Capryloyl glycine for use in methods to prevent or reduce hair loss

Abstract

A method and use for inhibiting protease activity and thereby preventing or reducing hair loss is disclosed, comprising applying capryloyl glycine or a composition containing capryloyl glycine to the scalp of an individual.

Description

Technical Field

[0001] The present invention relates to preventing or reducing hair loss. In particular, the present invention relates to the use of capryloyl glycine, and compositions containing capryloyl glycine, for inhibiting protease activity and thereby preventing or reducing hair loss.

Background Art

[0002] Hair follicles are a regenerative system whose main function is to produce hair fibers. The hair growth cycle consists of stages of active regeneration (anagen), apoptotic regression (catagen), and relative growth arrest (telogen), which occur continuously throughout the life of the hair follicle. Towards the end of catagen and at the beginning of telogen, a fully keratinized hair shaft with characteristic depigmentation and a club-like base, called a "hair club fibre", is firmly held by a special junctional complex at the base of the bulge (a group of keratinocytes with a slow cell cycle located under the sebaceous gland).

[0003] Many reports have supported the role of proteases, such as serine proteases, in the mechanism of action during hair loss. In humans, the presence of enzymes, such as transglutaminase, in or around the club fibres, and enzyme inhibitors such as plasminogen activator inhibitor type 2 and tissue metalloprotease inhibitors, have been shown by evidence to help hold the club fibres in the hair follicles. Some studies have shown upregulation of various serine proteases during hair shedding, specifically changes in the gradient of protein and / or RNA expression of proteolytic enzymes during the transition from early to late anagen. Shedding is a normal process, but if these enzymes are higher than normal levels, it can lead to excessive or early shedding and result in a decrease in hair density.

[0004] There is a continuing need for cosmetically acceptable treatments that can prevent or reduce hair loss by targeting processes involved in the shedding phase. The inventors have found that treating the scalp with capryloyl glycine can inhibit protease activity, thereby preventing or reducing hair loss even in the absence of conventional hair loss inhibitors. [Overview of the project] [Means for solving the problem]

[0005] In a first aspect, the present invention provides the use of capryloyl glycine or a composition comprising capryloyl glycine for inhibiting protease activity and thereby preventing or reducing hair loss.

[0006] The present invention may also be described in one or more of the following embodiments: Capryloyl glycine or a composition comprising capryloyl glycine for use as a pharmaceutical to inhibit protease activity and thereby prevent or reduce hair loss.

[0007] Use of capryloyl glycine or a composition containing capryloyl glycine to inhibit protease activity and thereby prevent or reduce hair loss.

[0008] Use of capryloyl glycine or a composition containing capryloyl glycine to inhibit protease activity.

[0009] Capryloyl glycine or a composition containing capryloyl glycine for use in preventing or reducing hair loss.

[0010] Capryloyl glycine or a composition comprising capryloyl glycine for use in inhibiting protease activity, wherein the composition offers a significant advantage in inhibiting protease activity compared to a composition that does not contain capryloyl glycine.

[0011] Capryloyl glycine or a composition comprising capryloyl glycine for use in preventing or reducing hair loss, wherein the composition offers a significant advantage in preventing or reducing hair loss compared to a composition that does not contain capryloyl glycine.

[0012] Use of capryloyl glycine or a composition containing capryloyl glycine in the manufacture of a pharmaceutical product to inhibit protease activity and thereby prevent or reduce hair loss.

[0013] A method for preventing or reducing hair loss, comprising applying to the scalp of an individual an amount of capryloyl glycine or a composition containing capryloyl glycine that is effective in inhibiting the protease activity involved in hair loss in the individual.

[0014] The present invention also provides capryloyl glycine or a composition comprising capryloyl glycine for use in preventing or reducing hair loss by inhibiting protease activity involved in hair shedding, thereby preventing or reducing the shedding of hair club fibers from hair follicles.

