Skin function improver and composition for improving skin function

Abstract

To provide a novel skin function improver and a composition for improving skin function.SOLUTION: A skin function improver containing naringenin. Also, a composition for improving skin function containing naringenin.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a skin function improving agent and a composition for improving skin function. [Background technology]

[0002] Flavonoids, a type of polyphenol found in plants, share a common structure of two benzene rings connected by three carbons and one oxygen atom, and thousands of variations are thought to exist in nature due to various modifications and sugar additions to this common structure. Some flavonoids are used as natural pigments, but there are also compounds that are believed to have beneficial effects on maintaining and promoting health through antioxidant and hormone-like effects, and these compounds are being investigated for application in foods, cosmetics, and pharmaceuticals.

[0003] Naringenin (4',5,7-trihydroxyflavanone) is a C 15 H 12 Naringenin is a flavonoid with a relatively simple structure of O5. Previous reports have shown that naringenin has antioxidant and anti-inflammatory properties. For example, Patent Document 1 discloses an invention that uses naringenin non-therapeutically in cosmetics or dermatology for the purposes of skin whitening, promoting skin tone uniformity, reducing pigmentation and darkening, and improving skin brightness. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] European Patent No. 2862600 Summary of the Invention [Problem to be solved by the invention]

[0005] In recent years, cosmetics have been required to have various functions to lead to beautiful skin, and there is a high demand for compounds that can be incorporated into cosmetics and have the effect of improving skin functions.

[0006] Therefore, an object of the present invention is to provide a novel skin function improving agent and skin function improving composition. [Means for solving the problem]

[0007] The present invention includes the following aspects. (1) A skin function improver containing naringenin. (2) A skin function improving agent according to (1), which improves at least one function selected from the group consisting of skin moisturizing function, skin barrier function, skin antioxidant function, skin wound healing function, skin turnover function, and skin anti-aging function. (3) A skin function improving agent according to (1) or (2), which enhances the expression of at least one gene selected from the group consisting of FLG, IVL, ITGB4, COL17A1, CAT, MT2A, MFN2, HNRNPD, and CD44. (4) The skin function improving agent according to any one of (1) to (3), further enhancing the expression of at least one gene selected from the group consisting of FOXO3, NMRK1, POLG, HMOX1, NQO1, TXN, TXNRD1, CASP14, KRT14, PPARD, GRHL3, KRT1, KRT10, PKP1, TGM1, DSC1, DSG1, DSG3 and CAPN1. (5) The skin function improving agent according to any one of (1) to (4), which suppresses the expression of the MMP9 gene. (6) The skin function improving agent according to any one of (1) to (5), which further suppresses the expression of MMP-1 gene. (7) A composition for improving skin function, comprising naringenin and a pharmaceutically acceptable carrier. (8) The composition for improving skin function according to (7), which is a cosmetic. [Effects of the Invention]

[0008] According to the present invention, a novel skin function improving agent and a novel skin function improving composition are provided. [Brief explanation of the drawings]

[0009] [Figure 1]FIG. 10 shows the results of a test evaluating the expression level of the MMP-1 gene in Experimental Example 3. [Figure 2] FIG. 10 shows the results of a test evaluating the expression level of the MMP-1 gene in Experimental Example 4. DETAILED DESCRIPTION OF THE INVENTION

[0010] Gene names in this specification are represented by the human gene symbols (official symbols of the Human Genome Nomenclature Committee (HGNC)) used in the NCBI nucleotide sequence database (GenBank®). When a specific gene name is represented by a human gene symbol, in animals other than humans, it refers to the ortholog of the gene for each animal (for example, one identified in the above-mentioned Gene database, etc.).

[0011] [Skin function improver] A first aspect of the present invention is a skin function improving agent containing naringenin. In the skin function improving agent, naringenin is contained as an active ingredient.

[0012] <Naringenin> Naringenin refers to 4',5,7-trihydroxyflavanone (also known as (2S)-2,3-dihydro-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one). Naringenin is a compound represented by the following chemical formula:

[0013] [ka]

[0014] The method for producing naringenin is not particularly limited, and naringenin can be produced by known methods. The method for producing naringenin is not particularly limited, and known methods can be used. Naringenin may be a naturally occurring compound, a compound chemically synthesized using natural or artificial raw materials, or a compound obtained by precision fermentation using microorganisms, etc. Naturally occurring naringenin includes naringenin extracted and purified from plants such as citrus fruits (e.g., grapefruit, orange, etc.). Naringenin obtained by precision fermentation includes naringenin extracted and purified from a naringenin-producing microorganism (e.g., genetically modified Escherichia coli, etc.) cultured in the presence of an organic carbon source (e.g., glycerol, sugar, organic acid, amino acid, or biomass containing these, etc.).

[0015] <Application> A skin function improving agent is a preparation having a skin function improving effect. "Skin function improving effect" refers to the effect of improving one or more functions of the skin. Examples of skin functions to be improved include at least one selected from the group consisting of skin moisturizing function, skin barrier function, skin antioxidant function, skin wound healing function, and skin anti-aging function. The skin functions to be improved may be one or more. The skin functions to be improved may be all of the skin moisturizing function, skin barrier function, skin antioxidant function, skin wound healing function, and skin anti-aging function. The "skin anti-aging function" may be the function of inhibiting aging of skin cells and maintaining normal skin cells. The skin anti-aging function may be the function of inhibiting the accumulation of unnecessary and abnormal substances in skin cells. The skin anti-aging function may be the function of maintaining skin firmness and inhibiting wrinkle formation. The skin functions to be improved may further include skin turnover function.

[0016] The skin cells whose functions are to be improved may be cells present in the epidermis layer or cells present in the dermis layer. Examples of cells present in the epidermis layer include granular cells, spinous cells, Langerhans cells, and basal cells. Examples of cells present in the dermis layer include fibroblasts.

[0017] The skin function improving agent of this embodiment may be used to enhance the expression of at least one gene selected from the group consisting of FLG, IVL, ITGB4, COL17A1, CAT, MT2A, MFN2, HNRNPD, and CD44, KRT14, PCNA, EGFR, GRHL3, HBEGF, FOXO3, NMRK1, POLG, HMOX1, NQO1, TXN, TXNRD1, CASP14, PPARD, GRHL3, KRT1, KRT10, PKP1, TGM1, DSC1, DSG1, DSG3, and CAPN1. The skin function improving agent of this embodiment may be used to enhance the expression of at least one gene selected from the group consisting of FLG, IVL, ITGB4, COL17A1, CAT, MT2A, MFN2, HNRNPD, CD44, FOXO3, NMRK1, POLG, HMOX1, NQO1, TXN, TXNRD1, CASP14, KRT14, PPARD, GRHL3, KRT1, KRT10, PKP1, TGM1, DSC1, DSG1, DSG3, and CAPN1. The skin function improving agent of this embodiment may be used to suppress the expression of at least one gene selected from the group consisting of MMP9 and MMP-1.

[0018] The "FLG gene" encodes FLG (filaggrin). Filaggrin is thought to be involved in the formation of the stratum corneum. Filaggrin is widely conserved in eukaryotes, including mammals. Filaggrin is expressed as a precursor, profilaggrin, which is phosphorylated to form keratohyalin granules in granular cells. When granular cells transition to keratinocytes, phosphorylated profilaggrin is dephosphorylated and hydrolyzed to form filaggrin. Filaggrin promotes the formation of keratin fibers in keratinocytes. During the process of keratinocyte migration from the lower to the upper layers, filaggrin is branched into amino acids by the action of proteases. The free amino acids generated by filaggrin degradation in the stratum corneum function as natural moisturizing factors. Filaggrin is thought to contribute to the skin's barrier function and moisture retention through the formation of the stratum corneum. Increased expression of the FLG gene is thought to improve skin's moisture retention and barrier function. An example of the nucleotide sequence of the human FLG gene is the nucleotide sequence registered in the GenBank database under accession number NM_002016. The nucleotide sequence of the FLG gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as FLG. The FLG gene encompasses homologs, paralogs, and orthologs of the FLG gene, as long as they encode a protein that functions as FLG.

[0019] The "IVL gene" is a gene that encodes IVL (involucrin). Involucrin is one of the major proteins that make up the cornified envelope of stratum corneum cells. During keratinization, involucrin is cross-linked with other involucrins or with other proteins by transglutaminase to form the cornified envelope. It is thought that increased expression of the IVL gene strengthens the skin's basement membrane and improves the skin's barrier function. An example of the nucleotide sequence of the human IVL gene is the nucleotide sequence registered in the GenBank database under accession number NM_005547. The nucleotide sequence of the IVL gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as an IVL. IVL genes encompass homologs, paralogs, and orthologs of the IVL gene, as long as they encode a protein that functions as an IVL.

[0020] The "ITGB4 gene" is a gene encoding ITGB4 (integrin subunit beta 4). The integrin beta 4 subunit associates with the integrin α subunit to form the heterodimer integrin. Integrins are widely conserved in eukaryotes, including mammals. Integrins are involved in adhesion between cells and the extracellular matrix, and between cells. Through such adhesion, integrins are thought to be involved in the formation of the epidermal barrier, adhesion of keratinocytes to the dermis, and migration of skin cells during wound healing. Increased expression of the ITGB4 gene is thought to strengthen the basement membrane and improve skin barrier function. An example of the nucleotide sequence of the human ITGB4 gene is the nucleotide sequence registered in the GenBank database under accession number NM_000213. The nucleotide sequence of the ITGB4 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as ITGB4. The ITGB4 gene encompasses homologs, paralogs, and orthologs of the ITGB4 gene, as long as they encode a protein that functions as ITGB4.

[0021] The "COL17A1 gene" encodes COL17A1 (collagen type XVII alpha 1). Collagen type XVII alpha 1 is a component of the protein complex hemidesmosome, and mediates the adhesion of keratinocytes to the basement membrane. Collagen type XVII alpha 1 is a transmembrane protein. Skin aging is thought to occur when cell competition between epidermal stem cells mediated by collagen XVII alpha 1 weakens with age. Increased expression of the COL17A1 gene is thought to promote the adhesion of keratinocytes to the basement membrane, strengthening the basement membrane and improving the skin's barrier function. An example of the nucleotide sequence of the human COL17A1 gene is the nucleotide sequence registered in the GenBank database under accession number NM_000494. The nucleotide sequence of the COL17A1 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as COL17A1. The COL17A1 gene encompasses homologs, paralogs, and orthologs of the COL17A1 gene, as long as they encode a protein that functions as COL17A1.

[0022] The "CAT gene" is a gene that encodes CAT (catalase). Catalase decomposes excess reactive oxygen species (hydrogen peroxide) in cells into water and oxygen, rendering them harmless, thereby reducing oxidative stress in cells. Catalase is widely conserved in eukaryotes and aerobic organisms, including mammals. Catalase is thought to protect the skin from damage and contribute to the maintenance and / or promotion of beautiful and healthy skin. Increased expression of the CAT gene is thought to improve the antioxidant function of the skin. An example of the nucleotide sequence of the human CAT gene is the nucleotide sequence registered in the GenBank database under accession number NM_001752. The nucleotide sequence of the CAT gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as CAT. The CAT gene encompasses homologs, paralogs, and orthologs of the CAT gene, as long as they encode a protein that functions as CAT.

[0023] The "MT2A gene" is a gene that encodes MT2A (metallothionein 2A). Metallothionein 2A is a protein of the metallothionein family that binds to divalent heavy metal ions and changes the concentration of heavy metals within cells. Metallothionein acts as an antioxidant, protecting cells from hydroxyl free radicals and participating in the homeostasis of metals within cells. Increased expression of the MT2A gene is thought to improve the antioxidant function of the skin. An example of the nucleotide sequence of the human MT2A gene is the nucleotide sequence registered in the GenBank database under accession number NM_005953. The nucleotide sequence of the MT2A gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as MT2A. The MT2A gene encompasses homologs, paralogs, and orthologs of the MT2A gene, as long as they encode a protein that functions as MT2A.

[0024] The "MFN2 gene" is a gene that encodes MFN2 (mitofusin 2). Mitofusin 2 is a mitochondrial membrane protein that is involved in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. Mitofusin 2 is also involved in mitophagy, which selectively removes damaged mitochondria. Mitofusin 2 is thought to eliminate abnormal mitochondria within cells and maintain cellular health. Increased expression of the MFN2 gene is thought to control mitochondrial fusion and improve the anti-aging function of the skin. An example of the nucleotide sequence of the human MFN2 gene is the nucleotide sequence registered in the GenBank database under accession number NM_014874. The nucleotide sequence of the MFN2 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as MFN2. MFN2 genes encompass homologs, paralogs, and orthologs of the MFN2 gene, as long as they encode a protein that functions as MFN2.

