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WO2024095793A1 - Composition - Google Patents

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Publication number
WO2024095793A1
WO2024095793A1 PCT/JP2023/037958 JP2023037958W WO2024095793A1 WO 2024095793 A1 WO2024095793 A1 WO 2024095793A1 JP 2023037958 W JP2023037958 W JP 2023037958W WO 2024095793 A1 WO2024095793 A1 WO 2024095793A1
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WO
WIPO (PCT)
Prior art keywords
component
salt
composition
antioxidant cosmetic
formula
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2023/037958
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French (fr)
Japanese (ja)
Inventor
育浩 鈴木
裕介 奥山
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shiseido Co Ltd
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Shiseido Co Ltd
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Publication date
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Priority to JP2024554396A priority Critical patent/JPWO2024095793A1/ja
Publication of WO2024095793A1 publication Critical patent/WO2024095793A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
    • 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
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/18—Antioxidants, e.g. antiradicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • 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
    • A61Q19/08—Anti-ageing preparations

Definitions

  • the present invention relates to antioxidant cosmetics and skin topical compositions.
  • Cyclic carboxamide derivatives have the effect of inhibiting heparanase activity, and have been proposed for use, for example, as wrinkle improving agents or as whitening agents effective in preventing or suppressing pigmentation such as blemishes (Patent Document 1).
  • 1-Piperidinepropionic acid has been proposed to act on the mechanism of wrinkle formation and to be used as an anti-wrinkle agent (Patent Document 2).
  • Dipotassium glycyrrhizinate has an anti-wrinkle effect, and its use as an anti-wrinkle agent has been proposed (Patent Document 3).
  • a cyclic carboxamide derivative or a salt thereof, an organic acid having a specific structure such as 1-piperidine carboxylic acid or a salt thereof, and glycyrrhizic acid or a salt thereof each have the ability to effectively remove reactive oxygen species.
  • a composition containing a combination of an organic acid having a specific structure, such as 1-piperidine carboxylic acid, or a salt thereof, and glycyrrhizinic acid or a salt thereof effectively inhibits tyrosinase activity.
  • the present invention is based on these findings.
  • An antioxidant cosmetic preparation comprising at least one member selected from the group consisting of (A) a cyclic carboxamide derivative represented by formula (a) or a salt thereof, (B) an organic acid represented by formula (b) or a salt thereof, and (C) glycyrrhizic acid or a salt thereof.
  • R 1 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom;
  • X is -CH2- or -N( R2 )-, where R2 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom, and na is an integer of 1 to 3.
  • nb is an integer of 2 to 5.
  • R 1 is a hydroxyalkyl group having 1 to 3 carbon atoms;
  • component (C) is dipotassium glycyrrhizinate.
  • a composition for external application to the skin comprising a combination of (B) an organic acid represented by formula (b) or a salt thereof and (C) glycyrrhizinic acid or a salt thereof.
  • nb is an integer of 2 to 5.
  • the present invention can provide an antioxidant cosmetic that has effective removal capabilities against reactive oxygen species.
  • the present invention can also provide a composition for external use on the skin that effectively inhibits tyrosinase activity.
  • One aspect of the present invention relates to an antioxidant cosmetic preparation comprising at least one selected from the group consisting of (A) a cyclic carboxamide derivative having a specific structure or a salt thereof, (B) an organic acid having a specific structure or a salt thereof, and (C) glycyrrhizinic acid or a salt thereof.
  • A a cyclic carboxamide derivative having a specific structure or a salt thereof
  • B an organic acid having a specific structure or a salt thereof
  • C glycyrrhizinic acid or a salt thereof.
  • the antioxidant cosmetic composition according to the present invention can contain a cyclic carboxamide derivative represented by formula (a) or a salt thereof (hereinafter, sometimes referred to as component (A).
  • component (A) Cyclic Carboxamide Derivative or Salt thereof
  • R 1 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom
  • X is —CH 2 — or —N(R 2 )—, where R 2 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom
  • na is an integer of 1 to 3.
  • the above-mentioned hydrocarbon group is not particularly limited and may be, for example, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, a cycloalkylalkyl group, a haloalkyl group, an alkoxyalkyl group, or an alkoxycarbonylalkyl group, and is preferably an alkyl group.
  • R 1 is a hydroxyalkyl group having 1 to 3 carbon atoms;
  • X is —CH 2 — or —NH—, and
  • na is 1.
  • Specific examples of the cyclic carboxamide derivative represented by formula (a) include the following.
  • the component (A) is most preferably 1-(2-hydroxyethyl)-2-imidazolidinone.
  • the (A) component may be a salt of a cyclic carboxamide derivative represented by formula (a).
  • the type of salt is not particularly limited as long as it is a pharmacologically acceptable salt, and may be an inorganic salt or an organic salt.
  • inorganic salts include hydrochlorides, sulfates, phosphates, hydrobromides, sodium salts, potassium salts, magnesium salts, calcium salts, magnesium salts, and ammonium salts.
  • organic salts include acetates, lactates, maleates, fumarates, tartrates, methanesulfonates, p-toluenesulfonates, triethanolamine salts, and amino acid salts.
  • the (A) component may be used in combination with one or more types.
  • the amount of the (A) component is preferably 10 to 200 mg/mL, more preferably 15 to 180 mg/mL, and even more preferably 50 to 150 mg/mL, based on the total amount of the antioxidant cosmetic.
  • the antioxidant cosmetic preparation according to the present invention may contain an organic acid represented by formula (b) or a salt thereof.
  • nb is an integer from 2 to 5.
  • Component (B) may be a salt of an organic acid represented by formula (b).
  • the type of salt is not particularly limited as long as it is a pharmacologically acceptable salt, and may be an inorganic salt or an organic salt.
  • inorganic salts include hydrochlorides, sulfates, phosphates, hydrobromides, sodium salts, potassium salts, magnesium salts, calcium salts, and ammonium salts.
  • organic salts include acetates, lactates, maleates, fumarates, tartrates, citrates, methanesulfonates, p-toluenesulfonates, triethanolamine salts, diethanolamine salts, and amino acid salts.
  • the (B) component may be used in combination with one or more types.
  • the amount of the (B) component is preferably 0.5 to 100 mg/mL, more preferably 3 to 95 mg/mL, even more preferably 8 to 90 mg/mL, and particularly preferably 15 to 85 mg/mL, relative to the total amount of the antioxidant cosmetic.
  • the antioxidant cosmetic according to the present invention may contain (C) glycyrrhizic acid or its salt.
  • the type of salt is not particularly limited as long as it is a pharmacologically acceptable salt, and may be an inorganic salt or an organic salt.
  • Examples of glycyrrhizinic acid salts include sodium salts, potassium salts, ammonium salts, basic amino acid salts, and alkanolamine salts, and specific examples include monoammonium glycyrrhizinate, dipotassium glycyrrhizinate, and trisodium glycyrrhizinate.
  • the (C) component is preferably dipotassium glycyrrhizinate.
  • the component (C) may be used alone or in combination with two or more other components.
  • the amount of component (C) to be used is preferably 0.01 to 10 mg/mL, more preferably 0.2 to 8 mg/mL, even more preferably 0.4 to 5 mg/mL, and particularly preferably 1.5 to 4.5 mg/mL, relative to the total amount of the antioxidant cosmetic.
  • the antioxidant cosmetic composition according to the present invention contains one or more of the components (A) to (C), and preferably contains one or two of them. In one embodiment of the present invention, the antioxidant cosmetic composition according to the present invention contains a combination of two or more of the components (A) to (C), and more preferably contains a combination of the component (B) and the component (C).
  • compositions for external application to the skin comprising a combination of (B) an organic acid having a specific structure or a salt thereof and (C) a glycyrrhizinic acid or a salt thereof component.
  • Pigmentation such as age spots, freckles, and dullness is generally caused by melanin accumulation, and it is believed that the accumulation of melanin in the epidermis is greatly influenced by tyrosinase activity in melanocytes.
  • the composition for external use on the skin according to the present invention has tyrosinase inhibitory activity and can effectively inhibit tyrosinase activity.
  • the composition according to the present invention is preferably a whitening cosmetic.
  • whitening mainly means suppressing the production of melanin and preventing age spots, freckles, dullness, etc.
  • the composition for topical application to the skin according to the present invention is a tyrosinase inhibitor active agent.
  • the composition for external application to skin contains an organic acid represented by formula (b) or a salt thereof.
  • nb is an integer from 2 to 5.
  • Component (B) may be a salt of an organic acid represented by formula (b).
  • the type of salt is not particularly limited as long as it is a pharmacologically acceptable salt, and may be an inorganic salt or an organic salt.
  • inorganic salts include hydrochlorides, sulfates, phosphates, hydrobromides, sodium salts, potassium salts, magnesium salts, calcium salts, and ammonium salts.
  • organic salts include acetates, lactates, maleates, fumarates, tartrates, citrates, methanesulfonates, p-toluenesulfonates, triethanolamine salts, diethanolamine salts, and amino acid salts.
  • the component (B) may be one or more types.
  • the amount of component (B) is preferably 0.5 to 15 mg/mL, more preferably 0.7 to 5 mg/mL, and even more preferably 1 to 2 mg/mL, based on the total amount of the topical skin composition.
  • the skin external composition according to the present invention comprises (C) glycyrrhizic acid or its salt.
  • Glycyrrhizic acid salts include, for example, sodium salts, potassium salts, ammonium salts, basic amino acids, or alkanolamine salts, and specifically, glycyrrhizinic acid monoammonium, glycyrrhizinic acid dipotassium, and glycyrrhizinic acid trisodium.
  • (C) component is preferably glycyrrhizinic acid dipotassium.
  • the component (C) may be used alone or in combination with two or more other components.
  • the amount of component (C) is preferably 0.01 to 0.8 mg/mL, more preferably 0.02 to 0.5 mg/mL, and even more preferably 0.03 to 0.1 mg/mL, relative to the total amount of the composition for topical skin application.
  • the amount of component (B) relative to the amount of component (C) ((B)/(C)) is preferably 5 to 200 by mass, and more preferably 10 to 50 by mass.
  • the antioxidant cosmetic and topical skin composition according to the present invention may further contain water.
  • water water used in cosmetics, quasi-drugs, etc. may be used, such as purified water, ultrapure water, ion-exchanged water, tap water, etc.
  • the antioxidant cosmetic and topical skin composition according to the present invention can contain optional ingredients that are normally used in cosmetics and pharmaceuticals, in addition to the above-mentioned ingredients.
  • Optional ingredients include, for example, moisturizers, lower alcohols, thickeners, surfactants, sequestering agents, neutralizing agents, pH adjusters, antioxidants, preservatives, medicines, UV absorbers, powdered ingredients, oily ingredients, fragrances, etc., and one or more of these can be contained as long as the effects of the present invention are achieved.
  • the formulation of the antioxidant cosmetic and topical skin composition according to the present invention is not particularly limited, and may take any formulation, such as a solution system, a solubilized system, an emulsion system, a powder dispersion system, a water-oil two-layer system, a water-oil-powder three-layer system, an ointment, a gel, an aerosol, etc.
  • the form of use is also not particularly limited, and may take any form, such as a lotion, milky lotion, cream, essence, jelly, gel, ointment, pack, mask, foundation, etc.
  • the antioxidant cosmetic and topical skin composition according to the present invention can be produced according to a conventional method.
  • antioxidant cosmetic preparation 1-(2-hydroxyethyl)-2-imidazolidinone as component (A), 1-piperidinepropionic acid as component (B), and dipotassium glycyrrhizinate as component (C) were added to ultrapure water in the amounts shown in Table 1, and the mixture was stirred to prepare the antioxidant cosmetics of Examples 101 to 118.
  • antioxidant cosmetic compositions of Examples 101 to 118 were evaluated for their radical scavenging ability against DPPH radicals by the following procedure. 60 ⁇ L of the antioxidant cosmetic of each Example or control (ultrapure water was used for the control), 60 ⁇ L of ethanol (CAS No. 64-17-5, Nippon Alcohol), and 40 ⁇ L of 0.25 M acetic acid buffer (pH 5.5) were added to a 96-well plate and incubated at 37° C. for 5 minutes. Ethanol was used as a blank instead of DPPH. Three wells were used for each treatment group.
  • DPPH 2,2-diphenyl-1-picrylhydrazyl
  • the 96-well plate was shaken at 270 rpm for 30 seconds and then incubated at 37° C. for 30 minutes.
  • the 96-well plate was shaken at 270 rpm for 10 seconds to uniformly disperse the dye in the wells, and then the optical density at 517 nm (OD 517 ) was measured using a microplate reader.
  • the DPPH scavenging rate of the antioxidant cosmetic of the Example was calculated from the OD 517 of the antioxidant cosmetic of the Example and the control according to the following formula.
  • phosphate buffer 100 mM phosphate buffer was used instead of the tyrosinase solution.
  • Three wells were used for one treatment group. After 3 minutes, 50 ⁇ L of 2.5 mM 3,4-L-dihydroxyphenylalanine (L-DOPA, CAS No. 59-92-7, Wako) solution was added, the 96-well plate was shaken at 270 rpm for 10 seconds, and the optical density at 490 nm (OD 490 ) was measured using a microplate reader (SPARK 10M, TECAN). The plate was incubated at 23° C. for 10 minutes, and the optical density at 490 nm (OD 490 ) was measured after 10 minutes.
  • L-DOPA 3,4-L-dihydroxyphenylalanine
  • the tyrosinase inhibitory activity rate of the examples and comparative examples was calculated according to the following formula.
  • Tyrosinase inhibitory activity rate (%) 100 - [ ⁇ (As10 - Ab10) - (As0 - Ab0) ⁇ / (Ac10 - Ac0) x 100]
  • Ac10 OD 490 of control after incubation
  • As0 OD 490 of each of the compositions for external use on the skin of each of the Examples and Comparative Examples before incubation As10: OD 490 of each of the compositions for external use on the skin of the Examples and Comparative Examples after incubation It is.
  • Table 2 The results obtained are shown in Table 2.

