Composition for improving skin wrinkles

Abstract

The present invention relates to a composition for reducing skin wrinkles and a method for providing information for selecting a customized substance for reducing wrinkles, the method comprising identifying bases at polymorphic sites of genetic polymorphism markers that have significance associated with the degree of skin wrinkles. The present invention also relates to a composition for diagnosing whether a skin type is prone to wrinkles, the composition comprising a probe capable of detecting or an agent capable of amplifying a genetic polymorphism marker that has significance associated with the degree of skin wrinkles, a kit or microarray including the composition, and a method for providing information on whether a skin type is prone to wrinkles using the genetic polymorphism marker or a combination of markers. The wrinkles relate to fine wrinkles, wrinkles in sagging pores, or nasolabial folds.

Description

[Technical Field]

[0001] The present invention relates to a composition for reducing skin wrinkles and a method for providing information for selecting a customized substance for reducing wrinkles, the method comprising identifying bases at polymorphic sites of genetic polymorphism markers that have significance associated with the degree of skin wrinkles. The present invention also relates to a composition for diagnosing whether or not a person has a wrinkle-prone skin type, the composition comprising a probe capable of detecting or an agent capable of amplifying a genetic polymorphism marker that has significance associated with the degree of skin wrinkles, a kit or microarray comprising the composition, and a method for providing information on whether or not a person has a wrinkle-prone skin type using the genetic polymorphism marker or a combination of markers. The wrinkles relate to fine wrinkles, wrinkles in sagging pores, or nasolabial folds. [Background technology]

[0002] The skin is a protective barrier with various physiological functions and also an important organ for achieving aesthetic appeal. Skin aging occurs in two main processes. Intrinsic aging refers to changes that occur over time without any specific environmental factors. Photoaging, or extrinsic aging, refers to changes that occur on the face, neck, and hands due to long-term exposure to environmental factors such as sunlight. Of these two aging processes, the loss of collagen in the dermis is most closely related to the development of wrinkles. One of the major causes of intrinsic aging is a decrease in the ability to produce new collagen fibers due to aging of skin fibroblasts. Another cause of extrinsic aging is a decrease in the ability to produce new collagen fibers due to damage to skin fibroblasts caused by ultraviolet rays and active oxygen, or a decrease in the total amount of collagen in the dermis due to an increase in collagen-degrading enzymes.

[0003] Skin aging, including skin aging, loss of elasticity, and pigmentation, naturally occurs with aging. Previously, the trend was to treat these signs after they appeared and then eliminate them. However, recent advances in genetic research have led to more proactive skin care that can maintain beautiful skin for longer by understanding genetic predispositions (Kemp et al., Molecules. 2017 Feb 26;22(3), 2017). In particular, various companies are now offering genetic testing services that analyze SNPs in an individual's DNA to identify various characteristics, such as through direct-to-consumer (DTC) testing. Skin genetic testing analyzes SNPs (Single Nucleotide Polymorphisms) in an individual's unique DNA that are associated with skin pigmentation, elasticity, aging, and vitamin C levels to identify skin characteristics and help prevent skin aging and provide effective skin care.

[0004] Currently, a wide variety of genetic polymorphism markers have been identified, but most are related to skin color, whitening, moisture, UV rays, etc., and it is rare for mechanistic research to be conducted. In particular, it appears that there have been few cases where the mechanisms of wrinkle-related polymorphism markers, specifically those related to microwrinkles in the skin, those related to wrinkles in sagging pores, and those related to nasolabial folds, have been studied or customized materials have been developed for them. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Kemp et al., Molecules. 2017 Feb 26;22(3), 2017 [Non-patent document 2] Wu and Wallace, Genomics 4, 560 (1989) [Non-patent document 3] Landegren et al., Science 241, 1077 (1988) [Non-patent document 4] Kwoh et al., Proc. Natl. Acad. Sci. USA 86, 1173 (1989) [Non-Patent Document 5] Guatelli et al., Proc. Natl. Acad. Sci. USA 87,1874 (1990) [Non-patent document 6] Cell Death & Disease volume 9,Article number:735 (2018) [Non-Patent Document 7] Neurology Apr 2019,92 (15 Supplement) P4.6-062 Summary of the Invention [Problem to be solved by the invention]

[0006] The inventors decided to establish a skin characteristic classification system for Koreans by building big data on genetic information and skin type information, and established scientific skin classification standards by understanding the genetic characteristics that determine individual skin characteristics. Based on this, they developed personalized active ingredients and made strenuous efforts to contribute to the development of customized cosmetics for each skin characteristic through the subdivision of various products. As a result, they selected specific single nucleotide polymorphism (SNP) markers that have a significant correlation with fine wrinkles, wrinkles caused by sagging pores, and nasolabial folds, and confirmed that they can provide personalized substances that are useful for improving fine wrinkles, wrinkles caused by sagging pores, and nasolabial folds based on genetic information. [Means for solving the problem]

[0007] One object of the present invention is to provide a composition for improving microwrinkles on the skin. Another object of the present invention is to provide a cosmetic composition or a quasi-drug composition containing the composition as an active ingredient.

[0008] Another object of the present invention is to provide an information providing method for selecting a customized substance for improving microwrinkles, which includes a step of identifying the base of a polymorphic site of a significant single nucleotide polymorphism marker associated with the degree of microwrinkles on the skin.

[0009] One object of the present invention is to provide a single nucleotide polymorphism (SNP) marker for diagnosing whether or not a skin type is prone to microwrinkles.

[0010] Another object of the present invention is to provide a composition for diagnosing whether or not a skin type is prone to microwrinkles, comprising a probe capable of detecting or amplifying a single nucleotide polymorphism (SNP) marker for diagnosing whether or not a skin type is prone to microwrinkles.

[0011] Another object of the present invention is to provide a kit or microarray containing the composition for diagnosing whether or not a person has a skin type prone to microwrinkles.

[0012] Another object of the present invention is to provide a method for providing information on whether a person has a skin type prone to microwrinkles, which method includes the step of identifying a polymorphic site of the single nucleotide polymorphism marker.

[0013] One object of the present invention is to provide a composition for improving wrinkles in sagging pores.

[0014] It is still another object of the present invention to provide a cosmetic composition or a quasi-drug composition containing the above composition as an active ingredient.

[0015] Another object of the present invention is to provide an information providing method for selecting a customized substance for improving wrinkles in sagging pores, which includes a step of identifying the base of a polymorphic site of a significant single nucleotide polymorphism marker associated with the degree of wrinkles in sagging pores.

[0016] One object of the present invention is to provide a single nucleotide polymorphism (SNP) marker for diagnosing whether or not a person has a skin type that is prone to wrinkles due to sagging pores.

[0017] Another object of the present invention is to provide a composition for diagnosing whether or not a skin type is prone to wrinkles due to sagging pores, comprising a probe capable of detecting or a preparation capable of amplifying a single nucleotide polymorphism (SNP) marker for diagnosing whether or not a skin type is prone to wrinkles due to sagging pores.

[0018] Another object of the present invention is to provide a kit or microarray containing the above composition for diagnosing whether a person has a skin type prone to wrinkles due to sagging pores.

[0019] Another object of the present invention is to provide a method for providing information on whether a person has a skin type prone to sagging pores and wrinkles, which method includes the step of identifying a polymorphic site of the single nucleotide polymorphism marker.

[0020] One object of the present invention is to provide a composition for improving nasolabial folds.

[0021] It is still another object of the present invention to provide a cosmetic composition or a quasi-drug composition containing the above composition as an active ingredient.

[0022] Another object of the present invention is to provide an information providing method for selecting a customized substance for improving nasolabial folds, which includes a step of identifying the base of a polymorphic site of a significant single nucleotide polymorphism marker associated with the degree of nasolabial folds.

[0023] One object of the present invention is to provide a single nucleotide polymorphism (SNP) marker for diagnosing whether or not a person has a skin type that is prone to developing nasolabial folds.

[0024] Another object of the present invention is to provide a composition for diagnosing whether or not a skin type is prone to the development of nasolabial folds, comprising a probe capable of detecting or amplifying a single nucleotide polymorphism (SNP) marker for diagnosing whether or not a skin type is prone to the development of nasolabial folds.

[0025] Another object of the present invention is to provide a kit or microarray containing the composition for diagnosing whether a person has a skin type prone to developing nasolabial folds.

[0026] Another object of the present invention is to provide a method for providing information on whether a person has a skin type prone to developing nasolabial folds, the method comprising the step of identifying a polymorphic site of the single nucleotide polymorphism marker. [Effects of the Invention]

[0027] The present invention provides a method for predicting the degree of skin wrinkles in an individual by using a genetic polymorphism marker having significance associated with the degree of skin wrinkles, and further provides a method for developing customized ingredients or products that alleviate the degree of skin wrinkles based on the information on the genetic polymorphism markers observed in an individual. The wrinkles relate to fine wrinkles, wrinkles due to sagging pores, or nasolabial folds. [Brief explanation of the drawings]

[0028] [Figure 1] This shows the promotion of collagen expression by treatment with phloretin and / or oryzanol. [Figure 2] This shows the promotion of collagen expression by treatment with lupeol and / or sucralfate. [Figure 3] This shows Antera 3D and the location of the analysis of fine wrinkles under the eyes. [Figure 4] 1 shows the reference image used for expert visual evaluation. [Figure 5]This shows the improvement rate of fine wrinkles compared to retinol when a cream containing phloretin, oryzanol, lupeol, and sucralfate was applied. [Figure 6] 1 shows the suppression of BNC2 expression by treatment with phloretin and / or oryzanol. [Figure 7] 1 shows the promotion of EDAR expression by treatment with lupeol and / or sucralfate. [Figure 8] This shows the improvement rate of fine wrinkles compared to retinol when a cream containing phloretin, oryzanol, lupeol, and sucralfate was applied to a high-risk group. [Figure 9] This shows the improvement rate of fine wrinkles compared to retinol when a cream containing phloretin, oryzanol, lupeol, and sucralfate was applied to a high-risk group. [Figure 10] This shows the promotion of collagen expression by treatment with fucoidan and / or N-feruloyl serotonin. [Figure 11] This shows the promotion of collagen expression by treatment with emodin and / or formononetin. [Figure 12] This shows the Antera 3D and cheek analysis position. [Figure 13] 1 shows the reference image used for expert visual evaluation. [Figure 14] This shows the improvement rate of sagging pores compared to retinol when a cream containing fucoidan, N-feruloyl serotonin, emodin, and formononetin was applied. [Figure 15] 1 shows the suppression of SGPP2 expression by treatment with fucoidan and / or N-feruloyl serotonin. [Figure 16] 1 shows the promotion of ADIPOQ expression by treatment with emodin and / or formononetin. [Figure 17]This shows the improvement rate of wrinkles in sagging pores compared to retinol when a cream containing fucoidan, N-feruloyl serotonin, emodin, and formononetin was applied to a high-risk group. [Figure 18] This shows the improvement rate of wrinkles in sagging pores compared to retinol when a cream containing fucoidan, N-feruloyl serotonin, emodin, and formononetin was applied to a high-risk group. [Figure 19] This shows the promotion of collagen expression by treatment with the substance of the present invention. [Figure 20] This shows the promotion of collagen expression by treatment with the substance of the present invention. [Figure 21] This shows the Antera 3D and the location of nasolabial fold analysis. [Figure 22] 1 shows the reference image used for expert visual evaluation. [Figure 23] This shows the improvement rate of nasolabial folds when a cream containing the substance of the present invention is applied, compared to retinol. [Figure 24] This shows the improvement rate of nasolabial folds in comparison with retinol when a cream containing the substance of the present invention was applied to a high-risk group. DETAILED DESCRIPTION OF THE INVENTION

[0029] This will be explained in more detail as follows. Meanwhile, each description and embodiment disclosed in the present invention also applies to each other description and embodiment. That is, any combination of various elements disclosed in the present application falls within the scope of the present invention. Furthermore, the following specific description is not considered to limit the category of the present application.

[0030] Additionally, those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein, and such equivalents are intended to be encompassed by the present invention.

[0031] In one aspect of the present invention, the present invention provides a composition for improving microwrinkles on the skin. For example, the composition contains, as an active ingredient, one or more substances selected from the group consisting of phloretin, oryzanol, lupeol, and sucralfate. For another example, the composition may contain, as active ingredients, (i) phloretin and oryzanol; (ii) lupeol and sucralfate; or (iii) phloretin, oryzanol, lupeol, and sucralfate, but is not limited thereto.

[0032] The term "phloretin" refers to a dihydrochalcone plant-derived phenol with a C6-C3-C6 skeleton, which is abundant in apples (mainly the skin) and apple leaves, and exists as the free or glucosidic form phloridzin (phloretin 2'-O-glucose). Phloretin has many biological functions, including antioxidant and anticancer activity, and is associated with the prevention of heart disease. The molecular formula of phloretin is C 15 H 14 It has a molecular weight of 274.272 and can be represented by the following chemical formula 1. The method for obtaining phloretin is not limited, and it can be chemically synthesized by a method known in the art or a commercially available substance.

[0033] [ka]

[0034] The term "oryzanol" refers to a substance extracted from rice bran, corn, barley, etc., and is a compound consisting of a ferulic acid nucleus and ester bonds between sterols, such as campesterol and β-sitosterol, and triterpene alcohols. Oryzanol is known as a major ingredient in drugs for treating menopausal disorders and autonomic nervous system disorders. The method for obtaining oryzanol is not limited, and it can be chemically synthesized by methods known in the art or commercially available. According to one embodiment of the present invention, the oryzanol may be, but is not limited to, gamma-oryzanol (HMARU PHAROUS CO.).

[0035] The term "lupeol" is a fat-soluble component derived from plants, specifically from legumes, that can directly dissolve sebum, penetrate into pores, kill acne bacteria, and suppress various causes of acne, such as sebum production, inflammation, and keratinization, which are the causes of acne. The molecular formula of lupeol is C 30 H 50 It has a molecular weight of 426.729 and can be represented by the following chemical formula 2. The method for obtaining lupeol is not limited, and it can be chemically synthesized by a method known in the art or a commercially available substance.

[0036] [ka]

[0037] The term "sucralfate" refers to a drug used to treat gastric ulcers, gastroesophageal reflux disease, gastric inflammation, etc., and to prevent stress ulcers. The salt portion of sucralfate binds with fibroin in the stomach wall to form a membrane, which coats the stomach wall and protects it from gastric acid, bile, etc., thereby relieving stomach pain and allowing sucralfate to function as an antacid. The method for obtaining sucralfate is not limited, and it can be chemically synthesized by methods known in the art or commercially available.

[0038] The substance of the present invention may be contained in an amount of about 0.0001 to 10% by weight based on the total weight of the composition, but is not limited thereto. For example, the material for improving skin microwrinkles of the present invention may be contained in an amount of about 0.0001 to 10% by weight, about 0.0005 to 5% by weight, about 0.001 to 5% by weight, about 0.01 to 5% by weight, about 0.0001 to 3% by weight, about 0.0005 to 3% by weight, about 0.001 to 3% by weight, about 0.01 to 3% by weight, about 0.0001 to 1% by weight, about 0.0005 to 1% by weight, about 0.001 to 1% by weight, or about 0.01 to 1% by weight based on the total weight of the composition.

[0039] For the purposes of the present invention, the substance provides the effect of promoting the improvement of fine wrinkles on the skin.

[0040] For the purposes of the present invention, the term "skin wrinkle" refers to the appearance of a deflated skin caused by a decrease in the elasticity of a certain area of ​​the skin. Due to the deflation of the skin, the wrinkled area appears darker than the surrounding skin. Furthermore, since most wrinkles are linear, a wrinkle is defined when the shaded areas are connected and observed to be longer than a certain length, but is not limited thereto.

[0041] The skin wrinkles are associated with human aging and form thin fine wrinkles around the eyes and mouth. The term "skin microwrinkles" may be interchangeable with terms such as "relief," "furrow," "wrinkle," "fine wrinkle," and "line." The skin microwrinkles may be, but are not limited to, those under the eyes or around the mouth.

