Topical compositions

Abstract

The present invention aims to provide a topical composition with enhanced whitening effect. The topical composition comprises (A) ascorbic acid and / or its derivatives, (B) an extract of a plant of the genus Magnolia in the family Magnoliaceae, (C) a plum extract, and (D) a cherry blossom leaf extract. The topical composition exhibits a further enhanced whitening effect by significantly enhancing the effect of inhibiting melanin production.

Description

Technical Field

[0001] The present invention relates to a composition for external use with enhanced whitening effect. Background Art

[0002] Skin pigmentation, such as spots, freckles, dullness, darkening, liver spots, and age-related pigmentation, is known to occur due to excessive melanin formation and accumulation in the skin caused by factors such as ultraviolet exposure, hormonal abnormalities, and physical stimulation. Such skin pigmentation is a major cosmetic concern, particularly for women.

[0003] Ingredients such as ascorbic acid and its derivatives that inhibit melanin production and / or dilute produced melanin are known as whitening ingredients and have been widely used in skin-whitening external-use compositions to achieve a skin pigmentation-inhibiting effect. However, currently, relying solely on the action of whitening ingredients to achieve a skin pigmentation-inhibiting effect cannot be said to fully meet consumer needs.

[0004] Therefore, research is underway to develop formulations that enhance the pigmentation-inhibiting effects of whitening ingredients. For example, Patent Document 1 describes a topical composition in which an extract from a plant of the genus Magnolia in the Magnoliaceae family is combined with ascorbic acid and its derivatives to enhance the melanin production inhibitory effect, thereby achieving an excellent whitening effect. Patent Document 1 further describes a composition in which an extract from the fruit pulp of a plant of the genus Prunus in the Rosaceae family, specifically plum ("Plum" in Japanese), is added to enhance the whitening effect.

[0005] Various studies have also been conducted on the perfumery and cosmetic effects of plant extracts. For example, regarding cherry blossom extract, Patent Document 2 discloses an antiallergic agent, active oxygen scavenger, and lipid peroxide inhibitor containing an extract obtained from cherry blossom leaves using water, ethanol, 1,3-butylene glycol, or a mixture of two or more thereof. Patent Document 3 discloses a skin moisturizer further containing a first component, which may be a cherry blossom extract, and a predetermined second component as active ingredients. The first component enhances skin moisturizing effects, improves cellular antioxidant capacity, and inhibits active oxygen. In other words, cherry blossom extract is known to have antiallergic effects, active oxygen scavenging effects, lipid peroxide inhibitory effects, and moisturizing enhancement effects.

[0006] Prior art literature

[0007] Patent Literature

[0008] Patent Document 1: Japanese Patent Application Laid-Open No. 2017-66080

[0009] Patent Document 2: Japanese Patent Application Laid-Open No. 8-245409

[0010] Patent Document 3: Japanese Patent Application Laid-Open No. 2008-115098 Summary of the Invention

[0011] Problems to be solved by the invention

[0012] Consumers' demands for whitening skin are increasing year by year, and considering that conventional whitening agents cannot meet these demands, the development of external-use compositions with even higher whitening effects is expected to meet these increasing consumer demands.

[0013] Therefore, an object of the present invention is to provide a composition for external use having a higher whitening effect.

[0014] Technical solutions to problems

[0015] The present inventors conducted intensive research and discovered that by adding a cherry blossom leaf extract, whose whitening effect had not been reported before, to a topical composition containing ascorbic acid and / or its derivatives, an extract from a plant of the genus Magnolia in the Magnoliaceae family, and an extract from plum, the topical composition's whitening effect was significantly enhanced. The present invention was completed through further research based on this finding. Specifically, the present invention provides the following aspects.

[0016] Item 1. A composition for external use, comprising (A) ascorbic acid and / or a derivative thereof, (B) an extract of a plant of the genus Magnolia of the family Magnoliaceae, (C) an extract of plum, and (D) an extract of cherry blossom leaves.

[0017] Item 2. The composition for external use according to Item 1, wherein the component (B) is an extract of Magnolia officinalis.

[0018] Item 3. The composition for external use according to Item 1 or 2, wherein the component (A) is ascorbic acid 2-glucoside.

[0019] Item 4. The composition for external use according to any one of Items 1 to 3, wherein the content of the component (D) is 0.00001 to 0.1% by weight on a dry weight basis.

[0020] Item 5. The composition for external use according to any one of Items 1 to 4, wherein the content of the component (D) is 0.008 to 0.1% by weight on a dry weight basis.

[0021] Item 6. The composition for external use according to any one of Items 1 to 5, wherein the composition for external use is used for whitening.

[0022] Effects of the Invention

[0023] According to the external use composition of the present invention, the melanin production inhibitory effect is significantly enhanced, thereby achieving a further enhanced whitening effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The figure shows the changes in melanin levels before and after application of the external use composition of the present invention to women with age-related pigmentation spots on their cheeks. DETAILED DESCRIPTION

[0025] The composition for external use of the present invention is characterized by containing ascorbic acid and / or its derivatives (sometimes referred to as component (A)), an extract of a plant of the genus Magnolia in the Magnoliaceae family (sometimes referred to as component (B)), a plum extract (sometimes referred to as component (C)), and a cherry blossom leaf extract (sometimes referred to as component (D)). The composition for external use of the present invention is described in detail below.

[0026] (A) Ascorbic acid and / or its derivatives

[0027] The composition for external use of the present invention contains ascorbic acid and / or its derivatives as component (A). Ascorbic acid and / or its derivatives are well-known ingredients having an antioxidant effect and a whitening effect.

