Composition for promoting hair sprouting or hair growth containing thymol ester-based compound

Abstract

To provide a composition for promoting hair sprouting or growth, including 3,4,5-trimethoxycinnamate thymol ester or a stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof as an active ingredient.SOLUTION: A composition according to the present disclosure can exhibit a significant effect on a subject in need of hair loss treatment or hair sprouting promotion and hair growth.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] This specification discloses a hair growth or hair growth promoting composition containing 3,4,5-Trimethoxycinnamate Thymol Ester or its stereoisomers, pharmaceutically acceptable salts, hydrates or solvates as an active ingredient.

Background Art

[0002] Human hair mainly functions as a defense mechanism to protect the scalp from external stimuli such as ultraviolet rays, and also as an aesthetic function to express an individual's appearance image.

[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. Different from the past when it was limited to adult men, hair loss occurs regardless of gender and age, so materials for its prevention and treatment are eagerly desired.

[0004] Currently, formulations for hair loss treatment are roughly classified into pharmaceuticals, quasi-drugs, and cosmetics. Among the prescription pharmaceuticals that can be purchased based on a doctor's prescription, there is "Propecia" developed and sold by Merck & Co., Inc. in the United States. Finasteride, its main ingredient, was approved as a hair loss treatment drug by the US FDA in December 1997. Finasteride is a drug that inhibits 5α-reductase, which converts testosterone to dihydrotestosterone (DHT), and plays a role in growing soft hair into thick and long hair. This is effective in improving hair loss in the short term, but side effects such as erectile dysfunction, decreased sexual function, and gynecomastia have been reported.

[0005] Among the drugs that have been recognized for safety and effectiveness and can be purchased without a doctor's prescription, there is Minoxidil, which was first approved by the US FDA as a topical alopecia treatment drug in December 1997. This drug has the effect of promoting hair growth by improving blood circulation and opening potassium channels, but it may cause local reactions such as itching and rash, or cause tachycardia.

[0006] Therefore, in addition to the preparations that are known to prevent hair loss and promote hair growth and hair regrowth, the development of a composition with guaranteed safety and effectiveness is required.

Prior Art Documents

Patent Documents

[0007]

Patent Document 1

Non-Patent Documents

[0008]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0009] In one aspect of the present disclosure, an object is to provide a composition having a hair growth or hair regrowth effect by containing 3,4,5-trimethoxycinnamic acid thymol ester as an active ingredient.

Means for Solving the Problems

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

Advantages of the Invention

[0011] In one aspect, the composition according to the present disclosure can be usefully used as a cosmetic composition for promoting hair growth or hair regrowth, a topical skin preparation or a pharmaceutical composition for the purpose of suppressing hair loss and treating hair growth.

Brief Description of the Drawings

[0012]

Figure 1

Modes for Carrying Out the Invention

[0013] Hereinafter, the present disclosure will be described more specifically by the following examples. However, the following examples are merely illustrative for helping the understanding of the present disclosure, and the scope and range of the present disclosure are not limited thereto.

[0014] In an exemplary implementation of the present disclosure, a composition for promoting hair growth or hair regrowth is provided, comprising 3,4,5-trimethoxycinnamate thymol ester or a stereoisomer thereof, a pharmaceutically acceptable salt, hydrate or solvate as an active ingredient.

[0015] In another exemplary implementation of the present disclosure, a method for promoting hair growth or hair regrowth is provided, comprising administering a composition comprising 3,4,5-trimethoxycinnamate thymol ester or a stereoisomer thereof, a salt, hydrate or solvate as an active ingredient.

[0016] In other exemplary embodiments of the present disclosure, there is provided the use of 3,4,5-trimethoxycinnamate thymol ester or a stereoisomer, salt, hydrate or solvate thereof for preparing a composition for promoting hair growth or hair regrowth.

[0017] In other exemplary embodiments of the present disclosure, there is provided a non-therapeutic use of thymol ester (3,4,5-trimethoxycinnamate thymol ester) or a stereoisomer, salt, hydrate or solvate thereof for promoting hair growth or hair regrowth.

[0018] In other exemplary embodiments of the present disclosure, there is provided thymol ester (3,4,5-trimethoxycinnamate thymol ester) or a stereoisomer, salt, hydrate or solvate thereof for promoting hair growth or hair regrowth.

[0019] In one embodiment, the 3,4,5-trimethoxycinnamate thymol ester is (5-methyl-2-propan-2-ylphenyl)(E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate represented by the following general formula (1).

[0020] [Chemical formula]

[0021] As used herein, the term "isomer" includes not only optical isomers (e.g., essentially pure enantiomers, essentially pure diastereomers or mixtures thereof), but also conformation isomers (i.e., isomers that differ only in the angle of at least one chemical bond), position isomers (in particular, tautomers) or geometric isomers (e.g., cis-trans isomers).

