Composition for improving skin vigor containing thymol ester compound

Abstract

The present specification relates to a composition capable of ameliorating skin viability due to reduced stress. The composition according to the present disclosure contains a thymol ester compound as an active ingredient, thereby being capable of promoting ATP production through mitochondrial activity, and further repairing skin cell viability reduced due to stress.

Description

Technical Field

[0001] The present specification relates to a composition for improving skin vitality containing thymol ester compounds, and discloses a composition capable of improving skin vitality reduced due to stress. Background Art

[0002] Factors that accumulate skin stress include ultraviolet rays, harmful environment, excessive use of cosmetics, psychological pressure, etc.

[0003] Due to these various factors, when the skin is stressed, the skin becomes sensitive and the skin regeneration ability becomes low, thereby reducing skin elasticity and darkening the skin color. In addition, due to harmful environment or psychological pressure, the skin vitality decreases, which has the problem of causing skin problems.

[0004] However, the specific mechanism or improvement method for the reduced skin vitality due to stress has not been studied. Therefore, it is necessary to study a method that can improve skin vitality from the cellular stage. Summary of the invention

[0005] Technical issues to be solved

[0006] In one aspect of the present invention, it is intended to provide a composition capable of restoring skin vitality reduced by stress through mitochondrial activation.

[0007] Technical Solution

[0008] In one aspect, the present disclosure provides a composition for enhancing skin vitality, comprising 3,4,5-trimethoxycinnamate thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or a stereoisomer, salt, hydrate or solvate thereof as an active ingredient.

[0009] Effects of the Invention

[0010] In one aspect, the composition according to the present disclosure can improve skin vitality through mitochondrial activation.

[0011] On the other hand, the composition according to the present disclosure can promote ATP production and improve skin vitality. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 is a diagram showing a procedure of OCR (oxygen consumption rate) detection according to an embodiment of the present disclosure;

[0013] Figure 2 is a graph showing mitochondrial activity, namely, oxygen consumption rate (OCR) according to an embodiment of the present disclosure;

[0014] Figures 3 to 5 is a graph showing the expression results of mitophagy marker genes (VDA C, Parkin, PINK) according to one embodiment of the present disclosure. DETAILED DESCRIPTION

[0015] 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.

[0016] In an exemplary implementation of the present invention, a composition for enhancing skin vitality is provided, which 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 invention, a method for improving skin vitality 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.

[0018] In another exemplary implementation of the present invention, there is provided a use of 3,4,5-trimethoxycinnamate thymol ester (3,4,5-Trimethoxycinnamate Thym ol Ester) or a stereoisomer, salt, hydrate or solvate thereof for preparing a composition for enhancing skin vitality.

[0019] In another exemplary implementation of the present invention, a non-therapeutic use of thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or a stereoisomer, salt, hydrate or solvate thereof for improving skin vitality is provided.

[0020] In another exemplary implementation of the present invention, a thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or a stereoisomer, salt, hydrate or solvate thereof for improving skin vitality is provided.

[0021] 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.

[0022]

Chemical formula 1

[0023]

[0024] In the present specification, "isomers" include not only optical isomers (for example, essentially pure enantiomers, essentially pure diastereomers or mixtures thereof), but also conformational isomers (i.e., isomers in which one or more chemical bonds differ only in their angles), positional isomers (especially, tautomers or geometric isomers) (for example, cis-trans isomers).

[0025] 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).

[0026] 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.

[0027] 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.

[0028] 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.

[0029] 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.

[0030] In one implementation example, the enhancement of skin vitality may be one or more of enhancing mitochondrial activity, enhancing mitochondrial autophagy activity, enhancing ATP generation, and inhibiting stress hormone activity.

[0031] In one implementation example, the stress hormone may be hydrocortisone.

[0032] In one embodiment, the thymol 3,4,5-trimethoxycinnamate or its stereoisomers, salts, hydrates or solvates can be administered in an amount of 1 ug / kg to 1000 mg / kg.

[0033] In one embodiment, the concentration of thymol 3,4,5-trimethoxycinnamate or its stereoisomers, salts, hydrates or solvates may be 0.0005 to 1% by weight relative to the total weight of the composition.

