External composition

Abstract

To provide an external composition that promotes production of KPRP protein, which is important for horny layer formation, leading to KPRP protein-involved horny layer normalization and repair, which in turn contributes to preventing or improving a decrease in skin moisture content or a deterioration of skin barrier function.SOLUTION: The present invention provides an external composition for preventing and / or improving a decrease in skin moisture content and / or a deterioration of skin barrier function, comprising a KPRP protein production promoting component as an active ingredient.SELECTED DRAWING: Figure 4

Description

[Technical field]

[0001] The present invention relates to a composition for external use, and more particularly to a composition for enhancing the expression of KPRP protein. The present invention relates to a composition for external use that is excellent in bringing about normalization and repair of the stratum corneum. [Background technology]

[0002] The human keratinocyte proline-rich protein (hKPRP) gene is located on human chromosome 1 The hKPRP gene is known to be located on q21. hK is a gene that constitutes the endocannabinoid system (EDC) and encodes the hKPRP protein. PRP protein is a protein that contains approximately 18% proline protein and is expressed normally. It is known to be expressed intermittently in the upper granular layer of the skin and is thought to be involved in the formation of the skin barrier function. It has been suggested (Non-Patent Documents 1 and 2).

[0003] In order to maintain the skin barrier function, the condition of the epidermis, which is the outermost layer of the skin, especially the stratum corneum, is important. The stratum corneum contains a sebum film, intercellular lipids (ceramides, etc.), and natural moisturizing factors (filaggrin cornified cell envelope (involucrin, loricrin, etc.) It prevents the evaporation of moisture from within the layer and also prevents the intrusion of foreign substances such as allergens and bacteria.

[0004] Recently, it has been reported that KPRP proteins are involved in the formation of desmosomes in the stratum corneum. It has been suggested that it plays an important role in intercellular adhesion between keratinocytes (Non-specific In addition, the same document also describes the stratum corneum as well as the granular layer that serves as its foundation. The presence of KPRP protein in the cytoskeleton of cells that compose the There are. [Prior art documents] [Patent documents]

[0005] [Non-Patent Document 1] Lee WH et al., J. Invest. Dermatol., 125:995-1000, 2005 [Non-Patent Document 2] Kong W et al., J. Biol. Chem. 22781-6, 2003 [Non-Patent Document 3] Suga H et al., J. Journal of Investigative Dermatology (JID), DOI: 10.1016 / j.jid.2019.02.030 Summary of the Invention [Problem to be solved by the invention]

[0006] These findings suggest that KPRP proteins play a key role in the formation and maintenance of skin barrier function. In addition to strengthening the three-dimensional structure of the stratum corneum, it also strengthens the foundation that supports the stratum corneum. It is thought that this accounts for a large proportion of the

[0007] However, there is no direct involvement of KPRP gene expression and KPRP protein-mediated There have been no fully verified reports on the ingredients that contribute to the normalization and repair of the stratum corneum.

[0008] The present invention has been made in view of the above, and provides a method for significantly enhancing the production of KPRP protein. By finding ingredients that promote KPRP protein-mediated stratum corneum normalization and repair, The present invention provides a composition for external use that contributes to preventing and improving the decline in skin moisture content and skin barrier function. The purpose is to provide. [Means for solving the problem]

[0009] In view of the above problems, we conducted extensive research and found that the product contains a component that promotes KPRP protein production. This leads to normalization and repair of the stratum corneum mediated by KPRP proteins, and promotes skin moisture The inventors have found that the amount of the active ingredient contributes to preventing and improving the decline of the skin barrier function, and have completed the present invention. I did.

[0010] That is, the present invention provides the topical compositions described below. Section 1. Contains KPRP protein production promoting ingredient as an active ingredient, and is effective in reducing skin moisture and skin balding. A composition for external application for preventing or improving functional decline. Section 2. Contains KPRP protein production promoting ingredients as active ingredients, and helps maintain moisture retention. A composition for external use for restoring skin irritation, promoting skin compatibility of cosmetics, or normalizing skin texture. Section 3. The KPRP protein production promoting component is (A) a plant of the Lamiaceae family and an extract thereof, a plant of the Leguminosae family Plants and their extracts, Paeoniaceae plants and their extracts, Houttuyniaceae plants and their extracts substances, Asteraceae plants and their extracts, myriocin, its derivatives and substances containing myriocin A small amount selected from the group consisting of heparinoids and higher fatty acids having 12 to 22 carbon atoms. Item 3. The composition for external use according to item 1 or 2, which contains at least one type of compound. Section 4. The genus names of the Lamiaceae plants are Thymus, Thymus vulgare, Thymus nigricans ... Scutellaria), Origanum, Mentha a), and at least one selected from the group consisting of Lavandula spp. Item 4. The composition for external use according to item 3, wherein the composition is one of the above. Section 5. The Lamiaceae plant is wild thyme, scutellaria, marjoram, peppermint, and la Item 3 or 4, which is at least one selected from the group consisting of vendors. thing. Section 6. The genus name of the legume plant is Aspalathus. 5. An external composition described in any one of claims 1 to 4. Section 7. Item 7. The method according to any one of items 3 to 6, wherein the legume is Aspalathus linearis. External composition. Section 8. The myriocin derivative is fingolimod hydrochloride (FTY720). 7. An external composition described in any one of claims 7. Section 9. Item 9. Any of items 3 to 8, wherein the myriocin-containing substance is cordyceps sinensis and / or an extract thereof. 2. An external composition as described in claim 1. Section 10. The total content of the component (A) is 0.0001 to 10% by mass based on the total amount of the topical composition. The composition according to any one of items 1 to 9. Effect of the Invention

[0011] The topical composition of the present invention contains as an active ingredient a component that enhances the production of KPRP protein. Its content helps prevent and improve the decline in skin moisture and skin barrier function. In addition, the present invention improves the skin condition mediated by KPRP protein. It is possible to do so. [Brief description of the drawings]

[0012] [Figure 1] FIG. 1 is a graph showing the results of confirming the expression level of the KPRP gene in epidermal keratinocytes in Test Example 1. [Diagram 2]FIG. 2 is a graph showing the results of confirming the expression level of the involucrin gene in epidermal keratinocytes in Test Example 1. [Diagram 3] FIG. 3 is a graph showing the results of confirming the expression level of the keratin 1 gene in epidermal keratinocytes in Test Example 1. [Figure 4] FIG. 4 is a graph showing the results of screening for components that affect KPRP protein production in epidermal keratinocytes in Test Example 2. [Diagram 5] FIG. 5 is a graph showing the effect of combining KPRP protein production-promoting components in Test Example 3. [Figure 6] FIG. 6 is a graph showing the results of screening for other components that affect the production of KPRP protein in epidermal keratinocytes in Test Example 4. [Figure 7] FIG. 7 is a graph showing the effect of the KPRP protein production-promoting component in a model of disruption of the barrier function of the stratum corneum in Test Example 5. [Figure 8] FIG. 8 is a graph showing the effect of the KPRP protein production-promoting component in a model of disruption of the barrier function of the stratum corneum in Test Example 6. [Figure 9] FIG. 9 is a graph showing the effect of the KPRP protein production-promoting component in a model of disruption of the barrier function of the stratum corneum in Test Example 7. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] The topical composition of the present invention contains a KPRP protein production promoting ingredient as an active ingredient. This makes it possible to improve the condition of the skin mediated by KPRP proteins. In the specification, the term "KPRP protein production-promoting component" refers to a component that promotes KPR production in epidermal keratinocytes. Gene expression and / or protein expression of P in the presence of the component compared to its absence. There are no particular limitations as long as the component can enhance the activity.

[0014] As a component that significantly enhances the production of KPRP protein, the present specification newly describes (A ) Lamiaceae plants and their extracts, legume plants and their extracts, myriocin and its derivatives and at least one selected from the group consisting of a heparinoid and a myriocin-containing substance. One species of each has been found.

[0015] [Component (A)] (Lamiaceae plants and their extracts) The Lamiaceae plant is not particularly limited as long as it exhibits the effects of the present invention. For example, Thymus, Scutella ia), Origanum, Lavandula, etc. Examples include:

[0016] Examples of Thymus plants include wild thyme (T hymus serpyllum, hymus serpyllum thyme, caraway thyme, citrus thyme, woolly thyme, etc. Among these, wild thyme is preferred from the viewpoint of significantly exhibiting the effects of the present invention. It is nice.

[0017] Examples of plants in the Scutellaria genus include Scutellaria baicalensis (Sc utellaria baicalensis Georgi, scutellaria, Yellow, Skullwort, Munin Skullwort, Yamashiro Skullwort, Namikisou, Blue Skull Among these, the effects of the present invention can be seen in From the viewpoint of exhibiting a remarkable effect, Scutellaria Root is preferred.

[0018] Examples of plants in the Origanum genus include marjoram (Origa num majorana), and oregano (Origanum vulgare). Among these, marjoram is preferred from the viewpoint of significantly exhibiting the effects of the present invention. stomach.

[0019] Examples of plants in the genus Mentha include peppermint (Mentha x piperita L.) Spearmint (Mentha spicata), Japanese Mentha canadensis var. piperascens, etc. Can be obtained.

[0020] Examples of plants in the genus Lavandula include lavender. andula angustifolia), spike lavender, Italian lavender Among these, the following are the most popular: From the viewpoint of significantly exhibiting the effects of the present invention, lavender is preferable.

[0021] The method for extracting the Lamiaceae plant is not limited as long as the effect of the present invention is achieved. The extract of the Lamiaceae plant is obtained by extracting the Lamiaceae plant or its pulverized product from water and / or organic solvent. The extract obtained by immersion extraction with a solvent and filtering off the residue, and the solvent is removed from this extract. The above extract or the solvent-removed product is then soaked in a suitable solvent. The term "solvent" refers to a substance that has been dissolved, dispersed, or diluted by means of a solvent, and commercially available products can also be used. As an example of another extraction method, extracts from Lamiaceae plants are obtained by processing the plants, such as by steaming them. It can also be extracted from

[0022] Extracts of Lamiaceae plants are made from the whole plant or the necessary parts (flowers, inflorescences, flower buds, buds, etc.) of Lamiaceae plants. , inflorescences, leaves, branches, foliage, rhizomes, root bark, roots, bark, fruit, pericarp, legumes, seeds, etc.) The crude extract may be used as it is, or may be further purified or concentrated. The extract may be a plant extract, a synthetic extract, or a commercially available product. The method for obtaining the substance is not particularly limited, and may be a conventional extraction method, purification method, concentration method, or synthesis method. , dry powdering method, etc. are adopted.

[0023] The extraction solvent for extracting the Lamiaceae plant is not limited as long as it exhibits the effects of the present invention. For example, methanol, ethanol, propanol, isopropyl alcohol, butanol, etc. Lower alcohols with prime numbers 1 to 4; glycerin, propylene glycol, polyethylene glycol polyhydric alcohols such as alcohol; polar solvents such as water, acetone, ethyl acetate, methyl acetate; hexadecyl sulfate, etc. Among these, one or two of them may be used in combination. Among these solvents, water, ethanol, 1,3-butylene glycol , propylene glycol, or a mixture thereof is preferred.

[0024] The Lamiaceae plant from which the extract is obtained is not limited as long as it can exhibit the effects of the present invention. For example, Thymus, Scutella ria), Origanum, Mentha, and Lavender At least one species selected from the group consisting of the genus Lavandula is preferred. , wild thyme, scutellaria, marjoram, peppermint, and lavender At least one selected from the following is more preferable.

[0025] When wild thyme extract is used as the extract of the Lamiaceae plant, the part to be extracted is the whole plant, The above-ground parts, leaves, flowers, roots or stems are preferred, and the extraction solvent is water, ethanol, 1, 3-butylene glycol, or a mixed solution thereof is preferred.

[0026] Commercially available products of wild thyme extract include, but are not limited to, Falcolex Wild Thyme. Dotime B, Cinderella Care (Manufacturer: Ichimaru Falcos Co., Ltd.), Wild Time Extracts such as Wild Thyme Extract BG (manufacturer: Maruzen Pharmaceutical Co., Ltd.) can be used. .

[0027] When Scutellaria root extract is used as the extract of the Lamiaceae plant, the part to be extracted is the whole plant or The root is preferred, and the extraction solvent is water, ethanol, 1,3-butylene glycol, Propylene glycol, glycerin or a mixed solution thereof is preferred.

[0028] Commercially available products of Scutellaria root extract include, but are not limited to, Falcorex Scutellaria root extract. Red B, Golden Liquid SE, Golden Liquid G (Manufacturer: Ichimaru Falcos) , Scutellaria Baicalensis Extract-J (manufacturer: Maruzen Pharmaceuticals), etc. can be used.

[0029] When marjoram extract is used as the extract of a plant of the Lamiaceae family, the part to be extracted is the whole plant, or , preferably leaves, and the extraction solvent is water, ethanol, 1,3-butylene glycol or a mixture thereof.

[0030] Commercially available marjoram extracts include, but are not limited to, Marjoram Extract BG (manufacturer (Maruzen Pharmaceutical Co., Ltd.) etc. can be used.

[0031] When peppermint extract is used as an extract of a Lamiaceae plant, the whole plant, The extract is preferably from the top, leaves, flowers, roots or stems, and the extracting solvent is water, ethanol, 1,3 -butylene glycol, or a mixture thereof.

[0032] Commercially available peppermint extracts include, but are not limited to, Peppermint Extract BG (manufactured by (Manufacturer: Maruzen Pharmaceutical Co., Ltd.) etc. can be used.

[0033] When lavender extract is used as the extract of the Lamiaceae plant, the part to be extracted is the flower or The leaves are preferred, and the extraction solvent is water, ethanol, 1,3-butylene glycol, Alternatively, it is preferably a mixed solution of these, and more preferably one obtained by steam distillation.