[0015] All other aspects of the present invention will become more readily apparent with reference to the following detailed description and examples. [Modes for carrying out the invention]

[0016] To avoid any doubt, any feature of one aspect of the present invention may be used in any other aspect of the present invention. The word “comprising” is intended to mean “including,” but not necessarily “consisting of” or “composed of.” In other words, the listed steps or options do not need to be exhaustive. Note that the examples shown in the following description are intended to illustrate the present invention and are not intended to limit the present invention to these examples in themselves. Similarly, all percentages are weight / weight percentages unless otherwise specified. Except for the examples and comparative examples, or unless otherwise explicitly indicated, all figures in this specification and the claims indicating the quantities of materials or conditions of a reaction, or the physical properties of materials and / or uses should be understood to be modified by the word “about.” Numerical ranges expressed in the form “x~y” are understood to include x and y. If multiple preferred ranges are described in the form “x~y” for a specific feature, it is understood that all ranges combining different endpoints are also to be considered. Where used herein, the indefinite articles "a" or "an" and their corresponding definite articles "the" mean at least one, or one or more, unless otherwise specified. The various features of the invention referred to in the individual sections above are applied to other sections as needed, with modifications as necessary. As a result, features specified in one section may be combined with features specified in other sections as needed. The headings of each section are added for convenience only and are not intended to limit the disclosure in any way.

[0017] As used herein, “hair care composition” means a composition for topical application to the hair and / or scalp of mammals, particularly humans. Such compositions can generally be classified as leave-on or rinse-off, and also include any product applied to the human body for improving appearance, cleansing, odor control, or general aesthetics. The compositions of the present invention may be in the form of liquids, lotions, creams, foams, scrubs, gels, or bars. Non-limiting examples of such compositions include leave-on hair lotions, creams, and rinse-off shampoos, conditioners, shower gels, or bar soaps.

[0018] As used herein, "hair loss" includes the shedding of hair from the hair follicle.

[0019] The capryloyl glycine used in this invention is also known as N-(1-oxooctyl)glycine (C10H19NO3). Its CAS number is 14246-53-8, and this compound has the following general formula (I):

[0020] [ka]

[0021] Capryloyl glycine can be used in substantially pure form or as part of a composition.

[0022] The process leading to the final step of hair shedding has been reported to be driven by proteolytic activity, contributing to the shedding of club hair. During the late resting and shedding phases, increased protease activity can lead to excessive and undesirable hair loss. Materials that can modify proteolytic activity may be beneficial in reducing excessive hair loss. Serine proteases have been shown to play a role in the shedding phase of the hair growth cycle.

[0023] Here, it has been found that capryloyl glycine inhibits protease activity that is thought to be involved in hair loss. Thus, a composition containing capryloyl glycine provides a significant advantage in inhibiting protease activity compared to a composition that does not contain capryloyl glycine. Further, a composition containing capryloyl glycine provides a significant advantage in preventing or reducing hair loss compared to a composition that does not contain capryloyl glycine. Accordingly, in a preferred embodiment, the present invention provides a composition, preferably containing no capryloyl glycine, for inhibiting protease activity, thereby preventing or reducing hair loss and thereby preventing or reducing hair shedding, which provides a greater advantage compared to a composition that does not contain capryloyl glycine. Hair loss is preferably the loss of club fibers from the hair follicles. Such inhibition is preferably non-therapeutic and more preferably cosmetic.

[0024] Capryloyl glycine can be used in a substantially pure form. However, in a preferred embodiment, capryloyl glycine is used in the present invention preferably in the form of a personal care composition suitable for topical application to the hair and scalp.

[0025] Personal care compositions suitable for use in the present invention include rinse-off or non-rinse-off hair and scalp care compositions such as shampoos, conditioners, creams, lotions, gels, serums, mousses or oils. Non-rinse-off hair and scalp care compositions are preferred. Alternatively, rinse-off hair and scalp care compositions such as shampoos and conditioners are preferred.

[0026] Capryloyl glycine is generally included in a composition for use in the present invention at a level of 0.01 to 10% by weight, preferably 0.05 to 5% by weight, more preferably 0.1 to 2% by weight, and even more preferably 0.1 to 1% by weight of the composition.