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Abstract

[Problem] To provide an antioxidant cosmetic. [Solution] Provided is an antioxidant cosmetic containing at least one component selected from the group consisting of (A) a cyclic carboxamide derivative having a specific structure or a salt thereof, (B) an organic acid having a specific structure or a salt thereof and (C) glycyrrhizic acid or a salt thereof.

Description

組成物Composition

　本発明は、抗酸化化粧料および皮膚外用組成物に関する。 The present invention relates to antioxidant cosmetics and skin topical compositions.

　環状カルボキサミド誘導体は、ヘパラナーゼ活性を阻害する効果を有しており、例えば、シワ改善剤として、またはしみ等の色素沈着の予防または抑制に有効な美白剤として、用いられることが提案されている（特許文献１）。
　１－ピペリジンプロピオン酸は、シワ形成メカニズムに作用し、抗シワ剤として用いられることが提案されている（特許文献２）。
　グリチルリチン酸ジカリウムは、シワ改善作用を有しており、シワ改善剤として用いられることが提案されている（特許文献３）。 Cyclic carboxamide derivatives have the effect of inhibiting heparanase activity, and have been proposed for use, for example, as wrinkle improving agents or as whitening agents effective in preventing or suppressing pigmentation such as blemishes (Patent Document 1).
1-Piperidinepropionic acid has been proposed to act on the mechanism of wrinkle formation and to be used as an anti-wrinkle agent (Patent Document 2).
Dipotassium glycyrrhizinate has an anti-wrinkle effect, and its use as an anti-wrinkle agent has been proposed (Patent Document 3).

　生体内の活性酸素種が、シワ等の皮膚の老化を促進する一因であることが一般的に知られており、老化抑制を目的として活性酸素種の消去能を有する化合物が探索されている。上記の化合物は、活性酸素種の除去能を有することは、本発明者の知る限り報告が見当たらない。 It is generally known that reactive oxygen species in the body are one of the factors that accelerate skin aging, such as wrinkles, and compounds that have the ability to eliminate reactive oxygen species are being sought for the purpose of inhibiting aging. To the inventor's knowledge, there have been no reports that the above compounds have the ability to eliminate reactive oxygen species.

