New use of cosmetic composition comprising 10-hydroxystearic acid

Abstract

The present invention relates to a novel use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, ester or amide thereof for topical application to the skin to modulate lipid balance in sebaceous gland cells, modulate sebaceous gland cell activity and / or inhibit a lipid production process induced by an inducer.

Description

Technical Field

[0001] The present invention relates to a novel use of a cosmetic composition comprising 10-hydroxystearic acid, its salts, esters or amides for topical application to the skin to regulate the lipid balance in sebaceous gland cells, to regulate sebaceous gland cell activity and / or to inhibit the lipogenic process induced by an inducing agent. Background Art

[0002] 10-Hydroxystearic acid (10-HSA), also known as 10-hydroxyoctadecanoic acid (10-HOA), is a saturated hydroxy fatty acid with 18 carbon atoms and a hydroxyl group at the 10-position. The hydroxyl group in the 10-HSA molecule gives the fatty acid special properties, which has high reactivity and is of great value in cosmetics, personal care, food, dietary supplements and pharmaceuticals. 10-HSA can be used as a surfactant, emulsifier, stabilizer, conditioner, antioxidant, etc. in cosmetics, and can also be used as an antibacterial, anti-inflammatory and anti-tumor active agent in the pharmaceutical industry.

[0003] It is known that 10-HSA can promote the production of collagen and reduce the production of melanin by activating peroxisome proliferator-activated receptors (PPAR). In PPAR-related skin care applications, 10-HSA has been reported to stimulate collagen I and III in cell culture models and improve facial age spots and enlarged pores in vivo (see, for example, "Bio-derived hydroxystearic acid ameliorates skin age spots and conspicuouspores", Schutz R. et al. Int J Cosmet Sci. 2019; 41: 240). However, the efficacy of 10-HSA as a cosmetic active ingredient for human skin has not yet been fully developed. Summary of the invention

[0004] The inventors surprisingly found that 10-hydroxystearic acid showed significant efficacy in sebum control even at relatively low concentrations. It has been found that 10-HSA is able to prevent 5α-reductase activity in vitro and prevent lipid accumulation in sebaceous gland cells, which are two major pathways that promote sebum accumulation and secretion.

[0005] Therefore, the present invention aims to provide a new use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof.

[0006] The inventors have now discovered that the object of the present invention can be achieved through the following aspects.

[0007] In one aspect, the present invention provides a non-therapeutic cosmetic treatment method for regulating lipid balance in sebocytes and / or for regulating sebocyte activity, comprising topically applying to the skin a cosmetic composition comprising 10-hydroxystearic acid, a salt, ester or amide thereof.

[0008] According to one embodiment, the amount of 10-hydroxystearic acid in the cosmetic composition used in the method of the present invention for regulating lipid balance in sebaceous gland cells and / or for regulating sebaceous gland cell activity may be from about 0.000625% to about 20% by weight, preferably from about 0.00125% to about 0.5% by weight relative to the total weight of the composition.

[0009] In another aspect, the present invention provides a non-therapeutic cosmetic treatment method for inhibiting the lipogenesis process induced by an inducer, which comprises topically applying to the skin a cosmetic composition comprising 10-hydroxystearic acid, a salt, ester or amide thereof before, simultaneously with or after the application of the inducer.

[0010] According to one embodiment, the inducing agent can be selected from linoleic acid (LA), dihydrotestosterone (5α-dihydrotestosterone, DHT), insulin, epidermal growth factor (EGF), palmitic acid (PA), insulin-like growth factor (IGF)-1, arachidonic acid and combinations thereof.

[0011] According to one embodiment, the amount of 10-hydroxystearic acid in the cosmetic composition used in the method of the present invention for inhibiting the lipogenesis process induced by an inducer may be from about 0.000625 wt % to about 20 wt %, preferably from about 0.005 wt % to about 0.1 wt % relative to the total weight of the composition.

[0012] In yet another aspect, the present invention provides non-therapeutic use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, ester or amide thereof for topical application to the skin to regulate lipid balance in sebocytes and / or to regulate sebocyte activity.

[0013] In yet another aspect, the present invention provides a non-therapeutic use of a cosmetic composition comprising 10-hydroxystearic acid, its salts, esters or amides for topical application to the skin to inhibit the lipogenic process induced by an inducer, such as linoleic acid, dihydrotestosterone, insulin, epidermal growth factor, palmitic acid, insulin-like growth factor-1, arachidonic acid or a combination thereof.

[0014] Other advantages of the present invention will become more clearly apparent upon reading the following detailed description and examples. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] In order to more completely understand the present invention, reference is now made to the following specific embodiments in conjunction with the accompanying drawings, in which:

[0016] Figure 1 is a histogram showing the inhibitory effect of 10-HSA on 5α-reductase activity at different concentrations;

[0017] Figure 2 is a histogram showing the lipid accumulation inhibitory effect of 10-HSA at different concentrations tested by Oil Red staining under basal conditions.

[0018] Figure 3 is a histogram showing the lipid accumulation inhibitory effect of 10-HSA at different concentrations tested by Nile red staining under basal conditions.

[0019] Figure 4 is a histogram showing the effect of 10-HSA in inhibiting LA-induced lipogenesis.

