Skin cell energy enhancing composition

Abstract

The present invention relates to the cosmetic use of a composition for enhancing skin cell energy metabolism in an individual, said composition comprising a compound of formula I TIFF2025514403000061.tif23170I, wherein: The carbon-carbon bond shown in TIFF2025514403000062.tif5170 may be a double or single bond, R 1 is an alkyl chain having 10 to 20 carbon atoms, R 2 is hydrogen or a substituted or unsubstituted acyl having 16 to 34 carbon atoms; R 3 teeth, If the carbon-carbon bond shown in TIFF2025514403000063.tif4170 is a double or single bond, it is hydrogen or R 3 teeth, If the carbon-carbon bond shown in TIFF2025514403000064.tif5170 is a single bond, then it is -OH, and R 4 teeth, If the carbon-carbon bond shown in TIFF2025514403000065.tif5170 is a double or single bond, it is hydrogen or R 4 teeth, When the carbon-carbon bond shown in TIFF2025514403000066.tif6170 is a double bond, it is hydrogen or -OH, and X is hydrogen, a glucosyl moiety or a lactosyl moiety.

Description

[Technical field]

[0001] FIELD OF THEINVENTION The present invention relates to the use of a composition for enhancing cellular energy metabolism in skin cells of an individual, and to a composition for enhancing skin cell energy metabolism. [Background technology]

[0002] 2. Background of the Invention Skin is the outer covering of the body and communicates with the external environment. Skin is a complex structure composed of several tissue layers, each with a different cellular composition. Skin has vital functions such as sensation, insulation and prevention of water loss, and acts as a physical barrier against pathogens. The upper layer of skin is the epidermis, a laminar structure interspersed with hair follicles. The outer epidermal surface is composed of keratinized keratinocytes or corneocytes that form a dense cytoskeletal network of keratin filaments. The basal layer harbors epidermal stem and progenitor cells. The dermis lies below the epidermis and is composed of dermal fibroblasts, which produce collagen and elastin that form the extracellular matrix (ECM), and melanocytes, which produce melanin, a photoprotective pigment. If repair mechanisms cannot keep pace, deleterious changes in skin structure can occur, affecting the skin's protective role against physicochemical and biological attacks, as well as its thermoregulatory, sensory, immune and hormonal functions. Both intrinsic and environmental factors affect the epidermal and dermal layers of the skin. The intrinsic aging process is the result of the chronological, inevitable aging of skin cells, which varies depending on ethnicity, hormones and the anatomical region of skin affected. Extrinsic skin aging is the result of all external factors including lifestyle, smoking, UV exposure and the environment, which have a cumulative effect over time.

[0003] Skin is an organ of high turnover and is constantly renewing the epidermis. Thus, epidermal progenitor cells are highly proliferative and metabolically active, which requires a lot of energy. Energy demands are met by mitochondrial respiration, an adenosine triphosphate (ATP) generating process driven by a series of protein complexes collectively called the electron transport chain (ETC) located on the inner membrane of mitochondria. The mammalian mitochondrial ETC is composed of the transmembrane proteins complex I (NADH dehydrogenase), complex II (succinate dehydrogenase), complex III (ubiquinol-cytochrome C oxidoreductase) and complex IV (cytochrome C oxidase) as well as the freely mobile electron transporters ubiquinone and cytochrome C. Complex I is the first enzyme of the respiratory chain and plays a central role in energy metabolism. Complex I oxidizes NADH generated through the Krebs cycle in the mitochondrial matrix and reduces ubiquinone to ubiquinol using two electrons. Ubiquinol is reoxidized by the cytochrome bc1 complex, transferring electrons to reduce molecular oxygen to water at complex IV. The redox energy released during this process is used to transfer protons from the mitochondrial matrix to the periplasmic space, generating the proton motive force across the inner mitochondrial membrane at complexes I, III, and IV.

[0004] To function properly, these complexes must assemble into specifically organized supercomplexes, and the assembled components, together with ATP synthase, are the basis for ATP production during oxidative phosphorylation. Natural by-products of respiration include reactive oxygen species (ROS), which play important roles in cell proliferation, hypoxic adaptation, and cell fate determination, but excess ROS can destroy macromolecular and cellular structures if not quenched by antioxidant systems. This oxidative damage caused by mitochondrial ROS production has been established as a key molecular basis of aging (Sreedhar et al., Cell Death and Disease (2020) 11: 444). Complexes I and III are generally considered the primary sites of electron leakage and ROS production, where one electron reacts with oxygen to generate superoxide anion. Complex I is involved in various cellular functions ranging from apoptosis and necrosis to cell proliferation. Complex I appears to be the most vulnerable site to oxidative stress.

[0005] The intrinsic aging process in cells and skin may be associated with the loss of proper function of the skin. Loss of proper function of the skin may result in increased oxidative damage, increased inflammation, dry skin, loss of skin firmness, increased skin unevenness, and increased fine lines and wrinkles. Factors that cause extrinsic aging may include exposure to ultraviolet (UV) radiation, irritants, and pollutants such as airborne particulates. Long-term UV exposure may cause mitochondrial DNA damage and oxidative stress in skin cells, which may progress to photoaging. UVB acts primarily on epidermal keratinocytes and melanocytes, whereas UVA can penetrate deeper into the dermis. The primary marker of photoaging is large-scale mitochondrial DNA (mtDNA) deletion. Phenotypic manifestations include loss of elasticity, wrinkling, and abnormal pigmentation.

[0006] As more research supports the close relationship between mitochondria and skin appearance and health, targeting mitochondria in skin, for example through enhanced ATP production, has attracted attention from medical and beauty professionals alike.Activating the respiratory chain and thus activating ATP production keeps metabolism high, provides energy for repair mechanisms, and keeps cells healthy and functional, resulting in healthy skin with a radiant glow.In addition, activated metabolism supports skin regeneration and helps fight signs of aging.

[0007] There remains a need for treatments that effectively address the above undesirable skin changes in a comprehensive manner and help maintain the appearance and function of radiant, healthy skin. Summary of the Invention

[0008] Summary of the Invention The inventors have surprisingly found that certain compounds can enhance cellular energy metabolism in skin cells.Accordingly, the present invention relates to the use of the composition for enhancing cellular energy metabolism in skin cells of an individual, and the composition for enhancing skin cell energy metabolism.

[0009] Specifically, the present invention includes the following aspects.

[0010] (1) A cosmetic use of a composition for enhancing skin cell energy metabolism in an individual, said composition comprising one or more compounds of formula I [ka] I, The compound includes During the ceremony, [ka] The carbon-carbon bond represented by is a double or single bond, R 1 is an alkyl chain having 10 to 20 carbon atoms, R 2is hydrogen or a substituted or unsubstituted acyl having 16 to 34 carbon atoms; R 3 teeth, [ka] If the carbon-carbon bond represented by is a double or single bond, it is hydrogen, or R 3 teeth, [ka] When the carbon-carbon bond represented by is a single bond, it is -OH; R 4 teeth, [ka] If the carbon-carbon bond represented by is a double or single bond, it is hydrogen, or R 4 teeth, [ka] When the carbon-carbon bond represented by is a double bond, it is hydrogen or -OH; X is hydrogen, a glucosyl moiety or a lactosyl moiety.

[0011] (2) A method for enhancing skin cell energy metabolism comprising topically administering onto the skin of an individual a composition comprising a compound of formula I. The beneficial effects of cosmetic treatment with topical compositions containing one or more compounds of formula I include the following: -Improves skin radiance; -Improves skin radiance; -Improves skin firmness; -Skin soothing; - Prevent or reduce skin aging, such as inflammation aging or photoaging; - Wrinkle smoothing; -Aids in skin regeneration; - Relieve signs of skin inflammation such as itching, redness or swelling; and / or - Reduces signs of skin fatigue Includes.

[0012] (3) A pharmaceutical topical composition comprising a compound of formula I for treating a skin condition in an individual.