[0022] As used herein, "essentially pure", when used in connection with an enantiomer or a diastereomer, means that the specific compound exemplified by the enantiomer or diastereomer is present at about 90% or more, preferably about 95% or more, more preferably about 97% or more or about 98% or more, still more preferably about 99% or more, and most preferably about 99.5% or more (w / w).

[0023] As used herein, "pharmaceutically acceptable" means that it can be approved by, approved by, described in a pharmacopoeia, or recognized as another common pharmacopoeia by a government or a regulatory agency equivalent thereto, by avoiding significant toxic effects when used at normal medicinal dosages, and can be used in animals, more specifically, humans.

[0024] As used herein, "pharmaceutically acceptable salt" means a salt that is pharmaceutically acceptable and has the desired pharmacological activity of the parent compound, and relates to a salt according to one embodiment of the present disclosure. The salt may be formed from (1) inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or acetic acid, propionic acid, hexanoic acid, cyclopentene propionic 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-ethane-disulfonic acid, 2-hydroxyethanesulfonic 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, muconic acid, etc. or an acid addition salt formed from an organic acid; or (2) a salt formed when an acidic proton present in the parent compound is substituted.

[0025] As used herein, "hydrate" means a compound to which water is bonded, and is a broad concept including inclusion compounds in which there is no chemical bonding force between water and the compound.

[0026] As used herein, "solvate" means a higher-order compound formed between the molecules or ions of a solute and the molecules or ions of a solvent.

[0027] In one implementation example, the composition may be for promoting hair length growth.

[0028] In one implementation example, the concentration of the active ingredient may be 0.1 to 100 g / L with respect to the total volume of the composition.

[0029] For example, the concentration of the active ingredient may 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 more with respect to the total volume of the composition, and may 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.

[0030] In one implementation example, the composition may be a cosmetic composition.

[0031] The appearance of the cosmetic composition includes a cosmetically or dermatologically acceptable medium or base. This can be in any dosage form suitable for topical application, for example, in the form of a solution, gel, solid, anhydrous product, emulsion obtained by dispersing an oil phase in an aqueous phase, suspension, microemulsion, microcapsule, microgranule, or ionic (liposome) and non-ionic vesicle dispersant, or in the form of a cream, lotion, milk, powder, ointment, spray, or stick concealer. These compositions 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 in the form of an aerosol composition further containing a compressed propellant.

[0032] The cosmetic composition according to an embodiment of the present disclosure is not particularly limited in its dosage form, and may be formulated into cosmetics such as softening lotion, astringent lotion, nutritive lotion, nutritive cream, massage cream, beauty essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, powder, body lotion, body cream, body oil, body essence, etc.

[0033] When the dosage form of the cosmetic composition of the present disclosure is a paste, cream or gel, as the carrier component, animal fiber, plant fiber, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide etc. may be used.

[0034] When the dosage form of the cosmetic composition of the present disclosure is a powder or spray, as the carrier component, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, and particularly in the case of a spray, it may further contain a propellant such as hydrofluorocarbon, propane / butane or dimethyl ether.

[0035] When the dosage form of the cosmetic composition of the present disclosure is a solution or emulsion, as the carrier component, a solvent, a solvating agent or an emulsifying agent is used, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerin fatty acid ester, polyethylene glycol or fatty acid ester of sorbitan.

[0036] When the dosage form of the cosmetic composition of the present disclosure is a suspension, as the carrier component, a liquid diluent such as water, ethanol, propylene glycol, and a suspending agent such as ethoxylated stearyl alcohol, polyoxyethylene sorbitol ester, polyoxyethylene sorbitan ester, and microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, tragacanth etc. may be used.

[0037] When the dosage form of the cosmetic composition of the present disclosure is surfactant-containing cleansing, as the carrier component, aliphatic alcohol sulfates, aliphatic alcohol ether sulfates, sulfosuccinic acid monoesters, isethionates, imidazolium derivatives, methyl taurates, sarcosinates, fatty acid amide ether sulfates, alkylamide betaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, ethoxylated glycerin fatty acid esters, etc. may be used.

[0038] In addition to the above active ingredients, the cosmetic composition of the present disclosure may further contain functional additives and components contained in general cosmetic compositions. The functional additives may include components selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular weight peptides, high molecular weight polysaccharides, sphingolipids, and seaweed extracts.

[0039] In the cosmetic composition of the present disclosure, in addition to the above functional additives, components contained in general cosmetic compositions may be blended as needed. Other blending components include oil and fat components, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, blood circulation promoters, cooling agents, antiperspirants, purified water, etc.

