CN113811538A - External composition - Google Patents
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- CN113811538A CN113811538A CN202080035059.8A CN202080035059A CN113811538A CN 113811538 A CN113811538 A CN 113811538A CN 202080035059 A CN202080035059 A CN 202080035059A CN 113811538 A CN113811538 A CN 113811538A
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
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- A61K8/67—Vitamins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
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- A61K8/9783—Angiosperms [Magnoliophyta]
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Abstract
The invention aims to provide an external composition with higher whitening effect. The external composition is characterized by containing (A) ascorbic acid and/or derivatives thereof, (B) an extract of a magnolia plant of the Magnoliaceae family, (C) an extract of plum, and (D) an extract of cherry leaves, and exhibits a further improved whitening effect by significantly improving a melanin production-inhibiting effect.
Description
Technical Field
The present invention relates to an external composition having an improved whitening effect.
Background
Pigmentation of the skin, such as spots, freckles, darkness, darkening, liver spots, age spots, and the like, is known to be caused by excessive formation of melanin pigment due to ultraviolet exposure, hormonal abnormality, physical irritation, and the like, and is deposited in the skin. Such pigmentation of the skin becomes a great cosmetic annoyance, particularly for women.
Conventionally, components such as ascorbic acid and derivatives thereof that inhibit the production of melanin and/or dilute the produced melanin are known as so-called whitening components, and are widely used in external compositions for whitening for the purpose of obtaining a skin pigmentation-inhibiting effect. However, it is not said that the effect of suppressing skin pigmentation depends only on the effect of the whitening component, and the consumer demand can be sufficiently satisfied.
Therefore, formulations for improving the effect of whitening components to suppress skin pigmentation have been studied. For example, patent document 1 describes that an excellent whitening effect is obtained by increasing the melanin production-inhibiting action by using an extract of a magnolia plant of the magnolia family in combination with ascorbic acid and a derivative thereof in a composition for external use, and further describes that the whitening effect can be increased by adding a pulp of a cherry plant of the rosaceae family, specifically, an extract of plum ("japanese original: プルーン of plum").
Various studies have also been made on the cosmetic effect of plant extracts. For example, patent document 2 discloses an anti-allergic agent, an active oxygen scavenger, and a lipid peroxidation inhibitor containing an extract obtained by using water, ethanol, 1, 3-butanediol, or a mixed solution of 2 or more kinds of these from cherry leaves, and patent document 3 discloses that in a skin moisturizer further containing a component 1 which can select a cherry extract and a predetermined component 2 as active ingredients, the component 1 enhances the skin moisturizing effect, and the antioxidant activity of cells, and inhibits active oxygen. Namely, cherry extract is known to have an antiallergic effect, an active oxygen scavenging effect, a lipid peroxide inhibitory effect, a moisturizing effect enhancing effect, and the like.
Documents of the prior art
Patent document
Patent document 1: japanese patent laid-open publication No. 2017-66080
Patent document 2: japanese laid-open patent publication No. 8-245409
Patent document 3: japanese laid-open patent publication No. 2008-115098
Disclosure of Invention
Problems to be solved by the invention
The demand for whitening by consumers has been increasing year by year, and it is considered that conventional whitening agents cannot satisfy the demand of consumers. In order to meet the increasing demands of consumers in the future, development of an external composition having a higher whitening effect is also desired.
Accordingly, an object of the present invention is to provide a composition for external use having a higher whitening effect.
Means for solving the problems
As a result of intensive studies, the present inventors have found that the whitening effect of an external composition containing ascorbic acid and/or a derivative thereof, an extract of magnolia belonging to the family magnolia, and an extract of plum is significantly improved by blending the cherry leaf extract, the whitening effect of which has not been reported so far, with the external composition. The present invention has been completed based on this finding through further and repeated studies. That is, the present invention provides the inventions of the following disclosed embodiments.
A composition for external use characterized by containing (A) ascorbic acid and/or a derivative thereof, (B) an extract of a plant of the genus Magnoliaceae, (C) an extract of plum, and (D) an extract of cherry leaves.
The composition of claim 2, wherein the component (B) is an extract of Cynanchum komarovii.
The composition of item 1 or 2, wherein the component (A) is ascorbic acid 2-glucoside.
The composition for external use according to any one of claims 1 to 3, wherein the content of the component (D) is 0.00001 to 0.1% by weight in terms of dry weight.
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 in terms of dry weight.
The external composition according to any one of claims 1 to 5, wherein the external composition is used for whitening.
Effects of the invention
According to the external composition of the present invention, the melanin production-inhibiting effect is significantly improved, and thus a further improved whitening effect can be obtained.
Drawings
Fig. 1 shows changes in melanin pigment values before and after application when the external composition of the present invention is applied to a woman having age pigment spots on the cheek.
Detailed Description
The external composition of the present invention is characterized by containing ascorbic acid and/or a derivative thereof (sometimes also referred to as component (a)), an extract of a magnolia plant of the family magnoliaceae (sometimes also referred to as component (B)), an extract of plum (sometimes also referred to as component (C)), and an extract of oriental cherry leaf (sometimes also referred to as component (D)). The composition for external use of the present invention will be described in detail below.
(A) Ascorbic acid and/or derivatives thereof
The composition for external use of the present invention contains ascorbic acid and/or a derivative thereof as the component (a). Ascorbic acid and/or a derivative thereof is a known component having an antioxidant effect and known to have a whitening effect.