国際公開２０１１／０４０４９６International Publication No. 2011/040496 特開２０１２－２４０９１１号公報JP 2012-240911 A 特開２０２０－７３５８５号公報JP 2020-73585 A

　本発明者の検討によると、驚くべきことに、環状カルボキサミド誘導体またはその塩、１－ピペリジンカルボン酸等の特定の構造を有する有機酸またはその塩、およびグリチルリチン酸またはその塩が、それぞれ、効果的に活性酸素種の除去能を有することがわかった。
　また、驚くべきことに、１－ピペリジンカルボン酸等の特定の構造を有する有機酸またはその塩と、グリチルリチン酸またはその塩との組み合わせを含む組成物が、効果的にチロシナーゼ活性を阻害することがわかった。
　本発明はこれらの知見に基づくものである。 According to the investigations of the present inventors, it was surprisingly found that a cyclic carboxamide derivative or a salt thereof, an organic acid having a specific structure such as 1-piperidine carboxylic acid or a salt thereof, and glycyrrhizic acid or a salt thereof each have the ability to effectively remove reactive oxygen species.
Furthermore, it has been surprisingly found that a composition containing a combination of an organic acid having a specific structure, such as 1-piperidine carboxylic acid, or a salt thereof, and glycyrrhizinic acid or a salt thereof effectively inhibits tyrosinase activity.
The present invention is based on these findings.

　本発明によれば、以下の発明が提供される。
[１]（Ａ）式（ａ）で表される環状カルボキサミド誘導体またはその塩、（Ｂ）式（ｂ）で表される有機酸またはその塩、および（Ｃ）グリチルリチン酸またはその塩からなる群より選択される１種以上を含んでなる抗酸化化粧料。

Figure JPOXMLDOC01-appb-C000004
（式（ａ）中、
　Ｒ１は、水酸基で置換されていてもよい炭素数１～６の炭化水素基、または水素原子であり、
　Ｘは、－ＣＨ２－または－Ｎ（Ｒ２）－であり、ここで、Ｒ２は、水酸基で置換されていてもよい炭素数１～６の炭化水素基、または水素原子であり、かつ
　ｎａは、１～３の整数である）
Figure JPOXMLDOC01-appb-C000005
 （式（ｂ）中、ｎｂは２～５の整数である）
[２]式（ａ）において、
　Ｒ１が、炭素数１～３のヒドロキシアルキル基であり、
　Ｘが、－ＣＨ２－または－ＮＨ－であり、かつ
　ｎａが、１である、[１]に記載の抗酸化化粧料。
[３]（Ａ）成分が、１－（２－ヒドロキシエチル）－２－イミダゾリジノンである、[１]または[２]に記載の抗酸化化粧料。
[４]（Ａ）成分の配合量が、１０～２００ｍｇ／ｍＬである、[１]～[３]のいずれかに記載の抗酸化化粧料。
[５]（Ｂ）成分が、１－ピペリジンプロピオン酸である、[１]～[４]のいずれかに記載の抗酸化化粧料。
[６]（Ｂ）成分の配合量が、０．５～１００ｍｇ／ｍＬである、[１]～[５]のいずれかに記載の抗酸化化粧料。
[７]（Ｃ）成分が、グリチルリチン酸ジカリウムである、[１]～[６]のいずれかに記載の抗酸化化粧料。
[８]（Ｃ）成分の配合量が、０．０１～１０ｍｇ／ｍＬである、[１]～[７]のいずれかに記載の抗酸化化粧料。
[９]活性酸素除去能を有する、[１]～[８]のいずれかに記載の抗酸化化粧料。
[１０]（Ａ）～（Ｃ）成分のうちの２種以上の組み合わせを含んでなる、[１]～[９]のいずれかに記載の抗酸化化粧料。
[１１]（Ｂ）式（ｂ）で表される有機酸またはその塩と、（Ｃ）グリチルリチン酸またはその塩と、の組み合わせを含んでなる皮膚外用組成物。
Figure JPOXMLDOC01-appb-C000006
 （式（ｂ）中、ｎｂは２～５の整数である）
[１２]（Ｂ）成分が、１－ピペリジンプロピオン酸である、[１１]に記載の皮膚外用組成物。
[１３]（Ｂ）成分の配合量が、０．５～２．５ｍｇ／ｍＬである、[１１]または[１２]に記載の皮膚外用組成物。
[１４]（Ｃ）成分が、グリチルリチン酸ジカリウムである、[１１]～[１３]のいずれかに記載の皮膚外用組成物。
[１５]（Ｃ）成分の配合量が、０．０１～０．１ｍｇ／ｍＬである、[１１]～[１４]のいずれかに記載の皮膚外用組成物。
[１６]美白化粧料である、[１１]～[１５]のいずれかに記載の皮膚外用組成物。
[１７]チロシナーゼ阻害活性を有する、[１１]～[１６]のいずれかに記載の皮膚外用組成物。 According to the present invention, the following inventions are provided.
[1] An antioxidant cosmetic preparation comprising at least one member selected from the group consisting of (A) a cyclic carboxamide derivative represented by formula (a) or a salt thereof, (B) an organic acid represented by formula (b) or a salt thereof, and (C) glycyrrhizic acid or a salt thereof.
Figure JPOXMLDOC01-appb-C000004
 (In formula (a),
R 1 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom;
X is -CH2- or -N( R2 )-, where R2 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom, and na is an integer of 1 to 3.
Figure JPOXMLDOC01-appb-C000005
 (In formula (b), nb is an integer of 2 to 5.)
[2] In formula (a),
R 1 is a hydroxyalkyl group having 1 to 3 carbon atoms;
The antioxidant cosmetic preparation according to [1], wherein X is —CH 2 — or —NH—, and na is 1.
[3] The antioxidant cosmetic composition according to [1] or [2], wherein the component (A) is 1-(2-hydroxyethyl)-2-imidazolidinone.
[4] The antioxidant cosmetic preparation according to any one of [1] to [3], wherein the blending amount of component (A) is 10 to 200 mg/mL.
[5] The antioxidant cosmetic preparation according to any one of [1] to [4], wherein the component (B) is 1-piperidinepropionic acid.
[6] The antioxidant cosmetic preparation according to any one of [1] to [5], wherein the blending amount of component (B) is 0.5 to 100 mg/mL.
[7] The antioxidant cosmetic preparation according to any one of [1] to [6], wherein component (C) is dipotassium glycyrrhizinate.
[8] The antioxidant cosmetic preparation according to any one of [1] to [7], wherein the blending amount of component (C) is 0.01 to 10 mg/mL.
[9] The antioxidant cosmetic composition according to any one of [1] to [8], which has active oxygen scavenging ability.
[10] The antioxidant cosmetic preparation according to any one of [1] to [9], which comprises a combination of two or more of the components (A) to (C).
[11] A composition for external application to the skin comprising a combination of (B) an organic acid represented by formula (b) or a salt thereof and (C) glycyrrhizinic acid or a salt thereof.
Figure JPOXMLDOC01-appb-C000006
 (In formula (b), nb is an integer of 2 to 5.)
[12] The topical skin composition according to [11], wherein component (B) is 1-piperidinepropionic acid.
[13] The composition for external use on the skin according to [11] or [12], wherein the amount of component (B) is 0.5 to 2.5 mg/mL.
[14] The composition for external use on the skin according to any one of [11] to [13], wherein component (C) is dipotassium glycyrrhizinate.
[15] The composition for external use on the skin according to any one of [11] to [14], wherein the amount of component (C) is 0.01 to 0.1 mg/mL.
[16] The composition for external use on the skin according to any one of [11] to [15], which is a whitening cosmetic.
[17] The composition for external use on skin according to any one of [11] to [16], which has tyrosinase inhibitory activity.

　本発明によれば、活性酸素種に対する効果的な除去能を有する抗酸化化粧料を提供することができる。また、本発明によれば、効果的にチロシナーゼ活性を阻害する皮膚外用組成物を提供することができる。 The present invention can provide an antioxidant cosmetic that has effective removal capabilities against reactive oxygen species. The present invention can also provide a composition for external use on the skin that effectively inhibits tyrosinase activity.

