MELALEUCA ALTERNIFOLIA EXTRACT AND COSMETIC USES OF IT

Description

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 composed of several cellular layers of keratinocytes. Among others, we distinguish the germinal layer of the epidermis, called the basal layer, which contains, in particular, skin stem cells, and the spinous layer. Stratum spinosum,consisting of several layers of polygonal cells, the granular layer, Granular layer, 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, keratin-rich cells 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, a process called desquamation. Cellular regeneration of the stratum corneum is based on a process of cell maturation in which cells from the basal layer of the epidermis differentiate and gradually migrate through the various strata of the epidermis until they reach the stratum corneum as corneocytes.

[0005] The skin is usually 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 family life. Women juggling family 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 appearance, along with dark circles and bags under their eyes. In other words, their face looks tired and marked, even unwell. Projecting an image of fitness can be a major concern for active individuals, especially those working in a competitive environment and / or in customer-facing roles.

[0007] Nevertheless, there remains a current need for new cosmetic active ingredients to prevent or treat the visible effects of fatigue on the skin. Document FR 2 748 204 discloses the use in cosmetics of a rectified oily extract of Melaleuca alternifolia containing at least 60% terpinen-4-ol. SUMMARY OF THE INVENTION

[0008] The invention relates to the cosmetic use of an oily extract of Melaleuca alternifolia, 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 are expressed in relation to the total content of volatile compounds present in the extract determined by gas chromatography coupled with a flame ionization detector (GC / FID).

[0009] Preferably, the percentages correspond 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.

[0010] Preferably, the said extract of Melaleuca alternifolia contains less than 15%, preferably less than 10%, and even better less than 2.0% terpineols. In particular, the extract of Melaleuca alternifolia The invention may include: 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. In certain embodiments, said extract of Melaleuca alternifolia comprises more than 30%, preferably more than 40%, of compounds selected from sesquiterpenes and sesquiterpenoids. In particular, said extract of Melaleuca alternifoliamay include: 5 to 15% aromadendrene, 10 to 25% ledene, 10 to 25% delta-cadinene, 1 to 5% globulol, and 1 to 5% viridifloral.

[0011] In one particular embodiment, the extract from Melaleuca alternifolia is obtained by fractional distillation of an essential oil from leaves and / or terminal branches of Melaleuca alternifolia.

[0012] In certain embodiments, said extract of Melaleuca alternifoliais used to treat or prevent one or more signs of skin fatigue selected from loss of skin radiance, dull complexion, dull complexion, loss of evenness of skin tone, drawn facial features, dark circles under the eyes, bags under the eyes, swollen eyelids, alteration of skin smoothness, 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.

[0013] In other embodiments, said extract from 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.

[0014] The said extract from Melaleuca alternifoliaaccording to the invention, it can also be used to increase the total duration of sleep, and / or that of deep sleep.

[0015] Typically, the said extract from Melaleuca alternifolia is present as a cosmetic active agent in a cosmetic composition, preferably a cream, balm, mask, serum or lotion.

[0016] The invention also relates to an extract of Melaleuca alternifolia as described above. An additional purpose 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 triheptanoin.

[0017] Another additional item is a cosmetic ingredient comprising 0.1% to 1% by weight, preferably 0.1% to 0.5% by weight, of an extract of Melaleuca alternifoliaAccording to the invention, in a cosmetically acceptable vehicle, preferably pentylene glycol or triheptanoin. Said cosmetic ingredient is preferably used as a regenerating, repairing, or anti-fatigue cosmetic agent for healthy skin.

[0018] The invention also relates to a cosmetic composition comprising the extract of Melaleuca alternifolia, the precursor composition, or the cosmetic ingredient according to the invention, in combination with at least one cosmetically acceptable excipient.

[0019] 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. 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 cosmetic ingredient or precursor composition.

[0020] 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.

[0021] The cosmetic composition according to the invention may be a treatment for addressing or preventing skin fatigue, for example, a serum, cream, mask, or balm, preferably for nighttime use. 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 a cosmetic composition according to the invention on the skin.

[0022] Finally, the invention relates to the use of an extract of Melaleuca alternifolia or a cosmetic ingredient as described in this application in the manufacture of a cosmetic composition to treat, prevent, or alleviate the signs of skin fatigue. Each of the aspects and embodiments described herein may be used together, unless this is explicitly excluded or clearly excluded from the context of the embodiment or aspect in question. FIGURES

[0023] There Figure 1 represents the modulation of various genes associated with skin repair and the melatonin signaling pathway in the presence of the extract according to the invention in skin explants subjected to UV stress compared to placebo explants (subjected to UV stress, in the absence of the extract according to the invention). Figure 2 demonstrates the effect of topical application of the extract according to the invention to the face on the total duration of sleep. Figure 3 demonstrates the effect of topical application of the extract according to the invention to the face on the duration of deep sleep. Figure 4 has 10 show the results of the clinical trial of Example 6. The Figure 4 shows the transepidermal water loss (TEWL) for the group treated with the "active" cream (Extract according to the Invention) and the group treated with the placebo cream (Placebo) at T 12h, J 7 and J 28 as a relative percentage compared to J0. The Figure 5 shows skin hydration assessed by corneometry for the group treated with the "active" cream (Extract according to the Invention) and the group treated with the placebo cream (Placebo) at T 12h, J 7 and J 28 as a relative percentage compared to J0. The Figure 6 shows the antioxidant potential of the skin as measured by the FRAP (Ferric Reducing Antioxidant Parameter) test from samples of the first layers of the stratum corneum p measurements taken on the cheeks at day 0 and day 28 using a Corneofix® type adhesive patch for the group treated with the "active" cream (Extract according to the Invention) and the group treated with the placebo cream (Placebo) at day 28 as a relative percentage compared to day 0. Figures 7, 8 And 9 show the results of experiments designed to evaluate the smoothness and biomechanical properties of the skin. Figure 7 shows the evolution of the Sa parameter (skin smoothness) at T12h, J7 and J28 as a relative percentage compared to J0. Figure 8And 9 show the parameters R0 (firmness) and R2 (elasticity) as a relative percentage compared to J0 for the group treated with the "active" cream (Extract according to the Invention) and the group treated with the placebo cream. Figure 10 shows the results of the evaluation of dark circles at T12h, J7 and J28 in relative percentage compared to J0 for the group treated with the "active" cream (Extract according to the Invention) and the group treated with the placebo cream.

[0024] Statistical analysis: *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001. DETAILED DESCRIPTION

[0025] 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 darkness. 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 circadian rhythms. This hormone is produced in various tissues. The process begins with tryptophan, which is converted into serotonin. awayVarious enzymes are involved in the transformation of the enzyme into melatonin through the successive actions 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 acts 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 helps maintain and protect mitochondrial activity.