The ascorbic acid and its derivatives used in the present invention are not particularly limited as far as they are pharmaceutically or cosmetically acceptable, and 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; ascorbyl monoesters such as ascorbyl monophosphate and magnesium salt thereof; dialkyl ascorbyl esters such as distearyl ascorbyl ester, dipalmityl ascorbyl ester, and dioleate ascorbyl ester; ascorbic acid diesters such as ascorbic acid diphosphate and salts thereof; trialkyl esters such as ascorbyl tristearate, ascorbyl tripalmitate, and ascorbyl trioleate; ascorbyl 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, 3-O-ethyl, 6-behenoyl-ascorbic acid (3-O- エチル,6- ベヘルミノイル - アスコルビン acid), and the like. These ascorbic acids and derivatives thereof may be either L-form or D-form, and L-form is preferably used.
These ascorbic acids and derivatives thereof may be used alone in 1 kind, or may be used in combination in 2 or more kinds. Among these ascorbic acids and derivatives thereof, from the viewpoints of stability, whitening effect, and the like, a derivative of ascorbic acid is preferable, and ascorbic acid 2-glucoside is more preferable.
The content of the component (a) in the composition for external use of the present invention may be appropriately set according to the form of the preparation 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.
(B) Extract of plant of Magnoliaceae and Magnoliaceae
The external composition of the present invention contains an extract of a plant of the genus magnolia of the family magnolia as the component (B). The composition for external use of the present invention contains the component (B), and thus has an improved melanin production-inhibiting effect and can exhibit an excellent whitening effect.
The extract of magnolia belonging to the family magnoliaceae may be obtained by subjecting a magnolia belonging to the family magnoliaceae as an extraction raw material to a solvent extraction treatment.
Examples of the magnolia plant of the magnolia family used as the extraction raw material include plants described in the "original color world plant atlas" (published in 20-month-4-month-old-year-showa, japan union, north-Longmen), and specifically include magnolia biloba, magnolia biondii, magnolia grandiflora, magnolia biondii, magnolia grandiflora (magnolia biondii, magnolia liliiflora), magnolia officinalis (magnolia tangutica), magnolia wushurica, magnolia grandiflora (magnolia grandiflora), magnolia grandiflora, and magnolia grandiflora (magnolia grandiflora). Of these extraction raw material plants, 1 plant may be used alone, or 2 or more plants may be used in combination. Among these extraction materials, japanese magnoliavine is preferable from the viewpoint of exerting a more excellent whitening effect.
The extract of a plant of the genus magnolia of the family magnolia may be any extract obtained from the bark of the plant, and the part to be extracted may include, in addition to the bark, flowers, spikes, pericarps, fruits, stems, leaves, branches, leaves, stems, rhizomes, roots, seeds, and the like, and may be a whole tree, as necessary.
Examples of the extraction solvent used in the solvent extraction treatment of magnolia belonging to the family magnoliaceae include water; lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propanol, isopropanol, butanol, and isobutanol; polyhydric alcohols such as propylene glycol, 1, 3-butylene glycol, and glycerin; and a mixture thereof. Among these extraction solvents, water, a mixed solution of a lower alcohol having 1 to 5 carbon atoms and water, and a mixed solution of a polyhydric alcohol and water are preferable, and water, a mixed solution of ethanol and water, a mixed solution of 1, 3-butanediol and water, and a mixed solution of propylene glycol and water are further preferable.
When a mixed solution of a lower alcohol and/or a polyhydric alcohol having 1 to 5 carbon atoms and water is used as the extraction solvent, the concentration of the lower alcohol and/or the polyhydric alcohol having 1 to 5 carbon atoms is not particularly limited, and examples thereof include 20 to 90% by weight, preferably 30 to 85% by weight, of the total of the lower alcohol and/or the polyhydric alcohol having 1 to 5 carbon atoms.
The extract of a plant of the genus Magnoliae of the family Magnoliaceae is obtained by extracting the plant part to be extracted with the extraction solvent directly or after drying, cutting, crushing, squeezing, treating with an enzyme, boiling or fermenting as necessary. As the solvent extraction treatment, a commonly used extraction method of a plant extract can be used, and specific examples thereof include an immersion method such as cold immersion and warm immersion; a method of stirring under heating; or diafiltration, etc.
The extract obtained by the solvent extraction treatment may be used as it is in a liquid state, or may be used in the form of a concentrate or a dried product by subjecting to a treatment such as concentration or drying as necessary. The concentrate or dried product obtained after concentration or drying may be used after being washed with a non-soluble solvent and purified, or may be further dissolved or suspended in an appropriate solvent.
Further, as the extract of a plant of the genus magnolia of the family magnolia, an extract which is commercially available in a simple manner may also be used. Examples of the extract of the bark of the Japanese hackberry include "PHARCOLEX HOONOKI B (ファルコレックスホオノキ B)" and "PHARCOLEX HOONOKI E (ファルコレックスホオノキ E)" manufactured by the company Ichimou PHARCOS.
The content of the component (B) in the composition for external use of the present invention may be appropriately set according to the form of the preparation of the composition for external use, and for example, is 0.00001 wt% or more, specifically, 0.00001 to 0.1 wt% in terms of the dry weight of the component (B). From the viewpoint of exerting a more excellent whitening effect, the content of the component (B) in the external composition of the present invention is preferably 0.00005 to 0.05 wt%, more preferably 0.0001 to 0.01 wt%, and particularly preferably 0.0008 to 0.003 wt%, in terms of the dry weight of the component (B).
The ratio of the component (a) to the component (B) in the composition for external use of the present invention is determined by the above-mentioned contents, and from the viewpoint of exerting a more excellent whitening effect, it is 0.001 part by weight or more, preferably 0.001 to 1 part by weight, more preferably 0.005 to 0.5 part by weight, further preferably 0.01 to 0.1 part by weight, and particularly preferably 0.04 to 0.1 part by weight in terms of the dry weight of the component (B) per 100 parts by weight of the component (a).
