Promoting hair growth

Abstract

The present invention relates to a method for promoting hair growth or preventing hair loss on the skin of a subject using formula I: TIFF2026516260000010.tif28170 (in the formula, R 1 R is an alkyl chain having 10 to 20 carbon atoms. 2 The present invention relates to the use of a composition comprising a compound in which (X is an acyl having 16 to 34 carbon atoms, and X is a hydrogen atom, a glucosyl moiety, or a lactosyl moiety).

Description

[Technical Field]

[0001] This invention relates to the use of a composition for promoting hair growth or preventing hair loss on the skin of a subject. [Background technology]

[0002] Hair is a thread-like biological substance that grows approximately 0.3 mm per day on the human scalp, with about 100 hairs falling out each day. Hair often refers to two structures: the hair bulb, the part beneath the skin, and the hair shaft, the stiff, thread-like part that extends above the skin's surface. Hair plays a role in thermoregulation, body protection, and social interaction. For humans, the primary function of hair is an important aspect of appearance. Alopecia, or hair loss, is defined as the loss of hair from a certain part of the body. Hair loss or slowed hair growth affects millions of people, including a significant number of women as well as over 40% of men over 30. Factors contributing to hair loss include scarring, disease, infection, reduced blood flow in the scalp's capillaries, and sensitivity to androgens. While alopecia is not life-threatening, it can affect an individual's sense of aesthetics, social activities, and quality of life. Hair growth is the result of the growth and differentiation of the hair follicle, which contains dermal papilla cells and epithelial cells. Hair follicle stem cells maintain the growth and cycle of hair follicles and reside in the homeostatic portion of the hair follicle known as the bulge. The cyclical changes in hair follicle growth are divided into various stages called anagene (growth), katagen (regression), terogen (resting), and exogen (shedding). The transitions in the human hair cycle are controlled by several growth stimulants or inhibitors. During anagenesis, rapidly proliferating progenitor cells within the hair bulb generate the hair and the surrounding inner root sheath. The onset of katagen is characterized by the cessation of proliferation and apoptosis of epithelial cells below the bulge. The mesenchymal-derived dermal papilla survives katagen, migrates upward to the bottom of the bulge, and then forms a secondary hair bud at its base during terogen. It is thought that mesenchymal-epithelial interactions, not yet fully understood, are involved via BMP and WNT signaling to induce the onset of the anagenetic phase and the formation of a new hair follicle base and shaft. As new hair grows, the old hair falls out during exogen. The duration of each stage varies depending on the type, location, and genetic programming of the hair follicle. In many cases, the hair growth phase shortens with age, resulting in shorter and / or thinner hair. A change in the ratio of actively growing hair to resting hair can lead to a decrease in hair density. In extreme cases, the hair growth cycle may stop completely, resulting in baldness.

[0003] While drug-based treatments are available for hair loss, they often cause various side effects in patients. Therefore, there is growing emphasis on new approaches that utilize bioactive products to promote hair growth. The cosmetics industry has introduced numerous compounds to mitigate the visible effects of alopecia. Some substances can prevent or reduce hair loss. Others can promote hair growth, particularly by activating hair follicles and initiating new hair growth cycles.

[0004] There is still a need for cosmetic ingredients that promote hair growth or prevent hair loss in subjects, with little to no side effects. [Overview of the project]

[0005] The inventors have surprisingly discovered that ceramide NG effectively promotes hair growth or reduces hair loss on the skin of subjects. Ceramide NG specifically targets the extension of the anagenetic growth phase of the hair cycle and the activation of hair follicle stem cells.

[0006] The present invention includes the following embodiments.

[0007] (1) Formula I for promoting hair growth or preventing hair loss on the skin of the subject: [ka] (In the formula, R 1 This is an alkyl chain having 10 to 20 carbon atoms. R 2 It is an acyl having 16 to 34 carbon atoms. Use of a composition containing a compound (where X is hydrogen, a glucosyl moiety, or a lactosyl moiety).

[0008] (2) A method for promoting hair growth or preventing hair loss on the skin of a subject, comprising administering a composition containing a compound of formula I to the skin.

[0009] (3) A method for activating the hair cycle on the skin of a subject, the method comprising administering to the skin a composition comprising a compound of formula I.

[0010] In particular, the composition is a topical composition and is used for cosmetic purposes on the human scalp and / or hair (i.e., a cosmetic hair composition), or on the hair or fur of a domestic animal.

[0011] Various non-limiting embodiments related to the above aspects of the present invention are described throughout the specification of the present invention and are illustrated by non-limiting examples.

Brief Description of the Drawings

[0012] [Figure 1] FIGURE showing a heat map depicting the upregulation (shown in black) or downregulation (shown in white) of each protein compared to a ceramide-free vehicle (VEH) when treated with 0.01% (01), 0.03% (03), and 0.15% (15) of ceramide NG in a vehicle, using a log2 scale. The detailed experimental setup is described in Example 1.

