Melaleuca alternifolia extract and cosmetic use thereof

Abstract

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

Description

Technical Field

[0001] The present invention relates to the field of cosmetics, and in particular to a cosmetic agent for counteracting the effects of fatigue on the skin. Background Art

[0002] The skin is the first barrier that protects the body from external aggressions. This organ is composed of multiple layers of tissue. A distinction is made between them: the epidermis, which is the outermost part of the skin, the dermis, a connective tissue composed of fibroblasts and extracellular matrix, which has the function of skin adhesion and nutrition, and the hypodermis, which is composed of fat cells.

[0003] The epidermis is composed of multiple cell layers of corneocytes. In particular, the germ layer of the epidermis (called the basal layer) contains, inter alia, skin stem cells, the spinous layer (the spinous cell layer) (composed of multiple layers of polygonal cells), the granular layer (the granular cell layer) (comprising one to three layers of flat cells containing cytoplasmic inclusions), the transparent keratin granules, and finally the epidermal stratum corneum (the stratum corneum composed of keratin-rich anucleated cells (called corneocytes), which corresponds to the terminal stage of keratinocyte differentiation).

[0004] The outermost cells of the epidermis are constantly removed and replaced by cells from the lower layers, a process called desquamation. Cell regeneration of the epidermis is based on a process of cell maturation, in which cells of the basal layer of the epidermis differentiate and gradually migrate to the various layers of the epidermis until they reach the epidermis in the form of keratinocytes.

[0005] The skin is often the first to show signs of fatigue. Fatigue can be caused by a variety of factors, such as lack of sleep, a poor or unbalanced diet, overwork, high intensity activity or lack of activity at work, or a disturbed home environment. Women who balance family life and work, as well as young workers in urban environments, are particularly at risk of chronic fatigue.

[0006] Individuals exposed to this type of fatigue may display haggard features, a dull or even pale complexion, or dark circles and eye bags. In other words, their face may look tired and worn, or even unhealthy. However, presenting the image of a healthy person may be a major concern for individuals who are active at work, especially in a competitive environment and / or when in contact with clients.

[0007] Nevertheless, there is still a need for new cosmetic actives to prevent or treat the visible effects of fatigue on the skin. Summary of the invention

[0008] A subject of the present invention is the cosmetic use of an oily extract of Melaleuca alternifolia as a regenerative, repairing or anti-fatigue cosmetic agent for healthy skin, wherein the extract comprises:

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

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

[0011] The percentages are expressed relative to the total content of volatile compounds present in the extract as determined by gas chromatography coupled with a flame ionization detector (GC / FID).

[0012] Preferably, the percentage corresponds to the percentage of the peak area corresponding to the compound of interest relative to the total area of ​​the peaks of the chromatogram obtained by GC / FID analysis on a non-polar column.

[0013] Preferably, the Melaleuca alternifolia extract contains less than 15%, preferably less than 10%, and better still less than 2.0% of terpineol. In particular, the Melaleuca alternifolia extract according to the present invention may contain:

[0014] - less than 5.0%, preferably less than 2.0%, more preferably less than 1.0% of terpinen-4-ol, and / or

[0015] Less than 5.0%, preferably less than 2.0%, more preferably less than 1.5% of alpha-terpineol.

[0016] In certain embodiments, the Melaleuca alternifolia extract comprises more than 30%, preferably more than 40%, of a compound selected from sesquiterpenes and sesquiterpenoids. Specifically, the Melaleuca alternifolia extract may comprise:

[0017] -5% to 15% aromandrene,

[0018] -10% to 25% ledene,

[0019] -10% to 25% delta-cadinene,

[0020] - 1% to 5% eucalyptol, and

[0021] -1% to 5% viridifloral.

[0022] In a specific embodiment, the Melaleuca alternifolia extract is obtained by fractionating the essential oils of the leaves and / or terminal shoots of Melaleuca alternifolia.

[0023] In certain embodiments, the Melaleuca alternifolia extract is used to treat or prevent one or more signs of skin fatigue selected from the group consisting of loss of skin radiance, dull skin tone, pale skin tone, loss of uniformity in skin tone, a haggard look, dark circles around the eyes, eye bags, puffy eyelids, changes in the smooth appearance of skin, increased skin roughness, loss of elasticity, loss of density, loss of firmness, loss of moisture, the appearance of wrinkles, the appearance of redness, and combinations thereof.

[0024] In other embodiments, the Melaleuca alternifolia extract is used as a cosmetic agent to promote or improve skin recovery during sleep and / or as a cosmetic agent to enhance the natural mechanisms of skin repair and regeneration controlled by melatonin.

[0025] The Melaleuca alternifolia extract according to the present invention may further be used to increase the total sleep duration and / or the duration of deep sleep.

[0026] Typically, the Melaleuca alternifolia extract is present as a cosmetic active agent in a cosmetic composition, preferably a cream, a balm, a mask, a serum or a lotion.

[0027] Another subject of the present invention is an extract of Melaleuca alternifolia as described above.

[0028] A further subject is a precursor composition for preparing a cosmetic composition comprising from 0.1% to 1% by weight, preferably from 0.1% to 0.5% by weight, of an extract of Melaleuca alternifolia according to the invention in a cosmetically acceptable carrier, preferably pentylene glycol or triheptanoin.

[0029] Another further subject is a cosmetic ingredient comprising 0.1% to 1% by weight, preferably 0.1% to 0.5% by weight, of a Melaleuca alternifolia extract according to the invention in a cosmetically acceptable carrier, preferably pentylene glycol or triheptanoin. The cosmetic ingredient is preferably used as a regenerative, repairing or anti-fatigue cosmetic agent for healthy skin.

[0030] Another subject of the present invention is a cosmetic composition comprising an extract of Melaleuca alternifolia, a precursor composition or a cosmetic ingredient according to the invention, in combination with at least one cosmetically acceptable excipient.

[0031] The cosmetic composition according to the present invention may comprise 0.0005% to 0.01% by weight, preferably 0.001% to 0.005% by weight of the Melaleuca alternifolia extract.

[0032] 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.

[0033] The cosmetic composition according to the invention can be chosen from aqueous solutions, hydroalcoholic solutions, oil-in-water (O / W) emulsions or water-in-oil (W / O) emulsions or multiple (triplet: W / O / W or O / W / O) emulsions, nanoemulsions, especially O / W nanoemulsions, aqueous gels, or globules-assisted dispersions of a fatty phase in an aqueous phase, suspensions (preferably in an aqueous or hydroalcoholic medium), liposomal suspensions, powders, lotions, emulsions, creams, unguents, gels, foams and ointments.

[0034] The cosmetic composition according to the invention may be a care product for treating or preventing skin fatigue, such as a serum, a cream, a mask or a balm, preferably for use at night.

[0035] A subject of the present invention is a cosmetic method for preventing or treating signs of skin fatigue in a subject, said method comprising applying on the skin a cosmetically effective amount of a Melaleuca alternifolia extract or a cosmetic composition according to the invention.

[0036] Finally, a subject of the present invention is the use of a Melaleuca alternifolia extract or a cosmetic ingredient as described in this application for the manufacture of a cosmetic composition for treating, preventing or alleviating the signs of skin fatigue.

[0037] Each aspect and embodiment described herein can be used together unless it is explicitly excluded or explicitly excluded from the context of the embodiment or aspect being considered. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 Represents the regulation of various genes related to skin repair and the melatonin signaling pathway in skin explants subjected to UV stress in the presence of an extract according to the invention compared to placebo explants (UV stressed in the absence of an extract according to the invention).

[0039] Figure 2 The effect of skin application of the extract according to the invention on the face during the entire sleep period is shown.

[0040] Figure 3 The effect of skin application of the extract according to the invention on the face during deep sleep is shown.

[0041] Figures 4 to 10 The results of the clinical trial of Example 6 are shown.

[0042] Figure 4 The transepidermal water loss (TEWL) at T12 h, D7 and D28 is shown as a relative percentage with respect to D0 for the group treated with the "active" cream (extract according to the invention) and the group treated with the placebo cream (Placebo).

[0043] Figure 5 The skin water content assessed by corneometry at T12 h, D7 and D28 is shown as a relative percentage with respect to D0 for the group treated with the "active" cream (extract according to the invention) and the group treated with the placebo cream (Placebo).

[0044] Figure 6 The first layer of stratum corneum samples collected on the cheek at D0 and D28 are shown by FRAP (Ferric Reduction Antioxidant Parameter) test using Adhesive patch pairs The antioxidant potential of the skin was measured at D28 as a relative percentage with respect to D0 for the group treated with the "active" cream (extract according to the invention) and the group treated with the placebo cream (placebo).

[0045] Figure 7 , 8 and 9 show the results of experiments designed to evaluate the smooth appearance and biomechanical properties of the skin. Figure 7 The changes in parameter Sa (smooth skin appearance) at T12 h, D7 and D28 are shown as relative percentages with respect to D0. Figure 8 and 9 The parameters R0 (firmness) and R2 (elasticity) are shown as relative percentages with respect to D0 for the group treated with the "active" cream (extract according to the invention) and the group treated with the placebo cream.

[0046] Fig.10 The results are shown for the change in dark circles at T12 h, D7 and D28, as relative percentages with respect to D0, for the group treated with the "active" cream (extract according to the invention) and the group treated with the placebo cream.

