Composition for promoting hair growth or hair growth containing thymol ester compound

Abstract

The present specification relates to a composition for promoting hair growth or hair growth, the composition comprising, as an active ingredient, thymol 3, 4, 5-trimethoxycinnamate (3, 4, 5-Trime thiocinnate Thymol Ester), or a stereoisomer, a pharmaceutically acceptable salt, a hydrate, or a solvate thereof, and to a method for promoting hair growth or hair growth, and more specifically, to a composition for promoting hair growth or hair growth, the composition comprising, as an active ingredient, thymol 3, 4, 5-trimethoxycinnamate (3, 4, 5-Trime thiocinnate Thymol Ester). The composition according to the present disclosure can exhibit a significant effect on a subject in need of treating alopecia or promoting hair growth and hair growth.

Description

Technical Field

[0001] The present specification discloses a composition for promoting hair growth or development, comprising 3,4,5-trimethoxycinnamate thymol ester or its stereoisomers, pharmaceutically acceptable salts, hydrates or solvates as an effective ingredient. Background Art

[0002] Human hair is responsible for the defensive function of protecting the scalp from external stimuli such as ultraviolet rays, and also for the aesthetic function of expressing the external image of an individual.

[0003] However, in modern society, hair loss frequently occurs due to natural factors such as environmental pollution and strong ultraviolet rays, and physiological factors such as stress and hormonal imbalance. Unlike in the past when hair loss was limited to adult males, hair loss occurs in both men and women, young and old, resulting in an urgent need for materials for preventing and treating hair loss.

[0004] Currently, the preparations used to treat hair loss are roughly divided into pharmaceuticals, quasi-pharmaceuticals, and cosmetics. As a professional pharmaceutical that requires a doctor's prescription to purchase, there is "Propecia" developed and marketed by Merck in the United States. Finasteride, the main ingredient in it, was approved as a hair loss treatment agent by the US FDA in December 1997. Finasteride is a drug that inhibits 5α-reductase, which converts testosterone into dihydrotestosterone (DHT), and plays a role in making soft hair grow into thick and long hair. It is effective in improving hair loss in the short term, but there are reports of side effects such as impotence, sexual dysfunction, and male breast hypertrophy.

[0005] Minoxidil is a drug that has been recognized for its safety and effectiveness and can be purchased without a doctor's prescription. It was approved by the U.S. FDA as the first spreadable hair loss treatment in December 1997. This drug improves blood circulation and opens potassium channels, thereby promoting hair growth. However, it may cause local reactions such as itching and rash, and may cause tachycardia.

[0006] Therefore, in addition to the conventionally known preparations that are effective in preventing hair loss and promoting hair growth and hair growth, it is necessary to develop a composition that ensures safety and efficacy. Summary of the invention

[0007] Technical issues to be solved

[0008] In one aspect of the present disclosure, it is intended to provide a composition comprising thymol 3,4,5-trimethoxycinnamate as an effective ingredient, thereby having a hair growth or growth effect.

[0009] Solution to the problem

[0010] In one aspect, the present disclosure provides a composition for promoting hair growth or development, comprising 3,4,5-trimethoxycinnamate thymol ester or a stereoisomer, a pharmaceutically acceptable salt, a hydrate or a solvate thereof as an effective ingredient.

[0011] Effects of the Invention

[0012] On the one hand, the composition according to the present disclosure can be effectively used as a cosmetic composition, a skin external preparation or a pharmaceutical composition for promoting hair growth or hair growth with the purpose of suppressing hair loss and treating hair growth. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 The results are obtained by using a two-cell assemblage assay to confirm the hair growth effect of the composition according to one embodiment of the present disclosure. DETAILED DESCRIPTION

[0014] Hereinafter, the present disclosure is further described in detail by the following examples. However, the following examples are only provided for the purpose of illustration to help understand the present disclosure, and the category and scope of the present disclosure are not limited thereto.

[0015] In an exemplary implementation of the present disclosure, a composition for promoting hair growth or development is provided, which includes 3,4,5-trimethoxycinnamate thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or its stereoisomers, pharmaceutically acceptable salts, hydrates or solvates as an active ingredient.

[0016] In another exemplary implementation of the present disclosure, a method for promoting hair growth or development is provided, which includes the step of administering a composition, wherein the composition includes 3,4,5-trimethoxycinnamate thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or its stereoisomers, salts, hydrates or solvates as an active ingredient.