[0020] Figure 5 is a bar graph showing the effect of 10-HSA in inhibiting the LA+DHT-induced lipogenesis process. DETAILED DESCRIPTION

[0021] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which the invention belongs. When the definition of a term in this specification conflicts with the meaning commonly understood by those skilled in the art to which the invention belongs, the definition described herein shall apply.

[0022] Unless otherwise indicated, all numbers used in the specification and claims to express quantities of ingredients, properties such as molecular weight, reaction conditions, and the like are to be understood as being modified in all instances by the term "about." When the term "about" is used herein in conjunction with a numerical value, it is intended to include not only the numerical value but also values ​​within a tolerance or range of ±5% of the exact numerical value associated with the word "about."

[0023] In addition, the ranges described in the present invention and claims are intended to specifically include the entire range, not just the endpoints. For example, the range of 0-10 described is intended to disclose all integers between 0-10, such as 1, 2, 3, 4, and any subranges formed by any two values ​​therein, all fractions between 0-10, such as 1.5, 2.3, 4.57, 6.1113, and any subranges formed by any two values ​​therein, as well as the endpoints 0 and 10.

[0024] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values ​​set forth in the specific examples are intended to be reported precisely as measured. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0025] As used herein, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. Thus, even if language such as "at least one" is used in one place, it is not intended to imply that other uses of "a", "an", and "the" exclude plural referents unless the context clearly dictates otherwise.

[0026] As used herein, the term "comprising" should be interpreted as including all specifically mentioned features as well as optional, additional, unspecified features. As used herein, the use of the term "comprising" also discloses embodiments in which features other than the specifically mentioned features are not present (i.e., "consisting of ...").

[0027] As used herein, the term "and / or," when used in a list of two or more items, means that any one of the listed items may be used alone, or any combination of two or more of the listed items may be used. For example, if a composition is described as containing components A, B, and / or C, the composition may contain A alone; B alone; C alone; a combination of A and B; a combination of A and C; a combination of B and C; or a combination of A, B, and C.

[0028] As used herein, the term "cosmetic composition" refers to compositions for caring for human skin, see also the title "Kosmetika" in RomppLexikon Chemie, 10th edition 1997, Georg Thieme Verlag Stuttgart, New York.

[0029] Unless otherwise indicated, all parts or percentages in the present invention refer to parts or percentages by weight and are based on the total weight of the composition.

[0030] Sebum is the oily substance secreted by the sebaceous glands in most mammalian skins. The secretion mechanism is the holocrine mechanism (holocrine mechanism) by which sebum is deposited on the skin surface. The importance of sebum balance in skin tissue and cells for healthy skin physiological homeostasis is known: excessive sebum secretion, called hyperseborrhea, is the cause of oily skin and greasy hair. In some cases, hyperseborrhea may also promote the development of acne-prone skin. On the contrary, in some cases, some unsightly discomfort symptoms (such as dry skin) and important skin disorders (such as photoaging premature aging) can be attributed to the lack or deficiency of sebum on the skin surface. Therefore, cosmetic users expect that sebum secretion can keep balance. Accordingly, the technology for regulating sebaceous gland cell activity is most important for realizing such effect / benefit.

[0031] Thus, in one aspect, the present invention relates to a novel use of a cosmetic composition comprising 10-hydroxystearic acid, its salts, esters or amides for topical application to the skin to regulate the lipid balance in sebaceous gland cells, to regulate sebaceous gland cell activity and / or to inhibit the lipogenic process induced by an inducing agent.

[0032] 10-Hydroxystearic acid (CAS: 638-26-6) has the following formula:

[0033]

[0034] According to the present disclosure, both enantiomers may be used, with the preferred enantiomeric form being (R)-10-hydroxystearic acid.

[0035] 10-hydroxystearic acid can be formed by dehydration and oxidation with cupric chloride and hydrogen peroxide from 10-hydroxydecanoic acid. Alternatively, 10-hydroxystearic acid can be synthesized by recombinant cells that have been transformed to express the gene of this molecule. Fatty acid can also be produced by Corynebacterium glutamicum when grown on a culture medium containing glucose as the sole carbon source. As commercially available products of 10-hydroxystearic acid, the product sold by DSM Nutritional Products Ltd. under the trade name "BEAUACTIVE" can be mentioned.

[0036] The ester or amide is preferably an alkyl ester or alkyl amide, wherein the term "alkyl" includes straight chain and branched chain alkyl, i.e., "C 1-4 -alkyl" includes straight chain C 1-4 -alkyl (methyl, ethyl, n-propyl, n-butyl) and branched C 3-4 -alkyl (isopropyl, isobutyl, tert-butyl).

[0037] The salts may be formed from any cosmetically acceptable cation, meaning any metal cation and any organic cation that is non-toxic to the skin and / or does not cause an allergic reaction. Examples of such cations are ammonium and alkylammonium cations, alkali metal cations such as sodium and potassium, and alkaline earth metal cations such as calcium and magnesium.