発明の具体的説明Description of the Invention

［抗酸化化粧料］
　本発明の一形態は、（Ａ）特定の構造を有する環状カルボキサミド誘導体またはその塩、（Ｂ）特定の構造を有する有機酸またはその塩、および（Ｃ）グリチルリチン酸またはその塩、からなる群より選択される１種以上を含んでなる抗酸化化粧料に関するものである。
　大気中に酸素が存在し、酸素は紫外線等の影響を受けて活性酸素種を生成することが知られている。一般的に、この活性酸素種は、生体に対してコラーゲン繊維の架橋や、ＤＮＡの損傷、連鎖的ラジカルの発生による組織の損傷等の影響を及ぼし、その結果として、しわやたるみといった皮膚の老化が促進されると考えられている。これらの抑制には、生体内に生成した活性酸素種の消去能を有する物質を適用することが効果的であると考えられている。本発明による抗酸化化粧料は、優れた活性酸素除去能を有しており、効果的に活性酸素種を消去することができる。 [Antioxidant cosmetics]
One aspect of the present invention relates to an antioxidant cosmetic preparation comprising at least one selected from the group consisting of (A) a cyclic carboxamide derivative having a specific structure or a salt thereof, (B) an organic acid having a specific structure or a salt thereof, and (C) glycyrrhizinic acid or a salt thereof.
It is known that oxygen exists in the atmosphere, and that oxygen generates reactive oxygen species when affected by ultraviolet rays and the like. In general, it is believed that these reactive oxygen species have effects on the living body, such as cross-linking of collagen fibers, damage to DNA, and damage to tissues due to the generation of chain radicals, and as a result, skin aging such as wrinkles and sagging is accelerated. In order to suppress these, it is believed that applying a substance capable of eliminating reactive oxygen species generated in the living body is effective. The antioxidant cosmetic composition according to the present invention has excellent reactive oxygen scavenging ability and can effectively eliminate reactive oxygen species.

（Ａ）環状カルボキサミド誘導体またはその塩
　本発明による抗酸化化粧料は、式（ａ）で表される環状カルボキサミド誘導体またはその塩（以下、（Ａ）成分と称することがある。他の成分についても同様である。）を含むことができる。

Figure JPOXMLDOC01-appb-C000007
式中、
　Ｒ１は、水酸基で置換されていてもよい炭素数１～６の炭化水素基、または水素原子であり、
　Ｘは、－ＣＨ２－または－Ｎ（Ｒ２）－であり、ここで、Ｒ２は、水酸基で置換されていてもよい炭素数１～６の炭化水素基、または水素原子であり、かつ
　ｎａは、１～３の整数である。
　上記の炭化水素基は、特に限定されず、例えば、アルキル基、シクロアルキル基、アルケニル基、アルキニル基、シクロアルキルアルキル基、ハロアルキル基、アルコキシアルキル基、アルコキシカルボニルアルキル基であってよく、好ましくはアルキル基である。 (A) Cyclic Carboxamide Derivative or Salt thereof The antioxidant cosmetic composition according to the present invention can contain a cyclic carboxamide derivative represented by formula (a) or a salt thereof (hereinafter, sometimes referred to as component (A). The same applies to the other components).
Figure JPOXMLDOC01-appb-C000007
 In the formula,
R 1 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom;
X is —CH 2 — or —N(R 2 )—, where R 2 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom, and na is an integer of 1 to 3.
The above-mentioned hydrocarbon group is not particularly limited and may be, for example, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, a cycloalkylalkyl group, a haloalkyl group, an alkoxyalkyl group, or an alkoxycarbonylalkyl group, and is preferably an alkyl group.

　好ましい形態において、（Ａ）成分の式（ａ）において、
　Ｒ１が、炭素数１～３のヒドロキシアルキル基であり、
　Ｘが、－ＣＨ２－または－ＮＨ－であり、かつ
　ｎａが、１である。
　式（ａ）で表される環状カルボキサミド誘導体の具体例としては、例えば、以下が挙げられる。

Figure JPOXMLDOC01-appb-C000008
　（Ａ）成分は、最も好ましくは、１－（２－ヒドロキシエチル）－２－イミダゾリジノンである。 In a preferred embodiment, in the formula (a) of the component (A),
R 1 is a hydroxyalkyl group having 1 to 3 carbon atoms;
X is —CH 2 — or —NH—, and na is 1.
Specific examples of the cyclic carboxamide derivative represented by formula (a) include the following.
Figure JPOXMLDOC01-appb-C000008
 The component (A) is most preferably 1-(2-hydroxyethyl)-2-imidazolidinone.

　（Ａ）成分は、式（ａ）で表される環状カルボキサミド誘導体の塩であってもよい。塩の種類は、薬理学的に許容される塩であれば特に限定されず、無機塩であっても有機塩であってもよい。無機塩としては、例えば、塩酸塩、硫酸塩、リン酸塩、臭化水素酸塩、ナトリウム塩、カリウム塩、マグネシウム塩、カルシウム塩、マグネシウム塩、アンモニウム塩等が挙げられる。有機塩としては、例えば、酢酸塩、乳酸塩、マレイン酸塩、フマル酸塩、酒石酸塩、メタンスルホン酸塩、ｐ－トルエンスルホン酸塩、トリエタノールアミン塩、アミノ酸塩等が挙げられる。 The (A) component may be a salt of a cyclic carboxamide derivative represented by formula (a). The type of salt is not particularly limited as long as it is a pharmacologically acceptable salt, and may be an inorganic salt or an organic salt. Examples of inorganic salts include hydrochlorides, sulfates, phosphates, hydrobromides, sodium salts, potassium salts, magnesium salts, calcium salts, magnesium salts, and ammonium salts. Examples of organic salts include acetates, lactates, maleates, fumarates, tartrates, methanesulfonates, p-toluenesulfonates, triethanolamine salts, and amino acid salts.

　（Ａ）成分は、１種または２種以上を配合することができる。（Ａ）成分の配合量は、抗酸化化粧料の総量に対して、好ましくは１０～２００ｍｇ／ｍＬであり、より好ましくは１５～１８０ｍｇ／ｍＬであり、さらに好ましくは５０～１５０ｍｇ／ｍＬである。 The (A) component may be used in combination with one or more types. The amount of the (A) component is preferably 10 to 200 mg/mL, more preferably 15 to 180 mg/mL, and even more preferably 50 to 150 mg/mL, based on the total amount of the antioxidant cosmetic.

（Ｂ）有機酸またはその塩
　本発明による抗酸化化粧料は、式（ｂ）で表される有機酸またはその塩を含むことができる。

Figure JPOXMLDOC01-appb-C000009
式中、ｎｂは２～５の整数である。
　この有機酸には、ｎｂの数によって、１－ピペリジンプロピオン酸（ｎｂ＝２）、４－（１－ピペリジニル）ブタン酸（ｎｂ＝３）、５－（１－ピペリジニル）ペンタン酸（ｎｂ＝４）、６－（１－ピペリジニル）ヘキサン酸（ｎｂ＝５）が包含されるが、これらのうち好ましくは１－ピペリジンプロピオン酸である。 (B) Organic Acid or Salt Thereof The antioxidant cosmetic preparation according to the present invention may contain an organic acid represented by formula (b) or a salt thereof.
Figure JPOXMLDOC01-appb-C000009
 In the formula, nb is an integer from 2 to 5.
This organic acid includes, depending on the nb number, 1-piperidinepropionic acid (nb=2), 4-(1-piperidinyl)butanoic acid (nb=3), 5-(1-piperidinyl)pentanoic acid (nb=4), and 6-(1-piperidinyl)hexanoic acid (nb=5). Of these, 1-piperidinepropionic acid is preferred.

　（Ｂ）成分は、式（ｂ）で表される有機酸の塩であってもよい。塩の種類は、薬理学的に許容される塩であれば特に限定されず、無機塩であっても有機塩であってもよい。無機塩としては、例えば、塩酸塩、硫酸塩、リン酸塩、臭化水素酸塩、ナトリウム塩、カリウム塩、マグネシウム塩、カルシウム塩、アンモニウム塩等が挙げられる。有機塩としては、例えば、酢酸塩、乳酸塩、マレイン酸塩、フマル酸塩、酒石酸塩、クエン酸塩、メタンスルホン酸塩、ｐ－トルエンスルホン酸塩、トリエタノールアミン塩、ジエタノールアミン塩、アミノ酸塩等が挙げられる。 Component (B) may be a salt of an organic acid represented by formula (b). The type of salt is not particularly limited as long as it is a pharmacologically acceptable salt, and may be an inorganic salt or an organic salt. Examples of inorganic salts include hydrochlorides, sulfates, phosphates, hydrobromides, sodium salts, potassium salts, magnesium salts, calcium salts, and ammonium salts. Examples of organic salts include acetates, lactates, maleates, fumarates, tartrates, citrates, methanesulfonates, p-toluenesulfonates, triethanolamine salts, diethanolamine salts, and amino acid salts.