Modes for Carrying Out the Invention

[0013] Here, surprisingly, it has been found that the compound of formula I promotes hair growth. In one aspect, the present invention relates to the use of a composition for promoting hair growth or preventing hair loss on the skin of a subject, the composition comprising a compound of formula I:

Chemical Formula

[0014] As used herein, the term “alkyl” refers to an acyclic linear hydrocarbyl group in which carbon atoms are saturated or may contain one or more double and / or triple bonds (thus forming, for example, alkenyl or alkynyl groups). Examples of “alkyl” include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, isobutyl, n-butyl, sec-butyl, tert-butyl, isopentyl, n-pentyl, neopentyl, 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 a saturated hydrocarbon group.

[0015] The compositions of the present invention are intended for topical application. “Topical compositions” as used herein include compositions suitable for topical application to keratinous tissue. Keratinous tissue includes keratin-containing layers that constitute the outermost protective layer of mammals, and in particular, skin, scalp, and hair. Topical compositions are typically dermatologically acceptable in that they do not exhibit excessive toxicity, incompatibility, instability, allergic reactions, etc., when applied to the skin.

[0016] The compositions of the present invention are particularly intended for cosmetic purposes on the scalp and hair of humans, preferably as cosmetic hair compositions, or for cosmetic purposes on the hair or coat of domesticated animals such as dogs, cats, or horses.

[0017] "Hair" is defined as stratified squamous keratinized epithelium, composed of multiple layers of squamous cells, in which rope-like filaments give structure and strength to the hair shaft. As used herein, hair refers to both the hair of the human scalp and the body hair of animals, which can be used herein without distinction from "fur."

[0018] Those skilled in the art will understand that the “subject” in the present invention refers to a furry mammal.

[0019] In some preferred embodiments, the subject is human. In some embodiments, the human is male. Men are more likely to suffer from hair loss than women. Men often suffer from a sex-specific type of hair loss called androgenetic alopecia or androgenic alopecia. This type of hair loss is hereditary and often develops at a young age. The main cause of this type of hair loss is the steroid hormone dihydrotestosterone (DHT). This is formed in the human body from the male hormone testosterone by steroid-5-alpha-reductase and, in cases of hereditary DHT hypersensitivity, leads to a shortening of the anagenetic phase of hair growth. Another form of hair loss, alopecia areata, refers to localized and circular hair loss. This type of hair loss is an inflammatory autoimmune disease caused by lymphocytes attacking the hair bulb of the hair follicle during the anagenetic phase and can occur at any stage.

[0020] In other embodiments, the human is female. One form of hair loss that is primarily seen in women is diffuse alopecia. Diffuse alopecia presents as temporary hair loss, but its possible causes are diverse, such as hormonal fluctuations, stress, or iron deficiency.

[0021] Factors that cause hair loss in humans include, in particular, decreased hair follicle function due to male hormones, decreased metabolic function of hair follicles and hair bulbs, decreased physiological function of the scalp, and localized circulatory disorders due to scalp tension.

[0022] In some preferred embodiments, the subjects are domesticated animals. Examples include dogs, cats, horses, sheep, rabbits, and hamsters. Preferred domesticated animals include dogs, cats, and horses.

[0023] While the hair of domesticated animals generally follows the same hair cycle as that of humans, there are some differences between human hair and animal hair. For example, human hair grows continuously as individual strands, whereas dog hair grows in bundles within each hair follicle, growing and falling out periodically. This cycle varies depending on the breed and is also affected by the season and temperature. These hair bundles consist of a primary outer coat, which can be coarse, and a soft secondary undercoat. Furthermore, the center of the hair follicle covers the hair, protecting it from heat, cold, and rain.

[0024] Pet animals can also suffer from various forms of alopecia. Alopecia can appear, for example, as circular patches of hair loss on parts of an animal's coat. Pet animals can develop alopecia due to parasitic infestations such as fleas, lice, and mosquitoes, improper diet, food allergies, and fungal or bacterial infections. Endocrine disorders such as hypothyroidism and Cushing's disease, or reactions to rabies and corticosteroid injections, can also cause alopecia. Other forms of alopecia known in dogs include seasonal flank alopecia, which appears on both sides of the abdomen in front of the hind legs during the cold winter months, or alopecia X.

[0025] Any variation of this term, such as “treatment” or “treating,” means addressing a condition with the aim of improving or stabilizing the outcome in the treated subject or addressing an underlying need. Therefore, treating includes managing the condition or dermatological needs of the treated subject. Treatment may include cosmetic or medical treatment. Treatment may include prophylactic and curative treatment. Prophylactic treatment may include primary and secondary prevention.

[0026] The compounds of formula I can be obtained by any technique known to those skilled in the art. The sphingoid base moiety can be obtained, for example, by a fermentation process as described in Schaffer, S. et al; Metabolic Engineering (2012) 14:412-426, or by a chemical process as described in, for example, WO 00 / 68238 or He, Linli et al; Journal of Organic Chemistry (2000) 65(22):7618-7626. The sphingoid base can then be acylated enzymatically by any known technique, such as the use of lipase, or chemically as described in, for example, WO 2013038985 or Drug. Del. Sci. Tech. 2014, 24, 689-693, Org. Process Res. Dev. 2019, 23, 452-461.

[0027] In a preferred embodiment, R of the compound of formula I 1 is -C 12 H 25 is.