(C) Plum extract
In the composition for external use of the present invention, an extract of plum is contained as the (C) component. The composition for external use of the present invention can further improve whitening effect by including the component (C).
The extract of plum may be obtained by subjecting plum as an extraction raw material to a solvent extraction treatment.
The plum used as the extraction raw material is a plum of the genus Prunus of the family Rosaceae, and specifically includes plum described in "original color world plant atlas" (published first 20 months in 4 months and 61 years, Japan Hippocampus, Japan Co., Ltd.), and more specifically includes prune (prune, European plum), apricot, plum (mume), Chinese plum (スモモ), and the like. Of these extraction raw material plants, 1 plant may be used alone, or 2 or more plants may be used in combination. Among these extraction materials, prunes (prunes, prunus humilis) are preferable from the viewpoint of further improving the whitening effect.
The extract of plum may be an extract extracted from the pulp of the plant, and the plant part to be extracted may contain, as necessary, a fruit peel, a seed, and the like in addition to the pulp.
Examples of the extraction solvent used in the extraction treatment of plum include water; lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propanol, isopropanol, butanol, and isobutanol; polyhydric alcohols 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, propyl paraben; and a mixture thereof. Among these extraction solvents, water, a mixture of a polyhydric alcohol and water, and a mixture of a lower alcohol having 1 to 5 carbon atoms and water are preferable, and a mixture of water, 1, 3-butanediol and water is more preferable.
When a mixed solution of a lower alcohol and/or a polyhydric alcohol having 1 to 5 carbon atoms and water is used as the extraction solvent, the concentration of the lower alcohol and/or the polyhydric alcohol having 1 to 5 carbon atoms is not particularly limited, and examples thereof include 20 to 90% by weight, preferably 30 to 85% by weight, of the total of the lower alcohol and/or the polyhydric alcohol having 1 to 5 carbon atoms.
The extract of plum is obtained by subjecting the plant part to be extracted to extraction treatment with the extraction solvent, either directly or after drying, fine cutting, crushing, squeezing, enzyme treatment, boiling or fermentation treatment as required. In particular, in the present invention, the plant of the genus cerasus of the family rosaceae subjected to the extraction treatment is preferably subjected to the enzyme treatment in advance. By using enzymatically treated plum as an extraction raw material, an extract having an extremely high effect of improving the whitening effect can be obtained.
The enzyme used for the enzymatic treatment of plum may be any cellulolytic enzyme capable of decomposing cellulose in the pulp, and specific examples thereof include cellulase, hemicellulase, pectinase, and the like. These enzymes may be used alone in 1 kind, or may be used in combination in 2 or more kinds.
The conditions for the enzyme treatment are not particularly limited as long as the conditions are set within the range of the temperature and pH at which the enzyme to be used acts and the reaction proceeds until the enzyme reaction proceeds to obtain the desired effect, and examples thereof include conditions for the reaction at 20 to 45 ℃ for 3 to 24 hours. After subjecting plums to enzyme treatment, the enzyme may be inactivated by heating or the like, if necessary, and subjected to solvent extraction treatment.
As the solvent extraction treatment, a commonly used extraction method of a plant extract can be used, and specific examples thereof include an immersion method such as cold immersion and warm immersion; a method of stirring under heating; or diafiltration, etc.
The extract obtained by the above-mentioned solvent extraction treatment may be used as it is in a liquid state, or may be used in the form of a concentrate or a dried product by subjecting to a treatment such as concentration or drying as necessary. The concentrate or dried product obtained after concentration or drying may be used after being washed with a non-soluble solvent and purified, or may be further dissolved or suspended in an appropriate solvent.
Further, as the extract of plum or the extract of enzymatically treated plum, commercially available extracts can be used. Examples of the enzymatically decomposed plum extract include "CREARGE (クレアージュ)" manufactured by ICHIMARU PHARCOS co.
The content of the component (C) in the external composition of the present invention may be appropriately set according to the form of the preparation of the external composition, and for example, may be 0.00001 wt% or more, specifically 0.00001 to 0.1 wt% in terms of the dry weight of the component (C). From the viewpoint of further improving the whitening effect, the content of the component (C) in the external composition of the present invention is preferably 0.00005 to 0.01 wt%, more preferably 0.0001 to 0.001 wt%, and particularly preferably 0.0005 to 0.001 wt%, in terms of the dry weight of the component (C).
In the composition for external use of the present invention, the ratio of the component (B) to the component (C) is determined by the above-mentioned contents, and from the viewpoint of further exhibiting excellent whitening effect, the component (C) is 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 based on 100 parts by weight of the component (B) (in terms of dry weight).
(D) Oriental cherry leaf extract
The external composition of the present invention contains an extract of oriental cherry leaves as the (D) component. The external composition of the present invention can further improve the whitening effect by including component (D) together with component (a), component (B), and component (C).
The oriental cherry leaf extract can be obtained by subjecting oriental cherry leaves to solvent extraction treatment using oriental cherry leaves as an extraction raw material.
The cherry tree used as the extraction raw material is a cherry of the genus cerasus of the family rosaceae, specifically, a material described in "primary color world plant cerasus japonicas" (published in the first 20 th 4 th month-61 th, the plant type society, northwest longum), more specifically, nephelin cherry (prunus mauritiana), cherokee butadiene, cherokee canina, cherokee upper ditch, cherokee mountain, cherokee bean (prunus fuginiana), cherokee ramosa (cherokee renbergiana), cherokee rose (red tassel), cherokee macrophylla, cherokee profundae, cherokee peak, cherokee kalada, cherokee jalaportae (east cherokee), cherokee majus, cherokee spinosa (prunus spinosa), prunus kummensensis (japanese cherry, prunus sylvestris), their bank (small bank), cherokee laevigata indica, cherokee rose, cherokee macrophylla ( ), and the like. Of these extraction raw material plants, 1 plant may be used alone, or 2 or more plants may be used in combination. Among these extraction materials, cherokee rose-dyed is preferable from the viewpoint of further improving the whitening effect.
