Composition for preventing or improving skin aging, containing thymol ester compound

Abstract

The present specification relates to a composition capable of preventing or ameliorating skin aging by adjusting the aging index of melanocytes. The composition according to the present disclosure contains a thymol ester-based compound as an active ingredient, thereby being capable of exhibiting an effect of preventing or improving skin aging when applied to a subject in which skin cells become flat or large or beta-galactosidase of melanocytes is activated.

Description

Technical Field

[0001] The present specification relates to a composition for preventing or improving skin aging containing a thymol ester compound, and discloses a composition capable of preventing or improving skin aging by regulating the cell senescence of melanocytes. Background Art

[0002] As the quality of life improves, various methods are being studied not only to delay the aging of the body's internal organs, but also to delay the aging of the external organs.

[0003] The area of ​​greatest concern in relation to external aging is the skin. Skin aging is divided into intrinsic aging and photoaging based on biological processes. Intrinsic aging is chronological aging that occurs over time, while photoaging is a combination of degenerative changes in areas exposed to the sun and chronological aging.

[0004] Due to this aging process, the skin becomes dry, wrinkles appear, and the skin loses its elasticity. In particular, it is known that the most important free radicals and reactive oxygen species (ROS) exert oxidative stress on skin cells and inhibit or reduce the production of high molecular weight matrix (collagen, hyaluronic acid, elastin) that maintains the elasticity of the skin.

[0005] Thus, skin aging may be promoted through multiple complex cellular influences, but research on the correlation between melanocyte senescence and skin aging or the anti-aging mechanism of melanocytes is still incomplete. Summary of the invention

[0006] Technical issues to be solved

[0007] One aspect of the present invention is to provide a composition capable of preventing or improving skin aging by regulating the cellular senescence of melanocytes.

[0008] Solution to 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 its stereoisomers, salts, hydrates or solvates as an effective ingredient to reduce the senescence of melanocytes.

[0010] Effects of the Invention

[0011] In one aspect, the composition according to the present disclosure can delay the change of melanin becoming flat or enlarged.

[0012] On the other hand, the composition according to the present disclosure is capable of reducing the degree of activation of β-galactosidase. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 is a result showing a query using RNA-seq for drugs having a transcriptome profile similar to that of the composition according to an embodiment of the present disclosure;

[0014] Figure 2 is the result of determining whether the predicted transcriptome age (RNA-age) of melanocytes is reduced when the composition according to one embodiment of the present disclosure is treated;

[0015] Figure 3 is the result of observing the change in cell morphology when treating the composition according to one embodiment of the present disclosure;

[0016] Figure 4 The result is to observe whether the β-galactosidase in melanocytes is reduced when the composition according to one embodiment of the present disclosure is treated. DETAILED DESCRIPTION

[0017] 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.

[0018] In an exemplary implementation of the present invention, a composition for preventing or improving skin aging 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 effective ingredient to reduce the cellular senescence of melanocytes.

[0019] In another exemplary implementation of the present invention, a method for preventing or improving skin aging is provided, which comprises the step of administering a composition, wherein the composition comprises 3,4,5-trimethoxycinnamate thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or its stereoisomers, salts, hydrates or solvates as an active ingredient.

[0020] In one implementation example, the method for preventing or improving skin aging may be a method for reducing aging indicators of melanocytes, thereby preventing or improving skin aging.

[0021] In another exemplary implementation of the present invention, a use of 3,4,5-trimethoxycinnamate thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or its stereoisomers, salts, hydrates or solvates for preparing a composition for preventing or improving skin aging is provided.

[0022] In one implementation example, the composition for preventing or improving skin aging may be a composition for reducing aging indicators of melanocytes, thereby preventing or improving skin aging.

[0023] In another exemplary implementation of the present invention, a non-therapeutic use of 3,4,5-trimethoxycinnamate thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or its stereoisomers, salts, hydrates or solvates for preventing or improving skin aging is provided.

[0024] In one implementation example, the non-therapeutic use may be to reduce aging indicators of melanocytes, thereby preventing or improving skin aging.

[0025] In another exemplary implementation of the present invention, provided is 3,4,5-trimethoxycinnamate thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or a stereoisomer, salt, hydrate or solvate thereof for preventing or improving skin aging.

[0026] In one embodiment, 3,4,5-trimethoxycinnamate thymol ester or its stereoisomers, salts, hydrates or solvates can reduce aging indicators of melanocytes, thereby being used to prevent or improve skin aging.

[0027] 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.

[0028]

Chemical formula 1

[0029]

[0030] In the present specification, "isomers" include not only optical isomers (e.g., essentially pure enantiomers, essentially pure diastereomers or mixtures thereof), but also conformational isomers (i.e., isomers that differ only in the angle of one or more chemical bonds), position isomers (especially, tautomers) or geometric isomers (e.g., cis-trans isomers).

[0031] In the present specification, "essentially pure" means that, for example, when using enantiomers or diastereomers, the specific compound, for example, the 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, further preferably about 99% or more, and even more preferably about 99.5% or more (w / w).

[0032] 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.

[0033] 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.

[0034] 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.

[0035] 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.