[0025] The "HNRNPD gene" is a gene that encodes HNRNPD (heterogeneous nuclear ribonucleoprotein D). Heterogeneous nuclear ribonucleoprotein D is a nucleic acid-binding protein that binds to pre-mRNA in the nucleus and is thought to be involved in pre-mRNA processing, mRNA metabolism, mRNA transport, etc. Heterogeneous nuclear ribonucleoprotein D is thought to be involved in normal mRNA processing and mRNA stability, maintaining cellular health. Increased expression of the HNRNPD gene is thought to control mRNA processing and stability, improving the anti-aging function of the skin. An example of the nucleotide sequence of the human HNRNPD gene is the nucleotide sequence registered in the GenBank database under accession number NM_031370. The nucleotide sequence of the HNRNPD gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as HNRNPD. The HNRNPD gene encompasses homologs, paralogs, and orthologs of the HNRNPD gene, as long as they encode a protein that functions as HNRNPD.

[0026] The "CD44 gene" is a gene that encodes CD44 (CD44 molecule (Indian blood group)). CD44 is a cell surface glycoprotein involved in cell-cell interactions, cell adhesion, cell migration, etc. CD44 is also known as extracellular matrix receptor III (ECMR-III) and is a receptor for hyaluronic acid. Downregulation of CD44 in epidermal keratinocytes leads to impairment of cell proliferation, survival, migration, lipid synthesis, differentiation, and epidermal barrier function. CD44 is thought to replenish moisture to the skin and have a skin regenerative effect. Increased expression of the CD44 gene is thought to improve the skin's moisturizing function. An example of the nucleotide sequence of the human CD44 gene is the nucleotide sequence registered in the GenBank database under accession number NM_001945. The nucleotide sequence of the CD44 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as CD44. The CD44 gene encompasses homologs, paralogs, and orthologs of the CD44 gene, as long as they encode a protein that functions as CD44.

[0027] The "MMP9 gene" is a gene that encodes MMP9 (matrix metalloproteinase 9; matrix metallopeptidase 9 or matrix metalloprotease 9). In the skin, MMP9 is thought to be involved in the degradation of extracellular matrix, including collagen. Suppression of MMP9 gene expression is thought to contribute to skin regeneration and the maintenance of beautiful skin. Suppression of MMP9 gene expression is thought to improve the skin's barrier function and anti-aging function. An example of the nucleotide sequence of the human MMP9 gene is the nucleotide sequence registered in the GenBank database under accession number NM_004994. The nucleotide sequence of the MMP9 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as MMP9. The MMP9 gene encompasses homologs, paralogs, and orthologs of the MMP9 gene, as long as they encode a protein that functions as MMP9.

[0028] The "KRT14 gene" is a gene that encodes KRT14 (keratin 14). Keratin 14 is present in the basal layer of the epidermis and is involved in the normal division and proliferation of basal cells. Increased expression of the KRT14 gene is thought to promote the division and proliferation of basal cells in the epidermis, which is thought to strengthen the basement membrane. Increased expression of the KRT14 gene is thought to improve skin turnover and barrier functions. An example of the nucleotide sequence of the human KRT14 gene is the nucleotide sequence registered in the GenBank database under accession number NM_000526. The nucleotide sequence of the KRT14 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as KRT14. The KRT14 gene encompasses homologs, paralogs, and orthologs of the KRT14 gene, as long as they encode a protein that functions as KRT14.

[0029] The "PCNA gene" is a gene that encodes PCNA (epidermal growth factor receptor; proliferating cell nuclear antigen). PCNA is a cofactor for DNA polymerase δ and is involved in DNA replication and repair, as well as cell cycle regulation. Increased expression of the PCNA gene is thought to promote epidermal turnover. Increased expression of the PCNA gene is thought to improve skin turnover function. An example of the nucleotide sequence of the human PCNA gene is the nucleotide sequence registered in the GenBank database under accession number NM_182649. The nucleotide sequence of the PCNA gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as PCNA. The PCNA gene encompasses homologs, paralogs, and orthologs of the human PCNA gene, as long as they encode a protein that functions as PCNA.

[0030] The "EGFR gene" is a gene that encodes EGFR (epidermal growth factor receptor). EGFR is a cell surface protein that induces cell proliferation by signal transduction through binding to epidermal growth factor. In normal skin, EGFR is expressed in the basal layer of the epidermis, outer root sheath, eccrine sweat glands, sebaceous glands, etc., and plays an important role in skin proliferation and differentiation. It is thought that increased expression of the EGFR gene promotes normal proliferation of epidermal cells and accelerates epidermal turnover. It is thought that increased expression of the EGFR gene improves skin turnover and wound healing functions. An example of the nucleotide sequence of the human EGFR gene is the nucleotide sequence registered in the GenBank database under accession number NM_005228. The nucleotide sequence of the EGFR gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as EGFR. The PCNA gene encompasses homologs, paralogs, and orthologs of the human EGFR gene, as long as it encodes a protein that functions as EGFR.

[0031] The "GRHL3 gene" encodes GRHL3 (grainyhead-like transcription factor 3). GRHL3 functions as a transcription factor. Deletion of GRHL3 results in decreased expression of many genes important for skin barrier formation, such as genes encoding lipid processing enzymes, cell adhesion molecules, and structural proteins. Increased expression of the GRHL3 gene is thought to maintain normal epidermal differentiation and promote epidermal turnover. Increased expression of the GRHL3 gene is thought to improve skin turnover and skin barrier functions. An example of the nucleotide sequence of the human GRHL3 gene is the nucleotide sequence registered in the GenBank database under accession number NM_001195010. The nucleotide sequence of the GRHL3 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as GRHL3. The GRHL3 gene encompasses homologs, paralogs, and orthologs of the human GRHL3 gene, as long as it encodes a protein that functions as GRHL3.

[0032] The "HBEGF gene" is a gene that encodes HB-EGF (heparin-binding EGF-like growth factor). HB-EGF is an epidermal growth factor with heparin-binding activity. HB-EGF functions as a growth factor for epidermal keratinocytes and as a growth factor necessary for the epithelialization process of wound healing. It is thought that increased expression of the HBEGF gene activates the proliferation of epidermal cells and promotes epidermal turnover. It is thought that increased expression of the HBEGF gene improves skin turnover and wound healing functions. An example of the nucleotide sequence of the human HBEGF gene is the nucleotide sequence registered in the GenBank database under accession number NM_001945. The nucleotide sequence of the HBEGF gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as HBEGF. The HBEGF gene encompasses homologs, paralogs, and orthologs of the human HBEGF gene, as long as it encodes a protein that functions as HBEGF.

[0033] The "FOXO3 gene" is a gene encoding FOXO3 (Forkhead Box O3). FOXO3 is considered a representative gene associated with longevity. FOXO3 has tumor suppression, aging delay, metabolism promotion, stress response, mitochondrial control, autophagy, and apoptosis promotion functions. Enhanced expression of the FOXO3 gene is thought to improve the skin's anti-aging function through improved antioxidant and anti-inflammatory functions. Examples of the nucleotide sequence of the human FOXO3 gene include the nucleotide sequence registered in the GenBank database under accession number NM_001455. The nucleotide sequence of the FOXO3 gene is not limited to the nucleotide sequence described above, as long as it encodes a protein that functions as FOXO3. The FOXO3 gene encompasses homologs, paralogs, and orthologs of the human FOXO3 gene, as long as it encodes a protein that functions as FOXO3.

[0034] The "NMRK1 gene" is a gene that encodes NMRK1 (nicotinamide riboside kinase 1). NMRK1 promotes NAD synthesis from NAD precursors and is involved in cellular metabolism. Increased expression of the NMRK1 gene is thought to improve the skin's anti-aging functions, such as suppressing wrinkle formation. An example of the nucleotide sequence of the human NMRK1 gene is the nucleotide sequence registered in the GenBank database under accession number NM_017881. The nucleotide sequence of the NMRK1 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as NMRK1. The NMRK1 gene encompasses homologs, paralogs, and orthologs of the human NMRK1 gene, as long as it encodes a protein that functions as NMRK1.

[0035] The "POLG gene" encodes POLG (DNA polymerase gamma, catalytic subunit). POLG is involved in maintaining mitochondrial function, repairing mitochondrial DNA damage, and energy metabolism. Increased expression of the POLG gene is thought to improve anti-aging functions through repairing mitochondrial DNA damage. An example of the nucleotide sequence of the human POLG gene is the nucleotide sequence registered in the GenBank database under accession number NM_002693. The nucleotide sequence of the POLG gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as POLG. POLG genes encompass homologs, paralogs, and orthologs of the human POLG gene, as long as they encode a protein that functions as POLG.

[0036] The "HMOX1 gene" is a gene encoding HMOX1 (heme oxygenase 1). HMOX1 is an enzyme whose expression is strongly induced by various factors that induce oxidative stress, such as heat shock, heavy metals, hypoxia, inflammatory cytokines, ultraviolet light, H2O2, and LPS. HMOX1 converts heme into carbon monoxide, biliverdin, and Fe. 2+ By breaking down into ions, it has cytoprotective effects against oxidative stress and anti-apoptotic activity. It is thought that increased expression of the HMOX1 gene improves the antioxidant function of the skin. An example of the nucleotide sequence of the human HMOX1 gene is the nucleotide sequence registered in the GenBank database under accession number NM_002133. The nucleotide sequence of the HMOX1 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as HMOX1. The HMOX1 gene encompasses homologs, paralogs, and orthologs of the human HMOX1 gene, as long as it encodes a protein that functions as HMOX1.

[0037] The "NQO1 gene" encodes NQO1 (NAD(P)H quinone dehydrogenase 1; NAD(P)H quinone oxidoreductase 1). NQO1 is a multifunctional enzyme that catalyzes the reduction of quinones and is involved in sensitivity to oxidative stress, stress response, and cell protection (prevention of apoptosis). Increased expression of the NQO1 gene is thought to improve the antioxidant function of the skin. An example of the nucleotide sequence of the human NQO1 gene is the nucleotide sequence registered in the GenBank database under accession number NM_000903. The nucleotide sequence of the NQO1 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as NQO1. The NQO1 gene encompasses homologs, paralogs, and orthologs of the human NQO1 gene, as long as it encodes a protein that functions as NQO1.

[0038] The "TXN gene" is a gene that encodes TXN (thioredoxin). TXN is involved in cellular redox metabolism, DNA synthesis, cell proliferation, and anti-apoptosis. Increased expression of the TXN gene is thought to improve the antioxidant function of the skin. An example of the nucleotide sequence of the human TXN gene is the nucleotide sequence registered in the GenBank database under accession number NM_003329. The nucleotide sequence of the TXN gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as TXN. TXN genes encompass homologs, paralogs, and orthologs of the human TXN gene, as long as they encode a protein that functions as TXN.

[0039] The "TXNRD1 gene" is a gene that encodes TXNRD1 (thioredoxin reductase 1). TXNRD1 is involved in cellular redox metabolism. Increased expression of the TXNRD1 gene is expected to improve the antioxidant function of the skin and, through this antioxidant function, to promote anti-aging of the skin. An example of the nucleotide sequence of the human TXNRD1 gene is the nucleotide sequence registered in the GenBank database under accession number NM_003330. The nucleotide sequence of the TXNRD1 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as TXNRD1. The TXNRD1 gene encompasses homologs, paralogs, and orthologs of the human TXNRD1 gene, as long as it encodes a protein that functions as TXNRD1.

[0040] The "CASP14 gene" is a gene that encodes CASP14 (Caspase 14). CASP14 belongs to the caspase family, which is involved in apoptosis and inflammation, and is the most recently discovered caspase in humans. CASP14 is a protease that is mainly expressed in the upper basal epidermis and is activated during keratinocyte cornification. CASP14 is involved in keratinocyte differentiation, filaggrin production, UVB sensitivity, and barrier function, and catalyzes the dephosphorylation of pro-FLG (filaggrin precursor) in the granular layer of the skin to form FLG. It is thought that increased expression of the CASP14 gene improves skin wound healing through improved barrier function. An example of the nucleotide sequence of the human CASP14 gene is the nucleotide sequence registered in the GenBank database under accession number NM_012114. The nucleotide sequence of the CASP14 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as CASP14. The CASP14 gene encompasses homologs, paralogs, and orthologs of the human CASP14 gene, as long as they encode a protein that functions as CASP14.

[0041] The "PPARD gene" encodes PPARD (Peroxisome proliferator-activated receptor delta). PPARD is involved in keratinocyte proliferation and skin repair. Increased expression of the PPARD gene is thought to improve skin wound healing. An example of the nucleotide sequence of the human PPARD gene is the nucleotide sequence registered in the GenBank database under accession number NM_006238. The nucleotide sequence of the PPARD gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as a PPARD. PPARD genes encompass homologs, paralogs, and orthologs of the human PPARD gene, as long as they encode a protein that functions as a PPARD.