[0042] For the purposes of the present invention, the substance may be characterized by its ability to promote collagen synthesis. Specifically, among the substances, phloretin and / or oryzanol can promote the synthesis of collagen type I or collagen type IV, and lupeol and / or sucralfate can promote the synthesis of collagen type III or collagen type IV, but this is not limiting.

[0043] As an example, when a cream containing the substance of the present invention, which is effective in promoting collagen synthesis, was applied to the eye area, it was confirmed that it showed a superior improvement rate in wrinkles compared to the control group, which was applied with retinol.

[0044] Although many wrinkle-improving ingredients targeting collagen are currently available on the market, the rate at which consumers actually experience wrinkle improvement is considered to be very low. Furthermore, there are few non-retinol ingredients that surpass retinol, the ingredient known to have the most effective wrinkle-improving effect among currently available ingredients. However, the present invention is significant in that it has been confirmed that a non-retinol substance has an excellent effect of promoting collagen synthesis.

[0045] For the purposes of the present invention, the substance may be characterized by promoting EDAR expression or suppressing BNC2 expression. Specifically, among the substances, treatment with phloretin and / or oryzanol can suppress BNC2 expression, while treatment with lupeol and / or sucralfate can promote EDAR expression, but is not limited to these. It has been found that responsiveness to the substance of the present invention varies depending on specific genetic polymorphisms, suggesting that providing a customized prescription for high-risk groups with a high risk of developing microwrinkles can increase the efficiency of improving microwrinkles.

[0046] In the present invention, the term "about" is used before a specific numerical value. As used in this application, the term "about" includes not only the exact number described after the term, but also approximately that number or a range close to that number. Whether a number is close to or approximately the specific number mentioned can be determined by considering the context in which the number is provided. For example, the term "about" can refer to a range of -10% to +10% of the numerical value. In another example, the term "about" can refer to a range of -5% to +5% of the given numerical value. However, the present invention is not limited thereto.

[0047] The composition is characterized by being personalized, and specifically, can be provided to individuals who have a significant single nucleotide polymorphism (SNP) marker associated with the degree of specific skin microwrinkles.

[0048] As an example, the significant single nucleotide polymorphism (SNP) marker associated with the degree of skin microwrinkles may be, but is not limited to, any one or more selected from Table 1.

[0049] In this application, the term "polymorphism" refers to the presence of two or more alleles at a single genetic locus, and a single nucleotide polymorphism (SNP) is a difference in only a single nucleotide at a polymorphic site between individuals. Preferred polymorphic markers have two or more alleles that occur at a frequency of 1% or more, more specifically, 10% or 20% or more, in a selected population. A "genetic polymorphic marker" generally refers to the presence of two or more alleles at the same genetic position (base), and generally, there are cases of major allele / major allele, major allele / minor allele, and minor allele / minor allele depending on the individual. In the present invention, the term "polymorphic marker" may be used interchangeably with "polymorphic marker" and may refer to the base and base site of a suballelic gene, or may be defined together with the chromosome number and base position, but is not limited thereto.

[0050] As used herein, the term "allele" refers to various types of a gene present at the same locus on homologous chromosomes. Alleles are sometimes used to indicate polymorphisms; for example, a SNP has two types of alleles. Alleles also refer to combinations of two or more bases that have the same chromosomal number and base position, including major alleles that occur more frequently in individuals of a particular population and minor alleles that occur less frequently than the major allele.

[0051] Specifically, the genetic polymorphism marker of the present invention is significant in relation to skin microwrinkles and can have two types of alleles, which can be divided into cases of major allele / minor allele, minor allele / minor allele, and major allele / major allele.

[0052] When an individual has an allele of a significant polymorphic marker associated with microwrinkles, the effect of improving microwrinkles on the skin may differ depending on the allele the individual has, depending on the responsiveness to the substance of the present invention. For example, when an individual has major allele / major allele, major allele / minor allele, or minor allele / minor allele, it can be determined whether the individual has skin characteristics that are highly responsive to the substance of the present invention, i.e., have a high or low degree of improvement in microwrinkles. This can provide information for selecting a customized substance to enhance the improvement of microwrinkles for individuals with four or more minor alleles.

[0053] In this application, the term "rs_id" refers to rs-ID, an independent marker assigned to all SNPs initially registered by NCBI, which began accumulating SNP information in 1998. The rs_ids listed in such tables refer to SNP markers, which are polymorphic markers of the present invention.

[0054] The single nucleotide polymorphism marker may be one or more single nucleotide polymorphism markers selected from the single nucleotide polymorphism markers shown in Tables 1 and 4. The single nucleotide polymorphism markers shown in Tables 1 and 4 may be used to determine whether or not they are associated with the degree of microwrinkles on the skin.

[0055] The degree of skin wrinkles of the single nucleotide polymorphism markers of the present invention was determined by measuring the frequency of each marker. Such significance is characterized by a p-value such as, but not limited to, a p-value of less than 0.05, less than 0.01, less than 0.001, less than 0.0001, less than 0.00001, less than 0.000001, less than 0.0000001, less than 0.00000001, or less than 0.000000001. Specifically, the p-value may be less than 0.01, more specifically, the p-value may be less than 0.001, and even more specifically, the p-value may be less than 0.0001, but is not limited thereto.

[0056] The single nucleotide polymorphism (SNP) marker of the present invention may be, but is not limited to, any one or more selected from the markers shown in Table 1 or Table 4. The single nucleotide polymorphism (SNP) marker may be one or more, or may be used in a combination of two or more, three or more, four or more, or any number of markers that can be used to determine wrinkles, but is not limited to this.

[0057] The marker may be, but is not limited to, the SNP itself, or a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the SNP position, or a polynucleotide consisting of a complementary sequence thereof.

[0058] For example, the significant single nucleotide polymorphism marker associated with the degree of microwrinkles may be one or more single nucleotide polymorphism markers present in a gene encoding an EDAR or BNC2 protein, specifically, any one or more selected from the group consisting of rs10865025, rs10756807, rs1952688, rs10116469, and rs12338608, but is not limited thereto.

[0059] For example, if the SNP ID is rs10865025, the Chr. Position (GRCh ver. 37) is described as "2:109511765," and the allele is disclosed as G>A, this indicates that the base at position 109511765 of human chromosome 2 is G or A, and the base to the left of the ">" in the allele represents the major allele, and the base to the right represents the minor allele.

[0060] In one specific example, the marker selected from Table 1 is a polynucleotide consisting of 5-100 consecutive DNA sequences including the base at position 109511765 of human chromosome 2, where the base is G or A (rs10865025); a polynucleotide consisting of 5-100 consecutive DNA sequences including the base at position 109511765 of human chromosome 9, where the base is G or A (rs10756807); a polynucleotide consisting of 5-100 consecutive DNA sequences including the base at position 16756041 of human chromosome 9, where the base is A or G (rs1952688); The polynucleotide may be, but is not limited to, one or more polynucleotides selected from the group consisting of a polynucleotide consisting of a contiguous DNA sequence of 5-100 bases including the 16783095th base of human chromosome 9, where the 16783095th base is A or T (rs10116469); a polynucleotide consisting of a 5-100 base sequence including the 16800470th base of human chromosome 9, where the 16800470th base is C or T (rs12338608); and complementary polynucleotides thereof.

[0061] In another embodiment, similar to Table 1, one or more single nucleotide polymorphism (SNP) markers shown in Table 4 may be selected, but are not limited thereto.

[0062] The composition of the present invention may be used as a cosmetic composition and may be formulated into various forms, including, but not limited to, a solution, an ointment for external use, a cream, a foam, a nourishing lotion, a softening lotion, a pack, a softening lotion, a milky lotion, a makeup base, an essence, a soap, a liquid cleanser, a bath additive, a sunscreen cream, a sun oil, a suspension, an emulsion, a paste, a gel, a lotion, a powder, a soap, a surfactant-containing cleanser, an oil, a powder foundation, an emulsion foundation, a wax foundation, a patch, and a spray.

[0063] Furthermore, the cosmetic composition of the present invention may further contain one or more cosmetically acceptable carriers that are commonly incorporated into skin cosmetics, and may contain appropriate amounts of conventional ingredients such as oils, water, surfactants, moisturizers, lower alcohols, thickeners, chelating agents, pigments, preservatives, and fragrances, but is not limited to these.

[0064] The cosmetically acceptable carrier contained in the cosmetic composition of the present invention varies depending on the formulation.

[0065] When the dosage form of the present invention is an ointment, paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or a mixture thereof can be used as a carrier component.

[0066] When the dosage form of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, or a mixture thereof may be used as a carrier component, and particularly when it is a spray, it may further contain a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether.

[0067] When the dosage form of the present invention is a solution or emulsion, a solvent, solubilizer, or emulsifier is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, and in particular, cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil, and sesame oil, glycerol fatty acid esters, polyethylene glycol, or fatty acid esters of sorbitan.

[0068] When the dosage form of the present invention is a suspension, the carrier component may be a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth.

[0069] When the dosage form of the present invention is a soap, carrier components that can be used include alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolysates, isethionates, lanolin derivatives, fatty alcohols, vegetable oils and fats, glycerol, sugars, and the like.

[0070] In another embodiment, the composition provides a quasi-drug composition for reducing or improving fine wrinkles on the skin.

[0071] In the present invention, the term "quasi-drug" means an article used for the purpose of diagnosing, curing, improving, mitigating, treating, or preventing a disease in humans or animals, which has a milder effect than a drug. For example, according to the Pharmaceutical Affairs Act of the Republic of Korea, quasi-drugs exclude articles used for the purpose of a drug, and include products used for the treatment or prevention of a disease in humans or animals, and products that have a mild effect on the human body or do not have a direct effect.

[0072] In one embodiment, the quasi-drug composition of the present invention may be prepared in a form selected from the group consisting of body cleanser, shampoo, conditioner, foam, soap, mask, ointment, cream, lotion, essence, and spray, but is not limited thereto.

[0073] In another aspect, the present invention provides a method for providing information for selecting a customized substance for improving microwrinkles, the method comprising: (a) obtaining a biological sample from an individual; (b) amplifying or hybridizing with a probe a polymorphic site of a single nucleotide polymorphism marker, the single nucleotide polymorphism marker being any one or more selected from the group consisting of rs10865025, rs10756807, rs1952688, rs10116469, and rs12338608, from the biological sample; and (c) identifying the base of the amplified or hybridized polymorphic site in step (b).

[0074] The selected customized material can be administered to individuals with a particular polymorphic site to improve the appearance of microwrinkles on the skin.

[0075] The term "individual" as used herein refers to a subject for diagnosing the degree of skin microwrinkles. DNA can be obtained from samples such as, but not limited to, hair, urine, blood, various body fluids, isolated tissues, isolated cells, or saliva.

[0076] The method for obtaining genomic DNA in step (a) can be any method known to those skilled in the art.

[0077] The step of amplifying the polymorphic site of the single nucleotide polymorphism marker from the DNA obtained in step (a) or hybridizing it with a probe can be performed by any method known to those skilled in the art. For example, the target nucleic acid can be amplified by PCR and purified. Alternatively, ligase chain reaction (LCR) (Wu and Wallace, Genomics 4, 560 (1989); Landegren et al., Science 241, 1077 (1988)), transcription amplification (Kwoh et al., Proc. Natl. Acad. Sci. USA 86, 1173 (1989)), self-sustained sequence replication (Guatelli et al., Proc. Natl. Acad. Sci. USA 87, 1874 (1990)), and nucleic acid-based sequence amplification (NASBA) can be used.

[0078] In the method, determining the base at the polymorphic site in step (b) includes, but is not limited to, sequencing analysis, microarray hybridization, allele-specific PCR, dynamic allele-specific hybridization (DASH), PCR extension analysis, SSCP, PCR-RFLP analysis or TaqMan technology, the SNPlex platform (Applied Biosystems), mass spectrometry (e.g., Sequenom's MassARRAY system), mini-sequencing methods, the Bio-Plex system (BioRad), the CEQ and SNPstream system (Beckman), Molecular Inversion Probe array technology (e.g., Affymetrix GeneChip), and BeadArray Technologies (e.g., Illumina GoldenGate and Infinium analysis methods). By using the above method or other methods available to those skilled in the art, one or more alleles at polymorphic markers, including microsatellites, SNPs, or other types of polymorphic markers, can be identified. Determining the base at such polymorphic sites can be performed, specifically, through an SNP chip.

[0079] The substance may be one or more selected from the group consisting of phloretin, oryzanol, lupeol, and sucralfate, but is not limited thereto.

[0080] For the purposes of the present invention, the significant genes associated with the degree of fine wrinkles can provide information for selecting a specific substance for each individual. For example, in the case of an individual having one or more single nucleotide polymorphism markers present in the gene encoding EDAR or BNC2 protein, treatment with one or more substances selected from the group consisting of lupeol, phloretin, oryzanol, lupeol, and sucralfate can enhance the improvement of fine wrinkles, and an optimal combination of substances can be provided depending on the genetic characteristics of each individual.

[0081] This suggests that it may be possible to select specific single nucleotide polymorphism (SNP) markers that have a significant correlation with skin microwrinkles, and provide information to select personalized substances that can maximize the effect of improving microwrinkles based on genetic information.

[0082] As an example, when four or more minor alleles in the bases rs10865025, rs10756807, rs1952688, rs10116469, and rs12338608 are present, a method for providing information to select phloretin and oryzanol; lupeol and sucralfate; or phloretin, oryzanol, lupeol, and sucralfate may be provided, but this is not limitative.

[0083] In this application, the term "SNP chip" refers to a type of DNA microarray that can identify each base of hundreds of thousands of SNPs at once.

[0084] The TaqMan method includes the steps of: (1) designing and preparing primers and TaqMan probes to amplify the target DNA fragment; (2) labeling probes for different alleles with FAM dye and VIC dye (Applied Biosystems); (3) using the DNA as a template and performing PCR using the primers and probes; (4) analyzing and verifying the TaqMan assay plate after the PCR reaction is completed using a nucleic acid analyzer; and (5) determining the genotype of the polynucleotide in step (1) from the analysis results.

[0085] In the above, the sequencing analysis can be performed using a conventional method for determining base sequences and can be carried out using an automated genetic analyzer. Allele-specific PCR refers to a PCR method in which a DNA fragment containing a SNP is amplified using a primer set containing a primer designed with the base corresponding to the SNP at its 3' end. The principle of this method is that, for example, if a specific base is substituted from A to G, a PCR reaction is performed using a primer containing the A at its 3' end and a reverse primer capable of amplifying a DNA fragment of an appropriate size. When the base at the SNP position is A, the amplification reaction proceeds normally, resulting in the observation of a band at the target position. When the base is substituted with G, the primer can complementarily bind to the template DNA, but the 3' end cannot complementarily bind, resulting in an incomplete amplification reaction. DASH can be performed using conventional methods, specifically, the method proposed by Prince et al.

[0086] Meanwhile, PCR extension analysis involves first amplifying a DNA fragment containing the base where the single nucleotide polymorphism is located with a primer pair, deactivating all nucleotides added to the reaction by dephosphorylation, and then adding an SNP-specific extension primer, a dNTP mixture, dideoxynucleotides, a reaction buffer, and DNA polymerase to carry out a primer extension reaction. The extension primer has its 3' end at the base immediately adjacent to the 5' end of the base where the SNP is located, and the dNTP mixture excludes nucleic acids having the same base as the dideoxynucleotide, with the dideoxynucleotide being selected from one of the types of bases that indicate an SNP. For example, in the case of an A to G substitution, if a mixture of dGTP, dCTP, and dTTP and ddATP are added to the reaction, the primer is extended by DNA polymerase at the base where the substitution occurred, and after several bases, the primer extension reaction is terminated by ddATP at the position where the first A base appears. If the substitution does not occur, the extension reaction terminates at that position, and the type of base that indicates the SNP can be determined by comparing the length of the extended primer.