[0034] Commercially available products of lavender extract include, but are not limited to, Falcorex Lavender (Manufacturer: Ichimaru Pharcos Co., Ltd.), Lavender Extract BG-J (Manufacturer: Maruzen Pharmaceutical Co., Ltd. (Company name, etc.) may be used.

[0035] (Leguminous plants and their extracts) The legume plant is not particularly limited as long as it exerts the effects of the present invention. For example, Aspalathus, Trifolius um), Astragalus, Glycyrrhiza, etc. Examples include:

[0036] Examples of plants in the genus Aspalathus include Aspalathus spp. Examples include Aspalathus linearis (rooibos).

[0037] Examples of plants in the Trifolium genus include red clover ( Examples include red clover and white clover.

[0038] Examples of plants in the Astragalus genus include Rengeso (lotus flower), Examples include Astragalus membranaceus and Astragalus natanshiroi.

[0039] Examples of plants in the genus Glycyrrhiza include Licorice, Urales, Examples include licorice, Spanish licorice, etc.

[0040] The method for extracting the legumes is not limited as long as the effect of the present invention is exhibited. The extract of the legumes is obtained by extracting the legumes or their crushed products from water and / or organic solvent. The extract obtained by immersion extraction with a solvent and filtering off the residue, and the solvent is removed from this extract. The above extract or the solvent-removed product is then soaked in a suitable solvent. The term "solvent" refers to a substance that has been dissolved, dispersed, or diluted by means of a solvent, and commercially available products can also be used. As an example of another extraction method, extracts from legumes are extracted by steaming the legumes and then processing them. It can also be extracted from

[0041] The extracts of legumes are made from the whole plant or the necessary parts (flowers, inflorescences, flower buds, buds, etc.) of legumes. , inflorescences, leaves, branches, foliage, rhizomes, root bark, roots, bark, fruit, pericarp, legumes, seeds, etc.) The crude extract may be used as it is, or may be further purified or concentrated. The extract may be a plant extract, a synthetic extract, or a commercially available product. The method for obtaining the substance is not particularly limited, and may be a conventional extraction method, purification method, concentration method, or synthesis method. , dry powdering method, etc. are adopted.

[0042] The extraction solvent for the legume extract is not limited as long as it exhibits the effects of the present invention. For example, methanol, ethanol, propanol, isopropyl alcohol, butanol, etc. Lower alcohols with prime numbers 1 to 4; glycerin, propylene glycol, butylene glycol , polyhydric alcohols such as polyethylene glycol; water, acetone, ethyl acetate, methyl acetate and non-polar solvents such as hexane and pyridine. Of these solvents, water, ethanol, 1,3 -Butylene glycol, propylene glycol, glycerin, or a mixture of these preferable.

[0043] The legumes from which the extract is obtained are not limited as long as the effects of the present invention are achieved. For example, the genus Aspalathus is preferred, and Aspalathus linearis is preferred. Squirrels are more preferable.

[0044] When using Aspalathus linearis extract as the extract of legumes, the part to be extracted is The extract is preferably made from the whole plant or leaves, and the extraction solvent is water, ethanol, 1,3-butylene, etc. It is preferable that the solvent used is ethylene glycol, ethylene glycol, or a mixed solution thereof.

[0045] Commercially available products of Aspalathus linearis extract include, but are not limited to, Falcolex Rooibos B(N) (manufacturer: Ichimaru Pharcos Co., Ltd.) or the like can be used.

[0046] (Peony plant and its extract) The peony family plant is not particularly limited as long as it can exhibit the effects of the present invention. For example, the genus Paeonia can be mentioned.

[0047] Examples of plants in the Paeonia genus include the peony (Paeonia lactiflora, and peony (Paeonia suffruticosa). Can be obtained.

[0048] The method for extracting the plant of the family Paeoniae is not limited as long as the effect of the present invention is achieved. The extract of the peony family plant is obtained by extracting the above-mentioned peony family plant or its crushed product from water and / or water. The extract is obtained by immersing the extract in an organic solvent and filtering the residue. The solvent is removed, or the fine powder of the above, or the above extract or the solvent-removed product, is dissolved in a suitable solvent. This refers to substances that have been dissolved, dispersed, or diluted using agents, and commercially available products can also be used. As an example of another extraction method, the extract of the peony plant can be obtained by subjecting the plant to a process such as steaming. It is also possible to perform processing and then extract the extract.

[0049] The extract of the Peony family is prepared by extracting the whole plant or the necessary parts (flower, inflorescence, flower bud, etc.) of the Peony family. Buds, inflorescences, leaves, branches, foliage, rhizomes, root bark, roots, bark, fruit, pericarp, legumes, seeds, etc.) The crude extract may be used as it is, or may be further purified or concentrated. It may be a plant-derived product, a synthetic product, or a commercially available product. The method for obtaining the extract is not particularly limited, and may be a conventional extraction method, a purification method, a concentration method, a synthesis method, or the like. Methods such as drying and powdering are used.

[0050] The extraction solvent for the extract of the Paeoniaceae plant is not limited as long as it can achieve the effects of the present invention. For example, methanol, ethanol, propanol, isopropyl alcohol, butanol, etc. Lower alcohols with 1 to 4 carbon atoms; glycerin, propylene glycol, butylene glycol polyhydric alcohols such as polyethylene glycol; water, acetone, ethyl acetate, methyl acetate polar solvents such as hexane and pyridine; and non-polar solvents such as hexane and pyridine. Of these solvents, water, ethanol, 1, 3-butylene glycol, propylene glycol, glycerin, or a mixture of these is preferred.

[0051] The plant of the family Paeoniae from which the extract is obtained is not limited as long as the effects of the present invention are achieved. However, for example, peonies and / or trees are preferred, with peonies being more preferred.

[0052] When using peony extract as the extract of the Paeoniaceae plant, the part to be extracted is the whole plant or The extractant is preferably a root, and the extractant is water, ethanol, 1,3-butylene glycol. It is preferable that the solvent is a mixture of these.

[0053] Commercially available products of peony extract include, but are not limited to, Peony Extract (manufacturer: Maru (Zen Pharmaceutical Co., Ltd.) etc. can be used.

[0054] (Houttuynia plants and their extracts) The Houttuynia family plant is not particularly limited as long as it exhibits the effects of the present invention. Examples of such plants include the genus Houttuynia, the genus Saururus, and the like. us L.) etc.

[0055] Examples of plants in the genus Paeonia include Houttuynia cordata (H. cordatum). a) etc.

[0056] Examples of plants in the genus Saururus include Saururus japonica ( S. chinensis) and S. cernuus. can be.

[0057] The method for extracting the Houttuynia cordata plant is not limited as long as the effect of the present invention is achieved. For example, the extract of a Houttuynia cordata plant may be prepared by extracting the above-mentioned Houttuynia cordata plant or its crushed product from water and and / or an organic solvent, and the residue is filtered off. The solvent is removed from the extract or the fine powder of the extract or the solvent-removed product. This refers to substances that have been dissolved, dispersed, or diluted using appropriate solvents, and commercial products can also be used. As an example of another extraction method, the extract of Houttuynia cordata can be obtained by steaming Houttuynia cordata. It is also possible to extract the data after processing such as grinding.

[0058] The extract of Houttuynia cordata is made from the whole plant or the necessary parts (flowers, inflorescences, flower buds, etc.) of the Houttuynia cordata plant. , buds, inflorescences, leaves, branches, foliage, rhizomes, root bark, roots, bark, fruit, pericarp, legumes, seeds, etc.) The crude extract extracted from the plant may be used as it is, or may be further purified, or may be concentrated. The plant material may be a commercially available product, or may be a synthetic product. The method for obtaining an extract of a substance is not particularly limited, and may be a conventional extraction method, a purification method, a concentration method, Synthesis methods, dry powder methods, etc. are used.

[0059] The extraction solvent for the extract of the Houttuynia cordata family plant is not limited as long as the effects of the present invention are achieved. For example, methanol, ethanol, propanol, isopropyl alcohol, butanol, etc. Lower alcohols with 1 to 4 carbon atoms; glycerin, propylene glycol, butylene glycol Polyhydric alcohols such as polyethylene glycol; water, acetone, ethyl acetate, methyl acetate polar solvents such as ethyl acetate; and non-polar solvents such as hexane and pyridine. Of these solvents, water, ethanol, 1 ,3-butylene glycol, propylene glycol, glycerin, or a mixture of these solvents A liquid is preferred.

[0060] The plant of the Houttuynia family from which the extract is obtained is not limited as long as the effects of the present invention are achieved. However, for example, Houttuynia cordata and / or Pinctada gracilis are preferred, and Houttuynia cordata is more preferred.

[0061] When Houttuynia cordata extract is used as the extract of the Houttuynia family plant, the whole plant or The extractant is preferably a root, and the extractant is water, ethanol, 1,3-butylene glycol. It is preferable that the solvent is a mixture of these.

[0062] Commercially available Houttuynia extracts include, but are not limited to, Falcorex Houttuynia B. , Falcorex Houttuynia cordata E, Falcorex Houttuynia cordata W (Manufacturer: Ichimaru Fu (ARCOS Co., Ltd.) etc. can be used.

[0063] (Asteraceae plants and their extracts) The Asteraceae plant is not particularly limited as long as it exhibits the effects of the present invention. For example, Matricaria, Cirsium, and Dandelion. Examples include the genus Taraxacum and the genus Chrysanthemum.

[0064] Examples of plants in the Matricaria genus include chamomile (M. r ecutita) etc.

[0065] The method for extracting the Asteraceae plant is not limited as long as the effect of the present invention is achieved. The extract of the Asteraceae plant is obtained by extracting the above-mentioned Asteraceae plant or its pulverized product from water and / or organic solvent. The extract obtained by immersion extraction with a solvent and filtering off the residue, and the solvent is removed from this extract. The above extract or the solvent-removed product is then soaked in a suitable solvent. The term "solvent" refers to a substance that has been dissolved, dispersed, or diluted by means of a solvent, and commercially available products can also be used. As an example of another extraction method, extracts of Asteraceae plants are obtained by processing the plants such as steaming them. It can also be extracted from

[0066] Extracts of Asteraceae plants are extracted from the whole plant or from the necessary parts (flowers, inflorescences, flower buds, buds, etc.) of Asteraceae plants. , inflorescences, leaves, branches, foliage, rhizomes, root bark, roots, bark, fruit, pericarp, legumes, seeds, etc.) The crude extract may be used as it is, or may be further purified or concentrated. The extract may be a plant extract, a synthetic extract, or a commercially available product. The method for obtaining the substance is not particularly limited, and may be a conventional extraction method, purification method, concentration method, or synthesis method. , dry powdering method, etc. are adopted.

[0067] The extraction solvent for the Asteraceae plant is not limited as long as it exhibits the effects of the present invention. For example, methanol, ethanol, propanol, isopropyl alcohol, butanol, etc. Lower alcohols with prime numbers 1 to 4; glycerin, propylene glycol, butylene glycol , polyhydric alcohols such as polyethylene glycol; water, acetone, ethyl acetate, methyl acetate and non-polar solvents such as hexane and pyridine. Of these solvents, water, ethanol, 1,3 -Butylene glycol, propylene glycol, glycerin, or a mixture of these preferable.

[0068] The Asteraceae plant from which the extract is obtained is not limited as long as the effects of the present invention are achieved. For example, chamomile is preferred.

[0069] When chamomile extract is used as the extract of the Asteraceae plant, the part to be extracted is the whole plant, or , preferably the root, and the extraction solvent is water, ethanol, 1,3-butylene glycol or a mixture thereof.

[0070] Commercially available chamomile extracts include, but are not limited to, Chamomile Extract (manufacturer: Maru (Zen Pharmaceutical Co., Ltd.) etc. can be used.

[0071] (Myriocin, its derivatives, or substances containing myriocin) Myriocin (ISP-I) is a compound represented by the following formula (1).

[0072] [ka]

[0073] Myriocin is a fungus derived from the genus Isaria and Mycelia. or Myriococcum sp., etc. Myriocin can be obtained from these fungal cells by known methods, and it can be synthesized. It may also be used.

[0074] Examples of the Isaria species include Isaria sincreirii ( Specific examples of the strain include Isaria sinclairii. Examples include Isaria sinclairii ATCC24400. can be done.

[0075] Examples of species of the genus Mycelia include Mycelia sterilia. (Mycelia sterillia), etc. Examples include Myceliasterillia ATCC20349. can be.

[0076] Examples of species of the genus Myriococcum include Myriococcum spp. Myriococcum albomyces, etc. Specific examples of the strain include Myriococcus albomyces. albomyces ATCC16425 and the like.

[0077] The method for obtaining myriocin from the cells is not limited to the above. The culture medium is used to culture the bacteria under optimal conditions, and the resulting culture solution is filtered or otherwise treated to remove the bacteria. After separating the bacteria and the culture filtrate, the bacteria and the culture filtrate were subjected to solvent extraction and column chromatography, respectively. A method for fractionating and purifying myriocin by fractionation treatment such as chromatography is provided. Some examples include:

[0078] There are no limitations on the myriocin derivatives as long as they achieve the effects of the present invention. For example, Examples include fingolimod hydrochloride (FTY720).

[0079] Examples of substances containing myriocin include, but are not limited to, cordyceps sinensis and / or its extracts. Specifically, the Cordyceps sinensis fungus (cordyceps fungus) that forms the Cordyceps sinensis is Isaria sp. , Myceria spp., Myriococcum spp., etc., and specific species include Isarii A. sincreilii, Myceria sterilia, Myriococcum albomyces, etc. The myriocin-containing substance can be produced by a known method, and The bacteria are cultured under optimal conditions using a medium or host suitable for their growth, and the resulting culture medium is It is possible to obtain the nutrient solution or the fruiting body by purifying and / or powdering it.

