Composition for preventing or improving skin-aging containing a thymol ester-based compound

Abstract

To provide a composition capable of preventing or improving skin aging by controlling a senescence biomarker of melanocytes.SOLUTION: A composition according to the present disclosure includes a thymol ester-based compound as an effective ingredient, whereby when applied to a subject in which skin cells are flattened or enlarged, or β-galactosidase of melanocytes is activated, it can exhibit effect of preventing or improving skin aging.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present specification relates to a composition for preventing or improving skin aging, which contains a thymol ester compound, and discloses a composition that can prevent or improve skin aging by controlling cellular senescence of melanocytes. [Background technology]

[0002] As people's lives become more affluent, various researches are being conducted to slow down not only internal aging but also external aging of the body.

[0003] The area of ​​greatest concern in external aging is the skin, which can be divided into intrinsic aging, which is chronological aging that occurs over time according to biological processes, and photogenic aging, which is a complex combination of degenerative changes and chronological aging that occurs in areas exposed to sunlight.

[0004] This aging process causes the skin to become dry, wrinkle, and lose elasticity. In particular, free radicals and reactive oxygen species, which are of particular importance in the study of skin aging, are known to cause oxidative stress in skin cells and inhibit or reduce the production of polymeric matrices (collagen, hyaluronic acid, elastin) that maintain skin elasticity.

[0005] Thus, skin aging may be accelerated by effects on a variety of complex cells; however, there is still insufficient research on the correlation between melanocyte senescence and skin aging, or the anti-aging mechanisms of melanocytes. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Korean Patent Publication No. 10-2017-0075364 [Non-patent literature]

[0007] [Non-Patent Document 1] Ren X, Kuan PF(2020).RNAAgeCalc:A multi-tissue transcriptional age calculators.PLOS ONE,15(8),-20.doi:10.1371 / journal.pone.0237006 Summary of the Invention [Problem to be solved by the invention]

[0008] In one aspect of the present invention, an object is to provide a composition capable of preventing or ameliorating skin aging by controlling cellular senescence of melanocytes. [Means for solving the problem]

[0009] In one aspect, the present disclosure provides a cosmetic composition for preventing or improving skin aging, comprising 3,4,5-trimethoxycinnamate thymol ester or a stereoisomer, salt, hydrate or solvate thereof as an active ingredient, and reducing cellular senescence of melanocytes. Effect of the Invention

[0010] In one aspect, the compositions of the present disclosure can reduce the flattening or enlargement of melanocytes.

[0011] In another aspect, the compositions of the present disclosure can reduce the extent of activation of beta-galactosidase. [Brief description of the drawings]

[0012] [Figure 1]FIG. 1 shows the results of using RNA-seq to investigate drugs that have similar transcriptome patterns to a composition according to one embodiment of the present disclosure. [Diagram 2] FIG. 1 shows the results of measuring whether the predicted transcriptome age (RNA-age) of melanocytes is reduced when treated with a composition according to one embodiment of the present disclosure. [Diagram 3] FIG. 1 is a diagram showing the results of observing changes in cell morphology when treated with a composition according to one embodiment of the present disclosure. [Figure 4] FIG. 2 is a graph showing the results of observing whether β-galactosidase in melanocytes is reduced when treated with a composition according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] 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.

[0014] In an exemplary embodiment of the present invention, a composition for preventing or improving skin aging is provided, which comprises 3,4,5-trimethoxycinnamate thymol ester or a stereoisomer, salt, hydrate or solvate thereof as an active ingredient, and reduces cellular senescence of melanocytes.

[0015] In another exemplary embodiment of the present invention, there is provided a method for preventing or improving skin aging, comprising administering a composition comprising 3,4,5-trimethoxycinnamate thymol ester or a stereoisomer, salt, hydrate or solvate thereof as an active ingredient.

[0016] In one embodiment, the method for preventing or ameliorating skin aging may be a method for preventing or ameliorating skin aging by reducing an aging indicator of melanocytes.

[0017] Another exemplary embodiment 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 preventing or improving skin aging.

[0018] In one embodiment, the composition for preventing or improving skin aging may be a composition for preventing or improving skin aging by reducing aging indicators of melanocytes.

