes such as abrasion, rays etc... or to stress related to lifestyle (jet lag, lack of sleep, night work etc...).

[0210] In addition or alternatively, the extract according to the invention is used to induce collagen synthesis in the skin.

[0211] In a particular embodiment, the Melaleuca altemifolia extract according to the invention is present as a cosmetic active agent in a cosmetic composition, preferably a cream, balm, mask, serum, or lotion, as described above. The concentration of the Melaleuca altemifolia extract according to the invention in such a cosmetic composition is advantageously low, so that it is not perceptible by smell. Typically, this concentration is 0.0005% to 0.01% by weight, preferably 0.001% to 0.005% by weight of said extract.

[0212] It goes without saying that such uses are intended for individuals exposed to fatigue as defined above.

[0213] The individuals targeted by the present invention can be of any age and gender. In a preferred embodiment, this refers to an individual under 65 years of age. This could be, for example, a woman or a man between 25 and 65 years of age, particularly between 25 and 55 years of age. By way of example, this refers to a woman between 25 and 45 years of age.

[0214] An additional object of the present invention is a cosmetic process for preventing or treating signs of skin fatigue in an individual, said process comprising the application of a cosmetically effective amount of an extract of Melaleuca altemifolia according to the invention, or of a cosmetic composition according to the invention, to the skin.

[0215] The cosmetic process according to the invention is intended to treat or prevent one or more skin effects of fatigue, preferably selected from among alterations in skin tone, in particular a dull complexion, a lack of radiance in the complexion or a loss of uniformity of complexion, including the appearance of pigment spots, drawn facial features, the appearance of bags and / or dark circles around the eyes, swollen eyelids, an alteration of the smooth appearance of the skin, an increase in skin roughness, a loss of elasticity, a loss of density, a loss of firmness, a loss of hydration, the appearance of wrinkles, the appearance of redness, and combinations thereof.

[0216] The method according to the invention can produce any one of the following effects in an individual exposed to fatigue:

[0217] - To prevent, treat or reduce dark circles and / or puffiness around the eyes,

[0218] - Prevent, treat or reduce eyelid swelling

[0219] - To prevent, treat or reduce skin pigmentation irregularities, including pigment spots induced by fatigue,

[0220] - To even out or unify the complexion of the face,

[0221] - To make the complexion of the face brighter and / or more radiant and / or clearer,

[0222] - To prevent or treat a dull complexion, a sallow complexion and / or drawn features,

[0223] - To make the skin, especially on the face, look fresher and brighter,

[0224] - Soothe facial features,

[0225] - To make the skin look less tired, more relaxed, fresher

[0226] - To make the eyes look less tired, more rested and brighter,

[0227] - To promote or accelerate the recovery of the epidermis, particularly at the level of the face,

[0228] - Revitalize the skin, especially on the face,

[0229] - To promote a healthy glow,

[0230] - To prevent, treat the alteration of, or restore, the skin's barrier function,

[0231] - To prevent, treat, or mitigate loss of skin firmness, particularly at the level of the face,

[0232] - To prevent, treat or alleviate skin dehydration (or in a way equivalent to "hydration loss"),

[0233] - To prevent, treat, delay, or reduce the appearance of wrinkles, and / or

[0234] - To prevent, treat or reduce the appearance of redness.

[0235] In the cosmetic methods and uses according to the invention, the dose to be administered and the frequency of administration of the combination according to the invention vary depending on the desired cosmetic effect, the characteristics of the individual, in particular their sex, age, and skin type. Typically, the Melaleuca alternifolia extract according to the invention, or the cosmetic composition comprising it, can be applied to the area to be treated once a day, preferably before bedtime, for several consecutive weeks or even several months, for example, at least 3 months. By way of example, the patient can apply a dose of 1 g to 2 g of cosmetic composition on her face in the evening. EXAMPLES

[0236] The invention will be better understood in the light of the following examples, which are given purely for illustrative purposes and are not intended to limit the scope of the invention.

[0237] EXAMPLE 1: Preparation of an extract according to the invention

[0238] 1. Obtaining an extract of Melaleuca alternifolia according to the invention

[0239] As stated in the description, the extract according to the invention can be obtained by fractional distillation of a standard essential oil of Melaleuca alternifolia. The essential oil was obtained from fresh leaves and terminal branches by steam distillation. The essential oil was then fractionated by distillation. A first fraction rich in gamma-terpinene was obtained, followed by a second fraction rich in both gamma-terpinene and terpinen-4-ol, and then a third and fourth fraction, both rich in terpinen-4-ol. Finally, the extract according to the invention, corresponding to the fifth fraction, was obtained.