[0047] Statistical analysis: *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001. DETAILED DESCRIPTION OF THE INVENTION

[0049] Melatonin is a hormone produced by the pineal gland (also known as the pineal gland). In the presence of light, the secretion of melatonin is inhibited, while in darkness it is stimulated. Through melatonin, the pineal gland informs the brain not only about the relative duration of dark and light periods within a 24-hour period (daily cycle), but also throughout the year (seasonal cycle). Melatonin is known as the "sleep hormone" and plays a central role in regulating the rhythm of the biological clock. This hormone is produced in various tissues. The process begins with tryptophan, which is converted into serotonin by various enzymes in order to finally convert serotonin into melatonin through the sequential action of arylalkylamine N-acetyltransferase and hydroxyindole-O-methyltransferase. Melatonin can act on the skin via two different pathways: receptor-independent and receptor-dependent. Melatonin is able to exert cellular antioxidant effects, in particular by directly capturing free radicals, but also indirectly by increasing the activity of antioxidant enzymes. This molecule has the potential to cross cell membranes and can also play a role in maintaining and protecting mitochondrial activity.

[0050] Melatonin also produces beneficial effects by activating melatonin receptors. Melatonin receptors are G protein-coupled receptors that exist in humans in two subtypes, MT1 and MT2. These two receptors produce a biological rhythm that induces sleep. Melatonin receptors are expressed not only in the brain, but also in the periphery. MT1 receptors are expressed in particular in the skin. MT1 receptors are involved in mechanisms that protect the skin from environmental stress and are also involved in skin aging or pigmentation.

[0051] Finally, melatonin interacts with the nuclear receptor RORα, which acts as an important transcription factor involved in various biological mechanisms, especially antioxidant mechanisms.

[0052] The applicant has developed a special Melaleuca alternifolia extract characterized by an original composition, namely a low content of terpinene-4-ol and a high content of terpene-type and terpene-like compounds. The extract comes from the fractionation of conventional essential oils of Melaleuca alternifolia. Surprisingly, the applicant has demonstrated that the extract has biological activity, enabling it to act on the signaling pathway of melatonin to mimic and enhance its activity. The applicant has particularly demonstrated that the extract according to the invention is able to activate specific genes of the signaling pathway of melatonin in skin explants subjected to UV exposure, such as ASMTL, RORα, SIRT3 and SLC15A1. Since ASMTL is an enzyme capable of synthesizing melatonin, and since SLC15A1 is a mitochondrial melatonin transporter, the extract has the ability to enhance the action of melatonin. In addition, like melatonin, the extract is able to activate RORα and SIRT3, which play an important role in resisting cell damage by limiting oxidative stress. In addition, the extract induces the expression of antioxidant enzymes such as CAT and GPX1.

[0053] The extract according to the invention is also able to induce genes involved in collagen synthesis (COL3A1 and COL1A2) and in DNA repair (OGG1), so as to promote the natural mechanisms of skin repair and regeneration controlled by melatonin.

[0054] Quite surprisingly, the Applicant has demonstrated that the application of the extract according to the invention to the skin in very low concentrations can improve the sleep quality of subjects suffering from mild sleep disorders due to their lifestyle, in particular by increasing the total sleep time as well as the time of deep sleep, thus promoting the natural repair mechanisms that occur in particular in this sleep stage.

[0055] Finally, the applicant demonstrated the anti-fatigue and regenerative effects of the Melaleuca alternifolia extract according to the invention during a clinical trial conducted in healthy volunteers suffering from sleep cycle disturbances (Example 6). This clinical trial showed that daily application of a cream comprising an extract according to the invention can prevent and / or treat signs of skin fatigue. Compared to a group of volunteers treated with a placebo cream, the extract according to the invention can significantly improve the barrier function of the skin, improve the antioxidant capacity of the skin, prevent and improve the smooth appearance and biomechanical properties of the skin and reduce the dark circles of the volunteers. The extract according to the invention can also reduce the depth of crow's feet, which highlights the anti-wrinkle effect.

[0056] All these results therefore support the cosmetic use of the extract according to the invention as an anti-fatigue agent (by topical application), that is to say, to treat or prevent signs of skin fatigue, and more generally as an agent to promote or improve skin recovery during sleep, in particular by enhancing the natural skin regeneration and repair mechanisms controlled by melatonin.

[0057] Without wishing to be bound by any theory, the applicant believes that these properties are caused by the specific composition of the extract prepared by fractionating the essential oil of M. alternifolia.

[0058] To the best of the applicant's knowledge, the extract according to the present invention and its use as an anti-fatigue agent for the skin has never been described or suggested in the prior art.

[0059] Melaleuca alternifolia is a plant endemic to Australia, traditionally used by Australian aborigines as a medicinal herb and preservative. The prior art essentially relates to essential oils of Melaleuca alternifolia, which have a different composition and use than the extract according to the invention. In particular, the essential oil of Melaleuca alternifolia is an essential oil generally obtained by steam distillation of the leaves and / or terminal branches of Melaleuca alternifolia (i.e. tea plant).

[0060] The main active ingredient of the essential oil of Melaleuca alternifolia is terpinen-4-ol. For example, the essential oil of Melaleuca alternifolia defined according to ISO 4730:2017 standard contains, in particular, 35-48% terpinen-4-ol, as well as 14-28% γ-terpinene, 6-12% α-terpinene and 0.2-5% α-terpineol.

[0061] The essential oil of Melaleuca alternifolia is traditionally used in dermatology or medicine due to its anti-acne, antibacterial and antifungal properties. Therefore, the essential oil of Melaleuca alternifolia is used on the skin or mucous membranes to treat infections such as fungal diseases, skin abscesses, boils or mouth sores. It is also used to treat certain ENT infections or as an insect repellent in aromatherapy.

[0062] A subject of the present invention is therefore said Melaleuca alternifolia extract and its use in the cosmetics sector.

[0063] a. Melaleuca alternifolia extract according to the present invention

[0064] Thus, according to a first aspect, the present invention relates to an extract of Melaleuca alternifolia low in terpinen-4-ol, or more generally low in terpineol and monoterpenes, and rich in sesquiterpenes and / or sesquiterpenoids.

[0065] The extract of Melaleuca alternifolia according to the invention is fat-soluble. More precisely, the extract according to the invention is an oily extract, which can also be indicated by the term oil.

[0066] Preferably, the extract of Melaleuca alternifolia according to the present invention comprises:

[0067] - more than 20% of a compound selected from sesquiterpenes and sesquiterpenoids, and

[0068] - Less than 6% of terpinen-4-ol.

[0069] Unless otherwise indicated, in the present application, the percentages of compounds contained in the extract of Melaleuca alternifolia correspond to the area percentage of the peak corresponding to the compound of interest relative to the total area of ​​the chromatogram peaks obtained by GC / FID analysis on a non-polar column (for example based on dimethylpolysiloxane), preferably carried out under the conditions described in Example 1.

[0070] In certain embodiments, an extract of Melaleuca alternifolia according to the invention comprises less than 5.0%, such as less than 4.5%, 4.0% or 3.5% terpinen-4-ol.

[0071] In certain embodiments, the extract according to the invention comprises less than 3.0%, such as less than 2.0% or 1.0% or even less than 0.5% terpinen-4-ol.

[0072] Terpinen-4-ol is also known as 4-terpineol, p-menth-1-en-4-ol or 1-isopropyl-4-methyl-3-cyclohexen-1-ol.

[0073] In certain embodiments, the Melaleuca alternifolia extract according to the invention comprises less than 5.0%, preferably less than 2.0%, or even less than 1.5% alpha-terpineol.

[0074] In certain embodiments, a Melaleuca alternifolia extract according to the invention typically 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% terpineol.

[0075] Terpineol is an unsaturated monocyclic monoterpene alcohol. In the context of the present invention, terpineol includes terpinen-4-ol, α-terpineol, β-terpineol, γ-terpineol, terpinen-1-ol and terpinen-5-ol.

[0076] In certain embodiments, the Melaleuca alternifolia extract according to the invention comprises less than 10%, preferably less than 5% or 2%, or even less than 1% monoterpenes.

[0077] Monoterpenes are terpenes composed strictly of two isoprene units.

[0078] In the context of the present invention, monoterpenes include in particular terpinenes, such as α-terpinene and γ-terpinene (or terpinene), α-phellandrene, α-dimethylstyrene, α-pinene, β-pinene, limonene, sabinene, p-cymene, α-thujene or myrcene.

[0079] In particular, the Melaleuca alternifolia extract according to the invention may contain less than 5%, preferably less than 2%, or even less than 1% or 0.5% terpinene.

[0080] In certain embodiments, the Melaleuca alternifolia extract according to the invention comprises less than 10%, preferably less than 5% or 2%, or even less than 1% of monoterpenoids other than terpineol, such as eucalyptol, camphor or trans-piperidinol.

[0081] In certain embodiments, the Melaleuca alternifolia 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.

[0082] Sesquiterpenes are terpenes composed strictly of three isoprene units.

[0083] In the context of the present invention, sesquiterpenes include in particular neroliene, viridiflorene, delta-cadinene, beta-caryophyllene, allo-neroliene, valencene, beta-phellandrene, bicycloelene, alpha-cuberene, beta-guaiacene, alpha-cubane, alpha-guiane, beta-ylangene, alpha-humulene or beta-cedrene, beta-malolene, gamma-murolene, gamma-curcumene, gamma-cadinene or 1,4-diene.

[0084] Sesquiterpenoids are derivatives of sesquiterpenes, usually formed by synthetic or biological modification (usually by oxidation and / or rearrangement) of sesquiterpenes.

[0085] In particular, sesquiterpenoids contain additional functional groups, in particular oxygen (eg ester, alcohol, ketone or ether oxide functional groups) and / or fewer alkyl groups (eg one less methyl group) compared to sesquiterpenes.

[0086] In the context of the present invention, sesquiterpenes include in particular acorus, α-corus, β-corus, δ-cadinol, elema-1,11-dien-15-al, eucalyptus alcohol, viridifloral, cadin-4-en-10-ol, rosifoliol, rosifoliol or spartol.

