JP2017081825A - Melanin production inhibitor - Google Patents
Melanin production inhibitor Download PDFInfo
- Publication number
- JP2017081825A JP2017081825A JP2015208187A JP2015208187A JP2017081825A JP 2017081825 A JP2017081825 A JP 2017081825A JP 2015208187 A JP2015208187 A JP 2015208187A JP 2015208187 A JP2015208187 A JP 2015208187A JP 2017081825 A JP2017081825 A JP 2017081825A
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- JP
- Japan
- Prior art keywords
- melanin production
- group
- production inhibitor
- present
- general 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.)
- Granted
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Landscapes
- Cosmetics (AREA)
Abstract
Description
本発明は、新規なメラニン産生抑制剤、及び該メラニン産生抑制剤を含有する化粧料に関する。尚、本発明の説明において、化粧料との用語は、医薬部外品を含むものとする。 The present invention relates to a novel melanin production inhibitor and a cosmetic containing the melanin production inhibitor. In the description of the present invention, the term cosmetics includes quasi drugs.
日焼けによる黒化のほか、しみ、くすみ、雀卵斑(そばかす)、肝斑等の色素沈着が関与する皮膚症状は、色素細胞(メラノサイト)のメラニン産生亢進が原因とされる。色素沈着が関与する皮膚症状は、他人による認識が容易であるため、見た目の印象に大きな影響を与える。このため、多くの人達が、肌の美観を維持することに関心を寄せている。この様な状況においては、色素沈着症状が関連する肌トラブル発生・悪化は、多くの人達にとっての大きな悩み事となり得る。 In addition to blackening due to sunburn, skin symptoms involving pigmentation such as blotches, dullness, sparrow eggspots and liver spots are caused by increased melanin production by pigment cells (melanocytes). Skin symptoms involving pigmentation are easy to recognize by others and have a significant impact on the visual impression. For this reason, many people are interested in maintaining the aesthetics of the skin. In such a situation, the occurrence and worsening of skin troubles associated with pigmentation symptoms can be a major concern for many people.
イタリアのDE ANGELI研究所により見出されたテルペン系抗潰瘍薬(例えば、特許文献1を参照)のゲファルナート(Gefarnate)には、消化管の粘膜抵抗性増強作用、粘液分泌亢進作用、粘膜微小循環改善作用等の薬理作用が確認され、抗潰瘍薬としての開発が進められた。ゲファルナートの抗潰瘍作用は、酸性ムコ多糖類の傷面への沈着の促進、胃粘膜中のヘキソサミン等の粘液の増量、内因性プロスタグランジンの増加等による粘膜の保護作用等により発揮される(例えば、非特許文献1を参照)。一方、ゲファルナートが有する抗潰瘍作用以外の薬理作用としては、ドライアイ、結膜炎等に対する角結膜疾患治療作用(例えば、特許文献2を参照)、肉芽増生及び痂皮形成促進作用による皮膚損傷治療作用(例えば、特許文献3を参照)、骨密度増加作用等による骨粗鬆症治療作用(例えば、特許文献4を参照)等の多様な薬理作用が報告されている。この様な薬理作用を基礎とし、抗潰瘍薬以外の用途拡大を目指した医薬品研究開発が進められている。一方、ゲファルナートの医薬品以外の用途としては、脱毛予防又は育毛効果が確認され、頭髪用化粧料(例えば、特許文献5を参照)への配合が知られている。さらに、ゲファルナートのエステル基部分を構造変換したファルネシル酢酸エステル誘導体に関しては、養毛作用(例えば、特許文献6を参照)、シワ改善作用(例えば、特許文献7を参照)等が報告されている。 Gefarnate, a terpene anti-ulcer drug found by DE ANGELI Institute in Italy (see, for example, Patent Document 1), has an effect of enhancing mucosal resistance, enhancing mucus secretion, and mucous membrane microcirculation in the digestive tract. Pharmacological action such as ameliorating action was confirmed, and development as an anti-ulcer drug was advanced. The antiulcer action of gefarnate is exerted by promoting the deposition of acidic mucopolysaccharides on the wound surface, increasing mucus such as hexosamine in the gastric mucosa, and protecting the mucosa by increasing endogenous prostaglandins ( For example, refer nonpatent literature 1.). On the other hand, as pharmacological actions other than the anti-ulcer action of gefarnate, keratoconjunctival disease treatment action for dry eye, conjunctivitis, etc. (see, for example, Patent Document 2), skin damage treatment action by granulation increase and crust formation promotion action For example, various pharmacological actions such as osteoporosis treatment action (see, for example, Patent Document 4) due to bone density increasing action and the like have been reported. Based on this pharmacological action, pharmaceutical research and development aimed at expanding applications other than anti-ulcer drugs is underway. On the other hand, as a use other than pharmaceuticals of gefarnate, hair loss prevention or hair growth effect has been confirmed, and blending into hair cosmetics (for example, see Patent Document 5) is known. Furthermore, with respect to farnesyl acetate derivatives obtained by converting the ester group portion of gefarnate, hair nourishing action (for example, see Patent Document 6), wrinkle improving action (for example, see Patent Document 7) and the like have been reported.
本発明は、上記の様な状況を鑑みてなされたものであり、化粧料等の成分として好適な、新規なメラニン産生抑制剤、及び該メラニン産生抑制剤を含有する化粧料を提供することを課題とする。 The present invention has been made in view of the above situation, and provides a novel melanin production inhibitor suitable as a component of cosmetics and the like and a cosmetic containing the melanin production inhibitor. Let it be an issue.
本発明者は、上記課題を解決するために新規なメラニン産生抑制剤を求めて、鋭意研究を重ねた結果、下記一般式(1)に表される化合物及び/又はその幾何異性体が、メラニン産生抑制作用を有することを見出した。また、前記一般式(1)に表される化合物及び/又はその幾何異性体は、化粧料に配合することにより優れた美白効果を発揮する。即ち、本発明は、以下に示す通りである。
<1> 下記一般式(1)に表される化合物及び/又はその幾何異性体からなる、メラニン産生抑制剤。
In order to solve the above-mentioned problems, the present inventor has sought for a novel melanin production inhibitor and conducted extensive research. As a result, the compound represented by the following general formula (1) and / or its geometrical isomer is melanin. It was found to have a production inhibitory effect. In addition, the compound represented by the general formula (1) and / or the geometric isomer thereof exhibits an excellent whitening effect when blended in cosmetics. That is, the present invention is as follows.
<1> A melanin production inhibitor comprising a compound represented by the following general formula (1) and / or a geometric isomer thereof.
[但し、式中R1は、炭素数1〜15の直鎖又は分岐の、飽和又は不飽和炭化水素基を表す。]
[Wherein, R 1 represents a linear or branched, saturated or unsaturated hydrocarbon group having 1 to 15 carbon atoms. ]
<2> 前記一般式(1)に表される化合物及び/又はその幾何異性体が、ゲファルナート(Gefarnate)及び/又はその幾何異性体である、<1>に記載のメラニン産生抑制剤。 <2> The melanin production inhibitor according to <1>, wherein the compound represented by the general formula (1) and / or a geometric isomer thereof is gefarnate and / or a geometric isomer thereof.
<3> <1>に記載のメラニン産生抑制剤を含有する、美白用化粧料。
<4> ゲファルナート(Gefarnate)及び/又はその幾何異性体からなるメラニン産生抑制剤を含有する、<3>に記載の美白用化粧料。
<5> <1>に記載のメラニン産生抑制剤を、美白用化粧料全量に対し0.0001質量%〜10質量%含有する、<3>又は<4>に記載の美白用化粧料。
<6> さらに、抗酸化剤を含有する、<3>〜<5>の何れかに記載の美白用化粧料。
<7> 前記抗酸化剤が、ビタミンE及び/又はその薬理学的に許容される塩である、<6>に記載の美白用化粧料。
<8> 美白用化粧料全量に対し、抗酸化剤を0.001質量%〜15質量%含有する、<6>又は<7>に記載の美白用化粧料。
<9> 前記一般式(1)に表される化合物及び/又はその幾何異性体と、ビタミンE及び/又はその薬理学的に許容される塩とを含有する、組成物。
<10> 美白のために用いる、<9>に記載の組成物。
<11> メラニン産生抑制剤としての使用のための上記一般式(1)に表される化合物及び/又はその幾何異性体。
<12> 美白剤としての使用のための上記一般式(1)に表される化合物及び/又はその幾何異性体。
<13> 上記一般式(1)に表される化合物及び/又はその幾何異性体を皮膚に投与することを含む、メラニンの産生を抑制する方法。
<14> 上記一般式(1)に表される化合物及び/又はその幾何異性体を皮膚に投与することを含む美白方法。
<3> A whitening cosmetic containing the melanin production inhibitor according to <1>.
<4> The whitening cosmetic according to <3>, comprising a melanin production inhibitor composed of Gefarnate and / or a geometric isomer thereof.
<5> The whitening cosmetic according to <3> or <4>, wherein the melanin production inhibitor according to <1> is contained in an amount of 0.0001% by mass to 10% by mass with respect to the total amount of the whitening cosmetic.
<6> The whitening cosmetic according to any one of <3> to <5>, further comprising an antioxidant.
<7> The whitening cosmetic according to <6>, wherein the antioxidant is vitamin E and / or a pharmacologically acceptable salt thereof.