[0026] Melatonin also has beneficial effects by activating melatonin receptors. Melatonin receptors are G protein-coupled receptors that exist in two subtypes in humans: 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.

[0027] Finally, melatonin interacts with the nuclear receptor RORα, which acts as an important transcription factor involved in many biological mechanisms, including antioxidant ones.

[0028] The Plaintiff has designed a particular extract of Melaleuca alternifoliacharacterized by an original composition, namely a low terpine-4-ol content and a high content of sesquiterpene and sesquiterpenoid compounds. This extract is obtained from the fractional distillation of a traditional essential oil of Melaleuca alternifolia.Surprisingly, the Applicant has shown that this extract possesses biological activities that act on the melatonin signaling pathway to mimic and enhance its activity. Specifically, the Applicant has demonstrated that the extract according to the invention is capable of activating specific genes of the melatonin signaling pathway in skin explants exposed to UV light, such as ASMTL, RORα, SIRT3, and SLC15A1. Since ASMTL is an enzyme involved in melatonin synthesis and SLC15A1 is a melatonin transporter at the mitochondrial level, the extract therefore has the capacity to potentiate the effect of melatonin. Furthermore, like melatonin, the extract is capable of activating RORα and SIRT3, which play a key role in combating cellular damage by limiting oxidative stress.Furthermore, the extract induced the expression of antioxidant enzymes such as CAT and GPX1. 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 the natural skin regeneration and repair mechanisms controlled by melatonin. Quite surprisingly, the Applicant demonstrated that applying the extract according to the invention in a very low concentration to the skin improves sleep quality in individuals with mild lifestyle-related sleep disturbances, notably by increasing both total sleep time and the duration of deep sleep, thereby promoting the natural repair mechanisms that occur during this sleep phase.

[0029] Finally, the Applicant confirmed the anti-fatigue and regenerative effect of the extract of Melaleuca alternifoliaaccording to the invention, during a clinical trial conducted on healthy volunteers with disrupted sleep cycles (Example 6). This clinical trial showed that daily application of a cream containing the extract according to the invention prevents and / or treats signs of skin fatigue. The extract according to the invention notably improved the skin's barrier function, enhanced the skin's antioxidant capacity, prevented and improved the skin's smooth appearance and biomechanical properties, and significantly reduced dark circles in the volunteers compared to the group of volunteers treated with the placebo cream. The extract according to the invention also reduced the depth of crow's feet wrinkles, highlighting its anti-wrinkle effect.

[0030] Thus, all 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.

[0031] Without wishing to be bound by any theory, the Plaintiff 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. alternifolia.

[0032] 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.

[0033] Melaleuca alternifoliais a plant endemic to Australia that Aboriginal people have traditionally used as a medicinal herb and antiseptic. Prior art mainly concerns the essential oil of Melaleuca alternifolia, which has a composition and uses distinct from the extract according to the invention. Indeed, the essential oil of Melaleuca alternifolia, is an essential oil typically obtained by steam distillation of leaves and / or twig tips of Melaleuca alternifolia, that is to say, the tea tree. The main active component of the essential oil of M. alternifolia is terpinene-4-ol. For example, the essential oil of Melaleuca alternifolia as defined according to ISO 4730:2017 includes, among other things, 35-48% terpinen-4-ol, as well as 14-28% gamma-terpinene, 6-12% alpha-terpinene, and 0.2-5% alpha-terpineol.

[0034] The essential oil of M. alternifoliais traditionally used in dermatology and medicine for its anti-acne, antibacterial, and antifungal properties. The essential oil of M. alternifolia It is thus used on the skin or mucous membranes to treat infections such as fungal infections, skin abscesses, boils, or canker sores. It is also used to treat certain ENT infections or as a repellent in aromatherapy.

[0035] The present invention therefore relates to the said extract of Melaleuca alternifolia and its uses in the cosmetic field. a. Excerpt from Melaleuca alternifolia according to the invention

[0036] Thus, according to a first aspect, the present invention relates to an extract of Melaleuca alternifolia poor in terpine-4-ol, or more generally in terpineols and monoterpenes, and enriched in sesquiterpenes and / or sesquiterpenoids.

[0037] The excerpt from Melaleuca alternifoliaaccording to the invention is liposoluble. More precisely, the extract according to the invention is an oily extract, also referred to as oil.

[0038] Preferably, the extract of Melaleuca alternifolia according to the invention comprises: more than 20% of compounds selected from sesquiterpenes and sesquiterpenoids, and less than 6% of terpinene-4-ol.

[0039] Unless otherwise stated in this application, the percentages of compounds included in the extract of Melaleuca alternifolia correspond to the percentages 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, for example based on dimethylpolysiloxane, preferably carried out under the conditions described in example 1.

[0040] In some embodiments, the extract from Melaleuca alternifoliaThe 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. 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.

[0041] Terpinen-4-ol is also called 4-terpineol, para-menth-1-en-4-ol, or 1-isopropyl-4-methyl-3-cyclohexen-1-ol.

[0042] In some embodiments, the extract from Melaleuca alternifolia according to the invention comprises less than 5.0%, preferably less than 2.0%, or even less than 1.5%, of alpha-terpineol.

[0043] In some embodiments, the extract from Melaleuca alternifolia according to the invention comprises, generally, 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.

[0044] 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.

[0045] In some embodiments, the extract from Melaleuca alternifolia according to the invention comprises less than 10%, preferably less than 5% or 2%, or even less than 1%, of monoterpenes.

[0046] Monoterpenes are terpenes formally composed of two isoprene units.

[0047] 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.

[0048] In particular, the extract from Melaleuca alternifoliaaccording to the invention may comprise less than 5%, preferably less than 2%, or even less than 1% or 0.5% of terpinenes.

[0049] In some embodiments, the extract from Melaleuca alternifolia 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.

[0050] In some embodiments, the extract from Melaleuca alternifolia 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.

[0051] Sesquiterpenes are terpenes formally composed of three isoprene units.

[0052] Within the scope 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-1,4-diene.

[0053] Sesquiterpenoids are derivatives of sesquiterpenes, generally formed by synthetic or biological modification of sesquiterpenes (typically, by oxidation and / or rearrangement).

[0054] In particular, sesquiterpenoids include additional functional groups compared to sesquiterpenes, notably an oxygen (e.g., an ester, alcohol, ketone, or ether function) and / or fewer alkyl groups (e.g., one less methyl).