[0013] Various non-limiting embodiments of the above aspects of the invention are described throughout the present specification and illustrated by way of non-limiting examples. [Brief description of the drawings]

[0014] drawing [Figure 1-3] Figures 1-3 show heat maps using a log2 scale with up- or down-regulation of each protein upon treatment with 0.01% (01), 0.03% (03) and 0.15% (15) of ceramide in vehicle compared to vehicle without ceramide (VEH); detailed experimental setup is described in Example 1. [Figure 4] FIG. 4 shows the activity of complex I (expressed in U / g protein) in tissue controls at day 0 (T0) and in skin explants at day 6, respectively, untreated controls (T), treated with basal emulsion (E) and treated with basal emulsion plus GlcCer (P). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] Detailed Description of the Invention It has now surprisingly been found that compounds of formula I enhance cellular energy metabolism in skin cells. As used herein, enhancing skin cell energy refers to improving mitochondrial function, including ATP production, and may also be referred to as skin vitalisation or skin energising.

[0016] As used herein, the following terms have the following meanings.

[0017] "Topical compositions" include compositions suitable for topical application to keratinous tissue, particularly to the skin. Such compositions are typically dermatologically acceptable in that they do not have undue toxicity, incompatibility, instability, allergic reactions, etc. when applied to the skin. Topical compositions typically include a topically acceptable carrier. The topical skin care compositions of the present invention can have a viscosity selected to avoid significant dripping or retention after application to the skin. Thus, topical compositions of the present invention that include one or more compounds of formula I typically include one or more other compounds useful for formulating these compositions. Typically, such "compounding" compounds do not have the biological activity of the compounds of the present invention.

[0018] "Cortex" includes the keratin-containing layer arranged as the outermost protective covering of mammals, including, but not limited to, the lips, skin, scalp, hair and nails.

[0019] The terms "about" or "approximately" are defined as close to the value or range that follows these terms, as understood by one of ordinary skill in the art, and include a deviation of up to 10% of the subsequent value or range.

[0020] The term "reducing" or any variation of this term, such as "reduction," includes any measurable decrease to achieve a desired effect.

[0021] The terms "promoting," "enhancing," "improving," or "increasing," or any variation of these terms, include any measurable increase to achieve a desired effect.

[0022] "Effective amount" means an amount sufficient to effect a desired treatment or management result in a human. To achieve the desired treatment or management result, an effective amount can be administered in one or more doses.

[0023] "Prophylactic treatment," "preventing," or "prevention" means a procedure given or action taken to reduce the risk of onset or recurrence of a cosmetic or medical condition, or of effects associated with disfiguring the visual appearance of the skin or a skin disease.

[0024] "Primary prevention" means preventing the initial manifestation of a cosmetic or medical condition in an individual.

[0025] "Secondary prevention" means (i) preventing the recurrence of a condition, (ii) increasing the duration of remission of a condition, and / or (iii) reducing the severity of symptoms of a condition in an individual who has or has had a cosmetic or medical condition.

[0026] "Treat" means to address a cosmetic or medical condition or disease with the goal of improving or stabilizing the outcome or addressing the underlying need in the person being treated. Treating thus includes the localized management of a cosmetic or medical condition or disease by addressing the dermatological needs of the person being treated. "Treat" and "treatment" have grammatically corresponding meanings.

[0027] "Treatment" means a procedure given or action taken to reduce or eliminate the symptoms of a disease or pathological condition.

[0028] The terms defined above and the embodiments described throughout this specification are applicable to all aspects of the present invention unless otherwise stated.

[0029] In one aspect, the present invention relates to a cosmetic use of a composition for enhancing cellular energy metabolism in an individual, said composition comprising a compound of formula I [ka] I, The compound includes During the ceremony, [ka] The carbon-carbon bond represented by is a double or single bond, R 1 is an alkyl chain having 10 to 20 carbon atoms, R 2 is hydrogen or a substituted or unsubstituted acyl having 16 to 34 carbon atoms; R 3 teeth, [ka] is a double or single bond, then it is hydrogen; or R 3 teeth, [ka] When the carbon-carbon bond represented by is a single bond, it is -OH; R 4 teeth, [ka] is a double or single bond, then it is hydrogen; or R 4 teeth, [ka] When the carbon-carbon bond represented by is a double bond, it is hydrogen or -OH; In relation to the cosmetic use, X is hydrogen, a glucosyl moiety or a lactosyl moiety.

[0030] As used herein, the term "alkyl" refers to an acyclic straight-chain hydrocarbyl group in which the carbon atoms may be saturated or may contain one or more double and / or triple bonds (to form, for example, an alkenyl or alkynyl). Examples of "alkyl" include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, isobutyl, n-butyl, sec-butyl, tert-butyl, isopentyl, n-pentyl, neo-pentyl, n-hexyl, ethenyl, propenyl, 1-butenyl, 2-butenyl, isobutenyl, 1-pentenyl, 2-pentenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 2-methyl-2-butenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, methylpentenyl, dimethylbutenyl, ethynyl, propynyl, 1-butynyl, 2-butynyl, pentynyl, and hexynyl. Typically, the term alkyl refers to saturated hydrocarbyl groups.

[0031] As used herein, the term "acyl" includes both saturated groups and groups having one or more double and / or triple bonds. In the context of acyl, the term "substituted" means that a carbon atom may be substituted one or several times, preferably one to three times, with a functional group.

[0032] In a preferred embodiment, R of compound I 2 is an unsubstituted acyl group. In a more preferred embodiment, R 2 is a saturated fatty acyl group or a fatty acyl group having one or more double bonds.

[0033] The compound of formula I can be obtained by any technique known to those skilled in the art, such as fermentation technique or biocatalytic process.For example, glucosylceramide can be produced by starting from glucosyl fluoride and then coupling to acylated sphingoid base by using endoglycoceramide synthase, as described in Rich et al., ChemComm (2011) 47:10806-10808.Sphingoid base can be produced by fermentation process, as described in WO 95 / 12683, in particular phytosphingosine or its precursor (European Patent No. 0726960, claim 1), for example.

[0034] In some embodiments, R of the compound of formula I 1 -C 12 H 25 and / or R 2 is hexadecanoyl, 2-hydroxyhexadecanoyl, octadecanoyl, 2-hydroxyoctadecanoyl, eicosanoyl, 2-hydroxyeicosanoyl, lignoceroyl, 2-hydroxytetracosanoyl or 30-(linoleyloxy)-triacontanoyl, preferably octadecanoyl or lignoceroyl.

[0035] In some embodiments, R of the compound of formula I 1 -C 12 H 25 and R 2 is octadecanoyl.

[0036] The composition comprising the compound of formula I may be a topical composition or an oral composition. Typically, the composition comprising the compound of formula I is a topical composition.

[0037] The compound of formula I may be formulated into a topical composition suitable for application to the skin. In general, the topical composition of the present invention contains about 0.0001% to about 10% weight / weight of the compound of formula I, for example, about 0.005% to about 5% weight / weight of the compound of formula I, or 0.01% to about 1% weight / weight of the compound of formula I. For example, the topical composition of the present invention may contain about 0.0001 to about 0.00025% weight / weight of the compound of formula I, about 0.0002 to about 0.0004% weight / weight of the compound of formula I, about 0.0003 to about 0.0005% weight / weight of the compound of formula I, about 0.0004 to about 0.0006% weight / weight of the compound of formula I, about 0.0005 to about 0.0008% weight / weight of the compound of formula I, about 0.0007 to about 0.001% weight / weight of the compound of formula I, , about 0.001 to about 0.005% weight / weight of the compound of formula I, about 0.003 to about 0.008% weight / weight of the compound of formula I, about 0.005 to about 0.01% weight / weight of the compound of formula I, about 0.008 to about 0.05% weight / weight of the compound of formula I, about 0.05 to about 0.08% weight / weight of the compound of formula I, about 0.06 to about 0.1% weight / weight of the compound of formula I, about 0.08 to about 0.1% weight / weight of the compound of formula I, etc.

[0038] In some embodiments, the topical compositions of the present invention contain an amount of about 0.01% to 5% w / w of the compound of formula I, or an amount of about 0.02% to 1% w / w of the compound of formula I. Examples are 0.05% w / w, 0.1% w / w or 0.2% w / w of the compound of formula I.