[0080] Examples of commercially available cordyceps extracts include, but are not limited to, cordyceps extract liquid (manufacturer (Maruzen Pharmaceutical Co., Ltd.) etc. can be used.

[0081] (heparinoids) Heparinoids are a general term for polysulfated mucopolysaccharides such as chondroitin polysulfate. An average of 0.5 to 5 molecules, preferably an average of 0.6 to 3 molecules, per monosaccharide molecule constituting mucopolysaccharide. More specifically, the heparinoid is heparin, Contains chondroitin sulfate D and chondroitin sulfate E, also known as androitin polysulfate. do.

[0082] Heparinoids can also be obtained by sulfated mucopolysaccharides, and are derived from bovine and bronchial Extraction and purification are performed using aqueous carriers from the internal organs of animals, including the bronchi, such as mice, and then, if necessary, Heparinoids are used as raw materials for pharmaceuticals and cosmetics. Since it has been developed as a commercial product, such a commercial product can also be used.

[0083] In the topical composition of the present invention, the heparinoid is Those that are available are preferably used.

[0084] These components (A) may be used alone or in any combination of two or more. This is also fine.

[0085] (Higher fatty acids with 12 to 22 carbon atoms) As higher fatty acids having 12 to 22 carbon atoms, There is no particular limitation as long as it is used as a component of an external skin preparation. As the fatty acid, a higher fatty acid having 12 to 22 carbon atoms is preferable, and a higher fatty acid having 14 to 22 carbon atoms is preferable. More preferred are higher fatty acids having 16 to 22 carbon atoms, and even more preferred are higher fatty acids having 16 to 22 carbon atoms.

[0086] The higher fatty acid having 12 to 22 carbon atoms is not limited, but is preferably lauric acid, milliglyceric acid, Succinic acid, palmitic acid, stearic acid, margaric acid, arachidonic acid, or behenic acid Any straight-chain saturated fatty acid (solid at room temperature); oleic acid, linoleic acid, linolenic acid, arachidonic acid acid, palmitoleic acid, eicosapentaenoic acid, paccenic acid or docosahexaenoic acid Any unsaturated fatty acid (liquid at room temperature); or, isostearic acid or lanolin fatty acid In the present invention, the following fatty acids are limited: Although it is not necessary to use the straight-chain saturated fatty acid, it is particularly preferable to use the straight-chain saturated fatty acid. From the viewpoint of significantly exhibiting the above, isostearic acid, lauric acid, myristic acid, palmitic acid , stearic acid, or behenic acid is preferred, and isostearic acid, myristic acid, palmitic acid, More preferred are stearic acid, stearic acid, and behenic acid, and more preferred are isostearic acid, palmitic acid, stearic acid, and The more preferred are stearic acid and behenic acid. The higher fatty acids of 1 to 22 can be used alone or in combination of two or more.

[0087] In the topical composition of the present invention, the total content of component (A) is determined based on the type of component (A), other ingredients, The amount is appropriately set depending on the type and amount of the ingredient, the formulation form, the method of use, etc. However, for example, the total content of the component (A) is preferably 0.000 to the total amount of the topical composition. 1% by mass or more, more preferably 0.0005% by mass or more, and even more preferably 0.0 0.01% by mass or more, particularly preferably 0.005% by mass or more, and further particularly preferably 0.01 The total content of the component (A) is preferably 0.05% by mass or more, and more preferably 0.05% by mass or more. , preferably 10% by mass or less, more preferably 5% by mass, based on the total amount of the topical composition. The content is particularly preferably 3% by weight or less, and most preferably 2% by weight or less. The total content of the composition for external use is preferably 0.0001 to 10% by mass based on the total amount of the composition for external use, More preferably, it is 0.0005 to 5 mass%, further preferably, it is 0.001 to 3 mass%, and particularly preferably The content is preferably 0.005 to 2% by mass. In this case, the content is calculated on a dry solids basis.

[0088] In a preferred embodiment, for example, wild thyme and / or its extract is used, but is not limited thereto. as component (A), wild thyme and / or its extract are contained alone. The amount is preferably 0.0001 to 5% by mass in terms of dry solid content based on the total amount of the composition for external use. More preferably, it is 0.0005 to 3 mass%, and further preferably, it is 0.001 to 2 mass%. The content is particularly preferably 0.005 to 1% by mass.

[0089] In a preferred embodiment, for example, Scutellaria Root and / or an extract thereof are used (A When Scutellaria Root and / or its extract are contained as an ingredient in the external preparation, The content is preferably 0.0001 to 5% by mass in terms of dry solid content based on the total amount of the composition, and more preferably Preferably, it is 0.0005 to 3 mass%, more preferably, it is 0.001 to 2 mass%, and particularly preferably The content is usually 0.005 to 1 mass %.

[0090] In a preferred embodiment, for example, marjoram and / or its extract is ( A) When contained as an ingredient, the content of marjoram and / or its extract alone is The content is preferably 0.0001 to 5% by mass in terms of dry solid content based on the total amount of the composition. More preferably, it is 0.0005 to 3 mass%, further preferably, it is 0.001 to 2 mass%, and particularly preferably The content is preferably 0.005 to 1% by mass.

[0091] In a preferred embodiment, for example, peppermint and / or its extracts are used, but are not limited thereto. When contained as an ingredient (A), the content of peppermint and / or its extract alone is The content is preferably 0.0001 to 5% by mass in terms of dry solid content based on the total amount of the topical composition. More preferably, it is 0.0005 to 3 mass%, further preferably, it is 0.001 to 2 mass%, and particularly preferably, it is 0.0005 to 3 mass%. The content is preferably 0.005 to 1% by mass.

[0092] In a preferred embodiment, for example, lavender and / or its extracts are used, but not limited to these. A) When contained as an ingredient, the content of lavender and / or its extract alone is The content is preferably 0.0001 to 5% by mass in terms of dry solid content based on the total amount of the composition. More preferably, it is 0.0005 to 3 mass%, further preferably, it is 0.001 to 2 mass%, and particularly preferably The content is preferably 0.005 to 1% by mass.

[0093] In a preferred embodiment, for example, but not limited to, Aspalathus linearis and / or its Aspalathus linearis and / or its extract as component (A), The content of the extract alone is preferably 0.0% by weight in terms of dry solid content relative to the total amount of the composition for external use. It is preferably 0.001 to 5 mass%, more preferably 0.0005 to 3 mass%, and even more preferably 0. The content is preferably 0.001 to 2% by mass, and more preferably 0.005 to 1% by mass.

[0094] In a preferred embodiment, for example, peony root and / or its extract are ( A) When contained as an ingredient, the content of peony and / or its extract alone is The content is preferably 0.0001 to 5% by mass in terms of dry solid content based on the total amount of the composition. More preferably, it is 0.0005 to 3 mass%, further preferably, it is 0.001 to 2 mass%, and particularly preferably The content is preferably 0.005 to 1% by mass.

[0095] In a preferred embodiment, for example, Houttuynia cordata and / or its extract are used as a non-limiting example. When Houttuynia cordata and / or its extract are contained as an ingredient, the content of the external composition is The content is preferably 0.0001 to 5% by mass in terms of dry solid content based on the total amount of the composition, and more preferably Preferably, it is 0.0005 to 3 mass%, more preferably, it is 0.001 to 2 mass%, and particularly preferably The content is usually 0.005 to 1 mass %.

[0096] In a preferred embodiment, for example, chamomile and / or its extract are used, but not limited to the above. A) When contained as an ingredient, the content of chamomile and / or its extract alone is The content is preferably 0.0001 to 5% by mass in terms of dry solid content based on the total amount of the composition. More preferably, it is 0.0005 to 3 mass%, further preferably, it is 0.001 to 2 mass%, and particularly preferably The content is preferably 0.005 to 1% by mass.

[0097] In a preferred embodiment, myriocin and its derivatives are used, but are not limited to these. When myriocin and its derivatives are contained as components, the concentration of each component is preferably is 0.01 to 500 nM, more preferably 0.05 to 300 nM, and even more preferably The concentration is 0.1 to 200 nM, and particularly preferably 0.5 to 150 nM.

[0098] In a preferred embodiment, the present invention is not limited to the above, but includes, for example, the use of Cordyceps sinensis and / or an extract thereof (A When the ingredient is contained in the formulation, the content of Cordyceps sinensis and / or its extract alone is The amount of the dry solid content is preferably 0.001 to 5% by mass, more preferably 0.001 to 5% by mass, based on the total amount of the composition. The content is preferably 0.005 to 3 mass%, more preferably 0.01 to 2 mass%, and particularly preferably 0. .05 to 1 mass %.

[0099] In a preferred embodiment, for example, a heparinoid is used as component (A), but is not limited thereto. When the heparinoid is contained, the content of the heparinoid alone is preferably about 100% based on the total amount of the composition for external use. The content is preferably 0.001% by mass to 5% by mass, more preferably 0.01% by mass to 1% by mass, and even more preferably The content is preferably 0.1 to 0.5 mass %, and particularly preferably 0.2 to 0.3 mass %.

[0100] In a preferred embodiment, for example, isostearic acid is used as component (A), but is not limited thereto. In the case where isostearic acid is contained, the content of isostearic acid alone is preferably about 100% based on the total amount of the composition for external use. The content is preferably 0.00005% by mass to 5% by mass, more preferably 0.0001% by mass to 2% by mass. The content is more preferably 0.0005 to 1% by mass, and particularly preferably 0.001 to 1% by mass.

[0101] [Application] The topical composition of the present invention contains as an active ingredient a component that significantly enhances the production of KPRP protein. It contains niacin, which prevents and improves the decline of skin moisture and skin barrier function. In addition, it is possible to improve or strengthen the skin barrier function, thereby improving the skin's moisture retention (skin It is possible to improve the skin's moisture retention ability. In the skin at the stratum corneum, production of KPRP protein is increased in the keratinocytes of the stratum corneum and / or in the upper granular layer. It is possible to increase the amount of KPRP and improve the condition of the skin mediated by KPRP protein. do.

[0102] In this specification, the stratum corneum of the skin (also called the keratinocyte layer) is the outermost layer of the skin. The epidermis is a layer of flattened keratinocytes that are formed by keratinization of the epidermis. It is divided into four layers: the stratum basale, the stratum spinosum, the stratum granulosum, and the stratum corneum at the top. Basal cells, which form the epidermis, divide and move to the upper layers as they mature. It is believed that it takes about 45 days for the skin to migrate to the stratum corneum and be removed. It is being done.

[0103] In the keratinocyte layer, KPRP protein is involved in the formation of desmosomes. It has been suggested that it plays an important role in intercellular adhesion between keratinocytes (Non-Patent Literature 3) Intercellular adhesion between keratinocytes occurs not only vertically from the basal layer to the skin surface, but also horizontally. It also affects the functioning of the skin, so increased production of KPRP proteins improves the skin barrier. Among its functions, it is particularly effective in strengthening the three-dimensional structure of the stratum corneum.

[0104] In addition, considering its functions and actions, KPRP protein is a skin barrier gene (causing They can also be called genes (factors) that improve skin barrier function.

[0105] In a normal stratum corneum, the three-dimensional structure of the stratum corneum and the structure called the peripheral zone prevent sunlight and ultraviolet rays from entering the skin. Air pollution, active oxygen, chemicals, temperature, dryness, smoking, over-cleaning of the skin, stress, etc. It is stable against physical and / or chemical stimuli (also called skin barrier function). However, When these structures become disordered, the stratum corneum becomes abnormal and the above-mentioned physical and / or chemical stimuli are activated. This condition is called sensitive skin. In addition, a state in which the skin reacts temporarily is sometimes called unstable skin. Increased expression of KPRP gene is related to increased expression of involucrin gene, which constitutes the marginal zone. It has been found that it has a beneficial effect on sensitive skin and unstable skin. In addition, the three-dimensional structure of the stratum corneum is damaged, This causes evaporation of moisture from within the stratum corneum, resulting in a decrease in skin moisture content. The invention shows that enhanced production of KPRP protein strengthens the three-dimensional structure of the stratum corneum and the structure of the peripheral zone. This leads to the reconstruction and regeneration of the skin barrier function, improving the skin barrier function and skin moisture content ( In addition, the composition for external use of the present invention is effective in maintaining or improving the skin's moisture-retaining ability. By continuing to use this product, the three-dimensional structure of the stratum corneum and the structure of the peripheral zone can be maintained and strengthened. This leads to a decrease in the skin barrier function and skin moisture content (or moisture retention ability). It prevents skin irritation caused by sensitive or unstable skin, and maintains a normal skin structure. Furthermore, continued use of the topical composition of the present invention can improve the skin's condition. It helps to improve the condition of the stratum corneum when it is rough or otherwise abnormal, and once it has returned to normal, it helps to prevent rough skin from occurring again. It is also expected to have the effect of

[0106] In addition, when the stratum corneum is normalized and repaired by increased production of KPRP protein, The surface is smooth and covered by a normal sebum film, making it easier to apply various cosmetics to the skin. Therefore, the present invention is a cosmetic agent that is suitable for use in skin care. It is also suitable for use in promoting skin compatibility.

[0107] In addition, when the stratum corneum is normalized and repaired by increased production of KPRP protein, The smooth surface also leads to a smooth skin texture. It is also suitable for use in the synthesis of fluororesin.