[0055] In the context of the present invention, the sesquiterpenoids include, among others, calamenene, alpha-calacorene, beta-calacorene, delta-cadinol, elema-1,11-dien-15-al, globulol, vidifloral, cadin-4-en-10-ol, ledol, rosifoliol, or spathulenol. The extract according to the invention may in particular comprise at least 20% (eg at least 25%) of the following sesquiterpene and sesquiterpenoid compounds: aromadendrene, ledene, delta-cadinene, globulol and viridifloral.

[0056] In one particular embodiment, said extract of Melaleuca alternifolia according to the invention comprises: 5 to 15% aromadendrene, 10 to 25% ledene, and 10 to 25% delta-cadinene.

[0057] In a more particular embodiment, said extract of Melaleuca alternifolia according to the invention comprises: 5 to 15% aromadendrene, 10 to 25% ledene, 10 to 25% delta-cadinene, 1.0 to 5.0% globulol, and 1.0 to 5.0% viridifloral.

[0058] In another additional embodiment, the extract according to the invention comprises: less than 6% (e.g., less than 5%, 4.5%, 4.0%, 3.5%, 3.0%, 2.0%, 1%, 0.5%) of terpinene-4-ol, less than 5% (e.g., less than 2.0% or 1.5%) of alpha-terpineol, less than 15.0% (e.g., less than 10.0%, 8.0%, 6.0%, 5.0%, 4.0%, 3.0%, or 2.0%) of terpineols, less than 10% (e.g., less than 5%, 2%, or 1%) of monoterpenes, less than 10% (e.g., less than 5%, 2%, or 1%) of monoterpenoids other than terpineols, at least 25% (for example, more than 30%, 40%, 50%, 60%, or 70%) of compounds selected from sesquiterpenes and sesquiterpenoids.

[0059] Preferably, the extract according to the invention comprises at least 25% of compounds selected from aromadendrene, ledene and delta-cadinene.

[0060] In particular, the extract according to the invention may include: 5 to 15% aromadendrene, 10 to 25% ledene, and 10 to 25% delta-cadinene.

[0061] In another additional embodiment, the extract according to the invention comprises: less than 6% (e.g., less than 5%, 4.5%, 4.0%, 3.5%, 3.0%, 2.0%, 1%, 0.5%) of terpinene-4-ol, less than 5% (e.g., less than 2.0% or 1.5%) of alpha-terpineol, less than 15.0% (e.g., less than 10.0%, 8.0%, 6.0%, 5.0%, 4.0%, 3.0% or 2.0%) of terpineols, less than 10% (e.g., less than 5%, 2%, or 1%) of monoterpenes, less than 10% (e.g., less than 5%, 2%, or 1%) of monoterpenoids other than terpineols, at least 27 % (for example more than 30%, 40%, 50%, 60%, or 70%) of compounds selected from sesquiterpenes and sesquiterpenoids.

[0062] Preferably, the extract according to the invention comprises at least 27% of compounds selected from aromadendrene, ledene, delta-cadinene, globulol and viridifloral.

[0063] In particular, the extract according to the invention may include: 5 to 15% aromadendrene, 10 to 25% ledene, 10 to 25% delta-cadinene, 1.0 to 5.0% globulol, and 1.0 to 5.0% viridifloral.

[0064] 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.

[0065] The starting essential oil is typically rich in terpinene-4-ol and is generally obtained by steam distillation or hydrodistillation of all or part of Melaleuca alternifolia, preferably leaves and / or twigs.

[0066] In some embodiments, the starting essential oil of Melaleuca alternifolia may include: 35 to 48% (e.g., 37 to 45%) of terpinene-4-ol, 10 to 28% (e.g., 14 to 28%) of gamma-terpinene, 5.0 to 13% (e.g., 6 to 12%) of alpha-terpinene, 0.2 to 8.0% (e.g., 0.2 to 5.0% or 1.5 to 8.0%) of alpha-terpineol, and

[0067] Preferably, it comprises less than 3.0% aromadendrene, less than 3.0% ledene, less than 3.0% delta-cadinene, less than 1.0% globulol, and less than 1.0% viridifloral. The extract of Melaleuca alternifolia according to the invention is advantageously a fraction obtained from the fractional distillation of an essential oil of Melaleuca alternifoliaFractional 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 to collect 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 (particularly terpin-4-ol). Once the fraction(s) enriched in monoterpene and monoterpenoid compounds have been collected, the fraction corresponding to the extract according to the invention can be collected.This fraction is typically obtained under reduced temperature and pressure conditions allowing the collection of compounds with a boiling point above 200°C at atmospheric pressure.

[0068] Fractional distillation being 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.

[0069] 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.

[0070] 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 being preferably 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 alternifolia. Compared to a conventional essential oil, the extract according to the invention is depleted in monoterpenes and monoterpinoids.

[0071] In certain embodiments, said extract of Melaleuca alternifolia is obtained by a process comprising: i) a hydrodistillation step of all or part of Melaleuca alternifolia, preferably its leaves and / or branch tips, so that a first essential oil is obtained, 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. b. Precursor composition, cosmetic ingredient And cosmetic composition comprising the extract according to the invention

[0072] The excerpt from Melaleuca alternifoliaaccording to the invention presents cosmetic effects and can therefore be used as a cosmetic agent.

[0073] In the context of the present invention, the term " cosmetic agent", an agent that exerts a cosmetic effect on the skin.

[0074] In the context of the present invention, by "cosmetic effect" any non-therapeutic effect, aimed at modifying and / or improving the appearance of the skin or mucous membranes such as the lips, or at protecting 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.

[0075] As will be detailed below, the extract according to the invention can be used as a cosmetic agent for skin regeneration, repair, or anti-fatigue. For this purpose, the extract of Melaleuca alternifoliaaccording to the invention is generally introduced as a cosmetic agent in a cosmetic composition. In other words, said extract is typically applied to the skin of the individual to be treated via a cosmetic composition. A precursor composition or cosmetic ingredient comprising the extract of Melaleuca alternifolia according to the invention can be prepared beforehand and then incorporated into the cosmetic composition.

[0076] 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 the extract of Melaleuca alternifolia according to the invention, in a cosmetically acceptable vehicle.

[0077] Another object of the present invention is a cosmetic ingredient comprising 0.1% to 1% by weight, preferably 0.1% to 0.5% by weight, of the extract of Melaleuca alternifoliaaccording to the invention, in a cosmetically acceptable vehicle

[0078] 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, triheptanoin, an aqueous solution of these, or a mixture of these.

[0079] Preferably, said vehicle is pentylene glycol or triheptanoin.