<8> The whitening cosmetic according to <6> or <7>, which contains 0.001% by mass to 15% by mass of an antioxidant relative to the total amount of the whitening cosmetic.
<9> A composition comprising the compound represented by the general formula (1) and / or a geometric isomer thereof, and vitamin E and / or a pharmacologically acceptable salt thereof.
<10> The composition according to <9>, which is used for whitening.
<11> A compound represented by the above general formula (1) and / or a geometric isomer thereof for use as a melanin production inhibitor.
<12> A compound represented by the above general formula (1) and / or a geometric isomer thereof for use as a whitening agent.
<13> A method for suppressing the production of melanin, comprising administering the compound represented by the general formula (1) and / or a geometric isomer thereof to the skin.
<14> A whitening method comprising administering the compound represented by the general formula (1) and / or a geometric isomer thereof to the skin.
本発明によれば、新規なメラニン産生抑制剤、並びに該メラニン産生抑制剤を含有する化粧料を提供することが出来る。 ADVANTAGE OF THE INVENTION According to this invention, the cosmetics containing a novel melanin production inhibitor and this melanin production inhibitor can be provided.
本発明は、医薬品、化粧料(但し、日本でいう医薬部外品を含む)に好適な、前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤、並びに該メラニン産生抑制剤を含有する皮膚外用剤及び化粧料に関する。本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤は、メラニン産生抑制作用を有する、前記一般式(1)に表される化合物及び/又はその幾何異性体であれば特段の限定なく適用することが出来る。 The present invention is a melanin production inhibitor composed of the compound represented by the general formula (1) and / or its geometric isomer, which is suitable for pharmaceuticals and cosmetics (including quasi-drugs in Japan), In addition, the present invention relates to an external preparation for skin and a cosmetic containing the melanin production inhibitor. The melanin production inhibitor comprising the compound represented by the general formula (1) and / or its geometric isomer of the present invention has a melanin production inhibitory action and / or the compound represented by the general formula (1) and / or Any geometric isomer can be applied without any particular limitation.
本明細書において美白効果とは、色素沈着の予防効果及び/又は改善効果を含む。色素沈着の改善効果としては、既に形成された色素沈着を元の状態に戻す又は緩和する効果を例示できる。また、色素沈着の予防効果としては、形成される過程又は今後形成される色素沈着に対する抑制効果を例示できる。 In this specification, the whitening effect includes an effect of preventing and / or improving pigmentation. As an effect of improving pigmentation, an effect of returning or mitigating already formed pigmentation can be exemplified. In addition, as an effect of preventing pigmentation, an inhibitory effect on the process of formation or pigmentation formed in the future can be exemplified.
本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤は、皮膚外用剤に含有させることにより優れた美白効果を発揮する。また、本発明のメラニン産生抑制剤を配合した皮膚外用剤が有する美白効果としては、メラニン産生亢進に起因する色素沈着症状の予防又は改善効果であれば特段の限定なく適用することが出来、例えば、既に形成された色素沈着を元の状態に戻す又は緩和する効果に加え、形成される過程又は今後形成される色素沈着に対する抑制効果等が好適に挙げられる。さらに、本発明の皮膚外用剤は、通常の日焼けによる色素沈着症状に対する予防又は改善効果に加え、しみ、くすみ、雀卵斑(そばかす)、肝斑等のメラニン産生亢進による色素沈着異常症状に対する予防、改善又は治療効果を発揮する。 The melanin production inhibitor consisting of the compound represented by the general formula (1) and / or a geometric isomer thereof according to the present invention exhibits an excellent whitening effect when it is contained in a skin external preparation. In addition, as a whitening effect of the external preparation for skin containing the melanin production inhibitor of the present invention, it can be applied without particular limitation as long as it is a preventive or ameliorating effect of pigmentation caused by increased melanin production. In addition to the effect of returning or mitigating the pigmentation that has already been formed, the effect of suppressing the pigmentation process that will be formed or the pigmentation that will be formed in the future is preferred. Furthermore, the external preparation for skin of the present invention has a preventive or ameliorating effect on pigmentation symptoms caused by normal sunburn, as well as prevention of abnormal pigmentation symptoms caused by increased melanin production such as stains, dullness, sparrow eggs spots, and liver spots. Show improvement or therapeutic effect.
本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤は、化粧料に含有させることにより優れた美白効果を発揮する。また、本発明のメラニン産生抑制剤を配合した化粧料が有する美白効果としては、メラニン産生亢進に起因する色素沈着症状の予防又は改善効果であれば特段の限定なく適用することが出来、例えば、既に形成された色素沈着を元の状態に戻す又は緩和する効果に加え、形成される過程又は今後形成される色素沈着に対する抑制効果等が好適に挙げられる。さらに、本発明の化粧料は、通常の日焼けによる色素沈着症状に対する予防又は改善効果に加え、しみ、くすみ、雀卵斑(そばかす)、肝斑等のメラニン産生亢進による色素沈着異常症状に対する予防又は改善効果を発揮する。本発明の化粧料は美白のために使用する。 The melanin production inhibitor consisting of the compound represented by the general formula (1) and / or a geometric isomer thereof of the present invention exhibits an excellent whitening effect when it is contained in cosmetics. In addition, as a whitening effect possessed by a cosmetic containing the melanin production inhibitor of the present invention, it can be applied without particular limitation as long as it is a preventive or ameliorating effect of pigmentation caused by increased melanin production. In addition to the effect of returning or mitigating the pigmentation that has already been formed, the effect of suppressing the pigmentation process that will be formed or the pigmentation that will be formed in the future is preferred. Furthermore, the cosmetic of the present invention can prevent or improve pigmentation symptoms due to increased melanin production such as stains, dullness, sparrow egg flecks, liver spots, etc. in addition to the prevention or improvement effect on pigmentation symptoms caused by normal sunburn. Demonstrate the improvement effect. The cosmetic of the present invention is used for whitening.
本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤が有するメラニン産生抑制作用としては、メラニン産生を抑制する作用であれば特段の限定なく適用出来る。また、本発明のメラニン産生抑制作用を評価する方法としては、メラニン産生抑制作用が評価出来る方法であれば特段の限定なく適用することが出来、例えば、細胞内のメラニン合成過程において、特異的に細胞に取り込まれるチオウラシルを用い測定する方法が好適に例示出来る。かかる方法は、放射性同位元素で標識したチオウラシルを用い、放射活性を測定することにより細胞内に取り込まれたチオウラシル量を測定することで、メラニン産生量を測定することが出来る。この場合、放射活性が少ないほどメラニン産生量が少なく、メラニン産生抑制効果が大きいと判断することが出来る。本発明のメラニン産生抑制剤の内、好ましいものを具体的に挙げれば、後述する実施例1に記載の「培養ヒト正常メラノサイトを用いたメラニン産生抑制試験」においてメラニン産生抑制作用を示す成分が好適に例示出来る。また、本発明の「培養ヒト正常メラノサイトを用いたメラニン産生抑制試験」においてメラニン産生抑制作用を示す成分としては、被験物質が細胞毒性を示さない濃度においてメラニン産生抑制作用を示す成分、さらに好ましくは、前記濃度において統計的な有意差をもってメラニン産生抑制作用を示す成分が好適に例示出来る。 The melanin production inhibitory action possessed by the melanin production inhibitor comprising the compound represented by the general formula (1) of the present invention and / or its geometric isomer is applicable without particular limitation as long as it is an action that suppresses melanin production. I can do it. In addition, as a method for evaluating the melanin production inhibitory action of the present invention, any method that can evaluate the melanin production inhibitory action can be applied without particular limitation. For example, in the intracellular melanin synthesis process, A preferred example is a method of measurement using thiouracil taken up by cells. In such a method, the amount of melanin produced can be measured by measuring the amount of thiouracil incorporated into cells by measuring radioactivity using thiouracil labeled with a radioisotope. In this case, it can be determined that the smaller the radioactivity, the smaller the melanin production amount and the greater the melanin production inhibitory effect. Of the melanin production inhibitors of the present invention, specific examples of preferred ones include components that exhibit melanin production inhibitory activity in the “melanin production inhibition test using cultured human normal melanocytes” described in Example 1 described later. Can be illustrated. In addition, as a component exhibiting a melanin production inhibitory action in the “melanin production inhibition test using cultured normal human melanocytes” of the present invention, a component exhibiting a melanin production inhibitory action at a concentration at which the test substance does not exhibit cytotoxicity, more preferably The component which shows a melanin production inhibitory effect with a statistically significant difference in the said density | concentration can be illustrated suitably.
