Composition for enhancing skin vitality containing thymol ester-based compound

Abstract

To provide a composition capable of improving skin vitality reduced by stress.SOLUTION: A composition disclosed herein includes a thymol ester-based compound as an active ingredient, thereby promoting ATP production through mitochondrial activity and further restoring the vitality of skin cells reduced due to stress.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present specification relates to a composition for enhancing skin vitality, which contains a thymol ester compound, and discloses a composition that can improve skin vitality that has been reduced by stress. [Background technology]

[0002] Factors that cause skin stress include ultraviolet rays, harmful environments, excessive use of cosmetics, and mental stress.

[0003] When the skin is stressed by these various factors, it becomes sensitive and its regenerative ability decreases, which leads to a decrease in skin elasticity and a dull skin color. In addition, harmful environmental factors and mental stress can reduce the vitality of the skin, causing skin problems.

[0004] However, there is still insufficient research on the specific mechanisms and methods of improving skin vitality, which is reduced by stress. Therefore, research on methods of improving skin vitality at the cellular level is needed. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Korean Patent Publication No. 10-2502512 Summary of the Invention [Problem to be solved by the invention]

[0006] In one aspect, the present invention aims to provide a composition that can restore skin vitality that has been reduced by stress by activating mitochondria. [Means for solving the problem]

[0007] In one aspect, the present disclosure provides a composition for enhancing skin vitality comprising 3,4,5-trimethoxycinnamate thymol ester, or a stereoisomer, salt, hydrate or solvate thereof as an active ingredient. Effect of the Invention

[0008] In one aspect, the compositions of the present disclosure can improve skin vitality through mitochondrial activation.

[0009] In another aspect, the compositions of the present disclosure can improve skin vitality by promoting ATP production. [Brief description of the drawings]

[0010] [Figure 1] FIG. 2 is a diagram showing a procedure of an OCR (oxygen consumption rate) test according to an embodiment of the present disclosure. [Diagram 2] 1 is a graph showing mitochondrial activity, i.e., oxygen consumption rate (OCR), according to one embodiment of the present disclosure. [Diagram 3] 1 is a graph showing the expression results of mitophagy marker genes (VDAC, Parkin, PINK) according to one embodiment of the present disclosure. [Figure 4] 1 is a graph showing the expression results of mitophagy marker genes (VDAC, Parkin, PINK) according to one embodiment of the present disclosure. [Diagram 5] 1 is a graph showing the expression results of mitophagy marker genes (VDAC, Parkin, PINK) according to one embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The present invention will be described in more detail with reference to the following examples. However, the following examples are merely illustrative to aid in understanding the present invention, and are not intended to limit the scope of the present invention.

[0012] In an exemplary embodiment of the present invention, a composition for enhancing skin vitality is provided, comprising 3,4,5-trimethoxycinnamate thymol ester, or a stereoisomer, salt, hydrate or solvate thereof as an active ingredient.

[0013] Another exemplary implementation of the present invention provides a method for improving skin vitality, comprising administering a composition comprising 3,4,5-trimethoxycinnamate thymol ester, or a stereoisomer, salt, hydrate or solvate thereof as an active ingredient.

[0014] Another exemplary implementation of the present invention provides a use of 3,4,5-trimethoxycinnamate thymol ester or a stereoisomer, salt, hydrate or solvate thereof for preparing a composition for enhancing skin vitality.

[0015] Another exemplary implementation of the present invention provides 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.

[0016] Another exemplary implementation of the present invention provides thymol ester (3,4,5-trimethoxycinnamate thymol ester) or a stereoisomer, salt, hydrate or solvate thereof for improving skin vitality.

[0017] In one embodiment, the 3,4,5-trimethoxycinnamic acid 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):

[0018] [ka]

[0019] As used herein, "isomer" includes in particular 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 (especially tautomers) or geometric isomers (e.g., cis-trans isomers).

[0020] As used herein, "essentially pure," when used in connection with, for example, an enantiomer or diastereomer, means that a particular compound, exemplified by an enantiomer or diastereomer, is present in an amount of about 90% or more, preferably about 95% or more, more preferably about 97% or more or about 98% or more, even more preferably about 99% or more, and most preferably about 99.5% or more (w / w).

[0021] As used herein, "pharmaceutical acceptable" means capable of being approved, approved by a governmental or equivalent regulatory agency, listed in a pharmacopoeia, or other commonly recognized pharmacopoeia, for use in animals, and more particularly, in humans, by avoiding significant toxic effects when used in normal medicinal dosages.