[0080] In a particular embodiment, the cosmetic ingredient or precursor composition according to the invention essentially consists of, or consists of, an extract of Melaleuca alternifolia according to the invention in a cosmetically acceptable vehicle selected from pentylene glycol and tripheptanoin.

[0081] The excerpt of Melaleuca alternifoliaaccording to the invention is preferably present in a content of 0.1% to 1% by weight, preferably 0.1 to 0.5% by weight, relative to the total weight of the cosmetic ingredient.

[0082] 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, the precursor composition or cosmetic ingredient according to the invention, in combination with at least one cosmetically acceptable excipient.

[0083] The cosmetically acceptable excipient(s) in the composition may be chosen from among diluents, dispersing agents, gelling agents, emollients, vectorizing agents (such as polycationic polymers, phospholipids, unilamellar or multilamellar liposomes, niosomes, ethosomes, lamellar systems, nanosomes, lipid or polymer vesicles, nanospheres, micro- or nanoparticles of natural or synthetic polymers, hydrogels), gums, resins, solvents, particularly lower alcohols including 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, and other agents. pearlescent pigments, 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.

[0084] In one embodiment, the cosmetic composition comprises 0.0005 to 0.01%, preferably 0.001% to 0.005% by weight of the extract of Melaleuca alternifolia according to the invention.

[0085] More specifically, the cosmetic composition in question may include: from 0.0005% to 0.01% by weight, preferably from 0.001% to 0.005% by weight of said e of Melaleuca alternifolia, and 99.99% to 99.9995% by weight of one or more cosmetically acceptable excipients.

[0086] 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 or of said cosmetic ingredient.

[0087] More specifically, the cosmetic composition in question may include: 0.5% to 5% by weight, preferably 1% to 3% by weight of said precursor composition or cosmetic ingredient, and 95% to 99.5% by weight of one or more cosmetically acceptable excipients.

[0088] In some embodiments, the cosmetic composition further comprises one or more active ingredients with an additional cosmetic effect. The term "active ingredient with a cosmetic effect," "active ingredient with a cosmetic effect," "cosmetic agent," or "active ingredient with a 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.

[0089] 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.

[0090] Specifically, the cosmetic composition may include tocopherols, and / or plant extracts such as flaxseed extracts, exopolysaccharide extracts of Vibrio, peptides such as trifluoroacetyl tripeptide-2.

[0091] In a particular mode, the cosmetic composition may include an active ingredient chosen from among 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 screen, and combinations thereof.

[0092] Examples of anti-pollution agents include extracts of Chrysanthellum Indicum polysaccharides, particularly marine polysaccharides, originating from a fermentation environment Alteromonas and Nigari salts.

[0093] Examples of under-eye concealers include extracts of Chrysanthelum Indicum or even sulfated algae extracts and polysaccharides, in particular of Ascophyllum nodosum Or of Asparagopsis Armata.

[0094] Examples of moisturizing agents include urea, pidolic acid (PCA) and its derivatives, particularly 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, hydrolysates of silk, keratin or soy, plant extracts rich in polysaccharides and / or polyphenols, for example extracts of Aloe, cornflower (Centaurea cyanus),extracts rich in polysaccharides, particularly those derived from the fermentation media of marine microorganisms such as Alteromonas and combinations thereof.

[0095] Examples of anti-aging agents include ascorbic acid and its derivatives such as magnesium ascorbyl phosphate, glycosaminoglycans and their derivatives, and polysaccharides. Cyathea, collagen, flaxseed extracts ( Flaxseed ), peptides such as Caprooyl-Tetrapeptide-3 and trifluoroacetyl tripeptide-2, extracts of Polygonum aviculare, extracts of brown algae, in particular of Ascophyllum nodosum, extracts of ferns, in particular Cyathea cumingii.

[0096] Examples of anti-stress agents include Rosality™ products (a combination of rose water and rose essential oil) and pink-flowered rockrose extract, marketed under the brand name IBR-Chill™.

[0097] Examples of soothing agents include allantoin, aloe extract, and birch extract (for example Betula alba ) , of willowherb ( Epilobium angustifolium ) , of chestnut (for example Castenea sativa ), of blueberry (for example Centaurea cyanus ), of centella (for example Asian Centella ), horsetail (for example Equisetum arvense ), fennel (for example Foeniculum vulgare ), witch hazel (for example Hamamelis virginiana ), ivy (for example Helix ivy ), of habiscus sabdariffa, of lilies (for example Lilium candidum ), mauve (for example Malva sylvestris ), lemon balm (for example Melissa officinalis ), of skullcap (for example Scutellaria baicalensis ), of mimosa (for example Mimosa tenuiflora ), of cinquefoil (for example Potentilla erecta ), an oligosaccharide extract or an oligosaccharide, for example from flax, peptides such as palmitoyl tripeptide-8, polysaccharide extracts, including exopolysaccharide extracts from the fermentation medium d'Alteromonas and combinations thereof.

[0098] Examples of antioxidant agents include HMR (hydroxymethyl resorcinol), ascorbic acid and its derivatives, vitamin B9, histidine hydrochloride, or willowherb extract ( Epilobium augustifolium ). 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.

[0099] Examples of sebum-regulating agents include flax lignans, rice powder, zinc gluconate, sarcosine, and an extract of Cinnamomum zeylanicum bark, an extract from a lawyer, an extract from Backhousia citriodora and combinations thereof.

[0100] Examples of anti-redness agents include saponins, flavonoids, ruscogenins, esculosides, and extracts containing them, for example, extracts of Ruscus, as well as certain essential oils, for example lavender or rosemary.

[0101] Examples of stain-removing agents include extracts such as licorice ( Glycyrrhiza glabra ), jackfruit extract ( Artocarpus heterophyllus ), extracts from Rumex ( R.occidentalis ) , plant extracts belonging to the citrus genus, resveratrol, peptides such as oligopeptide-68, nonapeptide-1, kojic acid, magnesium ascorbyl phosphate and combinations thereof.

[0102] 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.

[0103] In a more specific embodiment, said cosmetic composition comprises: from 0.0005% to 0.01% by weight, preferably from 0.001% to 0.005% by weight of said extract of Melaleuca alternifoliaaccording to the invention, from 69.99% to 99.9995% by weight of one or more cosmetically acceptable excipients, and from 0% to 30% by weight, for example from 0 to 15% by weight, of one or more additional cosmetic active agents.

[0104] In a more specific embodiment, said cosmetic composition comprises: 0.5% to 5% by weight, preferably 1% to 3% by weight of said precursor composition or of said cosmetic ingredient as described above, 65% to 99.5% by weight of one or more cosmetically acceptable excipients, and 0% to 30% by weight, for example 0 to 15% by weight, of one or more additional cosmetic active agents.