[0042] The "KRT1 gene" is a gene that encodes KRT1 (keratin 1). KRT1 is a protein that belongs to the keratin family and plays an important role as a cytoskeleton in cells such as skin and hair. KRT1 is involved in epidermal differentiation, filaggrin production, and maintaining the barrier function. It is thought that increased expression of the KRT1 gene improves the skin's barrier function. An example of the nucleotide sequence of the human KRT1 gene is the nucleotide sequence registered in the GenBank database under accession number NM_006121. The nucleotide sequence of the KRT1 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as KRT1. The KRT1 gene encompasses homologs, paralogs, and orthologs of the human KRT1 gene, as long as it encodes a protein that functions as KRT1.

[0043] The "KRT10 gene" is a gene that encodes KRT10 (keratin 10). KRT1 is a protein that belongs to the keratin family and plays an important role as a cytoskeleton in cells such as those in the skin. KRT10 is a protein whose expression increases during keratinization of epidermal cells and is involved in epidermal differentiation and maintaining barrier function. It is thought that increased expression of the KRT10 gene improves the skin's barrier function. An example of the nucleotide sequence of the human KRT10 gene is the nucleotide sequence registered in the GenBank database under accession number NM_000421. The nucleotide sequence of the KRT10 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as KRT10. The KRT10 gene encompasses homologs, paralogs, and orthologs of the human KRT10 gene, as long as it encodes a protein that functions as KRT10.

[0044] The "PKP1 gene" is a gene that encodes PKP1 (plakophilin 1). PKP1 is a protein involved in epidermal differentiation and cell adhesion. Increased expression of the PKP1 gene is thought to improve the skin's barrier function and moisturizing function. An example of the nucleotide sequence of the human PKP1 gene is the nucleotide sequence registered in the GenBank database under accession number NM_000299. The nucleotide sequence of the PKP1 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as PKP1. The PKP1 gene encompasses homologs, paralogs, and orthologs of the human PKP1 gene, as long as they encode a protein that functions as PKP1.

[0045] The "TGM1 gene" encodes TGM1 (transglutaminase 1). TGM1 is an enzyme involved in keratinocyte differentiation, skin barrier formation, blood coagulation, and extracellular matrix stabilization. Increased expression of the TGM1 gene is thought to improve skin barrier function. An example of the nucleotide sequence of the human TGM1 gene is the nucleotide sequence registered in the GenBank database under accession number NM_000359. The nucleotide sequence of the TGM1 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as TGM1. The TGM1 gene encompasses homologs, paralogs, and orthologs of the human TGM1 gene, as long as it encodes a protein that functions as TGM1.

[0046] The "DSC1 gene" is a gene that encodes DSC1 (Desmocollin-1). DSC1 is a desmosomal cadherin, an intercellular adhesion molecule that is involved in the formation of the skin barrier. Increased expression of the DSC1 gene is thought to improve the skin's barrier function. An example of the nucleotide sequence of the human DSC1 gene is the nucleotide sequence registered in the GenBank database under accession number NM_004948. The nucleotide sequence of the DSC1 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as DSC1. The DSC1 gene encompasses homologs, paralogs, and orthologs of the human DSC1 gene, as long as it encodes a protein that functions as DSC1.

[0047] The "DSG1 gene" is a gene that encodes DSG1 (Desmoglein-1). DSG1 is expressed in the surface layer of the skin (stratum corneum) and is involved in intercellular junctions, keratinocyte differentiation and proliferation, and skin barrier formation. Increased expression of the DSG1 gene is thought to improve skin barrier function. An example of the nucleotide sequence of the human DSG1 gene is the nucleotide sequence registered in the GenBank database under accession number NM_001942. The nucleotide sequence of the DSG1 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as DSG1. The DSG1 gene encompasses homologs, paralogs, and orthologs of the human DSG1 gene, as long as it encodes a protein that functions as DSG1.

[0048] The "DSG3 gene" is a gene that encodes DSG3 (Desmoglein-3). DSG1 is expressed in the lower layer of the skin (basal layer) and is involved in intercellular junctions, keratinocyte differentiation and proliferation, and skin barrier formation. Increased expression of the DSG3 gene is thought to improve skin barrier function. An example of the nucleotide sequence of the human DSG3 gene is the nucleotide sequence registered in the GenBank database under accession number NM_001944. The nucleotide sequence of the DSG3 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as DSG3. The DSG3 gene encompasses homologs, paralogs, and orthologs of the human DSG3 gene, as long as it encodes a protein that functions as DSG3.

[0049] The "CAPN1 gene" is a gene that encodes CAPN1 (calpain 1). CAPN1 is an enzyme that belongs to the calpain family and is involved in cell proliferation, cell differentiation, tissue remodeling, and fibrosis. Increased expression of the CAPN1 gene is thought to improve the wound healing and moisturizing functions of the skin. An example of the nucleotide sequence of the human CAPN1 gene is the nucleotide sequence registered in the GenBank database under accession number NM_005186. The nucleotide sequence of the CAPN1 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as CAPN1. The CAPN1 gene encompasses homologs, paralogs, and orthologs of the human CAPN1 gene, as long as it encodes a protein that functions as CAPN1.

[0050] The "MMP-1 gene" is a gene that encodes MMP-1 (matrix metallopeptidase 1; a type I collagen-degrading enzyme). MMP-1 is involved in cell repair and regeneration, inflammatory responses, the progression of aging, and cancer progression through the breakdown of type I collagen and the secretion of inflammatory cytokines. Suppressing the expression of the MMP-1 gene is thought to improve the anti-aging function of the skin through its anti-wrinkle, anti-aging, and anti-inflammatory effects. An example of the nucleotide sequence of the human MMP-1 gene is the nucleotide sequence registered in the GenBank database under accession number NM_002421. The nucleotide sequence of the MMP-1 gene is not limited to the above nucleotide sequence, as long as it encodes a protein that functions as MMP-1. The MMP-1 gene encompasses homologs, paralogs, and orthologs of the human MMP-1 gene, as long as it encodes a protein that functions as MMP-1.

[0051] As used herein, "enhanced gene expression" refers to an increase in the expression level of a target gene in cells cultured in the presence of a skin function improving agent of this embodiment, compared to the expression level of the target gene in control cells (control group) cultured in the absence of the skin function improving agent of this embodiment. The expression level of a target gene in cells cultured in the presence of a skin function improving agent of this embodiment may be increased by, for example, 1% or more, 3% or more, 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 98% or more, or 100% or more, compared to the expression level of the target gene in the control group.

[0052] As used herein, "suppressed gene expression" refers to a decrease in the expression level of a target gene in cells cultured in the presence of a skin function improving agent of this embodiment, compared to the expression level of the target gene in control cells (control group) cultured in the absence of the skin function improving agent of this embodiment. The expression level of a target gene in cells cultured in the presence of a skin function improving agent of this embodiment may be reduced by, for example, 1% or more, 3% or more, 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, or 98% or more, compared to the expression level of the target gene in the control group.

[0053] Changes in gene expression levels can be confirmed by known methods. For example, a method for measuring gene expression levels can be used, such as transcriptome analysis, which comprehensively obtains transcripts of target genes and enables measurement of the state of gene expression. Specific examples of transcriptome analysis methods include microarrays, real-time PCR (qPCR), RNA-seq, Northern blotting, and in situ hybridization.

[0054] The skin function improving agent of the present embodiment may be used as it is, or may be incorporated into pharmaceuticals or cosmetics for the purpose of imparting a skin function improving function. It may also be incorporated into a skin function improving composition described below.

[0055] [Composition for improving skin function] A second aspect of the present invention is a composition for improving skin function, containing naringenin. The composition for improving skin function contains naringenin as an active ingredient. The composition for improving skin function may contain the skin function improving agent according to the first aspect.

[0056] The composition for improving skin function of this embodiment can be produced by mixing naringenin and, if necessary, other ingredients and formulating them according to a conventional method (for example, the method described in the Japanese Pharmacopoeia).

[0057] Other ingredients include pharmaceutically acceptable carriers. A "pharmaceutically acceptable carrier" refers to a carrier that does not inhibit the physiological activity of the active ingredient and is not substantially toxic to the intended recipient. "Substantially non-toxic" means that the ingredient is not toxic to the intended recipient at the amount typically used. Pharmaceutically acceptable carriers include, but are not limited to, oily ingredients, moisturizers, texture improvers, surfactants, various polymers, thickeners, gelling agents, antioxidants, preservatives, antibacterial agents, chelating agents, pH adjusters, acids and alkalis, powders, UV absorbers, various active ingredients (e.g., whitening agents, anti-inflammatory agents, hair growth agents, blood circulation promoters, stimulants, anti-aging agents), vitamins and their derivatives, hormones, various extracts, fragrances, and coloring materials (dyes, colorants, dyes, pigments).