本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体に関し述べる。式中、R1は、炭素数1〜15の直鎖又は分岐の、飽和又は不飽和炭化水素基を表す。前記R1に関し、好ましいものを挙げれば、炭素数1〜15の、より好ましくは、炭素数4〜10の直鎖又は分岐のアルキル基、炭素数1〜15の、より好ましくは、炭素数4〜10の直鎖又は分岐のモノ、ジ又はトリアルケニル基、炭素数3〜15の、より好ましくは、炭素数4〜8の脂環式炭化水素基、炭素数6〜15の芳香族基などが好適に例示出来る。前記R1に関し、好ましいものを具体的に挙げれば、メチル基、エチル基、プロピル基、ブチル基、3−メチル−ブチル基、ペンチル基、ヘキシル基、ヘプチル基、オクチル基、3,7−ジメチルオクチル基、ノニル基、デシル基、ウンデシル基、ドデシル基、3,7,11−トリメチルドデシル基、トリデシル基、テトラデシル基、ペンタデシル基、2−プロペニル基、2−ブテニル基、3−メチル−2−ブテニル基、2−ペンテニル基、3−メチル−2−ペンテニル基、2−ヘキセニル基、3−メチル−2−ヘキセニル基、2−ヘプテニル基、3−メチル−2−ヘプテニル基、2−オクテニル基、3−メチル−2−オクテニル基、3,7−ジメチル−2−オクテニル基、2,6−オクタジエニル基、3,7−ジメチル−2,6−オクタジエニル基、2−ノネニル基、3−メチル−2−ノネニル基、2,6−ノナジエニル基、3,7−ジメチル−2,6−ノナジエニル基、3−メチル−2−ノネニル基、3,7−ジメチル2,6−ノナジエニル基、2−デセニル基、3−メチル−2−デセニル基、2,6−デカジエニル基、3,7−ジメチル−2,6−デカジエニル基、2−ウンデセニル基、3−メチル−2−ウンデセニル基、2,6−ウンデカジエニル基、3,7−ジメチル−2,6−ウンデカジエニル基、2−ドデセニル基、3−メチル−2−ドデセニル基、2,6−ドデカジエニル基、3,7−ジメチル−2,6−ドデカジエニル基、2,6,10−ドデカトリエニル基、3−メチル−2,6,10−ドデカトリエニル基、3,7−ジメチル−2,6,10−ドデカトリエニル基、3,7,11−トリメチル−2,6,10−ドデカトリエニル基、2−トリデセニル基、3−メチル−2−トリデセニル基、3,7−ジメチル−2−トリデセニル基、2,6−トリデカジエニル基、3−メチル−2,6−トリデカジエニル基、3,7−ジメチル−2,6−トリデカジエニル基、2,6,10−トリデカトリエニル基、3−メチル−2,6,10−トリデカトリエニル基、3,7−ジメチル−2,6,10−トリデカトリエニル基、3,7,11−トリメチル−2,6,10−トリフェカトリエニル基、2−テトラデセニル基、3−メチル−2−テトラデセニル基、2,6−テトラデカジエニル基、3−メチル−2,6−テトラデカジエニル基、2,6,10−テトラデカトリエニル基、3−メチル−2,6,10−テトラデカトリエニル基、2−ペンタデセニル基、2,6−ペネタデカジエニル基、2,6,10−ペンタデカトリエニル基、フェニル基、ナフチル基、ビフェニル基、シクロヘキシル基等が好適に例示出来、より好ましいものとしては、3−メチル−2−ブテニル基、3,7−ジメチル−2,6−オクタジエニル基、3,7,11−トリメチル−2,6,10−ドデカトエニル基が、さらに好ましいものとしては、3,7−ジメチル−2,6−オクタジエニル基が好適に例示出来る。かかる置換基を有する前記一般式(1)に表される化合物及び/又はその幾何異性体は、メラニン産生抑制作用を有し、化粧料に配合することにより優れた美白効果を発揮する。 The compound represented by the general formula (1) of the present invention and / or a geometric isomer thereof will be described. In the formula, R 1 represents a linear or branched, saturated or unsaturated hydrocarbon group having 1 to 15 carbon atoms. With regard to R 1 , preferable examples include straight-chain or branched alkyl groups having 1 to 15 carbon atoms, more preferably 4 to 10 carbon atoms, more preferably 1 to 15 carbon atoms, and more preferably 4 carbon atoms. -10 linear or branched mono-, di- or trialkenyl groups, C3-C15, more preferably C4-C8 alicyclic hydrocarbon groups, C6-C15 aromatic groups, etc. Can be suitably exemplified. Specific examples of preferred R 1 include methyl, ethyl, propyl, butyl, 3-methyl-butyl, pentyl, hexyl, heptyl, octyl, and 3,7-dimethyl. Octyl, nonyl, decyl, undecyl, dodecyl, 3,7,11-trimethyldodecyl, tridecyl, tetradecyl, pentadecyl, 2-propenyl, 2-butenyl, 3-methyl-2- Butenyl group, 2-pentenyl group, 3-methyl-2-pentenyl group, 2-hexenyl group, 3-methyl-2-hexenyl group, 2-heptenyl group, 3-methyl-2-heptenyl group, 2-octenyl group, 3-methyl-2-octenyl group, 3,7-dimethyl-2-octenyl group, 2,6-octadienyl group, 3,7-dimethyl-2,6-octadi Nyl group, 2-nonenyl group, 3-methyl-2-nonenyl group, 2,6-nonadienyl group, 3,7-dimethyl-2,6-nonadienyl group, 3-methyl-2-nonenyl group, 3,7- Dimethyl 2,6-nonadienyl group, 2-decenyl group, 3-methyl-2-decenyl group, 2,6-decadienyl group, 3,7-dimethyl-2,6-decadienyl group, 2-undecenyl group, 3-methyl 2-undecenyl group, 2,6-undecadienyl group, 3,7-dimethyl-2,6-undecadienyl group, 2-dodecenyl group, 3-methyl-2-dodecenyl group, 2,6-dodecadienyl group, 3,7 -Dimethyl-2,6-dodecadienyl group, 2,6,10-dodecatrienyl group, 3-methyl-2,6,10-dodecatrienyl group, 3,7-dimethyl-2,6,10-dodecatrienyl Group, 3,7,11-trimethyl-2,6,10-dodecatrienyl group, 2-tridecenyl group, 3-methyl-2-tridecenyl group, 3,7-dimethyl-2-tridecenyl group, 2,6 -Tridecadienyl group, 3-methyl-2,6-tridecadienyl group, 3,7-dimethyl-2,6-tridecadienyl group, 2,6,10-tridecatrienyl group, 3-methyl-2,6,10-tride Cattrienyl group, 3,7-dimethyl-2,6,10-tridecatrienyl group, 3,7,11-trimethyl-2,6,10-trifecatrienyl group, 2-tetradecenyl group, 3-methyl-2 -Tetradecenyl group, 2,6-tetradecadienyl group, 3-methyl-2,6-tetradecadienyl group, 2,6,10-tetradecatrienyl group, 3-methyl-2,6,10- Te A radecatrienyl group, 2-pentadecenyl group, 2,6-pentadecadienyl group, 2,6,10-pentadecatrienyl group, phenyl group, naphthyl group, biphenyl group, cyclohexyl group and the like can be suitably exemplified, and more Preferred examples include 3-methyl-2-butenyl group, 3,7-dimethyl-2,6-octadienyl group, and 3,7,11-trimethyl-2,6,10-dodecatoenyl group. 3,7-dimethyl-2,6-octadienyl group can be preferably exemplified. The compound represented by the general formula (1) having such a substituent and / or a geometric isomer thereof has a melanin production inhibitory action, and exhibits an excellent whitening effect when blended in a cosmetic.
本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体は、ファルネシル酢酸(5,9,13−trimethyl−4,8,12−tetradecatrienoic acid)と、炭素数1〜15の直鎖又は分岐の、飽和又は不飽和アルコールがエステル結合した化学構造を有するファルネシル酢酸エステル誘導体である。本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体の内、ゲファルナート(Gefarnate、3,7−dimethyl−2,6−octadienyl−5,9,13−trimethyl−4,8,12−tetradecatrienoate、CAS No 51−77−4)及びその幾何異性体は、市販の試薬を出発原料とし容易に合成することが出来る。ゲファルナート及びその幾何異性体の合成方法の内、好ましい方法を具体的に挙げれば、例えば、ファルネシル酢酸(5,9,13−trimethyl−4,8,12−tetradecatrienoic acid)及びゲラニオール(3,7−dimethyl−2,6−octadien−1−ol)を用い、エステル化反応により合成する方法が挙げられる。前記のエステル化反応においては、その反応条件の違いにより、ゲファルナート及びその幾何異性体の混合物等が生成するが、蒸留等の工程を経ることにより精製することが出来る。ゲファルナートは、淡黄色〜黄色の澄明な油状物質である。また、ゲファルナート及び/又はその幾何異性体以外の前記一般式(1)に表される化合物及び/又はその幾何異性体に関しては、通常市販されている化合物をそのまま、或いは蒸留等の常法に従い精製した後に使用することも可能である。かかる化合物は、ファルネシル酢酸と対応するアルコールから公知のエステル化反応により、或いは市販品のゲファルナートからエステル交換反応により容易に合成することが出来る。 The compound represented by the general formula (1) of the present invention and / or geometric isomers thereof are farnesyl acetic acid (5,9,13-trimethyl-4,8,12-tetradecatrienoic acid) and a carbon number of 1 to 15. A farnesyl acetate derivative having a chemical structure in which a linear or branched, saturated or unsaturated alcohol is ester-bonded. Among the compounds represented by the general formula (1) of the present invention and / or geometric isomers thereof, gefarnate (Gefarnate, 3,7-dimethyl-2,6-octadienyl-5,9,13-trimethyl-4, 8,12-tetradecatrienoate, CAS No 51-77-4) and geometric isomers thereof can be easily synthesized using commercially available reagents as starting materials. Among the methods for synthesizing gefarnate and its geometrical isomers, preferred methods are specifically mentioned. For example, farnesyl acetic acid (5,9,13-trimethyl-4,8,12-tetradecatrienoic acid) and geraniol (3,7- and dimethyl-2,6-octadien-1-ol). In the esterification reaction, gefarnate and a mixture of geometric isomers and the like are generated due to the difference in the reaction conditions, but it can be purified through a process such as distillation. Gefarnate is a pale yellow to yellow clear oil. In addition, with respect to the compound represented by the general formula (1) other than gefarnate and / or its geometric isomer and / or its geometric isomer, a commercially available compound is purified as it is or according to a conventional method such as distillation. It is also possible to use it after. Such a compound can be easily synthesized by a known esterification reaction from farnesyl acetic acid and the corresponding alcohol, or by a transesterification reaction from a commercially available gefarnate.
