WO2024090247A1 - Beauty composition, beauty method, and agent for promoting skin permeability of alkoxy salicylic acid or salt thereof - Google Patents

Beauty composition, beauty method, and agent for promoting skin permeability of alkoxy salicylic acid or salt thereof Download PDF

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Publication number
WO2024090247A1
WO2024090247A1 PCT/JP2023/037225 JP2023037225W WO2024090247A1 WO 2024090247 A1 WO2024090247 A1 WO 2024090247A1 JP 2023037225 W JP2023037225 W JP 2023037225W WO 2024090247 A1 WO2024090247 A1 WO 2024090247A1
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mass
salt
cosmetic composition
dicarboxylate
acid
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PCT/JP2023/037225
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French (fr)
Japanese (ja)
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隆史 岡
裕子 真鍋
沙織 家谷
祐仁 伊東
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株式会社 資生堂
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin

Definitions

  • the present invention relates to a cosmetic composition, a cosmetic method, and a transdermal penetration enhancer for alkoxysalicylic acid or its salt. More specifically, the present invention relates to a cosmetic composition and a cosmetic method containing alkoxysalicylic acid or its salt, and to the use of bisethoxydiglycol cyclohexane-1,4-dicarboxylate as a transdermal penetration enhancer for alkoxysalicylic acid or its salt.
  • Alkoxysalicylic acid or its salt is known as an active ingredient with excellent whitening effects for improving or preventing abnormal deposition of melanin in the skin (for example, Patent Document 1: JP-A-6-040886).
  • Patent Document 2 JP Patent Publication No. 2006-265140 discloses a skin whitening agent that is characterized by comprising one or more selected from tranexamic acid and its derivatives, alkoxysalicylic acid and its salts, and one or more selected from ⁇ -lipoic acid and its derivatives and its salts.
  • Neosolue TM -Aquilio (chemical name: bisethoxydiglycol cyclohexane-1,4-dicarboxylate) is known as an ester oil having an effect of promoting the penetration of vitamin C derivatives, tranexamic acid, and the like into the epidermis (for example, Non-Patent Document 1).
  • the present invention aims to improve the above situation, and its purpose is to provide a cosmetic composition that improves the skin permeability of alkoxysalicylic acid or its salt.
  • the present invention also provides a cosmetic method that improves the skin permeability of alkoxysalicylic acid or its salt.
  • the present invention further provides the use of bisethoxydiglycol cyclohexane-1,4-dicarboxylate as a percutaneous penetration enhancer for an alkoxysalicylic acid or a salt thereof.
  • the present invention which achieves the above objective, is as follows:
  • ⁇ Aspect 1> An alkoxysalicylic acid represented by the following formula (I) or a salt thereof, (wherein R represents an alkyl group having 1 to 6 carbon atoms) cyclohexane-1,4-dicarboxylate bisethoxydiglycol,
  • a cosmetic composition comprising: ⁇ Aspect 2> The cosmetic composition according to Aspect 1, wherein the alkoxysalicylic acid or a salt thereof is potassium 4-methoxysalicylate.
  • Aspect 3 A cosmetic composition according to aspect 1 or 2, wherein the amount of the bisethoxydiglycol cyclohexane-1,4-dicarboxylate is 20 to 1500 parts by mass per 100 parts by mass of the alkoxysalicylic acid or its salt.
  • ⁇ Aspect 4> A cosmetic composition according to any one of Aspects 1 to 3, wherein the content of the alkoxysalicylic acid or a salt thereof is 0.001 to 5.0% by mass.
  • ⁇ Aspect 5> The cosmetic composition according to any one of Aspects 1 to 4, wherein the bisethoxydiglycol cyclohexane-1,4-dicarboxylate is present in an amount of 0.001 to 10% by mass.
  • Aspect 7 A cosmetic composition according to any one of the preceding aspects, which is for topical application.
  • ⁇ Aspect 8> A cosmetic method comprising applying the cosmetic composition according to any one of Aspects 1 to 7 to skin.
  • the present invention provides a cosmetic composition that improves the skin permeability of alkoxysalicylic acid or its salt.
  • the present invention also provides a cosmetic method that improves the skin permeability of alkoxysalicylic acid or its salt.
  • the present invention also provides the use of bisethoxydiglycol cyclohexane-1,4-dicarboxylate as a percutaneous penetration enhancer for alkoxysalicylic acid or a salt thereof.
  • FIG. 1 is a graph showing the results of the cumulative permeation amount of potassium 4-methoxysalicylate in Example 1 and Comparative Example 1.
  • FIG. 2 is a graph showing the results of the cumulative permeation amount of nicotinamide in Comparative Example 2 and Comparative Example 2-1.
  • FIG. 3 is a graph showing the results of the cumulative permeation amount of the cosmetic ingredient in Examples 2 to 4.
  • Cosmetic Composition comprises: An alkoxysalicylic acid represented by the following formula (I) or a salt thereof, (wherein R represents an alkyl group having 1 to 6 carbon atoms) cyclohexane-1,4-dicarboxylate bisethoxydiglycol, A cosmetic composition comprising:
  • Bisethoxydiglycol cyclohexane-1,4-dicarboxylate has the following structure and is commercially available, for example, under the trade name Neosolue TM -Aquilio.
  • cyclohexane-1,4-dicarboxylate bisethoxydiglycol has been known as an ester oil that promotes the penetration of vitamin C derivatives, tranexamic acid, and other substances into the epidermis.
  • bis-ethoxydiglycol cyclohexane-1,4-dicarboxylate has a significantly high transdermal penetration enhancing effect for the alkoxysalicylic acid or a salt thereof represented by the above formula (I).
  • the cosmetic composition of the present invention contains an alkoxysalicylic acid represented by the following formula (I) or a salt thereof.
  • This expression means that the cosmetic composition of the present invention may contain an alkoxysalicylic acid represented by the following formula (I), a salt of an alkoxysalicylic acid represented by the following formula (I), or an alkoxysalicylic acid represented by the following formula (I) and a salt of an alkoxysalicylic acid represented by the following formula (I). (wherein R represents an alkyl group having 1 to 6 carbon atoms)
  • the alkoxy group (OR) may be a salicylic acid in which a hydrogen atom at any of the 3rd, 4th, or 5th position is replaced with an alkoxy group.
  • R represents an alkyl group having 1 to 6 carbon atoms.
  • the alkyl group is not particularly limited, and may be a branched alkyl group or a straight-chain alkyl group.
  • R may be, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, or a hexyl group.
  • R is preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, or an isobutyl group, and more preferably a methyl group or an ethyl group.
  • alkoxysalicylic acid compounds represented by formula (I) include, but are not limited to, 3-methoxysalicylic acid, 3-ethoxysalicylic acid, 4-methoxysalicylic acid, 4-ethoxysalicylic acid, 4-propoxysalicylic acid, 4-isopropoxysalicylic acid, 4-butoxysalicylic acid, 5-methoxysalicylic acid, 5-ethoxysalicylic acid, and 5-propoxysalicylic acid.
  • the salt of alkoxysalicylic acid represented by formula (I) is not particularly limited, and examples thereof include alkali metal salts or alkaline earth metal salts such as sodium salt, potassium salt, and calcium salt, ammonium salt, and amino acid salt.