[0028] In a preferred embodiment, R of the compound of formula I 2 is an unsubstituted acyl group. More preferably, R of the compound of formula I 2 is a saturated fatty acyl group or a fatty acyl group having one or more double bonds, particularly hexadecanoyl, 2-hydroxyhexadecanoyl, octadecanoyl, 2-hydroxyoctadecanoyl, eicosanoyl, 2-hydroxyicosanoyl, lignoceroyl, 2-hydroxytetracosanoyl and 30-(linoleoyloxy)-triacontanoyl. Even more preferably, R of the compound of formula I 2 is an unsubstituted acyl group having 18 to 26 carbon atoms.

[0029] In some preferred embodiments, R of the compound of formula I 1 is -C 12 H 25 is, and R 2It is octadecanoil.

[0030] In a preferred embodiment, X in the compound of formula I is hydrogen.

[0031] In the context of the present invention, it has been found that applying ceramide NG, also referred to herein as Cer NG or CNG, to keratinocytes results in upregulation of proteins related to the hair cycle.

[0032] The ceramides used herein 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 Masukawa et al., Journal of Lipid Research, 2008, 49, 1466-1476. For each species, the number of carbon atoms and the number of unsaturated bonds (if present) can be expressed in parentheses after the letters N, A, E, and O. Unless otherwise specified, the carbon chain length of the sphingoid base portion of the ceramides referred to herein is typically C 18 Unless otherwise specified, the carbon chain length of the acyl moiety of ceramides referred to herein is, for example, C 16 , C 17 , C 18 , C 19 , C 20 , C 22 , C 24 , C 26 , C 28 , C 30 , C 32 or C 34 It is possible.

[0033] Therefore, Cer NG refers to a ceramide containing a non-hydroxy acid as the acyl moiety and dihydrosphingosine as the sphingoid base moiety. Typically, the length of both carbon chains is C 18Ceramide NG is sometimes called ceramide NdS, and can be used interchangeably as described herein. Dihydrosphingosine is sometimes called sphinganine, and can be used interchangeably as described herein.

[0034] Generally, the compositions of the present invention contain 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 0.05% to about 0.2% (weight / weight), or 0.01% to about 1% (weight / weight) of the compound of formula I. For example, the topical composition of the present invention contains approximately 0.0001% to approximately 0.00025% (weight / weight) of the compound of formula I, approximately 0.0002% to approximately 0.0004% (weight / weight) of the compound of formula I, approximately 0.0003% to approximately 0.0005% (weight / weight) of the compound of formula I, approximately 0.0004% to approximately 0.0006% (weight / weight) of the compound of formula I, approximately 0.0005% to approximately 0.0008% (weight / weight) of the compound of formula I, and approximately 0.0007% to approximately 0.001% (weight / weight) of the compound of formula I. It may contain approximately 0.001% to approximately 0.005% (weight / weight) of the compound of formula I, approximately 0.003% to approximately 0.008% (weight / weight) of the compound of formula I, approximately 0.005% to approximately 0.01% (weight / weight) of the compound of formula I, approximately 0.008% to approximately 0.05% (weight / weight) of the compound of formula I, approximately 0.05% to approximately 0.08% (weight / weight) of the compound of formula I, approximately 0.06% to approximately 0.1% (weight / weight) of the compound of formula I, approximately 0.08% to approximately 0.1% (weight / weight) of the compound of formula I, etc.

[0035] In some embodiments, the topical composition of the present invention contains the compound of formula I in an amount of about 0.01% to 5% (weight / weight), or in an amount of about 0.02% (weight / weight) to 1% (weight / weight). Examples include 0.05% (weight / weight), 0.1% (weight / weight), or 0.2% (weight / weight) of the compound of formula I.

[0036] The terms “approximately” or “about” are defined, as understood by those skilled in the art, as close as possible to the value or range that follows them, and include a deviation of up to 10 percent from the value or range that follows.

[0037] In some embodiments, the composition may contain two or more compounds of formula I, which are collectively referred to herein as blends of compounds of formula I. In such blend compositions, each compound of formula I may be present in equal or different amounts. The ranges or amounts listed above may relate to the total content of the blend in the composition, or to the amount of one compound in the blend in the composition.

[0038] The composition according to the present invention may also include additional components typically found in hair care formulations, which may be selected considering their functions. Examples include surfactants, such as cationic surfactants, anionic surfactants, amphoteric surfactants, zwitterionic surfactants, and ionic surfactants; solvents such as water or alcohol; solubilizers such as ethanol, ethylene glycol, propylene glycol, etc.; humectants such as glycerin, trehalose, sorbitol, maltitol, dipropylene glycol, 1,3-butylene glycol, sodium hyaluronate, etc.; antioxidants such as tocopherol, BHT, etc.; benzophenone derivatives, para-aminobenzoic acid derivatives, etc. Examples of UV absorbers include toxicinic acid derivatives, UV scattering agents such as inorganic compounds like zinc oxide, zirconium oxide, and titanium dioxide, thickeners, metal chelating agents such as edetates, disinfectants, preservatives such as phenoxyethanol, formaldehyde solution, parabens, pentanediol, or sorbic acid, emollients, vitamins, anti-inflammatory agents, as well as anti-dandruff agents such as zinc pyrithione, selenium sulfide, salicylic acid, coal tar, sulfur, ketoconazole, and crimbazole, and pH adjusters such as citric acid, lactic acid, malic acid, and glycolic acid.