　（Ｂ）成分は、１種または２種以上を配合することができる。（Ｂ）成分の配合量は、抗酸化化粧料の総量に対して、好ましくは０．５～１００ｍｇ／ｍＬであり、より好ましくは３～９５ｍｇ／ｍＬであり、さらに好ましくは８～９０ｍｇ／ｍＬ、特に好ましくは１５～８５ｍｇ／ｍＬである。 The (B) component may be used in combination with one or more types. The amount of the (B) component is preferably 0.5 to 100 mg/mL, more preferably 3 to 95 mg/mL, even more preferably 8 to 90 mg/mL, and particularly preferably 15 to 85 mg/mL, relative to the total amount of the antioxidant cosmetic.

（Ｃ）グリチルリチン酸またはその塩
　本発明による抗酸化化粧料は、（Ｃ）グリチルリチン酸またはその塩を含むことができる。塩の種類は、薬理学的に許容される塩であれば特に限定されず、無機塩であっても有機塩であってもよい。グリチルリチン酸塩としては、例えば、ナトリウム塩、カリウム塩、アンモニウム塩、塩基性アミノ酸、またはアルカノールアミン塩等が挙げられ、具体的には、グリチルリチン酸モノアンモニウム、グリチルリチン酸ジカリウム、グリチルリチントリナトリウムが挙げられる。（Ｃ）成分は、好ましくはグリチルリチン酸ジカリウムである。 (C) Glycyrrhizic acid or its salt The antioxidant cosmetic according to the present invention may contain (C) glycyrrhizic acid or its salt. The type of salt is not particularly limited as long as it is a pharmacologically acceptable salt, and may be an inorganic salt or an organic salt. Examples of glycyrrhizinic acid salts include sodium salts, potassium salts, ammonium salts, basic amino acid salts, and alkanolamine salts, and specific examples include monoammonium glycyrrhizinate, dipotassium glycyrrhizinate, and trisodium glycyrrhizinate. The (C) component is preferably dipotassium glycyrrhizinate.

　（Ｃ）成分は、１種または２種以上を配合することができる。（Ｃ）成分の配合量は、抗酸化化粧料の総量に対して、好ましくは０．０１～１０ｍｇ／ｍＬであり、より好ましくは０．２～８ｍｇ／ｍＬであり、さらに好ましくは０．４～５ｍｇ／ｍＬ、特に好ましくは１.５～４．５ｍｇ／ｍＬである。 The component (C) may be used alone or in combination with two or more other components. The amount of component (C) to be used is preferably 0.01 to 10 mg/mL, more preferably 0.2 to 8 mg/mL, even more preferably 0.4 to 5 mg/mL, and particularly preferably 1.5 to 4.5 mg/mL, relative to the total amount of the antioxidant cosmetic.

　本発明による抗酸化化粧料は、（Ａ）～（Ｃ）成分のうちの１種以上を含むものであり、好ましくは１種または２種である。
　本発明の一形態において、本発明による抗酸化化粧料は、（Ａ）～（Ｃ）成分のうち２種以上の組み合わせを含み、より好ましくは（Ｂ）成分と（Ｃ）成分との組み合わせを含む。 The antioxidant cosmetic composition according to the present invention contains one or more of the components (A) to (C), and preferably contains one or two of them.
In one embodiment of the present invention, the antioxidant cosmetic composition according to the present invention contains a combination of two or more of the components (A) to (C), and more preferably contains a combination of the component (B) and the component (C).

［皮膚外用組成物］
　本発明の別の一形態は、（Ｂ）特定の構造を有する有機酸またはその塩と（Ｃ）グリチルリチン酸またはその塩成分との組み合わせを含んでなる皮膚外用組成物に関する。
　しみ、そばかす、くすみといった色素沈着は、一般的にメラニン蓄積に起因するものが多く、表皮におけるメラニンの蓄積には、メラノサイトにおけるチロシナーゼ活性が大きく影響すると考えられている。本発明による皮膚外用組成物はチロシナーゼ阻害活性を有しており、チロシナーゼ活性を効果的に阻害することができる。その結果、メラニンの生成を抑制することができ、色素沈着を予防および抑制することができる。したがって、本発明による組成物は、好ましくは美白化粧料である。本明細書において「美白」とは、主としてメラニンの生成を抑制し、しみ、そばかす、くすみ等を防ぐことを意味する。
　好ましい一形態において、本発明による皮膚外用組成物は、チロシナーゼ阻害活性剤である。 [External skin composition]
Another embodiment of the present invention relates to a composition for external application to the skin comprising a combination of (B) an organic acid having a specific structure or a salt thereof and (C) a glycyrrhizinic acid or a salt thereof component.
Pigmentation such as age spots, freckles, and dullness is generally caused by melanin accumulation, and it is believed that the accumulation of melanin in the epidermis is greatly influenced by tyrosinase activity in melanocytes. The composition for external use on the skin according to the present invention has tyrosinase inhibitory activity and can effectively inhibit tyrosinase activity. As a result, it is possible to suppress the production of melanin and prevent and suppress pigmentation. Therefore, the composition according to the present invention is preferably a whitening cosmetic. In this specification, "whitening" mainly means suppressing the production of melanin and preventing age spots, freckles, dullness, etc.
In a preferred embodiment, the composition for topical application to the skin according to the present invention is a tyrosinase inhibitor active agent.

（Ｂ）有機酸またはその塩
　本発明による皮膚外用組成物は、式（ｂ）で表される有機酸またはその塩を含む。

Figure JPOXMLDOC01-appb-C000010
式中、ｎｂは２～５の整数である。
　この有機酸には、ｎｂの数によって、１－ピペリジンプロピオン酸（ｎｂ＝２）、４－（１－ピペリジニル）ブタン酸（ｎｂ＝３）、５－（１－ピペリジニル）ペンタン酸（ｎｂ＝４）、６－（１－ピペリジニル）ヘキサン酸（ｎｂ＝５）が包含されるが、これらのうち好ましくは１－ピペリジンプロピオン酸である。 (B) Organic Acid or Salt Thereof The composition for external application to skin according to the present invention contains an organic acid represented by formula (b) or a salt thereof.
Figure JPOXMLDOC01-appb-C000010
 In the formula, nb is an integer from 2 to 5.
This organic acid includes, depending on the nb number, 1-piperidinepropionic acid (nb=2), 4-(1-piperidinyl)butanoic acid (nb=3), 5-(1-piperidinyl)pentanoic acid (nb=4), and 6-(1-piperidinyl)hexanoic acid (nb=5). Of these, 1-piperidinepropionic acid is preferred.

　（Ｂ）成分は、式（ｂ）で表される有機酸の塩であってもよい。塩の種類は、薬理学的に許容される塩であれば特に限定されず、無機塩であっても有機塩であってもよい。無機塩としては、例えば、塩酸塩、硫酸塩、リン酸塩、臭化水素酸塩、ナトリウム塩、カリウム塩、マグネシウム塩、カルシウム塩、アンモニウム塩等が挙げられる。有機塩としては、例えば、酢酸塩、乳酸塩、マレイン酸塩、フマル酸塩、酒石酸塩、クエン酸塩、メタンスルホン酸塩、ｐ－トルエンスルホン酸塩、トリエタノールアミン塩、ジエタノールアミン塩、アミノ酸塩等が挙げられる。 Component (B) may be a salt of an organic acid represented by formula (b). The type of salt is not particularly limited as long as it is a pharmacologically acceptable salt, and may be an inorganic salt or an organic salt. Examples of inorganic salts include hydrochlorides, sulfates, phosphates, hydrobromides, sodium salts, potassium salts, magnesium salts, calcium salts, and ammonium salts. Examples of organic salts include acetates, lactates, maleates, fumarates, tartrates, citrates, methanesulfonates, p-toluenesulfonates, triethanolamine salts, diethanolamine salts, and amino acid salts.