[0028] Ascorbic acid and its derivatives used in the present invention are not particularly limited as long as they are pharmaceutically or cosmetically acceptable. Examples thereof include ascorbic acid; ascorbic acid 2-glucoside; ascorbic acid monoalkyl esters such as ascorbic acid monostearate, ascorbic acid monopalmitate, and ascorbic acid monooleate; ascorbic acid monoesters such as ascorbic acid monophosphate and its magnesium salt; ascorbic acid dialkyl esters such as ascorbic distearate, ascorbic acid dipalmitate, and ascorbic acid dioleate; ascorbic acid diesters such as ascorbic diphosphate and its salts; ascorbic acid tristearate, ascorbic acid monophosphate, and its salts; Trialkyl esters such as ascorbyl tripalmitate and ascorbyl trioleate; ascorbic acid triesters such as ascorbyl triphosphate; 3-O-ethyl, 6-acetyl ascorbic acid, 3-O-ethyl, 6-butyl ascorbic acid, 3-O-ethyl, 6-lauroyl ascorbic acid, 3-O-ethyl, 6-palmitoyl ascorbic acid, 3-O-ethyl, 6-oleoyl ascorbic acid, 3-O-ethyl, 6-stearoyl ascorbic acid, and 3-O-ethyl, 6-behenoyl ascorbic acid. These ascorbic acids and their derivatives may be either L- or D-isomers, with the L-isomer being preferred.

[0029] These ascorbic acid and its derivatives can be used alone or in combination of two or more. Among these ascorbic acid and its derivatives, from the viewpoints of stability, whitening effect, etc., preferably, ascorbic acid derivatives can be mentioned, and more preferably, ascorbic acid 2-glucoside can be mentioned.

[0030] The content of the component (A) in the composition for external use of the present invention may be appropriately determined depending on the formulation form of the composition for external use, and is, for example, 0.1 to 10% by weight, preferably 0.3 to 8% by weight, and more preferably 0.5 to 7% by weight.

[0031] (B) Extracts from Magnolia plants of the Magnoliaceae family

[0032] The composition for external use of the present invention contains an extract of a plant of the genus Magnolia in the family Magnoliaceae as component (B). By containing component (B), the composition for external use of the present invention enhances the effect of inhibiting melanin production and can exhibit an excellent whitening effect.

[0033] The extract of the plant of the genus Magnolia in the family Magnoliaceae can be obtained by subjecting the plant of the genus Magnolia in the family Magnoliaceae to a solvent extraction process using the plant as an extraction raw material.

[0034] As the Magnoliaceae Magnolia plant used as the raw material for extracting, the plants recorded in "Original Color World Plant Atlas" (first edition issued on April 20, 1971, by Kita Long Hall Co., Ltd.) etc. can be enumerated. Specifically, Magnolia officinalis, Flos Ampelopsis Juveniles, Magnolia, Japanese Magnolia (Mountain Orchid, Magnolia Pepper, Taro Plant Flower), Magnolia (Magnolia, Purple Magnolia), Magnolia officinalis (Magnolia officinalis), Wudang Magnolia, Japanese Magnolia Tree (Plain Cypress, Magnolia officinalis, Horse Tongue) etc. can be enumerated. In these extraction raw material plants, one plant can be used alone, and two or more plants can also be used in combination in addition. In these extraction raw materials, from the viewpoint of giving play to a more excellent whitening effect, Japanese Magnolia Tree can be preferably enumerated.

[0035] The extract of the plant of the genus Magnolia in the family Magnoliaceae can be any substance extracted from the bark of the plant. In addition to the bark, the parts to be extracted may also include flowers, flower spikes, peels, fruits, stems, leaves, branches, twigs and leaves, trunks, rhizomes, roots, seeds, etc. as needed, and the whole tree may also be used.

[0036] Examples of extraction solvents used in solvent extraction of Magnolia plants of the Magnoliaceae family include water; lower alcohols having 1 to 5 carbon atoms, such as methanol, ethanol, propanol, isopropanol, butanol, and isobutanol; polyols such as propylene glycol, 1,3-butylene glycol, and glycerol; and mixtures thereof. Among these extraction solvents, water, mixtures of lower alcohols having 1 to 5 carbon atoms and water, and mixtures of polyols and water are preferred. More preferred are water, mixtures of ethanol and water, mixtures of 1,3-butylene glycol and water, and mixtures of propylene glycol and water.

[0037] When a mixture of a lower alcohol and / or polyol having 1 to 5 carbon atoms and water is used as the extraction solvent, the concentration of the lower alcohol and / or polyol having 1 to 5 carbon atoms is not particularly limited. For example, the total amount of the lower alcohol and / or polyol having 1 to 5 carbon atoms is 20 to 90% by weight, preferably 30 to 85% by weight.

[0038] Extracts of plants of the genus Magnolia in the family Magnoliaceae are obtained by extracting the aforementioned plant parts, either directly or after drying, finely chopping, crushing, squeezing, enzyme-treated, boiling, or fermenting as needed, with the aforementioned extraction solvent. Conventional plant extraction methods can be employed as solvent extraction methods, specifically immersion methods such as cold immersion and warm immersion; methods with stirring under heating; and percolation methods.

[0039] The extract obtained by the above-mentioned solvent extraction treatment may be used directly in a liquid state, or may be subjected to treatment such as concentration or drying as needed and used as a concentrate or dried product. Furthermore, after concentration or drying, the obtained concentrate or dried product may be washed with an insoluble solvent and purified before use, or may be further dissolved or suspended in an appropriate solvent before use.

[0040] In addition, as the extract of the plant of the genus Magnolia in the family Magnoliaceae, an extract that is easily commercially available can also be used. For example, as the extract of the bark of Magnolia officinalis, "PHARCOLEX HOONOKI B" and "PHARCOLEX HOONOKI E" manufactured by Ichimaru Pharmacos Co., Ltd. can be mentioned.

[0041] The content of component (B) in the external-use composition of the present invention can be appropriately set according to the formulation form of the external-use composition, and for example, it can be 0.00001% by weight or more, specifically 0.00001 to 0.1% by weight, based on the dry weight of component (B). From the viewpoint of exerting a more excellent whitening effect, the content of component (B) in the external-use composition of the present invention can be preferably 0.00005 to 0.05% by weight, more preferably 0.0001 to 0.01% by weight, and particularly preferably 0.0008 to 0.003% by weight, based on the dry weight of component (B).

[0042] In addition, in the external composition of the present invention, the ratio of component (A) to component (B) is determined according to the above-mentioned respective contents. From the viewpoint of exerting a more excellent whitening effect, the ratio of component (A) to component (B) is 0.001 parts by weight or more, preferably 0.001 to 1 parts by weight, more preferably 0.005 to 0.5 parts by weight, further preferably 0.01 to 0.1 parts by weight, and particularly preferably 0.04 to 0.1 parts by weight, based on the dry weight of component (B) per 100 parts by weight of component (A).