[0039] The compositions of the present invention may be formulated as leave-on compositions or rinse-off compositions, but preferably as rinse-off compositions. A "leave-on composition" typically refers to a composition that is applied after shampooing and remains on keratinous tissue such as hair and scalp. These leave-on compositions are distinguished from rinse-off compositions that are applied to the hair or scalp / skin before or after shampooing and are subsequently removed (typically after a few minutes) by washing, rinsing, wiping, or the like. Non-limiting examples of rinse-off formulations include shampoos, conditioners, and pre- or post-shampoo serums. Non-limiting examples of leave-on formulations include hair tonics, foams, or creams.

[0040] The formulation can be any type of preparation, such as a solid, semi-solid, liquid, or emulsion. It may also vary depending on the subject to which it is intended. For example, liquid shampoos are common for humans or dogs, while horses or cats may be treated with semi-solid or emulsion formulations, such as creams.

[0041] In particular, when the cosmetic composition according to the present invention is a hair cleansing composition such as a shampoo, it additionally contains surfactants such as anionic surfactants, nonionic surfactants, cationic surfactants, or amphoteric surfactants.

[0042] Anionic surfactants include C8-C24 alkyl sulfates, C8-C24 alkyl ether sulfates, CBC-4 alkylbenzene sulfonates, C8-C-4 alkyl phosphates, C8-C-4 polyoxyalkylene alkyl ether phosphates, C8-C24 alkyl sulfosuccinates, C8-C24 polyoxyalkylene alkyl ether sulfosuccinates, Cs-Cz-4 acylalanine, C8-C-4 acyl N-methyl-[beta]-alanine, C-C74 acyl glutamate, C8-C-4 acyl isethionate, C8-C-4 acyl sarcosinate, C8-C-4 taurate, and C8-C-4 acylmethyl taurate (acyl me10 thyl It may contain taurinate, [alpha]-sulfo fatty acid ester salts, ether carbonates, polyoxyalkylene fatty acid monoethanolamide sulfonates, or C8-C24 long-chain carboxylates.

[0043] Nonionic surfactants may include alkanolamides, glycerin fatty acid esters, polyoxy-15 alkylene alkyl ethers, polyoxyalkylene glycol ethers, polyoxyalkylene sorbitan fatty acid esters, sorbitan fatty acid esters, polyoxyalkylene sorbitan fatty acid esters, sorbitan fatty acid esters, polyoxyalkylene glycerin fatty acid esters, polyoxyalkylene fatty acid esters, polyoxyalkylene alkylphenyl ethers, tetrapolyoxyalkylene ethylenediamine condensates, sucrose fatty acid esters, polyoxyalkylene fatty acid amides, polyoxy-20 alkylene glycol fatty acid esters, polyoxyalkylene castor oil derivatives, polyoxyalkylene hydrogenated castor oil derivatives, or alkyl polyglycosides and polyglycerin fatty acid esters.

[0044] The amphoteric surfactant may include C8-C24 alkylamidopropyl betaine, C8-C24 alkyl carboxybetaine, C8-C4 alkyl sulfobetaine, C8-C4 alkyl sulfobetaine, C8-C4 alkyl hydroxysulfobetaine, C8-C24 alkylamidopropyl hydroxysulfobetaine, C8-C24 alkyl hydroxyphosphobetaine, C8-C4 alkylaminocarboxylate, C8-C24 alkylimidazolium betaine, C8-C74 alkylamine oxide, C8-C24 alkyl phosphate, or an ester containing a tertiary or quaternary nitrogen group, where C,-C, means having any number of carbon atoms from 8 to 24 and being linear or branched.

[0045] Cationic surfactants may include alkyltrimethylammonium salts, dialkyldimethylammonium salts, alkylpyridium salts, alkyldimethylbenzylammonium salts, benzethonium chloride, or benzalkonium chloride.

[0046] In particular, if the cosmetic composition according to the present invention is a hair conditioning composition such as a hair conditioner, it may additionally contain further conditioning agents.

[0047] The conditioning effect can be enhanced, for example, by adding silicone (methylpolysiloxane, 10-methylphenylsiloxane, highly polymerized methylpolysiloxane, cyclic polysiloxane, polyether-modified silicone, amino-modified silicone, etc.) to the hair treatment composition or skincare composition of the present invention. The amount of silicone added is preferably 5% by weight or less of the total weight of the composition.

[0048] In some embodiments, the composition may advantageously include one or more further active ingredients for promoting hair growth or preventing hair loss. Examples include various vitamins, particularly B vitamins, such as vitamin B7 or biotin; amino acids, particularly L-valine or L-arginine, and amino acid derivatives, such as creatine or L-carnitine (which, among other things, stimulate cellular metabolism); caffeine, which stimulates blood flow through the scalp and indirectly promotes hair growth; or plant extracts.

[0049] In some embodiments, the composition may contain one or more additional active ingredients for improving hair and scalp care and / or strengthening damaged hair.

[0050] The compositions according to the present invention preferably include at least one cosmetically acceptable carrier. The expression "cosmetically acceptable" means a composition or active substance that is non-toxic, physiologically acceptable, and optionally has a desirable appearance, scent, feel, and / or taste. Preferably, the carrier component is selected from water, water-miscible organic solvents, preferably C2-C4 alkanols, particularly ethanol, oils, fats, waxes, esters of C6-C30 monocarboxylic acids with monohydric, dihydric, or trihydric alcohols, saturated acyclic and cyclic hydrocarbons, fatty acids, fatty alcohols, propellant gases for spraying, and mixtures thereof.