[0034] For example, the concentration of the thymol 3,4,5-trimethoxycinnamate or its stereoisomers, salts, hydrates or solvates may be 0.0005% by weight or more, 0.001% by weight or more, 0.005% by weight or more, 0.01% by weight or more, 0.1% by weight or more or 0.5% by weight or more, relative to the total weight of the composition, and may be 1% by weight or less, 0.5% by weight or less, 0.1% by weight or less, 0.01% by weight or less, 0.005% by weight or less or 0.001% by weight or less.

[0035] Preferably, the concentration of the thymol 3,4,5-trimethoxycinnamate or its stereoisomers, salts, hydrates or solvates may be 0.01-0.5 wt % relative to the total weight of the composition.

[0036] In one implementation, the composition can be suitable for a subject whose skin vitality is reduced due to stress.

[0037] In one implementation example, the composition can be applied to a subject with reduced mitochondrial activity. For example, the composition can be applied to a subject with reduced mitochondrial activity in skin cells due to stress, thereby improving the vitality of the skin or skin cells.

[0038] Regarding mitochondrial activity, mitophagy, as an intracellular breakdown mechanism that removes damaged or unnecessary mitochondria, regulates mitochondrial function in multiple cells and is important in maintaining tissue function.

[0039] In one implementation example, the composition can be applied to a subject with reduced mitochondrial autophagy activity. For example, the composition can be applied to a subject with reduced mitochondrial autophagy activity in skin cells due to stress, thereby improving the vitality of the skin or skin cells.

[0040] In one implementation example, the composition can be applied to a subject with reduced ATP production. For example, the composition can be applied to a subject with reduced ATP production in skin cells due to stress, thereby improving the vitality of the skin or skin cells.

[0041] In one embodiment, the composition may be a composition for external use on the skin. The composition for external use on the skin is a general term for any type of composition that can be applied to the outside of the skin, and includes cosmetics and pharmaceuticals of various dosage forms.

[0042] In one embodiment, the composition can be an oral composition or a non-therapeutic oral composition.

[0043] The oral composition can be a liquid or solid dosage form, and can be a tablet, capsule, soft capsule, pill, granule, beverage (drink agent), fat-reducing bar, chocolate, caramel dosage form or biscuit dosage form, and its dosage form is not particularly limited. In addition to the active ingredient, the oral composition according to the present disclosure can include appropriate amounts of excipients, sugars, spices, pigments, oils, proteins, etc. as needed.

[0044] In one implementation example, the composition may be a cosmetic composition.

[0045] 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.

[0046] The dosage form of the cosmetic composition according to one embodiment of the present invention is not particularly limited, and can be, for example, 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.

[0047] 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.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] 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.

[0052] 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.

[0053] 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.

[0054] In one implementation example, the composition may be a pharmaceutical composition.

[0055] In one implementation, the pharmaceutical composition can be used to treat a subject with reduced skin vitality due to stress.

[0056] In one embodiment, the pharmaceutical composition can be used to treat a subject with reduced mitochondrial activity.

[0057] In one embodiment, the pharmaceutical composition can be used to treat a subject with reduced mitochondrial autophagy activity.

[0058] In one embodiment, the pharmaceutical composition can be used to treat a subject with reduced ATP production.

[0059] In one implementation example, the composition can be used to prevent or improve skin aging.

[0060] In one embodiment, the composition can be used to prevent, improve or treat skin mitochondrial dysfunction-related diseases.

[0061] For example, the skin mitochondrial dysfunction or disorder-related diseases may include one or more selected from the group consisting of psoriasis, atopic dermatitis (eczema), porphyria cutanea tarda, acne and rosacea.

[0062] The term "prevention" as used herein refers to all actions to inhibit or delay a disease by administering the pharmaceutical composition according to the present invention.

[0063] As used herein, the term "improvement" refers to any parameter related to the state of treatment, such as at least a reduction in symptoms.

[0064] The term "treatment" used herein refers to all actions to improve or ameliorate the symptoms of a disease by administering the pharmaceutical composition according to the present invention.

[0065] The pharmaceutical composition may further contain preservatives, stabilizers, wettable powders or emulsifiers, salts for adjusting osmotic pressure and / or buffers, and other pharmaceutical adjuvants and other therapeutically useful substances. According to conventional methods, the pharmaceutical composition may be formulated into various oral or parenteral dosage forms.