[0240] Table 1 details the physical and chemical characteristics of the steam-distilled Melaleuca alternifolia essential oil prior to fractional distillation. Table 2 details the composition of the starting material (“first essential oil”) and that of the fraction of interest (“essential oil according to the invention”).

[0241] GC / FID analyses were performed using an Agilent 6890 instrument (Agilent Technologies) equipped with a flame ionization detector (FID), an autosampler, and the same HP-IMS capillary column (100% dimethylpolysiloxane, 60 m x 0.15 mm ID, film thickness 0.25 µm; Agilent Technologies). The oven temperature was maintained at 60°C for 10 min, then programmed from 60 to 300°C at 2°C / min, and finally at 300°C for 10 min (transition time 140 min). The injector and detector temperatures were 250°C and 300°C, respectively; H2 (1.0 ml / min) was used as the carrier gas; injection was in split mode (1:50); and the injected volume was 0.1 ml. The O2, H2 and FID makeup gas flow rates were 350, 35 and 20 ml / min, respectively.

[0242] [Tables 1] Physicochemical characteristics of the starting essential oil: Appearance: Liquid; Color: Colorless - light yellow; Odor: Characteristic; Relative density (20°C / 20°C): 0.885 - 0.906; Refractive index (20°C): 1.475 - 1.482; Optical rotation (20°C): +5° to +15°; Moisture (visual): No visible water at 20°C; M1SC1B1L1TE IN 85% (v / v) ETHANOL: At 20°C, 1 volume of oil gives a clear solution in at most 2 volumes of 85% (v / v) ethanol; Flash point: 50°C - 60°C

[0243] [Tables2] Compounds CONTENT % (AREA GC-FID) STARTING ESSENTIAL OIL Extract ACCORDING TO INVENTION alpha-Pinene 1.0-6.0 - Sabinene Up to 3.5 - alpha-Terpinene 5.0-13.0 0.02 Limonene 0.5 - 1.5 - para-Cymene 0.5 - 4.0 0.22 1,8-Cineole Up to 5.0 - gamma-T erpinene 10.0-28.0 0.01 alpha-Terpinolene 1.5-5.0 0.01 Terpinen-4-ol 37.0 - 45.0 0.16 alpha-Terpineol 1.5-8.0 1.09 Aromadendrene UP TO 3.0 8.65 Ledene UP TO 3.0 17.80 delta-Cadinene UP TO 3.0 17.29 Globulol UP TO 1.0 3.25 Viridifloral UP TO 1.0 2.61

[0244] EXAMPLE 2: Evaluation of the extract according to the invention on skin expiants

[0245] Protocol: The aim of this study was to evaluate the repairing effect of the extract according to the invention on skin excipients and to demonstrate its melatonin-like activity on the skin. The extract according to the invention obtained in Example 1 was diluted in pentylene glycol to a concentration of 0.5% by weight. This precursor composition was then formulated in carbopol to a concentration of 1% by weight. This final composition was used in this experiment.

[0246] From an abdominoplasty of a 46-year-old Caucasian woman (reference: P2471-AB46, phototype II-III (according to the Fitzpatrick skin color classification)), 51 expiants with a mean diameter of 11 mm (+1 mm) were prepared. The expiants were kept alive in BEM (BIO-EC's Expiants Medium) at 37°C in a humid atmosphere at 5% CO2 for 2 days. On the 2nd day, the medium The culture was replaced with an HBSS solution, and then the expiry subjects were irradiated with UV light (group "UV-E" and group "UV-Extract") at a dose of 13.5 J / cm² of UVA, corresponding to 3 MEDs (minimum erythemal dose), and at a dose of 0.15 J / cm² of UVB, corresponding to 1 MED or not (group "E"). At the end of irradiation, the placebo product (for group "E" and group "UV-E") or the composition containing the extract according to the Invention ("UV-Extract") was applied topically to the skin surface of the corresponding expiry subjects at a rate of 2 qL per cm² of expiry (2 mg / cm²) for an additional 24 hours. On day 3, the expiry subjects were fixed in RNAlater prior to RNA extraction using Promega's ReliaPrep™ RNA Tissue Miniprep System (fibrous). The quality and concentration of the RNAs were assessed before performing the reverse transcriptase step with iScript (Bio-Rad, 20 ql / reaction). With the aid of a spike control, the ACq was calculated.The benchmarks evaluated for each qPCR reaction using CFX Manager 3.1 software are as follows: .