  • the salt of alkoxysalicylic acid is preferably, for example, sodium salt or potassium salt, and more preferably potassium salt.
  • Alkoxysalicylic acid can be converted into its salt form by known methods.
  • the cosmetic composition of the present invention contains a salt of alkoxysalicylic acid
  • the salt may be directly added to the composition, or the free acid and base may be added to convert the salt into the composition system.
  • the content of the alkoxysalicylic acid or its salt represented by formula (I) is not particularly limited, and may be, for example, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, or 1.0% by mass or more, and may be 5.0% by mass or less, 4.5% by mass or less, 4.0% by mass or less, 3.5% by mass or less, 3.0% by mass or less, 2.5% by mass or less, 2.0% by mass or less, 1.5% by mass or less, 1.0% by mass or less, 0.5% by mass or less, or 0.1% by mass or less.
  • the content of the alkoxysalicylic acid or its salt represented by formula (I) in the cosmetic composition is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, even more preferably 0.5% by mass or more, and particularly preferably 1.0% by mass or more. Furthermore, the content of the alkoxysalicylic acid represented by formula (I) or its salt in the cosmetic composition may be, for example, 3.0% by mass or less.
  • the expression "content of alkoxysalicylic acid represented by formula (I) or its salt” means the total content when the cosmetic composition of the present invention contains both alkoxysalicylic acid represented by formula (I) and its salt.
  • the amount of cyclohexane-1,4-dicarboxylate bisethoxydiglycol per 100 parts by mass of the alkoxysalicylic acid or salt thereof represented by the above-mentioned formula (I) may be, for example, 20 parts by mass or more, 30 parts by mass or more, 40 parts by mass or more, 50 parts by mass or more, 60 parts by mass or more, 70 parts by mass or more, 80 parts by mass or more, 90 parts by mass or more, 100 parts by mass or more, 120 parts by mass or more, 150 parts by mass or more, 180 parts by mass or more, 200 parts by mass or more, 250 parts by mass or more, or 300 parts by mass or more, and may be 1500 parts by mass or less, 1200 parts by mass or less, 1000 parts by mass or less, 800 parts by mass or less, 500 parts by mass or less, 300 parts by mass or less, 200 parts by mass or less, 100 parts by mass or less, 80 parts by mass or less, 50 parts by mass or less, or
  • the content of bisethoxydiglycol cyclohexane-1,4-dicarboxylate may be, for example, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, or 1.0% by mass or more, and may be 10% by mass or less, 9.5% by mass or less, 9.0% by mass or less, 8.5% by mass or less, 8.0% by mass or less, 7.5% by mass or less, 7.0% by mass or less, 6.5% by mass or less, 6.0% by mass or less, 5.0% by mass or less, 3.0% by mass or less, or 1.0% by mass or less.
  • the content of bisethoxydiglycol cyclohexane-1,4-dicarboxylate in the cosmetic composition of the present invention is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, even more preferably 1.0% by mass or more, and particularly preferably 3.0% by mass or more.
  • the content of bisethoxydiglycol cyclohexane-1,4-dicarboxylate in the cosmetic composition may be, for example, 5.0% by mass or less.
  • the cosmetic composition of the present invention may further contain other ingredients in addition to the above-mentioned ingredients, so long as the effects of the present invention are not impaired. More specifically, for example, the cosmetic composition of the present invention may further contain a base acceptable as a cosmetic.
  • the cosmetic base is not particularly limited, and examples include aqueous components, oily components, and surfactants.
  • the type and amount of these bases can be appropriately determined according to the desired form of the cosmetic.
  • the cosmetic composition of the present invention further contains a cosmetically acceptable base
  • the content thereof is not particularly limited and may be, for example, 5.0 to 99.5% by mass, 20 to 80% by mass, or 30 to 75% by mass relative to the total amount of the composition (100% by mass).
  • the cosmetic composition of the present invention may further contain other optional components in addition to those described above, so long as the effect of the present invention is not impaired.
  • other optional components include, but are not limited to, skin whitening agents other than those described above, sunscreens, antioxidants, salts, moisturizers, vitamins, water-soluble agents applicable to medicines, quasi-drugs, or cosmetics, thickeners, pigments, dyes, pigments, binders, biological additives, buffers, colorants, polymers, astringents, fragrances, opacifiers, conditioners, exfoliants, pH adjusters, preservatives, natural extracts, skin sensates, skin smoothing agents, and skin healing agents.
  • the content of each of these other optional components when they are included is not particularly limited, and may be any amount acceptable for cosmetics.
  • the cosmetic composition of the present invention refers to an external preparation that is applied to the skin for cosmetic purposes (e.g., whitening).
  • the cosmetic composition of the present invention may be for topical application to the skin.
  • examples of the product forms of the cosmetic composition of the present invention include, but are not limited to, ointments, lotions, milky lotions, creams, gels, foundations, masks, mousses, etc.
  • the cosmetic method of the present invention comprises applying the above-mentioned cosmetic composition of the present invention to the skin.
  • bis(ethoxydiglycol)cyclohexane-1,4-dicarboxylate can significantly improve the skin permeability of the above-mentioned alkoxysalicylic acid or a salt thereof.
  • the present invention therefore provides the use of bisethoxydiglycol cyclohexane-1,4-dicarboxylate as a percutaneous penetration enhancer for the above-mentioned alkoxysalicylic acid or its salt.
  • Example 1 and Comparative Examples 1, 2, and 2-1
  • Each of the cosmetic compositions of the Examples and Comparative Examples was prepared based on the formulation in Table 1.
  • a "cumulative permeation test" of each cosmetic ingredient into the skin was carried out.
  • a Franz cell having an effective permeation area of 1.77 cm2 was used as the Franz cell.
  • the pseudo-skin membrane which is a permeable membrane to be placed in the Franz cell
  • a Strat-M (trademark) membrane Merck Millipore
  • the pseudo-skin membrane was soaked in physiological phosphate buffer (PBS) before being set in the Franz cell to be fully hydrated.
  • PBS physiological phosphate buffer
  • the pseudo-skin membrane was firmly fixed between the receiver cell and the donor cell using a cell clamp so that air would not enter.
  • the surface temperature of the pseudo-skin membrane was maintained at about 32°C, which corresponds to the surface temperature of the skin, using a temperature regulator, and the PBS in the receiver cell was acclimated for more than 1 hour while being stirred with a stirrer bar.
  • the application of each composition to the pseudo-skin membrane was carried out by limited open application assuming practical use. Each composition was uniformly applied to the simulated skin membrane for 30 seconds. After a given time had elapsed since application (0, 1, 2, 4, 8, and 24 hours since application), the extract was collected from the receiver cell. The amount of drug in the collected extract was quantified using an HPLC system equipped with an LC-MS detector, and the cumulative permeation amount was calculated.
  • Figure 1 shows the results of the cumulative permeation amount of potassium 4-methoxysalicylate in Example 1 and Comparative Example 1.
  • Figure 2 shows the results of the cumulative permeation amount of nicotinamide in Comparative Example 2 and Comparative Example 2-1.
  • Example 1 which contains bisethoxydiglycol cyclohexane-1,4-dicarboxylate
  • the cumulative permeation amount of potassium 4-methoxysalicylate was significantly increased compared to Comparative Example 1, which did not contain bisethoxydiglycol cyclohexane-1,4-dicarboxylate.