[0017] In another exemplary implementation of the present disclosure, there is provided a use of 3,4,5-trimethoxycinnamate thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or its stereoisomers, salts, hydrates or solvates for preparing a composition for promoting hair growth or hair development.

[0018] In another exemplary implementation of the present disclosure, a non-therapeutic use of thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or its stereoisomers, salts, hydrates or solvates for promoting hair growth or development is provided.

[0019] In another exemplary implementation of the present disclosure, a thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or a stereoisomer, salt, hydrate or solvate thereof for promoting hair growth or development is provided.

[0020] In one embodiment, the thymol 3,4,5-trimethoxycinnamate is (5-methyl-2-propan-2-ylphenyl)(E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate which can be represented by the following chemical formula 1.

[0021]

Chemical formula 1

[0022]

[0023] In the present specification, "isomers" specifically include not only optical isomers (e.g., essentially pure enantiomers, essentially pure diastereomers or mixtures thereof), but also conformational isomers (i.e., isomers that differ only in the angle of one or more chemical bonds), positional isomers (especially, tautomers or geometrical isomers) (e.g., cis-trans isomers).

[0024] In the present specification, "essentially pure" means that, for example, when using enantiomers or diastereomers, the specific compound of the enantiomer or diastereomer mentioned is present in about 90% or more, preferably about 95% or more, more preferably about 97% or more or about 98% or more, further preferably about 99% or more, and further preferably about 99.5% or more (w / w).

[0025] In this specification, "pharmaceutically acceptable" means that when used according to the usual pharmaceutical dosage, it avoids considerable toxic effects, and can obtain or has obtained approval from the government or equivalent regulatory agency for use in animals, more specifically in humans, or is listed in the pharmacopoeia or is recognized as the content of other general pharmacopoeias.

[0026] In the present specification, "pharmaceutically acceptable salt" refers to a salt according to one aspect of the present invention that is pharmaceutically acceptable and has the preferred pharmacological activity of the parent compound. The salts may include (1) an acid addition salt formed from an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or an acid addition salt formed from an organic acid such as acetic acid, propionic acid, hexanoic acid, cyclopentylpropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethylsulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2,2,2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, hexanedioic acid. or (2) a salt formed when an acidic proton present in the parent compound is replaced.

[0027] In this specification, "hydrate" refers to a compound bound with water, and is a broad concept including inclusion compounds in which there is no chemical bonding force between water and the compound.

[0028] In the present specification, the term "solvate" refers to a high-valent compound generated between molecules or ions of a solute and molecules or ions of a solvent.

[0029] In one implementation, the composition can be used to promote the growth of hair length.

[0030] In one implementation example, the concentration of the active ingredient can be 0.1 to 100 g / L based on the total volume of the composition.

[0031] For example, the concentration of the active ingredient can be 0.1 g / L or more, 0.5 g / L or more, 1 g / L or more, 5 g / L or more, 10 g / L or more, 20 g / L or more, 30 g / L or more, 40 g / L or more, 50 g / L or more, 60 g / L or more, 70 g / L or more, 80 g / L or more, or 90 g / L or less, and can be 100 g / L or less, 90 g / L or less, 80 g / L or less, 70 g / L or less, 60 g / L or less, 50 g / L or less, 40 g / L or less, 30 g / L or less, 20 g / L or less, 10 g / L or less, 5 g / L or less, 1 g / L or less, or 0.5 g / L or less.

[0032] In one implementation example, the composition may be a cosmetic composition.

[0033] The cosmetic composition may contain a medium or matrix acceptable in cosmetics or dermatology. As all dosage forms suitable for topical use, it may be provided as, for example, a solution, gel, solid, anhydrous paste, an emulsion obtained by dispersing an oil phase in an aqueous phase, a suspension, a microemulsion, a microcapsule, a microparticle ball, or an ionic (liposome) and non-ionic capsule dispersion form, or a cream, a toner, a lotion, a powder, an ointment, a spray or a concealer stick form. The composition may be prepared according to conventional methods in the art. The composition according to the present disclosure may also be used in the form of a foam or an aerosol composition further containing a compressed propellant.

[0034] The dosage form of the cosmetic composition according to one embodiment of the present disclosure is not particularly limited. For example, it can be formulated into cosmetics such as soft lotion, astringent lotion, nourishing lotion, nourishing cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, makeup remover, facial mask, powder, body lotion, moisturizing cream, moisturizing oil and moisturizing essence.