[0038] More specifically, the present invention relates to a non-therapeutic cosmetic treatment method for regulating lipid balance in sebaceous gland cells and / or for regulating sebaceous gland cell activity, which comprises topically applying to the skin a cosmetic composition comprising 10-hydroxystearic acid, its salts, esters or amides. % , about 0.01 wt %, about 0.025 wt %, about 0.05 wt %, about 0.00625 wt %, about 0.0125 wt %, about 0.025 wt %, about 0.05 wt %, about 0.00625 wt %, about 0.01 wt %, about 0.0125 wt %, about 0.025 wt %, about 0.05 wt %, about 0.1 wt %, about 0.2 wt %, about 0.5 wt %, about 1 wt %, about 2 wt %, about 5 wt %, about 10 wt %, about 20 wt % of the total composition. By containing an appropriate amount of 10-hydroxystearic acid or a salt, ester or amide thereof, the composition of the present invention can achieve excellent effects of regulating lipid balance in sebaceous gland cells and / or regulating sebaceous gland cell activity.

[0039] In another embodiment, the present invention relates to a non-therapeutic cosmetic treatment method for inhibiting the lipogenic process induced by an inducer, comprising topically applying to the skin a cosmetic composition comprising 10-hydroxystearic acid, its salts, esters or amides, before, simultaneously or after the application of the inducer. The inducer may be selected from linoleic acid, dihydrotestosterone, insulin, epidermal growth factor, palmitic acid, insulin-like growth factor-1, arachidonic acid and combinations thereof. In such compositions according to the present invention, the amount of 10-hydroxystearic acid or its salt, ester or amide having the above definition and preferred items is suitably about 0.000625 wt % to about 20 wt % of the total composition, preferably about 0.005 wt % to about 0.1 wt %, more preferably about 0.05 wt % to about 0.1 wt %, such as about 0.005 wt %, about 0.01 wt %, about 0.0125 wt %, about 0.025 wt %, about 0.05 wt %, about 0.1 wt %, about 0.2 wt %, about 0.5 wt %, about 1 wt %, about 2 wt %, about 5 wt %, about 10 wt % and about 20 wt % of the total composition. By containing an appropriate amount of 10-hydroxystearic acid or its salt, ester or amide, the composition of the present invention can achieve an excellent effect of inhibiting the lipogenesis process induced by the inducing agent.

[0040] In yet another embodiment, the present invention relates to the non-therapeutic use of a cosmetic composition comprising 10-hydroxystearic acid, its salts, esters or amides for topical application to the skin to regulate lipid balance in sebocytes and / or to regulate sebocyte activity.

[0041] In yet another aspect, the present invention provides a non-therapeutic use of a cosmetic composition comprising 10-hydroxystearic acid, its salts, esters or amides for topical application to the skin to inhibit the lipogenic process induced by an inducer, such as linoleic acid, dihydrotestosterone, insulin, epidermal growth factor, palmitic acid, insulin-like growth factor-1, arachidonic acid or a combination thereof.

[0042] In another aspect, the present invention provides a non-therapeutic use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof for reducing sebum secretion of the skin.

[0043] In another aspect, the present invention provides non-therapeutic use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, ester or amide thereof for treating excess sebum in the skin.

[0044] In another aspect, the present invention provides a non-therapeutic use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof for inhibiting lipid accumulation in sebaceous gland cells of the skin.

[0045] In another aspect, the present invention provides a non-therapeutic use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof for improving lipid levels in sebaceous gland cells of the skin.

[0046] In another aspect, the present invention provides non-therapeutic use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof for treating seborrhea.

[0047] In another aspect, the present invention provides non-therapeutic use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof for treating acne (or acne-prone) skin.

[0048] In another aspect, the present invention provides use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof in the preparation of a cosmetic for regulating lipid balance in sebaceous gland cells and / or for regulating sebaceous gland cell activity.

[0049] In another aspect, the present invention provides a use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof in the preparation of a cosmetic for inhibiting the lipid production process induced by an inducer. The inducer may be selected from linoleic acid, dihydrotestosterone, insulin, epidermal growth factor, palmitic acid, insulin-like growth factor-1, arachidonic acid and a combination thereof.

[0050] In another aspect, the present invention provides use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof in the preparation of a cosmetic for reducing sebum secretion of the skin.

[0051] In another aspect, the present invention provides use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof in the preparation of a cosmetic for treating excess sebum of the skin.

[0052] In another aspect, the present invention provides use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof in the preparation of a cosmetic for inhibiting lipid accumulation in sebaceous gland cells of the skin.

[0053] In another aspect, the present invention provides use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof in the preparation of a cosmetic for improving lipid levels in sebaceous gland cells of the skin.

[0054] In another aspect, the present invention provides use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof in the preparation of a cosmetic for treating seborrhea.

[0055] In another aspect, the present invention provides use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof in the preparation of a cosmetic for treating acne (or acne-prone) skin.

[0056] Cosmetic composition

[0057] The cosmetic composition of the present invention may comprise 10-hydroxystearic acid, a salt, an ester or an amide thereof in an amount effective for regulating lipid balance in sebaceous gland cells, regulating sebaceous gland cell activity and / or inhibiting the lipogenesis process induced by an inducer.

[0058] Preferably, 10-HSA is used in the cosmetic composition in an amount effective to provide a 10-HSA concentration in the sebaceous gland cells of the skin above 0.01 μM, preferably above 1 μM, more preferably from 1 to 20 μM, in particular from 5 to 10 μM when the cosmetic composition is applied to the skin. The application is such that the desired effect is produced and depends on the individual and the desired effect. For example, the application is such that the amount of sebum on the skin surface is at a suitable level for healthy skin, for example, 100 to 200 μg / cm as shown by sebometer measurement. -2 .