[0105] The excerpt from Melaleuca alternifoliaAccording to the invention, the precursor composition or the cosmetic ingredient comprising it can be incorporated into any type of cosmetic composition. Preferably, it 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 W / O 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.

[0106] In some embodiments, the cosmetic composition according to the invention is a cream, a balm, a mask, a serum or a lotion.

[0107] 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. c. Cosmetic Uses and Procedures According to the Invention

[0108] According to a further aspect, the Invention also relates to the use of the extract of Melaleuca alternifolia as described above as a skin regenerating, repairing or anti-fatigue cosmetic agent, and more specifically, to treat or prevent one or more signs of skin fatigue.

[0109] 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.

[0110] For the purposes of the invention, the terms " skin " And " skin »refers to any part of the skin on the human body, particularly 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 lips, and on the neck.

[0111] In the context of the present invention, the extract or composition according to the invention is typically applied topically, preferably 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 (i.e., 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.

[0112] 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.

[0113] We mean by “anti-fatigue agent” a cosmetic agent capable of preventing, treating or mitigating the " skin effects or signs » fatigue, that is to say the effects of fatigue on the skin.

[0114] In the context of the present invention, the term " cutaneous signs or effects”, any non-pathological alteration or modification of the visual appearance or mechanical properties of the skin. Within the scope of the present invention, the " skin signs or effects » are caused by, or associated with, fatigue.

[0115] We mean by "to prevent a sign or effect," the act of delaying or preventing the appearance of said sign or effect on the skin. This is understood to mean " treat a sign or effect,”The act of reducing, mitigating, diminishing, correcting, or slowing the development of said sign or effect on the skin. The sign(s) of skin fatigue may, for example, be a loss of radiance, a dull complexion, a cloudy complexion, a loss of evenness of skin tone, drawn facial features, dark circles under the eyes, bags under the eyes, swollen eyelids, an alteration in the smoothness 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 fine lines or wrinkles, the appearance of redness, and combinations thereof.

[0116] Within the scope of the present invention, fatigue causing non-pathological changes or alterations to the skin can be of any type. It can be transient or chronic. This 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, a sedentary lifestyle, overwork, intense or unsuitable work activities, night work or shift work, significant screen time, stress, anxiety, or worries related to professional or family life.

[0117] Fatigue can also result from physiological situations such as pregnancy or menopause.

[0118] Preferably, the fatigue is not associated with or caused by a pathological condition in the individual. In some embodiments, the extract of Melaleuca alternifolia 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: Prevent, treat, or reduce dark circles and / or puffiness around the eyes; Prevent, treat, or reduce eyelid swelling; Prevent, treat, or reduce skin pigmentation irregularities, including age spots; Even out or unify skin tone; Make skin tone brighter, more radiant, and / or clearer; Prevent or treat dull, uneven, and / or drawn features; Make skin, especially on the face, look fresher and more luminous; Soothe facial features; Make skin look less tired, more relaxed, and fresher; Make eyes look less tired, more rested, and brighter; Promote or accelerate epidermal recovery, especially on the face; Revitalize skin, especially on the face; Promote a healthy glow; Prevent, treat, or restore the skin's barrier function; Prevent, treat, or reduceLoss of skin firmness, particularly on the face; preventing, treating, or alleviating skin dehydration (or equivalently, "moisture loss"); preventing, treating, delaying, or alleviating the appearance of wrinkles or fine lines; and / or preventing, treating, or alleviating the appearance of redness.

[0119] It goes without saying that the non-pathological alterations listed above are associated with or caused by fatigue on the skin.

[0120] In certain embodiments, the extract according to the invention can be used as a cosmetic agent to prevent, treat or alleviate one or more signs of skin fatigue selected from skin dehydration, loss of elasticity, loss of firmness, wrinkles, dark circles and combinations thereof.

[0121] In the context of the present invention, the term " regenerative agent Or repairman »A cosmetic agent capable of promoting or stimulating skin regeneration or 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 genes involved in collagen synthesis in the skin.

[0122] As illustrated in the examples, applying the extract to the skin at a very low concentration, notably imperceptible by smell, helps to improve sleep.

[0123] It has also been shown that the extract according to the invention is capable of activating melatonin signaling pathways, including those involved in DNA repair mechanisms and cellular defense against oxidative stress, as well as in melatonin synthesis and transport, for example induced by exposure to environmental stress such as excessive UV exposure

[0124] 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.

[0125] In one particular aspect, the extract according to the invention is used to promote or improve skin recovery, especially during sleep. The extract according to the invention is specifically used to enhance the skin's natural repair and regeneration mechanisms controlled by melatonin.

[0126] 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.

[0127] According to a further embodiment, the extract according to the invention is used to promote or aid skin recovery during the sleep phase.

[0128] 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.

[0129] The extract according to the invention can be used to repair / regenerate skin exposed to stress, including environmental stress such as exposure to sun, wind, humidity, dryness or chemicals or processes such as abrasion, rays etc... or stress related to lifestyle (jet lag, lack of sleep, night work etc...).

[0130] In addition or alternatively, the extract according to the invention is used to induce collagen synthesis in the skin.

[0131] Additionally or alternatively, the extract according to the invention can also be used as an agent to reduce the formation of reactive oxygen species (ROS) and / or to stimulate the expression of antioxidant proteins, particularly antioxidant enzymes in the skin. In one particular embodiment, the extract of Melaleuca alternifoliaAccording to the invention, the active cosmetic agent is present in a cosmetic composition, preferably a cream, balm, mask, serum, or lotion, as described above. The concentration of the extract Melaleuca alternifolia According to the invention, the concentration 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.

[0132] It goes without saying that such uses are intended for individuals exposed to fatigue as defined above.

[0133] 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. For example, this could be a woman or a man between 25 and 65 years of age, particularly between 25 and 55 years of age. As an example, this could be a woman between 25 and 45 years of age.

[0134] A further 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 alternifolia according to the invention, or a cosmetic composition according to the invention on the skin.

[0135] The cosmetic process according to the invention is intended to treat or prevent one or more cutaneous effects of fatigue, preferably chosen from among an alteration of the skin tone, in particular a dull complexion, a lack of radiance of the complexion or a loss of uniformity of the complexion, in particular the appearance of pigment spots, drawn facial features, the appearance of bags and / or dark circles 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 wrinkles, the appearance of redness, and combinations thereof.