[0043] (C) Plum extract

[0044] The composition for external use of the present invention contains a plum extract as the component (C). The composition for external use of the present invention can further enhance the whitening effect by containing the component (C).

[0045] The plum extract can be obtained by performing a solvent extraction process using plum as an extraction raw material.

[0046] The plum used as the extraction raw material is a plum of the subgenus Prunus in the genus Prunus of the Rosaceae family. Specifically, examples include the plums described in the "Original Color World Plant Atlas" (first edition published on April 20, 1971, by Hokuryukan Co., Ltd.), and more specifically, examples include Prunus virginiana (Western Prunus, European Prunus), apricot, mume, and Chinese plum (Sumomo). Among these extraction raw materials, one plant can be used alone, or two or more plants can be used in combination. Among these extraction raw materials, Prunus virginiana (Western Prunus, European Prunus) is preferably used from the perspective of further enhancing the whitening effect.

[0047] The plum extract may be any extract extracted from the pulp of the plant, and the plant parts to be extracted may include not only the pulp but also the peel, seeds, etc. as needed.

[0048] Examples of extraction solvents used in the plum extraction process include water; lower alcohols having 1 to 5 carbon atoms, such as methanol, ethanol, propanol, isopropanol, butanol, and isobutanol; polyols such as propylene glycol, 1,3-butanediol, 1,2-butanediol, 1,4-butanediol, 1,5-pentanediol, 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, and 1,3,5-pentanetriol; phenoxyethanol, parabens, ethyl paraben, methyl paraben, and propyl paraben; and mixtures thereof. Among these extraction solvents, water, mixtures of polyols and water, and mixtures of lower alcohols having 1 to 5 carbon atoms and water are preferred, with water and mixtures of 1,3-butanediol and water being more preferred.

[0049] When a mixed solution of a lower alcohol and / or polyol having 1 to 5 carbon atoms and water is used as the extraction solvent, there is no particular limitation on the concentration of the lower alcohol and / or polyol having 1 to 5 carbon atoms. For example, the total amount of the lower alcohol and / or polyol having 1 to 5 carbon atoms is 20 to 90% by weight, preferably 30 to 85% by weight.

[0050] Plum extracts are obtained by subjecting the aforementioned plant parts to extraction, either directly or after drying, finely chopped, crushed, pressed, enzyme-treated, boiled, or fermented, as needed, with the aforementioned extraction solvent. In particular, in the present invention, the Prunus genus plants of the Rosaceae family used for the extraction are preferably pre-enzymatically treated. Using enzyme-treated plums as the extraction raw material yields an extract with a significantly enhanced whitening effect.

[0051] The enzyme used in the enzyme treatment of plums may be any cellulolytic enzyme capable of decomposing cellulose in the pulp, and specific examples include cellulase, hemicellulase, pectinase, etc. These enzymes may be used alone or in combination of two or more.

[0052] The enzyme treatment conditions are not particularly limited, as long as the enzyme reaction proceeds within the temperature and pH ranges suitable for the enzyme being used and the desired effect is achieved. For example, a reaction temperature of 20-45°C for 3-24 hours is suitable. Following enzyme treatment, the plums can be inactivated by heating, etc., if necessary, and then subjected to solvent extraction.

[0053] As the solvent extraction treatment, a commonly used extraction method for plant extracts can be adopted. Specifically, there can be mentioned an immersion method such as cold immersion or warm immersion; a method of stirring under heating; or a percolation method.

[0054] The extract obtained by the above-mentioned solvent extraction treatment may be used directly in a liquid state, or may be subjected to treatment such as concentration or drying as needed and used as a concentrate or dried product. Furthermore, after concentration or drying, the obtained concentrate or dried product may be washed with an insoluble solvent and purified before use, or may be further dissolved or suspended in an appropriate solvent before use.

[0055] Commercially available plum extracts and enzyme-treated plum extracts may also be used. For example, enzyme-degraded plum extracts include "CREARGE" manufactured by Ichimaru Pharmacos Co., Ltd.

[0056] The content of component (C) in the external-use composition of the present invention can be appropriately set according to the formulation form of the external-use composition, and for example, 0.00001% by weight or more, specifically 0.00001 to 0.1% by weight, based on the dry weight of component (C) can be mentioned. From the viewpoint of further enhancing the effect of improving the whitening effect, the content of component (C) in the external-use composition of the present invention, based on the dry weight of component (C), can preferably be mentioned 0.00005 to 0.01% by weight, more preferably 0.0001 to 0.001% by weight, and particularly preferably 0.0005 to 0.001% by weight.

[0057] In addition, in the external composition of the present invention, the ratio of component (B) to component (C) is determined according to the above-mentioned respective contents. From the viewpoint of exerting a further excellent whitening effect, the ratio of component (C) to 100 parts by weight of component (B) (on a dry weight basis) can be 1 part by weight or more, preferably 1 to 5000 parts by weight, more preferably 5 to 500 parts by weight, further preferably 5 to 100 parts by weight, particularly preferably 10 to 100 parts by weight, and most preferably 50 to 80 parts by weight.

[0058] (D) Sakura leaf extract

[0059] The composition for external use of the present invention contains a cherry blossom leaf extract as component (D). The composition for external use of the present invention can further enhance the whitening effect by containing component (D) together with component (A), component (B), and component (C).

[0060] The cherry blossom leaf extract can be obtained by performing a solvent extraction process using the leaves of a cherry blossom tree as an extraction raw material.