[0058] Oily components include higher alcohols such as cetanol, myristyl alcohol, oleyl alcohol, lauryl alcohol, cetostearyl alcohol, stearyl alcohol, arachyl alcohol, behenyl alcohol, jojoba alcohol, chimyl alcohol, selachyl alcohol, batyl alcohol, hexyldecanol, isostearyl alcohol, 2-octyldodecanol, and dimer diol; aralkyl alcohols and derivatives such as benzyl alcohol; lauric acid, myristic acid, palmitic acid, stearic acid, and isostearic acid. Higher fatty acids such as behenic acid, undecylenic acid, 12-hydroxystearic acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, erucic acid, docosahexaenoic acid, eicosapentaenoic acid, isohexadecanoic acid, anteisohenicosanoic acid, long-chain branched fatty acids, dimer acids, hydrogenated dimer acids, and their aluminum salts, calcium salts, magnesium salts, zinc salts, sodium salts, potassium salts, and other metal soaps, amine salts such as ethanolamine salts, and nitrogen-containing derivatives such as amides; liquid paraffin (mineral oil), heavy liquid isopropyl alcohol, Carbonates such as isoparaffin, light liquid isoparaffin, α-olefin oligomer, polyisobutene, hydrogenated polyisobutene, polybutene, squalane, olive-derived squalane, squalene, petrolatum, and solid paraffin; waxes such as candelilla wax, carnauba wax, rice wax, Japan wax, beeswax, montan wax, ozokerite, ceresin, paraffin wax, microcrystalline wax, petrolatum, Fischer-Tropsch wax, polyethylene wax, and ethylene-propylene copolymer; coconut oil, Vegetable oils and fats such as palm oil, palm kernel oil, safflower oil, olive oil, castor oil, avocado oil, sesame oil, tea oil, evening primrose oil, wheat germ oil, macadamia nut oil, hazelnut oil, kukui nut oil, rosehip oil, meadowfoam oil, persic oil, tea tree oil, peppermint oil, corn oil, rapeseed oil, sunflower oil, wheat germ oil, linseed oil, cottonseed oil, soybean oil, peanut oil, rice bran oil, cocoa butter, shea butter, hydrogenated coconut oil, hydrogenated castor oil, jojoba oil, and hydrogenated jojoba oil; animal oils and fats such as beef tallow, milk fat, horse fat, egg yolk oil, mink oil, and turtle oil;Animal waxes such as spermaceti, lanolin, and orange roughy oil; lanolin derivatives such as liquid lanolin, reduced lanolin, adsorbed purified lanolin, acetated lanolin, acetated liquid lanolin, hydroxylanolin, polyoxyethylene lanolin, lanolin fatty acids, hard lanolin fatty acids, lanolin alcohol, acetated lanolin alcohol, and cetyl lanolyl acetate; lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. phospholipids such as phosphatidylinositol, sphingomyelin, etc., phosphatidic acid, lysolecithin, etc.; phospholipid derivatives such as hydrogenated soybean phospholipid, partially hydrogenated soybean phospholipid, hydrogenated egg yolk phospholipid, partially hydrogenated egg yolk phospholipid, etc.; sterols such as cholesterol, dihydrocholesterol, lanosterol, dihydrolanosterol, phytosterol, cholic acid, etc.; sapogenins; saponins; cholesteryl acetate, cholesteryl nonanoate , Cholesteryl stearate, Cholesteryl isostearate, Cholesteryl oleate, N-Lauroyl-L-glutamic acid di(cholesteryl / behenyl / octyldodecyl), N-Lauroyl-L-glutamic acid di(cholesteryl / octyldodecyl), N-Lauroyl-L-glutamic acid di(phytosteryl / behenyl / octyldodecyl), N-Lauroyl-L-glutamic acid di(phytosteryl / octyldodecyl), N-Lauroyl sarcosine isopropyl Sterol esters such as acyl sarcosine alkyl esters, cholesteryl 12-hydroxystearate, cholesteryl macadamiate, phytosteryl macadamiate, phytosteryl isostearate, cholesteryl soft lanolinate, cholesteryl hard lanolinate, cholesteryl long-chain branched fatty acids, and cholesteryl long-chain α-hydroxy fatty acids; lipid complexes such as phospholipid-cholesterol complexes and phospholipid-phytosterol complexes;Octyldodecyl myristate, hexyldecyl myristate, octyldodecyl isostearate, cetyl palmitate, octyldodecyl palmitate, cetyl octanoate, hexyldecyl octanoate, isotridecyl isononanoate, isononyl isononanoate, octyl isononanoate, isotridecyl isononanoate, isodecyl neopentanoate, isotridecyl neopentanoate, isostearyl neopentanoate, octyldodecyl neodecanoate, oleyl oleate, octyldodecyl oleate, ricinoleic acid Monoalcohol carboxylic acid esters such as octyldodecyl, lanolin fatty acid octyldodecyl, hexyldecyl dimethyloctanoate, octyldodecyl erucate, hydrogenated castor oil isostearate, ethyl oleate, avocado oil fatty acid ethyl, isopropyl myristate, isopropyl palmitate, octyl palmitate, isopropyl isostearate, lanolin fatty acid isopropyl, and triethyl citrate; oxyacid esters such as cetyl lactate, diisostearyl malate, and hydrogenated castor oil monoisostearate;Glyceryl trioctanoate, glyceryl trioleate, glyceryl triisostearate, glyceryl diisostearate, caprylic / capric triglyceride, caprylic / capric / myristic / stearic triglyceride, hydrogenated rosin triglyceride (hydrogenated ester gum), rosin triglyceride (ester gum), glyceryl behenate eicosandioate, glyceryl tetradecanedioate / eicosandioate, polyglyceryl-10 tetradecanedioate / eicosandioate, trimethylolpropane trioctanoate, trimethylolpropane triisostearate, neopentyl glycol dioctanoate, neopentyl glycol dicaprate, 2-butyl-2-ethyl-1,3-propanediol dioctanoate, 3-methyl-1,5-pentanediol dineopentanoate polyhydric alcohol fatty acid esters such as ethanol, 2,4-diethyl-1,5-pentanediol dineopentanoate, propylene glycol dioleate, pentaerythrityl tetraoctanoate, hydrogenated pentaerythrityl rosin, ditrimethylolpropane triethylhexanoate, ditrimethylolpropane isostearate / sebacic acid, pentaerythrityl triethylhexanoate, dipentaerythrityl hydroxystearate / stearate / rosinate, diglyceryl diisostearate, polyglyceryl tetraisostearate, polyglyceryl-10 nonaisostearate, polyglyceryl-8 deca(erucate / isostearate / ricinoleate), diglyceryl hexyldecanoate / sebacic acid oligoester, glycol distearate (ethylene glycol distearate), etc.;Diisopropyl Dimer Dilinoleate, Diisostearyl Dimer Dilinoleate, Di(isostearyl / phytosteryl) Dimer Dilinoleate, Phytosteryl / Behenyl Dimer Dilinoleate, Phytosteryl / Isostearyl / Cetyl / Stearyl / Behenyl) Dimer Dilinoleate, Dimer Dilinoleyl Dimer Dilinoleate, Dimer Dilinoleyl Bis(phytosteryl / behenyl / isostearyl) Dimer Dilinoleate, Dimer Dilinoleyl Diisostearate, Dimer Dilinoleyl Hydrogenated Rosin Condensate, Hydrogenated Castor Oil Dimer Dilinoleate, Hydroxyalkyl Dimer Derivatives of dimer acid or dimer diol such as immerdilinoleyl ether; fatty acid alkanolamides such as coconut oil fatty acid monoethanolamide (cocamide MEA), coconut oil fatty acid diethanolamide (cocamide DEA), lauric acid monoethanolamide (lauramide MEA), lauric acid diethanolamide (lauramide DEA), lauric acid monoisopropanolamide (lauramide MIPA), palmitic acid monoethanolamide (palmitamide MEA), palmitic acid diethanolamide (palmitamide DEA), and coconut oil fatty acid methylethanolamide (cocamide methyl MEA);Dimethicone (dimethylpolysiloxane), highly polymerized dimethicone (highly polymerized dimethylpolysiloxane), cyclomethicone (cyclic dimethylsiloxane, decamethylcyclopentasiloxane), phenyl trimethicone, diphenyl dimethicone, phenyl dimethicone, stearoxypropyl dimethylamine, (aminoethyl aminopropyl methicone / dimethicone) copolymer, dimethiconol, dimethiconol crosspolymer, silicone resin, silicone rubber, amino-modified silicones such as aminopropyl dimethicone and amodimethicone, cation-modified silicone, polyether-modified silicones such as dimethicone copolyol, polyglycerin Preferred examples of the silicone include silicones such as phosphorus-modified silicone, sugar-modified silicone, carboxylic acid-modified silicone, phosphate-modified silicone, sulfate-modified silicone, alkyl-modified silicone, fatty acid-modified silicone, alkyl ether-modified silicone, amino acid-modified silicone, peptide-modified silicone, fluorine-modified silicone, cation-modified and polyether-modified silicone, amino-modified and polyether-modified silicone, alkyl-modified and polyether-modified silicone, and polysiloxane-oxyalkylene copolymer; and fluorine-based oils such as perfluorodecane, perfluorooctane, and perfluoropolyether.

[0059] Moisturizing agents and feel improvers include polyols and their polymers such as glycerin, 1,3-butylene glycol, propylene glycol, 3-methyl-1,3-butanediol, 1,3-propanediol, 2-methyl-1,3-propanediol, trimethylolpropane, pentaerythritol, hexylene glycol, diglycerin, polyglycerin, diethylene glycol, polyethylene glycol, dipropylene glycol, polypropylene glycol, and ethylene glycol-propylene glycol copolymers; glycol alkyl ethers such as diethylene glycol monoethyl ether (ethoxydiglycol), ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, and diethylene glycol dibutyl ether; sugar alcohols such as sorbitol, xylitol, erythritol, mannitol, and maltitol; glucose, fructose, galactose, mannose, threose, xylose, arabinose, fucose, ribose, deoxyribose, maltose, trehalose, lactose, Natural products include raffinose, gluconic acid, glucuronic acid, β-glucan, chitin, chitosan, heparin and derivatives, pectin, arabinogalactan, dextrin, dextran, glycogen, ethyl glucoside, glucosyl ethyl methacrylate polymers or copolymers, and other sugars and derivatives thereof; hyaluronic acid, sodium hyaluronate; sodium chondroitin sulfate; mucoitin sulfate, caronin sulfate, keratosulfate, dermatan sulfate; Tremella fuciformis extract, Tremella fuciformis polysaccharides; fucoidan; and tuberose polysaccharides. derived polysaccharides; organic acids such as citric acid, tartaric acid, and lactic acid and their salts; urea; 2-pyrrolidone-5-carboxylic acid and its sodium salts, etc.; amino acids such as betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, tyrosine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine, leucine, isoleucine, valine, tryptophan, histidine, and taurine and their salts;Collagen, fish collagen, atelocollagen, gelatin, elastin, collagen degradation peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin degradation peptides, keratin degradation peptides, hydrolyzed keratin, conchiolin degradation peptides, hydrolyzed conchiolin, silk proteolytic peptides, hydrolyzed silk, sodium lauroyl hydrolyzed silk, soybean proteolytic peptides, wheat proteolytic peptides, hydrolyzed wheat protein, casein degradation peptides, acylated peptides and their derivatives; acylated peptides such as palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide Preferred examples of such ceramides include lactic acid bacteria culture medium, yeast extract, eggshell membrane protein, bovine submandibular gland mucin, hypotaurine, sesame lignan glycoside, glutathione, albumin, whey, choline chloride, phosphorylcholine, animal and plant extracts such as placenta extract, alastin, collagen, witch hazel water, loofah water, chamomile extract, licorice extract, comfrey extract, silk extract, rose rouge extract, yarrow extract, eucalyptus extract, and melilot extract, and natural ceramides (types 1, 2, 3, 4, 5, and 6), hydroxyceramides, pseudoceramides, sphingoglycolipids, ceramides, and glycoceramide-containing extracts.