Examples of the extract of oriental cherry leaves include water; lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propanol, isopropanol, butanol, and isobutanol; polyhydric alcohols 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, propyl paraben; and a mixture thereof. Among these extraction solvents, water, a mixture of a polyhydric alcohol and water, and a mixture of a lower alcohol having 1 to 5 carbon atoms and water are preferable, and a mixture of a lower alcohol having 1 to 5 carbon atoms and water is more preferable.
When a mixed solution of a lower alcohol and/or a polyhydric alcohol having 1 to 5 carbon atoms and water is used as the extraction solvent, the concentration of the lower alcohol and/or the polyhydric alcohol having 1 to 5 carbon atoms is not particularly limited, and examples thereof include 20 to 90% by weight, preferably 30 to 85% by weight, of the total of the lower alcohol and/or the polyhydric alcohol having 1 to 5 carbon atoms.
The oriental cherry leaf extract can be obtained by subjecting oriental cherry leaves to extraction treatment with the above extraction solvent as they are or if necessary, drying, fine-cutting, crushing, squeezing, enzyme treatment, boiling or fermentation treatment. As the solvent extraction treatment, a commonly used extraction method of a plant extract can be used, and specific examples thereof include an immersion method such as cold immersion and warm immersion; a method of stirring under heating; or diafiltration, etc.
The extract obtained by the above-mentioned solvent extraction treatment may be used as it is in a liquid state, or may be used in the form of a concentrate or a dried product by subjecting to a treatment such as concentration or drying as necessary. The concentrate or dried product obtained after concentration or drying may be used after being washed with a non-soluble solvent and purified, or may be further dissolved or suspended in an appropriate solvent.
Further, as the extract of oriental cherry leaves, an extract which can be easily obtained commercially can also be used. For example, the extract of oriental cherry leaves may be "sakuryex B (サクラエキス B)" manufactured by ichimau PHARCOS corporation.
The content of the component (D) in the external composition of the present invention may be appropriately set according to the form of the preparation of the external composition, and is, for example, 0.00001 wt% or more, specifically, 0.00001 to 0.1 wt% in terms of the dry weight of the component (D). From the viewpoint of further exhibiting an excellent whitening effect, the content of the component (D) in the external composition of the present invention is preferably 0.00005 to 0.1% by weight, more preferably 0.0001 to 0.1% by weight, in terms of the dry weight of the component (D). The content of the component (D) is more preferable from the viewpoint of further exhibiting excellent whitening effect and the viewpoint of formulation stability, when the composition for external application of the present invention is a lotion, the amount of the component (D) is 0.0001 to 0.01% by weight, preferably 0.0002 to 0.0005% by weight, when the composition for external application of the present invention is an emulsion, the amount of the component (D) is 0.0001 to 0.1% by weight, preferably 0.0002 to 0.1% by weight, more preferably 0.0005 to 0.01% by weight, still more preferably 0.001 to 0.005% by weight, when the composition for external use of the present invention is a cream, the content is 0.0001 to 0.1% by weight, preferably 0.0002 to 0.1% by weight, more preferably 0.008 to 0.1% by weight, still more preferably 0.01 to 0.05% by weight, and still more preferably 0.01 to 0.02% by weight, in terms of the dry weight of the component (D).
In the composition for external use of the present invention, the ratio of the component (a) to the component (D) is determined by the above-mentioned contents, and from the viewpoint of exerting a more excellent whitening effect, the component (D) is 0.0005 parts by weight or more, specifically 0.0005 to 5 parts by weight in terms of dry weight, based on 100 parts by weight of the component (a). From the viewpoint of exerting a more excellent whitening effect, the content of the component (D) in the composition for external use of the present invention is preferably 0.0025 to 5 parts by weight, more preferably 0.005 to 5 parts by weight, in terms of the dry weight of the component (D), relative to 100 parts by weight of the component (a). The content of the component (D) is more preferably 0.005 to 0.5 parts by weight, preferably 0.01 to 0.025 parts by weight, in terms of the dry weight of the component (D), based on 100 parts by weight of the component (a), in the case of the external composition of the present invention, as a lotion, 0.005 to 5 parts by weight, preferably 0.01 to 5 parts by weight, more preferably 0.025 to 0.5 parts by weight, and even more preferably 0.05 to 0.25 parts by weight, based on 100 parts by weight of the component (a), in terms of the dry weight of the component (D), based on 100 parts by weight of the component (a), in the case of the external composition of the present invention, as a cream, 0.005 to 5 parts by weight, preferably 0.01 to 25 parts by weight, based on 100 parts by weight of the component (D), more preferably 0.4 to 5 parts by weight, still more preferably 0.5 to 2.5 parts by weight, and still more preferably 0.5 to 1 part by weight.