[0027] Other active substances suitable for use in the present invention include zinc salts, preferably soluble zinc salts, or piroctone compounds, preferably piroctone olamines. Soluble zinc salts for use in the present invention preferably include one or more of the following: zinc acetate, zinc gluconate, ammonium zinc sulfate, zinc bromide, zinc chloride, zinc fluoride, zinc formate, zinc glycerophosphate, zinc iodide, zinc lactate, zinc nitrate, zinc salicylate, and zinc sulfate.

[0028] The compositions for use in the present invention generally include a cosmetically acceptable vehicle. The term "cosmetically acceptable" means that the vehicle is suitable for topical application to the skin, has good aesthetic properties, is compatible with at least one biotin-binding compound and at least one precursor for biotin biosynthesis selected from pimelic acid and / or its salts and any other components, and does not raise any safety or toxicity concerns.

[0029] The vehicle may contain an aqueous phase, an oil phase, an alcohol phase, a silicone phase, or a mixture thereof, and may be in the form of an emulsion. The emulsion can have a certain range of consistency, including dilute lotions (which may also be suitable for spray or aerosol delivery), creamy lotions, light creams, and heavy creams.

[0030] The compositions used in the present invention may also be formulated in a single-phase carrier such as a hydrophobic or hydrophilic liquid. Suitable hydrophobic liquid carriers include liquid polyorganosiloxanes, mineral oils, hydrogenated polyisobutenes, polydecenes, paraffins and isoparaffins with at least 10 carbon atoms, aliphatic or aromatic ester oils (e.g., isopropyl myristate, lauryl myristate, isopropyl palmitate, diisopropyl sebacate, diisopropyl adipate, and C12-C15 alkyl benzoates), polyglycol ethers (e.g., polyglycol butanol ethers), and mixtures thereof. Suitable hydrophilic liquid carriers include water, monohydric or polyhydric aliphatic alcohols having 2 to 8 carbon atoms, preferably 2 or 3 carbon atoms (e.g., ethanol and isopropanol), oligoglycol ethers having 2 to 5 repeating units (e.g., dipropylene glycol), and mixtures thereof.

[0031] Liquid compositions for use in the present invention may be thickened, for example, using one or more water-soluble or colloid-soluble polymer thickeners. Suitable water-soluble or colloid-soluble polymer thickeners include hydroxyethylcellulose, methylcellulose, hydroxypropylmethylcellulose, polyquaternium-10, carrageenan, guar gum, hydroxypropyl guar gum, xanthan gum, polyvinyl alcohol, acrylic acid / ethyl acrylate copolymer, carboxyvinyl polymer, crosslinked polyacrylate polymer, and polyacrylamide polymer.

[0032] Preferred types of compositions for use in the present invention include shampoos, oils, and lotions, which are intended for topical application to the hair and scalp.

[0033] The shampoo compositions used in the present invention are generally aqueous (i.e., having water or an aqueous solution as a main component) and preferably contain 50 to 98% by weight, preferably 60 to 90% by weight, of water (based on the total weight of the composition).

[0034] The shampoo compositions for use in the present invention typically contain one or an anionic surfactant such as sodium oleylsuccinate, ammonium lauryl sulfosuccinate, ammonium lauryl sulfate, sodium dodecylbenzenesulfonate, triethanolamine dodecylbenzenesulfonate, sodium cocoyl isethionate, sodium lauryl isethionate, sodium N-lauryl sarcosinate, sodium lauryl sulfate, sodium lauryl ether sulfate (n)EO (wherein n is in the range of 1 to 3), ammonium lauryl sulfate, and ammonium lauryl ether sulfate (n)EO (wherein n is in the range of 1 to 3).

[0035] Any mixture of the above materials may also be used.

[0036] The total amount of anionic surfactant in the shampoo composition for use in the present invention is generally in the range of 5 to 30% by weight, preferably 8 to 20% by weight (based on the total weight of the composition).

[0037] The shampoo composition for use in the present invention may also contain a nonionic surfactant in an amount ranging from 0.5 to 8% by weight, preferably 2 to 5% by weight (based on the total weight of the composition), and / or a cosurfactant such as an amphoteric or zwitterionic surfactant in an amount ranging from 0.5 to 8% by weight, preferably 1 to 4% by weight (based on the total weight of the composition). Typical nonionic surfactants include alkanolamides such as cocamide monoethanolamide and cocamide monoisopropanolamide; alkyl polyglucosides such as cocoglucoside and lauryl glucoside; and acyl glucamides such as cocoyl methyl glucamide.

