JP2020180065A - メラノサイト活性化因子の産生抑制剤 - Google Patents
メラノサイト活性化因子の産生抑制剤 Download PDFInfo
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- JP2020180065A JP2020180065A JP2019083361A JP2019083361A JP2020180065A JP 2020180065 A JP2020180065 A JP 2020180065A JP 2019083361 A JP2019083361 A JP 2019083361A JP 2019083361 A JP2019083361 A JP 2019083361A JP 2020180065 A JP2020180065 A JP 2020180065A
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- melanocyte
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Abstract
Description
このような色素沈着が関連する皮膚症状は外観から容易に認められるため、顔の印象に大きく影響する。そのため、皮膚の色素沈着の予防や改善に対する関心は、肌を美しく見せたいという願望を持つ人を中心にとても高く、美白剤や美白用化粧料の需要は近年大きいものとなっている。
そのような作用機序のひとつに、メラノサイトで産生されたメラニンがメラノサイトのデンドライト(触手)によりケラチノサイトへ輸送されるメカニズムがあり、これを作用点とするデンドライト伸長抑制剤を美白剤の有効成分とすることが提案されている(特許文献1)。また、メラノサイト活性化因子の制御因子の活性を指標として、色素沈着抑制剤をスクリーニングできることも開示されている。(特許文献2)。
特許文献3には、D−パントテニルアルコールを含有する皮膚化粧料が、肌荒れ、特に肌のかさつきを改善して、肌質を整えることが記載されている。
特許文献4には、D−パントテニルアルコールと他の美白成分とを組み合わせた組成物によれば、美白効果を早く得られることが記載されている。
を完成させるに至った。
[1]D−パントテニルアルコールを含有する、メラノサイト活性化因子の産生抑制剤。
[2]前記メラノサイト活性化因子が、アドレノメジュリン、エンドセリン、インターロイキン1α、及びインターロイキン6からなる群から選択される、[1]に記載の産生抑制剤。
[3][1]又は[2]に記載の産生抑制剤を含有する、色素沈着抑制用の組成物。
[4]皮膚外用剤である、[3]に記載の組成物。
[5]化粧料である、[4]に記載の組成物。
D−パントテニルアルコールは、パントテン酸のアルコール型誘導体であり、以下に示す構造を有する。
D−パントテニルアルコールは化粧料などの皮膚外用剤用の素材として用いられており、その入手に困難性はなく、市販品を適宜用いることができる。
ここで、メラノサイト活性化因子は、メラノサイトに何らかの刺激を与え活性化させる因子をいい、好ましくはアドレノメジュリン、エンドセリン、インターロイキン1α、及びインターロイキン6からなる群から選択され、本発明の剤によりこれらのうち一種又は二種以上の産生が抑制される。これらの因子のうち、アドレノメジュリンが特に好ましい。
アドレノメジュリンは、メラノサイトを活性化してデンドライトの数を増加させたり伸長させたりする作用を有する。増加し、また伸長したデンドライトは、メラニンのメラノサイトからケラチノサイトへの輸送に関与し、色素沈着の亢進に至る。
により表される。タンパク質又は遺伝子(通常はmRNA)の発現量は、常法により測定することができる。あるいは、該因子の産生量は、該因子の反応活性の測定値で表されてもよく、例えばアドレノメジュリン活性については、デンドライトを形態変化させる活性を任意の方法で測定した値であってもよい(特許文献1参照)。通常、メラノサイト活性化因子はケラチノサイトにおいて発現するため、活性量はケラチノサイトにおいて測定した値とすることができる。
なお、本明細書において美白とは、色素沈着の抑制(予防及び/又は改善)をいい、より具体的には、シミ、くすみ、そばかす、日焼け、皮膚の炎症や刺激による黒ずみ等のメラニン産生亢進、過剰蓄積、及び沈着異常等により生じる色素沈着症状、並びにステロイド等の薬物による皮膚の黒化症等の色素沈着をもたらす疾患等による色素沈着症状などの、予防及び/又は改善をいう。すなわち、本発明のメラノサイト活性化因子の産生抑制剤は、色素沈着抑制用の組成物に好適に含有させることができる。
また、本発明の色素沈着抑制用の組成物は、皮膚外用剤の態様とすることが好ましく、化粧料及び医薬部外品の態様よりが好ましい。
他の美白成分としては、一般的に化粧料に用いられているものであれば特に限定はない。例えば、4−n−ブチルレゾルシノール、アスコルビン酸グルコシド、3−О−エチルアスコルビン酸、アルブチン、エラグ酸、コウジ酸、リノール酸、ニコチン酸アミド、5,5'−ジプロピルビフェニル−2,2'−ジオール、5'−アデニル酸二ナトリウム、4