[0060] Preferred surfactants include anionic surfactants, nonionic surfactants, cationic surfactants, amphoteric surfactants, polymer surfactants, etc. There are no particular limitations on the HLB of the surfactant, and surfactants from as low as about 1 to as high as about 20 can be used, and it is also preferable to combine surfactants with low and high HLBs. Examples of preferred surfactants include anionic surfactants such as fatty acid salts, potassium laurate, and potassium myristate; alkyl sulfate salts, such as sodium lauryl sulfate, triethanolamine lauryl sulfate, and ammonium lauryl sulfate; polyoxyethylene alkyl sulfates, such as sodium laureth sulfate and triethanolamine laureth sulfate; acyl N-methylamino acid salts, such as sodium cocoyl methyl taurate, potassium cocoyl methyl taurate, sodium lauroyl methyl taurate, sodium myristoyl methyl taurate, sodium lauroyl methyl alanine, sodium lauroyl sarcosine, triethanolamine lauroyl sarcosine, and sodium lauroyl methyl alanine glutamate; sodium cocoyl glutamate, triethanolamine cocoyl glutamate, sodium lauroyl glutamate, sodium myristoyl glutamate, sodium stearoyl glutamate, and palmitoyl glutamate. Acyl amino acid salts such as ditriethanolamine aspartate and triethanolamine cocoyl alanine; polyoxyethylene alkyl ether acetates such as sodium laureth acetate; succinate esters such as sodium lauroyl monoethanolamide succinate; fatty acid alkanolamide ether carboxylates; acyl lactates; polyoxyethylene fatty amine sulfates; fatty acid alkanolamide sulfates; fatty acid glyceride sulfates such as sodium hydrogenated coconut oil fatty acid glycerin sulfate; alkyl benzene polyoxyethylene sulfates; olefin sulfonates such as sodium α-olefin sulfonate; alkyl sulfosuccinates such as disodium lauryl sulfosuccinate and dioctyl sodium sulfosuccinate; alkyl ether sulfosuccinates such as disodium laureth sulfosuccinate, sodium monolauroyl monoethanolamide polyoxyethylene sulfosuccinate, and sodium lauryl polypropylene glycol sulfosuccinate;Alkylbenzenesulfonates such as sodium tetradecylbenzenesulfonate and triethanolamine tetradecylbenzenesulfonate; alkylnaphthalenesulfonates; alkanesulfonates; α-sulfofatty acid methyl ester salts; acylisethionates; alkylglycidyl ether sulfonates; alkyl sulfoacetates; alkyl ether phosphate ester salts such as sodium laureth phosphate, sodium dilaureth phosphate, sodium trilaureth phosphate, and sodium monooleth phosphate; alkyl phosphate ester salts such as potassium lauryl phosphate; sodium caseinate; alkylaryl ether phosphates; fatty acid amide ether phosphates; phospholipids such as phosphatidylglycerol, phosphatidylinositol, and phosphatidic acid; silicone-based anionic surfactants such as carboxylic acid-modified silicone, phosphate-modified silicone, and sulfate-modified silicone; and nonionic surfactants such as laureth (polyoxyethylene lauryl ether), ceteth (polyoxyethylene lauryl ether), and Polyoxyethylene alkyl ethers with various polyoxyethylene addition numbers, such as polyoxyethylene cetyl ethers, steareths (polyoxyethylene stearyl ethers), beheneths (polyoxyethylene behenyl ethers), isosteareths (polyoxyethylene isostearyl ethers), and octyldodeceths (polyoxyethylene octyldodecyl ethers); polyoxyethylene alkyl phenyl ethers; castor oil and hydrogenated castor oil derivatives, such as polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil monoisostearate, polyoxyethylene hydrogenated castor oil triisostearate, polyoxyethylene hydrogenated castor oil monopyroglutamic acid monoisostearate diester, and polyoxyethylene hydrogenated castor oil maleic acid; polyoxyethylene phytosterols; polyoxyethylene cholesterol; polyoxyethylene cholestanol; polyoxyethylene lanolin; and polyoxyethylene reduced lanolin.Polyoxyethylene-polyoxypropylene alkyl ethers such as polyoxyethylene-polyoxypropylene cetyl ether, polyoxyethylene-polyoxypropylene 2-decyltetradecyl ether, polyoxyethylene-polyoxypropylene monobutyl ether, polyoxyethylene-polyoxypropylene hydrogenated lanolin, and polyoxyethylene-polyoxypropylene glycerin ether; polyoxyethylene-polyoxypropylene glycol; polyoxyethylene-polyoxypropylene diglyceryl; ) Glycerin polyoxypropylene glycol; glycerin fatty acid partial esters such as glyceryl stearate, glyceryl isostearate, glyceryl palmitate, glyceryl myristate, glyceryl oleate, glyceryl coconut oil fatty acid, glycerin mono-cottonseed oil fatty acid, glycerin mono-erucate, glycerin sesquioleate, glycerin α,α'-oleic acid pyroglutamate, glycerin monostearate malate, etc.; polyglyceryl-2, 3, 4, 5, 6, and 8 stearate , 10, Polyglyceryl-6 distearate, 10, Polyglyceryl-2 tristearate, Polyglyceryl-10 decaisostearate, Polyglyceryl-2 isostearate, 3, 4, 5, 6, 8, 10, Polyglyceryl-2 diisostearate (diglyceryl diisostearate), 3, 10, Polyglyceryl-2 triisostearate, Polyglyceryl-2 tetraisostearate, Polyglyceryl-10 decaisostearate, Polyglyceryl-2 oleate, 3, Nos. 4, 5, 6, 8, and 10, polyglycerin fatty acid esters such as polyglyceryl-6 dioleate, polyglyceryl-2 trioleate, and polyglyceryl-10 decaoleate; ethylene glycol mono-fatty acid esters such as ethylene glycol monostearate; propylene glycol mono-fatty acid esters such as propylene glycol monostearate; pentaerythritol partial fatty acid esters; sorbitol partial fatty acid esters; maltitol partial fatty acid esters; maltitol ethers;Sorbitan fatty acid esters such as sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexylate, and diglycerol sorbitan tetra-2-ethylhexylate; partial esters of sugar derivatives such as sucrose fatty acid esters, methyl glucoside fatty acid esters, and trehalose undecylenate; alkyl glucosides such as caprylyl glucoside; alkyl polyglycols Coside; Lanolin alcohol; Reduced lanolin; Polyoxyethylene fatty acid mono- and diesters such as polyoxyethylene distearate, polyethylene glycol diisostearate, polyoxyethylene monooleate, and polyoxyethylene dioleate; Polyoxyethylene propylene glycol fatty acid esters; Polyoxyethylene glycerin fats such as polyoxyethylene glycerin monostearate, polyoxyethylene glycerin monoisostearate, and polyoxyethylene glycerin triisostearate. Fatty acid esters; polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate, and polyoxyethylene sorbitan tetraoleate; polyoxyethylene sorbitol fatty acid esters such as polyoxyethylene sorbitol monolaurate, polyoxyethylene sorbitol monooleate, polyoxyethylene sorbitol pentaoleate, and polyoxyethylene sorbitol monostearate; polyoxyethylene methyl glucoside fatty acid esters; polyoxyethylene alkyl ether fatty acid esters; polyoxyethylene animal and vegetable oils and fats such as polyoxyethylene sorbitol beeswax; alkyl glyceryl ethers such as isostearyl glyceryl ether, chimyl alcohol, selachyl alcohol, and batyl alcohol; polyhydric alcohol alkyl ethers; polyoxyethylene alkylamines; tetrapolyoxyethylene-tetrapolyoxypropylene-ethylenediamine condensates; natural surfactants such as saponin and sophorolipids; polyoxyethylene fatty acid amides;Fatty acid alkanolamides such as coconut oil fatty acid monoethanolamide (cocamide MEA), coconut oil fatty acid diethanolamide (cocamide DEA), lauric acid monoethanolamide (lauramide MEA), lauric acid diethanolamide (lauramide DEA), lauric acid monoisopropanolamide (lauramide MIPA), palmitic acid monoethanolamide (palmitamide MEA), palmitic acid diethanolamide (palmitamide DEA), coconut oil fatty acid methylethanolamide (cocamide methyl MEA), etc.; lauramine oxide Alkyl dimethylamine oxides such as cocamine oxide, stearamine oxide, and behenamine oxide; alkyl ethoxydimethylamine oxide; polyoxyethylene alkyl mercaptan; silicone-based nonionic surfactants such as polyether-modified silicones such as dimethicone copolyol, polysiloxane-oxyalkylene copolymers, polyglycerin-modified silicones, and sugar-modified silicones; cationic surfactants include behentrimonium chloride, steartrimonium chloride, cetrimonium chloride, and lauryltrimonium chloride. alkyltrimethylammonium chlorides such as ammonium chloride; alkyltrimethylammonium bromides such as stearyltrimonium bromide; dialkyldimethylammonium chlorides such as distearyldimonium chloride and dicocodimonium chloride; fatty acid amidoamines and their salts such as stearamidopropyldimethylamine and stearamidoethyldiethylamine; alkyl ether amines and their salts or quaternary salts such as stearoxypropyldimethylamine; fatty acid amide quaternary ammonium salts such as ethyl sulfate of long-chain branched fatty acid (12-31) aminopropylethyldimethylammonium and ethyl sulfate of lanolin fatty acid aminopropylethyldimethylammonium; polyoxyethylene alkylamines and their salts or quaternary salts; alkylamine salts; fatty acid amide guanidinium salts; alkyl ether amine ammonium salts; alkyl trialkylene glycol ammonium salts; benzalkonium salts; benzethonium salts; pyridinium salts such as cetylpyridinium chloride; imidazolinium salts; alkylisoquinolinium salts; dialkylmorphonium salts; polyamine fatty acid derivatives;Silicone-based cationic surfactants such as amino-modified silicones such as aminopropyl dimethicone and amodimethicone, cation-modified silicones, cation-modified and polyether-modified silicones, and amino-modified and polyether-modified silicones; amphoteric surfactants include N-alkyl-N,N-dimethyl amino acid betaines such as lauryl betaine (lauryl dimethyl amino acetate betaine); fatty acid amidoalkyl-N,N-dimethyl amino acid betaines such as cocamidopropyl betaine and lauramidopropyl betaine; imidazoline-type betaines such as sodium cocoamphoacetate and sodium lauroamphoacetate; alkyl sulfobetaines such as alkyldimethyltaurine; sulfate-type betaines such as alkyldimethylaminoethanol sulfate esters; phosphate-type betaines such as alkyldimethylaminoethanol phosphate esters; sphingolipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin; Preferred examples of suitable surfactants include phospholipids such as lecithin, lysolecithin, hydrogenated soybean phospholipid, partially hydrogenated soybean phospholipid, hydrogenated egg yolk phospholipid, partially hydrogenated egg yolk phospholipid, and hydroxide lecithin; silicone-based amphoteric surfactants; and polymer surfactants such as polyvinyl alcohol, sodium alginate, starch derivatives, tragacanth gum, acrylic acid / alkyl methacrylate copolymer, and 2-methacryloyloxyethyl phosphorylcholine / stearyl methacrylate copolymer; and various silicone-based surfactants.

[0061] Various polymers, thickeners, and gelling agents include guar gum, locust bean gum, queen seed, carrageenan, galactan, gum arabic, tara gum, tamarind, furcellaran, karaya gum, aoi, caragam, tragacanth gum, pectin, pectinic acid and salts such as sodium salt, alginic acid and salts such as sodium salt, mannan; starch from rice, corn, potato, wheat, etc.; xanthan gum, dextran, succinoglucan, curdlan, hyaluronic acid and its salt, xanthan gum, pullulan, gellan gum, chitin, chitosan cellulose, agar, cassou extract, chondroitin sulfate, casein, collagen, gelatin, albumin; cellulose and its derivatives such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose and its sodium salts, methylhydroxypropyl cellulose, sodium cellulose sulfate, dialkyldimethylammonium cellulose sulfate, crystalline cellulose, cellulose powder; soluble starch, carboxymethyl starch, methylhydroxypropyl starch, methyl starch, etc. Starch-based polymers, starch derivatives such as hydroxypropyltrimonium starch chloride and corn starch aluminum octenylsuccinate; alginic acid derivatives such as sodium alginate and propylene glycol alginate; polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), vinylpyrrolidone-vinyl alcohol copolymer, polyvinyl methyl ether; polyethylene glycol, polypropylene glycol, polyoxyethylene-polyoxypropylene copolymer; amphoteric methacrylate copolymers such as (methacryloyloxyethyl carboxybetaine / alkyl methacrylate) copolymer and (acrylates / stearyl acrylate / ethylamine oxide methacrylate) copolymer; (dimethicone / vinyl dimethicone) crosspolymer, (alkyl acrylate / diacetone acrylamide) copolymer, (alkyl acrylate / diacetone acrylamide) copolymer AMP; partially saponified polyvinyl acetate, maleic acid copolymer; vinylpyrrolidone-dialkylaminoalkyl methacrylate copolymer; acrylic resins with alkanolamine; polyesters, water-dispersible polyesters;Polyacrylamide; polyacrylic acid ester copolymers such as polyethyl acrylate, carboxyvinyl polymers, polyacrylic acid and its salts such as sodium salt, acrylic acid-methacrylic acid ester copolymers; acrylic acid-alkyl methacrylate copolymers; cationized cellulose such as Polyquaternium-10, diallyldimethylammonium chloride-acrylamide copolymers such as Polyquaternium-7, acrylic acid-diallyldimethylammonium chloride copolymers such as Polyquaternium-22, acrylic acid-diallyldimethylammonium chloride-acrylamide copolymers such as Polyquaternium-39, acrylic acid-cationized methacrylic acid ester copolymers, acrylic acid-cationized methacrylic acid amide copolymers, acrylic acid-methyl acrylate-methacrylamidopropyltrimethylammonium chloride copolymers such as Polyquaternium-47, methacrylic acid choline ester chloride polymers; cationized oligosaccharides, cationized dextran, cationized guar hydroxypropyltrimonium chloride, etc. Preferred examples of the polymer include polysaccharides, polyethyleneimine, cationic polymers, 2-methacryloyloxyethyl phosphorylcholine polymers such as polyquaternium-51 and copolymers with butyl methacrylate copolymers, polymer emulsions such as acrylic resin emulsions, polyethyl acrylate emulsions, polyacrylic alkyl ester emulsions, polyvinyl acetate resin emulsions, natural rubber latex, and synthetic latex; nitrocellulose; polyurethanes and various copolymers; various silicones; various silicone copolymers such as acrylic-silicone graft copolymers; various fluorine-containing polymers; 12-hydroxystearic acid and its salts; dextrin fatty acid esters such as dextrin palmitate and dextrin myristate; silicic anhydride, fumed silica (ultrafine silicic anhydride particles), aluminum magnesium silicate, sodium magnesium silicate, metal soaps, dialkyl phosphate metal salts, bentonite, hectorite, organically modified clay minerals, sucrose fatty acid esters, and fructooligosaccharide fatty acid esters.

[0062] Preferred antioxidants include α-lipoic acid, α-lipoic acid salts, and α-lipoic acid derivatives; tocopherol derivatives such as tocopherol (vitamin E), tocotrienol, and tocopherol acetate; BHT, BHA; gallic acid derivatives such as propyl gallate; vitamin C (ascorbic acid) and / or its derivatives; erythorbic acid and its derivatives; sulfites such as sodium sulfite; bisulfites such as sodium bisulfite; thiosulfates such as sodium thiosulfate; metabisulfites; thiotaurine, hypotaurine; thioglycerol, thiourea, thioglycolic acid, and cysteine ​​hydrochloride. Preferred reducing agents include thioglycolic acid, cysteine, and cysteamine. Preferred oxidizing agents include hydrogen peroxide, ammonium persulfate, sodium bromate, and percarbonate.

[0063] Examples of preservatives and antibacterial agents include hydroxybenzoic acids and their salts or esters such as methylparaben, ethylparaben, propylparaben, and butylparaben; salicylic acid; sodium benzoate; phenoxyethanol; 1,2-diols such as 1,2-pentanediol and 1,2-hexanediol; isothiazolinone derivatives such as methylchloroisothiazolinone and methylisothiazolinone; imidazolinium urea; dehydroacetic acid and its salts; phenols; halogenated bisphenols such as triclosan; and acid amines. Preferred examples of the antibacterial agent include amides, quaternary ammonium salts; trichlorocarbanide, zinc pyrithione, benzalkonium chloride, benzethonium chloride, sorbic acid, chlorhexidine, chlorhexidine gluconate, halocarban, hexachlorophene, hinokitiol; other phenols such as phenol, isopropylphenol, cresol, thymol, parachlorophenol, phenylphenol, and phenylphenol sodium; phenylethyl alcohol, photosensitizers, antibacterial zeolites, and silver ions.