[0051] The cosmetic composition of the present invention contains substances commonly known to be included in cosmetic compositions for their multifunctional properties relating to cosmetic and / or formulation effects, such as amino acids (arginine, glutamic acid, etc.), higher alcohols, higher fatty acids (lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, isostearic acid, oleic acid, undecylenic acid, tall oil fatty acid, coconut oil fatty acid, palm oil fatty acid, palm kernel oil fatty acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, etc.), and their esters (e.g., hexyl laurate, isopropyl myristate, octyldodecyl myristate, myristate myristate, 2-hexyldecyl myristate, glycerin trimyristate, isopropyl palmitate, 2-heptylundecyl palmitate, 2-hexyldecyl palmitate, butyl stearate, isocetyl stearate, 12-hydroxys Cholesteryl therate, cetostearyl alcohol, cetyl octanoate, hexyldecyldimethyl octanoate, isocetyl isostearate, trimethylolpropane triisostearate, decyl oleate, oleic acid oil, cetyl lactate, myristyl lactate, ethyl acetate, butyl acetate / amyl acetate, lanolin acetate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, di-2-ethylhexyl acid (ethylhexyl(acid) Ethylene glycol, trimethylolpropane tri-2-ethylhexylate, glycerin tri-2-ethylhexylate, pentaerythritol tetra-2-ethylhexylate, cetyl-2-ethylhexanoate, diisobutyl adipate, 2-heptyl undecyl adipate, 2-hexyldecyl adipate, dipentaerythritol fatty acid ester, neopentyl glycol dicaprylate, diisostearyl malate, glycerin di-2-heptyl undecanoate, tri-2- The following may further be included: butyl undecanoate glyceride, castor oil fatty acid methyl ester, acetoglyceride, N-lauryl-L-glutamic acid-2-octyldodecyl ester, di-2-ethylhexyl sebacate, diisopropyl sebacate, 2-ethylhexyl succinate, triethyl citrate, ethyl laurate, mink oil fatty acid ester, etc., as well as waxes (e.g., carnauba wax, candelilla wax, etc.), hydrocarbon oils (e.g., liquid paraffin, squalane, etc.), or essential oils. Further examples of suitable additional ingredients can be found in other references cited herein, as well as in the International Cosmetic Ingredient Dictionary and Handbook.

[0052] Cosmetic products often contain added perfumes and fragrances, making the scent or fragrance of the applied cosmetic formulation important. Perfume oils that may be mentioned are mixtures of natural and synthetic fragrances. Natural fragrances are extracts from flowers (lily, lavender, rose, jasmine, neroli, ylang-ylang), stems and leaves (geranium, patchouli, petitgrain), fruits (anise, coriander, caraway, juniper), fruit peels (bergamot, lemon, orange), roots (mace, angelica, celery, cardamom, costus, iris, calamus), woods (pine, sandalwood, guaiacwood, cedarwood, rosewood), herbs and grasses (tarragon, lemongrass, sage, thyme), needles and branches (spruce, fir, pine, dwarf pine), resins and balsams (galbanum, elemi, benzoin, myrrh, olibanum, opoponax). For example, animal-derived ingredients such as civet cat and castoreum are also suitable. Typical synthetic fragrance compounds are ester, ether, aldehyde, ketone, alcohol, and hydrocarbon type products. Examples of ester-type fragrance compounds include benzyl acetate, phenoxyethyl isobutyrate, p-tert-butylcyclohexyl acetate, linalyl acetate, dimethylbenzylcarbyl acetate, phenylethyl acetate, linalyl benzoate, benzyl formate, ethylmethylphenylglycinate, allylcyclohexylpropionate, styrarylpropionate, and benzyl salicylate. Examples of ethers include benzyl ethyl ether; examples of aldehydes include linear alcanals having 8 to 18 carbon atoms, citral, citronellal, citronellyloxyacetaldehyde, cyclamenaldehyde, hydroxycitronellal, lilial, and burgeonal; examples of ketones include ionone, isomethylionone, and methylcedyl ketone; examples of alcohols include anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol, and terpineol; and examples of hydrocarbons include mainly terpenes and balsams. However, it is preferable to mix different fragrances to create a pleasant aroma.Essential oils with relatively low volatility are mainly used as aromatic components, but are also suitable as perfume oils. Examples include sage oil, chamomile oil, clove oil, melissa oil, mint oil, cinnamon leaf oil, linden blossom oil, juniper berry oil, vetiver oil, olibanum oil, galbanum oil, labranum oil, and lavandin oil. Preferably, bergamot oil, dihydromyrcenoyl, lilial, liral, citronellol, phenylethyl alcohol, hexyl cinnamaldehyde, geraniol, benzylacetone, cyclamenaldehyde, linalool, boisambrene forte, ambroxan, indole, hedione, sandelice, lemon oil, mandarin oil, orange oil, allyl amyl glycolate, cyclobeltal, lavandin oil, clary sage oil, -damascone, bourbon geranium oil, cyclohexyl salicylate, Vertofix Coeur, Iso-E-Super, Fixolide NP, evernyl, iraldine gamma, phenylacetic acid, geranyl acetate, benzyl acetate, rose oxide, romylate, ilotyl, and floramat are used individually or in mixtures. Suitable fragrances include, for example, peppermint oil, spearmint oil, anise oil, star anise oil, caraway oil, eucalyptus oil, fennel oil, lemon oil, wintergreen oil, clove oil, and menthol.