[0087] In this case, when the extension primer or dideoxynucleotide is fluorescently labeled, the SNP can be detected by detecting fluorescence using a genetic analyzer commonly used for determining base sequences (e.g., ABI Model 3700, etc.). When unlabeled extension primer and dideoxynucleotide are used, the SNP can be detected by measuring the molecular weight using MALDI-TOF (matrix assisted laser desorption ionization-time of flight) technique.

[0088] In one embodiment for achieving the object of the present invention, the present invention provides a single nucleotide polymorphism (SNP) marker for diagnosing the degree of skin microwrinkles.

[0089] In another aspect, the present invention provides a composition for diagnosing the degree of skin microwrinkles, comprising a probe capable of detecting or an agent capable of amplifying a single nucleotide polymorphism (SNP) marker for diagnosing the degree of skin microwrinkles.

[0090] For purposes of the present invention, the term "degree of skin microwrinkles" refers to, but is not limited to, the result of measuring the ratio of all measured areas when a linear area of ​​skin longer than a certain length due to skin wrinkles is observed to be relatively darker than the surrounding skin. Specifically, it refers to determining whether or not microwrinkles are likely to occur using one or more single nucleotide polymorphism (SNP) markers selected from Table 1 or Table 4. More specifically, a skin type that is likely to develop microwrinkles refers to a skin type that ages rapidly and therefore has a high rate of wrinkles per skin area.

[0091] The alleles of the present invention have the same number on a chromosome in each individual, and among them, there are major and minor alleles of the SNP. As the base at the polymorphic site of the polymorphic marker increases by one as a minor allele, the major allele decreases by one, and as the base at the polymorphic site of the polymorphic marker increases by one as a major allele, the minor allele decreases by one. However, the range in which the minor allele and the major allele can increase or decrease may be within three types: i) major allele / major allele, ii) major allele / minor allele, and iii) minor allele / minor allele. The allele may decrease or increase within the range of these three types, but is not limited thereto.

[0092] In the present application, the term "probe capable of detecting a marker for diagnosing the degree of microwrinkles in skin" refers to a composition capable of diagnosing the degree of microwrinkles in skin by specifically identifying the polymorphic site of the gene through a hybridization reaction, and the specific method of such gene analysis is not particularly limited and may be any gene detection method known in the technical field to which the present invention pertains. In addition, the term may be used interchangeably with the term "for diagnosing whether a skin type is prone to microwrinkles."

[0093] In the present application, the term "preparation capable of amplifying a marker for diagnosing the degree of microwrinkles in skin" refers to a composition capable of diagnosing the degree of microwrinkles in skin by identifying the polymorphic site of the gene through amplification, and more specifically, refers to a primer capable of specifically amplifying the polynucleotide of the marker for diagnosing the degree of microwrinkles in skin. In addition, the term may be used interchangeably with the term "for diagnosing whether a skin type is prone to microwrinkles."

[0094] The primers used to amplify the polymorphic markers are single-stranded oligonucleotides that can act as initiation points for template-directed DNA synthesis under appropriate conditions (e.g., four other nucleoside triphosphates and a polymerizing agent such as DNA or RNA polymerase or reverse transcriptase) in an appropriate buffer at an appropriate temperature. The appropriate length of the primer varies depending on the intended use, but is typically 15 to 30 nucleotides. Shorter primer molecules generally require lower temperatures to form stable hybrids with the template. The primer sequence does not need to be perfectly complementary to the template, but must be sufficiently complementary to hybridize with the template.

[0095] In this application, the term "primer" refers to a short base sequence with a short free 3' hydroxyl group that can form base pairs with a complementary template and serve as a starting point for copying the template strand. Primers can initiate DNA synthesis in the presence of a polymerization reagent (i.e., DNA polymerase or reverse transcriptase) and four different nucleoside triphosphates at an appropriate buffer solution and temperature. PCR amplification can be performed to predict skin type based on the degree of production of the desired product. PCR conditions and the lengths of sense and antisense primers can be varied based on what is known in the art.

[0096] The probes or primers of the present invention can be chemically synthesized using the phosphoramidite solid support method or other widely known methods. Such nucleic acid sequences can also be modified using a number of means known in the art. Non-limiting examples of such modifications include methylation, "capping," substitution of one or more analogs of natural nucleotides, and internucleotide modifications, such as uncharged linkages (e.g., methylphosphonates, phosphotriesters, phosphoramidates, carbamates, etc.) or charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.).

[0097] In another aspect, the present invention provides a kit for diagnosing the degree of skin microwrinkles, which includes the composition for diagnosing the degree of skin microwrinkles. The kit may be, but is not limited to, an RT-PCR kit or a DNA chip kit.

[0098] The kit of the present invention can diagnose the level of skin microwrinkles by amplifying SNP polymorphism markers, which are diagnostic markers for the level of skin microwrinkles, or by determining the expression level of the SNP polymorphism markers as mRNA. As a specific example, the kit for measuring the mRNA expression level of a diagnostic marker for the level of skin microwrinkles in the present invention may be a kit containing essential elements necessary for performing RT-PCR. In addition to primer pairs specific to the genes of diagnostic markers for the level of skin microwrinkles, the RT-PCR kit may also contain test tubes or other suitable containers, reaction buffers (with various pH and magnesium concentrations), deoxynucleotides (dNTPs), enzymes such as Taq polymerase and reverse transcriptase, DNase, RNase inhibitor, DEPC-water, sterile water, etc. It may also contain primer pairs specific to genes used as quantitative controls. More specifically, the kit of the present invention may be a kit for diagnosing the level of skin microwrinkles, containing essential elements necessary for performing DNA chip analysis. A DNA chip kit generally comprises a flat solid support, typically a glass surface no larger than a microscope slide, on which nucleic acid species are attached in a gridded array. Nucleic acids are arranged in a uniform pattern on the surface of the chip, and multiple hybridization reactions occur between the nucleic acids on the DNA chip and complementary nucleic acids contained in a solution applied to the surface of the chip, making it a tool that enables massively parallel analysis.

[0099] In another aspect, the present invention provides a microarray for diagnosing the degree of microwrinkles in the skin, comprising the composition for diagnosing the degree of microwrinkles in the skin.

[0100] The microarray may contain DNA or RNA polynucleotides. The microarray has the same structure as a conventional microarray, except that the probe polynucleotides contain the polynucleotides of the present invention.

[0101] Methods for preparing microarrays by immobilizing probe polynucleotides on a substrate are well known in the art. The term "probe polynucleotide" refers to a hybridizable polynucleotide, i.e., an oligonucleotide capable of sequence-specific binding to complementary strands of nucleic acid. The probe of the present invention is an allele-specific probe, which hybridizes to DNA fragments from one member but not to fragments from the other member, due to the presence of a polymorphic site in nucleic acid fragments derived from both members of the same species. In this case, the hybridization conditions must be sufficiently stringent to show a significant difference in hybridization intensity between alleles and hybridize to only one of the alleles. This can induce good hybridization differences between the forms of other alleles. The probe of the present invention can be used in methods such as skin type diagnosis by detecting alleles. Diagnostic methods include nucleic acid hybridization-based detection methods, such as Southern blot, and may be provided in a form pre-bound to a DNA chip substrate in a DNA chip-based method. The hybridization is usually performed under stringent conditions, such as a salt concentration of 1 M or less and a temperature of 25° C. or higher. For example, conditions of 5x SSPE (750 mM NaCl, 50 mM Na Phosphate, 5 mM EDTA, pH 7.4) and 25 to 30° C. are suitable for hybridization of allele-specific probes.

[0102] The process of immobilizing probe polynucleotides on a substrate in connection with the diagnosis of the degree of skin microwrinkles of the present invention can also be easily performed using such conventional techniques. Furthermore, nucleic acid hybridization on a microarray and detection of hybridization results are well known in the art. For example, the detection can be performed by labeling a nucleic acid sample with a labeling substance that generates a detectable signal, including fluorescent substances such as Cy3 and Cy5, hybridizing the nucleic acid sample on a microarray, and detecting the signal generated from the labeling substance to detect the hybridization results.

[0103] In another aspect, the present invention provides a method for providing information on the degree of skin microwrinkles, comprising: (a) amplifying or hybridizing with a probe a polymorphic site of the single nucleotide polymorphism marker in DNA obtained from a sample isolated from an individual; and (b) identifying the base of the amplified or hybridized polymorphic site in step (a).

[0104] The terms "individual, (a) stage, (b) stage" are as defined above.

[0105] The method may further include (c) determining that a subject is at high risk of developing microwrinkles when the amplified or hybridized polymorphic site contains four or more bases that are minor alleles of the single nucleotide polymorphism marker, but is not limited thereto.

[0106] In one aspect of the present invention, the present invention provides a composition for reducing wrinkles in sagging pores. For example, the composition contains one or more active ingredients selected from the group consisting of fucoidan, N-feruloylserotonin, emodin, and formononetin. For another example, the composition may contain, but is not limited to, (i) fucoidan and N-feruloylserotonin; (ii) emodin and formononetin; or (iii) fucoidan, N-feruloylserotonin, emodin, and formononetin as active ingredients.

[0107] The term "fucoidan" refers to a component of the smooth mucus found in brown algae. It is secreted from the mucous membranes in the leaves and plays a role in preventing bacterial invasion when the leaves and stems of seaweed are damaged by tidal currents or sand. Fucoidan has physiological properties similar to heparin, a sulfated polysaccharide found in blood, and various physiological functions have been identified, including anti-cancer, anti-viral, anti-allergic, and immune-boosting properties. Fucoidan is prepared by extracting brown algae such as wakame (seaweed), kombu (kelp), mozuku (seaweed), and hijiki (seaweed). Fucoidan can be obtained by any method known in the art, either chemically synthesized or commercially available.

[0108] The term "N-feruloylserotonin" refers to a derivative of serotonin, an alkaloid and polyphenol found in safflower seeds. Chemically, it is an amide formed between serotonin and ferulic acid, and is known to have anti-atherosclerotic activity. The molecular formula of N-feruloylserotonin is C 20 H 20 N2O4 has a molecular weight of 352.390 and can be represented by the following chemical formula 3. The method for obtaining N-feruloylserotonin is not limited, and it can be chemically synthesized by a method known in the art or commercially available.

[0109] [ka]

[0110] The term "emodin" refers to an anthraquinone compound that can be isolated from rhubarb, black rose, etc. The molecular formula of emodin is C 15 H 10 It has a molecular weight of 270.24 and can be represented by the following chemical formula 4. The method for obtaining emodin is not limited, and it can be chemically synthesized by a method known in the art or a commercially available substance.

[0111] [ka]

[0112] The term "formononetin" refers to an O-methylated isoflavone found in many plants and herbs. It is known to promote angiogenesis. The molecular formula of formononetin is C 16 H 12 It has a molecular weight of 284.26 and can be represented by the following chemical formula 5. The method for obtaining formononetin is not limited, and it can be chemically synthesized by a method known in the art or a commercially available substance.

[0113] [ka]

[0114] The substance of the present invention may be present in an amount of about 0.0001 to 10% by weight based on the total weight of the composition, but is not limited thereto. For example, the retinol booster of the present invention may be present in an amount of about 0.0001 to 10%, about 0.0005 to 5%, about 0.001 to 5%, about 0.01 to 5%, about 0.0001 to 3%, about 0.0005 to 3%, about 0.001 to 3%, about 0.01 to 3%, about 0.0001 to 1%, about 0.0005 to 1%, about 0.001 to 1%, or about 0.01 to 1% by weight based on the total weight of the composition.

[0115] For the purposes of the present invention, the substance provides the effect of promoting the improvement of wrinkles in sagging pores.

[0116] For the purposes of the present invention, the term "wrinkles caused by sagging pores" refers to pores that expand and sag in an oval shape due to aging, and these sagging pores connect to form wrinkles. Sagging pores are mainly oval pores that expand from the nostrils to the cheeks. Due to the contraction of the skin, the wrinkled area is shaded compared to the surrounding skin, and therefore appears relatively darker than the surrounding skin. Furthermore, since wrinkles are mostly linear, they can be defined as wrinkles when the shaded areas are connected and observed to be longer than a certain length, but this is not limited thereto.

[0117] For the purposes of the present invention, the substance may be characterized by its ability to promote collagen synthesis. Specifically, when fucoidan and / or N-feruloyl serotonin is added to the substance, the synthesis of type IV collagen can be promoted, and when emodin and / or formononetin is added to the substance, the synthesis of type I collagen or type IV collagen can be promoted, but is not limited thereto.

[0118] As an example, when a cream containing the substance of the present invention, which is effective in promoting collagen synthesis, was applied to the cheeks, it was confirmed that it showed a superior improvement rate in wrinkles compared to the control group, which was applied with retinol.

[0119] Although many wrinkle-improving ingredients targeting collagen are currently available on the market, the rate at which consumers actually experience wrinkle improvement is understood to be very low. Furthermore, there are few non-retinol ingredients that surpass retinol, the ingredient known to have the most effective wrinkle-improving efficacy among currently available ingredients. However, the present invention is significant in that it has been confirmed that a non-retinol substance can effectively promote collagen synthesis.

[0120] For the purposes of the present invention, the substance may be characterized by promoting the expression of ADIPOQ or inhibiting the expression of SGPP2. Specifically, among the substances, treatment with emodin and / or formononetin can promote the expression of ADIPOQ, while treatment with fucoidan and / or N-feruloyl serotonin can inhibit the expression of SGPP2, but is not limited thereto. It has been found that responsiveness to the substance of the present invention varies depending on the presence or absence of a specific gene, suggesting that providing a customized prescription to a high-risk group with a high risk of developing sagging pore wrinkles can increase the efficiency of improving sagging pore wrinkles.

[0121] In the present invention, the term "about" is as defined above.

[0122] The composition is characterized by being individually customized, and specifically, it can be provided to individuals who have a significant single nucleotide polymorphism (SNP) marker associated with the degree of wrinkles in specific sagging pores.

[0123] As an example, the significant single nucleotide polymorphism (SNP) marker associated with the degree of wrinkles in sagging pores may be, but is not limited to, any one or more selected from Table 2 or Table 5.

[0124] In this application, the terms "polymorphism," "allele," and "rs_id" are as defined above.

[0125] Specifically, the genetic polymorphism marker of the present invention has significance in relation to sagging pores and wrinkles, and can have two types of alleles, which can be divided into cases of major allele / minor allele, minor allele / minor allele, and major allele / major allele.

[0126] When an individual has an allele of a significant polymorphic marker associated with sagging pore wrinkles, the effect of improving sagging pore wrinkles may vary depending on the allele the individual has, depending on the responsiveness to the substance of the present invention. For example, when an individual has a major allele / major allele, a major allele / minor allele, or a minor allele / minor allele, it can be determined whether the individual has skin characteristics that are highly or poorly responsive to the substance of the present invention, i.e., have a high or low degree of improvement in sagging pore wrinkles. This can provide information for selecting a customized substance to enhance the improvement of sagging pore wrinkles for an individual having one or more minor alleles.

[0127] The single nucleotide polymorphism marker may be one or more single nucleotide polymorphism markers selected from the single nucleotide polymorphism markers shown in Tables 2 and 5. It may be used to determine whether the single nucleotide polymorphism markers shown in Tables 2 and 5 are associated with the degree of wrinkles in sagging pores.

[0128] The single nucleotide polymorphism (SNP) marker of the present invention may be, but is not limited to, any one or more selected from the markers shown in Table 2 or Table 5. The single nucleotide polymorphism (SNP) marker may be one or more, or may be used in a combination of two or more, or any number of markers that can be used to determine wrinkles, but is not limited to this. The marker may be, but is not limited to, the SNP itself, or a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the position of the SNP, or a polynucleotide consisting of a complementary sequence thereof.