  • the cumulative permeation amount of potassium 4-methoxysalicylate in Example 1 increased to about 42 times that of Comparative Example 1 after 4 hours, increased to about 15 times that of Comparative Example 1 after 8 hours, and further increased significantly to about 9 times that of Comparative Example 1 at 24 hours.
  • Examples 2 to 4 Cosmetic compositions (cream-like) of Examples 2 to 4 were prepared based on the formulations in Table 2. For each of the prepared compositions, a "cumulative permeation test" of each cosmetic ingredient into the skin was carried out in the same manner as in Example 1 described above.
  • Figure 3 shows the cumulative permeation results of the beauty ingredient (potassium 4-methoxysalicylate) in Examples 2 to 4.
  • each formulation example is based on a conventional method. For example, if the composition contains only water-soluble components, it is prepared by uniformly dissolving the water-soluble components in ion-exchanged water. If the composition is an emulsion, it is prepared by dissolving the water-soluble components in ion-exchanged water and then adding the oily components. If the composition is an emulsion containing inorganic particles, it is prepared by dissolving the water-soluble components in ion-exchanged water, uniformly dispersing the inorganic particles, and then adding the oily components.

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Abstract

Provided is a beauty composition in which skin permeability of an alkoxy salicylic acid or a salt thereof has been improved.　The beauty composition contains: an alkoxy salicylic acid represented by formula (I) or a salt thereof (in the formula, R is a C1-6 alkyl group); and bisethoxydiglycol cyclohexane-1,4-dicarboxylate.

Description

美容組成物、美容方法、及びアルコキシサリチル酸又はその塩の経皮浸透促進剤Cosmetic composition, cosmetic method, and percutaneous penetration enhancer for alkoxysalicylic acid or its salt
　本発明は、美容組成物、美容方法、及びアルコキシサリチル酸又はその塩の経皮浸透促進剤に関する。より具体的には、本発明は、アルコキシサリチル酸又はその塩を含む、美容組成物及び美容方法、並びにアルコキシサリチル酸又はその塩の、経皮浸透促進剤としてのシクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールの使用に関する。 The present invention relates to a cosmetic composition, a cosmetic method, and a transdermal penetration enhancer for alkoxysalicylic acid or its salt. More specifically, the present invention relates to a cosmetic composition and a cosmetic method containing alkoxysalicylic acid or its salt, and to the use of bisethoxydiglycol cyclohexane-1,4-dicarboxylate as a transdermal penetration enhancer for alkoxysalicylic acid or its salt.
　アルコキシサリチル酸又はその塩は、皮膚に対してメラニンの異常沈着を改善又は防止するための、優れた美白効果を有する活性成分として知られている（例えば、特許文献１：特開平６－０４０８８６号公報）。 Alkoxysalicylic acid or its salt is known as an active ingredient with excellent whitening effects for improving or preventing abnormal deposition of melanin in the skin (for example, Patent Document 1: JP-A-6-040886).
　アルコキシサリチル酸又はその塩を含む美容組成物に関して、様々な研究がなされている。 Various studies have been conducted on cosmetic compositions containing alkoxysalicylic acid or its salts.
　例えば、特許文献２（特開２００６－２６５１４０号公報）では、トラネキサム酸およびその誘導体、アルコキシサリチル酸およびその塩から選択される一種または二種以上と、α-リポ酸およびその誘導体およびその塩から選択される一種または二種以上とからなることを特徴とする美白剤が開示されている。 For example, Patent Document 2 (JP Patent Publication No. 2006-265140) discloses a skin whitening agent that is characterized by comprising one or more selected from tranexamic acid and its derivatives, alkoxysalicylic acid and its salts, and one or more selected from α-lipoic acid and its derivatives and its salts.
　なお、ＮｅｏｓｏｌｕｅＴＭ－Ａｑｕｌｉｏ（化学名称：シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコール）は、ビタミンＣ誘導体やトラネキサム酸等の表皮への浸透促進効果を有するエステル油剤として知られている（例えば、非特許文献１）。 Neosolue ™ -Aquilio (chemical name: bisethoxydiglycol cyclohexane-1,4-dicarboxylate) is known as an ester oil having an effect of promoting the penetration of vitamin C derivatives, tranexamic acid, and the like into the epidermis (for example, Non-Patent Document 1).
特開平６－０４０８８６号公報Japanese Patent Application Laid-Open No. 6-040886 特開２００６－２６５１４０号公報JP 2006-265140 A
　美白効果を更に高めるために、アルコキシサリチル酸又はその塩の肌への浸透性は、依然として、改善する余地がある。 There is still room for improvement in the skin permeability of alkoxysalicylic acid or its salts to further enhance the whitening effect.
　本発明は、上記の事情を改善しようとするものであり、その目的は、アルコキシサリチル酸又はその塩の肌への浸透性を向上させた美容組成物を提供することである。 The present invention aims to improve the above situation, and its purpose is to provide a cosmetic composition that improves the skin permeability of alkoxysalicylic acid or its salt.
　本発明はまた、アルコキシサリチル酸又はその塩の肌への浸透性を向上させた美容方法を提供する。 The present invention also provides a cosmetic method that improves the skin permeability of alkoxysalicylic acid or its salt.
　本発明は更に、アルコキシサリチル酸又はその塩の、経皮浸透促進剤としてのシクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールの使用を提供する。 The present invention further provides the use of bisethoxydiglycol cyclohexane-1,4-dicarboxylate as a percutaneous penetration enhancer for an alkoxysalicylic acid or a salt thereof.
　上記の目的を達成する本発明は、以下のとおりである。 The present invention, which achieves the above objective, is as follows:
　〈態様１〉
　下記式（Ｉ）で表されるアルコキシサリチル酸又はその塩と、
（式中、Ｒは炭素数１～６のアルキル基を示す）
　シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールと、
を含む、美容組成物。
　〈態様２〉
　前記アルコキシサリチル酸又はその塩が、４－メトキシサリチル酸カリウムである、態様１に記載の美容組成物。
　〈態様３〉
　１００質量部の前記アルコキシサリチル酸又はその塩に対して、前記シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールが、２０～１５００質量部である、態様１又は２に記載の美容組成物。
　〈態様４〉
　前記アルコキシサリチル酸又はその塩の含有量が、０．００１～５．０質量％である、態様１～３のいずれか一項に記載の美容組成物。
　〈態様５〉
　前記シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールが、０．００１～１０質量％である、態様１～４のいずれか一項に記載の美容組成物。
　〈態様６〉
　化粧品として許容される基剤を更に含む、態様１～５のいずれか一項に記載の美容組成物。
　〈態様７〉
　局所塗布用である、態様１～６のいずれか一項に記載の美容組成物。
　〈態様８〉
　態様１～７のいずれか一項に記載の美容組成物を皮膚に塗布することを含む、美容方法。
　〈態様９〉
　下記式（Ｉ）で表されるアルコキシサリチル酸又はその塩の、経皮浸透促進剤としてのシクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールの使用：
（式中、Ｒは炭素数１～６のアルキル基を示す） <Aspect 1>
An alkoxysalicylic acid represented by the following formula (I) or a salt thereof,
(wherein R represents an alkyl group having 1 to 6 carbon atoms)
cyclohexane-1,4-dicarboxylate bisethoxydiglycol,
A cosmetic composition comprising:
<Aspect 2>
The cosmetic composition according to Aspect 1, wherein the alkoxysalicylic acid or a salt thereof is potassium 4-methoxysalicylate.