−メトキシサリチル酸カリウム塩、ハイドロキノン等が挙げられる。
ビタミンA又はその誘導体(レチノール、レチナール、レチノイン酸、トレチノイン、イソトレチノイン、レチノイン酸トコフェロール、パルミチン酸レチノール、酢酸レチノール等)、ウルソール酸ベンジルエステル、ウルソール酸リン酸エステル、ベツリン酸ベンジルエステル、ベンジル酸リン酸エステルが挙げられる。
極性油としては、合成エステル油として、ミリスチン酸イソプロピル、オクタン酸セチル、ミリスチン酸オクチルドデシル、パルミチン酸イソプロピル、ステアリン酸ブチル、ラウリン酸ヘキシル、ミリスチン酸ミリスチル、オレイン酸デシル、ジメチルオクタン酸
ヘキシルデシル、乳酸セチル、乳酸ミリスチル、酢酸ラノリン、イソノナン酸2−エチルヘキシル、ステアリン酸イソセチル、イソステアリン酸イソセチル、12−ヒドロキシステアリン酸コレステリル、ジ−2−エチルヘキサン酸エチレングリコール、ジペンタエリスリトール脂肪酸エステル、モノイソステアリン酸N−アルキルグリコール、ジカプリン酸ネオペンチルグリコール、リンゴ酸ジイソステアリル、ジ−2−ヘプチルウンデカン酸グリセリル、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スリトール、トリ−2−エチルヘキサン酸グリセリル、トリイソステアリン酸トリメチロールプロパンを挙げることができる。
ル類(モノステアリン酸グリセリル等)、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シ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、等が挙げられる。
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
、等が挙げられる。
ヒト正常ケラチノサイト(成人、Lot#00702、クラボウ社製)を、6ウェルプレートに
7.5×104cells/wellずつ播種し、HuMedia-KG2培地にて37℃、5%C
O2環境下で24時間培養した。培養後に、D−パントテニルアルコールを100μg/mL含有する培地に交換した。また、D−パントテニルアルコールを含有しない培地に交換した対照群も設けた。培地交換後に、さらに37℃、5%CO2環境下で24時間培養した。培養後に、各ウェルをPBSで洗浄した後、RLTバッファーを350μL/wellずつ添加して細胞を剥離した。剥離した細胞をエッペンドルフチューブに回収し、QIAshredderホモジナイザー(キアゲン社製)をセットして4℃、15000rpm、2分間の条件で遠心分離してmRNAを回収した。回収したmRNAをQIAcubeスピンカラムシ
ステム(キアゲン社製)で処理することにより精製した。精製したmRNAに対して、解析アレイGeneChip Human Genome U133 Plus 2.0 Array(Thermo Fisher Scientific社製
)を用いてマイクロアレイ解析を行い、各遺伝子の発現量を測定した。
D−パントテニルアルコールを添加したケラチノサイトでは、アドレノメジュリン、インターロイキン1α、及びインターロイキン6の遺伝子発現が抑制されることが確認された。
ヒト正常ケラチノサイト(成人、Lot#00702、クラボウ社製)を、24ウェルプレート
に4.0×104cells/wellずつ播種し、HuMedia-KG2培地にて37℃、5%
CO2環境下で24時間培養した。培養後に、D−パントテニルアルコールを100μg/mL含有する培地に交換した。また、D−パントテニルアルコールを含有しない培地に交換した対照群も設けた。培地交換後に、さらに37℃、5%CO2環境下で24時間培養した。培養後に、培地をPBS500μLに置換し、UVBを照射し(照射群:50mJ/cm2、非照射群:0mJ/cm2)、D−パントテニルアルコール含有培地(添加群:100μg/mL、対照群:0μg/mL)に交換した。培地交換後に、さらに37℃、5%CO2環境下で24時間培養した。培養上清を回収し、Endothelin-1 Quantikine ELISA Kit(R&D Systems社製)を用い、培養上清中のエンドセリン量を測定した。
UVBを照射したケラチノサイトではエンドセリン量が増加するところ、D−パントテニルアルコールの添加によりエンドセリン量が抑制されることが確認された。
Claims (5)
- D−パントテニルアルコールを含有する、メラノサイト活性化因子の産生抑制剤。
- 前記メラノサイト活性化因子が、アドレノメジュリン、エンドセリン、インターロイキン1α、及びインターロイキン6からなる群から選択される、請求項1に記載の産生抑制剤。
- 請求項1又は2に記載の産生抑制剤を含有する、色素沈着抑制用の組成物。
- 皮膚外用剤である、請求項3に記載の組成物。
- 化粧料である、請求項4に記載の組成物。
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