[0129] For example, the significant single nucleotide polymorphism marker associated with the degree of wrinkles in sagging pores may be one or more single nucleotide polymorphism markers present in a gene encoding an ADIPOQ or SGPP2 protein, and specifically may be any one or more selected from the group consisting of rs10203329, rs4592839, rs76071583, and rs2036373, but is not limited thereto.

[0130] For example, if the SNP ID is rs10203329, and the Chr. Position (GRCh ver. 37) is described as "2:223350001" and the allele is disclosed as A>G, this indicates that the 223350001st base of human chromosome 2 is A or G, and the base to the left of the ">" in the allele may represent a major allele, and the base to the right may represent a minor allele.

[0131] In one specific example, the marker selected from Table 2 is a polynucleotide consisting of 5-100 consecutive DNA sequences including the 223350001 base of human chromosome 2, where the 223350001 base is A or G (rs10203329); a polynucleotide consisting of 5-100 consecutive DNA sequences including the 223350001 base of human chromosome 2, where the 223350001 base is T or C (rs4592839); a polynucleotide consisting of 5-100 consecutive DNA sequences including the 223412813 base of human chromosome 3, where the 186557872 base of human chromosome 3 is T or C (rs4592839). The polynucleotide may be, but is not limited to, one or more polynucleotides selected from the group consisting of a polynucleotide consisting of a 5-100 contiguous DNA sequence including the 186557872 base in chromosome 186557872, where the base in 186557872 is A or G (rs76071583); a polynucleotide consisting of a 5-100 contiguous DNA sequence including the 186570191 base in chromosome 3 of human beings, where the base in 186570191 is T or G (rs2036373); and complementary polynucleotides thereof.

[0132] In another embodiment, one or more of the single nucleotide polymorphism (SNP) markers shown in Table 5 may be selected in the same manner as in Table 2, but is not limited thereto.

[0133] The composition of the present invention may be used as a cosmetic composition, as described above.

[0134] In another embodiment, the composition provides a quasi-drug composition for reducing or improving wrinkles caused by sagging pores. The term "quasi-drug" in the present invention is as defined above.

[0135] In another aspect, the present invention provides a method for providing information for selecting a customized substance for improving sagging pores and wrinkles, the method comprising: (a) obtaining a biological sample from an individual; (b) amplifying or hybridizing with a probe a polymorphic site of a single nucleotide polymorphism marker, which is any one or more selected from the group consisting of rs4592839 and rs76071583, from the biological sample; and (c) confirming the base of the amplified or hybridized polymorphic site in step (b).

[0136] The selected customized substance can be administered to an individual having a specific polymorphic site to improve the appearance of sagging pores and wrinkles.

[0137] The term "individual" as used herein refers to a subject for whom the degree of sagging pores and wrinkles is to be diagnosed. DNA can be obtained from samples such as, but not limited to, hair, urine, blood, various body fluids, isolated tissues, isolated cells, or saliva. Steps (a) and (b) are also as described above.

[0138] The substance may be, but is not limited to, one or more selected from the group consisting of fucoidan, N-feruloyl serotonin, emodin, and formononetin.

[0139] For the purposes of the present invention, the significant genes associated with the degree of wrinkles in sagging pores can provide information for selecting specific substances for each individual. For example, in the case of an individual having one or more single nucleotide polymorphism markers present in the gene encoding the ADIPOQ or SGPP2 protein, treatment with one or more substances selected from the group consisting of emodin, fucoidan, N-feruloyl serotonin, emodin, and formononetin can enhance the improvement of wrinkles in sagging pores, and the optimal combination of substances can be provided depending on the genetic characteristics of each individual.

[0140] This suggests that it may be possible to select specific single nucleotide polymorphism (SNP) markers that have a significant correlation with wrinkles caused by sagging pores, and provide information that will enable the selection of personalized substances that can maximize the effect of improving wrinkles caused by sagging pores based on genetic information.

[0141] As an example, when one or more minor alleles in the bases rs4592839 and rs76071583 are present, fucoidan and N-feruloyl serotonin may be selected; emodin and formononetin may be selected; or a method of providing information that allows the selection of fucoidan, N-feruloyl serotonin, emodin, and formononetin may be provided, but this is not limited to this.

[0142] In this application, the term "SNP chip" is as defined above.

[0143] In one aspect of the present invention to achieve the object, the present invention provides a single nucleotide polymorphism (SNP) marker for diagnosing the degree of wrinkles in sagging pores.

[0144] In another aspect, the present invention provides a composition for diagnosing the degree of wrinkles in sagging pores, comprising a probe capable of detecting or amplifying a single nucleotide polymorphism (SNP) marker for diagnosing the degree of wrinkles in sagging pores.

[0145] For purposes of the present invention, the term "degree of wrinkles due to sagging pores" refers to, but is not limited to, the fact that pores become oval and sagging due to aging, and that these sagging pores connect to form wrinkles. Sagging pores are primarily oval pores that extend from the nostrils to the cheeks. As fibrous proteins such as collagen and elastin decrease with age, the skin sags, and the pores also become larger and appear wrinkled. When linear areas of a certain length or more due to sagging pore wrinkles are observed to be darker than the surrounding skin, the term refers to, but is not limited to, the result of measuring the ratio of all measured areas to the total measured area. Specifically, the term refers to determining the susceptibility of sagging pore wrinkles using one or more single nucleotide polymorphism (SNP) markers selected from Table 2 or Table 5. More specifically, a skin type that is prone to wrinkles due to sagging pores means a skin type that ages quickly and therefore has a high ratio of sagging pores per skin area.

[0146] In the present application, the term "probe capable of detecting a marker for diagnosing the degree of wrinkles in sagging pores" refers to a composition capable of diagnosing the degree of wrinkles in sagging pores by specifically identifying the polymorphic site of the gene through a hybridization reaction, and the specific method of such gene analysis is not particularly limited, and may be any gene detection method known in the technical field to which the present invention pertains. In addition, the term may be used interchangeably with the term "for diagnosing whether a skin type is prone to wrinkles in sagging pores." In the present application, the term "preparation capable of amplifying a marker for diagnosing the degree of wrinkles in sagging skin pores" refers to a composition capable of diagnosing the degree of wrinkles in sagging skin pores by amplifying the polymorphic site of the gene, and more specifically, refers to a primer capable of specifically amplifying a polynucleotide of the marker for diagnosing the degree of wrinkles in sagging skin pores. In addition, the term may be used interchangeably with the term "for diagnosing whether a skin type is prone to wrinkles in sagging skin pores."

[0147] The primers used in amplifying the polymorphic markers are single-stranded oligonucleotides that can act as initiation points for template-directed DNA synthesis under appropriate conditions (e.g., four different nucleoside triphosphates and a polymerizing agent such as DNA or RNA polymerase or reverse transcriptase) in an appropriate buffer at an appropriate temperature. The appropriate length of the primer varies depending on the intended use, but is typically 15 to 30 nucleotides. Shorter primer molecules generally require lower temperatures to form stable hybrids with the template. The primer sequence does not need to be perfectly complementary to the template, but must be sufficiently complementary to hybridize with the template.

[0148] In this application, the term "primer" is as defined above.

[0149] In another aspect, the present invention provides a kit for diagnosing the degree of wrinkles in sagging pores in skin, comprising the composition for diagnosing the degree of wrinkles in sagging pores. The kit may be, but is not limited to, an RT-PCR kit or a DNA chip kit.

[0150] In another aspect, the present invention provides a microarray for diagnosing the degree of wrinkles in sagging pores of the skin, comprising the composition for diagnosing the degree of wrinkles in sagging pores.

[0151] The process of immobilizing probe polynucleotides on a substrate, which is related to the diagnosis of the degree of wrinkles caused by sagging pores of the present invention, can also be easily performed using such conventional techniques. Furthermore, nucleic acid hybridization on a microarray and detection of hybridization results are well known in the art. For example, the detection can be performed by labeling a nucleic acid sample with a labeling substance that generates a detectable signal, including fluorescent substances such as Cy3 and Cy5, hybridizing the nucleic acid sample on a microarray, and detecting the signal generated by the labeling substance to detect the hybridization results.

[0152] In another aspect, the present invention provides a method for providing information on the degree of wrinkles in sagging pores, comprising: (a) amplifying or hybridizing with a probe a polymorphic site of the single nucleotide polymorphism marker in DNA obtained from a sample isolated from an individual; and (b) identifying the base of the amplified or hybridized polymorphic site in step (a).

[0153] The terms "individual, (a) stage, (b) stage" are as defined above.

[0154] The method may further comprise (c) determining that a subject is at high risk of developing wrinkles due to sagging pores when the bases of the amplified or hybridized polymorphic site include four or more bases of a minor allele determined by the single nucleotide polymorphism marker, but is not limited thereto.

[0155] In one aspect of the present invention, the present invention provides a composition for improving nasolabial folds. For example, the composition contains, as an active ingredient, one or more substances selected from the group consisting of niacinamide, tranexamic acid, pyridoxine hydrochloride, camphor, cordyceps extract, sodium mannose phosphate, and retinol. For another example, the composition may contain, as an active ingredient, but is not limited to, (i) camphor, niacinamide, and sodium mannose phosphate; (ii) tranexamic acid and pyridoxine hydrochloride; or (iii) retinol, camphor, niacinamide, sodium mannose phosphate, tranexamic acid, pyridoxine hydrochloride, and cordyceps extract.

[0156] The term "niacinamide," also known as nicotinamide, is a vitamin B3 derivative widely distributed in the plant kingdom along with nicotinic acid. It is known to be widely distributed in living organisms as a component of NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate). The molecular formula of niacinamide is C6H6N2O, which can be represented by the following chemical formula 6. Niacinamide can be obtained by any method known in the art, and can be chemically synthesized or commercially available.

[0157] [ka]

[0158] The term "tranexamic acid" is a type of amino acid, and is used in medicine as a blood coagulant, antiallergic, and anti-inflammatory agent, and in the cosmetic field, it is known to regulate melanocyte stimulators and control melanin production. The molecular formula of tranexamic acid is CH 15 NO2 has a molecular weight of 157.21 and can be represented by the following chemical formula 7. The method for obtaining tranexamic acid is not limited, and it can be chemically synthesized by a method known in the art or a commercially available substance.

[0159] [ka]

[0160] The term "pyridoxine hydrochloride" refers to vitamin B6, a water-soluble vitamin that is a component of enzymes important in protein metabolism and is involved in the production of neurotransmitters and the secretion of serotonin (a hormone). Homocysteine ​​is produced during protein digestion, and elevated levels of homocysteine ​​in the blood increase the risk of cardiovascular disease and dementia. Vitamin B6 significantly reduces the risk of heart disease by combining with folic acid and vitamin B12 to destroy homocysteine. It is also necessary for the conversion of tryptophan to vitamin B3 and the absorption of vitamin B12. Pyridoxine hydrochloride can be obtained by any method known in the art, and can be chemically synthesized or commercially available.

[0161] The term "camphor" refers to a monoterpene compound with the chemical formula C 10 H 16 It has a molecular weight of 156.2 and can be represented by the following chemical formula 8. The camphor is not limited to a method for obtaining it, and can be chemically synthesized by a method known in the art or can be a commercially available substance.

[0162] [ka]

[0163] The term "Cordyceps" refers to a small mushroom belonging to the family Cordycepsidae in the order Cordycepsalides of the class Ascomycetes. Its name comes from its appearance, which parasitizes insects in winter and grows like a grass in summer. While the components of Cordyceps vary slightly depending on the species, it is generally composed of water, fat, crude protein, carbohydrates, and ash. The protein contains approximately 18 amino acids essential for the human body. Cordyceps also contains special components, such as Cordyceps Polysaccharides and Cordycepic Acid, which have been known since ancient times for their therapeutic effects on tuberculosis, asthma, jaundice, and other conditions, as well as immune-boosting and anti-cancer properties. The Cordyceps extract is not limited to a specific method for its preparation, and commercially available extracts may be used, including those extracted by methods known in the art.

[0164] The term "sodium mannose phosphate" has the molecular formula CH 12 09PNa, with a molecular weight of 282.12. Specifically, the sodium mannose phosphate may be, but is not limited to, sodium mannose 6-phosphate or D-mannose-6-phosphate sodium salt, which can be represented by the following chemical formula 9. The method for obtaining the sodium mannose phosphate is not limited, and it can be chemically synthesized by a method known in the art or a commercially available substance.

[0165] [ka]

[0166] The six substances are non-retinol substances that act alone to have wrinkle improvement effects superior to those of retinol, an ingredient known to have the most excellent wrinkle improvement effect, and can also act together with retinol to serve as retinol boosters that enhance the wrinkle improvement effect. The substances of the present invention are not particularly limited as long as they act alone or together with retinol to increase the reactivity of retinol and help maximize the wrinkle improvement effect on skin.

[0167] The term "retinol" refers to a type of vitamin A, also known as a pure vitamin. It is a substance that plays an important role in maintaining the original function of epidermal cells. It is present in the mucosal cells of animal intestines and is found in large amounts in green and yellow plants. It can be transformed into its active form, retinoic acid, and is known to play an important role in maintaining the original function of epidermal cells. It is also known to promote cell differentiation by expressing RNA through DNA in the cell nuclei of skin cells, and to promote the biosynthesis of collagen, a hard protein present as a fibrous solid between animal cells, and elastin, a material made up of elastic fibers, thereby reducing wrinkles and increasing skin elasticity.

[0168] The substance of the present invention may be present in an amount of about 0.0001 to 10% by weight based on the total weight of the composition, but is not limited thereto. For example, the retinol booster of the present invention may be present in an amount of about 0.0001 to 10%, about 0.0005 to 5%, about 0.001 to 5%, about 0.01 to 5%, about 0.0001 to 3%, about 0.0005 to 3%, about 0.001 to 3%, about 0.01 to 3%, about 0.0001 to 1%, about 0.0005 to 1%, about 0.001 to 1%, or about 0.01 to 1% by weight based on the total weight of the composition.

[0169] For the purposes of the present invention, the substance provides the effect of promoting the improvement of nasolabial folds.

[0170] For purposes of the present invention, the term "laugh lines" refers to facial wrinkles that form deep, figure-eight folds around the mouth when smiling or speaking. Deep laugh lines are caused by sagging cheek flesh that loses elasticity due to aging. Skin deflation creates shadows around the wrinkled area, making it appear darker than the surrounding skin. Furthermore, because most wrinkles are linear, wrinkles are defined as lines when the shadowed areas are connected and observed to extend for a certain length or more, but this definition is not limited thereto. Laugh lines can appear in various forms, including sagging nasolabial folds that sag downward due to gravity, deeply recessed nasolabial folds without sagging, and a combination of sagging and recessed nasolabial folds, but are not limited thereto.

[0171] For the purposes of the present invention, the substance may be characterized by its ability to promote collagen synthesis. Specifically, but not limited to, among the substances, camphor, niacinamide, and sodium mannose phosphate; tranexamic acid and pyridoxine hydrochloride; or retinol, camphor, niacinamide, sodium mannose phosphate, tranexamic acid, pyridoxine hydrochloride, and cordyceps extract can promote the synthesis of collagen type I.

[0172] Although many wrinkle-improving ingredients targeting collagen are currently available on the market, the rate at which consumers actually experience wrinkle improvement is considered to be very low. Furthermore, there are few non-retinol ingredients that surpass retinol, the ingredient known to have the most effective wrinkle-improving effect among currently available ingredients. However, the present invention is significant in that it has been confirmed that a non-retinol substance is highly effective in promoting collagen synthesis.

[0173] For purposes of the present invention, the substance may be characterized by promoting the expression of PPARGC1B, SPATA5, or EN1. Specifically, among the substances, treatment with niacinamide, camphor, and / or sodium mannose phosphate can promote the expression of PPARGC1B, treatment with tranexamic acid and / or pyridoxine hydrochloride can promote the expression of SPATA5, and treatment with Cordyceps sinensis extract can promote the expression of EN1, but is not limited thereto. It has been found that responsiveness to the substance of the present invention varies depending on the presence or absence of specific genes, suggesting that providing a customized prescription for high-risk groups with a high risk of developing nasolabial folds can increase the efficiency of improving nasolabial folds.