[0061] The cherry trees used as the extraction raw materials are cherry trees of the subgenus Prunus in the genus Prunus of the Rosaceae family. Specific examples include those listed in the "Original Color World Plant Atlas" (first edition published on April 20, 1971, by Hokuryukan Co., Ltd.). More specific examples include Kasumizakura (Mountain cherry), Tingzi cherry, Dog cherry, Umizo cherry, Mountain cherry, Mame cherry (Fuji cherry), Weeping cherry (Ito cherry), Sekiyama cherry (Red tassel), Oshima cherry, Fukayama cherry, Mine cherry, Chishima cherry, Edohigan cherry (Eastern cherry), Oyama cherry, Spinosa cherry (Spinosa cherry), Sakhalin cherry (Japanese cherry, Fukayama dog cherry), Higan cherry (Small Higan cherry), Somei Yoshino cherry, Bigleaf laurel cherry (Prunus serrulata, Prunus serrulata), and Hanaka cherry. These extraction raw material plants may be used alone or in combination of two or more. Among these extraction materials, from the viewpoint of further enhancing the whitening effect, the Somei Yoshino cherry tree is preferably used.

[0062] Examples of extraction solvents used in the cherry blossom leaf extraction process include water; lower alcohols having 1 to 5 carbon atoms, such as methanol, ethanol, propanol, isopropanol, butanol, and isobutanol; polyols such as propylene glycol, 1,3-butanediol, 1,2-butanediol, 1,4-butanediol, 1,5-pentanediol, 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, and 1,3,5-pentanetriol; phenoxyethanol, parabens, ethyl paraben, methyl paraben, and propyl paraben; and mixtures thereof. Among these extraction solvents, water, mixtures of polyols and water, and mixtures of lower alcohols having 1 to 5 carbon atoms and water are preferred, with mixtures of lower alcohols having 1 to 5 carbon atoms and water being more preferred.

[0063] When a mixture of a lower alcohol and / or polyol having 1 to 5 carbon atoms and water is used as the extraction solvent, there is no particular limitation on the concentration of the lower alcohol and / or polyol having 1 to 5 carbon atoms. For example, the total amount of the lower alcohol and / or polyol having 1 to 5 carbon atoms is 20 to 90% by weight, preferably 30 to 85% by weight.

[0064] Cherry blossom leaf extract can be obtained by extracting the cherry blossom leaves directly or, if necessary, by drying, finely chopping, crushing, squeezing, enzymatically treating, boiling, or fermenting them, using the aforementioned extraction solvent. Solvent extraction can employ commonly used plant extract extraction methods, specifically immersion methods such as cold soaking or warm soaking; methods with stirring under heating; and percolation.

[0065] The extract obtained by the above-mentioned solvent extraction treatment may be used directly in a liquid state, or may be subjected to treatment such as concentration or drying as needed and used as a concentrate or dried product. Furthermore, after concentration or drying, the obtained concentrate or dried product may be washed with an insoluble solvent and purified before use, or may be further dissolved or suspended in an appropriate solvent before use.

[0066] Alternatively, a commercially available extract that is easily available may be used as the cherry blossom leaf extract. For example, "SAKURAEX B" manufactured by Ichimaru Pharmacos Co., Ltd. may be used as the cherry blossom leaf extract.

[0067] The content of component (D) in the external-use composition of the present invention can be appropriately set according to the formulation form of the external-use composition, and can be, for example, 0.00001% by weight or more, specifically 0.00001 to 0.1% by weight, based on the dry weight of component (D). From the viewpoint of exerting a further excellent whitening effect, the content of component (D) in the external-use composition of the present invention can be preferably 0.00005 to 0.1% by weight, more preferably 0.0001 to 0.1% by weight, based on the dry weight of component (D). As a further preferred content of the component (D), from the viewpoint of exerting a further excellent whitening effect and the viewpoint of formulation stability, when the external composition of the present invention is a lotion, the content of the component (D) can be 0.0001 to 0.01% by weight, preferably 0.0002 to 0.0005% by weight, based on the dry weight conversion of the component (D); when the external composition of the present invention is an emulsion, the content of the component (D) can be 0.0001 to 0.1% by weight, preferably 0.0 0.002 to 0.1 weight %, more preferably 0.0005 to 0.01 weight %, further preferably 0.001 to 0.005 weight %. When the external use composition of the present invention is a cream, the amount of component (D) calculated on a dry weight basis is 0.0001 to 0.1 weight %, preferably 0.0002 to 0.1 weight %, more preferably 0.008 to 0.1 weight %, further preferably 0.01 to 0.05 weight %, further preferably 0.01 to 0.02 weight %.

[0068] In addition, in the external use composition of the present invention, the ratio of component (A) to component (D) is determined according to the above-mentioned respective contents. From the viewpoint of exerting a more excellent whitening effect, the amount of component (D) can be 0.0005 parts by weight or more, specifically 0.0005 to 5 parts by weight, per 100 parts by weight of component (A). From the viewpoint of exerting a more excellent whitening effect, the amount of component (D) in the external use composition of the present invention can be preferably 0.0025 to 5 parts by weight, more preferably 0.005 to 5 parts by weight, per 100 parts by weight of component (A), per 100 parts by weight of component (D). As a further preferred content of the component (D), from the viewpoint of exhibiting a more excellent whitening effect and the viewpoint of formulation stability, when the external composition of the present invention is a lotion, the content of the component (D) can be 0.005 to 0.5 parts by weight, preferably 0.01 to 0.025 parts by weight, based on the dry weight conversion of the component (D) relative to 100 parts by weight of the component (A); and when the external composition of the present invention is an emulsion, the content of the component (D) can be 0.00 to 0.01 parts by weight, based on the dry weight conversion of the component (D) relative to 100 parts by weight of the component (A). The amount of component (D) is preferably 0.5 to 5 parts by weight, preferably 0.01 to 5 parts by weight, more preferably 0.025 to 0.5 parts by weight, and further preferably 0.05 to 0.25 parts by weight. When the external composition of the present invention is a cream, the amount of component (D) calculated on a dry weight basis relative to 100 parts by weight of component (A) is 0.005 to 5 parts by weight, preferably 0.01 to 25 parts by weight, more preferably 0.4 to 5 parts by weight, further preferably 0.5 to 2.5 parts by weight, and further preferably 0.5 to 1 part by weight.