[0108] The granular layer of the stratum corneum is distributed with spherical Odland corpuscles, and their contents, such as ceramides, By releasing which lipid, the intercellular lipid is formed, and the keratinization and / or moisturization of the stratum corneum are improved. In one embodiment, the topical composition of the present invention is applied mainly to the upper part of the granular layer. It acts on the skin, promoting the production of KPRP protein and promoting keratinization in the stratum corneum. The granular layer is the foundation that supports the stratum corneum, so the present invention It is also suitable for use in strengthening and maintaining the foundation (base) of the stratum corneum.

[0109] In addition, SNP analysis showed a relationship between atopic dermatitis and the KPRP gene. It has been found that there is a group of patients with atopic dermatitis in whom KPRP gene expression is decreased. It has been suggested (Non-Patent Document 3). Therefore, the present invention provides a method for preventing and / or treating atopic dermatitis. can be used for the treatment of atopic dermatitis, in particular, the atopic dermatitis associated with decreased expression of the KPRP gene. It is also suitable for use in the prevention and / or treatment of dermatitis.

[0110] The composition for external use of the present invention has a structure that improves the skin barrier function in order to significantly exhibit the effects of the present invention. It is preferable to apply it to areas where the skin barrier function is structurally insufficient. Examples of such areas include, but are not limited to, areas with a thin stratum corneum (including areas that have become thin due to wounds, etc.) These include areas with a thin sebum film (including areas without a sebum film) and areas where the stratum corneum is underdeveloped. do.

[0111] Areas with a thin stratum corneum include the lips, sensitive skin, hypersensitive skin, dry skin, sensitive skin, and rough skin. Among these, the lips have a thin stratum corneum and no sebum film, so they are more susceptible to the outside world. They are sensitive to stimuli from

[0112] Examples of areas where the stratum corneum is underdeveloped include the skin of infants. In this skin, the intercellular lipids are immature and the structure makes it difficult for moisture to be retained.

[0113] Therefore, by applying the topical composition of the present invention, the intercellular adhesion between keratinocytes is vertically enhanced. The pores are maintained in both the lateral and lateral directions, promoting the stabilization of keratinocytes and improving the skin barrier function. This becomes possible.

[0114] [(B) Component] The topical composition of the present invention further comprises (B) an antihistamine, an antipruritic, an anti-inflammatory, or a cooling agent. , local anesthetics, disinfectants (antibacterial agents), vitamins, anti-wrinkle agents, and skin whitening agents It is preferable that the component (B) contains at least one selected from the following. When applied to areas where normalization of skin tone is required, it can act to improve skin condition.

[0115] (Antihistamines) Examples of the antihistamine include chlorpheniramine, diphenhydramine, and Examples of the salts include hydrochloride, maleate, Salicylates are particularly preferred. Among them, diphenhydramine hydrochloride, diphenhydramine, salicylates, From diphenhydramine ricinate, chlorpheniramine maleate, and chlorpheniramine Preferably, one or more selected from the group consisting of diphenhydramine hydrochloride, diphenhydramine One or more selected from the group consisting of hydramine, chlorpheniramine maleate More preferably, it is selected from the group consisting of diphenhydramine hydrochloride and diphenhydramine. It is more preferable to use one or more of these.

[0116] When an antihistamine is used, its content should be less than 0.00% of the total amount of the composition for external use. The amount is preferably 1 to 10% by mass, more preferably 0.01 to 5% by mass, and even more preferably 0.1 to 3% by mass. It is more preferably 0.5 to 2 mass %, and even more preferably 0.5 to 2 mass %.

[0117] (Antipruritic) The antipruritic agent includes, for example, crotamiton.

[0118] When an antipruritic agent is added, the content thereof is 0.1 to 10 mass % based on the total amount of the external composition. %, more preferably 0.5 to 8 mass %, and even more preferably 1 to 5 mass %.

[0119] (Anti-inflammatory agent) Examples of the anti-inflammatory agent include allantoin and its derivatives (e.g., alcloxa , allantoin, etc.), tranexamic acid, glycyrrhizic acid or its derivatives or Salts thereof (e.g., dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc. ), glycyrrhetinic acid or its derivatives or salts thereof (e.g., glycyrrhetinic acid, Stearyl glycyrrhetinate, zinc oxide, aminocaproic acid, azulene and its derivatives Conductors (e.g., guaiazulene, azulene, etc.), salicylic acid or its derivatives, steroids or their derivatives or salts (e.g., hydrocortisone, prednisolone, etc.) etc.), ufenamate, bufexamac, ibuprofen piconol, azelaic acid, etc. Among them, allantoin, tranexamic acid, dipotassium glycyrrhizinate, Monoammonium ricyrrhizinate, glycyrrhetinic acid, stearyl glycyrrhetinate, a Minocaproic acid, guaiazulene, sodium azulene sulfonate, hydrocortisone, Prednisolone, prednisolone valerate acetate, hydrocortisone acetate, dexamethasone acetate , glycol salicylate, ufenamate, ibuprofen piconol, azelaic acid One or more selected from the group consisting of allantoin, tranexamic acid, and glycyrrhizin are preferred. Dipotassium tinate, glycyrrhetinic acid, monoammonium glycyrrhizinate, glycyrrhetinic acid Stearyl tincture, aminocaproic acid, prednisolone valerate acetate, dexamethasone acetate , hydrocortisone acetate, ufenamate, ibuprofen piconol, azelaic acid More preferably, one or more selected from the group consisting of allantoin, tranexamic acid, and glycyl Dipotassium ricinate, glycyrrhetinic acid, stearyl glycyrrhetinate, pre-valeric acid acetate More preferred are donisolone, dexamethasone acetate, and ibuprofen piconol.

[0120] When an anti-inflammatory agent is added, the content of the agent is 0.0001 to 0.001% based on the total amount of the composition for external use. The amount is preferably 10% by mass, more preferably 0.001 to 8% by mass, and even more preferably 0.01 to 5% by mass. It is more preferably 0.01 to 2 mass %, and even more preferably 0.01 to 2 mass %.

[0121] In particular, when steroids or their derivatives or salts are used as anti-inflammatory agents, The content is preferably 0.0001 to 2% by mass, and more preferably 0. The content is more preferably 0.01 to 1 mass %, and further preferably 0.01 to 0.5 mass %.

[0122] Anti-inflammatory agents, particularly allantoin, tranexamic acid, dipotassium glycyrrhizinate, When glycyrrhetinic acid or stearyl glycyrrhetinate is included, the content is The amount is preferably 0.0001 to 5% by mass, more preferably 0.001 to 2% by mass, based on the total amount of the composition. It is preferably 0.01 to 1 mass %, and more preferably 0.01 to 1 mass %.

[0123] Anti-inflammatory drugs, particularly ibuprofen piconol, ufenamate, and bufexamac When incorporated, the content is preferably 0.01 to 10% by mass based on the total amount of the topical composition. The content is preferably from 0.1 to 8 mass %, and more preferably from 1 to 5 mass %.

[0124] (Refreshing agent) Examples of the cooling agent include menthol and its derivatives, camphor, and chlorobutanol. ol, borneol, geraniol, cineole, anethole, limonene, eugenol Terpenes such as terpenes (which may be d-, l- or dl-isomers); eucalyptus oil, behenyl alcohol, Lugamot oil, peppermint oil, cool mint oil, spearmint oil, fennel oil, peppermint oil Examples of essential oils include cassia oil, cinnamon oil, rose oil, and turpentine oil. Among them, l-menthol , dl-menthol, menthyl glyceryl ether, menthyl lactate, menthyl 3-hydroxy xybutyrate, menthoxypropanediol, dl-camphor, eucalyptus oil, peppermint Preferably, one or more selected from the group consisting of menthol oil, peppermint oil, and turpentine oil are used. , Menthyl glyceryl ether, Menthyl lactate, Menthoxypropanediol, dl- One or more selected from camphor, eucalyptus oil, peppermint oil, and peppermint oil Preferred are l-menthol, menthyl glyceryl ether, menthyl lactate, dl-camphor More preferably, one or more selected from the group consisting of oleic acid, eucalyptus oil and peppermint oil are used.

[0125] When a cooling agent is added, the content of the cooling agent is 0.0001 to 0.0001% based on the total amount of the composition for external use. The amount is preferably 10% by mass, more preferably 0.001 to 8% by mass, and even more preferably 0.01 to 5% by mass. It is more preferably 0.1 to 2 mass %, and even more preferably 0.1 to 2 mass %.

[0126] (Local anesthetic) The local anesthetics include procaine, tetracaine, lidocaine, dibucaine, and the like. and ethyl aminobenzoate. Or two or more kinds may be used. As the salt, hydrochloride is particularly preferred. Among them, lidocaine, Selected from the group consisting of lidocaine hydrochloride, dibucaine hydrochloride, and ethyl aminobenzoate. One or more of the above are preferably selected from the group consisting of lidocaine, lidocaine hydrochloride, and aminobenzoic acid. One or more selected from the group consisting of ethyl are preferred.

[0127] When a local anesthetic is used, the content of the local anesthetic is 0.001 to 100% based on the total amount of the composition for external use. 10% by mass is preferable, 0.01 to 5% by mass is more preferable, and 0.1 to 2% by mass is even more preferable. preferable.

[0128] (Disinfectant (antibacterial agent)) Examples of the above-mentioned disinfectants (antibacterial agents) include chlorhexidine, salicylic acid, and benzyl chloride. Benzalkonium, Acrinol, Benzethonium chloride, Cetyltrimethylammonium chloride , cresol, gluconic acid and its derivatives, povidone-iodine, potassium iodide, iodine , isopropyl methylphenol, triclocarban, triclosan, zinc pyrithione , Photosensitizer No. 101, Photosensitizer No. 201, Alkyldiaminoglycine hydrochloride, Cetylpyridinium chloride nium, piroctone olamine, miconazole or a salt thereof. Citric acid, benzalkonium chloride, benzethonium chloride, cetyltrimethylammonium chloride gluconic acid, chlorhexidine gluconate, isopropyl methylphenol, zinc Pyrithione, cetylpyridinium chloride, piroctone olamine, miconazole or its Salts of salicylic acid, benzalkonium chloride, isopropyl alcohol, ethyl ... Preferably, one or more selected from the group consisting of propylmethylphenol and cetylpyridinium chloride. This is more preferable.

[0129] When a bactericidal disinfectant is added, its content shall be 0.0000 based on the total amount of the external composition. Preferably 1 to 10% by mass, more preferably 0.001 to 5% by mass, and more preferably 0.01 to 2% by mass. is more preferred.

[0130] (Vitamins) The vitamins may be either water-soluble or oil-soluble. For example, vitamin B6; pantothenic acid; nicotinic acid; vitamin B1; vitamin Vitamin B2; Vitamin B12; Vitamin C; Vitamin E; Vitamin A; Pyrroloquinone Vitamin-like factors such as ubiquinone or its salts, hesperidins, ubiquinone, and α-lipoic acid Children, etc.

[0131] When vitamins are included, their content should be less than 0.0000 based on the total amount of the external composition. The amount is preferably 1 to 10% by mass, more preferably 0.001 to 5% by mass, and more preferably 0.005 to 3% by mass. %, more preferably 0.01 to 2 mass %, and even more preferably 0.01 to 2 mass %.

[0132] When vitamins are added, specific vitamins include pyridoxine hydrochloride, pantothenate, etc. Panthenyl alcohol (panthenol), dl-α-tocopherol nicotinate, nicotinic acid Benzyl ester, nicotinamide, riboflavin, cyanocobalamin; ascorbic acid Acid, ascorbic acid derivatives, and their salts; dl-α-tocopherol acetate, dl-α -Tocopherol, δ-tocopherol, dl-α-tocopherol succinate, succinic acid dl-α-tocopherol calcium, vitamin A and its derivatives, provitamin A ;Pyrroloquinoline quinone or its salt;Hesperidin, glucosylherperidin;Ubideca Preferably, one or more selected from pyridoxine hydrochloride, pantothenyl arsenic acid salts, Cole (Panthenol), dl-α-tocopherol nicotinate, nicotinamide, Boflavin, cyanocobalamin; sodium ascorbate, ascorbyl phosphate Ascorbic Acid, Magnesium Ascorbyl Phosphate, Ascorbic Acid Ascorbic acid-2-glucoside, 3-O-ethyl ascorbic acid, 2-O-ethyl ascorbic acid Acid, Glyceryl Ascorbate, Bisglyceryl Ascorbate, Alkyl Glyceryl Ascorbic Acid, Disodium Isostearyl Ascorbyl Phosphate, L-Dipalmitate Ascorbyl, tetra-2-hexyldecanoate ascorbyl, palmitate ascorbyl Trisodium Phosphate, Methylsilanol Ascorbate, dl-α-Tocopherol Acetate, dl-α-tocopherol, δ-tocopherol, (ascorbyl / tocopheryl) phosphorus Retinol, Retinol Acetate, Retinol Palmitate, Retinol Propionate Retinol, linoleic acid retinol, hydrogenated retinol, retinoic acid, retinoic acid tocopherol carotene, α-carotene, β-carotene, γ-carotene, cryptoxanthin, lycopene, Axanthin; Pyrroloquinoline quinone or its salt; Glucosylherperidine; Ubidecare More preferably, one or more selected from pyridoxine hydrochloride, panthenol, Pantothenyl ethyl ether; dl-α-tocopherol nicotinate, nicotinamide ; Riboflavin; Cyanocobalamin; Ascorbic acid, ascorbic acid phosphate malate Magnesium, Ascorbic acid-2-glucoside, Sodium ascorbate, Ascorbic acid Sodium Phosphate, 2-O-Ethyl Ascorbic Acid, 3-O-Ethyl Ascorbic Acid ascorbic acid, tetra-2-hexyldecanoic acid ascorbyl; dl-α-tocopherol acetate, δ-tocopherol; retinol palmitate, retinol acetate, retinol propionate le, hydrogenated retinol; pyrroloquinoline quinone disodium salt; glucosyl herperidine; More preferably, one or more selected from ubidecarenone, ascorbyl phosphate Sodium ester, ascorbyl tetra 2-hexyldecanoate, delta-tocopherol, One or more selected from retinol acetate and pyrroloquinoline quinone disodium salt More preferred are pyridoxine hydrochloride, panthenol, nicotinamide, riboflavin, Cyanocobalamin, Ascorbic Acid, Magnesium Ascorbyl Phosphate, Ascorbic Acid Corbic acid-2-glucoside, sodium ascorbate, ascorbyl phosphate ester sodium ascorbate, 3-O-ethyl ascorbic acid, tetra-2-hexyldecanoic acid ascorbate dl-α-tocopherol acetate, δ-tocopherol, retinol palmitate, water One or more selected from the group consisting of retinol, pyrroloquinoline quinone disodium salt, More preferred are panthenol, nicotinamide, ascorbic acid, and ascorbic acid. Magnesium phosphate, ascorbic acid-2-glucoside, 3-O-ethyl ascorbic acid retinol, dl-α-tocopherol acetate, retinol palmitate, ascorbic acid Sodium Phosphate, Ascorbyl Tetra-2-Hexyldecanoate, δ-Tocopherol Particularly preferred are one or more selected from the group consisting of pyrroloquinoline quinone disodium salt. .