[0174] In the present invention, the term "about" is as defined above.

[0175] The composition is characterized by being individually customized, and specifically, it can be provided to individuals who have a significant single nucleotide polymorphism (SNP) marker associated with a specific degree of nasolabial folds.

[0176] As an example, the significant single nucleotide polymorphism (SNP) marker associated with the degree of nasolabial folds may be any one or more selected from Table 3 or Table 6, but is not limited thereto.

[0177] In this application, the terms "polymorphism," "allele," and "rs_id" are as defined above.

[0178] Specifically, the genetic polymorphism markers of the present invention have significance associated with nasolabial folds and can have two types of alleles, which can be divided into cases of major allele / minor allele, minor allele / minor allele, and major allele / major allele.

[0179] When an individual has an allele of a significant polymorphic marker associated with nasolabial folds, the responsiveness to the substance of the present invention varies depending on the allele the individual has. For example, when an individual has a major allele / major allele, a major allele / minor allele, or a minor allele / minor allele, it can be determined whether the individual has skin characteristics that are highly responsive to the substance of the present invention, i.e., have a high or low degree of improvement in nasolabial folds. This can provide information for selecting a customized substance to enhance the improvement of nasolabial folds for an individual having one or more minor alleles.

[0180] The single nucleotide polymorphism marker may be one or more single nucleotide polymorphism markers selected from the single nucleotide polymorphism markers shown in Tables 3 and 6. The single nucleotide polymorphism markers shown in Tables 3 and 6 may be used to determine whether or not there is an association with the severity of nasolabial folds.

[0181] The single nucleotide polymorphism (SNP) marker of the present invention may be, but is not limited to, any one or more selected from the markers shown in Table 3 or Table 6. The single nucleotide polymorphism (SNP) marker may be one or more, or may be used in a combination of two or more, or any number of markers that can be used to determine wrinkles, but is not limited to this.

[0182] For example, the significant single nucleotide polymorphism marker associated with the severity of nasolabial folds may be one or more single nucleotide polymorphism markers present in a gene encoding a protein of PPARGC1B, SPATA5, or EN1, and specifically may be any one or more selected from the group consisting of rs76148197, rs2166027, and rs41444645, but is not limited thereto.

[0183] For example, if the SNP ID is rs76148197, and the Chr. Position (GRCh ver. 37) is described as "2:119602515" and the allele is disclosed as A>G, this indicates that the base at position 119602515 of human chromosome 2 is A or G, and the base to the left of the ">" in the allele may represent a major allele, and the base to the right may represent a minor allele.

[0184] As a specific example, the marker selected from Table 3 may be, but is not limited to, one or more polynucleotides selected from the group consisting of: a polynucleotide consisting of 5-100 contiguous DNA sequences including base 119602515 on human chromosome 2, where base 119602515 is A or G (rs76148197); a polynucleotide consisting of 5-100 contiguous DNA sequences including base 124171618 on human chromosome 4, where base 124171618 is T or C (rs2166027); a polynucleotide consisting of 5-100 contiguous DNA sequences including base 149131368 on human chromosome 5, where base 149131368 is C or G (rs41444645); and complementary polynucleotides thereof.

[0185] In another embodiment, one or more of the single nucleotide polymorphism (SNP) markers shown in Table 6 as well as Table 3 may be selected, but is not limited thereto.

[0186] The composition of the present invention may be used as a cosmetic composition, as described above.

[0187] In another embodiment, the composition provides a quasi-drug composition for alleviating or improving nasolabial folds. In the present invention, the term "quasi-drug" is as defined above.

[0188] In another aspect, the present invention provides a method for providing information for selecting a customized substance for improving nasolabial folds, the method comprising: (a) obtaining a biological sample from an individual; (b) amplifying or hybridizing with a probe a polymorphic site of a single nucleotide polymorphism marker, the single nucleotide polymorphism marker being any one or more selected from the group consisting of rs76148197, rs2166027, and rs41444645, from the biological sample; and (c) identifying the base of the amplified or hybridized polymorphic site in step (b).

[0189] The selected customized substance can be administered to an individual having a particular polymorphic site to improve nasolabial folds.

[0190] The term "individual" as used herein refers to a subject for whom the severity of nasolabial folds is to be diagnosed. DNA can be obtained from samples such as, but not limited to, hair, urine, blood, various body fluids, isolated tissues, isolated cells, or saliva. Steps (a) and (b) are also as described above.

[0191] The substance may be one or more selected from the group consisting of, but not limited to, N-niacinamide, tranexamic acid, pyridoxine hydrochloride, camphor, cordyceps extract, sodium mannose phosphate, and retinol.

[0192] For the purposes of the present invention, the significant genes associated with the severity of nasolabial folds can provide information for selecting specific substances for each individual. For example, in the case of an individual having one or more single nucleotide polymorphism markers present in the genes encoding PPARGC1B, SPATA5, or EN1 proteins, treatment with one or more substances selected from the group consisting of niacinamide, tranexamic acid, pyridoxine hydrochloride, camphor, cordyceps extract, sodium mannose phosphate, and retinol can enhance the improvement of nasolabial folds, and an optimal combination of substances can be provided depending on the genetic characteristics of each individual.

[0193] This suggests that it may be possible to select specific single nucleotide polymorphism (SNP) markers that have a significant correlation with nasolabial folds, and provide information that will enable the selection of personalized substances that can maximize the effect of improving nasolabial folds based on genetic information.

[0194] As an example, when one or more minor alleles in the bases of rs76148197, rs2166027, and rs41444645 are present, a method for providing information may be provided that allows camphor, niacinamide, and sodium mannose phosphate to be selected; tranexamic acid and pyridoxine hydrochloride to be selected; or retinol, camphor, niacinamide, sodium mannose phosphate, tranexamic acid, pyridoxine hydrochloride, and cordyceps extract to be selected, but this is not limited to this.

[0195] In this application, the term "SNP chip" is as defined above.

[0196] In one embodiment for achieving the object of the present invention, the present invention provides a single nucleotide polymorphism (SNP) marker for diagnosing the degree of nasolabial folds.

[0197] In another aspect, the present invention provides a composition for diagnosing the degree of nasolabial folds, comprising a probe capable of detecting or an amplifying preparation of a single nucleotide polymorphism (SNP) marker for diagnosing the degree of nasolabial folds.

[0198] For purposes of the present invention, the term "degree of nasolabial folds" refers to, but is not limited to, facial wrinkles that form around the mouth when smiling or speaking. As cheek muscles lose elasticity and sag with aging, deep wrinkles form around the mouth, from the nostrils to the cheeks. Fibrous proteins such as collagen and elastin decrease with age, resulting in skin sagging and appearing as wrinkles. When linear areas of nasolabial folds exceeding a certain length are observed to be relatively darker than the surrounding skin, the term "degree of nasolabial folds" refers to, but is not limited to, the result of measuring the ratio of all measured areas to the total measured area. Specifically, the term refers to determining whether a person is susceptible to the development of nasolabial folds using one or more single nucleotide polymorphism (SNP) markers selected from Table 3 or Table 6. More specifically, a skin type prone to the development of nasolabial folds refers to a skin type that ages rapidly and therefore has a high rate of pore formation per skin area.

[0199] In the present application, the term "probe capable of detecting a marker for diagnosing the degree of nasolabial folds in skin" refers to a composition capable of diagnosing the degree of nasolabial folds by specifically identifying the polymorphic site of the gene through a hybridization reaction, and the specific method of such gene analysis is not particularly limited and may be any gene detection method known in the technical field to which the present invention pertains. In addition, the term may be used interchangeably with the term "for diagnosing whether a skin type is prone to developing nasolabial folds."

[0200] In the present application, the term "preparation capable of amplifying a marker for diagnosing the degree of nasolabial folds in skin" refers to a composition capable of diagnosing the degree of nasolabial folds by identifying the polymorphic site of the gene through amplification, and more specifically, refers to a primer capable of specifically amplifying the polynucleotide of the marker for diagnosing the degree of nasolabial folds in skin. In addition, the term may be used interchangeably with the term "for diagnosing whether a skin type is prone to developing nasolabial folds."

[0201] The primer used for amplifying the polymorphic marker is a single-stranded oligonucleotide that can act as an initiation point for template-directed DNA synthesis under appropriate conditions (e.g., four other nucleoside triphosphates and a polymerizing agent such as DNA or RNA polymerase or reverse transcriptase) in an appropriate buffer at an appropriate temperature. The appropriate length of the primer varies depending on the intended use, but is typically 15 to 30 nucleotides. Shorter primer molecules generally require lower temperatures to form stable hybrids with the template. The primer sequence does not need to be completely complementary to the template, but must be sufficiently complementary to hybridize with the template.

[0202] In this application, the term "primer" is as defined above.

[0203] In another aspect, the present invention provides a kit for diagnosing the degree of nasolabial folds in skin, comprising the composition for diagnosing the degree of nasolabial folds. The kit may be, but is not limited to, an RT-PCR kit or a DNA chip kit.

[0204] In another aspect, the present invention provides a microarray for diagnosing the extent of nasolabial folds in the skin, comprising the composition for diagnosing the extent of nasolabial folds.

[0205] The process of immobilizing probe polynucleotides on a substrate, which is relevant to the diagnosis of the severity of nasolabial folds of the present invention, can also be easily performed using such conventional techniques. Furthermore, nucleic acid hybridization on a microarray and detection of hybridization results are well known in the art. For example, the detection can be performed by labeling a nucleic acid sample with a labeling substance that generates a detectable signal, including fluorescent substances such as Cy3 and Cy5, hybridizing the sample to a microarray, and detecting the signal generated by the labeling substance to detect the hybridization results.

[0206] In another aspect, the present invention provides a method for providing information on the severity of nasolabial folds, the method comprising: (a) amplifying or hybridizing with a probe a polymorphic site of the single nucleotide polymorphism marker in DNA obtained from a sample isolated from an individual; and (b) identifying the base of the amplified or hybridized polymorphic site in step (a).

[0207] The terms "individual, (a) stage, (b) stage" are as defined above.

[0208] The method may further comprise (c) determining that the subject is at high risk of having many nasolabial folds when the amplified or hybridized bases of the polymorphic site include four or more bases of a minor allele determined by the single nucleotide polymorphism marker, but is not limited thereto.

[0209] The present invention will be described in more detail below through examples. These examples are merely illustrative of the present invention and are not to be construed as limiting the scope of the present invention. [Example]

[0210] Example 1: Derivation of significant genetic polymorphism markers associated with fine wrinkles, sagging pore wrinkles, and nasolabial folds We aimed to discover genomic regions (gene mutations) that affect the presence and severity (numerical value) of facial wrinkles in Korean women based on genetic information. This invention aims to discover genomic regions (gene mutations) related to wrinkles, and utilizes a microarray genotyping chip (manufactured by Illumina) that can screen the entire genome without pre-selecting candidate genes.

[0211] Specifically, in the present invention, an image-based skin diagnostic professional device (PIE Janus3) was used to evaluate the presence and degree of microwrinkles, the presence and degree of wrinkles due to sagging pores, and / or the presence and degree of nasolabial folds. In order to minimize external effects that may affect the presence and degree (values) of microwrinkles, the presence and degree (values) of wrinkles due to sagging pores, and / or the presence and degree (values) of nasolabial folds, the values ​​were used after adjustment for age, BMI, and the values ​​of the principal components of the community.

[0212] To confirm the association between genomic sites (gene mutations) and the presence and degree (number) of microwrinkles on the skin, the presence and degree (number) of wrinkles in sagging pores, and / or the presence and degree (number) of nasolabial folds, linear regression analysis was used to quantify the correlation significance and genetic effect.

[0213] 1-1: Evaluation method for the degree of fine wrinkles on the skin, the degree of wrinkles around sagging pores, and the degree of nasolabial folds To identify genetic polymorphism markers that could explain the severity of under-eye microwrinkles, sagging pores, and / or nasolabial folds, healthy Korean women in their 20s to 70s were recruited. For skin measurements, all subjects washed their faces with cleanser or soap and waited 30 minutes without applying any products to allow their skin to adapt to the measurement environment. The degree of skin wrinkles was then assessed using an image-based skin diagnostic device (PIE's Janus 3). Measurements and analysis were performed according to the device manufacturer's instructions. Specifically, subjects wore a hairband and a black cloth over their clothing. Their face was secured to the forehead and chin rests built into the device, and they maintained the measurement position with their eyes closed. High-resolution images of the subjects' faces were captured using the Janus 3 device's built-in camera. After extracting and de-identifying only the areas under both eyes, which were the target areas for evaluation, from the captured high-resolution images, one or more trained dermatologists judged the presence or absence of microwrinkles under the eyes and rated and quantified a grade according to the microwrinkle grading standard. One or more trained dermatologists also judged the presence or absence of wrinkles due to sagging pores and rated and quantified a grade according to the wrinkle grading standard. One or more trained dermatologists also judged the presence or absence of nasolabial folds and rated and quantified a grade according to the nasolabial fold grading standard.

[0214] For the visual evaluation, a high-resolution image of the subject's face was taken using a camera built into the Janus 3 device to obtain a facial image, and then facial landmark information was used to extract (de-identify) images of the designated under-eye area, central cheek area, and facial image to identify the areas to be evaluated. One or more trained skin specialists evaluated the presence and grade of microwrinkles under the eyes, the presence and grade of wrinkles around sagging pores, and the presence and grade of nasolabial folds. The reference images used to evaluate the grades are shown in Figures 4, 13, and 23, respectively. Figures 4 and 13 show a grade of 0 to 4 from the top left, and Figure 23 shows a grade of 0 to 5 from the top left.

[0215] Gene collection was performed through saliva collection, and for effective gene collection, all subjects were prohibited from consuming any food, including water, for 30 minutes prior to collection.

[0216] The subjects were excluded if they were: (1) pregnant, breastfeeding, or planning to become pregnant within the next six months; (2) had used topical skin preparations containing steroids for the treatment of skin diseases for more than one month; (3) had participated in the same type of study less than six months ago; (4) had sensitive or irritable skin; (5) had abnormal skin findings such as moles, acne, erythema, or telangiectasia in the study area; (6) had used the same or similar cosmetics or medicines in the study area within three months of the start of the study; (7) had undergone or planned to undergo treatment in the study area (thinning of the skin, Botox, or other skin management) within the last six months; (8) had a chronic wasting disease (asthma, diabetes, hypertension, etc.); (9) had atopic dermatitis; or (10) were otherwise deemed difficult to participate in the study by the principal investigator.

[0217] 1-2: Gene collection and analysis methods For gene analysis, human genomic DNA was extracted from saliva using a QIAamp mini prep kit (QIAGEN). The quality was confirmed by a band test on a 1x TAE 1% agarose gel at an absorbance (OD 260 / 280) of 1.7 and a concentration of 50 ng / ul. Genetic analysis was performed only on samples that passed the quality test.

[0218] Genetic analysis was carried out using Illumina's microarray genotyping chip, specifically, the genes of the subjects were analyzed using the company's global screening array product.

[0219] Genetic analysis experiments using Illumina's microarray genotyping chip were conducted according to the provided manual, and the processes of genomic DNA amplification, DNA fragmentation, precipitation, hybridization, staining, washing, coating, and scanning were performed using the provided reagents.

[0220] After the experiment, the microarray genotyping chips were scanned using iScan Control Software (Illumina). Upon completion of the scan, an idat file was automatically generated, and data quality control (sample call rate 98%, marker call rate 98%) and confirmation of gene information were performed using the GenomeStudio (Illumina) program.

[0221] In this experiment, only data that passed data quality control after genetic analysis was utilized.