[0059] As long as the objects of the present invention can be achieved, the composition may further comprise at least one cosmetically acceptable medium, such as an additive, excipient, diluent and / or additional active ingredients, in particular active ingredients for preventing or reducing excess sebum, acne, wrinkles, fine lines, dry skin, photoaging and inflammation.

[0060] The amount of additives, excipients, diluents and / or other active ingredients can be selected by those skilled in the art based on the end use of the cosmetic composition according to the present invention. As will be appreciated by those skilled in the art, the composition according to the present invention may contain a total of about 80-99.999375%, preferably about 90-99.95%, more preferably about 95-99.9% of one or more additional cosmetically acceptable media by weight of the composition.

[0061] Common cosmetic or pharmaceutical adjuvants and additives include, but are not limited to, preservatives / antioxidants, fatty substances / oils, water, organic solvents, silicones, thickeners, softeners, emulsifiers, sunscreens, defoamers, wetting agents, fragrances, surfactants, fillers, chelating agents, anionic polymers, cationic polymers, nonionic polymers or amphoteric polymers or mixtures thereof, propellants, acidulants or alkalizers, dyes, colorants, pigments or nanopigments, or any other ingredient commonly formulated into cosmetics or pharmaceuticals.

[0062] Additional amounts of antioxidants / preservatives are generally preferred. Based on the present invention, all known antioxidants which are usually formulated into cosmetics or medicaments can be used.Particularly preferred antioxidants are selected from amino acids (e.g. glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (e.g. imidazole acrylic acid) and their derivatives, peptides such as D,L-carnosine, D-carnosine, L-carnosine and their derivatives (e.g. anserine), carotenoids, carotenes (e.g. α-carotene, β-carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and its derivatives (e.g. dihydrolipoic acid), aurothioglucose, propylthiouracil and other sulfhydryl compounds (e.g. thioredoxine, glutathione, cysteine, cystine, cystamine and their glycosyl-, N-acetyl-, methyl-, ethyl-, propyl-, pentyl-, butyl- and lauryl-, palmitoyl- -, oleyl-, y-linoleyl-, cholesteryl- and glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and its derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and very low compatible doses (e.g. pmol to μmol / kg) of sulfoximine compounds (e.g. buthionine sulfoximine, homocysteine ​​sulfoximine, buthionine sulfoxide, pentyl-, hexyl-, heptyl- thionine sulfoximine), additional (metal) chelators (e.g. α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid (e.g. acid), gallic acid, gallic acid extract, bilirubin, biliverdin, EDTA, EGTA and its derivatives, BHA or BHT, unsaturated fatty acids and their derivatives (e.g., γ-linolenic acid, linoleic acid, oleic acid), folic acid and its derivatives, ubiquinone and ubiquinol and their derivatives, vitamin C and its derivatives (e.g., ascorbyl palmitate and ascorbyl tetraisopalmitate, magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl acetate, ascorbyl glucoside), tocopherol and its derivatives (e.g., vitamin E acetate), mixtures of natural or synthetic vitamin E, vitamin A and its derivatives (vitamin A palmitate and acetate) and coniferyl benzoate, rutinic acid acid) and its derivatives, α-glycosylrutin, ferulic acid, furfurylidenglucitol, carnosine, butylated hydroxytoluene, butylated hydroxyanisole, trihydroxybutyrophenone, urea and its derivatives, mannose and its derivatives, zinc and its derivatives (e.g. ZnO, ZnSO4), selenium and its derivatives (e.g. selenomethionine), stilbene and its derivatives (e.g. stilbene oxide, trans-stilbene oxide) and suitable derivatives (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of the active ingredients.One or more preservatives / antioxidants may be present in an amount of about 0.01 wt % to about 10 wt % of the total weight of the composition of the present invention. Preferably, one or more preservatives / antioxidants are present in an amount of about 0.1 wt % to about 1 wt %.

[0063] Usually, topical cosmetic compositions also contain surface active ingredients, such as emulsifiers, solubilizers, etc. Emulsifiers enable two or more immiscible components to be combined in a homogeneous manner. In addition, emulsifiers play a role in stabilizing compositions. Emulsifiers that can be used in the present invention to form O / W, W / O, O / W / O or W / O / W emulsions / microemulsions include sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, polyglycerol-3-diisostearate, polyglyceryl esters of oleic acid / isostearate, polyglyceryl-6 hexaricinoleate, polyglyceryl-4-oleate, polyglyceryl-4 oleate / PEG-8 propylene glycol cocoate, oleamide DEA, TEA myristate, TEA stearate, magnesium stearate, sodium stearate, potassium laurate, potassium ricinoleate, sodium cocoate, sodium tallowate, potassium ricinoleate, sodium oleate and mixtures thereof. Other suitable emulsifiers are phosphate esters and their salts, for example cetyl phosphate ( A) Cetyl alcohol phosphate diethanolamine salt Potassium cetyl phosphate ( K), sodium glycerol oleate phosphate, hydrogenated vegetable glycerol phosphate and mixtures thereof. In addition, one or more synthetic polymers can be used as emulsifiers. For example, PVP eicosene copolymer, acrylate / acrylic acid C 10-30 -alkyl esters crosspolymer, acrylates / steareth-20 methacrylate copolymer, PEG-22 / dodecyl glycol copolymer, PEG-45 / dodecyl glycol copolymer and mixtures thereof. Preferred emulsifiers are cetyl phosphate ( A) Cetyl alcohol phosphate diethanolamine salt Potassium cetyl phosphate ( K), PVP eicosene copolymer, acrylate / acrylic acid C 10-30 -alkyl ester crosspolymer, PEG-20 sorbitan isostearate, sorbitan isostearate and mixtures thereof. One or more emulsifiers are present in a total amount of about 0.01 wt % to about 20 wt % of the total weight of the cosmetic composition of the present invention. Preferably, about 0.1 wt % to about 10 wt % of the emulsifier is used.