Aspect 3
A cosmetic composition according to aspect 1 or 2, wherein the amount of the bisethoxydiglycol cyclohexane-1,4-dicarboxylate is 20 to 1500 parts by mass per 100 parts by mass of the alkoxysalicylic acid or its salt.
<Aspect 4>
A cosmetic composition according to any one of Aspects 1 to 3, wherein the content of the alkoxysalicylic acid or a salt thereof is 0.001 to 5.0% by mass.
<Aspect 5>
The cosmetic composition according to any one of Aspects 1 to 4, wherein the bisethoxydiglycol cyclohexane-1,4-dicarboxylate is present in an amount of 0.001 to 10% by mass.
<Aspect 6>
A cosmetic composition according to any one of the preceding aspects, further comprising a cosmetically acceptable base.
Aspect 7
A cosmetic composition according to any one of the preceding aspects, which is for topical application.
<Aspect 8>
A cosmetic method comprising applying the cosmetic composition according to any one of Aspects 1 to 7 to skin.
<Aspect 9>
Use of bisethoxydiglycol cyclohexane-1,4-dicarboxylate as a percutaneous penetration enhancer for an alkoxysalicylic acid or a salt thereof represented by the following formula (I):
(wherein R represents an alkyl group having 1 to 6 carbon atoms)
　本発明によれば、アルコキシサリチル酸又はその塩の肌への浸透性を向上させた美容組成物を提供することができる。 The present invention provides a cosmetic composition that improves the skin permeability of alkoxysalicylic acid or its salt.
　また、本発明によれば、アルコキシサリチル酸又はその塩の肌への浸透性を向上させた美容方法を提供することもできる。 The present invention also provides a cosmetic method that improves the skin permeability of alkoxysalicylic acid or its salt.
　更に、本発明によれば、アルコキシサリチル酸又はその塩の、経皮浸透促進剤としてのシクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールの使用を提供することもできる。 Furthermore, the present invention also provides the use of bisethoxydiglycol cyclohexane-1,4-dicarboxylate as a percutaneous penetration enhancer for alkoxysalicylic acid or a salt thereof.
図１は、実施例１及び比較例１の４－メトキシサリチル酸カリウムの累積透過量の結果を示す図である。FIG. 1 is a graph showing the results of the cumulative permeation amount of potassium 4-methoxysalicylate in Example 1 and Comparative Example 1. 図２は、比較例２及び比較例２－１のニコチン酸アミドの累積透過量の結果を示す図である。FIG. 2 is a graph showing the results of the cumulative permeation amount of nicotinamide in Comparative Example 2 and Comparative Example 2-1. 図３は、実施例２～４の美容成分の累積透過量の結果を示す図である。FIG. 3 is a graph showing the results of the cumulative permeation amount of the cosmetic ingredient in Examples 2 to 4.
　以下、本発明の実施の形態について詳述する。なお、本発明は、以下の実施の形態に限定されるものではなく、発明の本旨の範囲内で種々変形して実施できる。 The following describes in detail the embodiments of the present invention. Note that the present invention is not limited to the following embodiments, and can be modified in various ways within the scope of the invention.
　《美容組成物》
　本発明の美容組成物は、
　下記式（Ｉ）で表されるアルコキシサリチル酸又はその塩と、
（式中、Ｒは炭素数１～６のアルキル基を示す）
　シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールと、
を含む、美容組成物
である。 Cosmetic Composition
The cosmetic composition of the present invention comprises:
An alkoxysalicylic acid represented by the following formula (I) or a salt thereof,
(wherein R represents an alkyl group having 1 to 6 carbon atoms)
cyclohexane-1,4-dicarboxylate bisethoxydiglycol,
A cosmetic composition comprising:
　シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールは、以下の構造を有しており、例えば商品名ＮｅｏｓｏｌｕｅＴＭ－Ａｑｕｌｉｏで市販されている。
 Bisethoxydiglycol cyclohexane-1,4-dicarboxylate has the following structure and is commercially available, for example, under the trade name Neosolue ™ -Aquilio.
　これまでに、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールは、ビタミンＣ誘導体やトラネキサム酸等の表皮への浸透促進効果を有するエステル油剤として知られている。 　To date, cyclohexane-1,4-dicarboxylate bisethoxydiglycol has been known as an ester oil that promotes the penetration of vitamin C derivatives, tranexamic acid, and other substances into the epidermis.
　これに対して、本発明者らの鋭意研究により、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールと、上述した式（Ｉ）で表されるアルコキシサリチル酸又はその塩とを併用すると、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールは、上述した式（Ｉ）で表されるアルコキシサリチル酸又はその塩の、経皮浸透促進効果が著しく高いことが分かった。言い換えれば、本発明者らの鋭意研究により、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールは、上述した式（Ｉ）で表されるアルコキシサリチル酸又はその塩の経皮浸透促進剤としての新たな用途が見出されて、そしてこれによって、本発明の美容組成物、本発明の美容方法の完成に至った。 In response to this, the inventors' intensive research has revealed that when bis-ethoxydiglycol cyclohexane-1,4-dicarboxylate is used in combination with an alkoxysalicylic acid or a salt thereof represented by the above formula (I), bis-ethoxydiglycol cyclohexane-1,4-dicarboxylate has a significantly high transdermal penetration enhancing effect for the alkoxysalicylic acid or a salt thereof represented by the above formula (I). In other words, the inventors' intensive research has found a new use for bis-ethoxydiglycol cyclohexane-1,4-dicarboxylate as a transdermal penetration enhancer for the alkoxysalicylic acid or a salt thereof represented by the above formula (I), which has led to the completion of the cosmetic composition and cosmetic method of the present invention.
　本発明の美容組成物は、下記式（Ｉ）で表されるアルコキシサリチル酸又はその塩を含む。なお、この表現は、本発明の美容組成物は、下記式（Ｉ）で表されるアルコキシサリチル酸、下記式（Ｉ）で表されるアルコキシサリチル酸の塩、又は下記式（Ｉ）で表されるアルコキシサリチル酸及び下記式（Ｉ）で表されるアルコキシサリチル酸の塩を含んでよいことを意味する。
（式中、Ｒは炭素数１～６のアルキル基を示す） The cosmetic composition of the present invention contains an alkoxysalicylic acid represented by the following formula (I) or a salt thereof. This expression means that the cosmetic composition of the present invention may contain an alkoxysalicylic acid represented by the following formula (I), a salt of an alkoxysalicylic acid represented by the following formula (I), or an alkoxysalicylic acid represented by the following formula (I) and a salt of an alkoxysalicylic acid represented by the following formula (I).