[0064] Preferred examples of the chelating agent include edetates (ethylenediaminetetraacetates) such as EDTA, EDTA2Na, EDTA3Na, and EDTA4Na; hydroxyethylethylenediaminetriacetates such as HEDTA3Na; pentetates (diethylenetriaminepentaacetate); phytic acid; phosphonic acids such as etidronic acid and salts thereof such as sodium salts; sodium oxalate; polyamino acids such as polyaspartic acid and polyglutamic acid; sodium polyphosphate, sodium metaphosphate, phosphoric acid; sodium citrate, citric acid, alanine, dihydroxyethylglycine, gluconic acid, ascorbic acid, succinic acid, and tartaric acid.

[0065] Preferred examples of the pH adjuster and acid / alkali include citric acid, sodium citrate, lactic acid, sodium lactate, glycolic acid, succinic acid, acetic acid, sodium acetate, malic acid, tartaric acid, fumaric acid, phosphoric acid, hydrochloric acid, sulfuric acid, monoethanolamine, diethanolamine, triethanolamine, isopropanolamine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-hydroxymethyl-1,3-propanediol, arginine, sodium hydroxide, potassium hydroxide, aqueous ammonia, guanidine carbonate, and ammonium carbonate.

[0066] Powders include mica, talc, kaolin, sericite, montmorillonite, kaolinite, mica, muscovite, phlogopite, synthetic mica, lepidolite, biotite, vermiculite, magnesium carbonate, calcium carbonate, aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, metal tungstate, magnesium, zeolite, barium sulfate, calcined calcium sulfate, calcium phosphate, fluorapatite, hydroxyapatite, ceramic powder, bentonite, smectite, clay, mud, metal soaps (e.g., zinc myristate, calcium palmitate, aluminum stearate), calcium carbonate, red iron oxide, yellow iron oxide, black iron oxide, ultramarine, Prussian blue, carbon black, titanium oxide, fine and ultrafine titanium oxide particles, zinc oxide, fine and ultrafine zinc oxide particles, alumina, silica, fumed silica (ultrafine silicic anhydride particles), titanium mica Preferred examples include inorganic powders of various sizes and shapes, such as fish scale foil, boron nitride, photochromic pigments, synthetic fluorine-containing phlogopite, fine particle composite powders, gold, and aluminum, and inorganic powders obtained by treating these with silicones such as hydrogen silicone and cyclic hydrogen silicone, or other silanes, or various surface treatment agents such as titanium coupling agents to make them hydrophobic or hydrophilic; organic powders of various sizes and shapes, such as starch, cellulose, nylon powder, polyethylene powder, polymethyl methacrylate powder, polystyrene powder, styrene-acrylic acid copolymer resin powder, polyester powder, benzoguanamine resin powder, polyethylene terephthalate-polymethyl methacrylate laminate powder, polyethylene terephthalate-aluminum-epoxy laminate powder, urethane powder, silicone powder, and Teflon (registered trademark) powder, as well as surface-treated powders and organic-inorganic composite powders.Preferred examples of inorganic salts include sodium chloride-containing salts such as table salt, regular salt, rock salt, sea salt, and natural salt; potassium chloride, aluminum chloride, calcium chloride, magnesium chloride, bittern, zinc chloride, and ammonium chloride; sodium sulfate, aluminum sulfate, aluminum-potassium sulfate (alum), aluminum-ammonium sulfate, barium sulfate, calcium sulfate, potassium sulfate, magnesium sulfate, zinc sulfate, iron sulfate, and copper sulfate; and sodium phosphates such as mono-, di-, and tri-Na phosphate, potassium phosphates, calcium phosphates, and magnesium phosphates.

[0067] Examples of ultraviolet absorbers include benzoic acid-based ultraviolet absorbers such as para-aminobenzoic acid, para-aminobenzoic acid monoglycerin ester, N,N-dipropoxypara-aminobenzoic acid ethyl ester, N,N-diethoxypara-aminobenzoic acid ethyl ester, N,N-dimethylpara-aminobenzoic acid ethyl ester, N,N-dimethylpara-aminobenzoic acid butyl ester, and N,N-dimethylpara-aminobenzoic acid ethyl ester; anthranilic acid-based ultraviolet absorbers such as homomenthyl-N-acetylanthranilate; salicylic acid-based ultraviolet absorbers such as salicylic acid and its sodium salt, amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, and p-isopropanol phenyl salicylate; octyl cinnamate, Cinnamic acid-based UV absorbers such as ethyl 4-isopropyl cinnamate, methyl 2,5-diisopropyl cinnamate, ethyl 2,4-diisopropyl cinnamate, methyl 2,4-diisopropyl cinnamate, propyl p-methoxycinnamate, isopropyl p-methoxycinnamate, isoamyl p-methoxycinnamate, 2-ethylhexyl p-methoxycinnamate (octyl p-methoxycinnamate), 2-ethoxyethyl p-methoxycinnamate (cinoxate), cyclohexyl p-methoxycinnamate, ethyl α-cyano-β-phenylcinnamate, 2-ethylhexyl α-cyano-β-phenylcinnamate (octocurine), glyceryl mono-2-ethylhexanoyl di-paramethoxycinnamate, ferulic acid and its derivatives;Benzophenone-based UV absorbers such as 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone (oxybenzone-3), 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-phenylbenzophenone, 2-ethylhexyl-4'-phenyl-benzophenone-2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, and 4-hydroxy-3-carboxybenzophenone; 3-(4'-methylbenzylidene)-d,l-camphor, 3-benzylidene-d,l-camphor; 2-phenyl-5-methylbenzoxazole; 2,2'-hydroxy-5-methylphenylbenzotriazole; 2-(2'-hydroxy 2-(2'-hydroxy-5'-methylphenylbenzotriazole; Dibenzalazine; Dianisoylmethane; 5-(3,3-dimethyl-2-norbornylidene)-3-pentan-2-one; Dibenzoylmethane derivatives such as 4-t-butylmethoxydibenzoylmethane; Octyltriazone; Urocanic acid derivatives such as urocanic acid and ethyl urocanate; 2-(2'-hydroxy-5'-methylphenyl)benzotriazole Preferred examples thereof include hydantoin derivatives such as 1-(3,4-dimethoxyphenyl)-4,4-dimethyl-1,3-pentanedione, 2-ethylhexyl dimethoxybenzylidene dioxoimidazolidinepropionate, phenylbenzimidazolazole sulfonic acid, terephthalylidene dicamphor sulfonic acid, drometrizole trisiloxane, methyl anthranilate, rutin and its derivatives, and oryzanol and its derivatives;

[0068] Preferred examples of the whitening agent include ascorbic acid, ascorbic acid phosphate salts such as sodium ascorbyl phosphate and magnesium ascorbyl phosphate, ascorbic acid fatty acid esters such as ascorbic acid tetraisopalmitate, ascorbic acid alkyl ethers such as ascorbic acid ethyl ether, ascorbic acid glucoside and its fatty acid esters such as ascorbic acid-2-glucoside, ascorbic acid derivatives such as ascorbic acid sulfate and tocopheryl ascorbyl phosphate; and plant extracts such as kojic acid, ellagic acid, tranexamic acid and derivatives thereof, ferulic acid and derivatives thereof, placenta extract, glutathione, oryzanol, butylresorcinol, oil-soluble chamomilla extract, oil-soluble licorice extract, Nishikawa willow extract, and saxifrage extract.

[0069] Preferred examples of the anti-inflammatory agent include glycyrrhizinic acid and its derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, guaiazulene, allantoin, indomethacin, zinc oxide, hydrocortisone acetate, prednisone, diphedramine hydrochloride, chlorpheniramine maleate; and plant extracts such as peach leaf extract and mugwort leaf extract.

[0070] Preferred examples of hair growth agents, blood circulation promoters, and stimulants include plant extracts and tinctures such as Swertia japonica extract, capsicum tincture, ginger tincture, ginger extract, and cantharis tincture; capsaicin, nonylic acid valenylamide, zingerone, ichthammol, tannic acid, borneol, cyclandelate, cinnarizine, tolazoline, acetylcholine, verapamil, cepharanthine, γ-oryzanol, cepharanthine, vitamin E, and derivatives thereof such as tocopherol nicotinate and tocopherol acetate, γ-oryzanol, nicotinic acid, and derivatives thereof such as nicotinamide, nicotinic acid benzyl ester, inositol hexanicotinate, and nicotine alcohol, allantoin, photosensitizer 301, photosensitizer 401, capronium chloride, pentadecanoic acid monoglyceride, flavanonol derivatives, stigmasterol or stigmastanol and their glycosides, and minoxidil.

[0071] Other medicinal agents such as anti-wrinkle agents, anti-aging agents, firming agents, cooling agents, warming agents, wound healing promoters, irritation soothing agents, analgesics, and cell activators include retinols, retinoic acids, and tocopheryl retinoate; lactic acid, glycolic acid, gluconic acid, fruit acids, salicylic acid, and their derivatives such as glycosides and esters; α- or β-hydroxy acids and their derivatives such as hydroxycapric acid, long-chain α-hydroxy fatty acids, and long-chain α-hydroxy fatty acid cholesteryl; γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid; carnitine; carnosine; creatine; ceramides; sphingosines; caffeine, xanthine, and their derivatives; coenzyme Q10, carotene, lycopene, astaxanthin, lutein, etc. Preferred examples include antioxidants and active oxygen scavengers such as catechins; flavones such as quercetin; isoflavones; gallic acid and ester sugar derivatives; polyphenols such as tannin, sesamin, protoanthocyanidin, chlorogenic acid, and apple polyphenols; rutin and its derivatives; hesperidin and its derivatives; lignan glycosides; licorice extract-related substances such as glabridin, glabrene, liquiritin, and isoliquiritin; lactoferrin; shogaol, gingerol; fragrance substances and their derivatives such as menthol, camphor, and cedrol; capsaicin, vanillin, and their derivatives; insect repellents such as diethyltoluamide; and complexes of physiologically active substances and cyclodextrins.

[0072] Examples of antipruritic agents include diphenhydramine hydrochloride, chlorpheniramine maleate, camphor, substance P inhibitors, etc. Examples of keratin exfoliating / dissolving agents include salicylic acid, sulfur, resorcinol, selenium sulfide, pyridoxine, etc. Examples of antiperspirants include aluminum chlorohydrate, aluminum chloride, zinc oxide, zinc paraphenolsulfonate, etc. Examples of cooling agents include menthol and methyl salicylate, etc. Examples of astringents include citric acid, tartaric acid, lactic acid, aluminum potassium sulfate, tannic acid, etc. Examples of enzymes include superoxide dismutase, catalase, lysozyme chloride, lipase, papain, pancreatin, protease, etc. Examples of nucleic acids include ribonucleic acid and salts thereof, deoxyribonucleic acid and salts thereof, and adenosine triphosphate disodium, etc.

[0073] Vitamins and their derivatives include vitamin A such as retinol, retinol acetate, and retinol palmitate; vitamin B such as thiamine hydrochloride, thiamine sulfate, riboflavin, riboflavin acetate, pyridoxine hydrochloride, pyridoxine dioctanoate, pyridoxine dipalmitate, flavin adenine dinucleotide, cyanocobalamin, folic acids, nicotinic acids such as nicotinamide and benzyl nicotinate, and choline; vitamin C such as ascorbic acid and its sodium salts; vitamin D; vitamin E such as α-, β-, γ-, and δ-tocopherol; other vitamins such as pantothenic acid and biotin; and vitamin B such as ascorbic acid phosphate sodium salt and ascorbic acid phosphate magnesium salt. Preferred examples include ascorbic acid phosphate salts, ascorbic acid fatty acid esters such as ascorbic acid tetraisopalmitate, ascorbyl stearate, ascorbyl palmitate, and ascorbyl dipalmitate, ascorbic acid alkyl ethers such as ascorbic acid ethyl ether, ascorbic acid glucoside and its fatty acid esters such as ascorbic acid-2-glucoside, and ascorbic acid derivatives such as tocopheryl ascorbyl phosphate; vitamin derivatives such as tocopherol nicotinate, tocopherol acetate, tocopherol linoleate, tocopherol ferulate, and tocopherol phosphate; tocotrienols; and various other vitamin derivatives.

[0074] Preferred examples of hormones include estradiol, estrone, ethinylestradiol, cortisone, hydrocortisone, and prednisone.