[0019] 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 preventing or ameliorating skin aging.

[0020] In one implementation, the non-therapeutic use may be to prevent or ameliorate skin aging by reducing indicators of aging in melanocytes.

[0021] 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 preventing or improving skin aging.

[0022] In one embodiment, 3,4,5-trimethoxycinnamate thymol ester or a stereoisomer, salt, hydrate or solvate thereof may be used to prevent or ameliorate skin aging by reducing aging indicators of melanocytes.

[0023] 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):

[0024] [ka]

[0025] 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).

[0026] 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).

[0027] 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.

[0028] 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.

[0029] As used herein, the term "hydrate" refers to a compound to which water is bound, and is a broad concept that includes an encapsulated compound in which there is no chemical bonding between the water and the compound.

[0030] 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.

[0031] In one implementation, the composition may reduce indicators of cellular senescence in melanocytes.

[0032] In one implementation, the cellular senescence indicator may be beta-galactosidase.

[0033] In one implementation, the composition may be applied to a subject in which the melanocytes have been flattened or enlarged.

[0034] In one implementation, the composition may be applied to a subject in which melanocyte beta-galactosidase is activated.

[0035] In one implementation, the composition may reduce the RNA age of melanocytes.

[0036] In one embodiment, the composition may be administered at a dose of 0.001 to 2000 mg / kg / day.

[0037] For example, the dosage may be at least 0.001 mg / kg / day, at least 0.01 mg / kg / day, at least 0.1 mg / kg / day, at least 1 mg / kg / day, at least 10 mg / kg / day, at least 100 mg / kg / day, at least 500 mg / kg / day, at least 1000 mg / kg / day, or at least 1500 mg / kg / day, and at most 2000 mg / kg / day, at most 1500 mg / kg / day, at most 1000 mg / kg / day, at most 500 mg / kg / day, at most 100 mg / kg / day, at most 10 mg / kg / day, at most 1 mg / kg / day, at most 0.1 mg / kg / day, or at most 0.01 mg / kg / day.

[0038] For example, the composition may be administered at a dose of 0.5 to 1500 mg / kg / day.

[0039] In one embodiment, the concentration of the 3,4,5-trimethoxycinnamic acid thymol ester or its stereoisomers, salts, hydrates or solvates may be from 0.1 to 10% by weight relative to the total weight of the composition.

[0040] For example, the concentration of the 3,4,5-trimethoxycinnamic acid thymol ester or stereoisomer, salt, hydrate or solvate thereof may be 0.1 wt.% or more, 0.5 wt.% or more, 1 wt.% or more, 3 wt.% or more, 5 wt.% or more, 7 wt.% or more, and may be 10 wt.% or less, 7 wt.% or less, 5 wt.% or less, 3 wt.% or less, 1 wt.% or less, or 0.5 wt.% or less, based on the total weight of the composition.

[0041] In one implementation, the composition may be a cosmetic composition.

[0042] 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.

[0043] 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.

[0044] 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.

[0045] 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.

[0046] 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.

[0047] 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.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] In one implementation, the composition may be a skin topical composition.

[0052] The topical skin composition is a general term that may include anything that is applied to the skin, and may include cosmetics and pharmaceuticals in various dosage forms.

[0053] In one embodiment, the composition may be a food composition.

[0054] The food composition according to the present disclosure may be in a liquid or solid dosage form, and may be in the form of a tablet, capsule, soft capsule, pill, granule, beverage (drinkable), diet bar, chocolate, caramel, or confectionery, and the dosage form is not particularly limited.

[0055] The food composition according to the present disclosure may further contain, in addition to the active ingredients, excipients, sugars, flavorings, colorants, oils and fats, proteins, and the like, as necessary.

[0056] 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. EXAMPLES

[0057] 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).

[0058] [Test example] Test Example 1 - Comparative analysis of transcriptome patterns Using RNA-seq, we compared and analyzed drugs with similar transcriptome patterns to the RNA-seq data from 3,4,5-trimethoxycinnamate thymol ester (Melasolv).