[0069] In addition, in the external use composition of the present invention, the ratio of component (B) to component (D) is determined according to the above-mentioned respective contents. From the viewpoint of exerting a further excellent whitening effect, the amount of component (D) can be 0.08 parts by weight or more, specifically 0.08 to 8100 parts by weight, per 100 parts by weight of component (B). From the viewpoint of exerting a further excellent whitening effect, the amount of component (D) in the external use composition of the present invention can be preferably 4 to 8100 parts by weight, more preferably 8 to 8100 parts by weight, per 100 parts by weight of component (B), per 100 parts by weight of component (D). As a further preferred content of the component (D), from the viewpoint of exerting a further excellent whitening effect and the viewpoint of formulation stability, when the external composition of the present invention is a lotion, the content of the component (D) can be 8 to 820 parts by weight, preferably 16 to 45 parts by weight, relative to 100 parts by weight of the component (B), and when the external composition of the present invention is an emulsion, the content of the component (D) can be 8 to 8150 parts by weight, relative to 100 parts by weight of the component (B), relative to 100 parts by weight of the component (D). The amount of the component (D) is preferably 16 to 8150 parts by weight, more preferably 40 to 850 parts by weight, and even more preferably 80 to 450 parts by weight. In the case of the cream composition for external use of the present invention, the amount of the component (D) is 8 to 8150 parts by weight, calculated as the dry weight of the component (B) relative to 100 parts by weight. Preferably, the amount is 16 to 8150 parts by weight, more preferably 650 to 8150 parts by weight, even more preferably 810 to 4500 parts by weight, and even more preferably 810 to 1700 parts by weight.

[0070] In the external use composition of the present invention, the ratio of component (C) to component (D) is determined according to the above-mentioned respective contents. From the viewpoint of exerting a further excellent whitening effect, the amount of component (D) can be 1.2 parts by weight or more, specifically 1.2 to 13,000 parts by weight, per 100 parts by weight of component (C). From the viewpoint of exerting a further excellent whitening effect, the amount of component (D) in the external use composition of the present invention can be preferably 6.4 to 13,000 parts by weight, more preferably 12 to 13,000 parts by weight, per 100 parts by weight of component (C), per 100 parts by weight of component (D). As a further preferred content of the component (D), from the viewpoint of exerting a further excellent whitening effect and the viewpoint of formulation stability, when the external composition of the present invention is a lotion, the content of the component (D) can be 12 to 1300 parts by weight, preferably 25 to 65 parts by weight, based on the dry weight conversion of the component (D) per 100 parts by weight of the component (C). When the external composition of the present invention is an emulsion, the content of the component (D) can be 12 to 13000 parts by weight, based on the dry weight conversion of the component (D) per 100 parts by weight of the component (C). , preferably 25 to 13,000 parts by weight, more preferably 64 to 1,300 parts by weight, further preferably 120 to 650 parts by weight. When the external composition of the present invention is a cream, the amount of component (D) calculated on a dry weight basis, relative to 100 parts by weight of component (C), can be 12 to 13,000 parts by weight, preferably 25 to 13,000 parts by weight, more preferably 1,000 to 13,000 parts by weight, further preferably 1,200 to 6,500 parts by weight, and further preferably 1,200 to 2,600 parts by weight.

[0071] Other ingredients

[0072] The external use composition of the present invention may contain other pharmacological components as needed in addition to the above-mentioned components. Examples of such pharmacological ingredients include melanin production inhibitors (arbutin, tranexamic acid, L-cysteine, glutathione, kojic acid, etc.), antihistamines (diphenhydramine, diphenhydramine hydrochloride, chlorpheniramine maleate, etc.), local anesthetics (lidocaine, dibucaine, methylaminobenzoate, procaine, tetracaine, bupivacaine, mepivacaine, chloroprocaine, proparacaine, meprecaine or salts thereof, oxathiocaine, oxypolyethoxydecane, hyoscyamine solution, dibucaine powder (Japanese original: ペルカミンパーゼ), polyoxyethylene lauryl ether, etc.), anti-inflammatory agents (allantoin, glycyrrhizic acid, methyl glycyrrhizate, stearyl glycyrrhizate, dipotassium glycyrrhizate, monoammonium glycyrrhizate, glycyrrhetinic acid, pyrrolidone glycyrrhetinic acid, etc.), and anti-inflammatory agents. Pyridoxine, stearyl glycyrrhetinic acid, glyceryl glycyrrhetinic acid, glycyrrhetinic acid monoglucuronide, salicylic acid, methyl salicylate, glycol salicylate, indomethacin, felbinac, diclofenac sodium, loxoprofen sodium, flufenamic acid butyl, picoprofen, suprofen, benzyldexium chloride, suprofen, bufenamic acid, etc.), bactericides (benzalkonium chloride, dequalinium chloride, benzethonium chloride, cetylpyridinium chloride, chlorhexidine, chlorhexidine gluconate, isopropyl methylphenol, ammonia, sulfadiazine, lactic acid, phenol, etc.), skin protectants (cotton glue, castor oil, etc.), blood circulation promoters (nonanoic acid vanillylamide, benzyl nicotinate, capsaicin, chili extract, etc.), cooling agents (menthol, camphor, etc.), vitamins (vitamins A, B, D, E, etc.), mucopolysaccharides (sodium chondroitin sulfate, glucosamine, sodium hyaluronate, etc.), etc.