[0064] Exemplary fatty substances that can be incorporated into the oil phase of the emulsion, microemulsion, oleogel, aqueous dispersion or lipid dispersion according to the invention are advantageously chosen from esters of saturated and / or unsaturated, linear or branched alkyl carboxylic acids having from 3 to 30 carbon atoms with saturated and / or unsaturated, linear and / or branched alcohols having from 3 to 30 carbon atoms, and esters of aromatic carboxylic acids with saturated and / or unsaturated, linear or branched alcohols having from 3 to 30 carbon atoms. Such esters may advantageously be chosen from octyl palmitate, octyl cocoate, octyl isostearate, octyldodecanol myristate, cetearyl isononanoate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2-octyldodecanol palmitate, stearyl heptanoate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate, tridecyl stearate, tridecyl trimellitate, and synthetic, semisynthetic or natural mixtures of such esters, for example jojoba oil.

[0065] Other fatty components suitable for use in the cosmetic composition of the present invention include polar oils, such as lecithin and fatty acid triglycerides, i.e. triglycerides of saturated and / or unsaturated, linear or branched carboxylic acids having 8 to 24 carbon atoms, preferably 12 to 18 carbon atoms, wherein the fatty acid triglycerides are preferably selected from synthetic, semi-synthetic or natural oils (e.g. coconut oil glycerides, olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, sweet almond oil, palm oil, coconut oil, castor oil, hydrogenated castor oil, wheat oil, glucose grape seed oil, macadamia nut oil, etc.); non-polar oils, such as linear and / or branched hydrocarbons and waxes, such as mineral oil, vaseline (petrolatum); paraffins, squalane and squalene, polyolefins, hydrogenated polyisobutene and isohexadecane, the advantageous polyolefin being polydecene; dialkyl ethers, such as dioctyl ether; linear or cyclic silicone oils, such as preferably cyclopolydimethylsiloxane (octamethylcyclotetrasiloxane; hexadecyldimethicone, hexamethylcyclotrisiloxane, polydimethylsiloxane, poly(methylphenylsiloxane) and mixtures thereof.

[0066] The oil phase of the cosmetic composition of the present invention may also comprise natural vegetable or animal waxes, such as beeswax, China wax, bumblebee wax and other insect waxes, as well as shea butter and cocoa butter.

[0067] Wetting agent can be incorporated into the cosmetic composition of the present invention to maintain the moisture of skin or to moisturize the skin. The wetting agent that stops the moisture from the skin evaporation by providing a protective layer is called an emollient. In addition, emollient provides softening or soothing effect on the skin surface, and is generally considered to be safe for topical use. Preferred emollients include mineral oil, lanolin, vaseline, capric / caprylic triglyceride, cholesterol, silicones such as dimethicone, cyclomethicone, almond oil, jojoba oil, avocado oil, castor oil, sesame oil, sunflower oil, coconut oil and grape seed oil, cocoa butter, olive oil, aloe extract, fatty acids such as oleic acid and stearic acid, fatty alcohols such as cetyl alcohol and hexadecanol (ENJAY), diisopropyl adipate, hydroxybenzoic acid esters, the benzoic acid esters of C9-15-alcohol, isononyl isononanoate, ethers such as polyoxypropylene butyl ether and polyoxypropylene cetyl ether and benzoic acid C12-15-alkyl esters, and mixtures thereof. The most preferred emollients are hydroxybenzoates, aloe vera, C12-15-alkyl benzoates, and mixtures thereof. The emollient is present in an amount of about 1 wt % to about 20 wt % of the total weight of the composition. The preferred emollient amount is about 2 wt % to about 15 wt %, most preferably about 4 wt % to about 10 wt %.

[0068] Wetting agents that bind water and thus retain it on the surface of the skin are called humectants. Suitable humectants such as glycerol, polypropylene glycol, 1,2-pentanediol, polyethylene glycol, lactic acid, pyrrolidone carboxylic acid, urea, phospholipids, collagen, elastin, ceramide, lecithin, sorbitol, PEG-4, and mixtures thereof may be incorporated into the cosmetic composition of the present invention. Other suitable wetting agents are polymeric wetting agents of the polysaccharide family that are water-soluble and / or swellable and / or gelatinized with water, such as hyaluronic acid, chitosan and / or fucose-rich polysaccharides (which are, for example, polysaccharides such as SOLABIA S and polysaccharides such as PEG-4 ... 1000 (CAS-Nr. 178463-23-5)). One or more humectants are optionally present in the composition of the present invention at about 0.5% to about 8% by weight, preferably about 1% to about 5% by weight.