[0053] In the context of the present invention, it has been found that application of Cer NG to keratinocytes leads to the upregulation of biomarkers related to the hair cycle. More precisely, application of Cer NG results in the upregulation of ceramide synthase 4, keratin type I cytoskeleton 17 (also referred herein as keratin 17), and NAD-dependent protein deacetylase sirtuin-2 (also referred herein as sirtuin-2).

[0054] In some embodiments, Cer NS is used to upregulate the NAD-dependent protein deacetylase sirtuin-2.

[0055] In some embodiments, Cer NG is used to upregulate ceramide synthase 4.

[0056] In some embodiments, CerNS is used to upregulate the keratin type I cytoskeleton 17.

[0057] Hair follows a specific growth cycle, within which the anagenetic phase represents a period of active growth; the longer the anagenetic phase, the longer and thicker the hair. Shorter cycles result in thinner hair, as seen in aging and under stress. When immature hair enters the terogenous phase, it can lead to hair loss. Hair thinning and loss are generally thought to be due to depletion, dysfunction, and prolonged dormancy of the human hair follicle stem cell reservoir. Numerous transcription factors, including Sox9, Tbx1, Lhx2, TCF3 / 4, Foxc1, and Nfatc1, help maintain quiescent and undifferentiated human hair follicle stem cells. NFATc1 is essential for the quiescence of human hair follicle stem cells. During aging, excessive accumulation of NFATc1 in the nucleus prolongs the dormancy period of human hair follicle stem cells. Sirtuin-2 deacetylates Nfatc1, leading to its degradation, thereby activating human hair follicle stem cells.

[0058] Keratin 17 induces TNF-alpha, which is known to activate the hair cycle.

[0059] Ceramide synthase 4 plays a crucial role in maintaining epidermal stem cell homeostasis and regulating the hair cycle by regulating bone morphogenetic protein (BMP) and WNT signaling.

[0060] Therefore, without being bound by theory, it is thought that Cer NG can promote hair growth by activating the hair cycle.

[0061] The compositions of the present invention are generally intended for use in mammalian subjects. In particular, the subjects are humans. In preferred embodiments, the human subjects are adult subjects, for example, humans aged 20 years or older, especially 30 years or older, for example 40 years or older or 50 years or older.

[0062] In some embodiments, the subject may be exposed to stress. Exposure may occur before use of the composition of the present invention, during use of the composition of the present invention, and / or in the future as planned in connection with the use of the composition of the present invention. Those skilled in the art will understand that the term exposure typically relates to long-term exposure, such as one year or several years.

[0063] Stress can be psychological stress or environmental stress.

[0064] Environmental stressors include solar radiation, especially ultraviolet (UV) radiation, polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), ozone, nitrogen oxides and sulfur oxides, particulate matter (PM2.5), blue light, or cigarette smoke. Particulate matter (PM) is classified by particle size into PM10 (coarse particles), PM2.5 (fine particles), and PM0.1 (ultrafine particles), with diameters of less than 10 μm, less than 2.5 μm, and less than 0.1 μm, respectively.

[0065] It may be advantageous to administer the composition of the present invention to a subject for at least 7 days, for example, at least 14 days, or at least 21 days. For example, the composition may be administered for at least 28 days. In practice, there is no time limit on the duration of administration of the cosmetic composition of the present invention.

[0066] The composition of the present invention may be administered once a day, or multiple times a day, such as two or three times a day. Typically, the composition is administered for several consecutive days.

[0067] The various aspects of the present invention described above are illustrated in the following selected (but not limited to) embodiments.

[0068] (1) Formula I for promoting hair growth or preventing hair loss on the skin of the subject: [ka] (In the formula, R 1 This is an alkyl chain having 10 to 20 carbon atoms. R 2 It is an acyl having 16 to 34 carbon atoms. Use of a composition containing a compound (where X is hydrogen, a glucosyl moiety, or a lactosyl moiety).

[0069] (2) R of compound I 1 However, -C 13 H 27 and / or R 2 However, the use described in Embodiment 1 is an acyl having 18 to 26 carbon atoms.

[0070] (3) The use according to Embodiment 1 or 2, wherein the compound of formula I is present in an amount of 0.0001% to 10% (weight / weight), for example, 0.005% to 5% (weight / weight), or 0.05% to 0.2% (weight / weight).

[0071] (4) Use according to any one of Embodiments 1 to 3, comprising an increase in the expression level of one or more biomarkers related to the hair cycle of the subject, preferably ceramide synthase 4, keratin type I cytoskeleton 17 and / or NAD-dependent protein deacetylase sirtuin-2.

[0072] (5) Use according to any one of Embodiments 1 to 4, wherein promoting hair growth or preventing hair loss on the subject's skin includes activating the subject's hair cycle, extending the anagenetic growth phase of the hair cycle, and / or activating the subject's hair follicle stem cells.