[0087] The extract according to the invention may in particular contain at least 20% (for example at least 25%) of the following sesquiterpenes and sesquiterpenoid compounds: neroliene, calendulene, delta-cadinene, eucalyptol and viridifloral.

[0088] In a specific embodiment, the Melaleuca alternifolia extract according to the present invention comprises:

[0089] -5% to 15% of citronellal,

[0090] -10% to 25% hornene, and

[0091] -10% to 25% delta-cadinene.

[0092] In a more specific embodiment, the Melaleuca alternifolia extract according to the present invention comprises:

[0093] -5% to 15% of citronellal,

[0094] -10% to 25% of hornene,

[0095] -10% to 25% delta-cadinene,

[0096] - 1.0% to 5.0% eucalyptol, and

[0097] -1.0% to 5.0% viridifloral.

[0098] In another additional embodiment, the extract according to the invention comprises:

[0099] - less than 6% (e.g. less than 5%, 4.5%, 4.0%, 3.5%, 3.0%, 2.0%, 1%, 0.5%) of terpinen-4-ol,

[0100] - less than 5% (e.g. less than 2.0% or 1.5%) of alpha-terpineol,

[0101] - less than 15.0% (e.g. less than 10.0%, 8.0%, 6.0%, 5.0%, 4.0%, 3.0% or 2.0%) of terpineol,

[0102] - less than 10% (e.g. less than 5%, 2% or 1%) of monoterpenes,

[0103] - less than 10% (e.g. less than 5%, 2% or 1%) of monoterpenoids other than terpineol,

[0104] - At least 25% (e.g. more than 30%, 40%, 50%, 60% or 70%) of a compound selected from sesquiterpenes and sesquiterpenoids.

[0105] Preferably, the extract according to the invention comprises at least 25% of compounds selected from neroliene, claryene and delta-cadinene.

[0106] Specifically, the extract according to the present invention may contain:

[0107] -5% to 15% of citronellal,

[0108] -10% to 25% hornene, and

[0109] -10% to 25% delta-cadinene.

[0110] In another additional embodiment, the extract according to the invention comprises:

[0111] - less than 6% (e.g. less than 5%, 4.5%, 4.0%, 3.5%, 3.0%, 2.0%, 1%, 0.5%) of terpinen-4-ol,

[0112] - less than 5% (e.g. less than 2.0% or 1.5%) of alpha-terpineol,

[0113] - less than 15.0% (e.g. less than 10.0%, 8.0%, 6.0%, 5.0%, 4.0%, 3.0% or 2.0%) of terpineol,

[0114] - less than 10% (e.g. less than 5%, 2% or 1%) of monoterpenes,

[0115] - less than 10% (e.g. less than 5%, 2% or 1%) of monoterpenoids other than terpineol,

[0116] - At least 27% (e.g. more than 30%, 40%, 50%, 60% or 70%) of a compound selected from sesquiterpenes and sesquiterpenoids.

[0117] Preferably, the extract according to the invention comprises at least 27% of compounds selected from neroliene, claryene, delta-cadinene, eucalyptol and viridifloral.

[0118] Specifically, the extract according to the present invention may contain:

[0119] -5% to 15% of citronellal,

[0120] -10% to 25% of hornene,

[0121] -10% to 25% delta-cadinene,

[0122] - 1.0% to 5.0% eucalyptol, and

[0123] -1.0% to 5.0% viridifloral.

[0124] The extract according to the present invention can be obtained from the essential oil of Melaleuca alternifolia (hereinafter referred to as "first essential oil" or "starting essential oil") by fractional distillation.

[0125] The starting essential oil is usually rich in terpinen-4-ol and is generally obtained by steam distillation or by hydrodistillation of all or part of Melaleuca alternifolia (preferably leaves and / or branches).

[0126] In certain embodiments, the starting essential oil of Melaleuca alternifolia may include:

[0127] - 35% to 48% (e.g. 37% to 45%) of terpinen-4-ol,

[0128] - 10% to 28% (e.g. 14% to 28%) of gamma-terpinene,

[0129] - 5.0% to 13% (e.g. 6% to 12%) of alpha-terpinene,

[0130] - 0.2% to 8.0% (e.g. 0.2% to 5.0% or 1.5% to 8.0%) of alpha-terpineol, and

[0131] Preferably, it comprises less than 3.0% of euphorene, less than 3.0% of claryene, less than 3.0% of delta-cadinene, less than 1.0% of eucalyptol and less than 1.0% of viridifloral.

[0132] The extract of Melaleuca alternifolia according to the present invention is advantageously a fraction resulting from the fractionation of the essential oil of Melaleuca alternifolia. The fractionation is generally carried out under reduced pressure using a fractionation device comprising a boiler, a fractionation column, a condenser and a collector. The essential oil is slowly heated under reduced pressure to collect various successive fractions, each corresponding to a temperature step. The fractionation is carried out to first collect at least one (preferably 2, 3 or 4) distillation fractions rich in monoterpenoid and monoterpenoid compounds (particularly terpine-4-ol). Once the fractions rich in monoterpenoid and monoterpenoid compounds are collected, the fraction corresponding to the extract according to the present invention can be collected. The fraction is generally obtained under temperature and reduced pressure conditions so that compounds having a boiling point higher than 200° C. at atmospheric pressure can be collected.

[0133] Since fractional distillation is a well-known method, the person skilled in the art knows how to determine the heating temperature and pressure to be used in order to obtain from a given essential oil the fraction corresponding to the extract according to the invention, for example by carrying out routine tests and / or using nomograms.

[0134] In a preferred embodiment, the extract according to the invention is a distilled fraction of the essential oil of Melaleuca alternifolia, preferably obtained by fractional distillation.

[0135] The extract according to the invention may therefore also be indicated as a "distilled fraction of the essential oil of Melaleuca alternifolia", preferably obtained by steam or hydrodistillation of leaves and / or branches of Melaleuca alternifolia. The extract according to the invention is therefore typically an oily extract or oil of Melaleuca alternifolia. Compared to conventional essential oils, the extract according to the invention is depleted of monoterpenes and monoterpenoids.

[0136] In certain embodiments, the Melaleuca alternifolia extract is obtained by the steps comprising:

[0137] i) a step of hydrodistilling all or part of the Melaleuca alternifolia tree, preferably its leaves and / or terminal branches, thereby obtaining a first essential oil,

[0138] ii) a step of fractionating said first essential oil under conditions of reduced pressure and temperature, so that fractions corresponding to said extract can be collected.

[0139] b. Precursor composition, cosmetic ingredient and cosmetic composition comprising the extract according to the present invention

[0140] The extract of Melaleuca alternifolia according to the present invention exhibits a cosmetic effect and thus can be used as a cosmetic agent.

[0141] In the context of the present invention, the expression "cosmetic agent" is understood to mean an agent which exerts a cosmetic effect on the skin.

[0142] In the context of the present invention, the expression "cosmetic effect" is understood to mean any non-therapeutic effect aimed at changing and / or improving the appearance of the skin or mucous membranes (such as the lips) or protecting them from external aggressions (sun, wind, humidity, dryness, chemicals), for example preventing and / or correcting the phenomena associated with aging, or preventing or treating the effects caused by skin fatigue.

[0143] As will be described in detail below, the extract according to the invention can be used as a skin regeneration, repair or anti-fatigue cosmetic agent. For this purpose, the Melaleuca alternifolia extract according to the invention is usually introduced into a cosmetic composition as a cosmetic agent. In other words, the extract is usually applied to the skin of the subject to be treated via a cosmetic composition. A precursor composition or a cosmetic ingredient containing the Melaleuca alternifolia extract according to the invention can be prepared in advance and then incorporated into the cosmetic composition.

[0144] A subject of the present invention is therefore a precursor composition for preparing a cosmetic composition comprising from 0.1% to 1% by weight, preferably from 0.1% to 0.5% by weight, of an extract of Melaleuca alternifolia according to the invention, in a cosmetically acceptable carrier.

[0145] Another subject of the invention is a cosmetic composition comprising from 0.1% to 1% by weight, preferably from 0.1% to 0.5% by weight, of an extract of Melaleuca alternifolia according to the invention in a cosmetically acceptable carrier.

[0146] The cosmetically acceptable carrier may be of any type. For example, it may be a cosmetically acceptable solvent, in particular a lower alcohol, in particular ethanol, isopropanol, dipropylene glycol, butylene glycol, propylene glycol, glycerol, sorbitol, propylene glycol, pentylene glycol, triheptanoin, an aqueous solution thereof or a mixture thereof.

[0147] Preferably, the carrier is pentylene glycol or triheptanoin.

[0148] In a particular embodiment, the cosmetic ingredient or precursor composition according to the invention consists essentially of or consists of an extract of Melaleuca alternifolia according to the invention in a cosmetically acceptable carrier chosen from pentylene glycol and triheptanoin.

[0149] The Melaleuca alternifolia extract according to the present 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.

[0150] Another subject of the present invention is a cosmetic composition comprising an extract of Melaleuca alternifolia according to the invention, preferably as cosmetic agent, or a precursor composition or cosmetic ingredient according to the invention, in combination with at least one cosmetically acceptable excipient.