[0222] 1-3: Derivation of genetic polymorphism markers related to the presence or absence of fine wrinkles on the skin, wrinkles around sagging pores, and nasolabial folds To derive genetic polymorphism markers with significance related to the presence or absence of microwrinkles, wrinkles around sagging pores, and nasolabial folds, an association analysis was conducted between the presence or absence of microwrinkles under the eyes, wrinkles around sagging pores, and nasolabial folds and genetic polymorphism markers.Specifically, the phenotype was determined using visual evaluation data by experts who judged the presence or absence of microwrinkles under the eyes, wrinkles around sagging pores, and nasolabial folds for over 1,000 Korean women.

[0223] For the genotype, genes that are likely to functionally affect the development of wrinkles were selected, and genetic polymorphism marker data located on the genes were used.

[0224] To ensure quality control of the analyzed genetic polymorphism markers, only those exceeding the criteria of a minor allele frequency >0.01 and Hardy-Weinberg equilibrium >0.000001 were used in the analysis. Furthermore, the significance of the association between the presence or absence of under-eye microwrinkles, sagging pore wrinkles, and nasolabial folds and genetic polymorphism markers was assessed using logistic regression analysis F-statistics, with a P-value <0.05 as the criterion. The analysis was performed using PLINK v 1.90 and the SNP & Variation suite (Golden Helix, Inc., Bozeman, Montana, USA) programs.

[0225] To minimize external influences that affect the degree of skin micro-wrinkles, wrinkles caused by sagging pores, and nasolabial folds, and to derive the effect of genetic information, the presence or absence of micro-wrinkles under the eyes, wrinkles caused by sagging pores, and nasolabial folds can be corrected for using information on age, whether or not you have undergone menopause, BMI (body mass index), or lifestyle habits (drinking, smoking, eating habits, sleeping habits, etc.) for analysis.

[0226] First, representative examples of SNP markers that were significantly associated with the presence or absence of skin microwrinkles, particularly microwrinkles under the eyes, are shown in Table 1 below.

[0227] [Table 1] 1) National Institutes of Health (NIH) ID, sequence can be confirmed on the website 2) Meaning of (major allele) > (minor allele) 3)minor allele frequency=(2mm+Mm) / 2(MM+Mm+mm) 4) Statistical significance of phenotypic differences for the three genotypes (M / M, M / m, m / m) (M: major allele, m: minor allele) 5) The degree of change in phenotypic risk with each minor allele increase (-: Decreased risk of fine wrinkles under the eyes, +: Increased risk of fine wrinkles under the eyes) Presence or absence of micro-wrinkles under the eyes = Presence or absence of micro-wrinkles under the eyes (visual evaluation by an expert)

[0228] Representative examples of SNP markers significantly associated with the presence or absence of sagging pores are shown in Table 2 below.

[0229] [Table 2] 1) National Institutes of Health (NIH) ID, sequence can be confirmed on the website 2) Meaning of (major allele) > (minor allele) 3)minor allele frequency=(2mm+Mm) / 2(MM+Mm+mm) 4) Statistical significance of phenotypic differences for the three genotypes (M / M, M / m, m / m) (M: major allele, m: minor allele) 5) The degree of change in phenotype risk as the number of minor alleles increases (-: decreased risk of sagging pores, +: increased risk of sagging pores) Presence or absence of sagging pores and wrinkles = Presence or absence of sagging pores on the cheeks (visual evaluation by an expert)

[0230] Representative examples of SNP markers significantly associated with the presence or absence of nasolabial folds are shown in Table 3 below.

[0231] [Table 3] 1) National Institutes of Health (NIH) ID, sequence can be confirmed on the website 2) Meaning of (major allele) > (minor allele) 3)minor allele frequency=(2mm+Mm) / 2(MM+Mm+mm) 4) Statistical significance of phenotypic differences for the three genotypes (M / M, M / m, m / m) (M: major allele, m: minor allele) 5) The degree of change in phenotypic risk with each minor allele increase (-: decreased risk of nasolabial folds, +: increased risk of nasolabial folds) Presence or absence of nasolabial folds = Presence or absence of nasolabial folds (visual evaluation by an expert)

[0232] 1-4: Derivation of genetic polymorphism markers related to the degree of fine wrinkles on the skin, the degree of wrinkles around sagging pores, and the degree of nasolabial folds To identify genetic polymorphism markers significantly associated with the severity of skin microwrinkles, sagging pore wrinkles, and nasolabial folds, an association analysis was conducted between genetic polymorphism markers and the severity of microwrinkles under the eyes, sagging pore wrinkles, and nasolabial folds. Specifically, the phenotype was determined using visual evaluation data from experts who judged the presence or absence of microwrinkles under the eyes, sagging pore wrinkles, and nasolabial folds in over 2,000 Korean women. For the visual evaluation, high-resolution images of the subjects' faces were captured using a camera built into the Janus 3 device. Images of the designated areas under the eyes, central cheeks, and nasolabial folds were then extracted (de-identified) using facial landmark information to identify the areas to be evaluated. One or more trained skin specialists evaluated the presence and grade of fine wrinkles under the eyes, the presence and grade of wrinkles around sagging pores, and the presence and grade of nasolabial folds. The reference images used to evaluate the grades are shown in Figures 4 and 13, with grades ranging from 0 to 4 indicated from the top left of Figures 4 and 13. The reference images used to evaluate the presence and grade of nasolabial folds are shown in Figure 23, with grades ranging from 0 to 5 indicated from the top left of Figure 23.

[0233] Genotypes were analyzed using all polymorphic marker data observed at the genome-wide level generated through microarray chips. To ensure quality control of the polymorphic markers, only those polymorphic markers exceeding the following criteria were used: minor allele frequency > 0.01 and Hardy-Weinberg equilibrium > 0.000001. The significance of the association between the severity of under-eye microwrinkles and polymorphic markers was assessed using logistic regression analysis F-statistics, with a p-value < 0.0001. Analysis was performed using PLINK v 1.90 and the SNP & Variation suite (Golden Helix, Inc., Bozeman, Montana, USA).

[0234] In order to minimize external influences that affect the degree of fine wrinkles under the eyes, wrinkles caused by sagging pores, and nasolabial folds, and to derive the effect of genetic information, the degree of fine wrinkles under the eyes, wrinkles caused by sagging pores, and nasolabial folds can be adjusted using information on age, whether or not you have undergone menopause, BMI (body mass index), or lifestyle habits (drinking, smoking, eating habits, sleeping habits, etc.) and used in the analysis.

[0235] First, representative examples of SNP markers significantly associated with the degree of skin microwrinkles, particularly microwrinkles under the eyes, are shown in Table 4 below.

[0236] [Table 4] [Table 5] [Table 6] [Table 7] [Table 8] Table 9 Table 10 Table 11 Table 12 Table 13 Table 14 Table 15 Table 16 Table 17 Table 18 Table 19 Table 20 Table 21 Table 22 Table 23 Table 24 Table 25 Table 26 Table 27 Table 28 Table 29 Table 30 Table 31 Table 32 Table 33 Table 34 Table 35 Table 36 Table 37 Table 38 Table 39 Table 40 Table 41 Table 42 Table 43 [Table 44] [Table 45] [Table 46] [Table 47] [Table 48] [Table 49] [Table 50] [Table 51] [Table 52] [Table 53] [Table 54] [Table 55] [Table 56] 1) National Institutes of Health (NIH) ID, sequence can be confirmed on the website 2) Meaning of (major allele) > (minor allele) 3)minor allele frequency=(2mm+Mm) / 2(MM+Mm+mm) 4) Statistical significance of phenotypic differences for the three genotypes (M / M, M / m, m / m) (M: major allele, m: minor allele) 5) The degree of phenotypic change with each minor allele increase (-: decreased risk of fine wrinkles under the eyes, +: increased risk of fine wrinkles under the eyes) Presence or absence of micro-wrinkles under the eyes = Severity level of micro-wrinkles under the eyes (visual evaluation by an expert)

[0237] Representative examples of SNP markers significantly associated with wrinkles in sagging pores, particularly with the degree of wrinkles in sagging pores, are shown in Table 5 below.

[0238] [Table 57] [Table 58] [Table 59] [Table 60] [Table 61] [Table 62] [Table 63] [Table 64] [Table 65] [Table 66] [Table 67] [Table 68] [Table 69] Table 70 Table 71 Table 72 Table 73 Table 74 Table 75 Table 76 Table 77 Table 78 Table 79 Table 80 Table 81 Table 82 Table 83 Table 84 Table 85 Table 86 Table 87 Table 88 Table 89 Table 90 Table 91 Table 92 Table 93 Table 94 Table 95 Table 96 Table 97 Table 98 Table 99 Table 100 Table 101 Table 102 Table 103 Table 104 [Table 105] [Table 106] [Table 107] [Table 108] 1) National Institutes of Health (NIH) ID, sequence can be confirmed on the website 2) Meaning of (major allele) > (minor allele) 3)minor allele frequency=(2mm+Mm) / 2(MM+Mm+mm) 4) Statistical significance of phenotypic differences for the three genotypes (M / M, M / m, m / m) (M: major allele, m: minor allele) 5) The degree of phenotypic change with each minor allele increase (-: decreased risk of wrinkles due to sagging pores, +: increased risk of wrinkles due to sagging pores) Degree of wrinkles caused by sagging pores = Severity level of sagging pores on cheeks (visual evaluation by an expert)

[0239] Representative examples of SNP markers significantly associated with the degree of nasolabial folds are shown in Table 6 below.

[0240] [Table 109] [Table 110] [Table 111] [Table 112] [Table 113] Table 114 Table 115 Table 116 Table 117 Table 118 Table 119 Table 120 Table 121 Table 122

Table 123

[0241] Example 2: Analysis of the collagen synthesis promoting effect of various substances 2-1. Analysis of the collagen synthesis promoting effect of various substances for improving skin microwrinkles We decided to examine whether various substances that can promote collagen synthesis based on the gene and related mechanisms are effective in promoting collagen synthesis.

[0242] Specifically, the substances used were phloretin, oryzanol, lupeol, and sucralfate.

[0243] Human dermal fibroblasts (NHDF-Neo-Human Dermal Fibroblasts, Neonatal, Lonza, CC-2509) were purchased from Lonza and cultured in a medium containing Dulbecco Modified Eagle Medium (DMEM, Thermo Fisher Scientific) supplemented with 10% Fetal Bovine Serum (FBS) and 1% antibiotics (penicillin streptomycin) at 37°C in a 5% CO2 incubator.

[0244] To analyze the collagen mRNA synthesis promotion effect, human dermal fibroblasts were cultured in a 6-well plate at 1.5x10 5 Cells were dispensed into wells and cultured for 24 hours in a 37°C, 5% CO2 incubator. Substances were added to serum-free media at appropriate concentrations and combinations, and the cells were cultured again under the same conditions for 24 hours. mRNA was extracted using an RNA-spin total RNA extraction kit (Intron Biotechnology, 17211), and cDNA was synthesized using a cDNA synthesis kit (Phillia Technology, ET21100). Expression levels of each gene were analyzed by qPCR using the synthesized cDNA and TaqMan probes (assay ID: COL1A1-Hs00164004_m1, COL3A1-Hs00943809_m1, COL4A1-Hs00266237_m1, BNC2-Hs00417700_m1, EDAR-Hs00223468_m1).

[0245] As shown in Figure 1, the results confirmed that treatment with phloretin or oryzanol alone promoted the expression of Type I collagen (COL1A1), Type III collagen (COL3A1), and Type IV collagen (COL4A1), while combined treatment with phloretin and oryzanol demonstrated a synergistic effect on the gene expression of Type I collagen (COL1A1) and Type IV collagen (COL4A1).

[0246] Furthermore, as shown in Figure 2, it was confirmed that the expression of Type III collagen (COL3A1) was promoted when treated with lupeol or sucralfate alone, and that a synergistic effect on the gene expression of Type III collagen (COL3A1) and Type IV collagen (COL4A1) was observed when treated with a combination of lupeol and sucralfate.

[0247] 2-2. Analysis of the collagen synthesis promoting effect of various substances for improving sagging pores and wrinkles We decided to treat the gene and related mechanisms with various substances that can promote collagen synthesis to see if they are effective in promoting collagen synthesis.

[0248] Specifically, the substances used were fucoidan, N-feruloylserotonin, emodin, and formononetin.

[0249] Human dermal fibroblasts (NHDF-Neo-Human Dermal Fibroblasts, Neonatal, Lonza, CC-2509) were purchased from Lonza and used. The purchased cells were cultured in a medium made by mixing DMEM (Dulbecco Modified Eagle Medium, Thermo Fisher Scientific) with 10% FBS (Fetal Bovine Serum) and 1% antibiotics (Penicillin Streptomycin) in an incubator at 37°C and 5% CO2.

[0250] To analyze the collagen mRNA synthesis promotion effect, human dermal fibroblasts were cultured in a 6-well plate at 1.5x10 5 Cells were dispensed into wells and cultured for 24 hours in a 37°C, 5% CO2 incubator. Substances were added to serum-free media at appropriate concentrations and combinations, and the cells were cultured again under the same conditions for 24 hours. mRNA was extracted using an RNA-spin total RNA extraction kit (Intron Biotechnology, 17211), and cDNA was synthesized using a cDNA synthesis kit (Phillia Technology, ET21100). Expression levels of each gene were analyzed by qPCR using the synthesized cDNA and TaqMan probes (assay ID: COL1A1-Hs00164004_m1, COL4A1-Hs00266237_m1, sgpp2-Hs00544786_m1), ADIPOQ F primer (5'-CAGGCCGTGATGGCAGAGATG-3'), and ADIPOQ R primer (5'-GGTTTCACCGATGTCTCCCTTAG-3').

[0251] As a result, as shown in FIG. 10, it was confirmed that the expression of Type IV collagen (COL4A1) was promoted when treated with fucoidan or N-feruloyl serotonin alone, and that a synergistic effect on the gene expression of Type IV collagen (COL4A1) was observed when treated with a combination of fucoidan and N-feruloyl serotonin.

[0252] Furthermore, as shown in Figure 11, it was confirmed that treatment with emodin or formononetin alone promoted the expression of Type I collagen (COL1A1) and Type IV collagen (COL4A1), and that combined treatment with emodin and formononetin produced a synergistic effect on the gene expression of Type I collagen (COL1A1) and Type IV collagen (COL4A1).

[0253] 2-3. Analysis of the collagen synthesis promoting effect of various substances for improving nasolabial folds We decided to treat the gene and related mechanisms with various substances that can promote collagen synthesis to see if they are effective in promoting collagen synthesis.

[0254] Specifically, the substances used were niacinamide, tranexamic acid, pyridoxine HCl, camphor, cordyceps extract, and sodium mannose phosphate.

[0255] Human dermal fibroblasts (NHDF-Neo-Human Dermal Fibroblasts, Neonatal, Lonza, CC-2509) were purchased from Lonza and cultured in a medium containing Dulbecco Modified Eagle Medium (DMEM, Thermo Fisher Scientific) supplemented with 10% Fetal Bovine Serum (FBS) and 1% antibiotics (penicillin streptomycin) at 37°C in a 5% CO2 incubator.

[0256] To analyze the collagen mRNA synthesis promotion effect, human dermal fibroblasts were cultured in a 6-well plate at 1.5x10 5 Cells were dispensed into wells and cultured for 24 hours in a 37°C, 5% CO2 incubator. Substances were added to serum-free media at appropriate concentrations and combinations, and the cells were cultured again under the same conditions for 24 hours. mRNA was extracted using an RNA-spin total RNA extraction kit (Intron Biotechnology, 17211), and cDNA was synthesized using a cDNA synthesis kit (Phillia Technology, ET21100). Expression levels of each gene were analyzed by qPCR using the synthesized cDNA and TaqMan probes (assay ID: COL1A1-Hs00164004_m1, COL3A1-Hs00943809_m1, PPARGC1B-Hs00993805_m1, SPATA5-Hs01047535_m1, EN1-Hs00154977_m1).

[0257] As a result, as shown in FIG. 19, it was confirmed that the expression of Type I collagen (COL1A1) was promoted when treated with camphor, niacinamide, or sodium mannose phosphate alone, and that a synergistic effect on the gene expression of Type I collagen (COL1A1) was observed when treated with a combination of camphor, niacinamide, and sodium mannose phosphate.