[0040] In one implementation example, the composition may be a topical skin composition.

[0041] The topical skin composition is a general term that may include any thing applied to the outer skin, and various dosage forms of cosmetics and pharmaceuticals may be included therein.

[0042] In one embodiment, the composition may be a food composition.

[0043] The food composition according to the present disclosure may be in a liquid or solid dosage form, and may be a tablet, capsule, soft capsule, pill, granule, beverage (drink), diet bar, chocolate, caramel dosage form, or confectionery dosage form, and the dosage form is not particularly limited.

[0044] In addition to the active ingredient, the food composition according to the present disclosure may further contain excipients, saccharides, flavors, pigments, fats and oils, proteins, etc. as required.

[0045] In one implementation example, the composition may be a pharmaceutical composition.

[0046] The pharmaceutical composition may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, etc. Dosage forms for oral administration may be tablets, pills, soft and solid capsules, granules, powders, fine granules, solutions, emulsions or pellets, but are not limited thereto. Dosage forms for parenteral administration may be solutions, suspensions, emulsions, gels, injections, drip infusions, suppositories, patches or sprays, but are not limited thereto. The dosage form can be easily prepared according to ordinary methods in the art, and may further contain surfactants, excipients, hydrating agents, emulsification promoters, suspending agents, salts or buffers for osmotic pressure adjustment, colorants, spices, stabilizers, preservatives, preservatives or other commonly used adjuvants.

[0047] In one implementation example, the 3,4,5-trimethoxycinnamic acid thymol ester or its stereoisomer, salt, hydrate or solvate may be administered at a dose of 0.01 to 10 mg / kg / day.

[0048] 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 more, and may be 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.

[0049] The present disclosure will be described more specifically by the following examples. However, the following examples are merely illustrative for helping the understanding of the present disclosure, and the scope and range of the present disclosure are not limited thereto.

[0050] [Example] Preparation of 3,4,5-Trimethoxycinnamate Thymol Ester Thymol trimethoxycinnamate (Melasolv) with CAS number 504394-57-4 was obtained from COSMANN Co., Ltd. (located in Hwaseong City, Gyeonggi-do).

[0051] [Experimental Example] Evaluation of Hair Growth-Promoting Effect Using the “Two-Cell Assemblage” Assay (“Two-Cell Assemblage” Assay: A Simple in vitro Method for Screening Hair Growth-Promoting Compounds) (Front Cell Dev Biol. 2020 Nov 24;8:581528), the hair growth-promoting effect of 3,4,5-trimethoxycinnamate thymol ester (Melasolv) at concentrations of 10 ppm and 20 ppm was evaluated.

[0052] The “Two-Cell Assemblage” Assay is an evaluation method that co-cultures dermal papilla (DP) cells and outer root sheath (ORS) cells that make up the hair follicle to mimic the hair growth of an actual hair follicle. That is, the length growth of the “Two-Cell Assemblage” structure has the same mechanism as actual hair follicle growth and is used as a new evaluation method for hair growth-promoting efficacy.

[0053] 5,000 dermal papilla cells were seeded onto an ultra-low attachment 96-well plate to form 3D spheroids. After 24 hours, 5,000 outer root sheath cells (from the Industry-Academia Cooperation Foundation of Kyungpook National University) were added together with the test substance to create a "Two-Cell assemblage" structure, which was then cultured for 5 days under the conditions of 37 °C, 5% CO₂. After 5 days of culture, length growth was measured using a microscope (OLYMPUS, SZX16). The results are shown in Figure 1. (*p < 0.05, **p < 0.01, ***p < 0.001 compared to the control group)

[0054] Referring to Figure 1, when cultured for 5 days with the "Two-Cell Assemblage" structure after treatment with melasorb, a significant level of length growth promotion effect, i.e., hair growth effect, was confirmed.

Claims

1. A composition for promoting hair growth or hair growth, comprising 3,4,5-trimethoxycinnamate thymol ester or a stereoisomer, a pharma- ceutically acceptable salt, a hydrate or a solvate thereof as an active ingredient.

2. The composition of claim 1 , wherein the composition is for promoting hair length growth.

3. The composition according to claim 1, wherein the concentration of the active ingredient is from 0.1 to 100 g / L relative to the total volume of the composition.

4. The composition of claim 1 , wherein the composition is a cosmetic composition.

5. The composition according to claim 1 , wherein the composition is a skin topical agent.

6. The composition of claim 1 , wherein the composition is a food composition.

7. The composition of claim 1 , wherein the composition is a pharmaceutical composition.

8. The composition of claim 1, wherein the 3,4,5-trimethoxycinnamic acid thymol ester or a stereoisomer, salt, hydrate or solvate thereof is administered at a dose of 0.01 to 10 mg / kg / day.

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