[0133] When vitamins are used for pharmaceutical purposes, their content shall be: The content is preferably 0.001 to 10% by mass, more preferably 0.01 to 5% by mass, and more preferably 0.01 to 5 % by mass is more preferable, 0.1 to 5% by mass is even more preferable, and 0.5 to 2% by mass is even more preferable. is particularly most preferred.

[0134] When vitamins are used for other purposes, their content shall be based on the total amount of the composition for external use. The content is preferably 0.00001 to 10% by mass, more preferably 0.001 to 5% by mass, and more preferably 0.0 More preferably, the content is 1 to 3% by mass, even more preferably, 0.05 to 2% by mass, and even more preferably, 0.1 Up to 1% by mass is particularly preferred.

[0135] (Anti-wrinkle agent) Examples of the anti-wrinkle agent include hydrolyzed soy protein, nicotinamide, and retinol. le, retinal, retinoic acid, 3-dehydroretinol, 3-dehydroretinal, 3 - Vitamins such as dehydroretinoic acid, hydrogenated retinol, and tocopheryl retinoate Class A and its derivatives, retinol palmitate, retinol propionate, and linoleate Vitamin A derivatives such as retinol acid and retinol acetate, α-carotene, β-carotene , γ-carotene, cryptoxanthin and other provitamin A, glycolic acid, acylated Glucosamine, kinetin, vitamin C, vitamin E, aloe, collagen, hydrolyzed collagen Lagen, water-soluble collagen, hyaluronic acid, sodium hyaluronate, acetylated hyaluronic acid Rhonic acid, peptides (caproyl tetrapeptide-3, oligopeptide-24, etc.) Among them, hydrolyzed soy protein, nicotinamide, retinoic acid palmitate, Retinol, Retinol Propionate, Retinol Acetate, Kinetin, Collagen, Hydrolyzed Collagen Lagen, water-soluble collagen, sodium hyaluronate, acetylated hyaluronic acid, caproic acid Oil tetrapeptide-3, oligopeptide-24, or Two or more types are preferable, and hydrolyzed soy protein, nicotinamide, retinol palmitate , retinol acetate, hydrolyzed collagen, water-soluble collagen, acetylated hyaluronic acid, One or more selected from the group consisting of:

[0136] When nicotinamide is used as the anti-wrinkle agent, the content of the nicotinamide in the composition for external use is The amount is preferably 0.001 to 10% by mass, more preferably 0.01 to 8% by mass, based on the total amount. The content is more preferably 0.1 to 5 mass %, and even more preferably 0.5 to 3 mass %.

[0137] When a vitamin A derivative is used as the anti-wrinkle agent, the content of the vitamin A derivative in the external composition is The content is preferably 0.0001 to 1 mass%, more preferably 0.001 to 0.8 mass%, based on the total amount of the It is preferably 0.01 to 0.5 mass %, and more preferably 0.01 to 0.5 mass %.

[0138] When using anti-wrinkle agents other than nicotinamide and vitamin A derivatives, The content of is, for example, 0.0001 to 10% by mass based on the total amount of the composition for external use. The content is preferably 0.0005 to 5% by mass, more preferably 0.001 to 1% by mass, and more preferably 0.005 to 5% by mass. 0.5% by mass is even more preferable.

[0139] In the topical composition of the present invention, from the viewpoint of exhibiting the effects of the present invention more significantly, (A) The blending ratio of the (B) component to the total content of the (A) component is, for example, The total content of the (B) component can be 0.001 to 500 parts by mass, and 0.005 to 3 It is also possible to set the content to 00 parts by mass, 0.01 to 100 parts by mass, or 0.02 to 50 parts by mass.

[0140] (skin whitening agent) Examples of whitening agents include nicotinamide, placenta, arbutin, kojic acid, and ethylene glycol. Lacic acid; Phytic acid; Tranexamic acid; Rucinol; Chamomilla ET; Hydroquinone, 4 -Methoxysalicylic acid potassium salt; Linoleic acid and its derivatives; Ascorbic acid and its salts , ascorbic acid derivatives and other vitamin C compounds (sodium ascorbyl phosphate, Magnesium ascorbyl phosphate, ascorbyl tetra 2-hexyldecanoate , 2-O-ethyl ascorbic acid, 3-O-ethyl ascorbic acid, ascorbic acid glutamate Coside, disodium isostearyl ascorbyl phosphate, L-ascorbyl dipalmitate Ascorbyl Palmitate, Trisodium Ascorbyl Phosphate, Glyceryl Ascorbate, Bis Glyceryl ascorbate, alkyl glyceryl ascorbate, etc.), Vitamin A or and vitamins such as pantothenic acid and its derivatives. Plant ingredients having the function of whitening may be used as skin whitening agents. Such plant ingredients include iris (Iris), Iris), almonds, aloe, acerola, oolong tea, star anise, coptis, seaweed, China, Sophora root, Chlorella, Rice, Rice hyphae, Oryzanol, Rice bran, Saishin, Sa Peony root, Cnidium officinalis, Magnolia officinalis, Natto, Tea, Angelica acutiloba, Calendula officinalis, Hamamelis, safflower, peonies, coix seed, acacia, persimmon (Diospyros kaki), Wii, black beans, gentian, gentian, radish, azalea, parsley, holly, hops , cloves, tangerines, chamomile, prunes, meadowsweet, sorrel, grapefruit , thorn pear, lemon, kiwi, pine, neem, artichoke, horsetail, bark, Evening primrose, bilberry, geranium, glasswort, white willow, snowdrop These plant ingredients are derived from the plant extracts of the present invention. When used in a topical composition, the form of the plant ingredient is not particularly limited, but is usually a plant extract. It can be used in the form of plant extracts, essential oils, etc. The name in parentheses is the scientific name, synonym or herbal medicine name of the plant.

[0141] In the present invention, such a whitening ingredient is not particularly limited, but may be nicotinic acid a Mido, Placenta; Arbutin; Kojic Acid; Phytic Acid; Tranexamic Acid; Rucinol; Chamomilla ET; Hydroquinone; 4-Methoxysalicylic acid potassium salt; Ascorbic acid, Sodium Ascorbate, Sodium Ascorbyl Phosphate, Ascorbic Acid Magnesium phosphate, ascorbyl tetra 2-hexyldecanoate, 2-O-ethyl Luascorbic acid, 3-O-ethyl ascorbic acid, ascorbic acid glucoside; Iris Root extract, almond oil, aloe vera extract, acerola extract, rhizome extract, almond oil Koso extract, seaweed extract, chamomile extract, peony extract, sorrel extract, chi extract, white tea extract, calendula, witch hazel, coix seed, pearl barley extract , hop extract, prune extract, meadowsweet extract, alpinia katsumadai seed extract Grapefruit extract, Rosa rosa extract, Lemon extract, Kiwi extract, Pine extract, neem leaf extract, artichoke extract, horsetail extract, bark extract, Evening primrose extract, evening primrose oil, bilberry leaf extract, geranium extract, glasswort One selected from extract, white willow extract, centella asiatica extract, devil's claw Or preferably two or more types.

[0142] When a whitening agent is incorporated, the content of the agent is, for example, about 0.0% based on the total amount of the composition for external use. The amount is about 0.03 to 10% by mass, preferably about 0.01 to 5% by mass. The total content of the composition for external use is, for example, about 0. 00001 to 20% by mass, preferably about 0.0001 to 15% by mass, more preferably The content is 0.001 to 10% by volume.

[0143] [Other ingredients] In addition to the above-mentioned ingredients, the topical composition of the present invention contains purple hyaluronan to impart other useful effects. Radiation scattering agents, UV absorbers, components that have the effect of preventing and / or repairing DNA damage, organic acids , anti-glycation ingredients, cell activation ingredients, astringent ingredients, antioxidant ingredients, anti-aging ingredients, moisturizing ingredients, multivalent Alcohol, keratin softening ingredients, blood circulation promoting ingredients, sebum absorbing ingredients, peptides or their derivatives, Various ingredients such as amino acids or their derivatives may be blended in one or more combinations. These components can be used in the fields of medicines, quasi-drugs, cosmetics, etc. There are no particular limitations as long as the material is of a suitable type, and any material may be appropriately selected and used. Ingredients that fall under multiple categories below may be added as ingredients with any of the following efficacy. It shall be so.

[0144] Examples of the ultraviolet scattering agent include zinc oxide, titanium oxide, iron oxide, cerium oxide, Zirconium oxide, titanium silicate, zinc silicate, anhydrous silicic acid, cerium silicate, hydrous silica Inorganic compounds such as acids, and their derivatives such as hydrous silicic acid, aluminum hydroxide, mica, It is coated with inorganic powder such as talc, or is made of polyamide, polyethylene, polyester, polystyrene, etc. Compounds of resin powder such as polyethylene and nylon, as well as silicone oil and fatty acid aluminum Examples of such compounds include those treated with ethanol salts.

[0145] The ultraviolet absorbing agent is not limited, but is preferably a salicylic acid-based ultraviolet absorbing agent. agents, cinnamic acid-based UV absorbers, benzoylmethane-based UV absorbers, benzoic acid ester derivatives Body UV absorbers, triazine derivative UV absorbers, benzalmalonate derivative UV absorbers agents, octocrylene-based ultraviolet absorbers, imidazole sulfonic acid derivative ultraviolet absorbers, The ultraviolet absorber may be a zofenone derivative.

[0146] In addition, these UV scattering agents and UV absorbing agents can be compounded, supported, or encapsulated with other components. The combination of these is not particularly limited.

[0147] Examples of components having an effect of preventing and / or repairing DNA damage include those for animals (e.g. , Artemia); components derived from plants (e.g., Cat's Claw); DN A, nucleic acid components such as DNA salts, RNA, and RNA salts.

[0148] Examples of organic acids include gluconic acid, aspartic acid, aminoethylsulfonic acid, chlorine, and glycerol. Enic acid, glutamic acid, succinic acid, oxalic acid, fumaric acid, malonic acid, maleic acid, propyl acetic acid, malic acid, salicylic acid, glycolic acid, phytic acid, tartaric acid, acetic acid, lactic acid, bread acid Tothenic acid, glycyrrhetinic acid, alginic acid, ascorbic acid, benzoic acid, adipic acid, Examples of the salts include sulfuric acid, azelaic acid, and salts thereof. salts of mineral acids such as acid or phosphoric acid; salts of organic acids such as maleic acid or methanesulfonic acid; Alkaline metal salts such as potassium or alkaline earth metal salts, ammonium salts, basic amine salts, etc. Examples of the salt include salts of ethanolamine such as triethanolamine and salts of ethanolamine such as triethanolamine.

[0149] Examples of anti-glycation ingredients include Budreja axillaris leaf extract, plum fruit extract, and E. -Delweiss extract and other plant extracts, evening primrose oil, amla fruit, fruit juice or their extracts L-arginine, L-lysine, hydrolyzed casein, hydrolyzed tannins, carnosine etc.

[0150] Examples of cell activating components include amino acids such as γ-aminobutyric acid and ε-aminocaproic acid. Acids: Retinol, thiamine, riboflavin, pyridoxine hydrochloride, pyrroloxacin, pantothenate Vitamins such as quinones; gluconic acid, phytic acid, glycolic acid, lactic acid, etc. α-hydroxy acids; tannins, flavonoids, saponins, allantoin, photosensitizer No. 301, Ingredients derived from plants (for example, bilberry leaves, etc.)

[0151] Examples of astringent ingredients include alum, chlorohydroxyaluminum, and aluminum chloride. nium, aluminum allantoin, zinc paraphenolsulfonate, basic aluminum lactate Metal salts such as aluminum zinc, zinc sulfate, and potassium aluminum sulfate; tannic acid, citric acid Examples of organic acids include lactic acid and succinic acid.

[0152] Examples of the antioxidant include butyl hydroxyanisole and dibutyl hydroxytoluene. Ene, sodium hydrogen sulfite, sodium pyrosulfite, erythorbic acid and its salts, aspartame Corbic acid and its salts, flavonoids, glutathione, glutathione peroxidase, Glutathione-S-transferase, catalase, superoxide dismutase, Thioredoxin, taurine, thiotaurine, hypotaurine, plant extract (honeysuckle flower extract) Kissing, etc.