[0258] In addition, we confirmed that treatment with tranexamic acid or pyridoxine hydrochloride alone promoted the expression of Type I collagen (COL1A1), and that combined treatment with tranexamic acid and pyridoxine hydrochloride produced a synergistic effect on the gene expression of Type I collagen (COL1A1).

[0259] Furthermore, as shown in FIG. 20, it was confirmed that the most excellent synergistic effect on the gene expression of Type I collagen (COL1A1) was observed when a mixture of seven substances including six of the present invention (camphor, niacinamide, sodium mannose phosphate, tranexamic acid, pyridoxine hydrochloride, and cordyceps extract) and retinol was treated.

[0260] Example 3: Retinol ratio Human application test to confirm the degree of improvement of fine wrinkles on the skin, the degree of improvement of wrinkles around sagging pores, and the degree of improvement of nasolabial folds Based on the polymorphic markers obtained through Example 1 that show correlations with the presence or absence of microwrinkles on the skin, the presence or absence of wrinkles around sagging pores, and the presence and degree of nasolabial folds, we decided to discover substances that can maximize the effects of improving microwrinkles on the skin, the presence or absence of wrinkles around sagging pores, and the nasolabial folds, and to prescribe customized substances.

[0261] 3-1: Selection of subjects After receiving approval (LG-Wr_Fine-2021-1013) from the Institutional Review Board (IRB, Korea), the study was conducted in accordance with the standard operating guidelines and clinical trial standards of the Institutional Review Board of LG Household & Health Care Corporation. To confirm the degree of improvement in fine wrinkles on the skin, 11 healthy subjects in their 20s to 50s with many wrinkles around the eyes and under the eyes, no apparent abnormalities in the skin's appearance, and no history of dermatological treatment within the three months prior to the start of the study were selected.

[0262] In addition, to confirm the degree of improvement in wrinkles caused by sagging pores, eight healthy test subjects were selected from adults in their 20s to 50s who had many wrinkles caused by sagging pores around the cheeks, whose skin did not appear to be abnormal in appearance, and who had not undergone any dermatological treatment within the three months prior to the start of the study.

[0263] To confirm the degree of improvement in nasolabial folds, 10 healthy subjects in their 20s to 50s with normal skin appearance and no history of dermatological treatment within the three months prior to the start of the study were selected.

[0264] 3-2: Exclusion criteria for subjects Among the subjects, those who 1) had eczema / infectious skin diseases, 2) had specific allergic constitutions or hypersensitivity, 3) were pregnant or breastfeeding, 4) had severe nutritional disorders, 5) were addicted to drugs or alcohol, 6) had moles, acne, tattoos, erythema, burn marks, etc. at the test site, 7) had participated in the same test less than one month ago, or 8) had high blood pressure or diabetes were excluded from the study.

[0265] 3-3: Exam information 3-3-1: Test information for the degree of improvement of fine wrinkles on the skin The control cream was a 0.1% (3300 IU) retinol cream, which was applied to the outer corner of the left eye every other day in the evening from week 0 to week 2 as a skin adaptation period, and then every day in the evening from week 2 until the end of the experiment.

[0266] The experimental group cream was Phloretin 0.05%, oryzanol 0.1%, lupeol (raw material name: collageneer) 2%, and sucralfate (raw material name: sucralfatesome) 2% and was applied to the corner of the right eye twice a day, morning and evening.

[0267] The product was used for a total of 4 weeks, and wrinkles were measured before and after use using Antera 3D, and the overall texture size (Ra value) of the fine wrinkles under the eyes was calculated.

[0268] The overall size of microwrinkles - Ra value means the total volume of areas that are higher or lower than the surface area when measuring the antera, divided by the total area.

[0269] 3-3-2: Test information for the degree of improvement of sagging skin, pores, and wrinkles The control cream was a 0.1% (3300 IU) retinol cream, which was applied to the left cheek every other day in the evening from week 0 to week 2 as a skin adaptation period, and then every day in the evening from week 2 to week 4.

[0270] The experimental cream contained N-feruloylserotonin 0.3%, Fucoidan 2%, Emodin 0.5%, and Formononetin 1%, and was applied to the right cheek twice a day, morning and evening.

[0271] The device was used for a total of 4 weeks, and wrinkles were measured using the Antera 3D before the experiment (week 0) and after the experiment (week 4). The volume of sagging pores in the butterfly zone of the cheeks was then selected and analyzed using Image J.

[0272] 3-3-3: Test information for the degree of improvement of nasolabial folds The control group cream was a 0.1% (2500 IU) retinol cream, which was applied to the left nasolabial fold area every other day from week 0 to week 2 as a skin adaptation period, and from week 3 onwards it was applied to the left nasolabial fold area every evening.

[0273] The experimental group cream contained niacinamide 2%, tranexamic acid 2%, pyridoxine hydrochloride 0.1%, camphor 0.03%, cordyceps extract 1%, and sodium mannose phosphate 0.1% and was applied to the right nasolabial fold area twice daily, morning and evening.

[0274] The product was used for a total of 8 weeks, and wrinkles were measured every 4 weeks using the Antera 3D, followed by measurements of fold wrinkle length and depth in the area of ​​the nasolabial fold.

[0275] 3-4: Wrinkle measurement equipment and measurement / analysis methods 3-4-1: Under-eye microwrinkle measuring device and measurement / analysis method Using Antera 3D, photographs of the area around the eyes (left and right) were taken to obtain 3D images (three times) (Figure 3).

[0276] 1) Analysis item: texture 2) In the area designation tool, select stripe → Designate the skin under the eye directly below the eyelashes (designate as an under-eye patch, width 9mm), and automatically select the same area on the 0-week and 4-week images. 3) During texture analysis, the analysis is carried out using the Ra value among the score, Ra, Rq, and Rmax parameters, and the average of the values ​​taken three times is calculated and compared.

[0277] 3-4-2: Sagging pore wrinkle measurement equipment and measurement / analysis method Using the Antera 3D, 3D images were taken of the pores around the cheeks between the nose and cheek bones (on each cheek) (three times) (Figure 12).

[0278] 1) Analysis item: Volume 2) In the area designation tool, select stripe → Measure the area with noticeable pores diagonally to the side of the nose (width 19 mm), and automatically select the same area on the images at 0 and 4 weeks. 3) During volume analysis After analyzing with a threshold width of 2 mm, set the hue to 90-140 in Image J Adjust > Color Threshold and the size to 0-1000 in Filtered Analyze Particles mode. Then, proceed with the analysis using the average of the results corresponding to Major (the long axis length of the particle) from the analyzed results, and compare the average of the values ​​taken three times.

[0279] 3-4-3: Nasolabial fold measuring equipment and measurement / analysis method Using the Antera 3D, 3D images were taken of the nasolabial fold area (left and right) (three times) (Figure 22). 1) Analysis item: Fold (Maximal width of detected wrinkle=3mm fixed) 2) In the area designation tool, select a polygonal shape → Specify the area of ​​the nasolabial folds from both sides of the nostrils down to the mouth, and the same area will be automatically selected on the 0 and 4 week images. 3) During the Fold numerical analysis, the length value is used to analyze the length of the nasolabial folds, and the Max depth value is used to analyze the maximum depth of the nasolabial folds. The average of the values ​​obtained by taking three photographs is calculated and compared.

[0280] 3-5: Confirmation of improvement in skin wrinkles compared to retinol 3-5-1: Degree of improvement of fine wrinkles on the skin Four substances of the present invention (phloretin, oryzanol, lupeol, and sucralfate) effective in promoting collagen synthesis in Example 2 were mixed and applied to the corner of the right eye, and a control cream (retinol) was applied to the corner of the left eye.

[0281] As a result, as shown in Figure 5, after 4 weeks of application, it was confirmed that the cream containing phloretin, oryzanol, lupeol, and sucralfate showed a 2.1-fold improvement rate in fine wrinkles compared to retinol.

[0282] 3-5-2: Check the degree of improvement of sagging pores and wrinkles In Example 2, four substances of the present invention (fucoidan, N-feruloyl serotonin, emodin, and formononetin) that are effective in promoting collagen synthesis were mixed and applied to the right cheek, and a control cream (retinol) was applied to the left cheek.

[0283] As a result, as shown in Figure 14, after 4 weeks of application, it was confirmed that the cream containing fucoidan, N-feruloyl serotonin, emodin, and formononetin showed a 1.8 times better improvement rate in wrinkles caused by sagging pores than retinol.

[0284] Example 4: Confirmation of correlation between significant polymorphic markers associated with the degree of skin wrinkles and treatment with wrinkle-reducing substances 4-1: Confirmation of the correlation between significant polymorphism markers related to the degree of skin microwrinkles and treatment with substances that improve microwrinkles Based on the polymorphic markers associated with the degree of skin microwrinkles obtained in Example 1, the degree of improvement of microwrinkles by the substance of the present invention was confirmed.

[0285] For example, it has been reported that the higher the expression level of BNC2, a transcription factor in skin cells (especially keratinocytes), the darker the skin color, and that mutations in the BNC2 gene are associated with pigmented spots on the skin. Reducing the expression level of BNC2 reduces reactivity to reactive oxygen species, thereby preventing the progression of cellular aging and apoptosis. In other words, reducing the expression level of BNC2 by treating with the substance of the present invention is effective in improving wrinkles.

[0286] As shown in Figure 6, it was confirmed that BNC2 expression was suppressed when phloretin or oryzanol was treated alone, and that combined treatment with phloretin and oryzanol resulted in a synergistic effect that suppressed BNC2 expression more effectively than either treatment alone.

[0287] As another example, EDAR, known as an EDA receptor important in the development of the ectoderm during the development of living organisms, has been reported to induce hypohidrotic ectodermal dysplasia (HED), in which NF-kB signaling is suppressed as expression levels decrease, causing thinning and dryness of the skin, particularly around the eyes, and wrinkles and pigmentation.Increasing EDAR expression levels increases chemokines through NF-kB activity, thereby increasing the ability to recover from stimuli such as photoaging.In other words, increasing EDAR expression levels by treating the substance of the present invention is effective in improving wrinkles.

[0288] As shown in Figure 7, it was confirmed that EDAR expression increased when lupeol and sucralfate were treated alone, and that combined treatment with lupeol and sucralfate promoted EDAR expression more effectively than single treatment due to a synergistic effect.

[0289] This shows that the substance of the present invention, which has high reactivity in improving microwrinkles relative to retinol, can be treated to create a customized prescription depending on the type of polymorphic marker associated with the presence or absence of microwrinkles.

[0290] 4-2: Confirmation of the correlation between significant polymorphism markers related to the degree of wrinkles in sagging pores and treatment with substances that improve wrinkles in sagging pores Based on the polymorphic markers associated with the degree of wrinkles in sagging pores obtained through Example 1, the degree of improvement in wrinkles in sagging pores by the substance of the present invention was confirmed.

[0291] For example, SGPP2 is a gene that expresses an enzyme that primarily acts in inflammatory conditions, and when SGPP2 is overactive, the skin becomes more vulnerable to inflammatory signals. As inflammatory responses gradually accumulate during skin aging, when SGPP2 activity is high, the skin becomes vulnerable to inflammatory signals, and the inflammatory responses easily accumulate, leading to skin aging. Therefore, reducing the expression level of SGPP2 reduces reactivity to inflammation and prevents the progression of skin aging. In other words, reducing the expression level of SGPP2 by treating the substance of the present invention is effective in improving wrinkles.

[0292] As shown in Figure 15, it was confirmed that SGPP2 expression was suppressed when fucoidan and N-feruloyl serotonin were treated alone, and that when fucoidan and N-feruloyl serotonin were treated together, SGPP2 expression was more effectively suppressed than when treated alone due to a synergistic effect.

[0293] As another example, ADIPOQ is a gene that expresses adiponectin and is a substance primarily secreted from adipose tissue. In skin, ADIPOQ is known to have anti-inflammatory properties. Lower ADIPOQ reactivity in the skin reduces anti-inflammatory properties in the skin, making it more likely to induce an inflammatory environment. Furthermore, this can lead to the formation of triglycerides, a decrease in dermal elasticity, and the formation of sagging skin. Increasing the expression level of ADIPOQ reduces triglycerides, increases dermal elasticity, and reduces sagging skin. In other words, increasing the expression level of ADIPOQ by treating the substance of the present invention is effective in improving wrinkles.

[0294] As shown in Figure 16, it was confirmed that ADIPOQ expression increased when emodin and formononetin were treated alone, and that combined treatment with emodin and formononetin promoted ADIPOQ expression more effectively than single treatment due to a synergistic effect.

[0295] This shows that by treating the substance of the present invention, which has a high reactivity to improving wrinkles in sagging pores compared to retinol, customized prescriptions can be made depending on the type of polymorphic marker related to the presence or absence of wrinkles in sagging pores.

[0296] 4-3: Confirmation of the correlation between significant polymorphism markers related to the degree of nasolabial folds and treatment with substances that improve nasolabial folds Based on the polymorphic markers associated with the severity of nasolabial folds obtained through Example 1, the degree of improvement of nasolabial folds by the substance of the present invention was confirmed.

[0297] For example, PPARGC1B is a co-activator of peroxisome proliferator activated receptor-γ (PPARγ) and is known to be involved in melanogenesis in the skin. It has been reported that PPARGC1B is involved in the development of wrinkles due to impaired mitochondrial function and in the reduction of wrinkles due to the restoration of impaired mitochondrial function (Cell Death & Disease volume 9, Article number: 735 (2018)). Therefore, increasing the expression level of PPARGC1B plays a role in restoring the function of mitochondria, the cellular energy-generating organelle, thereby preventing and improving nasolabial folds, which are deep, depressed wrinkles that accumulate over a relatively long period of time. In other words, increasing the expression level of PPARGC1B by treating the substance of the present invention is effective in improving wrinkles.

[0298] As shown in Table 7 below, it was confirmed that PPARGC1B expression increased when treated with niacinamide, camphor, or sodium mannose phosphate.

[0299] [Table 396]

[0300] As another example, SPATA5 is a gene related to spermatogenesis, involved in the formation of mitochondrial morphology during early spermatogenesis. It has been shown to be involved in the regulation of mitochondrial remodeling and ATP production during brain development (Neurology Apr 2019, 92 (15 Supplement) P4.6-062). While its role in skin has not been studied, the study suggests that it may play a role in mitochondrial function and ATP production. Therefore, increasing SPATA5 expression levels may play a role in restoring the function of mitochondria, the cellular energy-producing organelle, thereby preventing and improving nasolabial folds, which are deep, depressed wrinkles that accumulate over a relatively long period of time. In other words, increasing SPATA5 expression levels by treating the substance of the present invention is effective in improving wrinkles.

[0301] As shown in Table 8 below, it was confirmed that the expression of SPATA5 increased when treated with tranexamic acid or pyridoxine hydrochloride.

[0302] [Table 397]

[0303] As another example, EN1 is a transcription factor gene known to play a role in the wound healing process in the skin. Increased expression of EN1 accelerates wound healing by rapidly increasing extracellular matrix (ECM) components, which also helps reduce wrinkles. In other words, increasing the expression level of EN1 through treatment with the substance of the present invention is effective in improving wrinkles.

[0304] As shown in Table 9 below, it was confirmed that the expression of EN1 increased when treated with Cordyceps sinensis extract. [Table 398]

[0305] This shows that by treating the substance of the present invention, which has high reactivity in improving nasolabial folds relative to retinol, a customized prescription can be made depending on the type of polymorphic marker associated with the presence or absence of nasolabial folds.

[0306] Example 5: Human application test to develop a customized wrinkle improvement formula for high-risk wrinkle groups Through the correlation between the significant polymorphic markers related to the degree of skin microwrinkles, wrinkles due to sagging pores, and / or nasolabial folds obtained through Example 3 and the treatment with the substance of the present invention, we have provided a substance that increases the efficiency of improving microwrinkles, wrinkles due to sagging pores, and / or nasolabial folds depending on the level of wrinkle risk.