In the composition for external use of the present invention, the ratio of the component (B) to the component (D) is determined by the above-mentioned contents, and from the viewpoint of exerting a further excellent whitening effect, the component (D) is 0.08 parts by weight or more, specifically 0.08 to 8100 parts by weight in terms of dry weight, based on 100 parts by weight of the component (B). From the viewpoint of exerting a more excellent whitening effect, the content of the component (D) in the composition for external use of the present invention is preferably 4 to 8100 parts by weight, more preferably 8 to 8100 parts by weight, in terms of the dry weight of the component (D), relative to 100 parts by weight of the component (B). From the viewpoint of further excellent whitening effect and formulation stability, the content of the component (D) is more preferably 8 to 820 parts by weight, preferably 16 to 45 parts by weight, in terms of the dry weight of the component (D), relative to 100 parts by weight of the component (B) in the case of the lotion of the external composition of the present invention, 8 to 8150 parts by weight, preferably 16 to 8150 parts by weight, more preferably 40 to 850 parts by weight, and still more preferably 80 to 450 parts by weight, in terms of the dry weight of the component (D), relative to 100 parts by weight of the component (B) in the case of the emulsion of the external composition of the present invention, 8 to 8150 parts by weight, preferably 16 to 8150 parts by weight, more preferably 650 to 8150 parts by weight, still more preferably 810 to 4500 parts by weight, and still more preferably 810 to 1700 parts by weight.
The ratio of the component (C) to the component (D) in the composition for external use of the present invention is determined by the above-mentioned contents, and from the viewpoint of further exhibiting excellent whitening effect, the component (D) is 1.2 parts by weight or more, specifically 1.2 to 13000 parts by weight in terms of dry weight, based on 100 parts by weight of the component (C). From the viewpoint of further exhibiting an excellent whitening effect, the content of the component (D) in the external composition of the present invention is preferably 6.4 to 13000 parts by weight, more preferably 12 to 13000 parts by weight in terms of the dry weight of the component (D) per 100 parts by weight of the component (C). From the viewpoint of further excellent whitening effect and the viewpoint of formulation stability, the content of the component (D) is more preferably 12 to 1300 parts by weight, preferably 25 to 65 parts by weight in terms of the dry weight of the component (D) relative to 100 parts by weight of the component (B) in the case where the external composition of the present invention is a lotion, 12 to 13000 parts by weight, preferably 25 to 13000 parts by weight, more preferably 64 to 1300 parts by weight, and still more preferably 120 to 650 parts by weight in terms of the dry weight of the component (D) relative to 100 parts by weight of the component (B) in the case where the external composition of the present invention is an emulsion, 12 to 13000 parts by weight, preferably 25 to 13000 parts by weight, more preferably 1000 to 13000 parts by weight, still more preferably 1200 to 6500 parts by weight, and still more preferably 1200 to 2600 parts by weight.
Other ingredients
The composition for external use of the present invention may contain other pharmacological ingredients, as required, in addition to the above ingredients. Examples of such pharmacological components include melanin production inhibitors (arbutin, tranexamic acid, L-cysteine, glutathione, kojic acid, etc.), antihistamines (diphenhydramine hydrochloride, chlorpheniramine maleate, etc.), local anesthetics (lidocaine, dibucaine, methyl aminobenzoate, procaine, tetracaine, bupivacaine, mepivacaine, chloroprocaine, proparacaine, mepivacaine or salts thereof, oxocaine, oxicaine, oxypolyethoxydecane (oxyphenoxydecanoe), hyoscyamine, dibucaine powder (japanese manuscript: ペルカミンパーゼ), polyoxyethylene lauryl ether, etc.), anti-inflammatory agents (allantoin, glycyrrhizic acid, methyl glycyrrhizinate, stearyl glycyrrhizinate, dipotassium, monoammonium, glycyrrhetinic acid, pyridoxine glycyrrhetinate, stearyl alcohol, glycyrrhetinate, and the like), Glycyrrhetinic acid glyceride, glycyrrhetinic acid monoglucuronide, salicylic acid, methyl salicylate, glycol salicylate, indometacin, felbinac acid, diclofenac sodium, loxoprofen sodium, flufenamic acid butyl ester, and ibuprofen, suprofen, benzydac, suprofen, bufexamac, etc.), bactericides (benzalkonium chloride, dequalinium chloride, benzethonium chloride, cetylpyridinium chloride, chlorhexidine gluconate, isopropylmethylphenol, ammonia water, sulfadiazine, lactic acid, phenol, etc.), skin protectants (cotton gum, castor oil, etc.), blood circulation promoters (vanillylnonanamide, benzyl nicotinate, capsaicin, capsicum extract, etc.), algefacients (menthol, camphor, etc.), vitamins (vitamin A, B, D, E, etc.), mucopolysaccharides (sodium chondroitin sulfate, glucosamine, sodium hyaluronate, etc.), etc.