本発明の化粧料は、本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤を含有することを特徴とするが、その含有量やその他の構成については特に限定されない。また、本発明の化粧料には、前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤より選択される1種又は2種以上を含有させることが出来る。さらに、本発明の化粧料の調製方法も特に限定されない。本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤の化粧料における含有量には、特段の限定はないが、通常、化粧料全量に対し0.0001質量%以上、好ましくは、0.001質量%以上、より好ましくは、0.01質量%以上であり、通常、10質量%以下、好ましくは、5質量%以下、より好ましくは、3質量%以下である。これは、本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤の化粧料全量に対する含有量が、少なすぎると、目的とする効果が低下する傾向があり、多すぎても効果が頭打ちになる傾向があり、この系の自由度を損なう場合があるためである。 The cosmetic of the present invention is characterized by containing a melanin production inhibitor consisting of the compound represented by the general formula (1) of the present invention and / or a geometric isomer thereof. The configuration is not particularly limited. Moreover, the cosmetics of this invention can contain 1 type, or 2 or more types selected from the melanin production inhibitor which consists of a compound represented by the said General formula (1), and / or its geometrical isomer. . Furthermore, the method for preparing the cosmetic of the present invention is not particularly limited. The content of the melanin production inhibitor consisting of the compound represented by the general formula (1) of the present invention and / or a geometric isomer thereof in the cosmetic is not particularly limited, but is usually based on the total amount of the cosmetic. 0.0001 mass% or more, preferably 0.001 mass% or more, more preferably 0.01 mass% or more, and usually 10 mass% or less, preferably 5 mass% or less, more preferably 3 It is below mass%. This is because if the content of the melanin production inhibitor consisting of the compound represented by the general formula (1) and / or its geometric isomer of the present invention with respect to the total amount of the cosmetic is too small, the intended effect is lowered. This is because there is a tendency, and if it is too much, the effect tends to reach its peak, and the degree of freedom of this system may be impaired.
本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤は、美白効果以外の作用を奏することもある。その様な美白作用以外の作用の発現を目的として本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤を含有する化粧料であっても、メラニン産生抑制作用、更には、美白作用が発揮されている場合には、本発明の効果を利用するものであるので、本発明の技術範囲に属する。 The melanin production inhibitor comprising the compound represented by the general formula (1) of the present invention and / or a geometric isomer thereof may exhibit actions other than the whitening effect. Even if it is a cosmetic containing a melanin production inhibitor consisting of a compound represented by the general formula (1) of the present invention and / or a geometric isomer thereof for the purpose of expression of an action other than the whitening action, Since the effect of the present invention is used when the melanin production inhibitory action and further the whitening action are exhibited, it belongs to the technical scope of the present invention.
本発明の美白用化粧料においては、必須成分の前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤のほかに、通常の化粧料製造で使用される任意の成分を含有することが出来る。この様な任意の成分としては、例えば、マカデミアナッツ油、アボカド油、トウモロコシ油、オリーブ油、ナタネ油、ゴマ油、ヒマシ油、サフラワー油、綿実油、ホホバ油、ヤシ油、パーム油、液状ラノリン、硬化ヤシ油、硬化油、モクロウ、硬化ヒマシ油、ミツロウ、キャンデリラロウ、カルナウバロウ、イボタロウ、ラノリン、還元ラノリン、硬質ラノリン、ホホバロウ等のオイル、ワックス類;流動パラフィン、スクワラン、プリスタン、オゾケライト、パラフィン、セレシン、ワセリン、マイクロクリスタリンワックス等の炭化水素類;オレイン酸、イソステアリン酸、ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸、ベヘン酸、ウンデシレン酸等の高級脂肪酸類;セチルアルコール、ステアリルアルコール、イソステアリルアルコール、ベヘニルアルコール、オクチルドデカノール、ミリスチルアルコール、セトステアリルアルコール等の高級アルコール等;イソオクタン酸セチル、ミリスチン酸イソプロピル、イソステアリン酸ヘキシルデシル、アジピン酸ジイソプロピル、セバチン酸ジ−2−エチルヘキシル、乳酸セチル、リンゴ酸ジイソステアリル、ジ−2−エチルヘキサン酸エチレングリコール、ジカプリン酸ネオペンチルグリコール、ジ−2−ヘプチルウンデカン酸グリセリン、トリ−2−エチルヘキサン酸グリセリン、トリ−2−エチルヘキサン酸トリメチロールプロパン、トリイソステアリン酸トリメチロールプロパン、テトラ−2−エチルヘキサン酸ペンタンエリトリット等の合成エステル油類;ジメチルポリシロキサン、メチルフェニルポリシロキサン、ジフェニルポリシロキサン等の鎖状ポリシロキサン;オクタメチルシクロテトラシロキサン、デカメチルシクロペンタシロキサン、ドデカメチルシクロヘキサンシロキサン等の環状ポリシロキサン;アミノ変性ポリシロキサン、ポリエーテル変性ポリシロキサン、アルキル変性ポリシロキサン、フッ素変性ポリシロキサン等の変性ポリシロキサン等のシリコーン油等の油剤類;脂肪酸セッケン(ラウリン酸ナトリウム、パルミチン酸ナトリウム等)、ラウリル硫酸カリウム、アルキル硫酸トリエタノールアミンエーテル等のアニオン界面活性剤類;塩化ステアリルトリメチルアンモニウム、塩化ベンザルコニウム、ラウリルアミンオキサイド等のカチオン界面活性剤類;イミダゾリン系両性界面活性剤(2−ココイル−2−イミダゾリニウムヒドロキサイド−1−カルボキシエチロキシ2ナトリウム塩等)、ベタイン系界面活性剤(アルキルベタイン、アミドベタイン、スルホベタイン等)、アシルメチルタウリン等の両性界面活性剤類;ソルビタン脂肪酸エステル類(ソルビタンモノステアレート、セスキオレイン酸ソルビタン等)、グリセリン脂肪酸類(モノステアリン酸グリセリン等)、プロピレングリコール脂肪酸エステル類(モノステアリン酸プロピレングリコール等)、硬化ヒマシ油誘導体、グリセリンアルキルエーテル、POEソルビタン脂肪酸エステル類(POEソルビタンモノオレエート、モノステアリン酸ポリオキエチレンソルビタン等)、POEソルビット脂肪酸エステル類(POE−ソルビットモノラウレート等)、POEグリセリン脂肪酸エステル類(POE−グリセリンモノイソステアレート等)、POE脂肪酸エステル類(ポリエチレングリコールモノオレート、POEジステアレート等)、POEアルキルエーテル類(POE2−オクチルドデシルエーテル等)、POEアルキルフェニルエーテル類(POEノニルフェニルエーテル等)、プルロニック型類、POE・POPアルキルエーテル類(POE・POP2−デシルテトラデシルエーテル等)、テトロニック類、POEヒマシ油・硬化ヒマシ油誘導体(POEヒマシ油、POE硬化ヒマシ油等)、ショ糖脂肪酸エステル、アルキルグルコシド等の非イオン界面活性剤類;ポリエチレングリコール、グリセリン、1,3−ブチレングリコール、エリスリトール、ソルビトール、キシリトール、マルチトール、プロピレングリコール、ジプロピレングリコール、ジグリセリン、イソプレングリコール、1,2−ペンタンジオール、2,4−ヘキサンジオール、1,2−ヘキサンジオール、1,2−オクタンジオール等の多価アルコール類;ピロリドンカルボン酸ナトリウム、乳酸、乳酸ナトリウム等の保湿成分類;表面を処理されていても良い、マイカ、タルク、カオリン、合成雲母、炭酸カルシウム、炭酸マグネシウム、無水ケイ酸(シリカ)、酸化アルミニウム、硫酸バリウム等の粉体類;表面を処理されていても良い、ベンガラ、黄酸化鉄、黒酸化鉄、酸化コバルト、群青、紺青、酸化チタン、酸化亜鉛の無機顔料類;表面を処理されていても良い、雲母チタン、魚燐箔、オキシ塩化ビスマス等のパール剤類;レーキ化されていても良い赤色202号、赤色228号、赤色226号、黄色4号、青色404号、黄色5号、赤色505号、赤色230号、赤色223号、橙色201号、赤色213号、黄色204号、黄色203号、青色1号、緑色201号、紫色201号、赤色204号等の有機色素類;ポリエチレン末、ポリメタクリル酸メチル、ナイロン粉末、オルガノポリシロキサンエラストマー等の有機粉体類;パラアミノ安息香酸系紫外線吸収剤;アントラニル酸系紫外線吸収剤;サリチル酸系紫外線吸収剤;桂皮酸系紫外線吸収剤;ベンゾフェノン系紫外線吸収剤;糖系紫外線吸収剤;2−(2’−ヒドロキシ−5’−t−オクチルフェニル)ベンゾトリアゾール、4−メトキシ−4’−t−ブチルジベンゾイルメタン等の紫外線吸収剤類;エタノール、イソプロパノール等の低級アルコール類;ビタミンA又はその誘導体、ビタミンB6塩酸塩、ビタミンB6トリパルミテート、ビタミンB6ジオクタノエート、ビタミンB2又はその誘導体、ビタミンB12、ビタミンB15又はその誘導体等のビタミンB類;α−トコフェロール、β−トコフェロール、γ−トコフェロール、δ−トコフェロール、ビタミンEアセテート等のビタミンE類、ビタミンD類、ビタミンH、パントテン酸、パンテチン、ピロロキノリンキノン等のビタミン類等;フェノキシエタノール等の抗菌剤などが好ましく例示出来る。 In the whitening cosmetic of the present invention, in addition to the essential component melanin production inhibitor comprising the compound represented by the general formula (1) and / or a geometric isomer thereof, it is used in normal cosmetic production. Arbitrary components can be contained. Such optional ingredients include, for example, macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, palm oil, palm oil, liquid lanolin, hardened palm Oils, hydrogenated oils, moles, hydrogenated castor oils, beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax, oils, waxes; liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, Hydrocarbons such as petroleum jelly and microcrystalline wax; higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid; cetyl alcohol, stearyl alcohol, isostear Higher alcohols such as alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, apple Diisostearyl acid, ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, glycerin tri-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, Synthetic ester oils such as trimethylolpropane