[0151] The cosmetically acceptable excipients present in the composition may be selected from diluents, dispersants, gelling agents, emollients, vectorizing agents (e.g. polycationic polymers, phospholipids, unilamellar or multilamellar liposomes, liposomes, ethosomes, lamellar systems, nanosomes, lipid or polymer vesicles, nanospheres, microparticles or nanoparticles of natural or non-natural polymers, hydrogels), gums, resins, solvents (in particular lower alcohols, in particular ethanol, isopropanol, dipropylene glycol, butylene glycol, propylene glycol, glycerol, sorbitol and propanediol), fillers (e.g. modified and polymerized starches, titanium dioxide or metal stearates), preservatives, essential oils, pearlescent agents, dyes, odor absorbers, pH regulators or neutralizers, lubricants, thickeners, additives. Water-soluble substances such as surfactants, including anionic, cationic, amphoteric or nonionic surfactants, moisturizers, wetting agents, stabilizers, fillers, dispersants, fragrances, organic or mineral pigments such as iron oxides, oily agents such as oils or fats of plant origin, fats of animal origin, synthetic oils such as petroleum jelly, silicone oils (cyclomethicone), fatty alcohol esters, fluorinated oils, waxes, modified clays, bentonites, metal salts of fatty acids, silica, polyethylene, mica, preservatives, antibacterial agents, carriers (such as mineral water, spring water or floral water) and / or other substances commonly used in preparations in the cosmetic or pharmaceutical fields.

[0152] In one embodiment, the cosmetic composition comprises 0.0005% to 0.01% by weight, preferably 0.001% to 0.005% by weight of the Melaleuca alternifolia extract according to the invention.

[0153] More specifically, the cosmetic composition may comprise:

[0154] - 0.0005% to 0.01% by weight, preferably 0.001% to 0.005% by weight of said Melaleuca alternifolia extract, and

[0155] - 99.99% to 99.9995% by weight of one or more cosmetically acceptable excipients.

[0156] In another embodiment, the cosmetic composition comprises 0.5% to 5% by weight, preferably 1% to 3% by weight of the precursor composition or the cosmetic ingredient.

[0157] More specifically, the cosmetic composition may comprise:

[0158] - 0.5% to 5% by weight, preferably 1% to 3% by weight of said precursor composition or said cosmetic ingredient, and

[0159] - 95% to 99.5% by weight of one or more cosmetically acceptable excipients.

[0160] In certain embodiments, the cosmetic composition further comprises one or more additional active agents having a cosmetic effect. The expression "active ingredient having a cosmetic effect" or "active agent having a cosmetic effect" or "cosmetic or active agent having a cosmetic effect" is to be understood as a compound capable of exerting at least one cosmetic effect on the skin or its appendages. The expression "cosmetic effect" is to be understood as any non-therapeutic effect intended to modify and / or improve the visual appearance and mechanical properties of the skin or mucous membranes (e.g. lips), to protect them from external aggressions (sun, wind, humidity, dryness, chemicals), to prevent and / or correct phenomena associated with aging thereof, or to prevent or treat the effects of stress or fatigue on the skin.

[0161] Examples of such agents are, inter alia, anti-wrinkle agents, anti-aging agents, antioxidants, moisturizers, soothing agents, anti-redness agents, decongestants, scrubs or exfoliants, matting agents, sebum regulating agents, whitening active agents, anti-dark spot active agents, agents for reducing dark circles and eye bags, anti-stress agents, anti-fatigue agents, anti-pollution active agents, tautening agents, sunscreens and sunblocks, and combinations thereof.

[0162] Of note, the cosmetic composition may comprise tocopherol and / or plant extracts, such as flaxseed extract, Vibrio exopolysaccharide extract, peptides such as trifluoroacetyl tripeptide-2.

[0163] In a specific embodiment, the cosmetic composition may include an active agent selected from the group consisting of anti-wrinkle agents, anti-redness agents, antioxidants, moisturizers, soothing agents, sebum regulating agents, anti-dark spot or whitening agents, firming agents, anti-pollution active agents, dark circle or puffiness correctors, sunscreens or sunblocks, and combinations thereof.

[0164] As examples of anti-pollution agents, mention may be made of extracts of Chrysantellum Indicum, polysaccharides (in particular marine polysaccharides from fermentation cultures of Alteromonas) and Nigari salts.

[0165] As examples of dark circles correcting agents, mention may be made of golden chamomile extracts or extracts of algae, in particular Ascophyllum nodosum or Asparagopsis armata, and sulfated polysaccharides.

[0166] As examples of moisturizers, mention may be made of urea, oxyproline (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, saccharose (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), glycerol, propylene glycol, butylene glycol, betaine, citrulline, collagen and its derivatives, histidine, silk hydrolysates, keratin hydrolysates or soy hydrolysates, plant extracts rich in polysaccharides and / or polyphenols, such as aloe vera, Centaurea cyanus, cyanus), polysaccharide-rich extracts, especially extracts produced from fermentation media of marine microorganisms (such as Alteromonas), and combinations thereof.

[0167] As examples of anti-aging agents, mention may be made of ascorbic acid and its derivatives, such as magnesium ascorbyl phosphate, glycosaminoglycans and their derivatives, Alsophila spinulosa polysaccharides, collagen, linseed (flax) extract, peptides such as hexanoyl tetrapeptide-3 and trifluoroacetyl tripeptide-2, extracts of Polygonum multiflorum, extracts of brown algae (especially Ascophyllum nodosum), extracts of ferns (especially Alsophila sphaerocarpa).

[0168] As examples of anti-stress agents, mention may be made of Rosality TM products (a combination of rose water and rose essential oil) and extracts of pink cistus, such as those sold under the brand name IBR-Chill TM For sale.

[0169] As examples of soothing agents, mention may be made of allantoin, extracts of aloe vera, extracts of birch (e.g. betula alba), extracts of willowherb (Epilobium angustifolium), extracts of chestnut (e.g. Casteneasativa), extracts of cornflower (e.g. Centaurea cyanus), extracts of centella (e.g. Centella asiatica), extracts of horsetail (e.g. Equisetum arvense), extracts of fennel (e.g. Foeniculum vulgare), extracts of witch hazel (e.g. Hamamelis virginiana), extracts of ivy (e.g. Hedera helix), extracts of roselle, extracts of lily (e.g. Lilium candidum), extracts of mallow (e.g. Malva sylvestris), extracts of thyme (e.g. sylvestris), extracts of lemon balm (e.g., lemon balm), extracts of skullcap (e.g., Scutellaria baicalensis), extracts of mimosa (e.g., Mimosa tenuiflora), extracts of Potentilla (e.g., Potentilla pubescens), extracts of oligosaccharides or oligosaccharides (e.g., flax), peptides (e.g., palmitoyl tripeptide-8), polysaccharide extracts (particularly extracts of exopolysaccharides produced by fermentation medium of Alteromonas), and combinations thereof.

[0170] As examples of antioxidants, mention may be made of HMR (hydroxymethylresorcinol), ascorbic acid and its derivatives, vitamin B9, histidine hydrochloride or extracts of willowherb ( Epilobium augustifolium ). Active ingredients having an antioxidant effect and of the vitamin type are generally used in a percentage by weight of at least 1% relative to the total weight of the cosmetic composition.

[0171] As examples of sebum regulating agents, mention may be made of flaxseed lignans, rice flour, zinc gluconate, sarcosine, extracts of Ceylon cinnamon bark, extracts of avocado, extracts of lemon myrtle, and combinations thereof.

[0172] As anti-redness agents, mention may be made of saponins, flavonoids, ruscosapogenin, esculin, and extracts containing them, for example extracts of Ruscus, and certain essential oils, for example of lavender or rosemary.

[0173] As examples of anti-dark spot agents, there may be mentioned extracts such as liquorice (Glycyrrhyza glabra), extracts of jackfruit (Artocarpus heterophyllus), extracts of sorrel (R. occidentalis), extracts of plants belonging to the genus citrus, resveratrol, peptides such as oligopeptide-68, nonapeptide-1, kojic acid, magnesium ascorbyl phosphate, and combinations thereof.

[0174] In a particular embodiment, the cosmetic composition comprises 0% to 30% by weight, for example 0 to 15% by weight, of one or more additional cosmetic active agents.

[0175] In a more specific embodiment, the cosmetic composition comprises:

[0176] - 0.0005% to 0.01% by weight, preferably 0.001% to 0.005% by weight, of a Melaleuca alternifolia extract according to the invention,

[0177] - 69.99% to 99.9995% by weight of one or more cosmetically acceptable excipients, and

[0178] - 0 to 30% by weight, for example 0 to 15% by weight, of one or more additional cosmetic active agents.

[0179] In a more specific embodiment, the cosmetic composition comprises:

[0180] - 0.5% to 5% by weight, preferably 1% to 3% by weight of said precursor composition or of said cosmetic ingredient as described above,

[0181] - 65% to 99.5% by weight of one or more cosmetically acceptable excipients, and

[0182] - 0 to 30% by weight, for example 0 to 15% by weight, of one or more additional cosmetic active agents.

[0183] The Melaleuca alternifolia extract, precursor composition or cosmetic ingredients contained according to the present invention can be incorporated into any type of cosmetic composition. Preferably, it is a cosmetic composition having a form suitable for topical application, particularly suitable for application on the skin. The cosmetic composition according to the present invention can be of any type. In one embodiment, the cosmetic composition is selected from aqueous solutions, water-alcohol solutions, oil-in-water (O / W) emulsions or water-in-oil (W / O) emulsions or multiple (triplet: W / O / W or O / W / O) emulsions, nanoemulsions (particularly O / W nanoemulsions, whose droplet size is generally less than 100nm), aqueous gels, or spherical auxiliary dispersions of fat phases in aqueous phases, suspensions (preferably in aqueous or water-alcoholic media), liposome suspensions, powders, lotions, emulsions, creams, ointments, gels, foams, balms and salves.

[0184] In some embodiments, the cosmetic composition according to the present invention is a cream, a balm, a mask, a serum or a lotion.

[0185] In a preferred embodiment, the cosmetic composition according to the invention is a serum, a cream, a mask or a balm, preferably for use at night.

[0186] c. Cosmetic uses and methods according to the invention

[0187] According to another aspect, another subject of the invention is the use of a Melaleuca alternifolia extract as described above as a skin regenerating, repairing or anti-fatigue cosmetic agent and more particularly for the treatment or prevention of one or more signs of skin fatigue.