[0038] Any mixture of the above materials may also be used.

[0039] The shampoo composition for use in the present invention may also contain one or more cationic polymers in an amount ranging from 0.01 to 5% by weight, preferably 0.05 to 2% by weight (based on the total weight of the composition). Typical cationic polymers include cationic polysaccharide polymers such as cationic cellulose derivatives and cationic guar gum derivatives such as guar hydroxypropyltrimethylammonium chloride.

[0040] The shampoo composition for use in the present invention may also contain one or more suspending agents in an amount ranging from 0.05 to 5% by weight, preferably 0.1 to 3% by weight (based on the total weight of the composition). Typical suspending agents include polyacrylic acid, crosslinked polymers of acrylic acid, copolymers of acrylic acid and hydrophobic monomers, copolymers of carboxylic acid-containing monomers and acrylic esters, crosslinked copolymers of acrylic acid and acrylic acid esters, heteropolysaccharide gums, and crystalline long-chain acyl derivatives such as ethylene glycol distearate.

[0041] The hair oils and lotions used in the present invention typically have an oil phase containing one or more cosmetically acceptable fatty substances that may be liquid or solid at room temperature (25°C). The lotions are typically aqueous emulsions having a water phase in addition to the oil phase.

[0042] Fatty substances acceptable as suitable cosmetics include naturally derived oils (e.g., sunflower oil, borage oil, soybean oil, castor oil, olive oil, and almond oil); monoalcohols or polyols and monocarboxylic acids or polycarboxylic acids, and at least one ester of alcohols and / or acids containing at least one hydrocarbon chain with at least six carbon atoms (e.g., octyl palmitate, isopropyl myristate, isopropyl palmitate, isopropyl isostearate, lar Hexyl laurate, isohexyl laurate, isohexyl palmitate, decyl oleate, isodecyl oleate, hexadecyl stearate, decyl stearate, dihexyldecyl adipate, lauryl lactate, myristyl lactate, cetyl lactate, oleyl stearate, oleyl oleate, oleyl myristate, lauryl acetate, cetyl propionate, isononyl isononanoate, propylene glycol dicaprate, diisopropyl adipate, dibutyl adipate, and oleyl adipate Iols; ethers (e.g., dicapryl ether); fatty alcohols (e.g., cetyl alcohol, stearyl alcohol, and behenyl alcohol); isoparaffins (e.g., isooctane, isododecane, and isohexadecane); silicone oils (e.g., cyclomethicone, dimethicone, and dimethiconol); hydrocarbon oils (e.g., mineral oil, petrolatum, and polyisobutene); fatty acids containing 8 to 30 carbon atoms (e.g., stearic acid, lauric acid, palmitic acid, and oleic acid) ; Vegetable fats (e.g., cocoa butter, coconut oil, palm oil, and shea butter); Petroleum-based, natural, and synthetic waxes (e.g., lanolin wax, beeswax, carnauba wax, candelilla wax, paraffin wax, lignite wax, microcrystalline wax, ceresin, ozokerite, and polyethylene wax); Hydrogenated oils that are solid at 25°C (e.g., hydrogenated castor oil, hydrogenated jojoba oil, hydrogenated palm oil, hydrogenated animal fat, and hydrogenated coconut oil); and fatty esters that are solid at 25°C (e.g., C 20~40 Examples include alkyl stearates.

[0043] The aqueous phase of the lotion used in the present invention may also contain one or more organic liquids that are miscible with water at room temperature (25°C). Examples of water-miscible organic liquids include monohydric and polyhydric alcohols and their derivatives, such as C2-C6 alkanols (e.g., ethanol and isopropanol); C2-C 10 Glycols and polyols (e.g., glycerol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol, dipropylene glycol, and diethylene glycol); C3-C 16 Examples include glycol ethers (e.g., mono-, di-, or tripropylene glycol (C1-C4) alkyl ethers and mono-, di-, or triethylene glycol (C1-C4) alkyl ethers) and polyethylene glycol having 2 to 12 oxyethylene units.