[0069] The aqueous phase of the preferred topical cosmetic compositions of the present invention may contain customary cosmetic additives, such as alcohols, especially lower alcohols, preferably ethanol and / or isopropanol, lower diols or polyols and their ethers, preferably propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl- or monobutyl ether, propylene glycol monomethyl- or monoethyl- or monobutyl ether, diethylene glycol monomethyl- or monoethyl ether and the like, polymers, foam stabilizers; electrolytes and in particular one or more thickeners. Thickeners that can be used in the formulations of the present invention to help give the product the right consistency include carbomers, silicon dioxide, magnesium and / or aluminum silicates, beeswax, stearic acid, stearyl polysaccharides and their derivatives, such as xanthan gum, hydroxypropylcellulose, polyacrylamide, acrylate crosspolymers, preferably carbomers, such as 980, 981, 1382, 2984, 5984 types alone. or mixtures thereof. Suitable neutralizing agents that may be included in the cosmetic composition of the present invention to neutralize components such as emulsifiers or foam builders / foam stabilizers include, but are not limited to, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; organic bases such as diethanolamine (DEA), triethanolamine (TEA), aminomethyl propanol, and mixtures thereof; amino acids such as arginine and lysine, and any combination of any of the foregoing. The neutralizing agent may be present in the cosmetic composition of the present invention in an amount of about 0.01% to about 8%, preferably 1% to about 5%, by weight.

[0070] The addition of electrolytes to the cosmetic composition of the present invention may be suitable for modifying the behavior of the hydrophobic emulsifier. Therefore, the emulsion / microemulsion may preferably contain one or more electrolytes including salts of anions, such as chlorides, sulfates, carbonates, borates and aluminates, but not limited thereto. Other suitable electrolytes may be based on organic anions, such as, but not limited to, lactates, acetates, benzoates, propionates, tartrates and citrates. As cations, ammonium, alkylammonium, alkali metals or alkaline earth metals, magnesium ions, iron ions or zinc ions are preferred. Particularly preferred salts are potassium chloride and sodium chloride, magnesium sulfate, zinc sulfate and mixtures thereof. Electrolytes may be present in the cosmetic composition of the present invention in an amount of about 0.01% by weight to about 8% by weight.

[0071] Preferably, the cosmetic composition according to the invention is a topical composition in the form of a suspension or dispersion in a solvent or a fatty substance, or in the form of an emulsion or microemulsion (in particular of the O / W or W / O type, O / W / O or W / O / W type), a PET-emulsion, a multiple emulsion, a bickering emulsion, a hydrogel, an alcohol gel, a lipogel, a monophasic or multiphasic solution or a vesicular dispersion and other conventional compositions, which can also be applied by means of a pen, as a mask or as a spray. The emulsion may also contain anionic, nonionic, cationic or amphoteric surfactants. Preferred compositions according to the invention are skin care formulations, hair care formulations, photoprotective formulations or functional formulations.

[0072] The cosmetic composition of the present invention may be in the form of a liquid, lotion, thickened lotion, gel, cream, milk, ointment, paste, powder, make-up or solid tube stick, may optionally be packaged as an aerosol, may be provided in the form of a mousse (e.g. an aerosol mousse), foam or spray foam, spray, stick, gel, plaster, powder, cleanser, soap or aerosol or wipes.

[0073] The amount of the cosmetic composition according to the invention to be applied to the skin depends on the concentration of the active ingredient in the composition and the desired cosmetic or pharmaceutical effect. For example, the application may be the application of a cream to the skin. Typically 2 mg cream / cm 2 However, the amount of composition applied to the skin is not critical, if the desired effect cannot be achieved with a certain amount of composition, a higher concentration of active ingredient can be used, for example by applying more composition or by applying a composition containing more active ingredient.

[0074] The cosmetic composition according to the present invention is preferably applied at least once a day, for example twice or three times a day. Generally, at least two weeks are required to achieve the desired effect. However, it may take several weeks or even months to fully maximize the desired effect.

[0075] Regarding the types of cosmetic compositions, the preparation of cosmetic compositions and other suitable additives, reference may be made to relevant literature, for example, Novak GA, Die kosmetischen 2.Diekosmetischen Rohstoffe, wissenschaftliche Grundlagen (Verlag für Chem. Industrie H. Ziolkowski KG, Augsburg).

[0076] The present invention will be further described in conjunction with the following examples, which are presented for purposes of illustration and are not limiting in nature.

[0077] Example

[0078] General: All solvents were purchased from Macklin Inc. and used as received.

[0079] Table 1. Raw material information

[0080]

[0081] Example 1

[0082] In this example, the inhibitory effect of 10-HSA on 5α-reductase activity was investigated by using a 5α-reductase assay.

[0083] The 5α-reductase test is commonly used to evaluate the efficacy of products designed to control sebum secretion in the skin. The secretion of sebum is regulated by many factors, including hormones such as testosterone and dihydrotestosterone (DHT). DHT is produced from testosterone under the action of 5α-reductase. This enzyme is present in the skin and plays a key role in regulating sebum secretion. Therefore, determining 5α-reductase activity is a routine method to measure sebum control activity under this driving pathway.