[0188] Another subject of the present invention is the use of a cosmetic composition according to the invention for treating or preventing one or more signs of skin fatigue.

[0189] For the purposes of the present invention, the terms "skin" and "cutaneous" refer to any part of human skin, in particular the skin of the face, including the lips and eyelids, the skin of the neck and the hands. Preferably, it is the skin on the face, including the area around the eyes and around the lips, and the skin on the neck.

[0190] In the context of the present invention, the extract or composition according to the invention is usually applied topically, preferably to the skin or mucous membranes. This is healthy skin or healthy mucous membranes, i.e. skin or mucous membranes without any wounds or skin lesions. In particular, the extract or composition according to the invention is applied to non-acne skin (i.e. skin that is not suffering from acne), which skin does not have any wounds (especially wounds caused by insect bites), or any skin infection (e.g. infections caused by fungi (mycosis), bacteria or protozoa).

[0191] In other words, when the extract or the composition according to the invention is used according to the invention, it does not produce a therapeutic effect on the skin.

[0192] The expression "anti-fatigue agent" is understood to mean a cosmetic agent capable of preventing, treating or alleviating the "cutaneous effects or signs" of fatigue, ie the effects of fatigue on the skin.

[0193] In the context of the present invention, the expression "skin effects or signs" is to be understood as any non-pathological change or alteration of the visual appearance or mechanical properties of the skin. In the context of the present invention, "skin effects or signs" are caused by or are related to fatigue.

[0194] The expression "preventing a sign or effect" is to be understood as the fact of slowing down or preventing the appearance of said sign or effect on the skin. The expression "treating a sign or effect" is to be understood as the fact of reducing, alleviating, alleviating, correcting or slowing down the development of said sign or effect on the skin.

[0195] Signs of skin fatigue can be, for example, loss of skin radiance, dull skin tone, pale skin tone, loss of uniformity in skin tone, a haggard look, dark circles around the eyes, eye bags, puffy eyelids, changes in the smooth appearance of the skin, increased skin roughness, loss of elasticity, loss of density, loss of firmness, loss of moisture, the appearance of fine lines or wrinkles, the appearance of redness, and combinations thereof.

[0196] In the context of the present invention, fatigue that causes non-pathological changes or alterations in the skin can be of any type. It can be temporary or chronic fatigue. It can especially be fatigue caused by one or more factors, especially environmental factors. These factors may be lack of sleep, for example due to work rhythm or family situation (e.g. having children), sleep disorders or jet lag, poor or unbalanced dietary health, drinking, lack or excessive physical activity, sedentary lifestyle, overwork, high intensity activity or lack of activity at work, night work or staggered working hours, a lot of screen exposure, stress, anxiety or worry related to career or family life.

[0197] Fatigue can also be caused by physical conditions such as pregnancy or menopause.

[0198] Preferably, fatigue is not related to or caused by a pathological state of the subject. In certain embodiments, the Melaleuca alternifolia extract according to the present invention can be used for at least one of the following purposes (1, 2, 3, 4, 5, 6, 7, 8, 9 or 10):

[0199] -Prevent, treat or reduce dark circles and / or eye bags,

[0200] -Prevent, treat or reduce eyelid puffiness,

[0201] -Prevent, treat or reduce skin pigmentation irregularities, including pigment spots caused by fatigue,

[0202] - Even out or unify the skin tone of the face,

[0203] - Makes the facial complexion brighter and / or more radiant and / or clearer,

[0204] -Prevent or treat dull, pale and / or haggard complexion,

[0205] - Makes the skin (especially the face) fresher and brighter,

[0206] - Soothes facial features,

[0207] - Makes skin look less tired, more relaxed and more refreshed,

[0208] - Makes eyes less tired, more relaxed, and brighter,

[0209] - Promote or accelerate the recovery of the epidermis, especially the epidermis of the face,

[0210] - Rejuvenate the skin, especially the facial skin,

[0211] - Promotes a brighter complexion effect,

[0212] -Prevent, treat or restore changes in skin barrier function,

[0213] - prevent, treat or reduce the loss of firmness of the skin, especially on the face,

[0214] - prevent, treat or reduce skin dehydration (or equivalently "water loss"),

[0215] - prevent, treat, slow down or reduce the appearance of wrinkles or fine lines, and / or

[0216] -Prevent, treat or reduce the appearance of redness.

[0217] It goes without saying that the non-pathological changes listed above are related to or caused by skin fatigue.

[0218] In certain embodiments, the extracts according to the present invention may be used as cosmetic agents to prevent, treat or reduce one or more signs of skin fatigue selected from the group consisting of skin dehydration, loss of elasticity, loss of firmness, wrinkles and combinations thereof.

[0219] In the context of the present invention, the expression "regenerative or repairing agent" is understood to mean a cosmetic agent capable of promoting or stimulating skin regeneration or skin repair during sleep, thereby reducing, treating or preventing the skin effects caused by fatigue. It is especially chronic fatigue or fatigue caused by one or more factors, especially environmental factors. In this regard, the Applicant has observed in particular that the extract according to the invention stimulates the genes involved in the synthesis of collagen in the skin.

[0220] As shown in the examples, application of extracts at very low concentrations on the skin, particularly extracts that are not detectable to the sense of smell, can improve sleep.

[0221] It has also been demonstrated that the extracts according to the invention are able to activate melatonin signaling pathways, in particular those involved in DNA repair mechanisms and cellular defense against oxidative stress, but also in the synthesis and transport of melatonin, for example caused by exposure to environmental stress, such as overexposure to UV.

[0222] Thus, in a particular embodiment, the extract according to the invention is used as an agent for activating the signaling pathway of melatonin and / or enhancing the effect of melatonin on the skin.

[0223] According to a specific aspect, the extract according to the invention is used to promote or improve skin recovery, in particular during sleep. The extract according to the invention is particularly useful for enhancing the natural mechanisms of skin repair and regeneration controlled by melatonin.

[0224] In an additional or alternative aspect, the extract according to the invention is used to improve sleep, in particular to increase total sleep time and / or deep sleep time.

[0225] According to an additional embodiment, the extract according to the invention is used to promote or facilitate skin recovery during the sleep phase.

[0226] According to an additional embodiment, the extract according to the invention is used to repair / regenerate the skin of a subject exposed to fatigue, in particular chronic fatigue.

[0227] The extracts according to the invention can be used to repair / regenerate skin exposed to stress, in particular environmental stress such as exposure to sunlight, wind, moisture, dryness or chemicals or abrasive processes, radiation, etc., or stress related to lifestyle (jet lag, lack of sleep, night work, etc.).

[0228] Additionally or alternatively, the extract according to the invention is used to induce collagen synthesis in the skin.

[0229] Additionally or alternatively, the extracts according to the invention may also be used as agents for reducing the formation of reactive oxygen species (ROS) and / or stimulating the expression of antioxidant proteins, in particular antioxidant enzymes in the skin.

[0230] In a particular embodiment, the Melaleuca alternifolia 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 alternifolia extract according to the invention in such a cosmetic composition is advantageously so low that it is not detectable by olfaction. Typically, the concentration is between 0.0005% and 0.01% by weight, preferably between 0.001% and 0.005% by weight of the extract.

[0231] It goes without saying that this use is directed to individuals exposed to fatigue as defined above.

[0232] The individual to which the present invention is directed can be of any age and sex. In a preferred embodiment, it is a subject less than 65 years old. It can be, for example, a female or male aged 25 to 65 years old, particularly 25 to 55 years old. For example, it can be a female aged 25 to 45 years old.

[0233] Another subject of the invention is a cosmetic method for preventing or treating signs of skin fatigue in a subject, said method comprising applying on the skin a cosmetically effective amount of an extract of Melaleuca alternifolia according to the invention, or a cosmetic composition according to the invention.

[0234] The cosmetic method according to the invention has the aim of treating or preventing one or more skin effects of fatigue, preferably selected from changes in the skin's complexion, in particular pale complexion, dull complexion, loss of radiance or loss of uniformity of complexion, in particular the appearance of pigmented spots, a haggard look, the appearance of bags under the eyes and / or dark circles around the eyes, puffiness of the eyelids, changes in the smooth appearance of the skin, increased skin roughness, loss of elasticity, loss of density, loss of firmness, loss of moisture, the appearance of wrinkles, the appearance of redness and combinations thereof.

[0235] According to the method of the present invention, any of the following effects can be obtained in a subject exposed to fatigue:

[0236] -Prevent, treat or reduce dark circles and / or eye bags,

[0237] -Prevent, treat or reduce eyelid puffiness,

[0238] -Prevent, treat or reduce skin pigmentation irregularities, including pigmentation spots caused by fatigue,

[0239] - Even out or unify the skin tone of the face,

[0240] - Makes the facial complexion brighter and / or more radiant and / or clearer,

[0241] -Prevent or treat dull, pale and / or haggard complexion,

[0242] - Makes the skin (especially the face) fresher and brighter,

[0243] - Soothes facial features,

[0244] - Makes skin look less tired, more relaxed and more refreshed,

[0245] - Makes eyes less tired, more relaxed, and brighter,

[0246] - Promote or accelerate the recovery of the epidermis, especially the epidermis of the face,

[0247] - Rejuvenate the skin, especially the facial skin,

[0248] - Promotes a brighter complexion effect,

[0249] -Prevent, treat or restore the deterioration of skin barrier function,

[0250] - prevent, treat or reduce the loss of firmness of the skin, especially on the face,

[0251] - prevent, treat or reduce skin dehydration (or equivalently "water loss"),

[0252] -Prevent, treat, slow down or reduce the appearance of wrinkles, and / or

[0253] -Prevent, treat or reduce the appearance of redness.