[0044] The lotion for use in the present invention may also contain surface-active ingredients such as emulsifiers and solubilizers to enable the uniform mixing of two or more immiscible components and to help stabilize the composition. Emulsifiers that may be used to form O / W or W / O emulsions include sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, PEG-20 sorbitan isostearate, polyglyceryl-3-diisostearate, polyglycerol ester of oleic acid / isostearate, polyglyceryl-6 hexalicinolate, polyglyceryl-4-oleate, polyglyceryl-4-oleate / PEG-8 propylene glycol cocoate, polyglyceryl-2 dipolyhydroxystearate, and PEG-30 dipolyhydroxystearate. Examples include oleamide DEA, TEA myristate, TEA stearate, magnesium stearate, sodium stearate, potassium laurate, potassium ricinoleate, sodium coconut fatty acid, sodium beef tallow fatty acid, potassium castor oil fatty acid, sodium oleate, cetyl phosphate, cetyl diethanolamine phosphate, potassium cetyl phosphate, sodium glyceryl oleate phosphate, dimethicone copolyol, cetyl dimethicone copolyol, octyl dimethicone ethoxyglucoside copolyol, dimethicone copolyol crosspolymer, and lauryl methicone copolyol.

[0045] Any combination of the above materials or product forms may also be used.

[0046] The compositions for use in the present invention (described above) may include additional active substances for improving the physical and / or aesthetic properties of the scalp and / or hair. Examples include amino acids, vitamins, minerals and / or antioxidants, emollients, moisturizers, sunscreens, anti-irritants, exfoliants, plant extracts (e.g., pomegranate extract, birch extract, green tea extract, chamomile extract, and licorice extract) and mixtures thereof.

[0047] The compositions for use in the present invention (described above) may include additional functional components to improve the physical and / or aesthetic properties of the compositions themselves. Examples include inorganic pigments (e.g., titanium dioxide, zirconium dioxide, cerium dioxide, zinc dioxide, iron dioxide, chromium dioxide, manganese violet, ultramarine, chromium hydrate, and ferric blue); organic pigments (e.g., carbon black and organic lakes of barium, strontium, calcium, or aluminum); pearlescent agents (e.g., mica coated with titanium dioxide and / or iron dioxide); dyes and preservatives (e.g., disodium EDTA, benzyl alcohol, methylparaben, phenoxyethanol, propylparaben, ethylparaben, butylparaben, and isobutylparaben); pH adjusters and fragrances (e.g., natural extracts from essential oils, flower oils, resins, gums, balsams, beans, mosses, and other plants, as well as synthetic aromatic materials).

[0048] Any mixture of the above materials may also be used.

[0049] method The present invention provides a method for preventing or reducing hair loss, comprising applying to the scalp of an individual an amount of capryloyl glycine or a composition containing capryloyl glycine effective in inhibiting the protease activity involved in hair loss in the individual. The method is essentially non-therapeutic. The method is preferably for cosmetic purposes.

[0050] The composition is applied appropriately to the hair and scalp and massaged into the surface of the scalp. Generally, an amount of the composition equivalent to about 1 to 15 ml per application is applied uniformly to the treatment area daily or at least once a week, over a time interval of at least 7 (7) days, preferably at least 28 days, more preferably at least 30 (30) days.

[0051] The present invention also provides capryloyl glycine or a composition comprising capryloyl glycine for use in preventing or reducing hair loss, preferably the composition having a greater advantage in preventing or reducing hair loss compared to a composition that does not contain capryloyl glycine. The present invention also provides capryloyl glycine or a composition comprising capryloyl glycine for use in preventing or reducing hair loss by inhibiting protease activity involved in hair loss, thereby preventing or reducing the shedding of hair club fibers from hair follicles, preferably the composition having the greater advantage described above compared to a composition that does not contain capryloyl glycine.

[0052] The present invention will be further explained by the following non-limiting embodiments.

[0053] [Examples] [Example 1] This example demonstrates the in vitro protease inhibitory activity of capryloylglycine.

[0054] Test solutions (samples 1 and 2) and a control solution (placebo) were prepared with the compositions shown in Table 1.