[0066] As the oral administration agent, for example, there are tablets, pills, hard capsules and soft capsules, liquids, suspensions, emulsifiers, syrups, powders, granules, granules, spheres, etc. In addition to the active ingredients, these dosage forms may contain surfactants, diluents (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine), lubricants (e.g., silicon dioxide, talcum powder, stearic acid and its magnesium or calcium salt and polyethylene glycol). Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinyl pyrrolidone, and may contain pharmaceutical additives such as disintegrants such as starch, agar, alginic acid or its sodium salt, absorbents, colorants, flavoring agents and sweeteners according to the circumstances. The tablets may be prepared by conventional mixing, granulation or coating methods. In addition, the non-oral administration form may be a transdermal dosage form, for example, an injection, a drip, an ointment, an emulsion, a gel, a cream, a spray, a suspension, an oil, a suppository, a patch, etc., but is not limited thereto.

[0067] The pharmaceutical composition according to the present disclosure can be administered parenterally, rectally, topically, transdermally, subcutaneously, etc. The pharmaceutical composition according to the present disclosure can be topically administered to the scalp, for example.

[0068] The dosage of the active ingredient is determined within the level of those skilled in the art. The daily dose of the drug depends on various factors such as the degree of disease progression, onset time, age, health status, complications, etc. of the subject. However, based on adults, the composition can generally be administered in an amount of 1 μg / kg to 1000 mg / kg. For example, 0.1 mg / Kg to 20 mg / Kg, 0.5 mg / Kg to 20 mg / Kg or 1 mg / Kg to 20 mg / Kg, preferably 5 mg / Kg to 10 mg / Kg, can be administered once to three times per day. The dosage does not limit the scope of the present invention in any way.

[0069] 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.

[0070] Example

[0071] Preparation of 3,4,5-Trimethoxycinnamate ThymolEster

[0072] Thymol trimethoxycinnamate (Melasolv) with CAS number 504394-57-4 was purchased from COSMANN Co., Ltd. (located in Hwaseong, Gyeonggi-do).

[0073] Test example

[0074] The stress hormone hydrocortisone was administered to skin fibroblasts to confirm whether mitochondrial activity decreased, and the mitochondrial activity-improving effect was confirmed by Melasolv (3,4,5-trimethoxycinnamic acid thymol ester). In addition, it was confirmed whether the increase in mitochondrial activity was based on the activation of mitophagy generated in mitochondria.

[0075] Test Example 1-Mitochondrial Activity

[0076] like Figure 1 As shown, skin fibroblasts were transplanted into OCR plates (8*10 3The skin fibroblasts were treated with stress hormone hydrocortisone (10uM, 24hrs) and 5ppm Melasolv for 24 hours, and the mitochondrial activity (ATP energy generation efficiency), i.e., the maximum oxygen consumption rate (OCR) was observed. Specifically, the mitochondrial activity (ATP energy generation efficiency), i.e., the maximum oxygen consumption rate (OCR) was observed using the Seahorse XF Pro analyzer from Agilent and the Seahorse XF Cell Mitochondrial Stress Assay Kit provided by the same company according to the standard protocol provided. Figure 2 ).

[0077] refer to Figure 2 The results of observing the maximum respiration rate showed that when Mela solv was treated (5ppm, 24hrs), it showed a significantly higher statistical value compared to the case of only treating hydrocortisone, and it was also confirmed that it increased above the control group without any treatment.

[0078] Finally, it was confirmed that the cellular respiration rate (OCR) decreased under the condition of hydrocortisone treatment (stress-induced condition) compared to the control group (Ctrl), and it was restored when Melasolv was treated. Finally, the mitochondrial function that was impaired by stress was restored by Melasolv treatment.

[0079] Experimental Example 2-Expression of Mitochondrial Autophagy Marker Genes (VDAC, Parkin, PINK)

[0080] To 10cm 2 Cell culture dishes were plated at 3x 10 5Fibroblasts were seeded at a concentration of 10 cells / dish and cultured in 10 ml of Minimum Essential Medium Eagle (MEM) medium containing 10% FBS (fetal bovine serum) and 1% penicillin streptomycin. After 24 hours, when the cells reached about 70%, the cells were treated with (1) DMSO (control group) or (2) hydrocortisone (10 μM) alone or (3) hydrocortisone (10 μM) and Melasolv (5.5 μg / ml) for 24 hours.

[0081] RNA was extracted using easy-BLUE (iNtRON) reagent. cDNA samples were generated from 0.5 μg of RNA using PrimeScript RT kit. TM The cDNA was amplified by PCR Premix and the PCR product was further analyzed using a fluorescent quantitative PCR instrument (PCR Thermal Cycler Dice).