[0039] In some embodiments, topical compositions may contain more than one compound of formula I, also referred to herein as a blend of compounds of formula I. In such blended compositions, each compound of formula I may be present in the same amount or in different amounts. The ranges or amounts listed above may relate to the total content of the blend in the topical composition, or the amount of one compound in the blend in the topical composition.

[0040] The amount of the compound of formula I in the composition of the present invention can vary depending on factors such as the age of the person, the risk and severity of any underlying condition, the environment to which the person is exposed, the form of the topical composition, its use for cosmetic or medical purposes, and any other skin care composition that is administered.The appropriate dose for any particular person or indication can be determined by methods known to skin care practitioners.The dose can also vary depending on whether the topical composition is a "leave-on" formulation or a "rinse-off" formulation, with "rinse-off" formulations generally containing lower doses.Furthermore, the dose can vary depending on whether the topical composition is applied in an intervention treatment phase or in a maintenance phase.Generally, higher doses can be applied in the early intervention phase than in the maintenance phase.

[0041] The composition according to the present invention may have a pH in the range of about 4.5 to about 8, for example about 4.5 to about 6.

[0042] In the context of the present invention, it has been surprisingly found that application of glucosylceramide (GlcCer) to keratinocytes leads to the upregulation of proteins of the mitochondrial respiratory chain. More precisely, application of GlcCer leads to the upregulation of several mitochondrial proteins related to the generation of ATP, in particular ATP synthase subunit g (mitochondrial), ATP synthase subunit delta (mitochondrial), cytochrome c oxidase subunit 6C, NADH dehydrogenase [ubiquinone] iron sulfur protein 2 (mitochondrial), NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8, ATP-dependent zinc metalloprotease YME1L1, NAD-dependent malic enzyme (mitochondrial) and phosphomevalonate kinase.

[0043] In some embodiments, glucosylceramide is used to upregulate ATP synthase subunit g.

[0044] In some embodiments, glucosylceramide is used to upregulate ATP synthase subunit delta.

[0045] In some embodiments, glucosylceramide is used to upregulate cytochrome c oxidase subunit 6C.

[0046] In some embodiments, glucosylceramide is used to upregulate NADH dehydrogenase [ubiquinone] iron sulfur protein 2.

[0047] In some embodiments, glucosylceramide is used to upregulate NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8.

[0048] In some embodiments, glucosylceramide is used to upregulate the ATP-dependent zinc metalloprotease YME1L1.

[0049] In some embodiments, glucosylceramide is used to upregulate NAD-dependent malic enzyme.

[0050] In some embodiments, glucosylceramide is used to upregulate phosphomevalonate kinase.

[0051] In the context of the present invention, it has further been found that application of lactosylceramide to keratinocytes results in upregulation of ATP synthase subunit g (mitochondrial), ATP synthase subunit delta (mitochondrial), cytochrome c oxidase subunit 6C, cytochrome c oxidase subunit 2, cytochrome c oxidase subunit NDUFA4, cytochrome b-c1 complex subunit 9, ATP-dependent zinc metalloprotease YME1L1, NAD-dependent malic enzyme (mitochondrial) and phosphomevalonate kinase.

[0052] In some embodiments, lactosylceramide is used to upregulate ATP synthase subunit g.

[0053] In some embodiments, lactosylceramide is used to upregulate ATP synthase subunit delta.

[0054] In some embodiments, lactosylceramide is used to upregulate cytochrome c oxidase subunit 6C.

[0055] In some embodiments, lactosylceramide is used to upregulate cytochrome c oxidase subunit 2.

[0056] In some embodiments, lactosylceramide is used to upregulate the cytochrome c oxidase subunit NDUFA4.

[0057] In some embodiments, lactosylceramide is used to upregulate cytochrome b-c1 complex subunit 9.

[0058] In some embodiments, lactosylceramide is used to upregulate the ATP-dependent zinc metalloprotease YME1L1.

[0059] In some embodiments, lactosylceramide is used to upregulate NAD-dependent malic enzyme.

[0060] In some embodiments, lactosylceramide is used to upregulate phosphomevalonate kinase.

[0061] In the context of the present invention, it has further been found that application of ceramide NG to the skin results in upregulation of ATP synthase subunit g (mitochondrial), ATP synthase subunit delta (mitochondrial), cytochrome c oxidase subunit 6C and phosphomevalonate kinase.

[0062] In some embodiments, ceramide NG is used to upregulate ATP synthase subunit g.

[0063] In some embodiments, ceramide NG is used to upregulate ATP synthase subunit delta.

[0064] In some embodiments, ceramide NG is used to upregulate cytochrome c oxidase subunit 6C.

[0065] In some embodiments, ceramide NG is used to upregulate phosphomevalonate kinase.

[0066] NADH dehydrogenase (ubiquinone) iron-sulfur protein 2 and NADH dehydrogenase (ubiquinone) 1α subcomplex subunit 8 form part of complex I of the ETC.

[0067] Cytochrome b-c1 complex subunit 9 forms part of complex III of the ETC.

[0068] Cytochrome C oxidase subunit 6C, cytochrome C oxidase subunit 2 and cytochrome C oxidase subunit NDUFA4 form part of complex IV of the ETC.

[0069] ATP synthase subunit g and ATP synthase subunit delta form part of the ATP synthase complex.

[0070] Phosphomevalonate kinase is part of the phosphomevalonate pathway that produces the precursor of ubiquinone, which is required in the respiratory chain for electron transport.

[0071] The NAD-dependent mitochondrial malic enzyme catalyzes the oxidative decarboxylation of malate to pyruvate, which is used in the three-carbon acid cycle to generate activated electrons for the respiratory chain.

[0072] ATP-dependent zinc metalloproteases ensure cell proliferation, maintain normal mitochondrial cristae morphology and complex I respiratory activity, promote anti-apoptotic activity, and protect mitochondria from the accumulation of oxidatively damaged membrane proteins.

[0073] Without being bound by theory, it is expected that the upregulation of these markers will lead to increased mitochondrial ATP production, resulting in enhanced cellular energy.Then, the expression of adverse phenotypes caused by mitochondrial dysfunction, including aging, especially inflammatory aging and photoaging, which further affect the healthy appearance of skin, including skin complexion, skin tone or skin radiance, is prevented or reduced.

[0074] Thus, the one or more compounds in the composition according to the invention may in particular be glucosylceramide, lactosylceramide and / or ceramide NG.

[0075] The glucosylceramide (GlcCER) referred to herein is preferably ceramide NS, C 18 The acyl chain length is C 18 Glucosylceramide NS having an acyl chain length of may be referred to herein as GlcCNS or GlcCNS18. Lactosylceramide (LacCER) as referred to herein is preferably, typically C 18 C is ceramide NS with an acyl chain length of 1. 18 Lactosylceramide NS having an acyl chain length of may also be referred to herein as LacCNS.

[0076] Most preferably, one compound in a composition according to the invention is GlcCNS18.

[0077] Ceramide NG, ceramide NS and ceramide NP are named according to the abbreviated nomenclature developed by Motta et al., Biochim Biophys Acta., 1993, 1182:147-151, and extended by Rabionet et al., Biochim Biophys Acta, 2014, 1841:422-434, and by Masukawa et al., Journal of Lipid Research, 2008, 49, 1466-1476. Ceramide NG may also be referred to as ceramide NdS. For each species, the number of carbons and unsaturations (if present) may be represented in parentheses following the letters N, A, E and O. If not specified, the carbon chain length of the sphingoid base moiety of the ceramides referred to herein is typically C. 18 Unless otherwise specified, the carbon chain length of the acyl moiety of the ceramides referred to herein is, for example, C 16 , C 17 , C 18 , C 19 , C 20 , C 22 or C 24 It could be.

[0078] The use of the present invention generally concerns an individual that is a mammal. In particular, the individual is a human. In some preferred embodiments, the human individual is an adult individual, i.e. a human aged 20 years or more, particularly aged 30 years or more, for example aged 40 years or more or aged 50 years or more, and in other preferred embodiments, the human individual can be a child or a teenager. The use of the topical composition of the present invention on younger individuals is particularly useful when prophylactic or preventive treatment is intended, or when the individual is in a situation where the visual appearance of the skin, particularly the skin of the face and neck, is adversely affected, for example, when the individual is prone to premature skin aging or suffers from a disease that affects the visual appearance of the skin.