(wherein R represents an alkyl group having 1 to 6 carbon atoms)
　式（Ｉ）において、アルコキシ基（ＯＲ）は、サリチル酸の３位、４位又は５位のいずれかの水素原子がアルコキシ基に置換されたものであってよい。また、Ｒは、炭素数１～６のアルキル基を示す。ここで、アルキル基としては、特に限定されず、分岐状のアルキル基であってもよく、直鎖のアルキル基であってもよい。より具体的には、Ｒは、例えば、メチル基、エチル基、ｎ－プロピル基、イソプロピル基、ｎ－ブチル基、イソブチル基、ｓｅｃ－ブチル基、ｔｅｒｔ－ブチル基、ペンチル基、又はヘキシル基等であってよい。これらのうち、Ｒは、メチル基、エチル基、プロピル基、イソプロピル基、ブチル基、又はイソブチル基であることが好ましく、メチル基又はエチル基であることがより好ましい。 In formula (I), the alkoxy group (OR) may be a salicylic acid in which a hydrogen atom at any of the 3rd, 4th, or 5th position is replaced with an alkoxy group. R represents an alkyl group having 1 to 6 carbon atoms. Here, the alkyl group is not particularly limited, and may be a branched alkyl group or a straight-chain alkyl group. More specifically, R may be, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, or a hexyl group. Of these, R is preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, or an isobutyl group, and more preferably a methyl group or an ethyl group.
　式（Ｉ）で表されるアルコキシサリチル酸の化合物名を例示すれば、３－メトキシサリチル酸、３－エトキシサリチル酸、４－メトキシサリチル酸、４－エトキシサリチル酸、４－プロポキシサリチル酸、４－イソプロポキシサリチル酸、４－ブトキシサリチル酸、５－メトキシサリチル酸、５－エトキシサリチル酸、及び５－プロポキシサリチル酸等が挙げられるが、これらに限定されない。 Examples of alkoxysalicylic acid compounds represented by formula (I) include, but are not limited to, 3-methoxysalicylic acid, 3-ethoxysalicylic acid, 4-methoxysalicylic acid, 4-ethoxysalicylic acid, 4-propoxysalicylic acid, 4-isopropoxysalicylic acid, 4-butoxysalicylic acid, 5-methoxysalicylic acid, 5-ethoxysalicylic acid, and 5-propoxysalicylic acid.
　また、式（Ｉ）で表されるアルコキシサリチル酸の塩としては、特に限定されず、例えば、ナトリウム塩、カリウム塩、カルシウム塩のようなアルカリ金属塩又はアルカリ土類金属塩、アンモニウム塩、及びアミノ酸塩等の塩が挙げられる。これらのうち、アルコキシサリチル酸の塩は、例えばナトリウム塩及びカリウム塩であることが好ましく、カリウム塩であることがより好ましい。 Also, the salt of alkoxysalicylic acid represented by formula (I) is not particularly limited, and examples thereof include alkali metal salts or alkaline earth metal salts such as sodium salt, potassium salt, and calcium salt, ammonium salt, and amino acid salt. Of these, the salt of alkoxysalicylic acid is preferably, for example, sodium salt or potassium salt, and more preferably potassium salt.
　なお、アルコキシサリチル酸は、既知の方法によって、その塩の形態にすることができる。また、本発明の美容組成物がアルコキシサリチル酸の塩を含む場合には、組成物にその塩の形態で直接配合してもよく、又は遊離酸と塩基を配合し、組成物の系内でその塩の形態になるようにしてもよい。 Alkoxysalicylic acid can be converted into its salt form by known methods. When the cosmetic composition of the present invention contains a salt of alkoxysalicylic acid, the salt may be directly added to the composition, or the free acid and base may be added to convert the salt into the composition system.
　本発明の美容組成物において、式（Ｉ）で表されるアルコキシサリチル酸又はその塩の含有量は、特に限定されず、例えば、０．００１質量％以上、０．００５質量％以上、０．０１質量％以上、０．０５質量％以上、０．１質量％以上、０．５質量％以上、又は１．０質量％以上であってよく、また、５．０質量％以下、４．５質量％以下、４．０質量％以下、３．５質量％以下、３．０質量％以下、２．５質量％以下、２．０質量％以下、１．５質量％以下、１．０質量％以下、０．５質量％以下又は０．１質量％以下であってよい。アルコキシサリチル酸の美白効果をより向上させる観点からは、式（Ｉ）で表されるアルコキシサリチル酸又はその塩の含有量は、美容組成物において、０．０１質量％以上であることが好ましく、０．１質量％以上であることがより好ましく、０．５質量％以上であることが更に好ましく、１．０質量％以上であることが特に好ましい。また、式（Ｉ）で表されるアルコキシサリチル酸又はその塩の含有量は、美容組成物において、例えば３．０質量％以下であってよい。 In the cosmetic composition of the present invention, the content of the alkoxysalicylic acid or its salt represented by formula (I) is not particularly limited, and may be, for example, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, or 1.0% by mass or more, and may be 5.0% by mass or less, 4.5% by mass or less, 4.0% by mass or less, 3.5% by mass or less, 3.0% by mass or less, 2.5% by mass or less, 2.0% by mass or less, 1.5% by mass or less, 1.0% by mass or less, 0.5% by mass or less, or 0.1% by mass or less. From the viewpoint of further improving the whitening effect of the alkoxysalicylic acid, the content of the alkoxysalicylic acid or its salt represented by formula (I) in the cosmetic composition is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, even more preferably 0.5% by mass or more, and particularly preferably 1.0% by mass or more. Furthermore, the content of the alkoxysalicylic acid represented by formula (I) or its salt in the cosmetic composition may be, for example, 3.0% by mass or less.
　なお、本明細書において、「式（Ｉ）で表されるアルコキシサリチル酸又はその塩の含有量」という表現は、本発明の美容組成物が式（Ｉ）で表されるアルコキシサリチル酸及びその塩の両方を含む場合には、その合計の含有量を意味する。 In this specification, the expression "content of alkoxysalicylic acid represented by formula (I) or its salt" means the total content when the cosmetic composition of the present invention contains both alkoxysalicylic acid represented by formula (I) and its salt.
　本発明の美容組成物において、上述した式（Ｉ）で表されるアルコキシサリチル酸又はその塩と共に、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールを配合すると、上述した式（Ｉ）で表されるアルコキシサリチル酸又はその塩の、肌への浸透性が向上される。 In the cosmetic composition of the present invention, when cyclohexane-1,4-dicarboxylate bisethoxydiglycol is blended together with the alkoxysalicylic acid or its salt represented by the above formula (I), the skin permeability of the alkoxysalicylic acid or its salt represented by the above formula (I) is improved.
　したがって、本発明の美容組成物において、１００質量部の上述した式（Ｉ）で表されるアルコキシサリチル酸又はその塩に対して、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールの配合量は、例えば、２０質量部以上、３０質量部以上、４０質量部以上、５０質量部以上、６０質量部以上、７０質量部以上、８０質量部以上、９０質量部以上、１００質量部以上、１２０質量部以上、１５０質量部以上、１８０質量部以上、２００質量部以上、２５０質量部以上、又は３００質量部以上であってよく、また、１５００質量部以下、１２００質量部以下、１０００質量部以下、８００質量部以下、５００質量部以下、３００質量部以下、２００質量部以下、１００質量部以下、８０質量部以下、５０質量部以下、又は３０質量部以下であってよい。 Therefore, in the cosmetic composition of the present invention, the amount of cyclohexane-1,4-dicarboxylate bisethoxydiglycol per 100 parts by mass of the alkoxysalicylic acid or salt thereof represented by the above-mentioned formula (I) may be, for example, 20 parts by mass or more, 30 parts by mass or more, 40 parts by mass or more, 50 parts by mass or more, 60 parts by mass or more, 70 parts by mass or more, 80 parts by mass or more, 90 parts by mass or more, 100 parts by mass or more, 120 parts by mass or more, 150 parts by mass or more, 180 parts by mass or more, 200 parts by mass or more, 250 parts by mass or more, or 300 parts by mass or more, and may be 1500 parts by mass or less, 1200 parts by mass or less, 1000 parts by mass or less, 800 parts by mass or less, 500 parts by mass or less, 300 parts by mass or less, 200 parts by mass or less, 100 parts by mass or less, 80 parts by mass or less, 50 parts by mass or less, or 30 parts by mass or less.