triisostearate and pentane erythritol tetra-2-ethylhexanoate; dimethylpolysiloxane, Linear polysiloxanes such as siloxane and diphenylpolysiloxane; cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexanesiloxane; amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, Oil agents such as silicone oils such as modified polysiloxanes such as fluorine-modified polysiloxanes; Anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine ether of alkyl sulfates; Cationic surfactants such as stearyltrimethylammonium, benzalkonium chloride and laurylamine oxide; imidazoline-based amphoteric surfactants (2-cocoyl-2-imi Amphoteric surfactants such as dacolinium hydroxide-1-carboxyethyloxy disodium salt), betaine surfactants (alkylbetaine, amidebetaine, sulfobetaine, etc.), acylmethyltaurine; sorbitan fatty acid esters ( Sorbitan monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (such as glyceryl monostearate), propylene glycol fatty acid esters (such as propylene glycol monostearate), hardened castor oil derivatives, glycerin alkyl ether, POE sorbitan fatty acid ester (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbite fatty acid esters (POE-sorbitol monolaurate, etc.), POE glycerin fatty acid Steal (POE-glycerin monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether, etc.), POE alkyl phenyl ethers (POE nonylphenyl) Ethers, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), Nonionic surfactants such as sucrose fatty acid esters and alkyl glucosides; polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propyre Polyhydric alcohols such as glycol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexanediol, 1,2-hexanediol, 1,2-octanediol; sodium pyrrolidone carboxylate Moisturizing ingredients such as lactic acid and sodium lactate; powders such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, barium sulfate, etc. whose surface may be treated Body; surface treated, bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide inorganic pigments; surface treated, mica titanium Pearls such as fish phosphorus foil, bismuth oxychloride; red 202 which may be raked, red Color 228, Red 226, Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, Red 213, Yellow 204, Yellow 203, Blue 1 No., green 201, purple 201, red 204, etc .; organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomer; para-aminobenzoic acid UV absorbers; anthranils Acid UV absorbers; salicylic acid UV absorbers; cinnamic acid UV absorbers; benzophenone UV absorbers; sugar UV absorbers; 2- (2′-hydroxy-5′-t-octylphenyl) benzotriazole; UV absorbers such as 4-methoxy-4'-t-butyldibenzoylmethane; lower alcohols such as ethanol and isopropanol Cole: Vitamin A or derivatives thereof, vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or derivatives thereof, vitamin B such as vitamin B12, vitamin B15 or derivatives thereof; α-tocopherol, β- Vitamin E such as tocopherol, γ-tocopherol, δ-tocopherol, and vitamin E acetate, vitamin D, vitamin H, pantothenic acid, panthetin, vitamins such as pyrroloquinoline quinone, etc .; antibacterial agents such as phenoxyethanol can be preferably exemplified .
本発明の化粧料には、前記任意成分の内、特に、抗酸化作用を有する成分を配合することが好ましい。本発明の化粧料に配合する抗酸化作用を有する成分としては、ビタミンA類、その誘導体及びそれらの塩、ビタミンB類、その誘導体及びそれらの塩、ビタミンD類、その誘導体及びそれらの塩、ビタミンE類、その誘導体及びそれらの塩、ジブチルヒドロキシトルエン(BHT)とブチルヒドロキシアニソール及びそれらの塩、フェルラ酸とカフェー酸、その誘導体及びそれらの塩などが好適に例示出来る。かかる抗酸化作用を有する成分の内、好ましいものとしては、α−、β−、γ−、δ−トコフェロール等のビタミンE及び/又はその薬理学的に許容される塩が、さらに好ましくは、δ−トコフェロール及びそれら薬理学的に許容される塩が好適に例示出来る。また、前記の抗酸化作用を有する成分としては、エーザイフード・ケミカル株式会社より市販され、δ−d−トコフェロールを主要な成分とするイーミックス−Dが、特に好ましい。ここで、前記抗酸化作用を有する成分の生理的に許容される塩としては、例えば、ナトリウム、カリウム等のアルカリ金属塩、カルシウム、マグネシウム等のアルカリ土類金属塩、トリエタノールアミンやトリエチルアミン等の有機アミン塩、アンモニウム塩、アルギニンやリジン等の塩基性アミノ酸塩等が好ましく例示出来る。かかる抗酸化作用を有する成分は、前記一般式(1)に表される化合物及び/又はその幾何異性体と共に化粧料等に含有することにより、前記一般式(1)に表される化合物及び/又はその幾何異性体の溶液又は製剤中の安定性を向上する。これにより、前記一般式(1)に表される化合物及び/又はそれらの薬理学的に許容される塩を含有する化粧料は、長期間保存した後においても優れた美白効果を発揮することが出来る。この様な効果を奏するためには、前記抗酸化作用を有する成分から選択される1種乃至は2種以上を、総量で、0.001質量%〜15質量%含有することが好ましく、0.01質量%〜10質量%含有することがより好ましい。これは少なすぎると前記効果を奏しない場合が存し、多すぎても、効果が頭打ちになり、この系の自由度を損なう場合が存するためである。 In the cosmetic of the present invention, it is preferable to blend a component having an antioxidant action among the above optional components. Ingredients having an antioxidant action to be blended in the cosmetics of the present invention include vitamins A, derivatives thereof and salts thereof, vitamins B, derivatives thereof and salts thereof, vitamins D, derivatives thereof and salts thereof, Preferable examples include vitamin E, derivatives thereof and salts thereof, dibutylhydroxytoluene (BHT) and butylhydroxyanisole and salts thereof, ferulic acid and caffeic acid, derivatives thereof and salts thereof, and the like. Among these components having an antioxidant action, vitamin E such as α-, β-, γ-, and δ-tocopherol and / or a pharmacologically acceptable salt thereof is more preferable. -Tocopherols and pharmacologically acceptable salts thereof can be preferably exemplified. Moreover, as a component which has the said antioxidant activity, Emix-D which is marketed from Eisai Food Chemical Co., Ltd. and uses (delta) -d-tocopherol as a main component is especially preferable. Here, as the physiologically acceptable salt of the component having an antioxidant action, for example, alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, triethanolamine, triethylamine and the like Preferred examples include organic amine salts, ammonium salts, and basic amino acid salts such as arginine and lysine. The component having such an antioxidant action is contained in cosmetics together with the compound represented by the general formula (1) and / or the geometric isomer thereof, so that the compound represented by the general formula (1) and / or Or the stability in the solution or formulation of the geometric isomer is improved. Thereby, the cosmetics containing the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof can exhibit an excellent whitening effect even after being stored for a long time. I can do it. In order to exert such effects, it is preferable to contain 0.001% by mass to 15% by mass in a total amount of one or more selected from the above-mentioned components having an antioxidant action. It is more preferable to contain 01 mass%-10 mass%. This is because if the amount is too small, the above-described effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.
また、本発明の化粧料における本発明のメラニン産生抑制剤の含有質量を1とした時に、前記抗酸化作用を有する成分の含有質量は、好ましくは0.001〜15、より好ましくは0.01〜10、さらに好ましくは0.02〜5である。 In addition, when the content of the melanin production inhibitor of the present invention in the cosmetic of the present invention is 1, the content of the component having an antioxidant action is preferably 0.001 to 15, more preferably 0.01. -10, more preferably 0.02-5.