[0247] -The logarithmic curve of the amplification for each sequence of interest.

[0248] -The melting curves are fluorescence intensities recorded after the last cycle. The temperature increases from 65° to 96°C in increments of 0.5°C every 5 seconds.

[0249] -The curves representing the inverse of the derivative of the fluorescence signal as a function of temperature (in °C), allow verification of a single amplicon.

[0250] All samples were subjected to gene expression profiling analysis. For quantification, the number of cycles was normalized to the B2M reference gene:

[0251] (i) Cq (relative quantity) per sample and per gene = E (gene) (Cq (control) - Cq (treaty)

[0252] E = primer pair efficiency = (% efficiency*0.01) + 1

[0253] Cq (control) = the quantitative threshold calculated by the CFX Maestro in "regression" mode for the control condition.

[0254] Cq (treated) = the quantitative threshold calculated by the CFX Maestro in "regression" mode for the treated condition.

[0255] gene = target gene

[0256] (ii) Expression of a normalized target gene = NE

[0257] NE=Expression of normalized sample (gene) = Cq sample (gene) / ((Cq sample (ref 1) * Cq sample (ref 2))1 / n

[0258] Cq = relative quantity

[0259] The denominator corresponds to the normalization factor including the two reference genes: ref 1 = B2M

[0260] gene = target gene

[0261] For each gene of interest, values ​​were calculated between triplicate treatment samples and triplicate matched explant control samples for each kinetic time point. A gene was considered induced if its expression showed an increase greater than or equal to 1.5 compared to the control (fold-change >1.5). Similarly, a gene was considered repressed if its expression showed a reduction compared to the control (fold-change <0.65). In addition, when homogeneous gene modulation is conserved between biological triplicates, a P-value <0.05 (according to the t-test) is indicated by an asterisk.

[0262] Results: Compared to the placebo UV (UV-E) condition, the extract triggered a strong induction of OGL1, which is involved in DNA repair. Furthermore, the extract induced a strong induction of antioxidant enzymes such as CAT and GPX1. An effect on COL3A1 and COL1A2 also tends to prove that the extract according to the invention acts on the extracellular matrix with an increase in collagen synthesis. Interestingly, the extract induced an increase in the expression of melatonin-associated genes (ASMTL, RORA, SIRT3, and SLC15A1), which tends to prove that the extract targets the same pathway as melatonin and is therefore capable of activating melatonin signaling pathways, particularly those involved in mechanisms of protection against oxidative stress, notably induced by UV. Stimulation of this signaling pathway would explain the stimulation or repression of the genes mentioned above.

[0263] All of these results support the use of the extract according to the invention as an anti-fatigue, skin regenerator or repairing agent.

[0264] [Tables3] UV-Extract vs UV-placebo P-Value ASMTL 1.55 0.042 RORA 1.63 0.040 SIRT3 1.62 0.008 SLC15A1 2.62 0.007 CAT 1.94 0.041 GPX1 1.70 0.033 COL3A1 2.56 0.013 COL1A2 1.97 0.012 OGG1 2.02 0.005 EXAMPLE 3: Improving sleep

[0265] Protocol: 32 healthy participants (16 men, 22-56 years, median age 41.5 years) with mild, self-reported sleep disturbances caused by lifestyle factors, but without a diagnosis of clinical sleep disorder were selected

[0266] The study consisted of evaluating 2 samples of face cream, 1 "active" cream and a "control" cream, used separately over 3 weeks:

[0267] - Product A-cream "active": generic unscented face cream comprising 1% of a precursor composition comprising 0.25% by weight of the extract of Example 1, in pentylene glycol (A-Leen® 5, Minasolve),

[0268] - "Control" cream: generic cream (see example 5, table 5 below) no perfumed face cream containing 1% pentylene glycol (A-Leen® 5, Minasolve) alone.