The composition for external use of the present invention may contain a base and additives as necessary in order to prepare a desired formulation. Such base and additive are not particularly limited as far as pharmaceutically acceptable, and examples thereof include water; aqueous bases such as lower monohydric alcohols (ethanol, isopropanol, etc.), polyhydric alcohols (propylene glycol, ethylene glycol, 1, 3-butylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, glycerin, etc.); oils (olive oil, safflower oil, soybean oil, tea oil, corn oil, rapeseed oil, sunflower seed oil, cottonseed oil, peanut oil, lard, squalane, fish oil, etc.), mineral oils (liquid paraffin, gelled hydrocarbon, vaseline, etc.), WAX-type waxes (beeswax, carnauba WAX, candelilla WAX, silodosin, rice bran WAX, microcrystalline WAX, etc.), ester oils (isopropyl myristate, isopropyl adipate, diethyl sebacate, isopropyl palmitate, cetyl ethylhexanoate, ethyl oleate, glyceryl tris (2-ethylhexanoate), glyceryl tris (caprylic/capric) ester, 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.), (olive oil, lard, etc.), (oil, castor oil, squalane, fish oil, etc.), (oil, lard, squalane, fish oil, etc.),) Oily base agents such as medium-chain fatty acid triglycerides, higher alcohols (e.g., stearyl alcohol, cetyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, cetyl alcohol, lanolin alcohol, cholesterol, dihydrocholesterol, phytosterol, lauryl alcohol, cetostearyl alcohol, linoleyl alcohol, octyldodecanol, hexyldecanol, isostearyl alcohol, etc.), cetyl ethylhexanoate, and silicone oils (e.g., dimethylpolysiloxane, cyclic silicone); nonionic surfactants (sorbitan fatty acid esters (sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, diglycerin sorbitan penta-2-ethylhexanoate, diglycerin sorbitan tetra-2-ethylhexanoate, etc.), glycerol polyglycerin fatty acid esters (glycerin monostearate, glycerin monoerucate, glycerin sesquioleate, glycerin monostearate, glycerin triethylhexanoate, glycerin α, α' -oleate pyroglutamate, glycerin monostearate, etc.), propylene glycol fatty acid esters (propylene glycol monostearate, etc.), hydrogenated castor oil derivatives, glycerol alkyl ethers, glycerin, 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-sorbitol monolaurate, POE-sorbitol monooleate, POE-sorbitol pentaoleate, POE-sorbitol monostearate, etc.); POE-glycerin fatty acid esters (POE-monooleate such as POE-glycerin monostearate, POE-glycerin monoisostearate and POE-glycerin triisostearate); POE-fatty acid esters (POE-distearate, POE-monooleate, ethylene 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-glyceryl ether, etc.); tetrapolye-tetrapod-ethylenediamine condensates (Tetronic, etc.); POE-castor oil hydrogenated castor oil derivatives (e.g., POE-castor oil, POE-hydrogenated castor oil monoisostearate, POE-hydrogenated castor oil triisostearate, POE-hydrogenated castor oil monopyroglutamic acid monoisostearic acid diester, POE-hydrogenated castor oil maleate (POE-hardened ヒマシ oil マレイン acid), etc.); alkanolamides (coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, etc.); sucrose fatty acid ester; alkyl ethoxy dimethyl amine oxide; triolein phosphoric acid, etc.), anionic surfactants (fatty acid soaps (sodium laurate, sodium palmitate, etc.); higher alkyl sulfate ester salts (sodium lauryl sulfate, potassium lauryl sulfate, etc.); alkyl ether sulfates (POE-triethanolamine lauryl sulfate, POE-sodium lauryl sulfate, etc.); n-acyl sarcosines (sodium lauroyl sarcosinate, etc.); higher fatty acid amide sulfonates (sodium N-myristoyl-N-methyltaurate, sodium coconut fatty acid methyltaurate, sodium lauryl methyltaurate, and the like); sulfosuccinates (sodium di-2-ethylhexyl sulfosuccinate, sodium monolauroyl monoethanolamide polyoxyethylene sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, etc.); alkyl benzene sulfonates (linear sodium dodecylbenzene sulfonate, linear triethanolamine dodecylbenzene sulfonate, linear dodecylbenzene sulfonic acid, etc.); higher fatty acid ester sulfate salts (sodium glycerin sulfate of hydrogenated coconut oil fatty acid, etc.); n-acyl glutamate (monosodium N-lauroyl glutamate, disodium N-stearoyl glutamate, monosodium N-myristoyl-L-glutamate, etc.); POE-alkyl ether carboxylic acids; POE-alkyl allyl ether carboxylate; an alpha-olefin sulfonate; lauroyl monoethanolamide sodium succinate; n-palmitoyl aspartic acid di (triethanolamine), etc.); aqueous thickeners (carboxyvinyl polymers, alkyl modified carboxyvinyl polymers, cellulose gums, xanthan gum, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, (ammonium acryloyldimethyltaurate/VP) copolymer, sodium polyacrylate, carrageenan, xanthan gum, sclerotium rolfsii gum, polystyrene sulfonate, karaya gum, pectin, etc.); porous powder (inorganic powder such as silica, talc, titanium oxide, mica, zinc oxide, kaolin, barium sulfate, bismuth oxychloride, aluminum hydroxide, aluminum silicate, anhydrous silicic acid, hydrated silicic acid, and montmorillonite; polymer powder such as polyester, polyethylene, polystyrene, methyl methacrylate resin, cellulose, nylon, copolymer of styrene and acrylic acid, polypropylene, and vinyl chloride); cooling agent (menthol, camphor, borneol, peppermint water, peppermint oil, etc.), antiseptic (phenoxyethanol, methylparaben, propylparaben, benzoic acid, sodium benzoate, sorbic acid, etc.), flavoring agent (citral, 1, 8-cineole, citronellal, farnesol, etc.), coloring agent (tar pigment (brown No. 201, blue No. 201, yellow No. 4, yellow No. 403, etc.), cacao pigment, chlorophyll, alumina, etc.), pH regulator (phosphoric acid, hydrochloric acid, citric acid, sodium citrate, succinic acid, tartaric acid, sodium hydroxide, potassium hydroxide, triethanolamine, triisopropanolamine, etc.), wetting agent (dl-pyrrolidone carboxylic acid sodium solution, D-sorbitol solution, polyethylene glycol, etc.), stabilizer (dibutylhydroxytoluene, butylhydroxyanisole, sodium edetate, sodium metaphosphate, etc.), stabilizer (dibutylhydroxytoluene, butylhydroxyanisole, etc.), L-arginine, L-aspartic acid, DL-alanine, glycine, sodium erythorbate, propyl gallate, sodium sulfite, sulfur dioxide, chlorogenic acid, catechin, rosemary extract, etc.), antioxidant, ultraviolet absorbent, chelating agent, binder, buffer, cosolvent, solubilizer, preservative, etc.