[0136] The method according to the invention can produce any one of the following effects in an individual exposed to fatigue: Prevent, treat, or reduce dark circles and / or puffiness around the eyes; Prevent, treat, or reduce eyelid swelling; Prevent, treat, or reduce skin pigmentation irregularities, including age spots; Even out or unify skin tone; Make skin tone brighter, more radiant, and / or clearer; Prevent or treat dull, uneven, and / or drawn features; Make skin, especially on the face, look fresher and more luminous; Soothe facial features; Make skin look less tired, more relaxed, and fresher; Make eyes look less tired, more rested, and brighter; Promote or accelerate epidermal recovery, especially on the face; Revitalize skin, especially on the face; Promote a healthy glow; Prevent, treat, or restore the skin's barrier function; Prevent, treat, or reduceLoss of skin firmness, particularly on the face; preventing, treating, or alleviating skin dehydration (or equivalently, "moisture loss"); preventing, treating, delaying, or alleviating the appearance of wrinkles; and / or preventing, treating, or alleviating the appearance of redness.

[0137] 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 extract of Melaleuca alternifoliaAccording to the invention, or the cosmetic composition comprising it, the product 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. For example, the patient can apply a dose of 1 g to 2 g of the cosmetic composition to their face in the evening. General Definitions:

[0138] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as that commonly understood by a person skilled in the technical field of this application.

[0139] This application is not limited by the examples of processes, uses and compositions described herein, and all processes, uses and compositions similar or equivalent to those described herein may be used in the embodiments of this application.

[0140] The headings and section titles provided herein shall not be construed as limitations on the various aspects or embodiments of this application. The headings and section titles are used herein for organizational purposes only and shall not be interpreted as limiting the invention described. All defined terms are more fully defined by reference to the application as a whole.

[0141] All publications, including patent documents and scientific articles, cited in this application are incorporated by reference in their entirety to the same extent as if each individual publication were incorporated individually by reference. The citation of such publications shall in no way be construed as an admission that such publications constitute prior art. If any definition stated in this application is contrary to or inconsistent with any definition stated in the patents, applications, published applications, and other publications incorporated herein by reference, the definition stated in this application shall prevail over the definition incorporated by reference. All features described in this application may be combined in any combination.Each feature described in this application may be replaced by another feature having the same, equivalent, or similar purpose. Therefore, unless expressly stated otherwise, each disclosed feature is only one example from a generic set of equivalent or similar features.

[0142] Definitions of terms may appear throughout the description. It should be understood that this description is not limited to the specific embodiments described, as these may, of course, vary. It should also be understood that the terminology used here is intended solely to describe specific embodiments and is not meant to be exhaustive.

[0143] It should be noted that, as used here and in the attached claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly indicates otherwise. For example, "a" or "an" include "at least one" and "one or more".

[0144] The terms "comprising," "includes," and "composed of" as used herein are synonymous with "including," "includes," "containing," "contains," and their grammatical variants. These terms are inclusive or open and do not preclude the presence of additional, unmentioned members, elements, or process steps.

[0145] Where a range of values ​​is provided, it is understood that each intermediate value between the upper and lower bounds of that range is also specifically disclosed and encompassed in that description. EXAMPLES

[0146] The invention will be better understood in light of the following examples, which are given purely for illustrative purposes and are not intended to limit the scope of the invention. EXAMPLE 1: Preparation of an extract according to the invention 1. Obtaining an extract of Melaleuca alternifolia according to the invention

[0147] As described, 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.

[0148] Table 1 details the physical and chemical characteristics of the essential oil of Melaleuca alternifolia steam distilled 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").

[0149] 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-1MS capillary column (100% dimethylpolysiloxane, 60 m x 0.15 mm ID, 0.25 µm film thickness; 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; hydrogen peroxide (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 makeup gas flow rates of the FID were 350, 35 and 20 ml / min, respectively. Table 1: Characteristics of the starting essential oil PHYSICO-CHEMICAL CHARACTERISTICS OF THE STARTING ESSENTIAL OIL APPEARANCE LIQUID COLOR COLORLESS - LIGHT YELLOW SMELL CHARACTERISTIC RELATIVE DENSITY (20°C / 20°C) 0,885 - 0,906 REFRACTION INDEX (20°C) 1,475 - 1,482 ROTARY POWER (20°C) +5° A + 15° VISUAL HUMIDITY NO WATER VISIBLE AT 20°C Miscibility in ethanol: 85% (v / v) 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 Table 2: Volatile compound composition of the starting essential oil and the Extract according to the Invention. COMPOUNDS % CONTENT (GC-FID AREA) STARTING ESSENTIAL OIL EXTRACT ACCORDING TO THE INVENTION alpha-Pinene 1,0 - 6,0 - Sabinène 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-Terpinene 10,0 - 28,0 0,01 alpha-Terpinolene 1,5 - 5,0 0,01 Terpinene-4-ol 37,0 - 45,0 0,16 alpha-Terpineol 1,5 - 8,0 1,09 Aromadendre UP TO 3.0 8,65 Ledène 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 EXAMPLE 2 : Evaluation of the extract according to the invention on skin explants

[0150] Protocol: The aim of this study was to evaluate the restorative effect of the extract according to the invention on skin explants 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 at a concentration of 0.5% by weight. This precursor composition (also called a cosmetic ingredient) was then formulated in carbopol at a concentration of 1% by weight. This final composition was used in this experiment.

[0151] From an abdominoplasty of a 46-year-old Caucasian woman (reference: P2471-AB46, phototype II-III according to the Fitzpatrick skin color classification), 51 explants with a mean diameter of 11 mm (+1 mm) were prepared. The explants were kept alive in BEM (BIO-EC's Explants Medium) at 37°C in a humid atmosphere with 5% CO2 for 2 days. On the second day, the culture medium was replaced with HBSS solution, and the explants were then irradiated with UV light (UV-Placebo group and UV-Extract group) with a dose of 13.5 J / cm² of UVA corresponding to 3 MED (minimum erythemal dose) and a dose of 0.15 J / cm² of UVB corresponding to 1 MED or not (Placebo group).At the end of irradiation, the placebo product (for the "Placebo" and "UV-Placebo" groups) or the composition containing the extract according to the Invention ("UV-extract") was applied topically to the skin surface of the corresponding explants at a rate of 2 µL per cm² explant (≈ 2 mg / cm²) for an additional 24 hours. On day 3, the explants were fixed in RNAlater before 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 µL / reaction). Using a spike control, the ΔCq was calculated. The benchmarks evaluated for each qPCR reaction using CFX Manager 3.1 software are as follows: . The logarithmic amplification curve for each sequence of interest. The melting curves represent fluorescence intensities recorded after the last cycle. The temperature increases from 65°C to 96°C in 0.5°C increments every 5 seconds. The curves representing the inverse of the derivative of the fluorescence signal with respect to temperature (in °C) allow for the verification of a single amplicon.