[0079] In some embodiments, topical composition can advantageously contain additional compound that is known to enhance or can enhance cellular energy metabolism in individual skin cells.Examples include enzyme cofactors such as coenzyme Q10, vitamins, such as vitamin B3 (niacin or niacinamide) or vitamin C, agents that can move mitochondrial ATP out of mitochondria and promote ATP recycling, such as creatine, antioxidants, such as resveratrol or astaxanthin, or combinations thereof.This additional compound can preferably be coenzyme Q10, vitamin B3 or creatine.

[0080] The cosmetic use or treatment with the composition comprising the compound of formula I is intended to improve the visual appearance of the skin of the treated individual.The expression "improving the visual appearance of the skin" refers to the fact that the cosmetic treatment with the composition of the present invention comprising the compound of formula I has, in particular, the following beneficial effects on the treated skin of the individual: -Improves skin radiance, -Improves skin radiance, -Improves skin firmness, -Soothing of the skin, - Prevent or reduce skin aging, such as inflammation aging or photoaging, - Wrinkle smoothing, -Aids in skin regeneration, - Relieving signs of skin inflammation such as itching, redness or swelling, - Reduces signs of skin fatigue This means that one or more of the following will result:

[0081] In some embodiments, the present invention relates to a method for improving the radiance of skin, comprising administering onto the skin of an individual a composition comprising a compound of formula I.

[0082] In some embodiments, the present invention relates to a method for improving skin radiance, comprising administering onto the skin of an individual a composition comprising a compound of formula I.

[0083] In some embodiments, the present invention relates to a method for improving skin firmness comprising administering onto the skin of an individual a composition comprising a compound of formula I.

[0084] In some embodiments, the present invention relates to a method for soothing the skin, comprising administering onto the skin of an individual a composition comprising a compound of formula I.

[0085] In some embodiments, the present invention relates to a method for preventing or reducing skin aging, such as inflammatory aging or photoaging, comprising administering onto the skin of an individual a composition comprising a compound of formula I.

[0086] In some embodiments, the present invention relates to a method for smoothing wrinkles, comprising administering onto the skin of an individual a composition comprising a compound of formula I.

[0087] In some embodiments, the present invention relates to a method for assisting skin regeneration comprising administering onto the skin of an individual a composition comprising a compound of formula I.

[0088] In some embodiments, the present invention relates to a method for reducing symptoms of skin inflammation, such as itching, redness, or swelling, comprising administering onto the skin of an individual a composition comprising a compound of formula I.

[0089] In some embodiments, the present invention relates to a method for reducing signs of skin fatigue comprising administering onto the skin of an individual a composition comprising a compound of formula I.

[0090] As used herein, improving skin radiance refers especially to the color and texture of the facial skin.

[0091] Improving skin radiance as used herein refers to the firmness, luminosity, elasticity and fading of skin (light dark circles and sun damage).

[0092] As used herein, improving skin firmness means normalizing the skin's natural tone, reducing redness, and / or reducing hyperpigmentation.

[0093] Skin soothing or skin calming, as used herein, means protection from skin irritation or relief of irritated skin, such as reducing, relieving, or soothing the pain from sunburn or dehydration of the skin.

[0094] Preventing or reducing skin aging includes both chronological aging and premature aging, such as signs of aging due to reduced production of essential molecules that support the skin's natural structure, loss of moisture, UV photodamage, or exposure of the skin to intrinsic and extrinsic factors such as exposure to internal chemical radicals generated within the body (due to unhealthy diet or lifestyle, disease, etc.) or external pollutants that are harmful to the skin.

[0095] Inflammation-aging is a chronic low-grade inflammation that develops with age in the absence of obvious infection, and may contribute to the clinical manifestation of other age-related conditions.More precisely, inflammation-aging as used herein refers to skin inflammation as a biological response of body tissues to both environmental stresses, such as sunlight and chemical pollutants, and internal triggers, such as diet, alcohol intake and smoking, as well as other potentially harmful stimuli, including pathogens, bacteria, viruses and other common irritants.Mechanistically, during inflammation-aging, a low-grade, chronic and progressive predominance of pro-inflammatory cytokines over anti-inflammatory cytokines typically occurs.

[0096] Photoaging refers to the process of chronic sun exposure, especially exposure to UV-A and UV-B radiation, resulting in extrinsic skin aging. The structural and functional manifestations of skin aging are typically premature and more severe in photoaged skin compared to chronologically aged skin. Photoaged skin tends to have a rather leathery appearance, with deeper wrinkles and uneven pigmentation.

[0097] Wrinkle smoothing, as used herein, refers specifically to facial skin wrinkles, both fine surface lines and deeper furrows, i.e., reducing the appearance of wrinkled skin and smoothing the skin surface.

[0098] Assisting skin regeneration refers to replacing damaged skin cells with new, fully functional cells. Skin regeneration typically occurs in two possible ways: by repairing or reconstructing what has been destroyed, or by restoring or replacing and rebuilding what has been destroyed.

[0099] The skin fatigue referred to herein is typically the result of long-term stress.This can be, for example, the stress induced by lifestyle, such as lack of sleep or exercise, smoking and unhealthy diet, but also various environmental aggressors, such as pollution and UV radiation, can cause skin fatigue.

[0100] Generally, the cosmetic compositions of the present invention support and enhance the healthy appearance of the skin, particularly the skin of the face and neck.

[0101] An individual undergoing cosmetic treatment according to the present invention may, in some embodiments, have a disease or condition that affects the visual appearance of the skin.

[0102] The disease that affects the visual appearance of the skin in this context is typically not a skin disease, i.e. a disease that directly affects the skin, but other diseases that are not primarily related to the skin and may also affect the visual appearance of the skin only secondarily.Non-limiting examples also include cardiovascular disease, metabolic disease, gastrointestinal disease and mental disorders such as depression.The physiological condition that may affect the visual appearance of the skin in this context may be, for example, pregnancy or post-pregnancy.Physiological trauma or surgical intervention are also considered in the context of the present invention as physiological conditions that may affect the visual appearance of the skin of individuals who experience any of these conditions.

[0103] An individual undergoing cosmetic treatment according to the present invention may, in some embodiments, have a genetic predisposition to premature skin aging, for example, an individual may have a biological family in which premature, severe wrinkling or sensitive skin is common.

[0104] In some embodiments, an individual undergoing a cosmetic treatment according to the present invention may have been exposed to harmful environmental factors, including, but not limited to, weather conditions such as UV light, or chemical pollutants such as polycyclic aromatic hydrocarbons (PAHs), particulate matter PM2.5, blue light, ozone, or tobacco smoke.

[0105] The topical composition of the present invention can be structured or formulated into various different forms.Non-limiting examples include emulsions (e.g., water-in-oil, water-in-oil, oil-in-water, silicone-in-water, water-in-silicone, oil-in-water-in-oil, oil-in-water-in-silicone emulsions), creams, lotions, solutions (both aqueous and hydroalcoholic), anhydrous bases (such as lipsticks and powders), gels, facial masks, peeling agents and ointments.Modifications and other structures are obvious to those skilled in the art and are suitable for use in the present invention.

[0106] In some embodiments, the topical composition may be formulated as an emulsion, oil, liquid, or gel. In some embodiments, the topical composition may be formulated as an emulsion.

[0107] The topical compositions of the present invention are typically intended to be applied to the face, body and / or hair. The topical compositions are preferably for application to the face and / or body.

[0108] In preferred embodiments, the topical compositions are formulated as emulsions, oils, liquids or gels and for application to the face and / or body.

[0109] In some embodiments, the present invention relates to a composition that can be used for medical treatment of the skin of an individual. In the context of using the composition for medical or pharmaceutical purposes, the topical composition can be referred to as a pharmaceutical composition or a medicinal composition.