[0022] As used herein, the term "pharmacologically acceptable salt" refers to a salt according to one embodiment of the present invention that is pharma-ceutically acceptable and has the preferred pharmacological activity of the parent compound. The salts are formed from (1) inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or from (2) acetic acid, propionic acid, hexanoic acid, cyclopentenepropionic 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-hydroxyethanes ... or (2) acid addition salts formed from organic acids such as benzoic 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, and muconic acid; or (3) salts formed when an acidic proton present in the parent compound is replaced.

[0023] As used herein, the term "hydrate" refers to a compound to which water is bound, and is a broad concept that includes an endocannabinoid compound in which there is no chemical bonding between the water and the compound.

[0024] As used herein, the term "solvate" refers to a higher-order compound formed between molecules or ions of a solute and molecules or ions of a solvent.

[0025] In one implementation, the enhancement of skin vitality may be at least one of enhancement of mitochondrial activity, enhancement of mitophagy activity, promotion of ATP production, and inhibition of stress hormone activity.

[0026] In one implementation, the stress hormone may be hydrocortisone.

[0027] In one embodiment, the 3,4,5-trimethoxycinnamic acid thymol ester or a stereoisomer, salt, hydrate or solvate thereof may be administered at a dose of 1 ug / kg to 1000 mg / kg.

[0028] In one embodiment, the concentration of the 3,4,5-trimethoxycinnamic acid thymol ester or its stereoisomer, salt, hydrate or solvate may be 0.0005-1% by weight based on the total weight of the composition.

[0029] For example, the concentration of the 3,4,5-trimethoxycinnamic acid thymol ester or a stereoisomer, salt, hydrate or solvate thereof 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.

[0030] Preferably, the concentration of said 3,4,5-trimethoxycinnamic acid thymol ester or a stereoisomer, salt, hydrate or solvate thereof may be 0.01-0.5% by weight based on the total weight of the composition.

[0031] In one implementation, the composition may be applied to a subject whose skin has become depleted due to stress.

[0032] In one embodiment, the composition may be applied to a subject with reduced mitochondrial activity, for example, the composition may be applied to a subject with reduced mitochondrial activity in skin cells due to stress to improve the vitality of the skin or skin cells.

[0033] Regarding mitochondrial activity, mitophagy is an intracellular degradation mechanism that removes damaged or unnecessary mitochondria and is important for controlling mitochondrial function in multiple cells and maintaining tissue function.

[0034] In one embodiment, the composition may be applied to a subject with reduced mitophagy activity. For example, the composition may be applied to a subject with reduced mitophagy activity in skin cells due to stress, thereby improving the vitality of the skin or skin cells.

[0035] In one embodiment, the composition may be applied to a subject with reduced ATP production. For example, the composition may 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.

[0036] In one embodiment, the composition may be a skin topical composition, which is a general term that may include anything that is applied to the skin, and may include cosmetics and pharmaceuticals in various dosage forms.

[0037] In one embodiment, the composition may be a food composition. The food composition may be in a liquid or solid form, such as a tablet, capsule, soft capsule, pill, granule, beverage (drink), diet bar, chocolate, caramel, or confectionery, and the form is not particularly limited. The food composition according to the present disclosure may contain excipients, sugars, flavors, colorants, oils and fats, proteins, etc., as necessary, in addition to the active ingredient.

[0038] In one implementation, the composition may be a cosmetic composition.

[0039] The appearance of said cosmetic composition comprises a cosmetically or dermatologically acceptable vehicle or base. It may be in any formulation suitable for topical application, for example in the form of a solution, gel, solid, paste-free anhydrous product, emulsion obtained by dispersing an oily phase in an aqueous phase, suspension, microemulsion, microcapsule, microgranule or vesicular dispersion of ionic (liposome) and non-ionic type, or in the form of a cream, lotion, milk, powder, ointment, spray or stick concealer. These compositions may be prepared according to the usual methods in the art. The composition according to the invention may also be used in the form of a foam or in the form of an aerosol composition further comprising a compressed propellant.

[0040] The cosmetic composition according to an embodiment of the present invention is not particularly limited in its formulation, and may be formulated into a cosmetic product such as, for example, a softening lotion, an astringent lotion, a nourishing lotion, a nourishing cream, a massage cream, a beauty serum, an eye cream, an eye essence, a cleansing cream, a cleansing foam, a cleansing water, a pack, a powder, a body lotion, a body cream, a body oil, or a body essence.

[0041] When the cosmetic composition of the present disclosure has a formulation of a paste, cream, or gel, animal fibers, plant fibers, wax, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide, or the like may be used as a carrier component.

[0042] When the cosmetic composition of the present disclosure is in the form of a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component, and particularly in the case of a spray, a propellant such as hydrochlorofluorocarbon, propane / butane, or dimethyl ether may be further included.

[0043] When the cosmetic composition of the present disclosure has a formulation of a solution or emulsion, a solvent, solvating agent, or emulsifier is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerin aliphatic esters, polyethylene glycol, and fatty acid esters of sorbitan.