[0059] As a result of the comparative analysis, the top 10 drugs with similar transcriptome patterns to Melasorb were analyzed and found to be highly related to anti-aging agents. In particular, as shown in Figure 1, the transcriptome patterns of CD-1530, Sirolimus, and Vorinostat, which are known to have excellent anti-aging effects, were found to be similar to Melasorb.

[0060] The PubChem and CAS numbers of the substances used above are as follows: #CD1530 PubChem CID:9952709 CAS:107430-66-0 #Sirolimus PubChem CID:5284616 CAS:53123-88-9 #Vorinostat PubChem CID:5311 CAS:149647-78-9

[0061] Test Example 2 - Observation of predicted transcriptome age (RNA-age) Melonocytes were purchased from Cascade Biologics as cultured cells derived from the foreskin of a newborn African-American male and cultured in Medium 254 medium supplemented with human melanocyte growth supplement (Life Technologies).

[0062] RNA was extracted from melanocytes treated with 10 ppm of Melasorb for 24 hours using TRIzol reagent (Life Technologies). A library was prepared using the Illumina TruSeq Stranded Total RNA Library Prep kit (Illumina, San Diego, CA, USA), and then RNA-sequencing was performed using the NovaSeq 6000 platform (Illumina).

[0063] We then applied a model to predict age based on over 16,000 gene expression values ​​from the RNA-seq data, and measured the RNA age of untreated control melanocytes (- in the graph in Figure 2) and the RNA age of Melasorb-treated melanocytes. Specifically, we used the RNAAgeCalc package, which can calculate the transcriptome age from RNAseq data, to calculate the RNA age. Among the transcriptome data, FPKM data was entered as input, and skin tissue was entered as argument. (RNAAgeCalc package: https: / / bioconductor.org / packages / release / bioc / html / RNAAgeCalc.html, Non-Patent Document 1)

[0064] As a result of the observation, as shown in Figure 2, it was confirmed that the RNA age of melanocytes treated with Melasorb was reduced by approximately 4 years.

[0065] Test Example 3: Observation of cell morphology Melanocytes were exposed to 1 UVB UV irradiator (Bio-Sun) at 5 mJ / cm 2The cells were exposed to UVB twice at 24-hour intervals, then treated with Melasorb and cultured for two weeks. The cells were photographed using an optical microscope (NIKON ECLIPSE TS100) to examine the cell morphology. Referring to Figure 3, when treated with UVB, which induces senescence (UVB) (Chr UVB in Figure 3), the skin cells were flattened or enlarged, as seen in the three spots in the center of the photo that are slightly larger than the others. However, when treated with Melasorb after UV treatment (UVB + Melasorb), no large spots were observed as in the case of UV treatment alone, and the cells looked similar to the control group that was not treated with UV, confirming that Melasorb reduces the changes in skin cells caused by UVB.

[0066] Test Example 4 - Observation of anti-aging indicator beta-galactosidase Melanocytes were exposed to 1 UVB UV irradiator (Bio-Sun) at 5 mJ / cm 2 The cells were irradiated with 10 ...

[0067] Referring to FIG. 4, it can be seen that when UVB irradiation was followed by Melasorb treatment, beta-galactosidase, an indicator of anti-aging in melanocytes, was reduced to a statistically significant extent compared to UVB exposure alone.

Claims

1. The present invention comprises 3,4,5-trimethoxycinnamate thymol ester or a stereoisomer, salt, hydrate or solvate thereof as an active ingredient, A composition for preventing or improving skin aging, which reduces cellular aging of melanocytes.

2. The composition for preventing or improving skin aging according to claim 1 , wherein the composition reduces indicators of cellular aging of melanocytes.

3. The composition for preventing or improving skin aging according to claim 2 , wherein the cellular aging indicator is beta-galactosidase.

4. The composition of claim 1 , wherein the composition is applied to a subject in which melanocytes have been flattened or enlarged.

5. The composition of claim 1 , wherein the composition is applied to a subject in which melanocyte beta-galactosidase is activated.

6. The composition of claim 1 , wherein the composition reduces the RNA age of melanocytes.

7. 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 0.1 to 2000 mg / kg / day.

8. 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 0.1 to 10% by weight relative to the total weight of the composition.

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

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.

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