[0269] Devices: For objective sleep measurements, participants used the SleepScore Max device (SleepScore Labs, Carlsbad, CA), a non-contact monitoring device that uses respiratory signal and motion detection to detect sleep and has been validated by polysomnography (PSG), the standard method for measuring sleep. All self-reported data were collected using Compusense, an online data collection software.

[0270] Study design and procedure:

[0271] - Contextual, randomized, and counterbalanced study using a non-control cream scented

[0272] - Participants applied the creams at bedtime, in their envi natural sleep snoring.

[0273] - The study lasted from Sunday evening to Friday morning for 3 weeks consecutive.

[0274] - Participants used a different sample each week. The sample A control group was used during the second week. Table 3 shows an overview of the study design.

[0275] - For each night of the study, participants completed questionnaires daily and monitored their sleep using the SleepScore Max device.

[0276] [Tables4] Participants Sample tested Week 1 Group (N=16) Extract according to the invention Week 2 Group (N=32) Control Week 3 Group (N=16) Extract according to the invention Data analysis:

[0277] Objective and self-reported data on nighttime sleep were analyzed at Using JMP Pro statistical software (version 15) and a mixed model, data were collected from the participants. An alpha level of 0.05 was used for all statistical tests. Comparisons were made between the control and the extract. Percentages were calculated relative to the control condition. Statistical methods:

[0278] The data obtained and the percentage changes were subjected to a two-way Student's t-test for paired data. The statistical significance value is p<0.05. Results :

[0279] The extract according to the invention significantly increased total sleep time (p < 0.05) compared to the control, particularly the duration of deep sleep (p < 0.05). Participants slept an average of 6.5 hours (392 minutes) per night with the unscented control cream versus 6.7 hours (402 minutes) with the cream containing the extract according to the invention. The duration of deep sleep also increased from 1.2 hours (73 minutes) with the control cream to 1.3 hours (79 minutes) with the cream containing the extract according to the invention (p < 0.05).

[0280] EXAMPLE 5: Cosmetic products incorporating the extract according to the invention

[0281] A) Night cream comprising 1% of a precursor composition comprising 0.25% by weight of the extract according to the invention prepared according to Example 1 in pentylene glycol Trade Name INCI % by weight DEIONIZED WATER AQUA (water) 71.65 CARBOPOL ULTREZ 20 ACRYLATES / C10-30 ALKYL ACRYLATE CROSSPOLYMER 0.30 ARLACEL 165 GLYCERYL STEARATE (and) PEG-100 STEARATE 6.00 DUB ININ ISONONYL ISONONANOATE 15.00 LIPEX SHEA™ Shea Butter (BUTYROSPERMUM PARKII (SHEA) BUTTER) 5.00 DEKABEN C4 PHENOXYETHANOL (and) METHYL-PARABENE (and) ETHYLPARABENE (and) BUTYLPARABENE (and) PROPYL-PARABENE 1.00 SODIUM HYDROXIDE SODIUM HYDROXIDE 0.05 "Extract" in A-Leen-5® Pentylene glycol and tea tree oil 1.00 100.00

[0283] B) Anti-fatigue cream comprising 1% a precursor composition comprising 0.25% by weight of the extract according to the invention prepared according to Example 1 in tri-heptanoin. Trade Name INCI % by weight DEIONIZED WATER AQUA (water) 79.30 SATIAXANE™ VPC 911 XANTHAN GUM 0.50 DERMOFEEL® GSC GLYCERYL STEARATE CITRATE 2.00 DERMOFEEL® PS POLYGLYCERYL-3 STEARATE 2.00 SWEET ALMOND OIL PRUNUS AMYGDALUS DULCIS OIL 3.00 LANETTE® 16 CETYL ALCOHOL 2.00 LIPEX SHEASOFT™ BUTY-ROSPERMUM PARKII BUTTER 3.00 CETIOL® C5 COCO-CAPRYLATE 3.00 VITAPHEROLE® E-1000 TOCOPHEROL (and) HELIANTHUS ANNUUS (sunflower) SEED OIL 0.20 DERMOSOFT® 1388 GLYCERIN (and) SODIUM ANISATE (and) SODIUM LE-VULINATE (and) AQUA (water) 4.00 "Extract" in Tri-heptanoin Triheptanoin and tea tree oil 1.00 100.00

Claims

Demands

1. Cosmetic use of an oily extract of Melaleuca altemifolia, as a cosmetic agent for regenerating, repairing or anti-fatigue of healthy skin, wherein said extract comprises: - more than 20% of compounds selected from sesquiterpenes and sesquiterpenoids, and - less than 6% of terpinen-4-ol, the percentages corresponding to the percentage of peak area corresponding to the chemical compounds of interest relative to the total peak area of ​​the chromatogram obtained by GC / FID analysis on a non-polar column.