　また、本発明の美容組成物において、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールの含有量は、例えば、０．００１質量％以上、０．００５質量％以上、０．０１質量％以上、０．０５質量％以上、０．１質量％以上、０．５質量％以上、又は１．０質量％以上であってよく、また、１０質量％以下、９．５質量％以下、９．０質量％以下、８．５質量％以下、８．０質量％以下、７．５質量％以下、７．０質量％以下、６．５質量％以下、６．０質量％以下、５．０質量％以下、３．０質量％以下、又は１．０質量％以下であってよい。アルコキシサリチル酸又はその塩の、肌への浸透性をより向上させる観点からは、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールの含有量は、本発明の美容組成物において、０．１質量％以上であることが好ましく、０．５質量％以上であることがより好ましく、１．０質量％以上であることが更に好ましく、３．０質量％以上であることが特に好ましい。また、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールの含有量は、美容組成物において、例えば５．０質量％以下であってよい。 In addition, in the cosmetic composition of the present invention, the content of bisethoxydiglycol cyclohexane-1,4-dicarboxylate may be, for example, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, or 1.0% by mass or more, and may be 10% by mass or less, 9.5% by mass or less, 9.0% by mass or less, 8.5% by mass or less, 8.0% by mass or less, 7.5% by mass or less, 7.0% by mass or less, 6.5% by mass or less, 6.0% by mass or less, 5.0% by mass or less, 3.0% by mass or less, or 1.0% by mass or less. From the viewpoint of further improving the permeability of the alkoxysalicylic acid or its salt into the skin, the content of bisethoxydiglycol cyclohexane-1,4-dicarboxylate in the cosmetic composition of the present invention is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, even more preferably 1.0% by mass or more, and particularly preferably 3.0% by mass or more. The content of bisethoxydiglycol cyclohexane-1,4-dicarboxylate in the cosmetic composition may be, for example, 5.0% by mass or less.
　本発明の美容組成物は、上述した成分の他に、本発明の効果を損なわない範囲で、その他の成分を更に含んでよい。より具体的には、例えば、本発明の美容組成物は、化粧品として許容される基剤を更に含んでよい。 The cosmetic composition of the present invention may further contain other ingredients in addition to the above-mentioned ingredients, so long as the effects of the present invention are not impaired. More specifically, for example, the cosmetic composition of the present invention may further contain a base acceptable as a cosmetic.
　ここで、化粧品基剤としては、特に限定されず、例えば水性成分、油性成分、及び界面活性剤等が挙げられる。なお、これらの基剤は、目的の化粧品の形態に合わせて、種類や配合量を適宜設定することができる。 The cosmetic base is not particularly limited, and examples include aqueous components, oily components, and surfactants. The type and amount of these bases can be appropriately determined according to the desired form of the cosmetic.
　例えば、本発明の美容組成物において、化粧品として許容される基剤を更に含む場合にはそれの含有量は、特に限定されず、例えば、組成物の全量（１００質量％）に対して、５．０～９９．５質量％、２０～８０質量％、又は３０～７５質量％であってよい。 For example, when the cosmetic composition of the present invention further contains a cosmetically acceptable base, the content thereof is not particularly limited and may be, for example, 5.0 to 99.5% by mass, 20 to 80% by mass, or 30 to 75% by mass relative to the total amount of the composition (100% by mass).
　また、本発明の美容組成物は、本発明の効果を損なわない範囲で、上述した以外に、その他の任意成分を更に含んでよい。その他の任意成分としては、例えば、上記成分以外の皮膚美白剤、日焼け止め剤、抗酸化剤、塩、保湿剤、ビタミン、医薬品、医薬部外品若しくは化粧品等に適用可能な水溶性薬剤、増粘剤、顔料、染料、色素、結合剤、生物学的添加物、緩衝剤、着色剤、ポリマー、収斂剤、香料、乳白剤、コンディショナー、角質除去剤、ｐＨ調整剤、防腐剤、天然抽出物、皮膚用知覚剤、皮膚スムージング剤、及び皮膚治癒剤等が挙げられるが、これらに限定されない。また、これらのその他の任意成分が含まれる場合のそれぞれの含有量は、特に限定されず、化粧品として許容される量であればよい。 The cosmetic composition of the present invention may further contain other optional components in addition to those described above, so long as the effect of the present invention is not impaired. Examples of other optional components include, but are not limited to, skin whitening agents other than those described above, sunscreens, antioxidants, salts, moisturizers, vitamins, water-soluble agents applicable to medicines, quasi-drugs, or cosmetics, thickeners, pigments, dyes, pigments, binders, biological additives, buffers, colorants, polymers, astringents, fragrances, opacifiers, conditioners, exfoliants, pH adjusters, preservatives, natural extracts, skin sensates, skin smoothing agents, and skin healing agents. In addition, the content of each of these other optional components when they are included is not particularly limited, and may be any amount acceptable for cosmetics.
　本発明の美容組成物は、美容（例えば、美白）を目的として皮膚に適用される外用剤を意味する。よって、本発明の美容組成物は、皮膚の局所塗布用であってよい。 The cosmetic composition of the present invention refers to an external preparation that is applied to the skin for cosmetic purposes (e.g., whitening). Thus, the cosmetic composition of the present invention may be for topical application to the skin.
　また、本発明の美容組成物の製品形態として、例えば、軟膏、ローション、乳液、クリーム、ゲル、ファンデーション、マスク又はムース等が挙げられるが、これらに限定されない。 Furthermore, examples of the product forms of the cosmetic composition of the present invention include, but are not limited to, ointments, lotions, milky lotions, creams, gels, foundations, masks, mousses, etc.
　《美容方法》
　本発明の美容方法は、上述した本発明の美容組成物を皮膚に塗布することを含む。 《Beauty Methods》
The cosmetic method of the present invention comprises applying the above-mentioned cosmetic composition of the present invention to the skin.
　《シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールの新たな用途》
　上述したように、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールは、上述したアルコキシサリチル酸又はその塩の、肌への浸透性を大幅に向上させることができる。 <New Uses for Bis-ethoxydiglycol Cyclohexane-1,4-dicarboxylate>
As described above, bis(ethoxydiglycol)cyclohexane-1,4-dicarboxylate can significantly improve the skin permeability of the above-mentioned alkoxysalicylic acid or a salt thereof.