[0035] When the dosage form of the cosmetic composition of the present invention is a paste, cream or gel, animal fiber, plant fiber, wax, paraffin, starch, tragacanth gum, cellulose derivatives, polyethylene glycol, silicone, bentonite, silicon dioxide, talc or zinc oxide can be used as the carrier component.

[0036] When the dosage form of the cosmetic composition of the present invention is a powder or a spray, lactose, talc, silicon dioxide, aluminum hydroxide, calcium silicate or polyamide powder can be used as a carrier component. In particular, when the dosage form is a spray, it can further contain a propellant such as chlorofluorocarbons, propane / butane or dimethyl ether.

[0037] When the dosage form of the cosmetic composition of the present invention is a solution or an emulsion, a solvent, a solvating agent or an emulsifying agent is used as a carrier component, for example, water, ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol oil, glycerol fatty ester, polyethylene glycol or fatty acid ester of sorbitol.

[0038] When the dosage form of the cosmetic composition of the present invention is a suspension, as the carrier component, liquid diluents such as water, ethanol or propylene glycol; suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitan esters and polyoxyethylene sorbitan esters; microcrystalline cellulose; aluminum metahydroxide; bentonite, agar or tragacanth gum, etc. can be used.

[0039] When the dosage form of the cosmetic composition of the present invention is a surfactant-containing cleanser, fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid monoesters, isethionates, imidazoline derivatives, methyl taurates, sarcosinates, fatty acid amide ether sulfates, alkylamide betaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated glyceryl fatty acid esters can be used as carrier components.

[0040] In addition to the active ingredients, the cosmetic composition of the present disclosure may also contain functional additives and ingredients contained in general cosmetic compositions. As the functional additives, the ingredients selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular weight peptides, high molecular weight polysaccharides, sphingolipids and seaweed juice may be included.

[0041] In addition, in the cosmetic composition of the present disclosure, together with the functional additives, the ingredients included in the general cosmetic composition are also formulated as needed. As the formulation ingredients included in addition, oil components, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH regulators, ethanol, pigments, fragrances, blood circulation promoters, cooling agents, antiperspirants, purified water, etc. can be cited.

[0042] In one implementation example, the composition may be a composition for external use on the skin.

[0043] The skin external preparation is a general term for any type of preparation that can be applied to the outside of the skin, and includes cosmetics, pharmaceuticals, and the like in various dosage forms.

[0044] In one implementation example, the composition may be an oral composition.

[0045] The oral composition according to the present disclosure may be in liquid or solid dosage form, and may be tablets, capsules, soft capsules, pills, granules, beverages (drinks), fat-reducing bars, chocolate, caramel dosage forms or biscuit dosage forms, and its dosage form is not particularly limited.

[0046] In addition to the active ingredients, the oral composition according to the present disclosure may further contain excipients, sugars, flavors, pigments, oils and fats, proteins, etc. as needed.

[0047] In one implementation example, the composition may be a pharmaceutical composition.

[0048] The pharmaceutical composition can be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, etc. The dosage form for oral administration can be tablets, pills, soft and hard capsules, granules, powders, fine particles, liquids, emulsions or spheres, but are not limited thereto. The dosage form for parenteral administration can be solutions, suspensions, emulsions, gels, injections, drops, suppositories, patches or sprays, but are not limited thereto. The dosage form can be easily prepared according to conventional methods in the field, and can further include surfactants, excipients, wettable powders, emulsifying agents, suspending agents, salts or buffers for adjusting osmotic pressure, colorants, spices, stabilizers, preservatives, preservatives or other commonly used adjuvants.

[0049] In one embodiment, the thymol 3,4,5-trimethoxycinnamate or its stereoisomer, salt, hydrate or solvate can be administered in an amount of 0.01 to 10 mg / kg / day.

[0050] For example, the dosage may be 0.01 mg / kg / day or more, 0.1 mg / kg / day or more, 1 mg / kg / day or more, or 5 mg / kg / day or less, or 10 mg / kg / day or less, 5 mg / kg / day or less, 1 mg / kg / day or less, 0.1 mg / kg / day or less, or 0.05 mg / kg / day or less.

[0051] Hereinafter, the present invention will be further described in detail by the following examples. However, the following examples are provided only for the purpose of illustrating to help understand the present invention, and the category and scope of the present invention are not limited thereto.