[0073] In addition, in order to prepare the desired preparation form, the external use composition of the present invention can contain bases and additives as needed. There is no particular limitation on such bases and additives as long as they are pharmaceutically acceptable. For example, water can be cited; aqueous bases such as lower monohydric alcohols (ethanol, isopropyl alcohol, etc.), polyols (propylene glycol, ethylene glycol, 1,3-butylene glycol, isopentyl glycol, diethylene glycol, dipropylene glycol, glycerol, etc.); oils (olive oil, safflower oil, soybean oil, tea oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, peanut oil, lard, squalane, fish oil, etc.), mineral oils (liquid paraffin, paraffin, gelled hydrocarbons, vaseline, etc.), WAX waxes (beeswax, carnauba wax, candelilla wax, psilocin, rice bran wax, microcrystalline wax, etc.), ester oils (isopropyl myristate, isopropyl adipate, diethyl sebacate, isopropyl sebacate, Isopropyl Palmitate, Cetyl Palmitate, Cetyl Ethylhexanoate, Ethyl Oleate, Tri(2-ethylhexanoin)glyceryl, Tri(caprylic / capric)glyceryl, etc.), Fatty Acid Alkyl Esters, Fatty Acids (Stearic Acid, Oleic Acid, Palmitic Acid, Behenic Acid, Linoleic Acid, Lanolin, etc.), Fatty Acid Esters (Cetyl Palmitate, Isopropyl Palmitate, Ethyl Linoleate, etc.), Medium Chain Fatty Acid Triglycerides, Higher Alcohols (Stearyl Alcohol, Cetyl Alcohol, Behenyl Alcohol, Myristyl Alcohol, Oleyl Alcohol, Cetyl Alcohol, Lanolin Alcohol, Cholesterol, Dihydrocholesterol, Phytosterols, Lauryl Alcohol, Cetearyl Alcohol, Linoleyl Alcohol, Octyldodecanol, Hexyldecanol, Isostearyl Alcohol, etc.), Cetyl Ethylhexanoate, Silicone Oils (Dimethicone, Cyclopentasiloxane, etc.), etc. base; nonionic surfactants (sorbitan fatty acid esters (sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, penta-2-ethylhexanoic acid diglycerol dehydrated sorbitan ester, tetra-2-ethylhexanoic acid diglycerol dehydrated sorbitan ester, etc.); glycerol polyglycerol fatty acid esters (monocottonseed oil fatty acid glyceryl ester, monoerucic acid glyceryl ester, sesquioleic acid glyceryl ester, monostearate glyceryl, triethylhexanoic acid glyceryl ester, α,α'-oleyl pyroglutamic acid glyceryl ester, monostearate glyceryl malate, etc.); propylene glycol fatty acid esters (propylene glycol monostearate Esters, etc.); hydrogenated castor oil derivatives; glycerol alkyl ethers, POE-sorbitan fatty acid esters (POE-sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan isostearate, POE-sorbitan monooleate, POE-sorbitan tetraoleate, etc.); POE sorbitol fatty acid esters (POE-sorbitan monolaurate, POE-sorbitan monooleate, POE-sorbitan pentaoleate, POE-sorbitan monostearate, etc.); POE-glycerol fatty acid esters (POE-glycerol monostearate, POE-glycerol monoisostearate, POE-glycerol triisostearate, etc. POE-monooleates, etc.);POE-fatty acid esters (POE-distearate, POE-mono-dioleate, glycol distearate, etc.); POE-alkyl ethers (POE-lauryl ether, POE-oleyl ether, POE-stearyl ether, POE-behenyl ether, POE-2-octyldodecyl ether, POE-cholestanol ether, etc.); Pluronic type (Pluronic, etc.); POE·POP-alkyl ethers (POE·POP-hexadecyl ether, POE·POP-2-decyltetradecyl ether, POE·POP-monobutyl ether, POE·POP-hydrogenated lanolin, POE·POP-glycerol ether, etc.); Tetra-POE·tetra-POP-ethylenediamine condensates (Tetronic, etc.) ); POE-castor oil hydrogenated castor oil derivatives (e.g., POE-castor oil, POE-hydrogenated castor oil, POE-hydrogenated castor oil monoisostearate, POE-hydrogenated castor oil triisostearate, POE-hydrogenated castor oil monopyroglutamic acid monoisostearate diester, POE-hydrogenated castor oil maleate (POE-hardened himasiyama acid), etc.); alkanolamides (coconut fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, etc.); sucrose fatty acid esters; alkyl ethoxydimethylamine oxide; trioleyl phosphoric acid, etc.); anionic surfactants (fatty acid soaps (sodium laurate, sodium palmitate, etc.); higher alkyl sulfates (sodium lauryl sulfate, potassium lauryl sulfate, etc.) ); alkyl ether sulfates (POE-lauryl sulfate triethanolamine, POE-sodium lauryl sulfate, etc.); N-acyl sarcosine (sodium lauroyl sarcosinate, etc.); higher fatty acid amide sulfonates (sodium N-myristoyl-N-methyl taurate, sodium coconut fatty acid methyl taurate, sodium lauryl methyl taurate, etc.); sulfosuccinates (sodium di-2-ethylhexyl sulfosuccinate, sodium monolauroyl monoethanolamide polyoxyethylene sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, etc.); alkylbenzene sulfonates (sodium linear dodecylbenzene sulfonate, linear dodecylbenzene sulfonic acid triethanolamine, linear dodecylbenzene sulfonic acid, etc.); higher fatty acid ester sulfates (sodium hydrogenated coconut fatty acid glycerol sulfate, etc.); N- Surfactants such as acyl glutamates (monosodium N-lauroyl glutamate, disodium N-stearoyl glutamate, monosodium N-myristoyl-L-glutamate, etc.); POE-alkyl ether carboxylic acid; POE-alkyl allyl ether carboxylate; α-olefin sulfonate; sodium lauroyl monoethanolamide succinate; di(triethanolamine)N-palmitoyl aspartate; etc.; aqueous thickeners (carboxyvinyl polymer, alkyl-modified carboxyvinyl polymer, cellulose gum, xanthan gum, hydroxypropyl methylcellulose, hydroxyethyl cellulose, carboxymethyl cellulose, (ammonium acryloyldimethyltaurate / VP) copolymer, sodium polyacrylate, carrageenan, xanthan gum, sclerotium gum, polystyrene sulfonate, karaya gum, pectin, etc.);Porous powders (inorganic powders such as silicon dioxide, talc, titanium oxide, mica, zinc oxide, kaolin, barium sulfate, bismuth oxychloride, aluminum hydroxide, aluminum silicate, anhydrous silicic acid, hydrated silicic acid, and montmorillonite; polymer powders such as polyester, polyethylene, polystyrene, methyl methacrylate resin, cellulose, nylon, copolymers of styrene and acrylic acid, polypropylene, and vinyl chloride); cooling agents (menthol, camphor, borneol, mint water, and mint oil); preservatives (phenoxyethanol, methyl paraben, propyl paraben, benzoic acid, sodium benzoate, and sorbic acid); flavoring agents (citral, 1,8-cineole, citronellal, and farnesol); colorants (tar pigments (brown No. 201, blue No. 201, yellow No. 4, and yellow Additives include: (acidity 500mg, color No. 403, etc.), cocoa pigment, chlorophyll, aluminum oxide, etc.), pH adjusters (phosphoric acid, hydrochloric acid, citric acid, sodium citrate, succinic acid, tartaric acid, sodium hydroxide, potassium hydroxide, triethanolamine, triisopropanolamine, etc.), wetting agents (sodium dl-pyrrolidonecarboxylate solution, D-sorbitol solution, polyethylene glycol, etc.), stabilizers (butylated hydroxytoluene, butylated hydroxyanisole, sodium edetate, sodium metaphosphate, L-arginine, L-aspartic acid, DL-alanine, glycine, sodium erythorbate, propyl gallate, sodium sulfite, sulfur dioxide, chlorogenic acid, catechin, rosemary extract, etc.), antioxidants, UV absorbers, chelating agents, binders, buffers, cosolvents, solubilizers, preservatives, etc.