　したがって、本発明は、上述したアルコキシサリチル酸又はその塩の、経皮浸透促進剤としてのシクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールの使用を提供する。 The present invention therefore provides the use of bisethoxydiglycol cyclohexane-1,4-dicarboxylate as a percutaneous penetration enhancer for the above-mentioned alkoxysalicylic acid or its salt.
　以下に実施例を挙げて、本発明について更に詳しく説明を行うが、本発明はこれらに限定されるものではない。なお、以下、特に断りのない限り、表中の数値は、各成分の配合量を意味し、単位は質量％である。 The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these. Unless otherwise specified, the numerical values in the tables below refer to the blend amounts of each component, and are expressed in mass %.
　《実施例１、並びに比較例１、２、及び２－１》
　表１の処方に基づき、実施例及び比較例のそれぞれの美容組成物を調製した。調製された各組成物に対して、それぞれの美容成分の皮膚への「累積透過試験」を行った。 Example 1, and Comparative Examples 1, 2, and 2-1
Each of the cosmetic compositions of the Examples and Comparative Examples was prepared based on the formulation in Table 1. For each of the prepared compositions, a "cumulative permeation test" of each cosmetic ingredient into the skin was carried out.
　〈累積透過試験〉
　調製された各組成物の透過性に関して経時のサンプリングが可能であり、日本薬局方にも収載されている縦型フランツ拡散セル（以下「フランツセル」と称する。）を用いて各種結晶性水溶性薬剤組成物の疑似皮膚膜透過性に関する評価を実施した。 Cumulative permeation test
The permeability of each prepared composition can be sampled over time, and the simulated skin membrane permeability of various crystalline water-soluble drug compositions was evaluated using a vertical Franz diffusion cell (hereinafter referred to as "Franz cell"), which is also listed in the Japanese Pharmacopoeia.
　より具体的には、フランツセルとして、１．７７ｃｍ２の有効透過面積を有するフランツセルを用いた。フランツセルに配置する透過膜である疑似皮膚膜として、フランツセルを構成するドナーセルの外径に合わせてポンチで切り抜いたＳｔｒａｔ－Ｍ（商標）メンブレン（Ｍｅｒｃｋ　Ｍｉｌｌｉｐｏｒｅ社製）を用いた。疑似皮膚膜は、フランツセルにセットする前に生理的リン酸緩衝液（ＰＢＳ）に浸して十分に水和させた。ウォーターバスとレシーバーセルジャケットとをホースでフランツセルに連結し、一連の恒温装置システムを組み立てた後、レシーバーセル内にＰＢＳを満たした。セル挟みを用い、レシーバーセルとドナーセルとの間に疑似皮膚膜を空気が入らないようにしっかりと固定した。疑似皮膚膜の表面温度を、温度調節器を用いて肌の表面温度に相当する約３２℃に保持し、レシーバーセル内のＰＢＳをスターラーバーで攪拌しながら１時間以上順化させた。各組成物の疑似皮膚膜への適用は、実使用を想定した有限開放適用で実施した。各組成物を３０秒間均一に疑似皮膚膜に塗布した。塗布してから所定時間経過後（塗布してから０、１、２、４、８及び２４時間経過後）、レシーバーセルから抽出液を採取した。ＬＣ－ＭＳ検出器を備えたＨＰＬＣシステムを用い、採取した抽出液中の薬剤量を定量して累積透過量を算出した。 More specifically, a Franz cell having an effective permeation area of 1.77 cm2 was used as the Franz cell. As the pseudo-skin membrane, which is a permeable membrane to be placed in the Franz cell, a Strat-M (trademark) membrane (Merck Millipore) cut out with a punch to match the outer diameter of the donor cell constituting the Franz cell was used. The pseudo-skin membrane was soaked in physiological phosphate buffer (PBS) before being set in the Franz cell to be fully hydrated. The water bath and the receiver cell jacket were connected to the Franz cell with a hose, and a series of thermostatic device systems were assembled, and then the receiver cell was filled with PBS. The pseudo-skin membrane was firmly fixed between the receiver cell and the donor cell using a cell clamp so that air would not enter. The surface temperature of the pseudo-skin membrane was maintained at about 32°C, which corresponds to the surface temperature of the skin, using a temperature regulator, and the PBS in the receiver cell was acclimated for more than 1 hour while being stirred with a stirrer bar. The application of each composition to the pseudo-skin membrane was carried out by limited open application assuming practical use. Each composition was uniformly applied to the simulated skin membrane for 30 seconds. After a given time had elapsed since application (0, 1, 2, 4, 8, and 24 hours since application), the extract was collected from the receiver cell. The amount of drug in the collected extract was quantified using an HPLC system equipped with an LC-MS detector, and the cumulative permeation amount was calculated.
　図１は、実施例１及び比較例１の４－メトキシサリチル酸カリウムの累積透過量の結果を示している。図２は、比較例２及び比較例２－１のニコチン酸アミドの累積透過量の結果を示している。 Figure 1 shows the results of the cumulative permeation amount of potassium 4-methoxysalicylate in Example 1 and Comparative Example 1. Figure 2 shows the results of the cumulative permeation amount of nicotinamide in Comparative Example 2 and Comparative Example 2-1.
　図１の結果から明らかなように、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールを含有している実施例１では、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールを含有していなかった比較例１の場合に比べて、４－メトキシサリチル酸カリウムの累積透過量が著しく増加したことが分かった。特に、実施例１の４－メトキシサリチル酸カリウムの累積透過量は、４時間経過時に、比較例１の場合の約４２倍に増加し、また、８時間経過時に比較例１の場合の約１５倍に増加し、更に、２４時間の時点で、比較例１の場合の約９倍に有意差をもって増加したことが分かった。 As is clear from the results in Figure 1, it was found that in Example 1, which contains bisethoxydiglycol cyclohexane-1,4-dicarboxylate, the cumulative permeation amount of potassium 4-methoxysalicylate was significantly increased compared to Comparative Example 1, which did not contain bisethoxydiglycol cyclohexane-1,4-dicarboxylate. In particular, it was found that the cumulative permeation amount of potassium 4-methoxysalicylate in Example 1 increased to about 42 times that of Comparative Example 1 after 4 hours, increased to about 15 times that of Comparative Example 1 after 8 hours, and further increased significantly to about 9 times that of Comparative Example 1 at 24 hours.
　これに対して、図２の結果からは、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールを含有している比較例２では、シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールを含有していなかった比較例２－１の場合に比べて、ニコチン酸アミドの累積透過量は多少増加したものの、有意差は見られず、上述した実施例１と比較例１とを比較した場合の増加率よりも遥かい小さかったことが分かった。 In contrast, the results in Figure 2 show that, in Comparative Example 2, which contains bisethoxydiglycol cyclohexane-1,4-dicarboxylate, the cumulative amount of nicotinamide permeation increased slightly compared to Comparative Example 2-1, which did not contain bisethoxydiglycol cyclohexane-1,4-dicarboxylate, but there was no significant difference, and the increase was much smaller than the increase rate when comparing Example 1 and Comparative Example 1 described above.
　《実施例２～４》
　表２の処方に基づき、実施例２～４のそれぞれの美容組成物（クリーム状）を調製した。調製された各組成物に対して、上述した実施例１と同様な手順で、それぞれの美容成分の皮膚への「累積透過試験」を行った。 Examples 2 to 4
Cosmetic compositions (cream-like) of Examples 2 to 4 were prepared based on the formulations in Table 2. For each of the prepared compositions, a "cumulative permeation test" of each cosmetic ingredient into the skin was carried out in the same manner as in Example 1 described above.