[0082] By reducing the expression of mitophagy marker genes (VDAC, Parkin, PINK), we examined whether this contributes to the activation of mitophagy, which removes unnecessary factors from mitochondria.

[0083] refer to Figure 3-5 It was confirmed that when Melasolv was treated, the expression of mitophagy genes increased, thereby contributing to the activation of mitophagy.

[0084] According to the present disclosure, the decrease in skin vitality (decrease in ATP production) caused by stress hormones can be repaired by treating 3,4,5-trimethoxycinnamic acid thymol ester, and compared with the control group, this exceeds the repair ability and can also be expected to be significantly increased above the normal level.

[0085] In addition, as a material that promotes skin energy production by activating mitophagy (a type of autophagy produced in mitochondria), 3,4,5-trimethoxycinnamic acid thymol ester can be proposed, and a composition comprising 3,4,5-trimethoxycinnamic acid thymol ester can be provided to repair the reduction of skin vitality and skin vitality caused by stress.

[0086] Specific example

[0087] Specific example 1: 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 enhancing skin vitality.

[0088] Specific example 2: A use according to Specific example 1, wherein the enhancement of skin vitality is one or more of enhancing mitochondrial activity, enhancing mitochondrial autophagy activity, enhancing ATP production and inhibiting stress hormone activity.

[0089] Specific example 3: A use according to specific example 1 or 2, wherein the stress hormone is hydrocortisone.

[0090] Specific example 4: A use according to any one of specific examples 1 to 3, wherein the 3,4,5-trimethoxycinnamic acid thymol ester or its stereoisomer, salt, hydrate or solvate is administered in a dosage of 1 ug / kg to 1000 mg / kg.

[0091] Specific example 5: A use according to any one of specific examples 1 to 4, wherein the concentration of 3,4,5-trimethoxycinnamic acid thymol ester or its stereoisomer, salt, hydrate or solvate is 0.0005 to 1 weight % relative to the total weight of the composition.

[0092] Specific example 6: A use, according to any one of specific examples 1 to 5, the composition is suitable for a subject whose skin vitality is reduced due to stress.

[0093] Specific example 7: A use, according to any one of specific examples 1 to 6, the composition is suitable for a subject with reduced mitochondrial activity.

[0094] Specific example 8: A use, according to any one of specific examples 1 to 7, the composition is suitable for a subject with reduced mitochondrial autophagy activity.

[0095] Specific example 9: A use, according to any one of specific examples 1 to 8, the composition is suitable for a subject with reduced ATP production.

[0096] Specific example 10: A use, according to any one of specific examples 1 to 9, the composition is a skin external application composition.

[0097] Specific example 11: A use, according to any one of specific examples 1 to 10, the composition is a cosmetic composition.

[0098] Specific example 12: A use, according to any one of specific examples 1 to 11, wherein the composition is a pharmaceutical composition.

Claims

1. Use of thymol 3,4,5-trimethoxycinnamate or its stereoisomers, salts, hydrates or solvates for preparing a composition for enhancing skin vitality.

2. The use according to claim 1, wherein: The improvement of skin vitality includes at least one of improving mitochondrial activity, improving mitochondrial autophagy activity, improving ATP generation and inhibiting stress hormone activity.

3. The use according to claim 2, wherein: The stress hormone is hydrocortisone.

4. The use according to claim 1, wherein: The thymol 3,4,5-trimethoxycinnamate or its stereoisomer, salt, hydrate or solvate is administered in an amount of 1 ug / kg to 1000 mg / kg.

5. The use according to claim 1, wherein: The concentration of thymol 3,4,5-trimethoxycinnamate or its stereoisomers, salts, hydrates or solvates is 0.0005 to 1% by weight relative to the total weight of the composition.

6. The use according to claim 1, wherein: The composition is suitable for use in subjects suffering from reduced skin vitality due to stress.

7. The use according to claim 1, wherein: The composition is suitable for use in subjects with reduced mitochondrial activity.

8. The use according to claim 1, wherein: The composition is suitable for a subject with reduced mitochondrial autophagy activity.

9. The use according to claim 1, wherein: The compositions are suitable for use in subjects with reduced ATP production.

10. The use according to claim 1, wherein: The composition is a composition for external use on the skin.

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

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

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