[0110] In some embodiments, the present invention provides a topical pharmaceutical composition for use in treating a skin condition in an individual, the composition comprising a compound of formula I [ka] I, The compound includes During the ceremony, X is hydrogen, a glucosyl moiety or a lactosyl moiety; [ka] The carbon-carbon bond represented by is a double or single bond, R 1 is an alkyl chain having 10 to 20 carbon atoms, R 2 is hydrogen or a substituted or unsubstituted acyl having 16 to 34 carbon atoms; R 3 teeth, [ka] If the carbon-carbon bond represented by is a double or single bond, it is hydrogen, or R 3 teeth, [ka] When the carbon-carbon bond represented by is a single bond, it is -OH; R 4 teeth, [ka] If the carbon-carbon bond represented by is a double or single bond, it is hydrogen, or R 4 teeth, [ka] When the carbon-carbon bond represented by is a double bond, it is hydrogen or -OH.

[0111] In some embodiments, the compound of formula I of the topical pharmaceutical composition has a (2S,3R,4E) stereochemical configuration; [ka] The carbon-carbon bond indicated is a double bond.

[0112] In some embodiments, the compound of formula I of the topical pharmaceutical composition has a (2S,3S,4R) or (2S,3S) stereochemical configuration; [ka] The carbon-carbon bond shown is a single bond.

[0113] In some embodiments, the R of the compound of formula I of the topical pharmaceutical composition 1 -C 12 H 25 and / or R 2 is selected from hexadecanoyl, 2-hydroxyhexadecanoyl, octadecanoyl, 2-hydroxyoctadecanoyl, eicosanoyl, 2-hydroxyeicosanoyl, lignoceroyl, 2-hydroxytetracosanoyl, 30-(linoleyloxy)-triacontanoyl.

[0114] The term "skin disease" according to the present invention is a disorder of structure or function in humans or animals that produces a specific symptom or affects a specific location, i.e., the skin, and is not merely the direct result of a physical injury. Non-limiting examples of skin diseases include acne, rosacea, erythrocouperosis, psoriasis, xerosis, ichthyosis, vascular disorders, diaper dermatitis, atopic dermatitis, eczema, contact dermatitis, irritant dermatitis, allergic dermatitis, and seborrheic dermatitis.

[0115] In some embodiments, the topical pharmaceutical composition further comprises a component that is pharma- ceutical active for treating a skin disorder and that is structurally distinct from the compound of formula I.

[0116] Non-limiting examples of such additional pharma- ceutical active agents include anti-acne agents, agents used to treat rosacea, analgesics, anesthetics, anorectals, antihistamines, anti-inflammatory agents including nonsteroidal anti-inflammatory drugs, antibiotics, antifungals, antivirals, antibacterial agents, anti-cancer actives, scabicides, pediculicides, antineoplastic agents, antiperspirants, antipruritics, antipsoriatic agents, antiseborrheic agents, bioactive proteins and peptides, burn treatments, cauterizing agents, depigmenting agents, antifungals, antivirals, antibacterial agents, anti-inflammatory agents, antifungals, antiseptics ... agents), depilatories, diaper rash treatments, enzymes, hair growth stimulants, hair growth retardants including DFMO and its salts and analogues, hemostatic agents, kerotolytics, stomatitis treatments, cold sore treatments, dental and periodontal treatments, photosensitizing actives, skin protectants / barrier agents, steroids including hormones and corticosteroids, sunburn treatments, sunscreens, transdermal actives, nasal actives, vaginal actives, wart treatments, wound treatments, wound healing agents, and the like.

[0117] The topical composition of the present invention can advantageously be administered on the skin of an individual for at least 7 days, for example at least 14 days or at least 21 days.For example, the topical composition is administered for at least 28 days.In fact, there is no time limit for the administration period of the cosmetic composition of the present invention.For the pharmaceutical composition of the present invention, the administration period is typically determined by medical personnel for each individual patient / animal.

[0118] Topical compositions (either cosmetic or pharmaceutical) may be administered once or several times daily, for example, two or three times daily. Typically, topical compositions are administered over consecutive days.

[0119] The topical composition of the present invention typically comprises or is incorporated into different types of vehicles and carriers.In some embodiments, the topical composition of the present invention further comprises a topically acceptable carrier.Vehicle or carrier can be a pharmaceutically and / or dermatologically acceptable vehicle or carrier.Non-limiting examples of vehicle or carrier include water, glycerin, alcohol, oil, silicon-containing compound, silicone compound and wax.Variations and other suitable vehicles will be obvious to those skilled in the art and are suitable for use in the present invention.In certain aspects, the concentration and combination of compounds, ingredients and agents can be selected so that the combination is chemically compatible and does not form complexes that precipitate from the final product.

[0120] In some embodiments, the topical composition comprises a C6-C aryl ester that serves as an acceptable carrier for one or more compounds of formula I. 100 The composition may contain an ester base. Suitable examples of the ester base include the following:

[0121] (1) C7~C 60 Neoalkanol estersThese esters are C1-C 22 They may be formed from the reaction of alkanoic acids with neopentyl alcohol, neopentyl glycol, 2-butyl-2-ethyl-1,3-propanediol, 2,2,4-trimethyl-1,3-pentanediol, trimethylolpropane, pentaerythritol, di-trimethylolpropane, di-pentaerythritol or pentaerythritol-trimethylolpropane dimer. Examples include isostearyl neopentanoate, palmityl neopentanoate, tetraoctyl pentaerythritol and diisopropyl neopentanoate. The amount of the ester may suitably range from 1% to 90%, preferably 20% to 75%, optimally 30% to 50% by weight of the topical composition.

[0122] (2) C alkoxylated with 1 to 100 moles of C2 to C3 alkylene oxide per mole of glyceride 12 ~C 40Fatty glyceride esters. C 12 ~C 40 The fatty glyceride ester alkoxylates preferably contain 4 to 20 moles of alkylene oxide per mole of glyceride. Preferred alkylene oxides are ethylene oxide and propylene oxide. Examples are PEG-6 caprylic / capric glyceride and PEG-8 caprylic / capric glyceride, which are polyethylene glycol derivatives of mixtures of mono-, di- and triglycerides of caprylic and capric acid, respectively, with 6 and 8 moles of ethylene oxide, respectively. The amount of the esters may suitably range from 1% to 90%, preferably 5% to 50%, optimally 10% to 20% by weight of the topical composition.

[0123] (3) Polyglycerol C8-C 22Mono- or di-fatty acid esters. Examples include polyglycerol-3 beeswax, polyglycerol-4 cocoate, polyglycerol-10 decalinolate, polyglycerol-10 decaoleate, polyglycerol-7 decaterate, polyglycerol-2 diisostearate, polyglycerol-3 diisostearate, polyglycerol-7 diisostearate, polyglycerol-2 dioleate, polyglycerol-3 dioleate, polyglycerol-6 dioleate, polyglycerol-10 dioleate, polyglycerol-3 distearate, polyglycerol-6 distearate, polyglycerol-10 distearate. Polyglycerol-10 heptaoleate, polyglycerol-10 heptastearate, polyglycerol-6 hexaoleate, polyglycerol-2 isostearate, polyglycerol-4 isostearate, polyglycerol-6 isostearate, polyglycerol-10 laurate, polyglycerol-10 myristate, polyglycerol-2 oleate, polyglycerol-3 oleate, polyglycerol-4 oleate, polyglycerol-6 oleate, polyglycerol-8 oleate, polyglycerol-10 oleate and combinations thereof. Most preferred is polyglycerol-6 dioleate, a diester of oleic acid and a glycerol polymer containing an average of 6 glycerol units. The amount of this ester may range from 1% to 50%, preferably 5% to 25%, and optimally 10% to 20% by weight of the topical composition.

[0124] (4) C8~C 22 Fatty acids C8 to C 22 Alkanol esters. Non-limiting examples include cetyl octanoate, lauryl pentanoate, palmityl palmitoate, isostearyl decanoate, oleyl heptanoate and combinations thereof. The amount of this material may range from 1% to 50%, preferably from 5% to 30%, optimally from 10% to 20% by weight of the topical composition.

[0125] The ester base may range from about 30% to 95%, preferably from 40% to 80%, optimally from 50% to 70% by weight of the topical composition.