[0044] When the cosmetic composition of the present disclosure has a dosage form of a suspension, liquid diluents such as water, ethanol, and propylene glycol, suspending agents such as ethoxylated stearyl alcohol, polyoxyethylene sorbitol esters, and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, and tragacanth may be used as carrier components.

[0045] When the formulation of the cosmetic composition of the present disclosure is a surfactant-containing cleanser, fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid monoesters, isethionates, imidazolium derivatives, methyl taurate salts, sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, ethoxylated glycerin fatty acid esters, and the like may be used as carrier components.

[0046] The cosmetic composition of the present disclosure may further contain functional additives and ingredients contained in general cosmetic compositions in addition to the active ingredients. The functional additives may include ingredients selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymeric peptides, polymeric polysaccharides, sphingolipids, and seaweed extracts.

[0047] The cosmetic composition of the present disclosure may further contain components contained in general cosmetic compositions together with the functional additives as necessary. Other components may include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, UV absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, colorants, fragrances, blood circulation promoters, cooling agents, antiperspirants, purified water, etc.

[0048] In one implementation, the composition may be a pharmaceutical composition.

[0049] In one implementation, the pharmaceutical composition may be for treating a subject suffering from reduced skin vitality due to stress.

[0050] In one implementation, the pharmaceutical composition may be for treating a subject with reduced mitochondrial activity.

[0051] In one embodiment, the pharmaceutical composition may be for treating a subject with reduced mitophagy activity.

[0052] In one implementation, the pharmaceutical composition may be for treating a subject with reduced ATP production.

[0053] In one implementation, the composition may be for preventing or improving skin aging.

[0054] In one implementation, the composition may be for preventing, ameliorating, or treating a disease associated with skin mitochondrial dysfunction.

[0055] For example, the disease associated with skin mitochondrial dysfunction or disorder may include at least one selected from the group consisting of psoriasis, atopic dermatitis (eczema), porphyria cutanea tarda, acne, and rosacea.

[0056] The term "prevention" as used herein refers to any action of suppressing or delaying the onset of a disease by administration of a pharmaceutical composition according to the present invention.

[0057] The term "amelioration" as used herein refers to any action that at least reduces a parameter associated with the condition being treated, e.g., the severity of a symptom.

[0058] The term "treatment" as used herein means any act of ameliorating or beneficially altering the symptoms of a disease by administration of a pharmaceutical composition according to the present invention.

[0059] The pharmaceutical composition may further contain pharmaceutical adjuvants such as preservatives, stabilizers, hydrating agents or emulsifying agents, salts for adjusting osmotic pressure and / or buffering agents, and other therapeutically useful substances, and may be formulated into various oral or parenteral dosage forms according to conventional methods.

[0060] The oral administration agent may be, for example, a tablet, a pill, a hard or soft capsule, a liquid, a suspension, an emulsion, a syrup, a powder, a powder, a fine granule, a granule, a pellet, etc., and these dosage forms may contain, in addition to the active ingredient, a surfactant, a diluent (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and glycine), a lubricant (e.g., silica, talc, stearic acid and its magnesium or calcium salt, and polyethylene glycol). The tablet may further contain a binder such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, and polyvinylpyrrolidine, and may optionally contain pharmaceutical additives such as disintegrants such as starch, agar, alginic acid or its sodium salt, an absorbent, a coloring agent, a flavoring agent, and a sweetener. The tablet may be prepared by a conventional mixing, granulating, or coating method. The parenteral administration form may be a transdermal administration form, such as, but not limited to, an injection, a drip infusion, an ointment, a lotion, a gel, a cream, a spray, a suspension, an emulsion, a suppository, or a patch.

[0061] Pharmaceutical compositions according to the present disclosure may be administered parenterally, rectally, topically, transdermally, subcutaneously, etc. Pharmaceutical compositions according to the present disclosure may be administered topically, for example, to the scalp.

[0062] Determining the dosage of the active ingredient is within the level of a person skilled in the art, and the daily dosage of the drug will vary depending on various factors such as the degree of progression, time of onset, age, health condition, and complications of the subject to be administered, but based on an adult, the composition may generally be 1 μg / kg to 1000 mg / kg, for example, 0.1 to 20 mg / Kg, 0.5 to 20 mg / Kg, or 1 to 20 mg / kg, preferably 5 to 10 mg / kg, administered 1 to 3 times a day, and the dosage is not intended to limit the scope of the present invention in any way.

[0063] The present invention will be described in more detail with reference to the following examples. However, the following examples are merely illustrative to aid in understanding the present invention, and are not intended to limit the scope of the present invention.