[0254] In the cosmetic method and use according to the invention, the dosage and frequency of application of the combination according to the invention vary according to the desired cosmetic effect, the characteristics of the individual, in particular their gender, age and skin type. Typically, the Melaleuca alternifolia extract or a cosmetic composition comprising the extract according to the invention can be applied to the area to be treated once a day (preferably before going to bed) for several weeks or even months, for example at least 3 months. For example, a patient can apply a 1 g to 2 g dose of the cosmetic composition to their face at night.

[0255] General Definition:

[0256] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

[0257] The present application is not limited by the embodiments of the methods, uses and compositions described herein, and all methods, uses and compositions similar or equivalent to those described herein can be used in the embodiments of the present application.

[0258] The section headings and themes provided herein should not be considered as limitations on the various aspects or embodiments of the present application. The section headings and themes used herein are for organizational purposes only and should not be interpreted as limiting the invention described. All defined terms are more fully defined by reference to the entire application.

[0259] All publications, including patent documents and scientific papers, mentioned in this application are incorporated by reference in their entirety to the same extent as if each individual publication was individually incorporated by reference. Citation of these publications should in no way be construed as an admission that these publications constitute prior art. If definitions described in this application are contrary to or inconsistent with definitions described in patents, applications, published applications, and other publications incorporated herein by reference, the definitions described in this application take precedence over the definitions incorporated herein by reference.

[0260] 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 purpose, or an equivalent or similar purpose. Therefore, unless otherwise expressly stated, each feature disclosed is merely an example of a general series of equivalent or similar features.

[0261] Definitions of terms may appear throughout the specification. It should be understood that this specification is not limited to the specific embodiments described, as these embodiments may of course vary. It should also be understood that the terminology used herein has the purpose of describing specific embodiments only and is not intended to be limiting.

[0262] It should be noted that, as used herein and in the appended claims, the singular forms "a(n)", "one", and "the" include plural references unless the context clearly dictates otherwise. For example, "a(n)" or "one" includes "at least one" and "one or more".

[0263] As used herein, the terms "comprising," "comprises," and "composed of" are synonymous with "including," "includes," "containing," "contains," and grammatical variations thereof. These terms are inclusive or open-ended and do not exclude the presence of additional members, elements, or process steps not recited.

[0264] Where a numerical range is provided, it is understood that every intervening value between the upper and lower limits of that range is specifically disclosed and encompassed within this specification. Example

[0265] In view of the fact that the present invention will be better understood by the following examples, these examples are given by way of illustration only and are not intended to limit the scope of the present invention.

[0266] Example 1: Preparation of the extract according to the present invention

[0267] 1. Preparation of Melaleuca alternifolia extract according to the present invention

[0268] As described in the description, the extract according to the invention can be obtained by fractionating the standard essential oil of Melaleuca alternifolia. The essential oil is obtained from fresh leaves and terminal branches by steam distillation. The essential oil is then fractionated by distillation. A first fraction rich in gamma-terpinene is obtained, followed by a second fraction rich in gamma-terpinene and terpinene-4-ol, followed by a third fraction and a fourth fraction both rich in terpinene-4-ol. Finally, an extract according to the invention corresponding to the fifth fraction is obtained.

[0269] Table 1 gives detailed information on the physical and chemical characteristics of the steam distilled essential oil of Melaleuca alternifolia before fractionation. Table 2 gives detailed information on the composition of the starting material ("first essential oil") and the fractions of interest ("essential oil according to the invention").

[0270] GC / FID analysis was performed on an Agilent 6890 machine (Agilent Technologies) equipped with a flame ionization detector (FID), an automatic liquid injector, and the same HP-1MS capillary column (100% dimethylpolysiloxane, 60m x 0.15mm id, film thickness 0.25μm; Agilent Technologies). The oven temperature was maintained at 60°C for 10min, then programmed from 60°C to 300°C at 2°C / min, and finally at 300°C for 10m (through time of 140min). The temperatures of the injector and detector were 250°C and 300°C, respectively; H2 (1.0ml / min) was used as the carrier gas; the sample was injected in split mode (1:50); and the injection volume was 0.1ml. The flow rates of O2, H2, and make-up gas for FID were 350, 35, and 20ml / min, respectively.

[0271]

[0272] Table 1: Characteristics of starting essential oils

[0273]

[0274] Table 2: Composition of volatile compounds of the starting essential oils and the extracts according to the invention.

[0275] Example 2: Evaluation of the extract according to the invention on skin explants

[0276] plan :The purpose of this study is 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 to a concentration of 0.5% by weight. The precursor composition (also called cosmetic ingredient) was then formulated in carbopol at a concentration of 1% by weight. It was this final composition that was used in this experiment.

[0277] 51 explants with an average diameter of 11 mm (+1 mm) were prepared from a 46-year-old Caucasian woman undergoing abdominal plastic surgery (reference: P2471-AB46, phototype II-III (according to Fitzpatrick skin color classification)). The explants were kept alive in BEM medium (BIO-EC explant medium) at 37°C in a humidified atmosphere containing 5% CO2 for 2 days. On the second day, the medium was replaced with HBSS solution and the explants were then irradiated with UV rays ("UV-placebo" group and "UV-extract" group) with a UVA dose of 13.5 J / cm 2 , equivalent to 3 MED (minimum erythema dose), and the UVB dose is 0.15 J / cm 2 , equivalent to 1 MED, or no such irradiation ("placebo" group). At the end of the irradiation, a placebo product ("placebo" group and "UV-placebo" group) or a composition comprising an extract according to the invention ("UV-extract") was topically applied to the skin surface of the corresponding explants at a rate of 100% per cm 2 Explant 2 μl (≈2 mg / cm 2 ) for another 24 hours. On day 3, explants were fixed in RNAlater and then cultured using ReliaPrep from Promega. TM RNA was extracted using the RNA tissue miniprep system (Fibrin). RNA quality and concentration were assessed prior to the reverse transcription step using iScript (Bio-Rad, 20 μl / reaction). ΔCq was calculated with the aid of a spike control. The benchmarks for evaluating each qPCR reaction using CFX Manager 3.1 software were as follows:

[0278] - Logarithmic amplification curve for each sequence of interest.

[0279] - Melting curve is the fluorescence intensity recorded after the last cycle. The temperature was increased from 65℃ to 96℃ with an increase of 0.5℃ every 5 seconds.

[0280] - A curve representing the inverse of the derivative of the fluorescence signal as a function of temperature (in °C) allows verification of individual amplicons.

[0281] All samples were analyzed for gene expression profiles. For quantification, cycle numbers were normalized to the reference gene B2M:

[0282] (i) Cq (relative amount) for each sample and each gene = E(gene)(Cq(control) - Cq(treated))

[0283] E = efficiency of primer pair = (% efficiency * 0.01) + 1

[0284] Cq(Control) = quantitation threshold calculated by CFX Maestro in "Regression" mode for the control condition.

[0285] Cq(Treatment) = quantitation threshold calculated by CFX Maestro in "Regression" mode for the Treatment condition.

[0286] Gene = Target Gene

[0287] (ii) Normalized target gene expression = NE

[0288] NE = Expression of normalized sample (gene) = Cq sample (gene) / ((Cq sample (reference 1) * Cq sample (reference 2)) 1 / n

[0289] Cq = relative amount

[0290] The denominator corresponds to the normalization factor including two reference genes: ref 1 = B2M

[0291] Gene = Target Gene

[0292] For each gene of interest, at each kinetic time point, the value between the treated samples of triplicates relative to the control samples of the matching explants of triplicates was calculated. If gene expression shows an increase greater than or equal to 1.5 (fold change ≥ 1.5) relative to the control, then the gene is considered to be induced. Similarly, if gene expression shows a reduction (fold change ≤ 0.65) relative to the control, then the gene is considered to be suppressed. In addition, when maintaining homogeneous gene regulation between triplicates of biology, P value < 0.05 (according to T test) is represented by an asterisk.

[0293] Results: The extract triggered a strong induction of OGG1, involved in DNA repair, compared to UV and placebo (UV-placebo) conditions. In addition, the extract induced a strong induction of antioxidant enzymes such as CAT and GPX1. The effects on COL3A1 and COL1A2 also tend to prove that the extract according to the invention acts on the extracellular matrix, increasing the synthesis of collagen. Interestingly, the extract induced an increase in the expression of genes related to melatonin (ASMTL, RORα, SIRT3 and SLC15A1), which tends to prove that the extract targets the same pathways as melatonin and is therefore able to activate the signaling pathways of melatonin, in particular those involved in the mechanisms of protection from oxidative stress, in particular those induced by UV rays. The stimulation of this signaling pathway would explain the stimulation or inhibition of the genes mentioned above.

[0294] All these results support the use of the extract according to the invention as an anti-fatigue, regenerative or repairing agent for the skin.

[0295]

[0296] Table 3: Gene expression results

[0297] Example 3: Sleep improvement

[0298] Methods: Thirty-two healthy participants (16 males, 22-56 years old, median age 41.5 years old) who self-reported mild sleep disturbances caused by lifestyle-related factors but had no clinical sleep disorder diagnosis were enrolled.

[0299] The study consisted of the evaluation of 2 samples of facial creams (1 "active" cream and 1 "placebo" cream), applied over a 3-week period:

[0300] - Product A - "Active" Cream: A fragrance-free, all-purpose face cream containing 1% of a precursor composition containing pentylene glycol ( 5, 0.25 wt. % of the extract from Example 1 in Minasolve,

[0301] - "Placebo" cream: a fragrance-free, general purpose face cream (see Example 5, Table 5 below), containing only 1% pentylene glycol ( 5,Minasolve).