本発明の化粧料は、本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤、及び前記の任意成分を常法に従って処理し、ローション、乳液、エッセンス、クリーム、パックなどの各種製剤に加工することにより、製造することが出来る。さらに、その剤形としては、化粧料の領域で知られているものであれば特段の限定はなく、ローション製剤、水中油乳化製剤、油中水乳化製剤、複合エマルション乳化製剤等に好ましく例示出来る。複合エマルジョン剤形では、水相を連続相とし、これに油中水乳化物が分散したW/O/W剤形、油相を連続相とし、これに水中油乳化物が分散したO/W/O乳化剤形、これらと油中水乳化剤形の混在系、これらと水中油乳化剤形の混在系などが存し、これらの何れもが適用可能である。 The cosmetic of the present invention is a lotion, emulsion obtained by treating a melanin production inhibitor comprising the compound represented by the general formula (1) of the present invention and / or a geometric isomer thereof, and the above-mentioned optional ingredients according to a conventional method. It can be produced by processing into various preparations such as essence, cream and pack. Furthermore, the dosage form is not particularly limited as long as it is known in the cosmetics field, and can be preferably exemplified as a lotion preparation, an oil-in-water emulsion preparation, a water-in-oil emulsion preparation, a composite emulsion emulsion preparation, and the like. . In the composite emulsion dosage form, an aqueous phase is a continuous phase, and a W / O / W dosage form in which a water-in-oil emulsion is dispersed therein. An O / W in which an oil phase is a continuous phase and an oil-in-water emulsion is dispersed therein. There are / O emulsifier type, mixed system of these and water-in-oil emulsifier type, mixed system of these and oil-in-water emulsifier type, and any of these can be applied.
本発明の前記一般式(1)に表される化合物及び/又はその幾何異性体からなるメラニン産生抑制剤、及び前記の任意成分を含む乳化剤形の化粧料の製造は、発明のメラニン産生抑制剤を含む油溶性成分と、水溶性成分をそれぞれ均一に混合してから乳化することにより行うことが好ましい。 The production of a melanin production inhibitor comprising the compound represented by the general formula (1) of the present invention and / or a geometric isomer thereof, and an emulsifier-type cosmetic comprising the above-mentioned optional ingredients is a melanin production inhibitor of the invention. It is preferable to carry out the emulsification after uniformly mixing the oil-soluble component containing water and the water-soluble component.
本発明は前記一般式(1)に表される化合物及び/又はその幾何異性体と、ビタミンE及び/又はその薬理学的に許容される塩とを含有する、組成物にも関する。本発明の組成物は、前記一般式(1)に表される化合物及び/又はその幾何異性体の安定性に優れ、長期間保存した後においても優れた生理活性を有する。
前記生理活性としては、粘膜抵抗性増強作用、粘液分泌亢進作用及び粘膜微小循環改善作用等の抗潰瘍作用;ドライアイ及び結膜炎等に対する角結膜疾患治療作用;肉芽増生及び痂皮形成促進作用による皮膚損傷治療作用;骨密度増加作用等による骨粗鬆症治療作用;脱毛予防、育毛作用などの養毛作用;シワ改善作用;美白作用が例示でき、特に好ましくは美白作用が例示できる。
本発明の組成物は、好ましくは美白のために用いる。本発明の組成物は、優れた美白効果を有する。
The present invention also relates to a composition comprising the compound represented by the general formula (1) and / or a geometric isomer thereof, and vitamin E and / or a pharmacologically acceptable salt thereof. The composition of the present invention is excellent in stability of the compound represented by the general formula (1) and / or its geometric isomer, and has excellent physiological activity even after being stored for a long period of time.
The physiological activity includes anti-ulcer action such as mucosal resistance enhancing action, mucus secretion enhancing action and mucosal microcirculation improving action; keratoconjunctival disease treatment action for dry eye and conjunctivitis, etc .; granulation increase and skin formation promoting action Injury treatment effect; osteoporosis treatment effect by bone density increasing action and the like; hair restoration action such as hair loss prevention and hair growth action; wrinkle improving action; whitening action, particularly preferably whitening action.
The composition of the present invention is preferably used for whitening. The composition of the present invention has an excellent whitening effect.
本発明においてビタミンE及び/又はその薬理学的に許容される塩としては、α−、β−、γ−、δ−トコフェロール及び/又はその薬理学的に許容される塩が、さらに好ましくは、δ−トコフェロール及びそれら薬理学的に許容される塩が好適に例示出来る。また、本発明においては、ビタミンE及び/又はその薬理学的に許容される塩として、エーザイフード・ケミカル株式会社より市販され、δ−d−トコフェロールを主要な成分とするイーミックス−Dを用いてもよい。ここで、ビタミンEの生理的に許容される塩としては、例えば、ナトリウム、カリウム等のアルカリ金属塩、カルシウム、マグネシウム等のアルカリ土類金属塩、トリエタノールアミンやトリエチルアミン等の有機アミン塩、アンモニウム塩、アルギニンやリジン等の塩基性アミノ酸塩等が好ましく例示出来る。 In the present invention, vitamin E and / or pharmacologically acceptable salt thereof is more preferably α-, β-, γ-, δ-tocopherol and / or pharmacologically acceptable salt thereof, Preferred examples include δ-tocopherol and pharmacologically acceptable salts thereof. In the present invention, vitamin E and / or its pharmacologically acceptable salt is commercially available from Eisai Food Chemical Co., Ltd. and uses Emix-D containing δ-d-tocopherol as a main component. May be. Here, physiologically acceptable salts of vitamin E include, for example, alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, organic amine salts such as triethanolamine and triethylamine, ammonium Preferred examples include salts and basic amino acid salts such as arginine and lysine.
本発明の組成物は、医薬品又は化粧料(但し、日本でいう医薬部外品を含む)として用いることが好ましい。
本発明の組成物の剤形は特に限定されず、例えば、カプセル剤、錠剤、顆粒剤、注射剤、坐剤、貼付剤、皮膚外用剤などの剤形とすることができる。製剤化においては、薬剤学的に許容される他の製剤素材、例えば、賦形剤、崩壊剤、滑沢剤、結合剤、酸化防止剤、着色剤、凝集防止剤、吸収促進剤、溶解補助剤、安定化剤などを適宜添加して調製することができる。
本発明の組成物を皮膚外用剤とする場合には、医薬品又は化粧料の領域で知られているものであれば特段の限定はなく、軟膏剤、ローション製剤、水中油乳化製剤、油中水乳化製剤、複合エマルション乳化製剤等の剤形とすることができる。複合エマルジョン剤形では、水相を連続相とし、これに油中水乳化物が分散したW/O/W剤形、油相を連続相とし、これに水中油乳化物が分散したO/W/O乳化剤形、これらと油中水乳化剤形の混在系、これらと水中油乳化剤形の混在系などが存し、これらの何れもが適用可能である。
The composition of the present invention is preferably used as a pharmaceutical or a cosmetic (including quasi-drugs in Japan).
The dosage form of the composition of this invention is not specifically limited, For example, it can be set as dosage forms, such as a capsule, a tablet, a granule, an injection, a suppository, a patch, and an external preparation for skin. In formulation, other pharmaceutically acceptable formulation materials such as excipients, disintegrants, lubricants, binders, antioxidants, colorants, anti-aggregation agents, absorption enhancers, solubilizers An agent, a stabilizer and the like can be added as appropriate.
When the composition of the present invention is used as an external preparation for skin, there is no particular limitation as long as it is known in the field of pharmaceuticals or cosmetics, and ointments, lotions, oil-in-water emulsions, water-in-oil It can be set as dosage forms, such as an emulsion formulation and a composite emulsion emulsion formulation. In the composite emulsion dosage form, an aqueous phase is a continuous phase, and a W / O / W dosage form in which a water-in-oil emulsion is dispersed therein. An O / W in which an oil phase is a continuous phase and an oil-in-water emulsion is dispersed therein. There are / O emulsifier type, mixed system of these and water-in-oil emulsifier type, mixed system of these and oil-in-water emulsifier type, and any of these can be applied.
本発明は、メラニン産生抑制剤としての使用のための上記一般式(1)に表される化合物及び/又はその幾何異性体に関する。
また、本発明は、美白剤としての使用のための上記一般式(1)に表される化合物及び/又はその幾何異性体である。
これらの発明の好ましい実施の形態は、上述の発明の実施の形態と同様である。
The present invention relates to a compound represented by the above general formula (1) and / or a geometric isomer thereof for use as a melanin production inhibitor.
Moreover, this invention is a compound represented by the said General formula (1) for use as a whitening agent, and / or its geometrical isomer.
Preferred embodiments of these inventions are the same as the above-described embodiments of the invention.
本発明は、上記一般式(1)に表される化合物及び/又はその幾何異性体を投与することを含む、メラニンの産生を抑制する方法に関する。
また、本発明は、上記一般式(1)に表される化合物及び/又はその幾何異性体を投与することを含む美白方法に関する。
これらの発明の好ましい実施の形態は、上述の発明の実施の形態と同様である。
The present invention relates to a method for suppressing melanin production, which comprises administering a compound represented by the above general formula (1) and / or a geometric isomer thereof.
Moreover, this invention relates to the whitening method including administering the compound represented by the said General formula (1), and / or its geometrical isomer.
Preferred embodiments of these inventions are the same as the above-described embodiments of the invention.
以下に、本発明に付いて、実施例を挙げて更に詳しく説明を加えるが、本発明がかかる実施例のみに限定されないことは言うまでもない。 In the following, the present invention will be described in more detail with reference to examples, but it goes without saying that the present invention is not limited to such examples.