[0064] [Example] Preparation of 3,4,5-Trimethoxycinnamate Thymol Ester Thymol trimethoxycinnamate thymol ester (Mellasorb) with CAS number 504394-57-4 was obtained from COSMANN Co., Ltd. (Hwaseong-si, Gyeonggi-do).

[0065] [Test example] We examined whether mitochondrial activity was reduced by treating skin fibroblasts with the stress hormone hydrocortisone, and confirmed that Melasorb (3,4,5-trimethoxycinnamic acid thymol ester) improved mitochondrial activity. Furthermore, we confirmed whether the increase in mitochondrial activity was due to the activation of mitophagy in mitochondria.

[0066] Test Example 1 - Mitochondrial activity As shown in Figure 1, skin fibroblasts were cultured on OCR plates (8 × 10 3The skin fibroblasts were transplanted into a 30-well plate (10 μM, 24 hours) and treated with the stress hormones hydrocortisone (10 μM, 24 hours) and melasolv (5 ppm) for 24 hours, respectively, to observe mitochondrial activity (ATP energy production efficiency), i.e., maximal oxygen consumption rate (OCR). Specifically, the mitochondrial activity (ATP energy production efficiency), i.e., maximal oxygen consumption rate (OCR) was observed using Agilent's Seahorse XF Pro analyzer and the Seahorse XF cell mitochondrial stress measurement kit provided by the company, according to the standard protocol provided (Figure 2).

[0067] Referring to Figure 2, the maximum respiration rate was observed, and the treatment with Melasorb (5 ppm, 24 hours) showed a statistically significant higher value than the treatment with hydrocortisone alone. This was confirmed to be even higher than the control group that was not treated with anything.

[0068] In conclusion, we confirmed that compared to the control group (Ctrl), the cellular respiration rate (OCR) was decreased under the hydrocortisone treatment (stress-induced condition) and was restored by the Melasorb treatment. In conclusion, the stress-inhibited mitochondria function was restored by the Melasorb treatment.

[0069] Test Example 2 - Expression of mitophagy marker genes (VDAC, Parkin, PINK) Fibroblasts 10cm 2 3 x 10 cells in a cell culture dish 5The cells were plated 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 approximately 70% of their capacity, the cells were treated with (1) DMSO (control group), (2) hydrocortisone (10 μM) alone, or (3) hydrocortisone (10 μM) and Melasorb (5.5 μg / mL) for 24 hours.

[0070] RNA was extracted with easy-BLUE (iNtRON) reagent. cDNA samples were generated from 0.5 μg of RNA using the PrimeScript RT Reagent Kit. The resulting cDNA was amplified using AccuPower™ PCR Premix. PCR products were further analyzed using a PCR Thermal Cycler Dice.

[0071] Whether this contributes to the activation of mitophagy, which removes unnecessary components from mitochondria, was confirmed by measuring the decrease in expression of mitophagy marker genes (VDAC, Parkin, and PINK).

[0072] 3 to 5, it was confirmed that the expression of mitophagy genes increased when cells were treated with Melasorb, which was due to activation of mitophagy.

[0073] According to the present disclosure, the decrease in skin vitality (decrease in ATP production) caused by stress hormones can be restored by treatment with 3,4,5-trimethoxycinnamic acid thymol ester, which is expected not only to result in a significantly better recovery compared to the control group, but also to an increase to a level higher than the normal state.

[0074] In addition, 3,4,5-trimethoxycinnamic acid thymol ester can be presented as a material that promotes skin energy generation by activating mitophagy, a type of autophagy that occurs in mitochondria, and by containing it, a composition can be provided that restores the loss of skin vitality and vitality caused by stress.

Claims

1. A composition for enhancing skin vitality, comprising 3,4,5-trimethoxycinnamate thymol ester, or a stereoisomer, salt, hydrate or solvate thereof as an active ingredient.

2. The composition of claim 1 , wherein the skin vitality enhancement comprises at least one of enhancing mitochondrial activity, enhancing mitophagy activity, promoting ATP production, and inhibiting stress hormone activity.

3. 3. The composition of claim 2, wherein the stress hormone is hydrocortisone.

4. 2. 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 1 μg / kg to 1000 mg / kg.

5. The composition according to claim 1, wherein the concentration of said 3,4,5-trimethoxycinnamic acid thymol ester or its stereoisomers, salts, hydrates or solvates is from 0.0005 to 1% by weight relative to the total weight of the composition.

6. The composition of claim 1 , wherein the composition is applied to a subject whose skin has lost vitality due to stress.

7. The composition of claim 1 , wherein the composition is applied to a subject with reduced mitochondrial activity.

8. The composition according to claim 1 , wherein the composition is applied to a subject having reduced mitophagy activity.

9. The composition of claim 1 , wherein the composition is applied to a subject with reduced ATP production.

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

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

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

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

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