　（Ｂ）成分は、１種または２種以上を配合することができる。（Ｂ）成分の配合量は、皮膚外用組成物の総量に対して、好ましくは０．５～１５ｍｇ／ｍＬであり、より好ましくは０．７～５ｍｇ／ｍＬ、さらに好ましくは１～２ｍｇ／ｍＬである。 The component (B) may be one or more types. The amount of component (B) is preferably 0.5 to 15 mg/mL, more preferably 0.7 to 5 mg/mL, and even more preferably 1 to 2 mg/mL, based on the total amount of the topical skin composition.

（Ｃ）グリチルリチン酸またはその塩
　本発明による皮膚外用組成物は、（Ｃ）グリチルリチン酸またはその塩を含む。グリチルリチン酸塩としては、例えば、ナトリウム塩、カリウム塩、アンモニウム塩、塩基性アミノ酸、またはアルカノールアミン塩等が挙げられ、具体的には、グリチルリチン酸モノアンモニウム、グリチルリチン酸ジカリウム、グリチルリチントリナトリウムが挙げられる。（Ｃ）成分は、好ましくはグリチルリチン酸ジカリウムである。 (C) Glycyrrhizic acid or its salt The skin external composition according to the present invention comprises (C) glycyrrhizic acid or its salt.Glycyrrhizic acid salts include, for example, sodium salts, potassium salts, ammonium salts, basic amino acids, or alkanolamine salts, and specifically, glycyrrhizinic acid monoammonium, glycyrrhizinic acid dipotassium, and glycyrrhizinic acid trisodium.(C) component is preferably glycyrrhizinic acid dipotassium.

　（Ｃ）成分は、１種または２種以上を配合することができる。（Ｃ）成分の配合量は、皮膚外用組成物の総量に対して、好ましくは０．０１～０．８ｍｇ／ｍＬであり、より好ましくは０．０２～０．５ｍｇ／ｍＬ、さらに好ましくは０．０３～０．１ｍｇ／ｍＬである。 The component (C) may be used alone or in combination with two or more other components. The amount of component (C) is preferably 0.01 to 0.8 mg/mL, more preferably 0.02 to 0.5 mg/mL, and even more preferably 0.03 to 0.1 mg/mL, relative to the total amount of the composition for topical skin application.

　（Ｃ）成分の配合量に対する（Ｂ）成分の配合量（（Ｂ）／（Ｃ））は、質量比で、好ましくは５～２００であり、より好ましくは１０～５０である。 The amount of component (B) relative to the amount of component (C) ((B)/(C)) is preferably 5 to 200 by mass, and more preferably 10 to 50 by mass.

　本発明による抗酸化化粧料および皮膚外用組成物は、水をさらに含むことができる。水としては、化粧品、医薬部外品等に使用される水を使用することができ、例えば、精製水、超純水、イオン交換水、水道水等を使用することができる。 The antioxidant cosmetic and topical skin composition according to the present invention may further contain water. As the water, water used in cosmetics, quasi-drugs, etc. may be used, such as purified water, ultrapure water, ion-exchanged water, tap water, etc.

　本発明による抗酸化化粧料および皮膚外用組成物には、上記成分の他、通常化粧品や医薬品に用いられる任意成分を配合することができる。任意成分としては例えば、保湿剤、低級アルコール、増粘剤、界面活性剤、金属イオン封鎖剤、中和剤、ｐＨ調整剤、酸化防止剤、防腐剤、薬剤、紫外線吸収剤、粉末成分、油性成分、香料等が挙げられ、本発明の効果を奏する限り、一種または二種以上を配合することができる。 The antioxidant cosmetic and topical skin composition according to the present invention can contain optional ingredients that are normally used in cosmetics and pharmaceuticals, in addition to the above-mentioned ingredients. Optional ingredients include, for example, moisturizers, lower alcohols, thickeners, surfactants, sequestering agents, neutralizing agents, pH adjusters, antioxidants, preservatives, medicines, UV absorbers, powdered ingredients, oily ingredients, fragrances, etc., and one or more of these can be contained as long as the effects of the present invention are achieved.

　本発明による抗酸化化粧料および皮膚外用組成物の剤型は特に限定されるものではなく、例えば、溶液系、可溶化系、乳化系、粉末分散系、水－油二層系、水－油－粉末三層系、軟膏、ゲル、エアゾール等の任意の剤型をとることができる。また、使用形態も特に限定されるものではなく、例えば、化粧水、乳液、クリーム、エッセンス、ゼリー、ジェル、軟膏、パック、マスク、ファンデーション等の任意の形態をとることができる。
　本発明による抗酸化化粧料および皮膚外用組成物は、常法に従って製造することができる。 The formulation of the antioxidant cosmetic and topical skin composition according to the present invention is not particularly limited, and may take any formulation, such as a solution system, a solubilized system, an emulsion system, a powder dispersion system, a water-oil two-layer system, a water-oil-powder three-layer system, an ointment, a gel, an aerosol, etc. The form of use is also not particularly limited, and may take any form, such as a lotion, milky lotion, cream, essence, jelly, gel, ointment, pack, mask, foundation, etc.
The antioxidant cosmetic and topical skin composition according to the present invention can be produced according to a conventional method.

　以下の例に基づいて本発明を具体的に説明するが、本発明はこれらの例に限定されるものではない。 The present invention will be specifically explained based on the following examples, but the present invention is not limited to these examples.

［抗酸化化粧料の調製］
　超純水中に、（Ａ）成分として１－（２－ヒドロキシエチル）－２－イミダゾリジノンを、（Ｂ）成分として１－ピペリジンプロピオン酸を、（Ｃ）成分として、グリチルリチン酸ジカリウムを表１に記載の配合量になるように添加し、撹拌して、実施例１０１～１１８の抗酸化化粧料を調製した。 [Preparation of antioxidant cosmetic preparation]
1-(2-hydroxyethyl)-2-imidazolidinone as component (A), 1-piperidinepropionic acid as component (B), and dipotassium glycyrrhizinate as component (C) were added to ultrapure water in the amounts shown in Table 1, and the mixture was stirred to prepare the antioxidant cosmetics of Examples 101 to 118.

［活性酸素（ＤＰＰＨ）消去能の評価］
　実施例１０１～１１８の抗酸化化粧料の、ＤＰＰＨラジカルに対するラジカル消去能を以下の手順で評価した。
　９６ウェルプレートに６０μＬの各実施例の抗酸化化粧料または対照（対照には超純水を用いた）、６０μＬのエタノール（ＣＡＳ　Ｎｏ．６４－１７－５、日本アルコール）、４０μＬの０．２５Ｍ酢酸ｂｕｆｆｅｒ（ｐＨ５．５）を加え、３７℃で５分間インキュベートした。ブランクはＤＰＰＨの代替としてエタノールを用いた。１つの処理群に対し、３ウェルを使用した。５分後に４０μＬの７８．４μＭ　２，２－ジンフェニル－１－ピクリルヒドラジル（ＤＰＰＨ、ＣＡＳ　Ｎｏ．１８９８－６６－４、Ｓｉｇｍａ－Ａｌｄｒｉｃｈ）溶液を添加した。９６ウェルプレートを２７０ｒｐｍで３０秒間振とうした後、３７℃で３０分間インキュベートした。９６ウェルプレートを２７０ｒｐｍで１０秒間振とうし、ウェル内の色素を均一に分散した後、マイクロプレートリーダーを用いて５１７ｎｍの吸光度（ＯＤ５１７）を測定した。
　実施例の抗酸化化粧料および対照のＯＤ５１７から実施例の抗酸化化粧料のＤＰＰＨ消去率を次式により算出した。
　ＤＰＰＨラジカル消去率（％）＝｛（Ｃ－ＣＢ）－（Ｓ－ＳＢ）｝／（Ｃ－ＣＢ）×１００
式中、
Ｃ：対照のＯＤ５１７
ＣＢ：対照のブランクＯＤ５１７
Ｓ：実施例の抗酸化化粧料のＯＤ５１７
ＳＢ：実施例の抗酸化化粧料のブランクＯＤ５１７
である。
　得られた結果を、表１に記載した。 [Evaluation of active oxygen (DPPH) scavenging ability]
The antioxidant cosmetic compositions of Examples 101 to 118 were evaluated for their radical scavenging ability against DPPH radicals by the following procedure.
60 μL of the antioxidant cosmetic of each Example or control (ultrapure water was used for the control), 60 μL of ethanol (CAS No. 64-17-5, Nippon Alcohol), and 40 μL of 0.25 M acetic acid buffer (pH 5.5) were added to a 96-well plate and incubated at 37° C. for 5 minutes. Ethanol was used as a blank instead of DPPH. Three wells were used for each treatment group. After 5 minutes, 40 μL of 78.4 μM 2,2-diphenyl-1-picrylhydrazyl (DPPH, CAS No. 1898-66-4, Sigma-Aldrich) solution was added. The 96-well plate was shaken at 270 rpm for 30 seconds and then incubated at 37° C. for 30 minutes. The 96-well plate was shaken at 270 rpm for 10 seconds to uniformly disperse the dye in the wells, and then the optical density at 517 nm (OD 517 ) was measured using a microplate reader.
The DPPH scavenging rate of the antioxidant cosmetic of the Example was calculated from the OD 517 of the antioxidant cosmetic of the Example and the control according to the following formula.
DPPH radical scavenging rate (%) = {(C-CB) - (S-SB)} / (C-CB) x 100
In the formula,
C: Control OD 517
CB: control blank OD 517
S: OD 517 of the antioxidant cosmetic of the example
SB: Blank OD of the antioxidant cosmetic of the embodiment 517
It is.
The results obtained are shown in Table 1.