　図３は、実施例２～４の美容成分（４－メトキシサリチル酸カリウム）の累積透過量の結果を示している。 Figure 3 shows the cumulative permeation results of the beauty ingredient (potassium 4-methoxysalicylate) in Examples 2 to 4.
　図３の結果から明らかなように、実施例２～４の組成物において、経皮浸透促進剤としてのシクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールの含有量の増加に伴い、４－メトキシサリチル酸カリウムの累積透過量が増加する傾向があることが分かった。 As is clear from the results in Figure 3, in the compositions of Examples 2 to 4, the cumulative amount of potassium 4-methoxysalicylate permeated tends to increase with an increase in the content of bisethoxydiglycol cyclohexane-1,4-dicarboxylate as a percutaneous penetration enhancer.
　《処方例》
　以下に、本発明の美容組成物のいくつかの処方例を挙げるが、本発明はこれらの例示に限定されるものではない。なお、以下の表中の数値は、各成分の配合量を意味し、単位は質量％である。 <Prescription Example>
Below, some formulation examples of the cosmetic composition of the present invention are shown, but the present invention is not limited to these examples. The numerical values in the following tables indicate the blending amount of each component, and the unit is mass %.
　また、各処方例の調製はいずれも常法に基づくものである。例えば、組成物は、水溶性成分のみの場合には、イオン交換水に水溶性成分を均一に溶解させることによって調製される。また、組成物は、乳化物である場合には、イオン交換水に水溶性成分を溶解した後に、油性成分を添加することによって調製される。また、組成物は、無機粒子等を含む乳化物である場合には、イオン交換水に水溶性成分を溶解し、無機粒子を均一に分散させた後に、油性成分を添加することによって調製される。 The preparation of each formulation example is based on a conventional method. For example, if the composition contains only water-soluble components, it is prepared by uniformly dissolving the water-soluble components in ion-exchanged water. If the composition is an emulsion, it is prepared by dissolving the water-soluble components in ion-exchanged water and then adding the oily components. If the composition is an emulsion containing inorganic particles, it is prepared by dissolving the water-soluble components in ion-exchanged water, uniformly dispersing the inorganic particles, and then adding the oily components.
　〈処方例１〉
 <Prescription Example 1>
　〈処方例２〉
 <Prescription Example 2>
　〈処方例３〉
 <Prescription Example 3>
　〈処方例４〉
 <Prescription Example 4>
　〈処方例５〉
 Formulation Example 5
　〈処方例６〉
 Formulation Example 6

Claims (9)

  1. 　下記式（Ｉ）で表されるアルコキシサリチル酸又はその塩と、
    （式中、Ｒは炭素数１～６のアルキル基を示す）
    　シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールと、
    を含む、美容組成物。     An alkoxysalicylic acid represented by the following formula (I) or a salt thereof,
    (wherein R represents an alkyl group having 1 to 6 carbon atoms)
    cyclohexane-1,4-dicarboxylate bisethoxydiglycol,
    A cosmetic composition comprising:
  2. 　前記アルコキシサリチル酸又はその塩が、４－メトキシサリチル酸カリウムである、請求項１に記載の美容組成物。 The cosmetic composition according to claim 1, wherein the alkoxysalicylic acid or its salt is potassium 4-methoxysalicylate.
  3. 　１００質量部の前記アルコキシサリチル酸又はその塩に対して、前記シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールが、２０～１５００質量部である、請求項１に記載の美容組成物。 The cosmetic composition according to claim 1, in which the amount of the cyclohexane-1,4-dicarboxylate bisethoxydiglycol is 20 to 1500 parts by mass per 100 parts by mass of the alkoxysalicylic acid or its salt.
  4. 　前記アルコキシサリチル酸又はその塩の含有量が、０．００１～５．０質量％である、請求項１に記載の美容組成物。 The cosmetic composition according to claim 1, wherein the content of the alkoxysalicylic acid or its salt is 0.001 to 5.0% by mass.
  5. 　前記シクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールが、０．００１～１０質量％である、請求項１に記載の美容組成物。 The cosmetic composition according to claim 1, in which the bisethoxydiglycol cyclohexane-1,4-dicarboxylate is present in an amount of 0.001 to 10% by mass.
  6. 　化粧品として許容される基剤を更に含む、請求項１に記載の美容組成物。 The cosmetic composition according to claim 1, further comprising a cosmetically acceptable base.
  7. 　局所塗布用である、請求項１に記載の美容組成物。 The cosmetic composition according to claim 1, which is for topical application.
  8. 　請求項１～７のいずれか一項に記載の美容組成物を皮膚に塗布することを含む、美容方法。 A beauty method comprising applying the beauty composition according to any one of claims 1 to 7 to the skin.
  9. 　下記式（Ｉ）で表されるアルコキシサリチル酸又はその塩の、経皮浸透促進剤としてのシクロヘキサン－１，４－ジカルボン酸ビスエトキシジグリコールの使用：
    （式中、Ｒは炭素数１～６のアルキル基を示す）     Use of bisethoxydiglycol cyclohexane-1,4-dicarboxylate as a percutaneous penetration enhancer for an alkoxysalicylic acid or a salt thereof represented by the following formula (I):
    (wherein R represents an alkyl group having 1 to 6 carbon atoms)
PCT/JP2023/037225 2022-10-28 2023-10-13 Beauty composition, beauty method, and agent for promoting skin permeability of alkoxy salicylic acid or salt thereof WO2024090247A1 (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07173023A (en) * 1993-12-16 1995-07-11 Shiseido Co Ltd Skin external preparation
JP2017171581A (en) * 2016-03-18 2017-09-28 日油株式会社 All-in-one gel cosmetic
CN111450008A (en) * 2020-04-30 2020-07-28 广州天玺生物科技有限公司 Whitening cream and preparation method thereof
JP2021011458A (en) * 2019-07-09 2021-02-04 株式会社ノエビア External preparation for skin
CN113116739A (en) * 2019-12-31 2021-07-16 广州市科能化妆品科研有限公司 Penetration enhancer, skin care product containing the same and preparation method thereof
CN113662882A (en) * 2021-10-09 2021-11-19 上海新高姿化妆品有限公司 Whitening, spot-fading and tightening essence and preparation method thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07173023A (en) * 1993-12-16 1995-07-11 Shiseido Co Ltd Skin external preparation
JP2017171581A (en) * 2016-03-18 2017-09-28 日油株式会社 All-in-one gel cosmetic
JP2021011458A (en) * 2019-07-09 2021-02-04 株式会社ノエビア External preparation for skin
CN113116739A (en) * 2019-12-31 2021-07-16 广州市科能化妆品科研有限公司 Penetration enhancer, skin care product containing the same and preparation method thereof
CN111450008A (en) * 2020-04-30 2020-07-28 广州天玺生物科技有限公司 Whitening cream and preparation method thereof
CN113662882A (en) * 2021-10-09 2021-11-19 上海新高姿化妆品有限公司 Whitening, spot-fading and tightening essence and preparation method thereof

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