[0153] Anti-aging ingredients include, for example, hydrolyzed soy protein, retinoids (retinol, tinoic acid, retinal, etc.), pangamic acid, ursolic acid, turmeric extract, sphingomyelin Syn derivatives, silicon, silicic acid, N-methyl-L-serine, mevalonolactone, peptides (Caprooyl tetrapeptide-3, oligopeptide-24, etc.)

[0154] Moisturizing ingredients include, for example, alanine, serine, aspartic acid, glycine, and proline. , hydroxyproline, glucosamine, theanine, arginine, and other amino acids and their derivatives Conductors; polyhydric alcohols such as glycerin, dipropylene glycol, and 1,3-butanediol Polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene Polyoxypropylene glycol, polyoxyethylene alkyl glucoside, polyoxy Butylene polyoxyethylene polyoxypropylene glyceryl ether (3B.O.) ( Polyhydric aryl ethers such as polyoxypropylene diglyceryl ether (5P.O.) and polyoxypropylene diglyceryl ether (8E.O.). Alcohol derivatives; sorbitol, xylitol, erythritol, maltose and sucrose disaccharides sugar alcohols such as glycosaminoglycans (gluco-oligosaccharides) and hydrolyzed xylans (xylo-oligosaccharides); Glycosyltrehalose, trehalose; ceramide, glucosylceramide, cholesterol , phytosterol, cholesterol derivative, phytosterol derivative, lecithin, water Phospholipids such as lecithin with added lactic acid, sodium lactate, sodium pyrrolidone carboxylate , urea and other NMF-derived components; hyaluronic acid (hydrolyzed hyaluronic acid, low molecular weight hyaluronic acid) acids, etc.); salts of hyaluronic acid (e.g., sodium hyaluronate, zinc hyaluronate , low molecular weight zinc hyaluronate, etc.); hyaluronic acid derivatives (acetylated hyaluronic acid or its Salts (e.g., sodium acetylated hyaluronate, zinc acetylated hyaluronate, etc.), crosslinking agents Bridge-type hyaluronic acid derivatives (sodium hyaluronic acid crosspolymer, etc.), carboxymethyl hyaluronate Sodium hyaluronate, unsaturated hyaluronic acid or its salt, hydrolyzed alkyl hyaluronate (C12 -13) Glyceryl, cationic hyaluronic acid derivative (hydroxypropyl hyaluronate) Trimonium, hyaluronic acid dimethylsilanol, etc.); collagen, elastin, Latin, chitin, chitosan, etc. and their hydrolysates; Hydroxyethylurea; 2-Methoxy Poly(methacrylate), copolymer of acryloyloxyethyl phosphorylcholine and butyl methacrylate phosphorylcholine-containing polymers such as ethyloxyethyl phosphorylcholine; Polyglyceryl-10 (tetradecanedicarboxylic acid / tetradecanedicarboxylic acid), bis(cyclohexanedicarboxylic acid) Divalent esters such as diethylhexyl succinate, diethoxydiglycol, diethoxyethyl succinate, and diethylhexyl succinate Carboxylic acid esters; plants (e.g., aloe, seaweed, chlorella, lemongrass, chamis These include ingredients derived from herbal medicines such as hamamelis, tea, grapefruit, and gynostemma. Can be given

[0155] Polyhydric alcohols and polyhydric alcohol derivatives include diols with two or more carbon atoms, hydroxyl groups, and cyclohexane groups. Examples of suitable polyhydric alcohols include polyhydric alcohols having three or more hydroxy groups, such as glycerin, diglycerin, Phosphorus, triglycerin, 1,2-propylene glycol, dipropylene glycol, 1, 3-Butanediol, Ethylene glycol, Diethylene glycol, Isoprene glycol 1,3-butylene glycol, 1,3-propanediol, 1,2-hexanediol 1,2-pentanediol, 1,2-octanediol, polyoxyethylene polyol propylene butyl ether, polyoxyethylene polyoxypropylene glycol, Polyoxyethylene methyl glucoside, Polyoxypropylene methyl glucoside, Polyoxyethylene methyl glucoside xybutylene polyoxyethylene polyoxypropylene glyceryl ether (3B.O. )(8E.O.)(5P.O.), Polyoxypropylene diglyceryl ether, Polyoxypropylene diglyceryl ether Polyoxyalkylene sorbitol ether, polyoxyethylene polyoxypropylene glycerol Examples thereof include aryl ether.

[0156] Examples of keratin softening ingredients include lanolin, urea, phytic acid, lactic acid, lactate, and glycosaminoglycans. Acid, salicylic acid, malic acid, citric acid, fruit acid, phytic acid, urea, sulfur, etc. Some examples include:

[0157] Examples of blood circulation promoting ingredients include plants (e.g., ginseng, angelica tree, arnica, etc.) , ginkgo, fennel, Dutch oak, chamomile, Roman chamomile, carrot, gentian Perilla, burdock, rice, hawthorn, shiitake mushroom, European hawthorn, European juniper, cnidium U, Swertia japonica, Clove, Chinpi, Touki, Tonin, Touhi, Carrot, Garlic, Cherbloom, Grape, Peony, Horse Chestnut, Yuzu, Coix Seed, Rosemary, Law (derived from peaches, apricots, walnuts, corn, and pineapples) Ingredients: dl-α-tocopherol acetate, tocopherol nicotinate, glucosyl hesperidin Examples of effective antibacterial agents include ginseng, hesperidin, and sodium polyoxyethylene sulfonate.

[0158] Examples of peptides or derivatives thereof include keratin decomposition peptides and hydrolyzed keratin. , collagen, fish-derived collagen, atelocollagen, succinylated atelocollagen, Gelatin, elastin, elastin decomposition peptides, collagen decomposition peptides, hydrolyzed collagen collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin hydrolyzed pe Peptide, conchiolin hydrolyzed peptide, hydrolyzed conchiolin, silk protein hydrolyzed peptide, Hydrolyzed silk, sodium lauroyl hydrolyzed silk, soy protein hydrolyzed peptide, dehydrated Soy protein, wheat protein, wheat proteolysis peptides, hydrolyzed wheat protein, casein hydrolysis peptides , acylated peptides (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl lumityl tetrapeptide, etc.

[0159] Examples of amino acids or derivatives thereof include betaine (trimethylglycine), proline, , hydroxyproline, arginine, lysine, serine, glycine, alanine, phenyl Alanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartate Paragic acid, cysteine, cystine, methionine, leucine, isoleucine, valine, hyaluronic acid Styridine, threonine, tyrosine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid Butyric acid, carnitine, carnosine, creatine, epsilon aminocaproic acid, triphosphatidylcholine, Tophan, Ornithine, Sodium N-Stearoyl-L-Glutamate, Dilaurami Lysine glutamate and its salts, di(phytosteryl / octyl) lauroyl glutamate dodecyl), di(octyldodecyl / phytosteryl / behenyl) lauroyl glutamate ) etc.

[0160] [Additives, etc.] In addition to the above-mentioned components, the topical composition of the present invention may further contain medicinal properties according to its application or formulation. Ingredients that are commonly used in the fields of medicines, quasi-drugs, cosmetics, and the like may be appropriately blended. The ingredients that can be added are not particularly limited, but may include, for example, a base or carrier, a surfactant, an enhancer, etc. Viscosity agent, antioxidant, preservative, pH adjuster, chelating agent, stabilizer, irritation reducer, Additives such as solubilizing agents, suspending agents, isotonicity agents, buffers, coloring agents, dispersing agents, coloring agents, and fragrances These ingredients can be used alone or in any combination of two or more. The content of these components may be varied from the conventionally known ranges to achieve the effects of the present invention. In addition, the amount of the ingredient that falls under the following multiple ingredients may be appropriately determined as long as the effect is not impaired. Those having any of these functions may be added as components.

[0161] The base or carrier may be an aqueous base such as water; liquid paraffin, liquid isoparaffin, or sucrose. Quaran, Vaseline, Paraffin, Microcrystalline Wax, Polybutene, Polyethylene Ethylene powder, gelling hydrocarbons (Plastibase, etc.), ozokerite, α-olefin oligomer Hydrocarbons such as methyl polysiloxane, light liquid paraffin, and light iso-liquid paraffin; Methylpolysiloxane, crosslinked methylpolysiloxane, highly polymerized methylpolysiloxane, methylphenyl Phenyl-modified silicones such as polysiloxanes, cyclic silicones such as decamethylcyclopentasiloxane, etc. Silicone, methyl hydrogen polysiloxane, methyl trimethicone, dimethicone Alkyl-modified silicones such as dimethiconol crosspolymer and caprylyl methicone , crosslinked alkyl-modified silicone, amino-modified silicone, polyether-modified silicone , polyglycerin modified silicone, cross-linked polyether modified silicone, cross-linked alkyl Polyether modified silicone, silicone / alkyl chain co-modified polyether modified silicone Silicone / alkyl chain co-modified polyglycerin modified silicone, polyether modified molecular weight Branched silicone, polyglycerin modified branched silicone, acrylic silicone, phenyl modified silicone Silicone oils such as silicone resins; cetanol, cetostearyl alcohol Alcohol, Stearyl Alcohol, Behenyl Alcohol, Octyldodecanol, Isostearate Higher alcohols such as ethyl alcohol, phytosterols, and cholesterol; cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, etc. Cellulose derivatives; Polyvinylpyrrolidone; Polyvinylbutyrate; Polyethylene Licor; Dioxane; Butylene glycol adipic acid polyester; Myristic acid iso Propyl, Octyldodecyl myristate, Isopropyl palmitate, CeO2 palmitate Isononyl isononanoate, diisopropyl adipate, decyl oleate, oleic acid Isodecyl dimethyloctanoate, hexyldecyl dimethyloctanoate, diisopropyl sebacate, sebacate Di-2-ethylhexyl cinnamate, 2-hexyldecyl myristate, 2-hexyl palmitate xyldecyl, diisopropyl adipate, isotridecyl isononanoate, cetyl lactate, Isostearyl isostearate, cholesteryl 12-hydroxystearate, stearyl Cholesteryl phosphate, cholesteryl oleate, phytosteryl macadamiate , Phytosteryl Oleate, Dextrin Palmitate, Inulin Stearate, Hydrogen Added jojoba oil, di-2-ethylhexyl ethylene glycol, dipentaerythritol Fatty acid ester, neopentyl glycol dicaprate, tri-2-ethylhexyl trimellitate xyl, tritridecyl trimellitate, trimethylolpropane tri-2-ethylhexyl Pan, trimethylolpropane triisostearate, tetra-2-ethylhexanoate Pentaerythritol, glycerin tri-2-ethylhexanoate, triisostearate Dimethylolpropane, Caprylic / Capric Triglyceride, Caprylic Triglyceride Glyceryl Caprate, Myristic Acid, Stearic Acid, Oleyl Oleate, Lauroyl Phytosteryl / Octyldodecyl Lauroyl Glutamate (Octyldodecyl / Phytosteryl / Behenyl), Triethyl Citrate, Dimer Dilyl Nolic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimer -Dimer dilinoleyl dilinoleate, dipentaerythritol tripolyhydroxystearate Esters such as glyceryl tri(behenate / isostearate / eicosanedioate) Jojoba oil, Miu wax, Candelilla wax, Rice bran wax, Cotton wax, Carnauba wax, Waxes such as lanolin; avocado oil, linseed oil, camellia oil, macadamia nut oil, kukuina Nut oil, hazelnut oil, corn oil, olive oil, safflower oil, apricot oil , cinnamon oil, jojoba oil, grape seed oil, sunflower oil, almond oil, shea butter, camellia Oil, rapeseed oil, sesame oil, cocoa butter, coconut oil, hardened coconut oil, palm oil, palm kernel oil, mocro Corn kernel oil, Japanese laurel, wheat germ oil, rice germ oil, rice bran oil, cottonseed oil, soybean oil, peanut oil, tea seed oil Fats and oils such as oil, evening primrose oil, shea butter, etc.; polysaccharides such as dextrin and maltodextrin; vinyl polymers such as carboxyvinyl polymers and alkyl-modified carboxyvinyl polymers; Lower alcohols such as ethanol and isopropanol; sorbitol and xylitol sugar alcohols such as erythritol, mannitol, etc.; water, etc. The base or carrier selected from the following may be used alone or in combination of two or more. The amount of each of these used may be appropriately selected from the range known to those skilled in the art.

[0162] Examples of surfactants include sorbitan monoisostearate, sorbitan monostearate, Diglycerol sorbitan tetra-2-ethylhexyl ester, sorbitan monophosphate sorbitan isostearate, sorbitan monoisostearate, and sorbitan monolaurate Polyoxyethylene monolaurate (20) Sorbitan monolaurate, Polyoxyethylene (80) Sorbitan Monostearate, Polyoxyethylene (2 0) Sorbitan, Polyoxyethylene Monooleate (20) Sorbitan, Isostearate Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene phosphate (20) sorbitan ester; glycerol monooleate, glycerol monostearate, and glycerol mono Glycerol fatty acid esters such as myristate; monoisostearyl glyceryl ether; Glycerol alkyl ethers such as monomyristyl glyceryl ether; diglyceryl mono Stearate, Decaglyceryl Decastearate, Decaglyceryl Decaisostearate and polyglycerol fatty acid esters such as diglyceryl diisostearate; monostearate Propylene glycol fatty acid esters such as propylene glycol phosphate; polyoxyethylene Polyoxyethylene hydrogenated castor oil 40, Polyoxyethylene hydrogenated castor oil 50, Polyoxyethylene hard Hydrogenated castor oil derivatives such as polyoxyethylene hydrogenated castor oil 60 and polyoxyethylene hydrogenated castor oil 80; Polyoxyethylene glycerin fatty acid esters such as oxyethylene monococonut oil fatty acid glyceryl Polyoxyethylene (20) phytosterol, polyoxyethylene (30) phytosterol tosterol, polyoxyethylene (25) phytostanol, polyoxyethylene (3 0) Polyoxyethylene sterols such as cholestanol, hydrogenated sterols; sucrose fats Fatty acid esters; polyoxyalkylene alkyl (or alkenyl) ether sulfates, ethers Terephthalic acid salts, alkyl phosphate ester salts, N-acyl amino acid salts, acylated taure esters; amines such as stearylamine and oleylamine; polyoxyethylene methyl Polysiloxane Copolymer, Lauryl PEG-9 Polydimethylsiloxyethyl Dimethicone, Silicone surfactants such as PEG-9 polydimethylsiloxyethyl dimethicone or Lecithin, hydrogenated lecithin, saponin, sodium surfactin, cholesterol , bile acids, and other naturally occurring surfactants.