[0036] In one embodiment, the composition can reduce cell senescence indicators of melanocytes.

[0037] In one implementation example, the cell senescence indicator may be β-galactosidase.

[0038] In one implementation, the composition can be applied to a subject whose melanocytes are flattened or enlarged.

[0039] In one implementation example, the composition can be applied to a subject whose melanocyte β-galactosidase is activated.

[0040] In one embodiment, the composition can reduce the RNA age of melanocytes.

[0041] In one implementation example, the composition can be administered in an amount ranging from 0.001 mg / kg / day to 2000 mg / kg / day.

[0042] For example, the dosage may be 0.001 mg / kg / day or more, 0.01 mg / kg / day or more, 0.1 mg / kg / day or more, 1 mg / kg / day or more, 10 mg / kg / day or more, 100 mg / kg / day or more, 500 mg / kg / day or more, 1000 mg / kg / day or more, or 1500 mg / kg / day or more; and may be 2000 mg / kg / day or less, 1500 mg / kg / day or less, 1000 mg / kg / day or less, 500 mg / kg / day or less, 100 mg / kg / day or less, 10 mg / kg / day or less, 1 mg / kg / day or less, 0.1 mg / kg / day or less, or 0.01 mg / kg / day or less.

[0043] For example, the composition can be administered in an amount of 0.5 mg / kg / day to 1500 mg / kg / day.

[0044] In one embodiment, the concentration of the thymol 3,4,5-trimethoxycinnamate or its stereoisomers, salts, hydrates or solvates may be 0.1 to 10% by weight based on the total weight of the composition.

[0045] For example, the concentration of the 3,4,5-trimethoxycinnamic acid thymol ester or its stereoisomers, salts, hydrates or solvates thereof, relative to the total weight of the composition, can be 0.1% by weight or more, 0.5% by weight or more, 1% by weight or more, 3% by weight or more, 5% by weight or more, 7% by weight or more, and can be 10% by weight or less, 7% by weight or less, 5% by weight or less, 3% by weight or less, 1% by weight or less, or 0.5% by weight or less.

[0046] In one implementation example, the composition may be a cosmetic composition.

[0047] 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.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] 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.

[0052] 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.

[0053] 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.

[0054] 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.

[0055] 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.

[0056] In one implementation example, the composition may be a composition for external use on the skin.

[0057] The skin external preparation composition is a general term for any type of composition that can be applied to the outside of the skin, and includes cosmetics of various dosage forms and the like.

[0058] In one embodiment, the composition can be an oral composition or a non-therapeutic oral composition.

[0059] The oral composition according to the present disclosure may be in liquid or solid dosage form, and may be tablets, capsules, soft capsules, pills, granules, beverages (drinks), fat-reducing bars, chocolate, caramel dosage forms or biscuit dosage forms, and its dosage form is not particularly limited.

[0060] In addition to the active ingredients, the oral composition according to the present disclosure may further include excipients, sugars, flavors, pigments, oils, proteins, etc. as needed.

[0061] 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.

[0062] Example

[0063] Preparation of 3,4,5-Trimethoxycinnamate ThymolEster

[0064] Thymol trimethoxycinnamate (Melasolv) with CAS number 504394-57-4 was purchased from COSMANN Co., Ltd. (located in Hwaseong, Gyeonggi-do).

[0065] Test example

[0066] Experimental Example 1 - Comparative Analysis of Transcriptome Profiles

[0067] Using RNA-seq, comparative analysis of drugs having transcriptome profiles similar to the RNA-seq data of 3,4,5-trimethoxycinnamate thymol ester (hereinafter, Melasolv) was performed.

[0068] Comparative analysis results of the top 10 properties of drugs with transcriptome patterns similar to Melasolv confirmed that they were highly correlated with anti-aging agents. Figure 1 As shown, it was confirmed that the transcriptome profiles of CD-1530, Sirolimus, and Vorinostat, which are known to have excellent anti-aging effects, were similar to that of Melasolv.

[0069] The PubChem and CAS numbers of the substances used above are shown below.

[0070] #CD 1530

[0071] PubChem CID:9952709

[0072] CAS:107430-66-0

[0073] #Sirolimus

[0074] PubChem CID:5284616

[0075] CAS:53123-88-9

[0076] #Vorinostat

[0077] PubChem CID:5311

[0078] CAS:149647-78-9

[0079] Experimental Example 2- Observation of Predicted Transcriptome Age (RNA-age)

[0080] Melanocytes were purchased from Cascade Biologics and cultured in the foreskin of newborn African-American males using Medium 254 mixed with human melanocyte growth supplement (Life technologies).

[0081] RNA was extracted from melanocytes treated with 10 ppm Melasolv for 24 hours using TRIzol reagent (Life technologies). The RNA was used to construct a library using the Illumina TruSeq Stranded Total RNA Library Prep kit (Illumina, San Diego, CA, USA), and then RNA-sequence analysis (transcriptome sequencing technology (RNA-sequencing)) was performed using a sequencing platform (NovaSeq 6000 platform; Illumina).