[0152] All samples underwent gene expression profiling. For quantification, the number of cycles was normalized to the B2M reference gene: (i) Cq quantité relative par échantillon et par gène = E gène Cq contrô l e − Cq traité E = efficacité des paires d ' amorces = % efficacité * 0 , 01 + 1 Cq (control) = the quantitative threshold calculated by the CFX Maestro in "regression" mode for the control condition. Cq (treated) = the quantitative threshold calculated by the CFX Maestro in "regression" mode for the treated condition. gene = target gene (ii) Normalized target gene expression = NE Cq = relative quantity; the denominator corresponds to the normalization factor including the two reference genes: ref 1 = B2M gene = target gene

[0153] 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). Furthermore, when homogeneous gene modulation is conserved between biological triplicates, a P-value <0.05 (according to the t-test) is indicated by an asterisk.

[0154] Results: Compared to the UV-placebo condition, the extract triggered a strong induction of OGG1, 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 suggests that the extract according to the invention acts on the extracellular matrix, increasing collagen synthesis. Interestingly, the extract induced an increase in the expression of melatonin-associated genes (ASMTL, RORα, SIRT3, and SLC15A1), which suggests that the extract targets the same pathway as melatonin and is therefore capable of activating melatonin signaling pathways, particularly those involved in mechanisms protecting against oxidative stress, notably UV-induced stress. Stimulation of this signaling pathway would explain the stimulation or repression of the genes mentioned above.

[0155] All of these results support the use of the extract according to the invention as an anti-fatigue, regenerating or repairing agent for the skin. Table 3: Gene expression results UV-Extract vs UV-Placebo P-Value ASMTL 1,55 0,042 RORα 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

[0156] 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

[0157] The study consisted of evaluating two samples of face cream, one "active" cream and one "placebo" cream, used separately over three weeks: Product A-cream “active”: unscented generic 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), “Placebo” cream: unscented generic face cream (see example 5, table 5 below) comprising 1% pentylene glycol (A-Leen ®< 5, Minasolve) alone.

[0158] Devices: For objective sleep measurements, participants used the SleepScore Max device (SleepScore Labs, Carlsbad, CA), a non-contact monitoring device that uses respiratory signals 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.

[0159] Study design and procedure: This was a randomized, controlled, in-context study using an unscented control cream. Participants applied the creams at bedtime in their natural sleep environment. The study ran from Sunday night to Friday morning for three consecutive weeks. Participants used a different sample each week. The control sample was used during the second week. Table 3 provides an overview of the study design. For each night of the study, participants completed daily questionnaires and monitored their sleep using the SleepScore Max device. Table 4: Clinical trial details Participants Sample tested Week 1 Group (N=16) Extract according to the invention Week 2 Group (N=32) Placebo Week 3 Group (N=16) Extract according to the invention Data analysis:

[0160] Objective and self-reported data on nighttime sleep were analyzed using JMP Pro statistical software (version 15) with a mixed-methods model. An alpha level of 0.05 was used for all statistical tests. Comparisons were made between the control and the extract group. Percentages are calculated relative to the control group. Statistical methods:

[0161] The data obtained and the percentage changes were subjected to a two-way Student's t-test for paired data. The statistical significance value was p < 0.05. Results :

[0162] 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). EXAMPLE 5 : Cosmetic products incorporating the extract according to the invention

[0163] A) Night cream comprising 1% of a precursor composition (also called a cosmetic ingredient) comprising 0.25% by weight of the extract according to the invention prepared according to Example 1 in pentylene glycol Table 5: Composition of a night cream 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) METHYLPARABEN (and) ETHYLPARABEN (and) BUTYLPARABEN (and) PROPYLPARABEN 1,00 SODIUM HYDROXIDE SODIUM HYDROXIDE 0,05 "Extract" in A-Leen-5 ®< Pentylene glycol and tea tree oil 1,00 100,00 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 triheptanoin. [Table 6]

[0164] Table 6: Composition of an anti-fatigue cream 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 ™< BUTYROSPERMUM 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 LEVULINATE (and) AQUA (water) 4,00 "Excerpt" from Triheptanoin Triheptanoin and tea tree oil 1,00 100,00 EXAMPLE 6 : Improvement of signs of skin fatigue

[0165] Protocol: A clinical trial was conducted to confirm the anti-fatigue effect of the extract according to the Invention. Forty-four volunteers were divided equally into two groups (22 individuals in the test group: "active" cream and 22 individuals in the placebo group: Placebo cream).

[0166] The volunteers recruited were people working irregular hours, young adults who were very socially active and used to going out and going to bed late or traveling (jet lag), or new mothers. The volunteers therefore had disrupted sleep cycles but were not being treated for sleep disorders.

[0167] The study was conducted over 28 days with measurements taken on day 0, 12 hours, day 7 and day 28. The products were applied once a day by the volunteers, in the evening before going to bed.

[0168] The two creams tested are: "Active" cream: generic unscented face cream comprising 1% of a cosmetic ingredient comprising 0.25% by weight of the extract of Example 1, in Triheptanoin (see example 5, table 5 above), "Placebo" cream: generic (see example 5, table 5 above without the extract) unscented face cream comprising 1% of Triheptanoin alone.

[0169] Devices: To observe signs of fatigue, the following parameters were measured: Transepidermal water loss (TEWL), assessed using the Tewameter® TM 300 (Courage+Khazaka, electronic GmbH). Skin hydration, assessed with a Corneometer®. Skin antioxidant potential, measured from samples of the outermost stratum corneum taken from the cheeks on days 0 and 28 by the experimenter using Corneofix® (Courage+Khazaka, electronic GmbH). The FRAP (Ferric Reducing Antioxidant Parameter) test is then performed. Crow's feet wrinkles, measured with the Primos 3D (GFMesstechnik GmbH). Skin elasticity and firmness, measured by the suction / stretching method (Cutometer® MPA 580, Courage+Khazaka, electronic GmbH). This device applies negative pressure (suction) where the skin is drawn into the measuring cup of the probe which allows its depth of penetration to be measured by an optical measuring system.The assessment of dark circles, based on original images taken with the Bio blue light scanner for each volunteer and processed by specific software, was measured using the individual typology angle (ITA°). Method statistics:

[0170] For each time point, a statistical study was conducted to analyze the significance of the parameter changes. The data obtained and the percentage changes were subjected to a two-way ANOVA. The statistical significance value was p < 0.05 (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001). Results :

[0171] The results of this clinical trial are illustrated by the Figures 4 has 10 .