<試験例1: 培養ヒト正常メラノサイトを用いたメラニン産生抑制試験>
細胞内のメラニン合成過程において特異的にメラニンに取り込まれる2−チオウラシル(本試験では、14Cラベルした2−チオウラシルを使用)を用い、本発明のメラニン産生抑制剤(ゲファルナート)と、ゲファルナートの加水分解物であるゲラニオールについてメラニン産生抑制作用を評価した。尚、本試験に用いたゲファルナートは、AK Scientific, Inc.より、ゲラニオールは、Sigma-Aldrich Co. LLC.より購入したものである。24ウェルのプレートを使用し、メラノサイト培養用完全培地(倉敷紡績株式会社)を用い、9ウェルにそれぞれ1.0×104cells/well/0.5mLの濃度でヒト正常メラノサイト(倉敷紡績株式会社)を播種した。5%二酸化炭素雰囲気下、37℃で24時間培養を行った。その後、全てのウェルについて、以下の条件で培地交換した。即ち、3ウェルは新しいメラノサイト培養用完全培地(コントロール群)に交換し、3ウェルずつ合計6ウェルは100μMの濃度でゲファルナート又はゲラニオールを含有するメラノサイト培養用完全培地に交換した。更に、これらの9ウェルに2−[2−14C]チオウラシル(第一クラリティ株式会社)を0.5μCi/well添加した。そして上記培養条件と同様の条件で更に6日間培養した。培養終了後、各ウェルから培養液を除去し、PBS(リン酸緩衝生理食塩水)で洗浄後、WST−8試薬(株式会社同仁化学研究所)を用い細胞数を測定した。WST−8試薬を除去し、PBSで洗浄後、100(w/v)%トリクロロ酢酸(和光純薬工業株式会社)を使用しウェルの底面より細胞を剥離後、トリクロロ酢酸濃度が10(w/v)%となるように水を加えて希釈し、冷蔵庫で30分間静置した。遠心分離にて細胞を回収した後、各ウェルから回収した細胞における14C−チオウラシル量を液体シンチレーションカウンター(アロカ株式会社)にて測定した。コントロールのウェルから回収した細胞の放射線量に対する、被検物質を含む培地で培養した細胞の放射線量の百分率をそれぞれ求め、メラニン量(%)とした。すなわち、各細胞内に取り込まれた放射線量性が小さい程、メラニン量が小さいと判断することができ、よって、添加された成分のメラニン抑制力価が大きいと判断することが出来る。また、コントロール群と各群間の統計処理は、ダネット検定により行った。結果を図1に示す。
<Test Example 1: Melanin production inhibition test using cultured normal human melanocytes>
Using 2-thiouracil (in this test, 14 C-labeled 2-thiouracil), which is specifically taken into melanin during the intracellular melanin synthesis process, the melanin production inhibitor (gefarnate) of the present invention and the hydrolysis of gefarnate The melanin production inhibitory effect was evaluated about geraniol which is a decomposition product. The gefarnate used in this test was purchased from AK Scientific, Inc., and geraniol was purchased from Sigma-Aldrich Co. LLC. Using a 24-well plate and using a complete medium for melanocyte culture (Kurashiki Boseki Co., Ltd.), normal human melanocytes (Kurashiki Boseki Co., Ltd.) at a concentration of 1.0 × 10 4 cells / well / 0.5 mL each in 9 wells. ). Culturing was performed at 37 ° C. for 24 hours in a 5% carbon dioxide atmosphere. Thereafter, the medium was changed under the following conditions for all wells. That is, 3 wells were replaced with a new complete culture medium for melanocyte culture (control group), and 3 wells were replaced with a total medium for melanocyte culture containing gefarnate or geraniol at a concentration of 100 μM in total of 6 wells. Furthermore, 2- [2- 14 C] thiouracil (Daiichi Clarity Co., Ltd.) was added to these 9 wells at 0.5 μCi / well. The culture was further continued for 6 days under the same conditions as described above. After completion of the culture, the culture solution was removed from each well, washed with PBS (phosphate buffered saline), and the number of cells was measured using WST-8 reagent (Dojindo Laboratories). After removing the WST-8 reagent and washing with PBS, the cells were detached from the bottom of the well using 100 (w / v)% trichloroacetic acid (Wako Pure Chemical Industries, Ltd.), and the trichloroacetic acid concentration was 10 (w / w). v) Water was added to dilute the solution, and the mixture was allowed to stand for 30 minutes in a refrigerator. After recovering the cells by centrifugation, the amount of 14 C-thiouracil in the cells recovered from each well was measured with a liquid scintillation counter (Aloka Co., Ltd.). The percentage of the radiation dose of the cells cultured in the medium containing the test substance with respect to the radiation dose of the cells recovered from the control wells was determined and used as the melanin amount (%). That is, it can be determined that the smaller the radiation dose taken into each cell, the smaller the amount of melanin, and thus the greater the melanin inhibitory potency of the added component. Statistical processing between the control group and each group was performed by Dunnett's test. The results are shown in FIG.
図1に示すように、本発明のメラニン産生抑制剤(ゲファルナート)はメラニン産生抑制作用を示した。しかし、ゲファルナートの加水分解物であるゲラニオールは、メラニン産生抑制作用を示さなかった。
この結果より、ゲファルナートのメラニン産生抑制作用は、その加水分解物によってもたらされるものではないことが明らかとなった。
As shown in FIG. 1, the melanin production inhibitor (gefarnate) of the present invention exhibited a melanin production inhibitory action. However, geraniol, a hydrolyzate of gefarnate, did not show a melanin production inhibitory action.
From this result, it became clear that the melanin production inhibitory action of gefarnate was not brought about by the hydrolyzate.
<製造例1: 本発明の美白用化粧料の製造方法1>
以下の表1に示す処方に従い、本発明の美白用化粧料(乳化剤形)を作製した。即ち、イ及びロの成分を80℃に加熱し、溶解させた後、ロの成分に10質量%水酸化カリウム水溶液を適量加え、pHを6.5に調整した。その後、撹拌しながら、イの成分をロの成分に徐々に加え乳化し、ホモジナイザーで粒子を均一にした後、撹拌冷却し、本発明の美白用化粧料(化粧料1、乳化剤形)を作製した。また同時に、表1の処方成分中、「ゲファルナート」を「水」に置換した比較例1を作製した。
<Production Example 1: Method 1 for producing whitening cosmetic composition of the present invention>
The whitening cosmetic (emulsifier form) of the present invention was prepared according to the formulation shown in Table 1 below. That is, after the components (a) and (b) were heated to 80 ° C. and dissolved, an appropriate amount of a 10 mass% potassium hydroxide aqueous solution was added to the component (b) to adjust the pH to 6.5. Then, while stirring, the component a is gradually added to the component b, emulsified, and the particles are homogenized with a homogenizer, followed by cooling with stirring to produce the whitening cosmetic of the present invention (cosmetic 1, emulsifier type). did. At the same time, Comparative Example 1 in which “gefarnate” was replaced with “water” in the formulation components of Table 1 was produced.
<製造例2: 本発明の美白用化粧料の製造方法2>
以下の表2に示す処方に従い、本発明の美白用化粧料(クリーム剤形)を作製した。即ち、ロの成分を80℃に加熱し、撹拌し、溶解させた後、10質量%水酸化カリウム水溶液を適量加え、pHを6.5に調整した。最後に水を追加し、総重量が524(g)となるようにした(混合物A)。また、イの成分を80℃に加熱し、撹拌し、溶解させた(混合物B)。80℃に加熱した混合物Aを、混合物Bに撹拌しながら徐々に加え、乳化し、ホモジナイザーで粒子を均一化した後、撹拌冷却し、本発明の美白用化粧料(化粧料2、クリーム剤形)を作製した。また同時に、表2の処方成分中、「ゲファルナート」を「水」に置換した比較例2を作製した。
<Production Example 2: Method 2 for producing whitening cosmetic material of the present invention>
According to the formulation shown in Table 2 below, the whitening cosmetic (cream dosage form) of the present invention was prepared. That is, the component B was heated to 80 ° C., stirred and dissolved, and then an appropriate amount of 10% by mass aqueous potassium hydroxide solution was added to adjust the pH to 6.5. Finally, water was added so that the total weight was 524 (g) (mixture A). In addition, component (a) was heated to 80 ° C., stirred and dissolved (mixture B). The mixture A heated to 80 ° C. is gradually added to the mixture B with stirring, emulsified, and the particles are homogenized with a homogenizer, followed by stirring and cooling. The whitening cosmetic composition of the present invention (cosmetics 2, cream dosage form) ) Was produced. At the same time, Comparative Example 2 in which “gefarnate” was replaced with “water” in the formulation components of Table 2 was prepared.