[0073] (6) The use according to any one of Embodiments 1 to 5, wherein the composition further comprises ceramide, for example ceramide NP or ceramide NS, glycosylated ceramide, for example lactosylceramide or glucosylceramide, sphingolipid, for example sphinganine, phytosphingosine or sphingosine, or a combination thereof.

[0074] (7) The use according to any one of Embodiments 1 to 6, wherein the composition comprises further active substances for promoting hair growth or preventing hair loss, such as ginkgo biloba, aloe vera, asarum sieboldii, proanthocyanidins, arginine, castor oil, minoxidil, taurine, caffeine, carnitine, azelaic acid, hydrolyzed keratin, biotin, creatine, niacin, panthenol, ximenylic acid, argunolic acid, vitamin B6, zinc, copper, magnesium, ginseng, or a combination thereof.

[0075] (8) The use according to any one of Embodiments 1 to 7, wherein the subject is a human or a domesticated animal such as a dog, cat or horse.

[0076] (9) The use according to any one of Embodiments 1 to 8, wherein the skin is the scalp.

[0077] (10) The use according to any one of Embodiments 1 to 9, wherein the subject is an elderly subject.

[0078] (11) The use according to any one of Embodiments 1 to 10, wherein the subject is exposed to or has been exposed to stress such as psychological stress or environmental stress.

[0079] (12) The subject is as follows: Hormonal imbalances that cause hair loss, Diseases that cause hair loss Treatments that cause hair loss, Genetic premature hair loss, The use described in any one of embodiments 1 to 11, having one or more of the above.

[0080] (13) The use according to Embodiment 12, wherein the subject is human and the hormonal imbalance causing hair loss is due to menopause or postpartum.

[0081] (14) The use according to Embodiment 12, which includes alopecia, wherein the disease causing hair loss includes lichen planus pilaris, discoid lupus erythematosus, and alopecia areata.

[0082] (15) The use according to Embodiment 12, wherein the treatment causing hair loss includes radiotherapy and / or chemotherapy.

[0083] (16) The use according to any one of Embodiments 1 to 15, wherein the composition is administered to a subject for at least 2 days, particularly at least 7 days, or at least 14 days, for example, 28 days.

[0084] (17) The use according to any one of Embodiments 1 to 16, wherein the composition is a cosmetic composition.

[0085] (18) The use according to any one of Embodiments 1 to 17, wherein the composition is formulated as a shampoo, tonic, hair conditioner, pre-shampoo or post-shampoo serum, foam, or cream.

[0086] (19) A method for promoting hair growth or preventing hair loss on the skin of a subject, wherein formula I: [ka] (In the formula, R 1 This is an alkyl chain having 10 to 20 carbon atoms. R 2 It is an acyl having 16 to 34 carbon atoms. A method comprising administering to the skin a composition comprising a compound (where X is hydrogen, a glucosyl moiety, or a lactosyl moiety), or a composition according to any of Embodiments 1 to 17.

[0087] (20) A method for activating the hair cycle on the skin of a subject, wherein formula I: [ka] (In the formula, R1 This is an alkyl chain having 10 to 20 carbon atoms. R 2 It is an acyl having 16 to 34 carbon atoms. A composition comprising a compound (where X is hydrogen, a glucosyl moiety, or a lactosyl moiety), A method comprising administering to the skin any of the compositions described in Embodiments 1 to 17. [Examples]

[0088] The following examples are for illustrative purposes only. The scope of the present invention is not limited to the embodiments described in the examples.

[0089] Example 1: Characterization of the effects of ceramide NG as an active ingredient in cosmetics Materials and Methods: Reconstructed human epidermis (RHE) cell cultures were used, and this system mimics the in vivo 3D structure of epidermal tissue, as well as the conditions and processes that occur in normal epidermis. RHE cells were cultured using manufacturer-provided media until analysis. RHE cells were kept viable for 24 hours, and then topically treated with each ceramide in a base emulsion for 24 hours. Three RHE cells were treated with the base emulsion alone, and three more were left untreated as a control batch (Ctrl). RHE cells were incubated under conventional cell culture conditions (37°C, 5% CO2).

[0090] 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. The proteins were mixed with Laemmli buffer and heated at 37°C for 30 minutes. Protein concentrations were determined by the BCA method and standardized for all samples. Samples were separated by SDS-PAGE and digested overnight with trypsin. The resulting peptides were acidified and separated. Mass spectra were searched using Proteome Discoverer (version 2.5). The obtained MS / MS data were searched against the Homo sapiens proteome UP000005640 (20371 reviewed entries). Results were filtered based on more than two unique peptides and the global peptide score. To confirm overall sample quality, analysis was performed using Proteome Discoverer 2.5.

[0091] Bioinformatics and Statistical Analysis: Proteomic analysis yielded an average total of 34,961 high-quality peptides, corresponding to an average of 2,422 identifiable and quantifiable RHE proteins across conditions. Proteins with a p-value of ≤0.05 at at least one of the concentrations tested for lipids were considered significant and used for pairwise comparisons. Relevant proteins were classified by biological process and associated pathway using public gene ontology (GO) databases provided by the Gene Ontology Consortium and Reactome. Interactome analysis was performed using a combination of Cytoscape and STRING.