[0172] The group treated with the "active" cream showed a significant decrease in transepidermal water loss (TEWL), which increases over time, compared to the group treated with the "placebo" cream. This highlights an improvement in the skin's barrier function ( Figure 4 ). A significant improvement in skin hydration was also observed in the group treated with the "active" cream, with an increase of +7.5%**, +7.9%** and +12%**** after 12 hours, 7 days and 28 days, respectively ( Figure 5 ).

[0173] A significant increase in the skin's antioxidant potential was also observed in the group treated with the "active" cream compared to the group treated with the placebo cream (reduction of Fe3+ to Fe2+ of +17% at 28 days compared to the placebo group, Figure 6An improvement in the smoothness of the skin and its biomechanical properties was observed in the group treated with the "active" cream compared to the "placebo" group. Thus, the "active" cream, comprising the extract according to the Invention, smoothed the skin and rapidly reduced the appearance of wrinkles, as evidenced by the decrease in the Sa parameter of -6.9%*** and -9%**** after 7 days and 28 days ( Figure 7 ).

[0174] A clear reduction in crow's feet wrinkles was also visually observable on the images taken at 0J and 28J and also confirmed by measurements taken by the Primos 3D.

[0175] The "active" cream also improved the skin's biomechanical properties by increasing its firmness and elasticity, as illustrated by a significant decrease in the R0 parameter ( Figure 8 ) and a significant increase in the R2 parameter ( Figure 9 ) compared to the placebo group.

[0176] Finally, the "active" cream induced a rapid and significant lightening of dark circles under the eyes compared to the placebo group ( Figure 10 ).

[0177] In conclusion, this clinical trial showed that the extract of Melaleuca alternifolia is a powerful skin anti-fatigue agent. Daily application of a cream containing 0.0025% of the extract according to the invention improved the signs of skin fatigue in people with disturbed sleep cycles.

[0178] The Extract according to the Invention notably improved the skin's barrier function, enhanced the skin's antioxidant power, prevented and improved the smooth appearance and biomechanical properties of the skin, and reduced dark circles in volunteers, significantly compared to the group of volunteers treated with the placebo cream.

[0179] The present invention is not intended to be limited in scope to the particular embodiments described, which are provided, for example, to illustrate various aspects of the invention. Various modifications or variations of the compositions and processes described will become evident from the description and teachings given in this application. Such modifications may be made without departing from the true scope and spirit of this application and are intended to be included within the scope of this patent application. Although the invention may be described in relation to specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments.Indeed, the various modifications or variants of the embodiments of the invention which are obvious to a person skilled in the art in the cosmetic field or related fields are intended to fall within the scope of the following claims.

Claims

1. A cosmetic use of an oily extract of Melaleuca alternifolia, as a regenerative, repairing or anti-fatigue cosmetic agent in a 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 being expressed relative to the total content of volatile compounds present in the extract determined by gas chromatography coupled with a flame ionization detector (GC / FID).

2. The cosmetic use of claim 1, characterized in that said extract of Melaleuca alternifolia comprises less than 15%, preferably less than 10%, better still less than 2.0% of terpineols.

3. The cosmetic use of claim 1 or 2, characterized in that said extract of Melaleuca alternifolia comprises: - less than 5.0%, preferably less than 2.0%, better still less than 1.0%, of terpinen-4-ol, and / or - less than 5.0%, preferably less than 2.0%, better still less than 1.5%, of alpha-terpineol, and / or - more than 30%, preferably more than 40% of compounds selected from sesquiterpenes and sesquiterpenoids.

4. The cosmetic use of any one of claims 1 to 3, characterized in that said extract of Melaleuca alternifolia comprises: - from 5% to 15% of aromadendrene, - from 10% to 25% of ledene, - from 10% to 25% of delta-cadinene, - from 1% to 5% of globulol, and - from 1% to 5% of viridifloral.

5. The cosmetic use of any one of claims 1 to 4, characterized in that said extract of Melaleuca alternifolia is obtained by fractional distillation of an essential oil of leaves and / or terminal branches of Melaleuca alternifolia.

6. The cosmetic use of any one of claims 1 to 5, wherein said extract of Melaleuca alternifolia is used to treat or prevent one or more signs of skin fatigue selected from a loss of radiance of the skin, a dull complexion, a peaky complexion, a loss of uniformity of the complexion, haggard facial features, dark circles around the eyes, bags under the eyes, puffy eyelids, an alteration in 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, an appearance of wrinkles, an appearance of redness, and combinations thereof.

7. The cosmetic use of any one of claims 1 to 5, wherein said extract of Melaleuca alternifolia is used as a cosmetic agent for promoting or improving skin recovery during sleep and / or as a cosmetic agent for potentiating the natural mechanisms of skin repair and regeneration controlled by melatonin.

8. The cosmetic use of any one of claims 1 to 7, wherein said extract of Melaleuca alternifolia is further used for increasing the total duration of sleep, and / or that of deep sleep.

9. The cosmetic use of any one of claims 1 to 8, wherein said extract of Melaleuca alternifolia is present as a cosmetic active agent in a cosmetic composition, preferably a cream, a balm, a mask, a serum or a lotion.

10. An oily extract of Melaleuca alternifolia comprising: - more than 20% of compounds selected from sesquiterpenes and sesquiterpenoids, and - less than 6% of terpinen-4-ol, the percentages being expressed relative to the total content of volatile compounds present in the extract determined by gas chromatography coupled with a flame ionization detector (GC / FID), preferably said oily extract of Melaleuca alternifolia is as defined in any one of claims 2 to 5.

11. A cosmetic ingredient comprising an extract of Melaleuca alternifolia of claim 10, preferably comprising from 0.1% to 1.0% by weight, or more preferably from 0.1% to 0.5% by weight, of the extract of Melaleuca alternifolia in a cosmetically acceptable carrier selected from pentylene glycol or triheptanoin.

12. A cosmetic composition comprising the extract of Melaleuca alternifolia of claim 10, or the cosmetic ingredient of claim 11, in combination with at least one cosmetically acceptable excipient.

13. The cosmetic composition of 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 or from 0.5% to 5% by weight, preferably from 1% to 3% by weight, of said cosmetic ingredient.

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

15. The cosmetic composition of any one of claims 12 to 14, said composition being a care product for use in the treatment or prevention of skin fatigue, for example a serum, a cream, a mask or a balm, preferably for use at night.

16. A cosmetic method for preventing, reducing or treating signs of skin fatigue in subject, said method comprising the application of a cosmetically effective amount of an extract of Melaleuca alternifolia of claim 10, or that of a cosmetic composition of any one of claims 12 to 15 on the skin.