2. Cosmetic use according to claim 1, characterized in that said extract of Melaleuca altemifolia comprises less than 15%, preferably less than 10%, better still less than 2.0% of terpineols.

3. Cosmetic use according to claim 1 or 2, characterized in that said extract of Melaleuca altemifolia comprises: - less than 5.0%, preferably less than 2.0%, better less than 1.0%, of terpinen-4-ol, and / or - less than 5.0%, preferably less than 2.0%, better less than 1.5%, of alpha-terpineol.

4. Cosmetic use according to any one of claims 1 to 3, characterized in that said extract of Melaleuca altemifolia comprises more than 30%, preferably more than 40%, of compounds selected from sesquiterpenes and sesquiterpenoids.

5. Cosmetic use according to any one of claims 1 to 4, characterized in that said extract of Melaleuca altemifolia comprises: - 5 to 15% aromadendrene, - 10 to 25% ledene, - 10 to 25% delta-cadinene, - 1 to 5% globulol, and - 1 to 5% viridifloral.

6. Cosmetic use according to any one of claims 1 to 5, characterized in that said extract of Melaleuca altemifolia is obtained by fractional distillation of an essential oil from leaves and / or terminal branches of Melaleuca altemifolia.

7. Cosmetic use according to any one of claims 1 to 6, wherein said extract of Melaleuca altemifolia is used to treat or prevent one or more signs of skin fatigue chosen from loss of skin radiance, dull complexion, cloudy complexion, loss of evenness of complexion, drawn facial features, dark circles under the eyes, bags under the eyes, swollen eyelids, alteration of the smooth appearance of the skin, increase in skin roughness, loss of elasticity, loss of density, loss of firmness, loss of hydration, appearance of wrinkles, appearance of redness, and combinations thereof.

8. Cosmetic use according to any one of claims 1 to 6, wherein said extract of Melaleuca alternifolia is used as a cosmetic agent to promote or enhance skin recovery during sleep and / or as a cosmetic agent to potentiate the natural skin repair and regeneration mechanisms controlled by melatonin.

9. Cosmetic use according to any one of claims 1 to 8, wherein said extract of Melaleuca alternifolia is further used to increase the total duration of sleep, and / or that of deep sleep in a tired subject in whom the fatigue is not associated with or caused by a pathological condition.

10. Cosmetic use according to any one of claims 1 to 9, wherein said extract of Melaleuca alternifolia is present as a cosmetic active agent in a cosmetic composition, preferably a cream, balm, mask, serum or lotion.

11. Extract of Melaleuca alternifolia as defined in any one of claims 1 to 6.

12. Cosmetic composition comprising Melaleuca alternifolia extract according to claim 11 in combination with at least one cosmetically acceptable excipient.

13. Cosmetic composition according to claim 12, characterized in that it comprises from 0.0005 to 0.01%, preferably from 0.001% to 0.005% by weight of said extract of Melaleuca alternifolia.

14. A cosmetic composition according to any one of claims 12 to 13, said cosmetic composition being selected from the group consisting of aqueous solutions, hydroalcoholic solutions, oil-in-water (O / W) or water-in-oil (W / O) or multiple (triple: W / O / W or W / O / O) emulsions, nanoemulsions, in particular W / O nanoemulsions, aqueous gels, or dispersions of an oil phase in an aqueous phase using spherules, suspensions, preferably in media aqueous or hydroalcoholic, liposome suspensions, powders, lotions, milks, creams, ointments, gels, foams, and salves.

15. Cosmetic composition according to any one of claims 12 to 14, said composition being a treatment for the treatment or prevention of skin fatigue, for example a serum, a cream, a mask or a balm, preferably for nighttime use.

16. A cosmetic method for preventing or treating signs of skin fatigue in an individual, said method comprising applying a cosmetically effective amount of an extract of Melaleuca altemifolia according to claim 11, or of a composition according to any one of claims 12 to 15, to the skin.

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