[0082] Then, a model predicting age (age) based on the expression values ​​of more than 16,000 genes based on RNA-seq data was applied to determine the age of melanocytes in the untreated control group (in Figure 2 The chart shows the RNA-age of melanocytes treated with Melasolv (-) and melanocytes. Specifically, for RNA-age, the RNAAgeCalc package, which can calculate the age of the transcriptome from RNAseq data, was used. In the transcriptome data, FPKM data was entered as input, and skin tissue was entered as argument for calculation.

[0083] (RNAAgeCalc pakage:https: / / bioconductor.org / packages / release / bioc / html / RNAAgeCalc.html,

[0084] Ren

[0085] Observe the results, such as Figure 2 As shown, it was confirmed that the RNA-age of melanocytes treated with Melasolv was reduced by about 4 years.

[0086] Experimental Example 3-Observation of cell morphology

[0087] Melanocytes were irradiated with 5 mJ / cm2 twice at 24-hour intervals using 1UVB UV irradiator (Bio-Sun). 2 After UVB, Melasolv was applied and cultured for 2 weeks. Photographs of cells were taken using an optical microscope (ECLIPSE TS100 from NIKON) to observe the shape of the cells. Figure 3 It was confirmed that when treated with ultraviolet rays (UVB) that cause cell senescence (in Figure 3 In the experiment, the skin cells were flattened or enlarged, as shown in the three spots in the middle of the photo that are slightly larger than the others. However, when Melasolv was further treated after UVB treatment (UVB+Melasolv), no large spots were seen, similar to the case of UVB treatment alone, and the condition was similar to the control group without UVB treatment, confirming that Melasolv reduced the changes in skin cells caused by UVB.

[0088] Test Example 4-Observation of the anti-aging index β-galactosidase

[0089] Melanocytes were irradiated with 5 mJ / cm2 twice at 24-hour intervals using 1UVB UV irradiator (Bio-Sun). 2 After UVB, the cells were treated with Melasolv and incubated for 2 weeks. In order to determine the degree of cell senescence, a beta-gal staining kit from Lifetechnologies was used for beta-galactosidase assay. After taking pictures using an optical microscope (ECLIPSE TS100 from NIKON), the number of cells stained with beta-galactosidase was counted.

[0090] refer to Figure 4 It was confirmed that when Melasolv was treated after ultraviolet (UVB) irradiation, β-galactosidase, an anti-aging indicator, in melanocytes was reduced to a statistically significant degree compared to the case of UVB irradiation alone.

[0091] Specific example

[0092] Specific example 1: A use of 3,4,5-trimethoxycinnamate thymol ester (3,4,5-Trimethoxycinnamate Thymol Ester) or its stereoisomers, salts, hydrates or solvates for preparing a composition for preventing or improving skin aging, wherein the composition reduces the senescence of melanocytes.

[0093] Specific example 2: A use, according to specific example 1, the composition reduces cell aging indicators of melanocytes.

[0094] Specific example 3: A use according to specific example 1 or 2, wherein the cell aging indicator is β-galactosidase.

[0095] Specific example 4: A use, according to any one of specific examples 1 to 3, the composition is suitable for an object whose melanocytes are flattened or enlarged.

[0096] Specific example 5: A use, according to any one of specific examples 1 to 4, the composition is suitable for an object whose melanocyte β-galactosidase is activated.

[0097] Specific example 6: A use according to any one of specific examples 1 to 5, wherein the composition reduces the RNA age of melanocytes.

[0098] Specific example 7: A use according to any one of specific examples 1 to 6, wherein the 3,4,5-trimethoxycinnamic acid thymol ester or its stereoisomer, salt, hydrate or solvate is administered in a dosage of 0.1 to 2000 mg / kg / day.

[0099] Specific example 8: A use, according to any one of specific examples 1 to 7, relative to the total weight of the composition, the concentration of 3,4,5-trimethoxycinnamic acid thymol ester or its stereoisomer, salt, hydrate or solvate is 0.1 to 10 weight %.

[0100] Specific example 9: A use, according to any one of specific examples 1 to 8, the composition is a cosmetic composition.

[0101] Specific example 10: A use, according to any one of specific examples 1 to 9, the composition is a skin external application composition.

Claims

1. A use of thymol 3,4,5-trimethoxycinnamate or its stereoisomers, salts, hydrates or solvates for preparing a composition for preventing or improving skin aging. The composition reduces cellular senescence of melanocytes.

2. The use according to claim 1, wherein: The composition reduces indicators of cellular senescence in melanocytes.

3. The use according to claim 2, wherein: The cell senescence indicator is β-galactosidase.

4. The use according to claim 1, wherein: The composition is suitable for subjects whose melanocytes are flattened or enlarged.

5. The use according to claim 1, wherein: The composition is suitable for a subject whose melanocyte β-galactosidase is activated.

6. The use according to claim 1, wherein: The composition reduces the RNA age of melanocytes.

7. 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 0.1 to 2000 mg / kg / day.

8. The use according to claim 1, wherein: The concentration of the thymol 3,4,5-trimethoxycinnamate or its stereoisomer, salt, hydrate or solvate is 0.1 to 10 wt % relative to the total weight of the composition.

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

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

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