[0052] Example

[0053] Preparation of 3,4,5-Trimethoxycinnamate ThymolEster

[0054] Thymol trimethoxycinnamate (Melasolv) with CAS number 504394-57-4 was purchased from COSMANN Co., Ltd. (located in Hwaseong, Gyeonggi-do).

[0055] Experimental example - Evaluation of hair growth promoting effect

[0056] The hair growth promoting effect of 3,4,5-trimethoxycinnamic acid thymol ester (Melasolv) at different concentrations (10 ppm, 20 ppm) was evaluated using a two-cell combined analysis ("Two-Cell Ass emblage" Assay: A Simple in vitro Method for Screening Hair Growth-Promoting Compounds)(Front Cell Dev Biol. 2020 Nov 24; 8: 581528).

[0057] The Two-Cell Assemblage Assay is an evaluation method that simulates the hair growth of actual hair follicles by culturing the dermal papilla (DP) cells and outer root sheath (ORS) cells that make up the hair follicles together. That is, the length growth of the Two-Cell Assemblage structure has a mechanism similar to that of actual hair follicle growth, and is used as a new method for evaluating the effect of promoting hair growth.

[0058] 5,000 hair follicle dermal papilla cells were seeded into an ultra-low attachment 96-well plate to form a 3D spheroid. After 24 hours, 5,000 outer hair root sheaths (Kyungpook National University Industry-Academic Cooperation Group) were added together with the test substance to make a two-cell assembly structure ("Two-Cell Assemblage" structure) and incubated at 37°C and 5% CO 2 After 5 days of culture, the length growth was measured using a microscope (OLYMPUS, SZX16), and the results were as follows: Figure 1As shown (*p<0.05, **p<0.01, ***p<0.001 vs. control group).

[0059] refer to Figure 1 It was confirmed that when Melasolv was treated and cultured with a two-cell assembly structure ("Two-Cell Assemblage" structure) for 5 days, it showed a significant effect of promoting length growth, that is, a hair growth effect.

[0060] Specific example

[0061] Specific example 1: Use of 3,4,5-trimethoxycinnamate thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or its stereoisomers, pharmaceutically acceptable salts, hydrates or solvates for preparing a composition for promoting hair growth or development.

[0062] Specific example 2: A use, according to specific example 1, the composition is used to promote the growth of hair length.

[0063] Specific example 3: A use according to Specific example 1 or 2, wherein the concentration of 3,4,5-trimethoxycinnamate thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or its stereoisomers, pharmaceutically acceptable salts, hydrates or solvates is 0.1 to 100 g / L based on the total volume of the composition.

[0064] Specific example 4: A use, according to any one of specific examples 1 to 3, the composition is a cosmetic composition.

[0065] Specific example 5: A use, according to any one of specific examples 1 to 4, the composition is a skin external preparation.

[0066] Specific example 6: A use, according to any one of specific examples 1 to 5, the composition is an oral composition.

[0067] Specific example 7: A use, according to any one of specific examples 1 to 6, the composition is a pharmaceutical composition.

[0068] Specific example 8: A use according to any one of specific examples 1 to 7, wherein the 3,4,5-trimethoxycinnamic acid thymol ester or its stereoisomer, salt, hydrate or solvate is administered in a dosage of 0.01-10 mg / kg / day.

Claims

1. Use of thymol 3,4,5-trimethoxycinnamate or its stereoisomers, pharmaceutically acceptable salts, hydrates or solvates for preparing a composition for promoting hair growth or hair development.

2. The use according to claim 1, wherein: The composition is used to promote the growth of hair length.

3. The use according to claim 1, wherein: The concentration of the thymol 3,4,5-trimethoxycinnamate or its stereoisomers, pharmaceutically acceptable salts, hydrates or solvates is 0.1 to 100 g / L based on the total volume of the composition.

4. The use according to claim 1, wherein: The composition is a cosmetic composition.

5. The use according to claim 1, wherein: The composition is an external preparation for skin.

6. The use according to claim 1, wherein: The composition is a pharmaceutical composition.

7. The use according to claim 1, wherein: The thymol 3,4,5-trimethoxycinnamate or its stereoisomer, pharmaceutically acceptable salt, hydrate or solvate is administered in an amount of 0.01 to 10 mg / kg / day.

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