[0126] The topical composition contains glycerol C8-C 22 The topical composition may further comprise a solubilizer in the form of a mono-fatty acid ester. Non-limiting examples of the solubilizer include glycerol monoisostearate, glycerol monobehenate and glycerol monopalmitate. The solubilizer may comprise about 0.1% to 20%, preferably 0.5% to 10%, optimally 1% to 5% of the weight of the topical composition.

[0127] The topical composition may contain other carriers such as silicone oils. Silicone oils may be cyclic or linear polydimethylsiloxanes containing 3 to 9, preferably 4 to 5, silicon atoms, or polyalkylsiloxanes, polyalkylarylsiloxanes and polyethersiloxane copolymers. Silicones may generally be present in an amount ranging from 1% to 50%, preferably 2% to 25%, optimally 10% to 20% by weight of the topical composition.

[0128] The topical compositions may also include additional ingredients typically found in cosmetic and skin care formulations, such as cosmetic ingredients and pharmaceutical active ingredients.

[0129] Examples of further ingredients in the topical composition of the present invention in different embodiments may include chalk, talc, fullers, earth, kaolin, starch, smectite clay, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, aluminum starch octenyl succinate. Also, surfactants may be added, including alkyl sulfates such as sodium lauryl sulfate, sodium laureth sulfate, sodium coco sulfate and sodium trideceth sulfate, betaines such as cocobetaine, carbohydrates such as lauryl glucoside and coco glucoside. Other ingredients are colorants, opacifiers and perfumes. The amount of these auxiliary materials may conveniently range from 0.001% to 20% by weight of the composition.

[0130] The CTFA International Cosmetic Ingredient Dictionary and Handbook (2004 and 2008) describes a wide variety of non-limiting cosmetic ingredients that can be used in the context of the present invention. Examples of these ingredient classes include fragrance agents (artificial and natural; e.g., gluconic acid, phenoxyethanol, and triethanolamine), dyes and coloring ingredients (e.g., Blue 1, Blue 1 Lake, Red 40, titanium dioxide, D&C blue no. 4, D&C green no. 5, D&C orange no. 4, D&C red no. 17, D&C red no. 33, D&C violet no. 2, D&C yellow no. 10, and D&C yellow no.11), flavoring agents / aroma agents (e.g., Stevia rebaudiana (sweet leaf) extract, and menthol), adsorbents, lubricants, solvents, moisturizers (including, e.g., emollients, humectants, film-forming agents, occlusive agents, and agents that affect the skin's natural moisturizing mechanisms), water repellents, UV absorbers and / or reflectors (physical and chemical absorbers such as para-aminobenzoic acid ("PABA" and corresponding PABA derivatives, titanium dioxide, zinc oxide, etc.), essential oils, vitamins (e.g., A, B, C, D, E, and K), trace metals (e.g., zinc, calcium, and selenium), anti-irritants (e.g., steroidal and non-steroidal anti-inflammatory drugs), plant extracts (e.g., Aloe vera, chamomile, cucumber extract, Ginkgo biloba extract, and others), and / or other additives. biloba), ginseng and rosemary), antibacterial agents, antioxidants (e.g., BHT and tocopherol), chelating agents (e.g., disodium EDTA and tetrasodium EDTA), preservatives (e.g., methylparaben and propylparaben), pH adjusters (e.g., sodium hydroxide and citric acid), absorbents (e.g., aluminum starch octenyl succinate, kaolin, corn starch, oat starch, cyclodextrin, talc and zeolite), skin depigmenting and whitening agents (e.g., hydroquinone and niacinamide lactate), moisturizers (humect Examples of suitable skin care ingredients include: antioxidants (e.g., sorbitol, urea, methyl gluceth-20, sucrose isomerate, and mannitol), exfoliants, waterproofing agents (e.g., magnesium stearate / aluminum hydroxide), skin conditioning agents (e.g., aloe extract, allantoin, bisabolol, ceramides, dimethicone, hyaluronic acid, biosaccharide gum-1, ethylhexylglycerin, pentylene glycol, hydrogenated polydecene, octyldodecyl oleate, and dipotassium glycyrrhizinate). Some non-limiting examples of these ingredients are provided in the following subsections.

[0131] The topical compositions may also include fatty alcohols and acids having from 10 to 36 carbon atoms. Compounds such as cetyl, myristyl, palmityl, isostearyl, and stearyl alcohols and acids are particularly preferred.

[0132] The topical composition may further comprise an α-hydroxycarboxylic acid. Suitable examples include α-hydroxyethanoic acid, α-hydroxypropanoic acid, α-hydroxyhexanoic acid, α-hydroxyoctanoic acid, α-hydroxydecanoic acid, α-hydroxydodecanoic acid, α-hydroxytetradecanoic acid, α-hydroxyhexadecanoic acid, α-hydroxyoctadecanoic acid, α-hydroxyeicosanoic acid, α-hydroxydocosanoic acid, α-hydroxyhexacosanoic acid and α-hydroxyoctacosanoic acid. The α-hydroxycarboxylic acid may be in the acid form or in the salt form. Exemplary salts include alkali metal, ammonium and C2-C4 hydroxyalkyl esters. 30 Ammonium salts, such as sodium, potassium, triethanolammonium and ammonium salt forms. Typical salts are alkali metal, ammonium and C2-C 30 Ammonium salts such as sodium, potassium, triethanolammonium and ammonium salts. The alpha-hydroxycarboxylic acid will generally be present in the range of 0.001% to 20%, preferably 0.01% to 15%, optimally 0.5% to 10% by weight of the topical composition.

[0133] Topical compositions can also contain vitamins. Examples include sources or derivatives of vitamin C, such as ascorbyl palmitate, ascorbyl glucoside, magnesium ascorbyl phosphate, ascorbyl lysostearate, vitamin A palmitate (retinyl palmitate) and vitamin E linoleate (tocopheryl linoleate). Other esters of vitamin C, vitamin A and vitamin E can also be utilized.

[0134] The topical composition may also include a typical emulsifier. The emulsifier may be nonionic, anionic, cationic or amphoteric in nature. Examples of suitable emulsifiers include polyoxypropylene-polyoxyethylene ether of cetyl alcohol and glycerol monoisostearate. The emulsifier may suitably range from 0.5% to 30%, preferably from 1% to 15%, optimally from 3% to 8% by weight of the topical composition.

[0135] The topical composition may also include a thickening agent. Examples include cross-linked polyacrylate materials and gums, such as xanthan, carrageenan, gelatin, karaya, pectin, and locust bean gum. The thickening agent may be present in an amount of about 0.1% to 20%, preferably 0.5% to 10%, by weight of the topical composition.

[0136] The topical composition may also contain a suitable preservative. Suitable preservatives include alkyl esters of p-hydroxybenzoic acid, phenoxyethanol, hydantoin derivatives, propionate salts, and various quaternary ammonium compounds, such as methylparaben, propylparaben, imidazolidinyl urea, sodium dehydroxyacetate, and benzyl alcohol. Preservatives are typically used in amounts ranging from 0.1% to 2% by weight of the topical composition.

[0137] Topical compositions may also include materials such as p-anisic acid, sodium anisate, levulinic acid, sodium levulinate, sodium hydroxide, caprylyl glycol, 1,2-hexanediol, pentylene glycol, glyceryl caprylate, glyceryl caprate, ethylhexylglycerin, undecylenamidopropyl-trimonium methosulfate, propylene glycol, phenylpropanol, phenethyl alcohol, methylpropanediol, dipropylene glycol, or combinations thereof.

[0138] Various aspects of the present invention discussed above are described in the following selected, but non-limiting, embodiments.

[0139] 1. A cosmetic use of a composition for enhancing skin cell energy metabolism in an individual, said composition comprising one or more compounds of formula I [ka] I, The compound includes During the ceremony, [ka] The carbon-carbon bond represented by is a double or single bond, R 1 is an alkyl chain having 10 to 20 carbon atoms, R 2 is hydrogen or a substituted or unsubstituted acyl having 16 to 34 carbon atoms; R 3 teeth, [ka] is a double or single bond, then it is hydrogen; or R 3 teeth, [ka] When the carbon-carbon bond represented by is a single bond, it is -OH; R 4 teeth, [ka] is a double or single bond, then it is hydrogen; or R 4 teeth, [ka] When the carbon-carbon bond represented by is a double bond, it is hydrogen or -OH; X is hydrogen, a glucosyl moiety or a lactosyl moiety.