[0163] Examples of thickeners include polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl Vinyl thickeners such as methyl ether, carboxyvinyl polymer, methyl cellulose, etc. cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxy Hydroxypropyl cellulose, Hydroxypropyl methylcellulose, Carboxymethyl cellulose cellulose-based thickeners such as cellulose, carboxyethyl cellulose, guar gum, sclerotium Mugum, tamarind gum, xanthan gum, dextran, pectin, pullulan, gelatin Locust bean gum, carrageenan, agar, acrylates and methacrylates alkyl copolymers Copolymer, sodium polyacrylate, bentonite, dextrin fatty acid ester, dimethy Distearyl ammonium hectorite, sodium alginate, propylene glycol Glycol ester, polyethylene glycol, macrogol, (hydroxy acrylate Diethyl / Sodium Acryloyldimethyl Taurate Copolymer, (Acryloyldimethyl Taurate Ammonium uranyl / vinylpyrrolidone copolymers. Gum, acrylic acid alkyl methacrylate copolymer, hydroxyethyl cellulose, hydrochloride Hydroxypropyl cellulose, Hydroxypropyl methylcellulose, Carboxyvinyl poly Rimer, Dimethyl Distearyl Ammonium Hectorite, (Hydroxyethyl Acrylate Acryloyldimethyltaurate / Na acryloyldimethyl taurate copolymer, Ammonium / vinylpyrrolidone copolymers are preferred.

[0164] Examples of the antioxidant include dibutylhydroxytoluene and butylhydroxyanisole. ethanol, sorbic acid, sodium sulfite, ascorbic acid, ascorbic acid derivatives, tocopherol Erythorbic acid, sodium erythorbate, L-cysteine, tocopherol derivatives Stains hydrochloride, ubiquinones such as coenzyme Q10, lignans such as sesamin, curcumin Min, capsaicin, gingerol, resveratrol, anthocyanin, cyanidin, Examples include bilberry extract and its analogs or derivatives.

[0165] Preservatives or antiseptics include, for example, benzoic acid, sodium benzoate, dehydroacetic acid, Sodium dehydroacetate, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate Pill, Butyl Parahydroxybenzoate, Ethyl Parahydroxybenzoate, Propyl Parahydroxybenzoate Pill, benzyl parahydroxybenzoate, methyl parahydroxybenzoate, phenoxyethanol , benzyl alcohol, chlorobutanol, sorbic acid and its salts, chlorgluconate Hexidine, methylisothiazolinone, iodide propynyl butylcarbamate, capryl Hydroxamic acid, phenethyl alcohol, ethylhexylglycerin, capric glycerin methylphenol, isopropyl methylphenol, etc.

[0166] Examples of pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, etc.), and citric acid, sodium citrate, succinic acid, sodium succinate, etc.), inorganic bases (potassium hydroxide, sodium hydroxide, etc.), organic bases (triethanolamine, diisopropyl propanolamine, triisopropanolamine, etc.

[0167] Examples of chelating agents include ethylenediaminetetraacetic acid (edetic acid), ethylenediamine Disodium edetate (Japanese Pharmacopoeia, EDTA-2Na, etc.) , potassium salts, etc.), phytic acid, gluconic acid, polyphosphoric acid, metaphosphoric acid, etc. Of these, sodium edetate is preferred.

[0168] Examples of the stabilizer include sodium polyacrylate and dibutylhydroxytoluene. (BHT), butyl hydroxyanisole, etc.

[0169] Examples of irritation reducers include licorice extract, gum arabic, polyvinylpyrrolidone, etc. Some examples include:

[0170] Suitable examples of the solubilizing agent include polyethylene glycol and propylene glycol. D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol roll, triethanolamine, sodium carbonate, sodium citrate, etc. .

[0171] Suitable examples of the suspending agent include stearyl triethanolamine and lauryl sulfate. Sodium lauryl aminopropionate, lecithin, benzalkonium chloride, benzyl chloride Surfactants such as Zethonium, glyceryl monostearate, etc.; polyvinyl alcohol, etc. cellulose, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose , Hydroxymethylcellulose, Hydroxyethylcellulose, Hydroxypropylcellulose Examples of the hydrophilic polymers include cellulose.

[0172] Preferable examples of the isotonicity agent include sodium chloride, glycerin, and D-mannitol. etc.

[0173] Suitable examples of the buffer include, for example, buffers such as phosphate, acetate, carbonate, and citrate. Liquids, etc.

[0174] The coloring agent includes inorganic pigments and natural dyes.

[0175] [Application area] The site to which the topical composition of the present invention is applied is particularly any site involving the stratum corneum, such as the skin. For example, but not limited to, the face, lips, neck, chest, back, arms, elbows, hands, armpits, abdomen, vulva, It may be at least one selected from the group consisting of buttocks, anus, legs, fingers, toes, and soles. do.

[0176] Effective application to areas that are easily affected by skin barrier function, skin moisture content, sensitive skin, etc. The application areas are the face, lips, neck, chest, back, arms, elbows, hands, groin, and back of the knees. At least one selected from the group consisting of the following is preferred. In areas susceptible to physical and / or chemical irritation, etc., the topical composition of the present invention should be applied continuously. By using this product, you can improve abnormalities in the skin barrier function, skin moisture content, sensitive skin, etc. Not only will this prevent the abnormality from occurring, but it will also be possible to take preventative action before the abnormality occurs. It is expected that the effect of improving the condition and, once normalization has been achieved, acting as a preventative measure will also be achieved. do.

[0177] [Applicable persons] The subject to which the topical composition of the present invention is applied is a person who has a reduced amount of skin moisture or skin barrier function, sensitive skin, There are no particular limitations on the subject, so long as the subject has skin problems or may have skin problems. The subjects were newborns whose skin was immature and who were prone to developing rashes due to external stimuli such as diapers. (up to 28 days after birth), Infants (28 days after birth and under 1 year old), Toddlers (1 year old to preschool age) It is also possible that acne is more likely to occur during adolescence (from around 10 to 18 years old) and adult acne. This can be during adolescence (from around 15 to around 30 years old) when the skin is easily damaged, or during any age when sensitive skin is a concern, such as on the face. (Ages 15 and over), middle-aged people (ages 45 to 55) and older people (ages 5 5 years old or older). In addition, regardless of age, skin problems caused by external or internal factors can be treated. It can also be used by people with sensitive skin, who are prone to skin irritation.

[0178] In view of the above-mentioned target users, the composition for external use of the present invention is suitable for, for example, babies and infants. , for children, for those with sensitive skin, for sensitive skin, for hypersensitive skin, for dry skin, for sensitive skin, for troubled skin, Can be used for temporary sensitive skin.

[0179] [pH] The pH of the topical composition of the present invention depends on the type of component (A), the types and contents of other blended components, the preparation, The dosage form and method of use should be appropriately determined, and the dosage should be within the physiologically or pharma- ceutical acceptable range. Although not limited thereto, the pH can be, for example, 2 to 9. From the viewpoint of efficacy, the pH of the composition for external use of the present invention is preferably 2 to 9.5, more preferably 3 to 9, even more preferably 4 to 8.5, even more preferably 4.5 to 8, even more preferably Or it can be 5 to 7.

[0180] [Dosage form] The composition for external use of the present invention may be in any form known in the art as a drug, quasi-drug, or cosmetic. For example, but not limited to, liquids, suspensions, emulsions, creams, ointments, gels, linime This product is used in creams, lotions, aerosols, powders, sprays, non-woven sheets, etc. The composition of the present invention is impregnated into a sheet, stick, or other form of preparation, and is formulated by a known method. Among them, preferred are liquids, suspensions, emulsions, creams, ointments, gels, etc. It is used in the form of creams, lotions, and gels.

[0181] Specific formulations include, for example, lotions, milky lotions, gels, creams, beauty essences, and sunscreens. Skincare products, packs, masks, hand creams, all-in-one gels, all-in-one Basic cosmetics such as creams, body lotions, and body creams; facial cleansers, hand lotions, and other cosmetics. Soap, makeup remover, body shampoo, shampoo, rinse, and treatment Cleansing cosmetics such as foundation, makeup base, BB cream, CC cream, etc. Face makeup cosmetics; lip balm, lip liner and other lip cosmetics; hair Among these, compositions for external use on the skin are particularly preferred. The composition for external use of the present invention is a composition for external use on the skin for use as a medicine, a quasi-drug, or a cosmetic. The formulation of the external composition for skin application may be the same as that of the external composition of the present invention. Also, usable bases or carriers, additives, and active ingredients, and preferred ones thereof The same applies to the topical composition of the present invention.

[0182] The topical composition of the present invention may be stored in a container of a shape and material appropriately selected depending on the purpose and application of the composition. Specific containers include, for example, spray types and bottles. Type, tube type, jar type, dropper type, dispenser type, stick type Examples include sticky types, pouches, and cheer packs.

[0183] The materials used for these containers include polyethylene terephthalate, polypropylene, and polyethylene. Ethylene (HDPE, LDPE, LLDPE, etc.), ABS resin, ethylene vinyl alcohol Examples include resin, polystyrene, glass, and metal (aluminum, etc.). The materials are selected based on strength, flexibility, weather resistance, and stability of the components, and are given various coating treatments. These materials can be combined, for example by mixing, or laminated to produce a container. It can be used as a container material. The coating material is polyethylene terephthalate. Examples of the resins include polypropylene, epoxy resin, and polyamideimide. Polyethylene (HDPE, LDPE, LLDPE, etc.), ethylene vinyl alcohol resin, It is preferable to use metal (aluminum, etc.). The resin that coats the inner surface is polyamide. For example, polyethylene terephthalate or polyethylene terephthalate can be used.

[0184] When applying the topical composition of the present invention, in order to make it easier to apply to affected areas that are difficult to reach, It is also possible to use a spray-type container. The spray-type container can be turned upside down to spray. It is also possible to use a mist-type spray container that can be used. The shape of the spray container is Although not particularly limited, examples thereof include pump sprays, trigger sprays, and aerosol sprays. In the case of a pump spray, for example, a pump is used. The trigger nozzle can be attached to the container, making it versatile and portable. For example, a sprayer with a pistol-shaped nozzle may be attached to the container. This allows for a small amount of force to be used to spray the liquid. For example, carbon dioxide gas, Nitrogen gas, oxygen gas, fluorocarbon gas, liquefied petroleum gas (LPG), dimethyl ether (DME) It is possible to spray finer droplets by filling the container with a propellant such as It becomes possible.

[0185] Another embodiment of the composition for external use of the present invention is a foam agent that is discharged in the form of foam (also called a foam preparation). The foam agent can be used, for example, when the barrier function of the skin is weakened. Depending on the condition of your sensitive skin, it may be possible to reduce the physical irritation caused by application. It is also preferable when used in nursing care because it is easy for the caregiver to handle. The foam is provided in a known form, such as an aerosol container or a pump foamer. It is possible.

[0186] [How to use] The method of using the topical composition of the present invention depends on the condition of the subject, the condition of the application site, age, etc. The dosage may be varied as appropriate, for example, once or several times a day (for example, about 1 1 to 5 times, preferably 2 to 3 times) according to the known or commonly used dosage and administration method. It can be used by applying it to the skin of the application site. The application period depends on the subject's The amount of the drug may be changed depending on the condition, the condition of the application site, age, etc. For example, in the case of pharmaceutical use, If desired, the period can be about 1 to 90 days, preferably about 7 to 30 days. For cosmetics or quasi-drugs, continuous daily use will improve skin balding. Not only can it improve abnormalities in the skin's function, moisture content, and sensitive skin, but it can also prevent abnormalities This will enable preventative action to be taken before the problem occurs.

[0187] The composition for external use of the present invention can be produced by a known method. If necessary, it may be sterilized. The process may include: EXAMPLES

[0188] Next, the present invention will be described in detail with reference to examples and test examples. The present invention is not limited to the above examples.

[0189] (Test Example 1. Examination of the effect of KPRP gene expression on stratum corneum formation) According to the following test method, when KPRP gene expression is enhanced in epidermal keratinocytes, Effects on the expression of involucrin gene and keratin 1 gene, which are important in stratum corneum formation. I considered it. Involucrin is a protein that lines the cell membrane of epidermal keratinocytes and plays a key role in the development of skin Keratin 1 is a marker for the spinous and granular layers of the epidermis. These markers are proteins that regulate the differentiation of epidermal cells in the skin. is an indicator of normal stratum corneum formation in the skin. and / or keratin 1 are sufficiently produced in epidermal keratinocytes to promote the development of skin It is possible to suppress a decrease in moisture content and a decrease in the skin barrier function, etc.