［有意差検定］
　評価ごとに、対照と、各実施例の抗酸化化粧料を、対応のないｔ検定で有意差検定を行った。検定はいずれも両側で有意水準を５％未満とした。Ｐ値を表１に記載した。

Figure JPOXMLDOC01-appb-T000011
[Significance test]
For each evaluation, a significant difference test was performed between the control and each example antioxidant cosmetic composition using an unpaired t-test. The significance level for all tests was set at less than 5% on both sides. The p-values are shown in Table 1.
Figure JPOXMLDOC01-appb-T000011

［皮膚外用組成物の調製］
　超純水中に、（Ｂ）成分として１－ピペリジンプロピオン酸を、（Ｃ）成分としてグリチルリチン酸ジカリウムを、表２に記載の配合量になるように添加し、撹拌して、実施例２０１および比較例２０１、２０２の皮膚外用組成物を調製した。 [Preparation of topical skin composition]
1-Piperidinepropionic acid as component (B) and dipotassium glycyrrhizinate as component (C) were added to ultrapure water in the amounts shown in Table 2 and stirred to prepare topical skin compositions of Example 201 and Comparative Examples 201 and 202.

［チロシナーゼ阻害活性効果の評価］
　実施例２０１および比較例２０１、２０２の皮膚外用組成物の、ジヒドロキシフェニルアラニン（ＤＯＰＡ）を基質としたチロシナーゼ活性に及ぼす効果を以下の手順で評価した。
　９６ウェルプレート（Ｃｏｒｎｉｎｇ）に２０μＬの各実施例および比較例の皮膚外用組成物または対照（対照には超純水を用いた）、４０μＬの４０ｕｎｉｔｓ／ｍＬチロシナーゼ（ＣＡＳ　Ｎｏ．９００２－１０－２、Ｓｉｇｍａ－Ａｌｄｒｉｃｈ）溶液および１００μＬの１００ｍＭリン酸ｂｕｆｆｅｒ（ｐＨ６．８）を加え、２３℃で３分間インキュベートした。ブランクはチロシナーゼ溶液の代替として１００ｍＭリン酸ｂｕｆｆｅｒを用いた。１つの処理群に対し、３ウェルを使用した。３分後に５０μＬの２．５ｍＭ３，４－Ｌ－ジヒドロキシフェニルアラニン（Ｌ－ＤＯＰＡ、ＣＡＳ　Ｎｏ．５９－９２－７、和光）溶液を添加し、９６ウェルプレートを２７０ｒｐｍで１０秒間振とうし、マイクロプレートリーダー（ＳＰＡＲＫ　１０Ｍ、ＴＥＣＡＮ）を用いて４９０ｎｍの吸光度（ＯＤ４９０）を測定した。測定したプレートを２３℃で１０分間インキュベートし、１０分後、４９０ｎｍの吸光度（ＯＤ４９０）を測定した。
　実施例および比較例のチロシナーゼ阻害活性率を次式により算出した。
　チロシナーゼ阻害活性率（％）＝１００－［｛（Ａｓ１０－Ａｂ１０）－（Ａｓ０－Ａｂ０）｝／（Ａｃ１０－Ａｃ０）×１００］
式中、
Ａｂ０：インキュベート前のブランクのＯＤ４９０
Ａｂ１０：インキュベート後のブランクのＯＤ４９０
Ａｃ０：インキュベート前の対照のＯＤ４９０
Ａｃ１０：インキュベート後の対照のＯＤ４９０
Ａｓ０：インキュベート前の各実施例および比較例の皮膚外用組成物のＯＤ４９０
Ａｓ１０：インキュベート後の各実施例および比較例の皮膚外用組成物のＯＤ４９０
である。
　得られた結果を、表２に記載した。 [Evaluation of tyrosinase inhibitory activity]
The effect of the skin topical compositions of Example 201 and Comparative Examples 201 and 202 on tyrosinase activity using dihydroxyphenylalanine (DOPA) as a substrate was evaluated by the following procedure.
20 μL of each of the skin topical compositions of Examples and Comparative Examples or a control (ultrapure water was used for the control), 40 μL of 40 units/mL tyrosinase (CAS No. 9002-10-2, Sigma-Aldrich) solution, and 100 μL of 100 mM phosphate buffer (pH 6.8) were added to a 96-well plate (Corning), and incubated for 3 minutes at 23° C. For the blank, 100 mM phosphate buffer was used instead of the tyrosinase solution. Three wells were used for one treatment group. After 3 minutes, 50 μL of 2.5 mM 3,4-L-dihydroxyphenylalanine (L-DOPA, CAS No. 59-92-7, Wako) solution was added, the 96-well plate was shaken at 270 rpm for 10 seconds, and the optical density at 490 nm (OD 490 ) was measured using a microplate reader (SPARK 10M, TECAN). The plate was incubated at 23° C. for 10 minutes, and the optical density at 490 nm (OD 490 ) was measured after 10 minutes.
The tyrosinase inhibitory activity rate of the examples and comparative examples was calculated according to the following formula.
Tyrosinase inhibitory activity rate (%) = 100 - [{(As10 - Ab10) - (As0 - Ab0)} / (Ac10 - Ac0) x 100]
In the formula,
Ab0: Blank OD 490 before incubation
Ab10: Blank OD 490 after incubation
Ac0: OD 490 of control before incubation
Ac10: OD 490 of control after incubation
As0: OD 490 of each of the compositions for external use on the skin of each of the Examples and Comparative Examples before incubation
As10: OD 490 of each of the compositions for external use on the skin of the Examples and Comparative Examples after incubation
It is.
The results obtained are shown in Table 2.