[0055] [Table 1]

[0056] Test method Protease inhibition was determined using the EnzChek® Protease Assay Kit, a direct fluorescence-based assay for detecting metalloproteases, serine proteases, acid proteases, and sulfhydrylproteases. This assay contains casein derivatives labeled with pH-insensitive green fluorescent BODIPY® FL peptide, which has excitation and emission maxima at approximately 505 / 513 nm and 589 / 617 nm, respectively. A standard fluorescein filter was used for detecting the BODIPY FL-labeled peptide according to the manufacturer's instructions.

[0057] A reaction mixture containing trypsin (1.0 μg / mL), BODIPY® casein substrate (final concentration 5 μg / mL), and Tris-HCl (pH 7.8, 10 mmol / L) was set up in a 96-well plate, covered with foil, and incubated at 37°C. Placebo or the above sample was added to the reaction mixture. After 1 hour of incubation, fluorescence was measured at excitation / emission wavelengths of 485 / 530 nm. The increase in fluorescence was proportional to the protease activity.

[0058] The presence of protease activity in human hair follicles has been previously demonstrated using enzyme-based in vitro assays. This assay allows the use of trypsin as a control serine protease enzyme, where an increase in fluorescence units is proportional to an increase in protease activity. Conversely, the addition of a protease inhibitor to the reaction mixture allows for the detection of a decrease in fluorescence activity. Experiments were conducted to investigate whether samples containing different concentrations of capryloylglycine could attenuate trypsin activity.

[0059] The results are summarized in Table 2.

[0060] [Table 2]

[0061] The results for samples 1 and 2 showed significantly better (lower) trypsin activity (P<0.05) than the placebo sample. This indicates that samples containing capryloyl glycine inhibit protease activity, thereby preventing hair shedding of hair claw fibers from hair follicles. Furthermore, this showed that such inhibitory activity increased with increasing concentration.

Claims

1. Use of capryloyl glycine or a composition containing capryloyl glycine to inhibit protease activity and thereby prevent or reduce hair loss.

2. Use of capryloyl glycine or a composition containing capryloyl glycine to inhibit protease activity.

3. The use according to claim 1 or 2, which is essentially non-therapeutic.

4. Capryloyl glycine or a composition comprising capryloyl glycine for use in inhibiting protease activity, thereby preventing or reducing hair loss.

5. Capryloyl glycine or a composition comprising capryloyl glycine for use in inhibiting protease activity.

6. Capryloyl glycine or a composition comprising capryloyl glycine for use in inhibiting protease activity, wherein the composition offers a significant advantage in inhibiting protease activity compared to a composition that does not contain capryloyl glycine.

7. Capryloyl glycine or a composition comprising capryloyl glycine for use in preventing or reducing hair loss, wherein the composition offers a significant advantage in preventing or reducing hair loss compared to a composition that does not contain capryloyl glycine.

8. Use of capryloyl glycine or a composition containing capryloyl glycine in the manufacture of a pharmaceutical product to inhibit protease activity and thereby prevent or reduce hair loss.

9. A method for preventing or reducing hair loss, comprising applying to the scalp of an individual an amount of capryloyl glycine or a composition containing capryloyl glycine that is effective in inhibiting the protease activity involved in hair loss in the individual.

10. The method according to claim 9, which is essentially non-therapeutic.

11. The use, method, compound, or composition according to any one of claims 1 to 10, wherein the composition comprising capryloylglycine further comprises a zinc salt, preferably a soluble zinc salt.

12. The use, method, compound, or composition according to any one of claims 1 to 11, wherein the composition comprising capryloylglycine further comprises a piroctone compound, preferably piroctone olamine.

13. The use, method, compound, or composition according to any one of claims 1 to 12, wherein the composition comprises capryloylglycine at a level of 0.01 to 10% by weight, preferably 0.05 to 5% by weight, and more preferably 0.1 to 2% by weight of the composition.

14. The use, method, compound, or composition according to any one of claims 1 to 13, wherein the composition comprising capryloyl glycine is a non-washable composition.

15. The use, method, compound, or composition according to any one of claims 1 to 14, wherein the composition comprising capryloyl glycine is a rinse-off composition, preferably a shampoo.

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