[0140] 2. The cosmetic use according to embodiment 1, wherein the composition is a topical composition.

[0141] 3. R ​​of the compound of formula I 1 Ga-C 12 H 25 and / or R 2 The cosmetic use according to embodiment 1 or 2, wherein is selected from hexadecanoyl, 2-hydroxyhexadecanoyl, octadecanoyl, 2-hydroxyoctadecanoyl, eicosanoyl, 2-hydroxyeicosanoyl, lignoceroyl, 2-hydroxytetracosanoyl, 30-(linoleyloxy)-triacontanoyl.

[0142] 4. The cosmetic use according to any one of embodiments 1 to 3, wherein the compound of formula I is present in an amount of from about 0.0001% to about 10% weight / weight, such as from about 0.005% to about 5% weight / weight, or from about 0.05% to about 0.2% weight / weight.

[0143] 5. The composition, -X is glucosyl, and R 2 is a substituted or unsubstituted acyl having 16 to 34 carbon atoms, -X is lactosyl, and R 2 is a substituted or unsubstituted acyl having 16 to 34 carbon atoms, and / or -X is hydrogen and R 1 Ga-C 12 H 25 and R 2 is a substituted or unsubstituted acyl having 16 to 34 carbon atoms. The cosmetic use according to any one of embodiments 1 to 4, comprising:

[0144] 6. The cosmetic use according to any one of the preceding embodiments, wherein the composition further comprises coenzyme Q10, vitamin B3, vitamin C, creatine and / or resveratrol.

[0145] 7. The following beneficial effects on an individual's skin: -Improves skin radiance, -Improves skin radiance, -Improves skin firmness, -Skin soothing, - Prevent or reduce skin aging, such as inflammation aging or photoaging, - Wrinkle smoothing, -Aids in skin regeneration, - Relieving signs of skin inflammation such as itching, redness or swelling, - Reduces signs of skin fatigue The cosmetic use according to any one of embodiments 1 to 6, comprising one or more of the following:

[0146] 8. Cosmetic use according to any one of embodiments 1 to 7 for activating the respiratory chain and the production of ATP in skin cells.

[0147] 9. Cosmetic use according to any one of embodiments 1 to 8 for the activation of complex I.

[0148] 10. A method for enhancing skin cell energy metabolism comprising administering to a subject a compound of formula I [ka] I, topically administering onto the skin of an individual a composition comprising a compound of During the ceremony, [ka] The carbon-carbon bond represented by is a double or single bond, R 1 is an alkyl chain having 10 to 20 carbon atoms, R 2 is hydrogen or a substituted or unsubstituted acyl having 16 to 34 carbon atoms; R 3 teeth, [ka] If the carbon-carbon bond represented by is a double or single bond, it is hydrogen, or R 3 teeth, [ka] When the carbon-carbon bond represented by is a single bond, it is -OH; R 4 teeth, [ka] If the carbon-carbon bond represented by is a double or single bond, it is hydrogen, or R 4 teeth, [ka] When the carbon-carbon bond represented by is a double bond, it is hydrogen or -OH; The method, wherein X is hydrogen, a glucosyl moiety, or a lactosyl moiety.

[0149] 11. The cosmetic use according to any one of embodiments 1 to 9 or the method according to embodiment 10, wherein the individual is a human individual.

[0150] 12. The individual, - a disease affecting the visual appearance of said skin, - inherited premature skin aging, and / or - Exposure to harmful environmental factors The cosmetic use or method according to any one of embodiments 1 to 11, comprising one or more of the following:

[0151] 13. The cosmetic use or method according to embodiment 12, wherein the harmful environmental factors include climatic conditions such as UV light, or chemical pollutants such as polycyclic aromatic pollutants (PAHs), particulate matter PM2.5, blue light, ozone or tobacco smoke.

[0152] 14. The cosmetic use or method according to any one of the preceding embodiments, wherein the composition is administered onto the skin of an individual for at least 2 days, in particular for at least 7 days or at least 14 days, for example for 28 days.

[0153] 15. A cosmetic topical composition for enhancing skin cell energy metabolism in an individual, said topical composition comprising one or more compounds of formula I [ka] I, The compound includes During the ceremony, [ka] The carbon-carbon bond represented by is a double or single bond, R 1 is an alkyl chain having 10 to 20 carbon atoms, R 2 is hydrogen or a substituted or unsubstituted acyl having 16 to 34 carbon atoms; R 3 teeth, [ka] If the carbon-carbon bond represented by is a double or single bond, it is hydrogen, or R 3 teeth, [ka] When the carbon-carbon bond represented by is a single bond, it is -OH; R 4 teeth, [ka] If the carbon-carbon bond represented by is a double or single bond, it is hydrogen, or R 4 teeth, [ka] When the carbon-carbon bond represented by is a double bond, it is hydrogen or -OH; X is hydrogen, a glucosyl moiety or a lactosyl moiety; The composition has the following beneficial effects on the skin of an individual: -Improves skin radiance, -Improves skin radiance, -Improves skin firmness, -Skin soothing, - Prevent or reduce skin aging, such as inflammation aging or photoaging, - Wrinkle smoothing, -Aids in skin regeneration, - Relieving signs of skin inflammation such as itching, redness or swelling, - Reduces signs of skin fatigue A cosmetic topical composition comprising one or more of the following:

[0154] 16. A pharmaceutical composition comprising a compound of formula I for treating a skin disease in an individual, such as psoriasis, keratoderma, dermatitis or atopic dermatitis.

[0155] 17.- structurally different from the compounds of formula I, and - Pharmacologically active for the treatment of skin diseases, 17. The pharmaceutical composition of embodiment 16, further comprising a compound. EXAMPLES

[0156] The examples set forth below are for illustrative purposes only, and the scope of the invention is not limited to the embodiments set forth in the examples.

[0157] Example 1: Characterization of the efficacy of glucosylceramide as a cosmetic active ingredient Materials and Methods: Reconstructed human epidermis (RHE) cell cultures were used because the RHE cell culture system mimics the in vivo 3D structure of epidermal tissue as well as the conditions and processes occurring in normal epidermis. RHE were cultured using the medium provided by the manufacturer until analysis. After keeping the RHE in a viable state for 24 hours, the RHE were treated topically with lipids in base emulsion for 24 hours. Three RHE were treated with base emulsion only and three more were left untreated as control batches (Ctrl). RHE were incubated under classical cell culture conditions (37°C, 5% CO2).

[0158] Sample preparation and LC-MS / MS analysis: Proteins were extracted using the Pierce Total Protein Extraction Kit (Thermo Fisher) according to the manufacturer's recommendations. Proteins were mixed with Laemmli buffer and heated to 37 °C for 30 min. Protein concentration was determined by the BCA method and normalized for all samples. Samples were separated by SDS-PAGE and digested with trypsin overnight. Generated peptides were acidified and separated. Mass spectra were queried using Proteome Discoverer (version 2.5). The obtained MS / MS data were queried against the Homo sapiens proteome UP000005640 (20371 reviewed entries). Results were filtered based on unique peptides greater than 2 and global peptide score. Analysis was performed using Proteome Discoverer 2.5 to check the overall sample quality.

[0159] Bioinformatics and statistical analysis: Proteomic analysis returned an average total of 34961 high-quality peptides, representing an average of 2422 identifiable and quantifiable RHE proteins among conditions. Proteins with a p-value of 0.05 or less in at least one of the concentrations tested for lipids were considered significant and used for pairwise comparisons. Associated proteins were classified by biological process and associated pathway using the publicly available Gene Ontology (GO) database provided by the Gene Ontology Consortium and Reactome. Interactome analysis was performed using Cytoscape combined with STRING.

[0160] Example 2: Characterization of the effect of glucosylceramide on skin cell energetics using skin explants The aim of this study is to evaluate the effect of glucosylceramide on cellular energetics using live human skin explants. Activity is assessed by biochemical quantification of complex I.

[0161] Complex I, found in mitochondria, is the first of five mitochondrial complexes that carry out the multistep process called oxidative phosphorylation through which cells obtain much of their energy. The analysis was based on the determination of complex I activity in skin explants.