[0302] Equipment: For objective sleep measurements, participants used the SleepScore Max device (SleepScoreLabs, Carlsbad, CA), a contactless monitoring device that uses breathing signals and movement detection to detect sleep and which is validated by polysomnography (PSG), a standard method for measuring sleep. All self-reported data were recorded using Compusense, an online data collection software.

[0303] Study Design and Procedures:

[0304] - A contextual, randomized and balanced study using a fragrance-free control cream.

[0305] - Participants applied the cream in their natural sleeping environment before bedtime.

[0306] -The study lasted from Sunday evening to Friday morning for 3 consecutive weeks.

[0307] - Participants used different samples each week. A control sample was used during the second week. Table 3 shows an overview of the study design.

[0308] - Each night of the study, participants filled out daily questionnaires and had their sleep monitored using a SleepScore Max device.

[0309]

[0310] Table 4: Clinical trial details

[0311] Data Analysis:

[0312] Objective and self-reported nighttime sleep data were analyzed among participants using mixed models using JMP Pro (version 15) statistical software. An alpha level of 0.05 was used for all statistical tests. Comparisons were made between the control group and the extracts. Percentages were derived from calculations relative to the control condition.

[0313] Statistical methods:

[0314] The obtained data and percentage changes were subjected to a two-way Student's t-test for paired data. The statistical significance value was p < 0.05.

[0315] result:

[0316] The extract according to the invention significantly increased total sleep duration (p<0.05), especially deep sleep duration (p<0.05), compared to the control. Participants using the fragrance-free control cream slept an average of 6.5 hours (392 minutes) per night, while participants using the cream containing the extract according to the invention slept an average of 6.7 hours (402 minutes) per night. Deep sleep time also increased from 1.2 hours (73 minutes) using the control cream to 1.3 hours (79 minutes) using the cream containing the extract according to the invention (p<0.05).

[0317] Example 5: Cosmetic product incorporating the extract according to the invention

[0318] A) A night cream comprising 1% of a precursor composition (also called cosmetic ingredient) comprising 0.25% by weight of an extract according to the invention prepared according to Example 1 in pentylene glycol

[0319]

[0320] Table 5: Composition of night cream

[0321] B) Anti-fatigue 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 triheptanoin.

[0322] [Table 6]

[0323]

[0324]

[0325] Table 6: Composition of anti-fatigue cream

[0326] Example 6: Improvement of signs of skin fatigue

[0327] plan : A clinical trial was conducted to confirm the anti-fatigue effect of the extract according to the invention. 44 volunteers were equally divided into two groups (22 in the test group: "active" cream, 22 in the placebo group: placebo cream).

[0328] The volunteers who registered were people who worked staggered hours, young people who were very socially active and used to going out, staying up late or traveling (jet lag), or young mothers. Therefore, the volunteers had disrupted sleep cycles but did not receive treatment for sleep disorders.

[0329] The study was conducted for 28 days, with measurements taken at D0, T12 h, D7 and D28. Volunteers applied the product once every night before going to bed.

[0330] The 2 creams tested were:

[0331] - "Active" cream: a fragrance-free universal face cream containing 1% of a cosmetic ingredient comprising 0.25% by weight of the extract from Example 1 (see Example 5, Table 5 above) in triheptanoin,

[0332] - "Placebo" cream: a fragrance-free, generic face cream (see Example 5, Table 5 below), containing only 1% of triheptanoin.

[0333] equipment : To observe signs of fatigue, the following parameters were measured:

[0334] - Transepidermal water loss (TEWL), via The evaluation was carried out using TM 300 (Courage+Khazaka, Electronic GmbH).

[0335] - Skin moisture content, use Conduct an assessment

[0336] - Antioxidant potential of the skin, as used by experimenters (Courage+Khazaka, Electronic GmbH) The first layer of the stratum corneum samples collected from the cheeks at D0 and D28 were measured, followed by FRAP (Ferric Reduction Antioxidant Parameter) testing.

[0337] - Crow's feet, measured with Primos 3D (GFMesstechnik GmbH).

[0338] - Skin elasticity and firmness, through suction / stretching method ( MPA 580, Courage+Khazaka, Electronic GmbH). The device applies negative pressure (suction) and the skin is sucked into the measuring cup of the probe, which allows its penetration depth to be measured by an optical measuring system.

[0339] - Assessment of dark circles (from raw images taken for each volunteer with a bio-blue light scanner and processed by specific software) was measured using the Individual Typology Angle (ITA°).

[0340] Statistical methods:

[0341] Statistical studies were performed each time to analyze the significance of the evolution of parameters. Two-way A-NOVA was performed on the obtained data and percentage changes. Statistical significance values ​​were p<0.05 (*p<0.05; **p<0.01; ***p<0.001; ****p<0.0001).

[0342] result:

[0343] The results of this clinical trial are Figures 4 to 10 shown.

[0344] The group treated with the "active" cream showed a significant reduction in transepidermal water loss (TEWL) of the skin compared to the group treated with the "placebo" cream, which increased over time. This highlights an improvement in barrier function ( Figure 4 A significant improvement in skin hydration was also observed in the group treated with the "active" cream, with increases of +7.5%**, +7.9%** and +12%**** after 12h, 7 days and 28 days, respectively ( Figure 5 ).

[0345] A significant increase in the antioxidant potential of the skin was also observed in the group treated with the "active" cream compared to the group treated with the placebo cream (Fe 3+ to Fe 2+ Reduced by +17%, Figure 6 ).

[0346] Compared to the "placebo" group, an improvement in the smooth appearance of the skin and in its biomechanical properties was observed in the group treated with the "active" cream. Thus, the "active" cream comprising the extract according to the invention smoothes the skin and rapidly reduces the appearance of wrinkles, as demonstrated by a decrease in the parameter Sa of -6.9%*** and -9%**** after 7 and 28 days ( Figure 7 ).

[0347] A significant reduction in crow’s feet can also be visually observed in the images taken at D0 and D28, and this is also confirmed by Primos 3D measurements.

[0348] The “active” cream also improved the biomechanical properties of the skin by increasing its firmness and elasticity, as evidenced by a significant decrease in the parameter R0 compared to the placebo group ( Figure 8 ), and the parameter R2 increased significantly ( Fig. 9 ) proved by.

[0349] Finally, the "active" cream induced a rapid and significant reduction in dark circles compared to the placebo group ( Fig.10 ).

[0350] In conclusion, this clinical trial shows that Melaleuca alternifolia extract is a powerful skin anti-fatigue agent. Daily application of a cream containing 0.0025% of the extract according to the invention can improve signs of skin fatigue in people with disturbed sleep cycles.

[0351] Compared with the group of volunteers treated with placebo cream, the extract according to the present invention can significantly improve the barrier function of the volunteers' skin, improve the antioxidant capacity of the skin, prevent and improve the smooth appearance and biomechanical properties of the skin, and reduce dark circles in a significant manner.

[0352] The scope of the present invention is not intended to be limited to the specific embodiments described, and these embodiments are provided, for example, to illustrate various aspects of the present invention. According to the description and teachings of the present application, various modifications or variations of the described compositions and methods will become apparent. Such modifications can be made without departing from the true scope and spirit of the present application, and are intended to be included in the scope of the present patent application. Although the present invention can be described in conjunction with specific preferred embodiments, it should be understood that the claimed invention should not be overly limited to such specific embodiments. In fact, various modifications or variations of the embodiments of the present invention that are apparent to those skilled in the art in the field of cosmetics or related fields are intended to fall within the scope of the claims.

[0353] Exemplary embodiments:

[0354] 1. A cosmetic use of an oily extract of Melaleuca alternifolia as a cosmetic agent for regeneration, repair or anti-fatigue of healthy skin, wherein the extract comprises:

[0355] - more than 20% of a compound selected from sesquiterpenes and sesquiterpenoids, and

[0356] - less than 6% of terpinen-4-ol,

[0357] The percentages are expressed relative to the total content of volatile compounds present in the extract, as determined by gas chromatography coupled to a flame ionization detector (GC / FID).

[0358] 2. The cosmetic use according to embodiment 1, characterized in that the Melaleuca alternifolia extract contains less than 15%, preferably less than 10%, and more preferably less than 2.0% terpineol.

[0359] 3. The cosmetic use according to embodiment 1 or 2, characterized in that the Melaleuca alternifolia extract comprises:

[0360] - less than 5.0%, preferably less than 2.0%, more preferably less than 1.0% of terpinen-4-ol, and / or

[0361] Less than 5.0%, preferably less than 2.0%, more preferably less than 1.5% of alpha-terpineol.

[0362] 4. The cosmetic use according to any one of embodiments 1 to 3, characterized in that the Melaleuca alternifolia extract contains more than 30%, preferably more than 40%, of compounds selected from sesquiterpenes and sesquiterpenoids.

[0363] 5. The cosmetic use according to any one of embodiments 1 to 4, characterized in that the Melaleuca alternifolia extract comprises:

[0364] -5% to 15% of citronellal,

[0365] -10% to 25% of hornene,

[0366] -10% to 25% delta-cadinene,

[0367] - 1% to 5% eucalyptol, and

[0368] -1% to 5% viridifloral.

[0369] 6. The cosmetic use according to any one of embodiments 1 to 5, characterized in that the Melaleuca alternifolia extract is obtained by fractionating the essential oil of Melaleuca alternifolia leaves and / or terminal branches.

[0370] 7. The cosmetic use according to any one of embodiments 1 to 6, wherein the Melaleuca alternifolia extract is used to treat or prevent one or more signs of skin fatigue selected from the group consisting of loss of skin radiance, dull skin tone, pale skin tone, loss of uniformity of skin tone, haggard look, dark circles around the eyes, eye bags, puffy eyelids, changes in the smooth appearance of the skin, increased skin roughness, loss of elasticity, loss of density, loss of firmness, loss of moisture, appearance of wrinkles, appearance of redness, and combinations thereof.