Form of preparation
The external composition is not particularly limited as long as it is in a form capable of being applied transdermally, and may be in any form of liquid, solid, semisolid (cream, gel, paste), and the like. The composition for external use of the present invention may be a non-emulsified preparation such as an aqueous preparation or an oily preparation, or an emulsified preparation such as an oil-in-water emulsified preparation or a water-in-oil emulsified preparation.
The formulation of the external composition is preferably in a liquid or cream form, and more preferably in a cream form, from the viewpoint of more effectively exerting the whitening effect.
The composition for external use may be in any form of preparations such as a pharmaceutical preparation for external use on the skin, a cosmetic preparation, and a skin cleanser, as long as it can be applied to the skin. Preferably, the skin care preparation is a pharmaceutical preparation for external use or a cosmetic preparation.
Specific examples of the formulation forms of the above-mentioned external composition include skin external pharmaceuticals such as liquid formulations (including lotions, sprays, aerosols and emulsions), water-soluble ointments, greasy ointments, creams, foams, gels, and patches; cosmetics such as ointment, cream, milky lotion, astringent, lotion, pack, gel, etc.; skin cleansers such as body wash, shampoo, hair conditioner, etc. Among these preparation forms, preferred are skin external drugs, more preferred are liquids and creams, still more preferred are lotions, emulsions and creams, still more preferred are emulsions and creams, and particularly preferred are creams. These preparations can be prepared by formulating the preparations with additives according to the preparation forms by a known method described in the sixteenth revised Japanese pharmacopoeia general guidelines and the like.
Use of
The external composition of the present invention can inhibit melanin production, and can prevent and improve skin spots, freckles, dark spots, liver spots, age spots, darkening due to physical irritation, and the like, and thus is suitable for use as a whitening external composition.
Examples
The present invention will be described more specifically with reference to the following examples, but the present invention is not limited to these examples.
The manufacturers and the like of the main components used in the following test examples and formulation examples are as follows.
L-ascorbic acid 2-glucoside: trade name "AA 2G" (original forest Co., Ltd.)
Magnolia obovata Thunb extract: under the trade name "PHARCOLEX HOONOKI B" (manufactured by ICHIMARU PHARCOS CORPORATION), liquid, and dryThe dry solid content of the extract was 0.175 wt%, and the extract was obtained by subjecting the bark (and Magnolia officinalis) of Cynanchum komarovii (Magnolia officinalis) to solvent extraction treatment with 1, 3-butanediol aqueous solution
Plum extract: trade name of "CREARGE" (product of ICHIMARU PHARCOS CORPORATION), liquid, and dried solid content of 7.78 wt%, and extract obtained by adding water and 1, 3-butanediol to pulp of plum (Prunus domestica Lindl. (Rosaceae)) decomposed with cellulolytic enzyme
Peony extract: trade name "PHARCOLEX BOTANNPI B (ファルコレックスボタンピ B)" (manufactured by ICHIMARU PHARCOS CORPORATION), liquid, dried solid content of 0.9 wt%, and extract obtained by subjecting the root bark of peony (Paeonia suffruticosa Andrews (Paeonia moutan Sims) (Paeoniacea)) to solvent extraction treatment with ethanol solution
Oriental cherry leaf extract: under the trade name "sakuralex B" (product of ICHIMARU PHARCOS), liquid, dry solid content 2 wt%, extract obtained by solvent extraction of leaves of rosa laevigata (Prunus yedonsis Matsum.) with an aqueous ethanol solution
Test example 1: evaluation of melanogenesis inhibitory Effect (in vitro)
vitro))
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.
MEL-300 skin model cups were placed in each well of a 6-well plate to which 0.9ml of maintenance medium (EPI-100LLMM) warmed to 37 ℃ was added, and placed in an incubator (37 ℃, 5% CO)2) And standing for 1 hour. Next, 50. mu.l of a composition for external use (pH6.5) having a composition shown in Table 1 was placed in each cup of the skin model, and the mixture was cultured in an incubator (37 ℃ C., 5% CO)2) Medium for 24 hours. Then, the cells were irradiated with ultraviolet (UV-B) light at a rate of 0.5mW for 12 seconds every 1 time, and further cultured for 24 hours. In addition, UVB lamp (TOSHIBA Lightin) is used for ultraviolet irradiationg&Fluorescent lamp for Toshiba health line manufactured by Technology Co., Ltd.) and UV detector (UV-1 manufactured by TOPCON Co., Ltd.). Then, the medium was changed and further cultured for 24 hours. In addition, 50. mu.l of a predetermined sample solution was added to the skin model cup every time the medium was changed. Further, the ultraviolet irradiation and the medium replacement were repeated 4 times under the same conditions, thereby carrying out a total of 5 times of ultraviolet irradiation (total ultraviolet irradiation amount 30 mJ/cm)2) And 5 total medium changes. Then, the cell viability and the amount of melanin production were measured by the following methods. In addition, as a control, an aqueous solution containing 0.5 wt% of 1, 3-butanediol was used as a sample solution, and the test was performed under the same conditions as described above.
< determination of cell Activity >
Cell viability was determined by the MTT assay. Specifically, 0.75ml of MTT test agent and 8.25ml of maintenance medium (EPI-100LLMM) were mixed and added to the mixture in an amount of 300. mu.l per 1 well. The skin model cup was transferred to a medium to which the above-prepared MTT was added, and accurately cultured in an incubator for 3 hours. The bottom surface of the tissue was then gently washed with PBS wash and transferred to a new plate. 0.04N HCl acid isopropyl alcohol (1 ml) was added to each inside of the skin model cups, cover slips were applied to the plates in a non-evaporative manner to block light, and blue formazan (blue formazan) was extracted overnight in an incubator. After extraction, isopropanol was mixed well and 200. mu.l of it was transferred to a 96-well plate. The optical concentrations at 570nm and 620nm were measured by a microplate reader, and the difference was taken as the cell activity.