［有意差検定］
　評価ごとに、対照と、各実施例および比較例の皮膚外用組成物を、対応のないｔ検定で有意差検定を行った。検定はいずれも両側で有意水準を５％未満とした。Ｐ値を表２に記載した。

Figure JPOXMLDOC01-appb-T000012
[Significance test]
For each evaluation, a significant difference test was performed between the control and each of the skin topical compositions of the Examples and Comparative Examples using an unpaired t-test. The significance level for all tests was set to less than 5% on both sides. The P values are shown in Table 2.
Figure JPOXMLDOC01-appb-T000012

［処方例１～１４］
　以下の表に本発明の処方例を示す。表中の数値は質量％を示す。

Figure JPOXMLDOC01-appb-T000013
Figure JPOXMLDOC01-appb-T000014
Figure JPOXMLDOC01-appb-T000015
Figure JPOXMLDOC01-appb-T000016
Figure JPOXMLDOC01-appb-T000017
Figure JPOXMLDOC01-appb-T000018
Figure JPOXMLDOC01-appb-T000019
 [Formulation Examples 1 to 14]
Formulation examples of the present invention are shown in the following table. The values in the table indicate mass %.
Figure JPOXMLDOC01-appb-T000013
Figure JPOXMLDOC01-appb-T000014
Figure JPOXMLDOC01-appb-T000015
Figure JPOXMLDOC01-appb-T000016
Figure JPOXMLDOC01-appb-T000017
Figure JPOXMLDOC01-appb-T000018
Figure JPOXMLDOC01-appb-T000019

Claims (17)

　（Ａ）式（ａ）で表される環状カルボキサミド誘導体またはその塩、（Ｂ）式（ｂ）で表される有機酸またはその塩、および（Ｃ）グリチルリチン酸またはその塩からなる群より選択される１種以上を含んでなる抗酸化化粧料。
Figure JPOXMLDOC01-appb-C000001
 （式（ａ）中、
　Ｒ１は、水酸基で置換されていてもよい炭素数１～６の炭化水素基、または水素原子であり、
　Ｘは、－ＣＨ２－または－Ｎ（Ｒ２）－であり、ここで、Ｒ２は、水酸基で置換されていてもよい炭素数１～６の炭化水素基、または水素原子であり、かつ
　ｎａは、１～３の整数である）
Figure JPOXMLDOC01-appb-C000002
 （式（ｂ）中、ｎｂは２～５の整数である） An antioxidant cosmetic preparation comprising at least one selected from the group consisting of (A) a cyclic carboxamide derivative represented by formula (a) or a salt thereof, (B) an organic acid represented by formula (b) or a salt thereof, and (C) glycyrrhizinic acid or a salt thereof.
Figure JPOXMLDOC01-appb-C000001
 (In formula (a),
R 1 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom;
X is -CH2- or -N( R2 )-, where R2 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom, and na is an integer of 1 to 3.
Figure JPOXMLDOC01-appb-C000002
 (In formula (b), nb is an integer of 2 to 5.) 　式（ａ）において、
　Ｒ１が、炭素数１～３のヒドロキシアルキル基であり、
　Ｘが、－ＣＨ２－または－ＮＨ－であり、かつ
　ｎａが、１である、請求項１に記載の抗酸化化粧料。 In formula (a),
R 1 is a hydroxyalkyl group having 1 to 3 carbon atoms;
2. The antioxidant cosmetic preparation according to claim 1, wherein X is —CH 2 — or —NH—, and na is 1. 　（Ａ）成分が、１－（２－ヒドロキシエチル）－２－イミダゾリジノンである、請求項１または２に記載の抗酸化化粧料。 The antioxidant cosmetic according to claim 1 or 2, in which component (A) is 1-(2-hydroxyethyl)-2-imidazolidinone. 　（Ａ）成分の配合量が、１０～２００ｍｇ／ｍＬである、請求項１または２に記載の抗酸化化粧料。 The antioxidant cosmetic according to claim 1 or 2, in which the amount of component (A) is 10 to 200 mg/mL. 　（Ｂ）成分が、１－ピペリジンプロピオン酸である、請求項１または２に記載の抗酸化化粧料。 The antioxidant cosmetic according to claim 1 or 2, in which component (B) is 1-piperidinepropionic acid. 　（Ｂ）成分の配合量が、０．５～１００ｍｇ／ｍＬである、請求項１または２に記載の抗酸化化粧料。 The antioxidant cosmetic according to claim 1 or 2, in which the amount of component (B) is 0.5 to 100 mg/mL. 　（Ｃ）成分が、グリチルリチン酸ジカリウムである、請求項１または２に記載の抗酸化化粧料。 The antioxidant cosmetic according to claim 1 or 2, wherein component (C) is dipotassium glycyrrhizinate. 　（Ｃ）成分の配合量が、０．０１～１０ｍｇ／ｍＬである、請求項１または２に記載の抗酸化化粧料。 The antioxidant cosmetic according to claim 1 or 2, in which the amount of component (C) is 0.01 to 10 mg/mL. 　活性酸素除去能を有する、請求項１または２に記載の抗酸化化粧料。 An antioxidant cosmetic according to claim 1 or 2, which has the ability to remove active oxygen. 　（Ａ）～（Ｃ）成分のうちの２種以上の組み合わせを含んでなる、請求項１または２に記載の抗酸化化粧料。 The antioxidant cosmetic composition according to claim 1 or 2, which contains a combination of two or more of the components (A) to (C). 　（Ｂ）式（ｂ）で表される有機酸またはその塩と、（Ｃ）グリチルリチン酸またはその塩と、の組み合わせを含んでなる皮膚外用組成物。
Figure JPOXMLDOC01-appb-C000003
 （式（ｂ）中、ｎｂは２～５の整数である） A composition for external application to the skin comprising a combination of (B) an organic acid represented by formula (b) or a salt thereof and (C) glycyrrhizinic acid or a salt thereof.
Figure JPOXMLDOC01-appb-C000003
 (In formula (b), nb is an integer of 2 to 5.) 　（Ｂ）成分が、１－ピペリジンプロピオン酸である、請求項１１に記載の皮膚外用組成物。 The topical skin composition according to claim 11, wherein component (B) is 1-piperidinepropionic acid. 　（Ｂ）成分の配合量が、０．５～２．５ｍｇ／ｍＬである、請求項１１または１２に記載の皮膚外用組成物。 The composition for external use on skin according to claim 11 or 12, wherein the amount of component (B) is 0.5 to 2.5 mg/mL. 　（Ｃ）成分が、グリチルリチン酸ジカリウムである、請求項１１または１２に記載の皮膚外用組成物。 The composition for external use on skin according to claim 11 or 12, wherein component (C) is dipotassium glycyrrhizinate. 　（Ｃ）成分の配合量が、０．０１～０．１ｍｇ／ｍＬである、請求項１１または１２に記載の皮膚外用組成物。 The composition for external use on skin according to claim 11 or 12, wherein the amount of component (C) is 0.01 to 0.1 mg/mL. 　美白化粧料である、請求項１１または１２に記載の皮膚外用組成物。 The composition for external use on skin according to claim 11 or 12, which is a whitening cosmetic. 　チロシナーゼ阻害活性を有する、請求項１１または１２に記載の皮膚外用組成物。 The composition for external use on skin according to claim 11 or 12, which has tyrosinase inhibitory activity.
PCT/JP2023/037958 2022-11-02 2023-10-20 Composition Ceased WO2024095793A1 (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4017641A (en) * 1975-01-31 1977-04-12 The Procter & Gamble Company Skin moisturizing compositions containing 2-pyrrolidinone
JPS52151738A (en) * 1976-04-06 1977-12-16 Wella Ag Cosmetics
JP2012240911A (en) * 2011-05-13 2012-12-10 Shiseido Co Ltd Anti-wrinkle agent, matrix metalloprotenase (mmp) inhibitor and/or laminin 5 production promoter, each comprising 1-piperidine propionate
JP2019006697A (en) * 2017-06-22 2019-01-17 小林製薬株式会社 Active oxygen scavenger
WO2020204191A1 (en) * 2019-04-05 2020-10-08 株式会社 資生堂 Cosmetic containing ultraviolet wavelength conversion substance and medicinal agent
WO2022131108A1 (en) * 2020-12-15 2022-06-23 株式会社 資生堂 Dermis regeneration promoter

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4017641A (en) * 1975-01-31 1977-04-12 The Procter & Gamble Company Skin moisturizing compositions containing 2-pyrrolidinone
JPS52151738A (en) * 1976-04-06 1977-12-16 Wella Ag Cosmetics
JP2012240911A (en) * 2011-05-13 2012-12-10 Shiseido Co Ltd Anti-wrinkle agent, matrix metalloprotenase (mmp) inhibitor and/or laminin 5 production promoter, each comprising 1-piperidine propionate
JP2019006697A (en) * 2017-06-22 2019-01-17 小林製薬株式会社 Active oxygen scavenger
WO2020204191A1 (en) * 2019-04-05 2020-10-08 株式会社 資生堂 Cosmetic containing ultraviolet wavelength conversion substance and medicinal agent
WO2022131108A1 (en) * 2020-12-15 2022-06-23 株式会社 資生堂 Dermis regeneration promoter

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