[0307] 5-1: Selection of subjects 5-1-1: Selection of subjects for the degree of fine wrinkles After receiving approval (LG-Wr_Fine-2021-1013) from the Institutional Review Board (IRB, Korea), the study was conducted in accordance with the standard operating guidelines and clinical trial standards of the Institutional Bioethics Committee of LG Household & Health Care Corporation. Ten healthy subjects were selected, who were adults in their 20s to 50s with many wrinkles around the eyes and under the eyes, had no apparent abnormalities in their skin appearance, and had not undergone any dermatological treatment within the three months prior to the start of the study.

[0308] Based on the genetic polymorphism markers associated with the presence or absence of under-eye microwrinkles in Table 1, subjects were classified into a low-risk group and a high-risk group according to the level of risk for developing microwrinkles, as follows:

[0309] Low risk group (n=5) containing 3 or fewer minor alleles out of 5 markers High risk group (n=5) containing 4 or more minor alleles out of 5 markers

[0310] 5-1-2: Selection of subjects for the degree of sagging pores and wrinkles After receiving approval (LG-Wr_Fine-2021-1013) from the Institutional Review Board (IRB, Korea), the study was conducted in accordance with the standard operating guidelines and clinical trial standards of the Institutional Bioethics Committee of LG Household & Health Care Corporation. Eight healthy subjects were selected from adults in their 20s to 50s with many wrinkles and sagging skin around the cheeks, no apparent abnormalities in the skin's appearance, and no history of dermatological treatment within one month prior to the start of the study.

[0311] Of the four genetic polymorphism markers associated with the presence or absence of wrinkles in sagging pores shown in Table 2, the subjects were classified into low-risk and high-risk groups according to the level of risk of developing wrinkles in sagging pores based on the two markers with effect size values, SGPP2 (rs4592839) and ADIPOQ (rs76071583), as shown below.

[0312] Low risk group (n=4) with 0 or fewer minor alleles among 2 markers High risk group (n=4) containing one or more minor alleles among two markers

[0313] 5-1-3: Selection of subjects for the degree of nasolabial folds After receiving approval (LG-Wr_Deep-2021-1018) from the Institutional Review Board (IRB, Korea), the study was conducted in accordance with the standard operating guidelines and clinical trial standards of the Institutional Bioethics Committee of LG Household & Health Care Corporation. Ten healthy subjects were selected, who were adults in their 20s to 50s with many nasolabial folds around the cheeks, had no apparent abnormalities in their skin appearance, and had not undergone any dermatological treatment within one month prior to the start of the study.

[0314] Subjects were classified into low-risk and high-risk groups according to the risk level of developing nasolabial folds based on the three gene polymorphism markers related to nasolabial folds in Table 3, as follows:

[0315] The sum of the number of minor alleles of each marker * Effect size (β) is 0.08 or more > High risk group (n=5) The sum of the number of minor alleles of each marker * Effect size (β) is less than 0.08 > Low risk group (n=5) * Example 1: If the number of minor alleles of markers of subject 1 is PPARGC1B = 1, SPATA5 = 1, EN1 = 2, the risk level = 1 * 0.57 + 1 * (-0.23) + 2 * 0.27 = 0.88 high risk group * Example 2: If the number of minor alleles of markers for subject 2 is PPARGC1B=0, SPATA5=2, and EN1=0, the risk level = 2*(-0.23)=-0.46 (low risk group)

[0316] 5-2: Subject Exclusion Criteria Same as Example 3-2

[0317] 5-3: Exam information Same as Example 3-3

[0318] 5-4: Wrinkle measurement equipment and measurement / analysis methods Same as Example 3-4

[0319] 5-5: Confirmation of wrinkle improvement rate by treatment with the substance of the present invention 5-5-1: Confirmation of improvement rate of fine wrinkles When a cream containing the four substances of the present invention (phloretin, oryzanol, lupeol, and sucralfate) was applied, the length of fine wrinkles under the eyes improved to a similar level in the low-risk group when a customized retinol-only formulation was applied, as shown in Figures 8 and 9, but the improvement rate of fine wrinkles under the eyes increased by about 3.6 times in the high-risk group when a customized retinol-only formulation was applied.

[0320] This shows that responsiveness to substances varies depending on whether or not a person has a specific gene SNP allele, and that providing a customized prescription to high-risk groups with a high risk of developing microwrinkles can increase the efficiency of improving microwrinkles.

[0321] 5-5-2: Confirmation of improvement rate of sagging pores and wrinkles A retinol prescription and a customized prescription (N-feruloylserotonin 0.3%, Fucoidan 2%, Emodin 0.5%, Formononetin 1%) were prescribed to low-risk and high-risk groups, and it was confirmed that the customized prescription was 2.26 times more effective in improving sagging pores and wrinkles in the high-risk group compared to the low-risk group.

[0322] In the low-risk group, the average length of wrinkles around sagging pores improved to a similar level when a customized retinol-only formulation was applied, while in the high-risk group, the average length of wrinkles around sagging pores improved 2.7 times more when a customized retinol-only formulation was applied.

[0323] This shows that responsiveness to substances varies depending on whether or not a person has an allele of a specific gene SNP, and that by providing a customized prescription to a high-risk group with a high risk of developing wrinkles due to sagging pores, the efficiency of improving wrinkles due to sagging pores can be increased.

[0324] 5-5-3: Check the improvement rate of nasolabial folds In the low-risk group, the length of nasolabial folds improved to a similar level to that of retinol when the customized formula was applied, and the maximum depth was significantly improved by approximately 44% (Figure 21).

[0325] In the high-risk group, application of the customized formula not only significantly improved the length of nasolabial folds by more than 58.2% compared to retinol, but also significantly improved the maximum depth by approximately 173.9% (Figure 21).

[0326] This shows that responsiveness to substances varies depending on whether or not a person has an allele of a specific gene SNP, and that providing a customized prescription to high-risk groups with a high level of risk for developing nasolabial folds can increase the efficiency of improving nasolabial folds.

[0327] From the above description, those skilled in the art to which the present invention pertains will understand that the present invention may be embodied in other specific forms without changing the technical spirit or essential characteristics thereof. In this regard, it should be understood that the above-described embodiments are merely illustrative and not limiting. The scope of the present invention should be interpreted as including within the meaning and scope of the claims below, and any modifications or variations derived from the equivalent concepts thereof, rather than the above detailed description.

Claims

1. A composition for improving fine wrinkles on the skin, comprising one or more active ingredients selected from the group consisting of phloretin, oryzanol, lupeol, and sucralfate.

2. The composition (i) phloretin and oryzanol; (ii) lupeol and sucralfate; or (iii) The composition according to claim 1, comprising phloretin, oryzanol, lupeol and sucralfate as active ingredients.

3. 2. The composition according to claim 1, wherein the substance is contained in an amount of 0.0001 to 10% by weight based on the total weight of the composition.

4. The composition of claim 1 , wherein the microwrinkles on the skin are microwrinkles under the eyes or microwrinkles around the mouth.

5. The composition of claim 1 , wherein the composition is characterized by promoting collagen synthesis.

6. 6. The composition according to claim 5, wherein the substances for promoting the synthesis of collagen type I or collagen type IV are phloretin and oryzanol.

7. 6. The composition according to claim 5, wherein the substances for promoting the synthesis of collagen type III or collagen type IV are lupeol and sucralfate.

8. The composition according to claim 1, wherein the substance promotes the expression of EDAR or inhibits the expression of BNC2.

9. The composition according to claim 8, wherein the substance for inhibiting the expression of BNC2 is phloretin or oryzanol.

10. The composition according to claim 8, wherein the substance for promoting the expression of EDAR is lupeol or sucralfate.

11. The composition according to claim 1, wherein the wrinkle improvement is customized for an individual having one or more single nucleotide polymorphism markers present in a gene encoding an EDAR or BNC2 protein.

12. The composition of claim 11, wherein the single nucleotide polymorphism marker is any one or more selected from the group consisting of rs10865025, rs10756807, rs1952688, rs10116469, and rs12338608.

13. The single nucleotide polymorphism marker is a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the 109511765th base of human chromosome 2, in which the 109511765th base is G or A (rs10865025); a polynucleotide consisting of a continuous DNA sequence of 5-100 bases including the 16756041st base of human chromosome 9, in which the 16756041st base is G or A (rs10756807); a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the 16782156th base of human chromosome 9, in which the 16782156th base is A or G (rs1952688); a polynucleotide consisting of a continuous DNA sequence of 5-100 bases including the 16783095th base of human chromosome 9, in which the 16783095th base is A or T (rs10116469); a polynucleotide consisting of a continuous DNA sequence of 5-100 bases including base 16800470 of human chromosome 9, in which the base at base 16800470 is C or T (rs12338608); and complementary polynucleotides thereof.

14. (a) obtaining a biological sample from an individual; (b) amplifying or hybridizing with a probe a polymorphic site of a single nucleotide polymorphism marker selected from the group consisting of rs10865025, rs10756807, rs1952688, rs10116469, and rs12338608 from the biological sample; and (c) A method for providing information to select a customized substance for improving fine wrinkles, comprising a step of identifying the base of the amplified or hybridized polymorphic site in step (b).

15. 15. The method for providing information according to claim 14, wherein the substance is one or more selected from the group consisting of phloretin, oryzanol, lupeol, and sucralfate.

16. The information providing method according to claim 14, wherein, when four or more minor alleles are present among the bases rs10865025, rs10756807, rs1952688, rs10116469, and rs12338608, the customized substance for improving fine wrinkles is selected from phloretin and oryzanol; lupeol and sucralfate; or phloretin, oryzanol, lupeol, and sucralfate.

17. A composition for improving wrinkles in sagging pores, comprising one or more active ingredients selected from the group consisting of fucoidan, N-feruloylserotonin, emodin, and formononetin.

18. The composition comprises: (i) fucoidan and N-feruloyl serotonin; (ii) emodin and formononetin; or (iii) The composition according to claim 17, comprising fucoidan, N-feruloyl serotonin, emodin, and formononetin as active ingredients.

19. The composition according to claim 17, wherein the substance is contained in an amount of 0.0001 to 10% by weight based on the total weight of the composition.

20. The composition of claim 17, wherein the composition is characterized by promoting collagen synthesis.

21. 21. The composition according to claim 20, wherein the substances for promoting the synthesis of collagen type IV are fucoidan and N-feruloyl serotonin.

22. 21. The composition according to claim 20, wherein the substances for promoting the synthesis of collagen type I or collagen type IV are emodin and formononetin.

23. The composition according to claim 17, wherein the substance promotes the expression of ADIPOQ or inhibits the expression of SGPP2.

24. The composition according to claim 23, wherein the substance for promoting the expression of ADIPOQ is emodin or formononetin.

25. The composition according to claim 23, wherein the substance for inhibiting the expression of SGPP2 is fucoidan or N-feruloylserotonin.

26. The composition according to claim 17, wherein the wrinkle improvement is customized for an individual having one or more single nucleotide polymorphism markers present in a gene encoding an ADIPOQ or SGPP2 protein.

27. 27. The composition of claim 26, wherein the single nucleotide polymorphism marker is any one or more selected from the group consisting of rs10203329, rs4592839, rs76071583, and rs2036373.

28. The single nucleotide polymorphism marker is a polynucleotide consisting of a 5-100 contiguous DNA sequence including the 223350001 base of human chromosome 2, where the 223350001 base is A or G (rs10203329); a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including base 223412813 of human chromosome 2, in which the base at base 223412813 is T or C (rs4592839); a polynucleotide consisting of a continuous DNA sequence of 5-100 bases including base 186557872 of human chromosome 3, in which the base at base 186557872 is A or G (rs76071583); a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the 186570191st base of human chromosome 3, in which the 186570191st base is T or G (rs2036373); and complementary polynucleotides thereof.

29. (a) obtaining a biological sample from an individual; (b) amplifying or hybridizing with a probe a polymorphic site of a single nucleotide polymorphism marker selected from the group consisting of rs4592839 and rs76071583 from the biological sample; and (c) An information providing method for selecting a customized substance for improving sagging pores and wrinkles, comprising a step of confirming the base of the amplified or hybridized polymorphic site in step (b).

30. 30. The information providing method according to claim 29, wherein the substance is one or more selected from the group consisting of fucoidan, N-feruloyl serotonin, emodin, and formononetin.

31. The information providing method of claim 30, wherein when one or more minor alleles in the bases of rs4592839 and rs76071583 are contained, the customized substance for improving wrinkles in sagging pores is selected from fucoidan and N-feruloyl serotonin; emodin and formononetin; or fucoidan, N-feruloyl serotonin, emodin, and formononetin.

32. A composition for improving nasolabial folds, comprising one or more active ingredients selected from the group consisting of niacinamide, tranexamic acid, pyridoxine HCl, camphor, cordyceps extract, sodium mannose phosphate, and retinol.

33. The composition comprises: (i) camphor, niacinamide, and sodium mannose phosphate; (ii) tranexamic acid and pyridoxine hydrochloride; or (iii) The composition of claim 32, comprising retinol, camphor, niacinamide, sodium mannose phosphate, tranexamic acid, pyridoxine hydrochloride, and cordyceps extract as active ingredients.

34. The composition according to claim 32, wherein the substance is contained in an amount of 0.0001 to 10% by weight based on the total weight of the composition.

35. 33. The composition of claim 32, wherein the composition is characterized by the promotion of collagen synthesis.

36. 36. The composition of claim 35, wherein the collagen is collagen type I.

37. The composition of claim 32, wherein the substance promotes the expression of PPARGC1B, SPATA5, or EN1.

38. The composition of claim 37, wherein the substance for promoting the expression of PPARGC1B is niacinamide, camphor, or sodium mannose phosphate.

39. The composition of claim 37, wherein the substance for promoting the expression of SPATA5 is tranexamic acid or pyridoxine hydrochloride.

40. The composition of claim 37, wherein the substance for promoting the expression of EN1 is a Cordyceps sinensis extract.

41. The composition of claim 32, wherein the wrinkle improvement is customized for an individual having one or more single nucleotide polymorphism markers present in a gene encoding a protein of PPARGC1B, SPATA5, or EN1.

42. The composition of claim 41, wherein the single nucleotide polymorphism marker is any one or more selected from the group consisting of rs76148197, rs2166027, and rs41444645.

43. The single nucleotide polymorphism marker is a polynucleotide consisting of a 5-100 contiguous DNA sequence including the 119602515th base of human chromosome 2, in which the 119602515th base is A or G (rs76148197); a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the 124171618th base of human chromosome 4, in which the 124171618th base is T or C (rs2166027); a polynucleotide consisting of a continuous DNA sequence of 5-100 bases including the 149131368th base of human chromosome 5, in which the 149131368th base is C or G (rs41444645); and complementary polynucleotides thereof.

44. (a) obtaining a biological sample from an individual; (b) amplifying or hybridizing with a probe a polymorphic site of a single nucleotide polymorphism marker selected from the group consisting of rs76148197, rs2166027, and rs41444645 from the biological sample; and (c) A method for providing information to select a customized substance for improving nasolabial folds, comprising a step of identifying the base of the amplified or hybridized polymorphic site in step (b).

45. 45. The method for providing information according to claim 44, wherein the substance is one or more selected from the group consisting of niacinamide, tranexamic acid, pyridoxine hydrochloride, camphor, cordyceps extract, sodium mannose phosphate, and retinol.

46. The information providing method of claim 44, wherein, when one or more minor alleles in the bases rs76148197, rs2166027, and rs41444645 are contained, the customized substance for improving nasolabial folds is selected from camphor, niacinamide, and sodium mannose phosphate; tranexamic acid and pyridoxine hydrochloride; or retinol, camphor, niacinamide, sodium mannose phosphate, tranexamic acid, pyridoxine hydrochloride, and cordyceps extract.

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