< measurement of amount of melanin production >
After the MEL-300 skin model cup was washed with PBS, the cell tissue was peeled off with a scalpel and recovered. The resulting cell tissue was immersed in PBS, disrupted and centrifuged (2000rpm, 10 minutes). Then, the supernatant was removed, and a mixed solution of ethanol and dimethyl ether (ethanol: dimethyl ether: 3: 1 (volume ratio)) was further added thereto, followed by stirring and centrifugation (2000rpm, 10 minutes). Next, the supernatant was removed and dried. To the dried product, a 1N aqueous solution of sodium hydroxide (containing 10 wt% DMSO) was added, and the mixture was treated in a water bath at 90 ℃ for 20 minutes to be melted by heating. Then, the melted solution was gently stirred with a vortex shaker and cooled to room temperature, and then absorbance at 405nm was measured to determine the amount of melanin production.
The melanin production amount per cell was determined by dividing the melanin production amount by the cell survival rate. The ratio of the amount of melanin production per 1 cell (melanin production ratio) when each sample solution was added was calculated, assuming that the amount of melanin production per 1 cell in reference example 1 (negative control; NC) was 100.
The obtained results are shown in table 1. From the results, it was found that the melanin production-inhibiting effect of the external compositions (examples 1 and 2) containing the oriental cherry leaf extract in addition to the ascorbic acid 2-glucoside, the magnolia japonica extract and the plum extract was significantly improved as compared with the melanin production-inhibiting effect of the external composition (comparative example 1) containing the ascorbic acid 2-glucoside, the magnolia japonica extract and the plum extract. The effect of improving the melanin production-inhibiting effect was excellent to a level close to that of arbutin (reference example 2: positive control; PC) known for its high whitening effect in the case of the external composition (example 1) containing only 0.002 wt% of cherry leaf extract on a dry weight basis, and excellent to a level exceeding that of arbutin in the case of the external composition (example 2) containing 0.01 wt% of cherry leaf extract on a dry weight basis. On the other hand, in the case of the external compositions (comparative examples 2 and 3) containing a peony extract, which is known to have an anti-inflammatory effect similar to the cherry leaf extract, in addition to ascorbic acid 2-glucoside, the magnolia japonica extract and the plum extract, no enhancement of the melanin production inhibitory effect was observed at all.
[ Table 1]
In the table, the unit of the numerical value indicating the content of each component is% by weight.
The parenthesized numerical values are in terms of dry weight, and the unit is wt%.
Test example 2: evaluation of Melanin production inhibitory Effect (in vivo)
A cream of the composition described in table 2 was prepared. The cream prepared was applied to age spots on the cheeks of 17 women for 6 weeks 2 times a day for 1 day. The melanin values of age spots before and after application were determined using a Mexameter (Mexameter MX 18).
[ Table 2]
In the table, the unit of the numerical value indicating the content of each component is% by weight.
The parenthesized numerical values are in terms of dry weight, and the unit is wt%.
The results are shown in figure 1 (paired t-test, p < 0.001). As shown in fig. 1, the change in melanin value before (initial) and after (6 weeks after) coating was: and is significantly reduced.
Formulation examples
Creams, emulsions and lotions were prepared with the formulations shown in tables 3 to 5. In any of the formulations, the melanin production-inhibiting effect was improved.
[ Table 3]
Cream formulation
In the table, the unit of the numerical value indicating the content of each component is% by weight.
The parenthesized numerical values are in terms of dry weight, and the unit is wt%.
[ Table 4]
Emulsion agent
In the table, the unit of the numerical value indicating the content of each component is% by weight.
The parenthesized numerical values are in terms of dry weight, and the unit is wt%.
[ Table 5]
Lotion formulation
In the table, the unit of the numerical value indicating the content of each component is% by weight.
The parenthesized numerical values are in terms of dry weight, and the unit is wt%.
Claims (6)
1. A composition for external use characterized by containing (A) ascorbic acid and/or a derivative thereof, (B) an extract of a plant belonging to the genus Magnoliaceae, and (C) an extract of plum and (D) an extract of cherry leaf.
2. The composition for external use according to claim 1, wherein the component (B) is an extract of Cynanchum komarovii.
3. The composition for external use according to claim 1 or 2, wherein the component (a) is ascorbic acid 2-glucoside.
4. The composition for external use according to any one of claims 1 to 3, wherein the content of the component (D) is 0.00001 to 0.1% by weight in terms of dry weight.
5. The composition for external use according to any one of claims 1 to 4, wherein the content of the component (D) is 0.008 to 0.1% by weight in terms of dry weight.
6. The external composition according to any one of claims 1 to 5, wherein the external composition is used for whitening.
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PCT/JP2020/023102 WO2020255865A1 (en) | 2019-06-20 | 2020-06-11 | Topical composition |
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WO2017057419A1 (en) * | 2015-09-30 | 2017-04-06 | 小林製薬株式会社 | External composition |
CN108785117A (en) * | 2018-07-25 | 2018-11-13 | 广州依露美化妆品有限公司 | A kind of fair-skinned bright white Pure natural mask |
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WO2017057419A1 (en) * | 2015-09-30 | 2017-04-06 | 小林製薬株式会社 | External composition |
CN108785117A (en) * | 2018-07-25 | 2018-11-13 | 广州依露美化妆品有限公司 | A kind of fair-skinned bright white Pure natural mask |
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