[0084] Inhibition of 5α-reductase activity

[0085] 1. Add reaction components, including buffer (Tris-HCl, pH 7.4, Sigma T3253), liver microsomes (Xenotech, H0610), sample (0.03125%, 0.0625%, 0.125%, 0.25% or 0.5% of 10-HSA), testosterone (Sigma-Aldrich, T1500), NADPH (reduced nicotinamide adenine dinucleotide phosphate, Sigma 93205) to form a relatively uniform reaction system. After 30 minutes, terminate the reaction. Centrifuge the mixture. Take the supernatant for further analysis.

[0086] 2. The testosterone content in the sample mixture was quantified using the UPLC-MS method (Q Exactive, ThermoFisher Scientific), which reflects the enzyme activity by consuming the substrate testosterone. When the testosterone consumption in the test sample tube is lower than the testosterone consumption in the reaction tube without the inhibitor, it is considered to have the effect of inhibiting 5α-reductase.

[0087] The inhibition rate was calculated according to the following formula:

[0088] Inhibition rate (%) = [(BQ) - (BR)] / (BQ) × 100,

[0089] Wherein, B represents the testosterone content in the blank control group, Q represents the testosterone content in the reaction group without adding the inhibitor, and R represents the testosterone content in the reaction group with adding the tested inhibitor.

[0090] The results of the 5α-reductase assay are shown in Figure 1 It shows that 10-HSA exhibits effective inhibition of 5α-reductase activity at a concentration as low as 0.0625 wt %. The inhibitory efficacy increases in a dose-dependent manner.

[0091] Example 2

[0092] In this example, the inhibitory effect of 10-HSA on lipid accumulation under basal conditions was investigated by using the Oil Red staining method.

[0093] Cell culture

[0094] The cells were cultured in a 5% CO2 humidified incubator at 37°C in a solution supplemented with 10% fetal bovine serum (Corning), 1 mM CaCl2, 5 ng / ml human recombinant epidermal growth factor (Pufei, China), 1% Antibiotic-Antimycotic (Gibco TM ,Thermo Fisher Scientific Immortalized SZ95 human sebocytes derived from human facial sebaceous glands (Zouboulis et al., 1999) were cultured in basal medium (Sigma-Aldrich). The medium was changed every other day and cells were subcultured at 60-80% confluence.

[0095] Cell treatment

[0096] Then use TrypLE TM Express (Gibco) to separate cells and inoculate into 96-well black / clear bottom plates (PE View plates) at a density of 10,000 cells / well. The cells were maintained overnight at 37°C and 5% CO2 in supplemented human sebaceous gland cell growth medium (Sigma, FB205). The cells were then treated with 10-HSA samples (0.005%, 0.01%, in DMSO and further diluted with supplemented human sebaceous gland cell growth medium) for 72 hours.

[0097] Oil red staining and lipid accumulation value (%)

[0098] After cultivation, cells were washed twice with DPBS buffer, all cells were fixed in 4% paraformaldehyde for 5 minutes, and then 100 μl of 3mg / ml oil red (Sigma-Aldrich) phosphate buffered saline solution was added to each well and cultured for 20 minutes at 37°C. All wells were then rinsed three times with DPBS and blotted with suction and cotton yarn. Next, 300 μl of isopropanol was added to each well to extract the stained lipids in the sebaceous gland cells. Extraction was performed on a shaker for 20 minutes. The 100 μl extracts in each well were then transferred to another 96-well transparent plate to measure the absorbance at 520 nm. The relative lipid accumulation value was calculated using the following equation.

[0099] Lipid accumulation value % = (average OD of active group 520 / Average OD of control group 520 )×100%,

[0100] Relative integrated optical density (IOD) values ​​were calculated in the tables and figures to show relative values ​​normalized to the control group.

[0101] The results are shown in Figure 2 2 and 3, which show that 10-HSA significantly reduced lipid droplet accumulation in sebaceous gland cells compared to the blank control. It is noted that 10-HSA exhibited an inhibitory effect on lipid accumulation at a concentration as low as 0.005 wt%, and this effect was more pronounced at a higher concentration of 0.01 wt%.

[0102] Table 2. 10-HSA causes a decrease in the accumulation of lipid droplets stained with Oil Red in SZ95 sebocytes.

[0103]

[0104] Example 3

[0105] In this example, the inhibitory effect of 10-HSA on lipid accumulation under basal conditions was investigated by using Nile red staining. The cell culture and cell treatment procedures in this example were performed in a similar manner to that in Example 2.

[0106] Cell treatment

[0107] Cell treatment was performed in a similar manner as in Example 2.

[0108] Nile red staining and lipid accumulation value (%)

[0109] After incubation, cells were washed twice with DPBS buffer, all cells were fixed in 4% paraformaldehyde for 5 minutes, and then 100 μl of 1 μg / ml Nile Red (Sigma-Aldrich) phosphate buffered saline solution was added to each well and incubated at 37°C for 20 minutes. Fluorescence was measured on an Operetta CLS high-content imaging system (PE). Results are expressed as relative fluorescence units / cell, using 485 nm excitation wavelength, 565 nm emission wavelength to determine neutral lipids, and 540 nm excitation wavelength, 620 nm emission wavelength to determine polar lipids (Alestas et al., 2006). Nuclear DNA was labeled with DAPI (Invitrogen). Relative lipid accumulation values ​​were calculated using the following equation:

[0110] Relative lipid accumulation value % = (average fluorescence intensity value of active group / average fluorescence intensity value of control group) × 100%

[0111] The results are shown in Figure 3 3, which shows that 10-HSA significantly reduced the neutral lipid content in sebaceous gland cells compared to the blank control. Note that 10-HSA reduced the relative lipid content to 83% at a concentration as low as 0.000625 wt%, and further reduced it to 35% at a concentration of 0.005 wt%, compared to the control.