[0092] Example 2: Effect of ceramide NG on hair growth in human scalp using skin explants Cer NG was applied topically to 4mm x 6mm scalp skin samples at three different concentrations. One vehicle was used as a control.

[0093] The parameters evaluated include hair shaft elongation using bright-field microscopy, skin morphology and integrity using H&E staining, proliferation and apoptosis of hair matrix keratinocytes (Ki-67 / Tunel immunostaining), hair cycle staging using Ki-67 / Tunel immunostaining and Masson Fontana histochemistry, and the number and proliferation of bulge stem cells by K15 / Ki-67 immunostaining.

[0094] This disclosure should not be considered in any way limited to the embodiments described herein, and those skilled in the art will foresee many of the possible modifications.

[0095] The embodiments described above can be combined with each other.

[0096] Specific embodiments of the present disclosure are further defined in the attached claims.

Claims

1. Formula I for promoting hair growth or preventing hair loss on the skin of a subject: 【Chemistry 1】 (In the formula, R １ This is an alkyl chain having 10 to 20 carbon atoms. R ２ It is an acyl having 16 to 34 carbon atoms. Use of a composition containing a compound (where X is hydrogen, a glucosyl moiety, or a lactosyl moiety).

2. R of compound I １ However, -C １３ H ２７ and / or R ２ The use according to claim 1, wherein the acyl group has 18 to 26 carbon atoms.

3. The use according to claim 1 or 2, wherein the compound of formula I is present in an amount of 0.0001% to 10% (weight / weight), for example, 0.005% to 5% (weight / weight), or 0.05% to 0.2% (weight / weight).

4. The use according to any one of claims 1 to 3, comprising an increase in the expression level of one or more biomarkers related to the hair cycle of the subject, preferably ceramide synthase 4, keratin type I cytoskeleton 17 and / or NAD-dependent protein deacetylase sirtuin-2.

5. The use according to any one of claims 1 to 4, wherein promoting hair growth or preventing hair loss on the skin of the subject includes activating the hair cycle of the subject, extending the anagenetic growth phase of the hair cycle, and / or activating the hair follicle stem cells of the subject.

6. The use according to any one of claims 1 to 5, wherein the composition further comprises a ceramide, for example, ceramide NP or ceramide NS; a glycosylated ceramide, for example, lactosylceramide or glucosylceramide; a sphingolipid, for example, sphinganine, phytosphingosine or sphingosine; or a combination thereof.

7. The use according to any one of claims 1 to 6, wherein the composition comprises further active substances for promoting hair growth or preventing hair loss, such as ginkgo biloba, aloe vera, asarum sieboldii, proanthocyanidins, arginine, castor oil, minoxidil, taurine, caffeine, carnitine, azelaic acid, hydrolyzed keratin, biotin, creatine, niacin, panthenol, ximenylic acid, argunolic acid, vitamin B6, zinc, copper, magnesium, ginseng, or a combination thereof.

8. The use according to any one of claims 1 to 7, wherein the subject is a human or a domesticated animal such as a dog, cat, or horse.

9. The use according to any one of claims 1 to 8, wherein the skin is the scalp.

10. The use according to any one of claims 1 to 9, wherein the subject is an elderly subject.

11. The use according to any one of claims 1 to 10, wherein the subject has been exposed to or has been exposed to stress such as mental stress, psychological stress, or environmental stress.

12. The aforementioned subject is as follows: Hormonal imbalances that cause hair loss, Diseases that cause hair loss Treatments that cause hair loss, Genetic premature hair loss, The use according to any one of claims 1 to 11, having one or more of the above.

13. The use according to claim 12, wherein the subject is human and the hormonal imbalance causing the hair loss is due to menopause or postpartum period.

14. The use according to claim 12, comprising alopecia, wherein the disease causing the hair loss includes lichen planus pilaris, discoid lupus erythematosus, and alopecia areata.

15. The use according to claim 12, wherein the treatment that causes the hair loss includes radiotherapy and / or chemotherapy.

16. The use according to any one of claims 1 to 15, wherein the composition is administered to a subject for at least two days, particularly at least seven days, or at least fourteen days, for example, 28 days.

17. The use according to any one of claims 1 to 16, wherein the composition is a cosmetic composition.

18. The use according to any one of claims 1 to 17, wherein the composition is formulated as a shampoo, tonic, hair conditioner, serum, foam, or cream for use before or after shampooing.

19. A method for promoting hair growth or preventing hair loss on the skin of a subject, comprising formula I: 【Chemistry 2】 (In the formula, R １ This is an alkyl chain having 10 to 20 carbon atoms. R ２ It is an acyl having 16 to 34 carbon atoms. A method comprising administering to the skin a composition comprising a compound in which X is hydrogen, a glucosyl moiety, or a lactosyl moiety, or the composition according to any one of claims 1 to 17.

20. A method for activating the hair cycle on the skin of a subject, wherein formula I: 【Transformation 3】 (In the formula, R １ is an alkyl chain having 10 to 20 carbon atoms, R ２ It is an acyl having 16 to 34 carbon atoms. A method comprising administering to the skin a composition comprising a compound in which X is hydrogen, a glucosyl moiety, or a lactosyl moiety, or the composition according to any one of claims 1 to 17.

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