[0074] Preparation form

[0075] The external use composition is not particularly limited in its form as long as it is a formulation that can be applied transdermally, and may be in any of liquid, solid, semisolid (cream, gel, ointment, paste), etc. Furthermore, the external use composition of the present invention may be a non-emulsified formulation such as an aqueous formulation or an oily formulation, or an emulsified formulation such as an oil-in-water emulsion formulation or a water-in-oil emulsion formulation.

[0076] As the preparation form of the external composition, from the viewpoint of more effectively exhibiting the whitening effect, preferably, it is a liquid form or a cream form, and more preferably, it is a cream form.

[0077] Furthermore, the external composition may be in any formulation form, such as a skin external medicine, a cosmetic, a skin cleanser, etc., as long as it can be applied to the skin. Preferred examples include skin external medicines and cosmetics.

[0078] As the preparation form of the above-mentioned external-use composition, specifically, liquid (including lotion, spray, aerosol and emulsion), water-soluble ointment, grease-based ointment, cream, foam, gel, patch and other skin external medicines can be enumerated; Ointment, cream, emulsion, toner, lotion, facial mask, gel and other cosmetics; Skin cleansers such as shower gel, shampoo, conditioner etc. can be enumerated. In these preparation forms, skin external medicines can be preferably enumerated, liquid, cream can be further preferably enumerated, lotion, emulsion, cream can be more preferably enumerated, emulsion, cream can be further preferably enumerated, and cream can be particularly preferably enumerated. To become these preparation forms, it is possible to prepare by using the additive corresponding to the preparation form to carry out formulation according to the known method recorded in the sixteenth revision of the Japanese Pharmacopoeia Preparation General Rules etc.

[0079] use

[0080] The external composition of the present invention can inhibit the production of melanin and prevent or improve spots, freckles, dullness, liver spots, age-related pigmentation, darkening caused by physical irritation, etc. on the skin, and is therefore suitable as a whitening external composition.

[0081] Example

[0082] Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples.

[0083] In addition, the manufacturers etc. of the main components used in the following test examples and formulation examples are as follows.

[0084] L-Ascorbic acid 2-glucoside : Trade name "AA2G" (manufactured by Hayashihara Co., Ltd.)

[0085] Magnolia officinalis Extract : Trade name "PHARCOLEX HOONOKI B" (manufactured by Ichimaru Pharmacos Co., Ltd.), liquid, dry solids concentration 0.175% by weight, an extract obtained by solvent extraction of the bark of Magnolia obovata Thunberg (Magnoliaceae) using a 1,3-butanediol aqueous solution

[0086] Plum Extract : Trade name "CREARGE" (manufactured by Ichimaru Pharmacos Co., Ltd.), liquid, dry solid content concentration 7.78% by weight, an extract obtained by adding water and 1,3-butanediol to the pulp of plums (Prunus domestica Lindl. (Rosaceae)) decomposed with cellulolytic enzymes

[0087] Peony Extract : Trade name "PHARCOLEX BOTANNPI B" (manufactured by Ichimaru Pharmacos Co., Ltd.), liquid, dry solids concentration 0.9% by weight, an extract obtained by solvent extraction of the root bark of Paeonia suffruticosa Andrews (Paeonia moutan Sims) (Paeoniaceae) using an ethanol solution

[0088] Sakura Leaf Extract : Trade name "SAKURAEX B" (manufactured by Ichimaru Pharmacos Co., Ltd.), liquid, dry solid content concentration 2% by weight, obtained by solvent extraction of leaves of Somei Yoshino cherry (Prunus yedoensis Matsum.) using an ethanol aqueous solution

[0089] Test Example 1: Evaluation of the melanin production inhibitory effect (in vitro (in vitro vitro))

[0090] The melanin production inhibitory effect was evaluated using a three-dimensional cultured skin model (MEL-300-A, manufactured by MatTek). The specific test method is as follows.

[0091] The MEL-300 skin model cup was placed in each well of a 6-well plate to which 0.9 ml of a maintenance medium (EPI-100LLMM) heated to 37°C was added, and the cup was placed in an incubator (37°C, 5% CO2) and allowed to stand for 1 hour. Next, 50 μl of the external use composition (pH 6.5) shown in Table 1 was added to the inside of the skin model cup, and cultured in an incubator (37°C, 5% CO2) for 24 hours. Then, ultraviolet light (UV-B) was irradiated at 0.5 mW × 12 seconds per time, and the culture was further cultured for 24 hours. It should be noted that ultraviolet irradiation was performed using a UVB lamp (manufactured by TOSHIBA Lighting & Technology, fluorescent lamp for Toshiba health line) and a UV detector (manufactured by TOPCON, UV-1). Then, the culture medium was replaced and the culture was further cultured for 24 hours. It should be noted that each time the culture medium was replaced, 50 μl of the specified sample liquid was added to the skin model cup. Furthermore, ultraviolet irradiation and culture medium replacement were repeated 4 times under the same conditions, thereby performing ultraviolet irradiation 5 times in total (total ultraviolet irradiation dose 30 mJ / cm 2), a total of 5 medium changes. Then, cell viability and melanin production were measured using the following methods. In addition, as a control, an aqueous solution containing 0.5% by weight of 1,3-butanediol was used as the sample solution, and the test was conducted under the same conditions as above.