[0112] Table 3. 10-HSA causes a decrease in the content of neutral lipids stained by Nile red in SZ95 sebocytes.

[0113]

[0114] Example 4

[0115] In this example, the effect of 10-HSA on inhibiting the lipid production process induced by linoleic acid (LA) was studied by using the oil red staining method. This example was performed in a similar procedure to Example 2, except that the cells were treated with LA (0.25 mM in supplemented human sebaceous gland cell growth medium) and different concentrations of 10-HSA.

[0116] The results are shown in Figure 4 In Table 4, it is shown that in the presence of the inducer LA, lipid droplet accumulation in sebaceous gland cells increased. 10-HSA significantly inhibited the lipid production process induced by LA.

[0117] Table 4. 10-HSA reduces LA-induced lipid droplet accumulation in SZ95 sebocytes.

[0118]

[0119] Example 5

[0120] In this example, the effect of 10-HSA on inhibiting the lipogenic process induced by LA and DHT was studied by using the oil red staining method. This example was performed in a similar procedure to Example 2, except that the cells were treated with LA and DHT (0.25 mM LA and 100 mM DHT in supplemented human sebocyte growth medium) and different concentrations of 10-HSA.

[0121] The results are shown in Figure 5 In Table 5, it is shown that in the presence of inducers LA and DHT, lipid droplet accumulation in sebaceous gland cells increased. 10-HSA significantly inhibited the lipid production process induced by LA+DHT.

[0122] Table 5. 10 - HSA reduces LA+DHT-induced lipid droplet accumulation in SZ95 sebocytes.

[0123]

[0124] Although the present invention and its advantages have been described in detail, it should be understood that various changes, substitutions and modifications can be made here without departing from the spirit and scope of the present invention as defined by the appended claims. In addition, the scope of the present application is not intended to be limited to the specific embodiments of the process, instrument, preparation, material composition, device, method and step described in the specification. As will be easily understood by those of ordinary skill in the art from the present invention, according to the present invention, it is possible to utilize the process, instrument, preparation, material composition, device, method or step of performing the function substantially the same as the corresponding embodiment described herein or realizing the result substantially the same as the corresponding embodiment described herein that currently exists or is developed later. Therefore, the appended claims are intended to include these processes, instruments, preparation, material composition, device, method or step within their scope.

Claims

1. A non-therapeutic cosmetic treatment method for regulating lipid balance in sebaceous gland cells and / or for regulating sebaceous gland cell activity, which comprises topically applying to the skin a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof.

2. The non-therapeutic method of claim 1, wherein the amount of 10-hydroxystearic acid in the cosmetic composition is from about 0.000625 wt. % to about 20 wt. % relative to the total weight of the composition.

3. The non-therapeutic method according to claim 1 or 2, wherein the amount of 10-hydroxystearic acid in the cosmetic composition is from about 0.00125 wt. % to about 0.5 wt. % relative to the total weight of the composition.

4. A non-therapeutic cosmetic treatment method for inhibiting the lipogenesis process induced by an inducer, which comprises topically applying to the skin a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof before, simultaneously with or after the application of the inducer.

5. The non-therapeutic method of claim 4, wherein the inducing agent is selected from the group consisting of linoleic acid, dihydrotestosterone, insulin, epidermal growth factor, palmitic acid, insulin-like growth factor-1, arachidonic acid, and combinations thereof.

6. The non-therapeutic method according to claim 4 or 5, wherein the amount of 10-hydroxystearic acid in the cosmetic composition is from about 0.000625 wt. % to about 20 wt. % relative to the total weight of the composition.

7. The non-therapeutic method according to any one of claims 4 to 6, wherein the amount of 10-hydroxystearic acid in the cosmetic composition is from about 0.005% to about 0.1% by weight relative to the total weight of the composition.

8. Non-therapeutic use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof for topical application to the skin to regulate lipid balance in sebocytes and / or to regulate sebocyte activity.

9. The non-therapeutic use according to claim 8, wherein the amount of 10-hydroxystearic acid is from about 0.00125 wt% to about 0.5 wt% relative to the total weight of the composition.

10. Non-therapeutic use of a cosmetic composition comprising 10-hydroxystearic acid, a salt, an ester or an amide thereof for topical application to the skin to inhibit the lipogenesis process induced by an inducing agent.

11. The non-therapeutic use according to claim 10, wherein the inducing agent is selected from linoleic acid, dihydrotestosterone, insulin, epidermal growth factor, palmitic acid, insulin-like growth factor-1, arachidonic acid and combinations thereof.

12. The non-therapeutic use according to claim 10 or 11, wherein the amount of 10-hydroxystearic acid in the cosmetic composition is from about 0.005 wt% to about 0.1 wt% relative to the total weight of the composition.

Images