[0075] Various extracts of plants, animals, microorganisms, etc. include iris extract, angelica extract, dolabrata extract, asparagus extract, avocado extract, hydrangea extract, almond extract, althea extract, arnica extract, apricot extract, apricot kernel extract, ginkgo extract, chinko extract, fennel extract, turmeric extract, oolong tea extract, uva-ursi extract, angelica tree extract, echinacea leaf extract, emmeiso extract, scutellaria root extract, phellodendron bark extract, coptis japonica extract, barley extract, ginseng extract, St. John's wort extract, and nettle extract. Grass extract, Ononis extract, Netherlands mustard extract, orange extract, dried seawater, seaweed extract, oyster leaf extract, oak extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk, Pueraria root extract, chamomilla extract, oil-soluble chamomilla extract, carrot extract, artemisia capillaris extract, oat extract, kalk extract, licorice extract, oil-soluble licorice extract, kiwi extract, angelica tree extract, wood ear extract, cinchona extract, cucumber extract, paulownia leaf extract, guanosine, guava extract, lily of the valley extract, gardenia extract, kumazasa extract , Sophora flavescens extract, walnut extract, chestnut extract, grapefruit extract, clematis extract, black rice extract, brown sugar extract, black vinegar, chlorella extract, mulberry extract, gentian extract, geranium extract, black tea extract, yeast extract, magnolia bark extract, coffee extract, burdock extract, rice extract, fermented rice extract, fermented rice bran extract, rice germ oil, comfrey extract, collagen, cowberry extract, Chinese radish extract, Bupleurum Root extract, umbilical cord extract, saffron extract, salvia extract, soapwort extract, bamboo grass extract, hawthorn extract, Chinese radish extract , Zanthoxylum extract, Shiitake mushroom extract, Rehmannia root extract, Lithospermum root extract, Perilla extract, Tilia extract, Meadowsweet extract, Jatoba extract, Peony extract, Angelica root extract, Calamus root extract, Birch extract, White wood ear extract, Horsetail extract, Stevia extract, Stevia fermented product, Nishikawa willow extract, Ivy extract, Hawthorn extract, Elderberry extract, Yarrow extract, Peppermint extract, Sage extract, Mallow extract, Cnidium extract, Swertia japonica extract, Sophora japonica extract, Rhubarb extract,Soybean extract, Chinese laurel extract, thyme extract, dandelion extract, lichen extract, tea extract, clove extract, Imperata cylindrica extract, tangerine extract, tea tree oil, sweet tea extract, chili pepper extract, angelica extract, calendula extract, peach kernel extract, spruce extract, Houttuynia cordata extract, tomato extract, natto extract, carrot extract, garlic extract, wild rose extract, hibiscus extract, burdock extract, lotus extract, parsley extract, birch extract, honey, witch hazel extract, parietaria extract, jasmine extract, bisabolol, cypress extract, bifidobacteria extract, loquat extract, coltsfoot extract, butterbur shoot extract, poria cocos extract, butcher's broom extract, grape extract Examples of extracts that can be used include ginseng, grape seed extract, propolis, loofah extract, safflower extract, peppermint extract, linden extract, peony extract, hop extract, squid extract, pine extract, horse chestnut extract, skunk cabbage extract, soapberry extract, melissa extract, mozuku extract, peach extract, cornflower extract, eucalyptus extract, saxifrage extract, lily extract, coix seed extract, mugwort extract, lavender extract, green tea extract, eggshell membrane extract, apple extract, rooibos tea extract, lychee extract, lettuce extract, lemon extract, forsythia extract, astragalus extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract, and burnet extract.

[0076] Fragrance: acetyl cedrene, amyl cinnamaldehyde, allyl amyl glycolate, β-ionone, isoe super, isobutylquinoline, iris oil, iron, indole, ylang-ylang oil, undecanal, undecenal, γ-undecalactone, estragole, eugenol, oakmoss, opoponax resinoid, orange oil, eugenol, aurantiol, galacsolids, carvacrol, L-carvone, camphor, cannon, carrot seed oil, clove oil, methyl cinnamate, geraniol, geranyl nitrile, isobornyl acetate, geranyl acetate, dimethylbenzylcarbinyl acetate, styraryl acetate, cedryl acetate, terpineol acetate, pt-butylcyclohexyl acetate Al, vetiveryl acetate, benzyl acetate, linalyl acetate, isopentyl salicylate, benzyl salicylate, sandalwood oil, santalol, cyclamen aldehyde, cyclopentadecanolide, methyl dihydrojasmonate, dihydromyrcenol, jasmine absolute, jasmine lactone, cis-jasmone, citral, citronenol, citronellal, cinnamon bark oil, 1,8-cineole, cinnamaldehyde, styrax resinoid, cedarwood oil, cedrene, cedrol, celery seed oil, thyme oil, damascone, damascenone, thymol, tuberose absolute, decanal, decalactone, terpineol, gamma-terpinene, tripluran, nerol, nonanal, 2,6-Nonadienol, Nonalactone, Patchouli Alcohol, Vanilla Absolute, Vanillin, Basil Oil, Patchouli Oil, Hydroxycitronellal, Alpha-Pinene, Piperitone, Phenethyl Alcohol, Phenylacetaldehyde, Petitgrain Oil, Hexyl Cinnamaldehyde, cis-3-Hexenol, Balsam of Peru, Vetiver Oil, Vetiverol, Peppermint Oil, Pepper Oil, Heliotropin, Bergamot Oil, Benzyl Benzene Preferred examples of the fragrance include synthetic and natural fragrances such as maltodextrin, borneol, myrrhizoid, musk ketone, methylnonylacetaldehyde, γ-methylionone, menthol, L-menthol, L-menthone, eucalyptus oil, β-ionone, lime oil, lavender oil, D-limonene, linalool, lyral, lilial, lemon oil, rose absolute, rose oxide, rose oil, rosemary oil, and various essential oils, as well as various blended fragrances.

[0077] Colorants, dyes, and pigments include Brown No. 201, Black No. 401, Purple No. 201, Purple No. 401, Blue No. 1, Blue No. 2, Blue No. 201, Blue No. 202, Blue No. 203, Blue No. 204, Blue No. 205, Blue No. 403, Blue No. 404, Green No. 201, Green No. 202, Green No. 204, Green No. 205, Green No. 3, Green No. 401, Green No. 402, and Red Color No. 102, Red No. 104-1, Red No. 105-1, Red No. 106, Red No. 2, Red No. 201, Red No. 202, Red No. 203, Red No. 204, Red No. 205, Red No. 206, Red No. 207, Red No. 208, Red No. 213, Red No. 214, Red No. 215, Red No. 218, Red No. 219, Red No. 220, Red No. 221, Red No. 223, Red No. 22 No. 5, Red No. 226, Red No. 227, Red No. 228, Red No. 230-1, Red No. 230-2, Red No. 231, Red No. 232, Red No. 3, Red No. 401, Red No. 404, Red Color No. 405, Red No. 501, Red No. 502, Red No. 503, Red No. 504, Red No. 505, Red No. 506, Orange No. 201, Orange No. 203, Orange No. 204, Orange No. 205, Orange No. 206, Orange No. 207, Orange No. 401, Orange No. 402, Orange No. 403, Yellow No. 201, Yellow No. 202-1, Yellow No. 202-2, Yellow No. 203, Yellow No. 204, Yellow Legal dyes such as No. 205, Yellow No. 4, Yellow No. 401, Yellow No. 402, Yellow No. 403-1, Yellow No. 404, Yellow No. 405, Yellow No. 406, Yellow No. 407, Yellow No. 5; Acid Other acidic dyes such as Red 14; Basic dyes such as Arianor Sienna Brown, Arianor Madder Red, Arianor Steel Blue, Arianor Straw Yellow; HC Yellow 2, HC Yellow 5, HC Red 3, 4-hydroxypropylamino-3-nitrophenol, N,N'-bis(2-hydroxyethyl)-2-nitro-p- Nitro dyes such as phenylenediamine, HC Blue 2, and Basic Blue 26; disperse dyes; inorganic white pigments such as titanium dioxide and zinc oxide; inorganic red pigments such as iron oxide (red iron oxide) and iron titanate; inorganic brown pigments such as gamma-iron oxide; inorganic yellow pigments such as yellow iron oxide and ochre; inorganic black pigments such as black iron oxide and low-order titanium oxide; inorganic purple pigments such as mango violet and cobalt violet; inorganic green pigments such as chromium oxide, chromium hydroxide, and cobalt titanate; inorganic blue pigments such as ultramarine and iron blue; titanium dioxide-coated mica, titanium dioxide-coated oxy Pearl pigments such as bismuth chloride, titanium dioxide-coated talc, colored titanium dioxide-coated mica, bismuth oxychloride, and fish scale foil; aluminum powder, copper powder, gold, and other metal powder pigments; surface-treated inorganic and metal powder pigments; Red No. 201, Red No. 202, Red No. 204, Red No. 205, Red No. 220, Red No. 226, Red No. 228, Red No. 405, Orange No. 203, Orange No. 204, Yellow No. 205, Yellow No. 401, Blue No. 404, Red No. 3, Red No. 104, Red No. 106, and Red No. 22 Organic pigments such as zirconium, barium or aluminum lakes, such as No. 7, Red 230, Red 401, Red 505, Orange 205, Yellow 4, Yellow 5, Yellow 202, Yellow 203, Green 3, and Blue 1; surface-treated organic pigments; anthraquinones such as astaxanthin and alizarin, anthocyanidins, β-carotene, catenal, capsanthin, chalcone, carthamine, quercetin, crocin, chlorophyll, curcumin, cochineal, and shikonin, naphthoquinones, bixylanthus, benzoin, benzoyl benzoates ... Preferred examples thereof include natural pigments and dyes such as amines, flavones, betacyanidin, henna, hemoglobin, lycopene, riboflavin, and rutin; oxidation dye intermediates and couplers such as p-phenylenediamine, toluene-2,5-diamine, o-, m-, or p-aminophenol, m-phenylenediamine, 5-amino-2-methylphenol, resorcinol, 1-naphthol, 2,6-diaminopyridine, and salts thereof; autoxidation dyes such as indoline; and dihydroxyacetone.

[0078] The other ingredients may be ingredients listed in the Cosmetic Ingredient Standards, Cosmetic Type Ingredient Standards, Japan Cosmetic Industry Association Ingredient Labeling Name List, INCI Dictionary (The International Cosmetic Ingredient Dictionary and Handbook), Quasi-drug Ingredient Standards, Japanese Pharmacopoeia, Pharmaceutical Additive Standards, and Food Additives Official Specification, as well as known cosmetic ingredients and pharmaceutical ingredients, etc. The above-mentioned ingredients may be contained in the skin function improving composition of this embodiment to the extent that the skin function improving effect of naringenin can be obtained.

[0079] The composition for improving skin function of this embodiment may contain an effective amount of naringenin. "An effective amount" refers to the amount of naringenin that is effective for the cell-activating effect of naringenin to be exerted. The effective amount may vary depending on the age, sex, weight, etc. of the subject. In the composition for improving skin function of this embodiment, the effective amount of naringenin is, for example, 0.001 to 10% by mass, 0.01 to 5% by mass, 0.01 to 1% by mass, 0.01 to 0.5% by mass, 0.01 to 0.1% by mass, etc., in terms of the content of naringenin in the composition for improving skin function.

[0080] The dosage form of the composition for improving skin function of this embodiment is not particularly limited, and examples of the dosage form of the composition for improving skin function of this embodiment include ampoules, capsules, pills, tablets, powders, granules, solids, liquids, gels, foams, emulsions, sheets, mists, sprays, and the like.

[0081] The composition for improving skin function of this embodiment may be a pharmaceutical product, a quasi-drug, or a cosmetic. The composition for improving skin function of this embodiment is preferably a topical skin preparation. The composition for improving skin function of this embodiment is preferably a cosmetic, and more preferably a cosmetic for skin.

[0082] When the composition for improving skin function of this embodiment is a cosmetic product, examples thereof include basic cosmetics such as lotion, emulsion, cream, ointment, lotion, oil, and pack; skin cleansing products such as face wash and body cleanser; massage cosmetics such as massage agents; cleansing cosmetics such as cleansing agents; body hair treatment cosmetics such as depilatories and hair removers; shaving cosmetics such as shaving treatment products, aftershave lotion, pre-shave lotion, and shaving cream; makeup cosmetics such as foundation, lipstick, blush, eye shadow, eyeliner, and mascara; and other topical cosmetics such as perfumes, nail polish, nail enamel, nail enamel remover, poultices, plasters, tapes, sheets, patches, and aerosols. The skin function improving composition of this embodiment may be a preparation for the scalp and / or hair. Examples of scalp and / or hair preparations include shampoos, rinses, hair treatments, pre-hair treatments, permanent solutions, hair dyes, hair styling products, hair tonics, hair growth and tonics, scalp poultices, scalp plasters, scalp tapes, scalp sheets, scalp patches, and aerosols for hair or scalp. The skin function improving composition of this embodiment may also be a bath additive to be added to bathwater. The skin function improving composition of this embodiment may also be used in anti-armpit odor agents, deodorants, deodorants, antiperspirants, sanitary products, sanitary cotton, wet tissues, toothpastes, mouth fresheners, mouthwashes, dishwashing agents, and the like.