<試験例2: 本発明の美白用化粧料の色素沈着改善作用評価>
実施例2及び3に記載の方法に従い製造された本発明の美白用化粧料(化粧料1及び2)、比較例1及び2に関し、以下の手順に従い色素沈着抑制作用を評価した。自由意思で参加したパネラーの上腕内側部に1.5cm×1.5cmの部位を合計5ケ所設けた。設けた部位に最少紅斑量(1MED)の紫外線照射を1日1回、3日連続して3回照射した。試験1日目の紫外線照射終了時(一回目照射終了後)より、1日2回35日連続して化粧料1及び2、比較例1及び2を50μL塗布した。5部位のうち1部位は無処置部位とした。35回の塗布終了24時間後に色彩色差計(CR-300、コニカミノルタ株式会社)にて各試験部位の皮膚明度(L*値)を測定し、処理部位のL*値と無処理部位L*値の差(ΔL*値=処理部位のL*値−無処理部位L*値)を算出した。L*値は、色素沈着の程度が強いほど低い値となる。従って、ΔL*値が大きいほど、色素沈着が改善されたと判断することが出来る。結果を表3に示す。表3の結果によれば、本発明の化粧料1は、比較例1と比べ高い値を示し、本発明の化粧料2は、比較例2と比べ高い値を示した。このことは、本発明の化粧料1及び2が、優れた美白効果(色素沈着改善効果)示すことが分かる。これは、本発明の化粧料1及び2に含有されるメラニン産生抑制剤(ゲファルナート)による美白効果である。
<Test Example 2: Evaluation of pigmentation-improving action of whitening cosmetic of the present invention>
With respect to the whitening cosmetics of the present invention (Cosmetics 1 and 2) and Comparative Examples 1 and 2 produced according to the methods described in Examples 2 and 3, the pigmentation inhibitory action was evaluated according to the following procedure. A total of 5 sites of 1.5 cm × 1.5 cm were provided on the inner side of the upper arm of the panelists who participated freely. The provided site was irradiated with UV radiation of a minimum erythema amount (1 MED) once a day for 3 consecutive days. 50 μL of cosmetics 1 and 2 and Comparative Examples 1 and 2 were applied twice a day for 35 consecutive days from the end of the ultraviolet irradiation on the first day of the test (after the completion of the first irradiation). One of the five sites was an untreated site. 24 hours after the completion of 35 times of application, the skin lightness (L * value) of each test site was measured with a color difference meter (CR-300, Konica Minolta Co., Ltd.), and the L * value of the treated site and the untreated site L * The difference in value (ΔL * value = L * value of treated area−L * value of untreated area) was calculated. The L * value decreases as the degree of pigmentation increases. Therefore, it can be determined that the greater the ΔL * value, the better the pigmentation. The results are shown in Table 3. According to the results in Table 3, the cosmetic 1 of the present invention showed a higher value than the comparative example 1, and the cosmetic 2 of the present invention showed a higher value than the comparative example 2. This shows that the cosmetics 1 and 2 of the present invention exhibit an excellent whitening effect (pigmentation improving effect). This is a whitening effect by the melanin production inhibitor (gefarnate) contained in the cosmetics 1 and 2 of the present invention.
図1に示すように本発明のメラニン産生抑制剤(ゲファルナート)の加水分解物についてはメラニン産生抑制作用が認められない。したがって、表3に示す本発明のメラニン産生抑制剤(ゲファルナート)による美白効果は、皮膚への塗布後に生成したゲファルナートの加水分解物による効果ではない。 As shown in FIG. 1, the melanin production inhibitory effect is not recognized about the hydrolyzate of the melanin production inhibitor (gefarnate) of this invention. Therefore, the whitening effect by the melanin production inhibitor (gefarnate) of the present invention shown in Table 3 is not the effect of the hydrolyzate of gefarnate produced after application to the skin.
<試験例3: 本発明のメラニン産生抑制剤(ゲファルナート)の安定性試験>
以下の手順に従い、本発明のメラニン産生抑制剤(ゲファルナート)の抗酸化剤(イーミックス−D)による製剤安定性(溶液安定性)試験を実施した。即ち、表4に記載の成分を含有する製剤(溶液)を調製し、60℃にて2週間保管し、その後、高速液体クロマトグラフィーにて製剤(溶液)中のゲファルナート濃度を測定した。測定条件を以下に示す。また、製剤(溶液)中のゲファルナートの残存率は、保管開始時のゲファルナート濃度を100%とし、保管開始時のゲファルナート濃度に対する保管2週間後のゲファルナート濃度の比率として算出した。尚、本試験の製剤(溶媒)としては、トリエチルヘキサノイン(日清オイリオグループ株式会社)、2−エチルヘキサン酸セチル(BASF株式会社)、スクワラン(株式会社岸本特殊肝油工業所)を用いた。また、ゲファルナートは、AK Scientific, Inc.より購入したもの、イーミックス−Dは、エーザイフード・ケミカル株式会社より購入したものを使用した。結果を表4に示す。
<Test Example 3: Stability test of melanin production inhibitor (gefarnate) of the present invention>
In accordance with the following procedure, the formulation stability (solution stability) test with the antioxidant (Emix-D) of the melanin production inhibitor (gefarnate) of the present invention was carried out. Specifically, a preparation (solution) containing the components shown in Table 4 was prepared, stored at 60 ° C. for 2 weeks, and then the gefarnate concentration in the preparation (solution) was measured by high performance liquid chromatography. The measurement conditions are shown below. Further, the residual rate of gefarnate in the preparation (solution) was calculated as a ratio of the gefarnate concentration after 2 weeks of storage to the gefarnate concentration at the start of storage, with the gefarnate concentration at the start of storage being 100%. In addition, as a formulation (solvent) of this test, triethylhexanoin (Nisshin Oilio Group Co., Ltd.), cetyl 2-ethylhexanoate (BASF Corporation), and squalane (Kishimoto Special Liver Oil Industry Co., Ltd.) were used. Gefarnate was purchased from AK Scientific, Inc., and Emix-D was purchased from Eisai Food Chemical Co., Ltd. The results are shown in Table 4.
<測定条件>
測定装置: ACQUITY UPLC(Waters)
カラム: ACQUITY UPLC BEH C18、1.7μm、2.1φ×100mm(Waters)
ガードカラム: Van Guard BEH C18、1.7μm(Waters)
カラム温度: 40℃
移動相: アセトニトリル(和光純薬工業株式会社)/メタノール(和光純薬工業株式会社)=45/55
流速: 0.35mL/min
注入量: 0.5μL
検出: 210nm
<Measurement conditions>
Measuring device: ACQUITY UPLC (Waters)
Column: ACQUITY UPLC BEH C18, 1.7 μm, 2.1φ × 100 mm (Waters)
Guard column: Van Guard BEH C18, 1.7 μm (Waters)
Column temperature: 40 ° C
Mobile phase: Acetonitrile (Wako Pure Chemical Industries, Ltd.) / Methanol (Wako Pure Chemical Industries, Ltd.) = 45/55
Flow rate: 0.35mL / min
Injection volume: 0.5μL
Detection: 210nm
表4の結果より、本発明のメラニン産生抑制剤のゲファルナートは、抗酸化剤と共に配合することにより製剤(溶液)中における分解又は異性化反応が抑制され、安定性が向上することが分かった。上記試験結果より、前記一般式(1)に表される化合物及び/又はその幾何異性体と、抗酸化剤を含有する化粧料は、製剤(溶液)中の安定性が向上し、長期間保存した後においても優れた美白効果を発揮する。 From the results in Table 4, it was found that gefarnate, a melanin production inhibitor of the present invention, was mixed with an antioxidant to suppress degradation or isomerization reaction in the preparation (solution) and improve stability. From the above test results, the cosmetics containing the compound represented by the general formula (1) and / or the geometric isomer thereof and the antioxidant are improved in stability in the preparation (solution) and stored for a long time. Excellent whitening effect even after finishing.
本発明は、美白用化粧料等に応用出来る。 The present invention can be applied to whitening cosmetics and the like.
Claims (10)
[但し、式中R1は、炭素数1〜15の直鎖又は分岐の、飽和又は不飽和炭化水素基を表す。] A melanin production inhibitor comprising a compound represented by the following general formula (1) and / or a geometric isomer thereof.
[Wherein, R 1 represents a linear or branched, saturated or unsaturated hydrocarbon group having 1 to 15 carbon atoms. ]
[但し、式中R1は、炭素数1〜15の直鎖又は分岐の、飽和又は不飽和炭化水素基を表す。] A composition comprising a compound represented by the following general formula (1) and / or a geometric isomer thereof, and vitamin E and / or a pharmacologically acceptable salt thereof.
[Wherein, R 1 represents a linear or branched, saturated or unsaturated hydrocarbon group having 1 to 15 carbon atoms. ]
The composition according to claim 9, which is used for whitening.
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0616532A (en) * | 1992-03-17 | 1994-01-25 | Eisai Co Ltd | Whitening and beautifying agent |
JPH0971525A (en) * | 1995-09-07 | 1997-03-18 | Pola Chem Ind Inc | Melanogenesis suppressing agent and skin preparation for external use |
JP2002114645A (en) * | 2000-10-02 | 2002-04-16 | Shiseido Co Ltd | Hair tonic |
JP2005179189A (en) * | 2003-12-16 | 2005-07-07 | Kanebo Cosmetics Inc | Wrinkle ameliorating agent |
WO2016121962A1 (en) * | 2015-01-30 | 2016-08-04 | 株式会社ファルネックス | Melanin production inhibitor |
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
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JPH0616532A (en) * | 1992-03-17 | 1994-01-25 | Eisai Co Ltd | Whitening and beautifying agent |
JPH0971525A (en) * | 1995-09-07 | 1997-03-18 | Pola Chem Ind Inc | Melanogenesis suppressing agent and skin preparation for external use |
JP2002114645A (en) * | 2000-10-02 | 2002-04-16 | Shiseido Co Ltd | Hair tonic |
JP2005179189A (en) * | 2003-12-16 | 2005-07-07 | Kanebo Cosmetics Inc | Wrinkle ameliorating agent |
WO2016121962A1 (en) * | 2015-01-30 | 2016-08-04 | 株式会社ファルネックス | Melanin production inhibitor |
Non-Patent Citations (1)
Title |
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ニプロ株式会社, ゲファルナート細粒10%「NP」, JPN6019025715, February 2014 (2014-02-01), JP, ISSN: 0004070538 * |
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