[0371] 8. The cosmetic use according to any one of embodiments 1 to 6, wherein the Melaleuca alternifolia extract is used as a cosmetic agent to promote or improve skin recovery during sleep and / or as a cosmetic agent to enhance the natural mechanism of skin repair and regeneration controlled by melatonin.

[0372] 9. The cosmetic use according to any one of embodiments 1 to 8, wherein the Melaleuca alternifolia extract is further used to increase total sleep duration and / or deep sleep duration.

[0373] 10. The cosmetic use according to any one of embodiments 1 to 9, wherein the Melaleuca alternifolia extract is present as a cosmetic active agent in a cosmetic composition, preferably a cream, a balm, a mask, a serum or a lotion.

[0374] 11. An oily extract of Melaleuca alternifolia comprising:

[0375] - more than 20% of a compound selected from sesquiterpenes and sesquiterpenoids, and

[0376] - less than 6% of terpinen-4-ol,

[0377] The percentages are expressed relative to the total content of volatile compounds present in the extract, as determined by gas chromatography coupled to a flame ionization detector (GC / FID).

[0378] 12. The oily extract of Melaleuca alternifolia according to embodiment 11, characterized in that it is as defined in any one of embodiments 2 to 6.

[0379] 13. A cosmetic ingredient or precursor composition for preparing a cosmetic composition, comprising the Melaleuca alternifolia extract of embodiment 11 or 12.

[0380] 14. The cosmetic ingredient or precursor composition of embodiment 13, comprising 0.1% to 1.0% by weight, preferably 0.1% to 0.5% by weight, of the Melaleuca alternifolia extract of embodiment 11 or 12 in a cosmetically acceptable carrier.

[0381] 15. The cosmetic ingredient or precursor composition of embodiment 14, comprising or consisting essentially of 0.1% to 1.0% by weight of the Melaleuca alternifolia extract of embodiment 11 or 12 in a cosmetically acceptable carrier selected from pentylene glycol or triheptanoin.

[0382] 16. The cosmetic ingredient or precursor composition of any one of embodiments 13 to 15, wherein the Melaleuca alternifolia extract is present as a regenerative, repairing or anti-fatigue active agent for healthy skin.

[0383] 17. A cosmetic composition comprising the Melaleuca alternifolia extract of embodiment 11 or 12, or the cosmetic ingredient or precursor composition of any one of embodiments 13 to 15, and at least one cosmetically acceptable excipient.

[0384] 18. The cosmetic composition according to embodiment 17, characterized in that it comprises 0.0005% to 0.01% by weight, preferably 0.001% to 0.005% by weight of the Melaleuca alternifolia extract.

[0385] 19. The cosmetic composition according to embodiment 17, characterized in that it comprises 0.5% to 5% by weight, preferably 1% to 3% by weight of the cosmetic ingredient.

[0386] 20. The cosmetic composition according to any one of embodiments 17 to 19, which is chosen from aqueous solutions, hydroalcoholic solutions, oil-in-water (O / W) emulsions or water-in-oil (W / O) emulsions or multiple (triplet: W / O / W or O / W / O) emulsions, nanoemulsions, in particular O / W nanoemulsions, aqueous gels, or globules-assisted dispersions of a fatty phase in an aqueous phase, suspensions, preferably in an aqueous or hydroalcoholic medium, liposomal suspensions, powders, lotions, emulsions, creams, ointments, gels, foams and salves.

[0387] 21. Cosmetic composition according to any one of embodiments 16 to 20, which is a care product intended for the treatment or prevention of skin fatigue, such as a serum, a cream, a mask or a balm, preferably for use at night.

[0388] 22. A cosmetic method for preventing, reducing or treating signs of skin fatigue in a subject, the method comprising applying to the skin a cosmetically effective amount of the Melaleuca alternifolia extract of embodiment 11 or 12, or a cosmetically effective amount of a cosmetic composition of any one of embodiments 17 to 21.

[0389] 23. Use of the Melaleuca alternifolia extract according to embodiment 11 or 12 or the cosmetic ingredient according to any one of embodiments 13 to 15 in the manufacture of a cosmetic composition for treating, preventing or reducing signs of skin fatigue.

Claims

1. A cosmetic use of an oily extract of Melaleuca alternifolia as a cosmetic agent for regeneration, repair or anti-fatigue of healthy skin, wherein the extract comprises: - more than 20% of a compound selected from sesquiterpenes and sesquiterpenoids, and - less than 6% of terpinen-4-ol, The percentages are expressed relative to the total content of volatile compounds present in the extract, as determined by gas chromatography coupled to a flame ionization detector (GC / FID).

2. The cosmetic use according to claim 1, It is characterized in that The Melaleuca alternifolia extract contains less than 15%, preferably less than 10%, and more preferably less than 2.0% terpineol.

3. The cosmetic use according to claim 1 or 2, It is characterized in that The Melaleuca alternifolia extract comprises: - less than 5.0%, preferably less than 2.0%, more preferably 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.

4. The cosmetic use according to any one of claims 1 to 3, It is characterized in that The Melaleuca alternifolia extract comprises more than 30%, preferably more than 40%, of compounds selected from sesquiterpenes and sesquiterpenoids.

5. The cosmetic use according to any one of claims 1 to 4, It is characterized in that The Melaleuca alternifolia extract comprises: -5% to 15% of citronellal, -10% to 25% of hornene, -10% to 25% delta-cadinene, - 1% to 5% eucalyptol, and -1% to 5% viridifloral.

6. The cosmetic use according to any one of claims 1 to 5, It is characterized in that The Melaleuca alternifolia extract is obtained by fractionating the essential oil of Melaleuca alternifolia leaves and / or terminal branches.

7. The cosmetic use of any one of claims 1 to 6, wherein the Melaleuca alternifolia extract is used to treat or prevent one or more signs of skin fatigue selected from the group consisting of loss of skin radiance, dull skin tone, pale skin tone, loss of uniformity of skin tone, haggard look, dark circles around the eyes, eye bags, puffy eyelids, changes in the smooth appearance of the skin, increased skin roughness, loss of elasticity, loss of density, loss of firmness, loss of moisture, the appearance of wrinkles, the appearance of redness, and combinations thereof.

8. The cosmetic use of any one of claims 1 to 6, wherein the Melaleuca alternifolia extract is used as a cosmetic agent for promoting or improving skin recovery during sleep and / or as a cosmetic agent for enhancing the natural mechanism of skin repair and regeneration controlled by melatonin.

9. The cosmetic use according to any one of claims 1 to 8, wherein the Melaleuca alternifolia extract is further used to increase total sleep duration and / or deep sleep duration.

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

11. An oily extract of Melaleuca alternifolia comprising: - more than 20% of a compound selected from sesquiterpenes and sesquiterpenoids, and - less than 6% of terpinen-4-ol, The percentages are expressed relative to the total content of volatile compounds present in the extract, as determined by gas chromatography coupled to a flame ionization detector (GC / FID).

12. The oily extract of Melaleuca alternifolia according to claim 11, It is characterized in that It is defined as in any one of claims 2 to 6.

13. A cosmetic ingredient comprising the Melaleuca alternifolia extract according to claim 11 or 12.

14. The cosmetic ingredient of claim 13, comprising 0.1 wt% to 1.0 wt%, preferably 0.1 wt% to 0.5 wt% of the Melaleuca alternifolia extract of claim 11 or 12 in a cosmetically acceptable carrier.

15. The cosmetic ingredient of claim 14, comprising or consisting essentially of 0.1% to 1% by weight of the Melaleuca alternifolia extract of claim 11 or 12 in a cosmetically acceptable carrier selected from pentylene glycol or triheptanoin.

16. The cosmetic ingredient of any one of claims 13 to 15, wherein the Melaleuca alternifolia extract is present as a regenerative, repairing or anti-fatigue active agent in healthy skin.

17. A cosmetic composition comprising the Melaleuca alternifolia extract according to claim 11 or 12, or the cosmetic ingredient according to any one of claims 13 to 15, and at least one cosmetically acceptable excipient.

18. The cosmetic composition according to claim 17, Features It contains 0.0005 wt % to 0.01 wt %, preferably 0.001 wt % to 0.005 wt % of the Melaleuca alternifolia extract.

19. The cosmetic composition according to claim 17, Features It contains 0.5 to 5 wt%, preferably 1 to 3 wt% of the cosmetic ingredient.

20. The cosmetic composition of any one of claims 17 to 19, selected from aqueous solutions, hydroalcoholic solutions, oil-in-water (O / W) emulsions or water-in-oil (W / O) emulsions or multiple (triplet: W / O / W or O / W / O) emulsions, nanoemulsions, in particular O / W nanoemulsions, aqueous gels, or globules-assisted dispersions of a fatty phase in an aqueous phase, suspensions, preferably suspensions in an aqueous or hydroalcoholic medium, liposomal suspensions, powders, lotions, emulsions, creams, ointments, gels, foams and salves.

21. The cosmetic composition according to any one of claims 17 to 20, which is a care product for treating or preventing skin fatigue, such as a serum, cream, mask or balm, preferably for use at night.

22. A cosmetic method for preventing, reducing or treating signs of skin fatigue in a subject, said method comprising applying to said skin a cosmetically effective amount of a Melaleuca alternifolia extract according to claim 11 or 12, or a cosmetically effective amount of a cosmetic composition according to any one of claims 17 to 21.

23. Use of the Melaleuca alternifolia extract of claim 11 or 12 or the cosmetic ingredient of any one of claims 13 to 15 in the manufacture of a cosmetic composition for treating, preventing or alleviating signs of skin fatigue.

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