[0083] The composition for improving skin function of this embodiment contains naringenin as an active ingredient, thereby exhibiting a skin function improving effect. The skin function may include at least one selected from the group consisting of skin moisturizing function, skin barrier function, skin antioxidant function, skin wound healing function, and skin anti-aging function. The skin function to be improved may be skin turnover function. The composition for improving skin function of this embodiment contains naringenin as an active ingredient, and has the effect of enhancing the expression of at least one gene selected from the group consisting of FLG, IVL, ITGB4, COL17A1, CAT, MT2A, MFN2, HNRNPD, CD44, FOXO3, NMRK1, POLG, HMOX1, NQO1, TXN, TXNRD1, CASP14, KRT14, PPARD, GRHL3, KRT1, KRT10, PKP1, TGM1, DSC1, DSG1, DSG3, and CAPN1. Enhanced expression of these genes is thought to contribute to the improvement of at least one skin function selected from the group consisting of barrier function, antioxidant function of the skin, wound healing function of the skin, and anti-aging function of the skin. The composition for improving skin function of this embodiment may contain naringenin as an active ingredient, and thereby have the effect of enhancing the expression of at least one gene selected from the group consisting of KRT14, PCNA, EGFR, GRHL3, and HBEGF. Enhanced expression of these genes is thought to contribute to the improvement of at least one skin function selected from the group consisting of skin turnover function and skin wound healing function. The composition for improving skin function of this embodiment may contain naringenin as an active ingredient, and thereby have the effect of suppressing the expression of at least one gene selected from the group consisting of MMP9 and MMP-1. Suppression of the expression of the MMP9 gene or MMP-1 gene is thought to contribute to the improvement of at least one skin function selected from the group consisting of the skin barrier function and the skin anti-aging function. Since the composition for improving skin function of this embodiment has the skin function improving effect described above, it can be used for improving dry skin, improving skin pigmentation (age spots, dullness, etc.), improving rough skin, improving skin firmness, improving wrinkles, improving pimples, etc., promoting wound healing, anti-aging of the skin, etc.

[0084] In another aspect, the present invention provides an agent for enhancing the expression of at least one gene selected from the group consisting of FLG, IVL, ITGB4, COL17A1, CAT, MT2A, MFN2, HNRNPD, CD44, KRT14, PCNA, EGFR, GRHL3, HBEGF, FOXO3, NMRK1, POLG, HMOX1, NQO1, TXN, TXNRD1, CASP14, PPARD, GRHL3, KRT1, KRT10, PKP1, TGM1, DSC1, DSG1, DSG3 and CAPN1. The present invention also provides an agent for enhancing the expression of at least one gene selected from the group consisting of FLG, IVL, ITGB4, COL17A1, CAT, MT2A, MFN2, HNRNPD, CD44, FOXO3, NMRK1, POLG, HMOX1, NQO1, TXN, TXNRD1, CASP14, KRT14, PPARD, GRHL3, KRT1, KRT10, PKP1, TGM1, DSC1, DSG1, DSG3, and CAPN1. The present invention also provides an agent for inhibiting the expression of at least one gene selected from the group consisting of MMP9 and MMP-1. In another aspect, the present invention provides use of naringenin for producing a skin function improving agent or composition for improving skin function. In another aspect, the present invention provides a method for improving skin function, comprising administering naringenin to a subject. In another aspect, the present invention provides a use of naringenin for improving skin function, preferably for non-therapeutic purposes, more preferably for cosmetic purposes. In another aspect, the present invention provides naringenin for improving skin function. The skin function includes at least one selected from the group consisting of a moisturizing function of the skin, a barrier function, an antioxidant function of the skin, a wound healing function of the skin, and an anti-aging function of the skin. [Example]

[0085] The present invention will be described below with reference to examples, but the present invention is not limited to the following examples.

[0086] (Experimental Example 1: Evaluation of the expression level of genes related to improvement of skin function 1) The effect of naringenin on the expression levels of genes related to improvement of skin function was evaluated by the following procedure.

[0087] The 3D epidermal model was prepared using LabCyte EPI-MODEL from Japan Tissue Engineering Co., Ltd. (J-TEC). The 3D epidermal model was pre-cultured for 24 hours in a CO2 incubator at 37°C according to the manufacturer's instructions. Naringenin (Sigma-Aldrich) was then added to the 3D epidermal model at a concentration of 0.1% (w / v). The 3D epidermal model was then incubated at 37°C in a CO2 incubator for 24 hours. Each well was washed with Dulbecco's phosphate-buffered saline (D-PBS) and then post-cultured at 37°C in a CO2 incubator for 24 hours. The cells in the wells were then treated with "RNAlater" (registered trademark, Thermo Fisher Scientific). The cells were then collected from the wells using a spatula or similar. RNA was extracted and purified from the cells using "QIAzol Lysis Reagent" (trade name, manufactured by QIAGEN) and a spin column from the "RNeasy Mini kit" (trade name, manufactured by QIAGEN) according to the protocol provided with the product. The purity and concentration of the purified RNA were measured using "Nanodrop" (registered trademark; manufactured by Thermo Fisher Scientific). RNA that was not sufficiently purified was purified again using a spin column. RT-qPCR was performed using the RNA purified as described above. The primers used are shown in Table 1. In Table 1, "F" indicates the forward primer and "R" indicates the reverse primer.

[0088] [Table 1]

[0089] The results are shown in Table 2. The expression level of each gene was calculated relative to the expression level of each gene in cells cultured without the addition of naringenin, which was set at 1.00.

[0090] [Table 2]

[0091] It was confirmed that the expression of the FLG, IVL, ITGB4, COL17A, CAT, MT2A, MFN2, HNRNPD, CD44, KRT14, PCNA, EGFR, GRHL3, and BEGF genes was increased by the addition of naringenin. The increased expression of these genes contributes to skin moisturizing function (FLG, CD44, etc.), skin barrier function (KRT14, IVL, ITGB4, COL17A1, etc.), skin antioxidant function (CAT, MT2A, etc.), skin anti-aging function (MFN2, HNRNPD), and skin turnover function (KRT14, PCNA, EGFR, GRHL3, HBEGF), and is thought to have an effect on improving skin function. Furthermore, it was confirmed that the expression of the MMP9 (MMP-9) gene was suppressed by the addition of naringenin. The suppression of MMP9 gene expression is thought to contribute to skin barrier function, skin anti-aging function, and other functions, and is thought to have an effect on improving skin function.

[0092] The above results confirmed that naringenin has the effect of improving skin function.

[0093] (Experimental Example 2: Evaluation of the expression level of genes related to the improvement of skin function 2) The effect of naringenin on the expression levels of genes related to improvement of skin function was evaluated by the following procedure. A three-dimensional culture model of human normal epidermis (Japan Tissue Engineering, "LabCyte EPI-MODEL") was pre-cultured for 24 hours in a CO2 incubator at 37°C according to the manufacturer's instructions. Naringenin (Sigma-Aldrich) was then dissolved in DEMSO and water to a final concentration of 0.1% (w / v). The solution was then added to the three-dimensional culture model and incubated at 37°C for 24 hours. The cells were then washed with D-PBS and incubated again at 37°C for another 24 hours. The cells were then treated with RNAlater, harvested using a spatula, and RNA was extracted and purified using QIAzol Lysis Reagent and the RNeasy Mini kit. After measuring the purity and concentration of RNA using Nanodrop, gene expression was analyzed using a gene expression analysis microarray (GeneChip®, Thermo Fisher Scientific) with extracted RNA samples of predetermined purity and concentration. The results of extracting genes whose expression levels were significantly changed in cells cultured in the presence of naringenin compared to control cells without naringenin are shown in the table below.

[0094] [Table 3]

[0095] These results confirmed that the expression of the following genes was increased by the addition of naringenin: FOXO3, NMRK1, POLG, CAT, HMOX1, NQO1, TXN, TXNRD1, CASP14, KRT14, PPARD, FLG, GRHL3, IVL, KRT1, KRT10, PKP1, TGM1, DSC1, DSG1, DSG3, and CAPN1. The increased expression of these genes contributes to skin anti-aging, antioxidant, wound healing, barrier, and moisturizing functions, and is thought to improve skin function. Therefore, it was confirmed that naringenin has the effect of improving skin function.

[0096] (Experimental Example 3: Evaluation of the expression levels of genes related to improving skin function during inflammation 1) 3 × 10 cells were cultured in 10% FBS-containing medium (DMEM, Kurabo Industries, Ltd.). 5 A cell suspension of human normal fibroblasts (NHDF-NB) was prepared to give a concentration of 1000 cells / mL. 1000 μL of this cell suspension was seeded into a 12-well tissue culture plate. The well plate was then cultured at 37°C in a CO2 incubator for 24 hours. Next, a DMSO solution containing naringenin (Sigma-Aldrich) was prepared and added to the 12-well plate at 1 μL each to a final concentration of 5 ppm or 20 ppm. To control cells, 1 μL of DMSO solution without naringenin was added. To confirm changes in the expression of genes related to the improvement of skin function during inflammation, lipopolysaccharide (LPS; Sigma-Aldrich "Lipopolysaccharides from Escherichia coli 0127:B8" (trade name)) was added as an inflammation inducer to some cells at a final concentration of 1 μg / mL. Next, the cells were cultured at 37°C for 6 hours in a CO2 incubator, treated with RNAlater, and the cells were collected using a spatula or the like, and RNA was extracted and purified using QIAzol Lysis Reagent and an RNeasy Mini kit. The purity and concentration of RNA were measured using Nanodrop, and then the expression level of the MMP-1 gene was confirmed by RT-qPCR using extracted RNA of a predetermined purity and concentration as a sample. The primers used are shown in Table 4, and the expression levels of the MMP-1 gene are shown in Figure 1. Primers "F" are forward primers and "R" are reverse primers. The expression levels were calculated relative to the expression level of the MMP-1 gene in the target cells, which was set at 1.00.

[0097] [Table 4]

[0098] The results shown in Figure 1 confirm that the addition of naringenin suppresses MMP-1 gene expression. Naringenin also suppresses MMP-1 gene expression under simulated inflammatory conditions induced by LPS stimulation. Suppression of MMP-1 gene expression is thought to contribute to the skin's barrier function and anti-aging function, and to have an effect on improving skin function. Therefore, it was suggested that naringenin has a skin function improving effect on normal cells and cells in an inflammatory state.

[0099] (Experimental Example 4: Evaluation of the expression levels of genes related to the improvement of skin function during inflammation 2) Human normal fibroblasts were cultured in a 12-well plate in the same manner as in Experimental Example 3. A DMSO solution containing naringenin (Sigma-Aldrich) was prepared and added in an amount of 1 μL to each well (final naringenin concentration: 20 ppm). For control cells, 1 μL of DMSO solution without naringenin was added. The well plates were then cultured at 37°C for 24 hours in a CO2 incubator, and then irradiated with UVA. After UVA irradiation, the well plates were cultured at 37°C for 6 hours in a CO2 incubator. RNA was extracted and purified as in Experimental Example 3, and the expression level of the MMP-1 gene was confirmed by RT-qPCR. The expression level of the MMP-1 gene is shown in Figure 2.

[0100] The results shown in Figure 2 confirm that the addition of naringenin suppresses MMP-1 gene expression. Naringenin also suppresses MMP-1 gene expression under a simulated inflammatory condition caused by UVA irradiation. Suppression of MMP-1 gene expression is thought to contribute to the skin's barrier function and anti-aging function, and to have an effect on improving skin function. Therefore, it was suggested that naringenin has a skin function improving effect on normal cells and cells in an inflammatory state.

Claims

1. A skin function improver containing naringenin.

2. 2. The skin function improving agent according to claim 1, which improves at least one function selected from the group consisting of skin moisturizing function, skin barrier function, skin antioxidant function, skin wound healing function, skin turnover function, and skin anti-aging function.

3. The skin function improving agent according to claim 1 or 2, which enhances the expression of at least one gene selected from the group consisting of FLG, IVL, ITGB4, COL17A1, CAT, MT2A, MFN2, HNRNPD, CD44, FOXO3, NMRK1, POLG, HMOX1, NQO1, TXN, TXNRD1, CASP14, KRT14, PPARD, GRHL3, KRT1, KRT10, PKP1, TGM1, DSC1, DSG1, DSG3 and CAPN1.

4. 3. The skin function improving agent according to claim 1, which suppresses the expression of at least one gene selected from the group consisting of MMP9 and MMP-1.

5. A composition for improving skin function, comprising naringenin and a pharmaceutically acceptable carrier.

6. The composition for improving skin function according to claim 5, which is a cosmetic.

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