[0162] 2.1 Explant preparation: Human skin explants with a mean diameter of 11 mm (±1 mm) from a 57-year-old Caucasian woman with type II phototype according to the Fitzpatrick skin classification were prepared at abdominoplasty. Explants were kept viable in BEM culture medium (BIO-EC's Explants Medium) at 37°C in a humidified, 5% CO2 atmosphere.

[0163] [Table 1]

[0164] [Table 2]

[0165] 2.2 Product application: 1cm 2 2 μL per explant (approximately 2 mg / cm 2 The products E and P to be tested were applied topically at a rate of 100 µg / well and spread with a small spatula on day 0 (D0), D1, D2 and D5. The control explants T did not receive any treatment except for the change of the culture medium. The culture medium was changed halfway on D1, D2 (1 ml per well) and completely on D5 (2 mL per well).

[0166] 2.3 Sampling: On D0, three explants from batch T0 were collected and cut into three parts: 1 / 3 was fixed in a buffered formalin solution, 1 / 3 was frozen at -80 °C for histological analysis, and 1 / 3 was frozen at -80 °C for administration of ATP complex I (NADH dehydrogenase) achieved by Integracell. On D6, four explants from the relevant batch were collected and treated the same as on D0. The culture medium BEM of all batches was collected on D6 (2 mL per explant) and stored at -20 °C for administration.

[0167] 2.4 Histological processing and cell viability: After 24 hours of fixation in buffered formalin, samples were dehydrated and impregnated in paraffin using a Leica PEARL dehydration automat. Samples were embedded using a Leica EG 1160 embedding station. 5 μm thick sections were made using a Leica RM 2125 Minot type microtome and mounted on Superfrost® tissue glass slides. Microscopic observation was achieved using a Leica DMLB, Olympus BX43 or BX63 microscope. Images were digitized by a numeric DP72 or DP74 Olympus camera (Olympus) equipped with cellSens storage software.

[0168] Cell viability of epidermal and dermal structures was assessed by Masson's trichrome staining and microscopic observation of formalin-fixed paraffin-embedded (FFPE) skin sections after the Goldner modification. Staining was assessed by microscopic observation.

[0169] 2.5 Biochemical and enzymatic quantitative assays: Frozen explants (1 / 3) were ground in phosphate buffer pH=7.8 using an ultra homogenizer (Turax) and then cell disruption was performed using an ultrasonic disintegrator (Bransonic). After centrifugation at +4000 tr / min at 18°C, the supernatants of all explants were collected for total protein dosage, citrate synthase (CS) activity and complex I (NADH dehydrogenase) activity by Integracell.

[0170] 2.5.1 Total Protein Dose: Total protein was quantified by the automated Bradford technique using Bradford reagent. The total protein concentration of each explant was expressed in g / L.

[0171] 2.5.2 Citrate synthase activity assay: Citrate synthase is commonly used as a quantitative enzymatic marker for the presence of intact mitochondria. An enzymatic method was used to achieve a citrate synthase activity assay. The enzyme catalyzes the reaction between acetyl coenzyme A (acetyl-CoA) and oxaloacetate to form citrate. The reaction capacity of citrate synthase was examined by measuring the formation of -SH groups liberated from CoA-SH through the use of reactive Ellman's reagent (5,5'-dithiobis[2-nitrobenzoic acid], DTNB) and monitoring the absorbance at 415 nm.

[0172] This assay was used to measure citrate synthase activity on days 0 and 6. Citrate synthase activity was measured in international units per gram of total protein (U / g protein).

[0173] 2.5.3 Complex I Activity Assay: An enzymatic method was used to achieve complex I (CP1) activity assay. This assay is based on the conversion of NADH by NADH dehydrogenase followed by monitoring of absorbance at 340 nm. This assay was used to measure complex I activity on days 0 and 6.

[0174] Complex I activity was expressed in units of complex per unit of citrate synthase (U / CS), which represents the complex I activity in mitochondria. Complex I activity was also expressed in units of complex per gram of total protein (U / g protein), which represents the overall complex I activity in cells.

[0175] 2.6 Results: 2.6.1 Cell viability: At D0 and D6, cell viability is good in the epidermis and dermis. Products E and P do not induce any alterations in cell viability.

[0176] 2.6.2 Dosage of Complex I: The activity of complex I (NADH dehydrogenase) in the explants (expressed in U / g protein) represents the total complex I activity in the cells for all batches presented here below. [Table 3]

[0177] Product E induces a non-significant increase of 8% in complex I activity compared to T6. Product P induces a significant increase of 24% in complex I activity compared to T6. The results are also shown graphically in FIG. 4.

[0178] The above-mentioned embodiments can be combined. The following dependent claims set forth particular embodiments of the invention.

Claims

1. A composition for enhancing the energy metabolism of skin cells in an individual, comprising one or more formulas I 【Chemistry 1】 I, Contains the compound, During the ceremony, 【Chemistry 2】 The carbon-carbon bonds shown are either double or single bonds. R １ This is an alkyl chain having 10 to 20 carbon atoms. R ２ This is a substituted or unsubstituted acyl having hydrogen or 16 to 34 carbon atoms. R ３ teeth, 【Transformation 3】 If the carbon-carbon bond shown is a double or single bond, it is hydrogen, or R ３ teeth, 【Chemistry 4】 When the carbon-carbon bond shown is a single bond, it is -OH, R ４ teeth, 【Transformation 5】 If the carbon-carbon bond shown is a double or single bond, it is hydrogen, or R ４ teeth, 【Transformation 6】 When the carbon-carbon bond shown is a double bond, it is either hydrogen or -OH. X is a hydrogen atom, a glucosyl moiety, or a lactosyl moiety. A composition for enhancing skin cell energy metabolism in an individual, wherein the compound of formula I is present in an amount of about 0.0001% to about 10% by weight, for example, about 0.005% to about 5% by weight, or about 0.05% to about 0.2% by weight.

2. -X is glucosyl, and R ２ A compound of formula I in which is a substituted or unsubstituted acyl having 16 to 34 carbon atoms, -X is lactosyl, and R ２ A compound of formula I in which is a substituted or unsubstituted acyl having 16 to 34 carbon atoms, and / or -X is hydrogen, and R １ is -C １２ H ２５ and R ２ is a substituted or unsubstituted acyl having 16 to 34 carbon atoms, a compound of formula I A composition for enhancing skin cell energy metabolism in an individual according to claim 1, comprising:

3. A composition for enhancing skin cell energy metabolism in an individual according to claim 1 or 2, further comprising an enzyme cofactor such as coenzyme Q10, a vitamin such as vitamin B3 or vitamin C, an antioxidant such as astaxanthin or resveratrol, and / or a substance that promotes ATP regeneration such as creatine.

4. The following beneficial effects on the skin of individuals: - Improves skin radiance, - Improves skin radiance, - Improves skin firmness, - Soothing the skin, - Prevents or reduces skin aging such as inflammatory aging or photoaging. - Smoothing of wrinkles, - To assist in skin regeneration, - Relieves signs of skin inflammation such as itching, redness, or swelling. - Reduces signs of skin fatigue A composition for enhancing skin cell energy metabolism in an individual according to claim 1 or 2, comprising one or more of the above.

5. A composition for enhancing skin cell energy metabolism in an individual according to claim 1 or 2, which is for activating the production of the respiratory chain and / or ATP in skin cells.

6. A composition for enhancing skin cell energy metabolism in an individual according to claim 1 or 2, for activating complex I.

7. The composition for enhancing skin cell energy metabolism in the individual according to claim 1 or 2, wherein the individual is a human individual.

8. The aforementioned individual, - Diseases or physiological conditions that affect the visual appearance of the skin, such as physical or psychological trauma, - Genetics of early skin aging, - Exposure to harmful environmental factors A composition for enhancing skin cell energy metabolism in an individual according to claim 1 or 2, having or possessing one or more of the following.

9. The composition for enhancing skin cell energy metabolism in an individual according to claim 1 or 2, wherein the composition is administered onto the skin of the individual for at least two days, particularly at least seven days or at least fourteen days, for example, 28 days.

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