[0092] <Measurement of cell activity>

[0093] The cell viability was determined by MTT assay. Specifically, 0.75 ml of MTT test drug and 8.25 ml of maintenance medium (EPI-100LLMM) were mixed and added in a manner to achieve 300 μl per well. The skin model cup was transferred to the culture medium to which the MTT prepared above was added, and cultured in an incubator for exactly 3 hours. Then, the bottom surface of the tissue was gently washed with PBS washing solution and transferred to a new plate. 1 ml of 0.04 N HCl acidic isopropanol was added to the inner side of each skin model cup, and a cover slip was pasted on the plate to shield it from light in a non-evaporating manner, and blue formazan was extracted in an incubator overnight. After extraction, the isopropanol was thoroughly mixed and 200 μl of it was transferred to a 96-well plate. The optical density at 570 nm and 620 nm was measured using a microplate reader, and the difference between them was used as cell activity.

[0094] <Measurement of melanin production>

[0095] After washing the MEL-300 skin model cup with PBS, the cell tissue was peeled off with a scalpel and recovered. The obtained cell tissue was immersed in PBS, crushed and centrifuged (2000rpm, 10 minutes). Then, the supernatant was removed, and a mixture of ethanol and dimethyl ether (ethanol: dimethyl ether = 3: 1 (volume ratio)) was further added, stirred and centrifuged (2000rpm, 10 minutes). Next, the supernatant was removed and dried. A 1N sodium hydroxide aqueous solution (containing 10% by weight DMSO) was added to the dried product, and it was heated and melted in a 90°C water bath for 20 minutes. The heated and molten solution was then gently stirred with a vortex oscillator, cooled to room temperature, and the absorbance at 405nm was measured to determine the amount of melanin produced.

[0096] The melanin production per cell was calculated by dividing the melanin production by the cell viability. Furthermore, the melanin production per cell of Reference Example 1 (negative control; NC) was set to 100, and the ratio of the melanin production per cell when each sample solution was added (melanin production ratio) was calculated.

[0097] The results are shown in Table 1. These results demonstrate that the melanin production inhibitory effect of the external application compositions containing ascorbic acid 2-glucoside, Japanese magnolia extract, and plum extract (Comparative Example 1) in addition to ascorbic acid 2-glucoside, Japanese magnolia extract, and plum extract (Examples 1 and 2) was significantly enhanced. The enhanced melanin production inhibitory effect of the external application composition containing only 0.002% by weight of the cherry blossom leaf extract (Example 1) was comparable to that of arbutin (Reference Example 2: positive control; PC), which is known for its high whitening effect. Furthermore, the external application composition containing 0.01% by weight of the cherry blossom leaf extract (Example 2) was superior to arbutin, which is known for its high whitening effect. On the other hand, in the case of external-use compositions containing, in addition to ascorbic acid 2-glucoside, Japanese magnolia officinalis extract, and plum extract, a peony extract known to have anti-inflammatory effects similar to cherry blossom leaf extract (Comparative Examples 2 and 3), no enhancement of the melanin production inhibitory effect was observed at all.

[0098] [Table 1]

[0099]

[0100] In the tables, the unit of the numerical values indicating the content of each component is % by weight.

[0101] The values in parentheses are calculated on a dry weight basis, and the unit is % by weight.

[0102] Test Example 2: Evaluation of the Melanin Production Inhibitory Effect (in vivo)

[0103] A cream with the composition described in Table 2 was prepared. Seventeen women with age-related pigmentation spots on their cheeks were tested. The cream was applied to the spots twice daily for six weeks. The melanin level of the age-related pigmentation spots was measured before and after application using a Mexameter (Mexameter MX18).

[0104] [Table 2]

[0105]

[0106] In the tables, the unit of the numerical values indicating the content of each component is % by weight.

[0107] The values in parentheses are calculated on a dry weight basis, and the unit is % by weight.

[0108] The results are shown in Figure 1 (Paired t-test, *** indicates p < 0.001). Figure 1As shown, the change in melanin value before application (initial) and after application (after 6 weeks) was: a significant decrease.

[0109] Recipe Example

[0110] Creams, emulsions, and lotions were prepared according to the formulations shown in Tables 3 to 5. The melanin production inhibitory effect was enhanced in all formulations.

[0111] [Table 3]

[0112] Cream

[0113]

[0114] In the tables, the unit of the numerical values indicating the content of each component is % by weight.

[0115] The values in parentheses are calculated on a dry weight basis, and the unit is % by weight.

[0116] [Table 4]

[0117] Emulsion

[0118]

[0119] In the tables, the unit of the numerical values indicating the content of each component is % by weight.

[0120] The values in parentheses are calculated on a dry weight basis, and the unit is % by weight.

[0121] [Table 5]

[0122] lotion

[0123]

[0124] In the tables, the unit of the numerical values indicating the content of each component is % by weight.

[0125] The values in parentheses are calculated on a dry weight basis, and the unit is % by weight.

Claims

1. A composition for external use, characterized in that Contains (A) ascorbic acid and / or its derivatives, (B) an extract of a plant of the genus Magnolia in the family Magnoliaceae, (C) an extract of plum, and (D) an extract of cherry blossom leaves. The component (B) is an extract of Magnolia officinalis. The content of the component (A) is 0.5% to 7% by weight on a dry weight basis. The content of the component (B) is 0.0008 wt% to 0.003 wt% on a dry weight basis. The content of the component (C) is 0.0005% to 0.001% by weight on a dry weight basis. The content of the component (D) is 0.008% by weight to 0.1% by weight on a dry weight basis. When the external composition is an emulsion, the amount of the component (D) is 120 to 1300 parts by weight based on dry weight per 100 parts by weight of the component (C). When the external composition is a cream, the amount of the component (D) is 1200 to 2600 parts by weight based on dry weight per 100 parts by weight of the component (C).

2. The external use composition according to claim 1, wherein The component (A) is ascorbic acid 2-glucoside.

3. The external use composition according to claim 1 or 2, wherein The content of the component (D) is 0.01% by weight to 0.05% by weight on a dry weight basis.

4. The external use composition according to claim 1 or 2, wherein The external composition is used for skin whitening.

Images