[0190] [Test Method] The following procedure was used to confirm the effect of increased KPRP gene expression in epidermal keratinocytes. Ta. A KPRP expression vector was transfected into a human normal epidermal keratinocyte cell line, and KP RP stable cell lines were created and incubated at 5 × 10 4 24 wells with cells / well The cells were seeded on a plate (BD Falcon, No. 353219) and cultured at 37°C for 2 days. After confirming under a microscope that there were no problems with cell growth, calcium chloride was added at a final concentration. The cells were then cultured at 37°C for 3 days. After the culture, the cells were washed with PBS(-). The cells were washed twice and RNA was extracted using the RNeasy Mini Kit (Qiagen). After extraction, TOYOBO ReverTra Ace qPCR RT Mast cDNA was removed using eluter Mix with gDNA Remover (TOYOBO). The cDNA was then purified using Premix Ex Taq TM Using qRT -Analyzed by PCR. A human normal epidermal keratinocyte cell line transfected with a control vector was used as a control. The ratio of the expression level, assuming the present value to be 1, is shown in FIG.

[0191] As shown in Figures 1 to 3, when KPRP gene expression was enhanced in epidermal keratinocytes, It was newly discovered that the expression of the involucrin gene and the keratin 1 gene was significantly increased. It was served.

[0192] These results suggest that an active ingredient that enhances KPRP gene expression in epidermal keratinocytes If so, involucrin and / or keratin 1 are produced in epidermal keratinocytes. This leads to the development of a new type of active ingredient that suppresses the loss of skin moisture and / or It is believed that this can suppress the decline in skin barrier function.

[0193] (Test Example 2. Screening of ingredients that affect KPRP protein production in epidermal keratinocytes ning1) [Test Method] The KPRP protein produced by epidermal keratinocytes was measured according to the following procedure. Human normal epidermal keratinocytes (NHEK) (Kuraray Industries, Inc.) were added at 9 × 10 4 cells / 96-well plate (BD Falcon, No. 353219) The cells were seeded on the plate and cultured at 37°C for 2 days. Microscopic observation confirmed that there were no problems with cell growth. After confirming the above, calcium chloride was added to a final concentration of 1 mM, and the various components listed in Table 1 were added at final concentrations The cells were then cultured at 37°C for 5 days. The proteins were stained by immunostaining with anti-KPRP antibody (Abcam), and the cell nuclei were stained with Ho After staining with echst33342 (Dojindo Laboratories), The stained area, intensity and number of nuclei were measured using a CT scanner (Molecular Devices). The protein production was evaluated.

[0194] The samples were treated in the same manner as above, except that the various components to be evaluated were not added. The rank (control) was determined, and the amount of KPRP protein produced in the blank was 100%. The amount (%) of KPRP protein produced in each sample is also shown in Table 1. The results are shown in a graph in FIG.

[0195] [Table 1]

[0196] As shown in Table 1 and Figure 4, wild thyme extract, Scutellaria root extract, marjoram extract, Extract, lavender extract, aspalathus linearis extract, myriocin, and hepa Phosphorus analogues promote the production of KPRP protein in epidermal keratinocytes Wild thyme extract, scutellaria extract, marjoram extract, and lavender extract. -The extract is an extract of a plant of the Lamiaceae family, and Aspalathus linearis extract is an extract of a plant of the Fabaceae family. It is an extract of.

[0197] These results suggest that the above ingredients promote the production of KPRP protein, thereby improving the skin It is possible to suppress the decrease in moisture content and / or the decrease in barrier function. This suggests that...

[0198] (Test Example 3. Combination of ingredients that affect KPRP protein production in epidermal keratinocytes (Confirmation of effectiveness by [Test Method] Effect of combining KPRP protein production promoting components found in Test Example 2 The results were as follows: Each component listed in Table 2 was added to the medium to the final concentration as specified in Table 2. Except for the above, the evaluation was carried out in the same manner as in Test Example 2. Blank (Control) The KPRP protein production in each sample was calculated based on the amount of KPRP protein produced in the The amount of protein produced (%) is also shown in Table 2. The results are shown in a graph in Figure 5.

[0199] [Table 2]

[0200] When multiple KPRP protein production promoting ingredients were combined, KPRP production in epidermal keratinocytes It has been confirmed that it further promotes the production of PRP protein. When myriocin is used as a protein production promoting component, the application concentration of myriocin is shown. Even at a lower concentration compared to 1, it is effective when combined with other KPRP protein production-promoting ingredients. It was found that the production of KPRP protein was significantly promoted by these two methods.

[0201] (Test Example 4. Screening of ingredients that affect KPRP protein production in epidermal keratinocytes ning2) [Test Method] Screening of other KPRP protein production promoting components by the same method as in Test Example 2 The various components listed in Table 3 were used to investigate the activity of KPRP protein in epidermal keratinocytes. It was confirmed that KPRP protein production was promoted. The amount of KPRP protein produced in each sample (%) when the amount of protein produced in the control sample was taken as 100%. The results are also shown in Table 3. The graph of the results is shown in Figure 6.

[0202] [Table 3]

[0203] As shown in Table 3 and FIG. 6, the peony extract, Houttuynia cordata extract, peppermint ( Peppermint extract, chamomile extract, and isostearic acid also have the same effect on the epidermis. It was confirmed that it promotes the production of KPRP protein in keratinocytes. The bleeding liquid is an extract of a plant of the Paeoniaceae family, and the Houttuynia cordata extract is an extract of a plant of the Houttuynia cordata family. Peppermint extract is an extract of a plant of the Lamiaceae family, and chamomile extract is an extract of a plant of the Asteraceae family. It is an extract of something.

[0204] (Test Example 5. KPRP protein production promoting ingredients in a model of barrier function destruction of the stratum corneum Confirmation of effectiveness by 1) [Test Method] The following procedure will be used to induce an inflammatory response in epidermal keratinocytes using IL-1β. We evaluated the effect of KPRP protein production-promoting ingredients in inhibiting the decline in barrier function.

[0205] Using the 3D cultured skin model Advanced Skin (manufactured by Organ Technologies), IL-1β was added to the medium at a concentration of 10 ng / ml and cultured for 5 days. On the third day, a PBS solution containing a heparinoid was added to the stratum corneum side for 30 minutes and then removed. After that, the epidermis and dermis of the cultured skin were peeled off, and RIPA buffer (Nacalaithe) was added to the epidermis. Proteins were extracted using an anti-KPRP antibody (Abcam). Analysis was performed using ES (Protein Simple).

[0206] The samples were treated in the same manner as above, except that the various components to be evaluated were not added. The rank (control) was determined, and the amount of KPRP protein produced in the blank was 100%. The amount (%) of KPRP protein produced in each sample was calculated under these conditions. The results of the production amount (%) of KPRP protein are shown in FIG.

[0207] As shown in Figure 7, IL-1β treatment of epidermal keratinocytes induces an inflammatory response. It was confirmed that this induces KPRP protein production in epidermal keratinocytes. However, even when an inflammatory response was induced in epidermal keratinocytes, KPRP tissue By applying protein production-promoting ingredients to the stratum corneum, the production of KPRP protein is restored. Although the results are not shown, as confirmed in Test Examples 1 to 3, Similarly, the KPRP protein production promoting ingredient acts on epidermal keratinocytes, It is speculated that the production amount of KPRP protein is restored.

[0208] (Test Example 6. KPRP protein production promoting ingredients in a model of barrier function destruction of the stratum corneum Confirmation of effectiveness by 2) [Test Method] In the process of inducing an inflammatory response in epidermal keratinocytes, KPRP was The effect of protein production-promoting ingredients in inhibiting the decline of barrier function was evaluated.

[0209] Using the 3D cultured skin model Advanced Skin (manufactured by Organ Technologies), IL-1β was added to the medium at a concentration of 10 ng / ml and cultured for 5 days. On the third day, a solution of heparinoid dissolved in PBS was added to the stratum corneum side for 30 minutes, and then removed. The cultured skin was then fixed in 4% paraformaldehyde, dehydrated, and then resuspended in paraffin. After thin sectioning, anti-KPRP and anti-FLG antibodies (Abcam) were used. The expression and localization of KPRP were confirmed by immunostaining. The results are shown in Figure 8.

[0210] As shown in Figure 8, in epidermal keratinocytes, KPRP was observed in all layers of the epidermis, mainly in the upper part of the basal layer. It was confirmed that the protein was expressed in the keratinocytes (Fig. 8 (A)). This maintains the intercellular adhesion in both the vertical and horizontal directions, stabilizing the three-dimensional structure of the stratum corneum. Therefore, in a normal stratum corneum, the skin is not susceptible to physical and / or chemical stimuli from the outside world. It is stable against sebum and maintains the skin barrier function.

[0211] When IL-1β treatment of epidermal keratinocytes induces an inflammatory response, It was confirmed that the expression level of KPRP protein in skin keratinocytes was decreased (Figure 8( B) In such a condition, the skin barrier function is weakened, and the skin's ability to retain moisture and absorb cosmetics is reduced. It is believed to affect the texture of the skin.

[0212] However, even when an inflammatory response was induced in epidermal keratinocytes, KPRP By applying protein production promoting ingredients, the expression level of KPRP protein is increased throughout the entire epidermis. The expression of KPRP protein was found to be restored in the control group (Fig. 8(C)). The recovery effect was most pronounced in the stratum corneum of the epidermis. Even in cases where the function of the blood vessels is impaired, by applying ingredients that promote KPRP protein production, After improving and normalizing the stratum corneum from conditions such as rough skin, it is possible to prevent rough skin from occurring. It is also expected to have the effect of preventing

[0213] (Test Example 7. KPRP protein production promoting ingredients in a model of barrier function destruction of the stratum corneum Confirmation of effectiveness by 3) [Test Method] In the process of inducing an inflammatory response in epidermal keratinocytes, KPRP was The effect of protein production-promoting ingredients in inhibiting the decline of barrier function was evaluated.

[0214] Using the 3D cultured skin model Advanced Skin (manufactured by Organ Technologies), IL-1β was added to the medium at a concentration of 10 ng / ml and cultured for 5 days. On the third day, a PBS solution containing a heparinoid was added to the stratum corneum side for 30 minutes and then removed. Then, FITC dissolved in PBS was added to the stratum corneum side of the cultured skin for 30 minutes and then removed. After that, the cultured skin was fixed in 4% paraformaldehyde, dehydrated, and then paraffin-broken. After slicing, the cell nuclei were soaked in Hoechst 33342 (Dojindo Laboratories). The tissue was stained and examined under a microscope. The results are shown in Figure 9.

[0215] As shown in Test Example 6, in epidermal keratinocytes, KPRP protein is expressed throughout the entire epidermis. The expression of keratinocytes indicates that the intercellular adhesion between keratinocytes is maintained both vertically and horizontally, and that the keratinocytes are in good condition. The three-dimensional structure of the layers is stable. Therefore, as shown in Figure 9 (A), It was confirmed that the stratum corneum permeability was kept low and the skin barrier function was stably maintained. .

[0216] When IL-1β treatment of epidermal keratinocytes induces an inflammatory response, It has been confirmed that the permeability of the stratum corneum from the outside world increases in keratinocytes, and the skin barrier function decreases. In this state, moisture evaporates from the epidermis and the moisture retention capacity decreases. It is presumed that this leads to a decrease in the elasticity of the skin and a loss of skin texture.

[0217] However, even when an inflammatory response was induced in epidermal keratinocytes, KPRP It has been shown that the application of protein production-promoting ingredients restores the stratum corneum's permeability to the outside world. The results showed that the cutaneous barrier function was reduced even in a state where the cutaneous barrier function was impaired (Figure 9 (C)). By applying ingredients that promote KPRP protein production, the decline of skin barrier function is suppressed, After improving and normalizing the stratum corneum from conditions such as rough skin, it is possible to prevent rough skin from occurring. It is expected to have a preventive effect.

[0218] [Formulation example] The following are examples of the formulations of the present invention. Cosmetic essence (Formulation Example 1) , emulsion (Formulation Examples 2, 3, 4, 5, 6), lotion (Formulation Example 7), liquid (Formulation Example 8), gel (Formulation Examples 9 and 10), gel cream (Formulation Example 11), cream (Formulation Examples 12 and 13) ), sunscreen (Formulation Example 14), ointment (Formulation Examples 15 and 16), spray (Formulation Examples 17 and 18), 18) were prepared by standard methods. These preparations were newly shown to enhance KPRP protein expression. (A) Lamiaceae plants and their extracts, Leguminosae plants and their extracts, Myliaceae plants and their extracts, From the group consisting of osin, its derivatives, myriocin-containing substances, and heparinoids Since it contains at least one selected type, it is effective in preventing the stratum corneum normalization mechanism mediated by KPRP protein. It can be effectively used for various applications brought about by enhanced performance.

[0219] [Table 4]

[0220] [Table 5]

[0221] [Table 6]

[0222] [Table 7]

[0223] [Table 8]

[0224] [Table 9]

[0225]

Table 10

[0226]

Table 11

[0227]

Table 12

[0228]

Table 13

[0229]

Table 14

[0230]

Table 15

[0231]

Table 16

[0232]

Table 17

[0233]

Table 18

[0234]

Table 19

[0235] [Table 20]

[0236] [Table 21]

[0237] (A) Lamiaceae plants and their extracts that have been newly found to enhance KPRP protein production substances, legumes and their extracts, myriocin, its derivatives and substances containing myriocin At least one selected from the group consisting of, but not limited to, heparinoids. However, from the viewpoint of significantly exhibiting the effects of the present invention, the preferred combination of the two types is as shown in Table 22 below. In addition to these two preferred combinations, other (A) components may be combined. You may use it.

[0238] [Table 22]

Claims

[Claim 1] A composition for external application for preventing and / or improving a decrease in skin moisture content and / or skin barrier function, comprising a KPRP protein production promoting component as an active ingredient.

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