JP4497853B2 - Topical skin preparation - Google Patents
Topical skin preparation Download PDFInfo
- Publication number
- JP4497853B2 JP4497853B2 JP2003192094A JP2003192094A JP4497853B2 JP 4497853 B2 JP4497853 B2 JP 4497853B2 JP 2003192094 A JP2003192094 A JP 2003192094A JP 2003192094 A JP2003192094 A JP 2003192094A JP 4497853 B2 JP4497853 B2 JP 4497853B2
- Authority
- JP
- Japan
- Prior art keywords
- genus
- extract
- acid
- plant
- hydroquinone
- 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.)
- Expired - Fee Related
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 235000019512 sardine Nutrition 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002884 skin cream Substances 0.000 description 1
- 231100000370 skin sensitisation Toxicity 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229920001864 tannin Polymers 0.000 description 1
- 235000018553 tannin Nutrition 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 235000007920 tremoceiro branco Nutrition 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- HTJNEBVCZXHBNJ-XCTPRCOBSA-H trimagnesium;(2r)-2-[(1s)-1,2-dihydroxyethyl]-3,4-dihydroxy-2h-furan-5-one;diphosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.OC[C@H](O)[C@H]1OC(=O)C(O)=C1O HTJNEBVCZXHBNJ-XCTPRCOBSA-H 0.000 description 1
- 235000017468 valeriana Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000010698 whale oil Substances 0.000 description 1
- 239000010497 wheat germ oil Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- 235000014692 zinc oxide Nutrition 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Description
【0001】
【発明の属する技術分野】
本発明は、皮膚外用剤に関する。さらに詳しくは、美白剤の経皮吸収を促進し、美白効果を有効に発揮させることができる皮膚外用剤に関する。
【0002】
【従来の技術】
従来、ローション剤、軟膏剤、クリーム剤、パップ剤等の皮膚外用剤においては、経皮吸収により種々の薬効を発揮する成分が配合されている。ところが、皮膚は、本来体外からの異物の侵入を防ぐための機能を有するものであるため、通常の外用剤基剤中に薬効成分を配合しただけでは、十分な経皮吸収が得られず、十分な薬効が得られない場合が多い。
【0003】
そこで、薬効成分の経皮吸収を向上させるべく、ジメチルスルホキシド、N,N−ジメチルホルミルアミド等の非プロトン溶媒(特許文献1参照)、陰イオン性又は両性界面活性剤(特許文献2,特許文献3参照)、1−ドデシルアザシクロヘプタン−2−オン(特許文献4参照)、l−カルボン,メントン,ピペリトン等のテルペンケトン(特許文献5参照)、d−リモネン(特許文献6参照)、N−モノ又はジ置換−p−メンタン−3−カルボキシアミド(特許文献7参照)等が、開示されている。しかしながら、これらの経皮吸収促進剤を用いても薬剤の充分な経皮吸収性が得られない場合があり、特に水溶性アスコルビン酸誘導体のような親水性薬剤に対して有効な経皮吸収促進剤はほとんど見いだされていない。また、上記の経皮吸収促進剤の多くは皮膚刺激性が強く、これを配合した製剤を適用することによって皮膚に紅斑を生じるなど、安全性の面においても満足できる経皮吸収促進剤は得られていないのが現状である。
【0004】
N−アセチルグルタミンは、グルタミンのN−アセチル化誘導体でありグルタミンに比べて熱安定性に優れており(特許文献8参照)、皮膚に適用することにより角質層の水分保持を高めること(特許文献9参照)が知られている。
【0005】
【特許文献1】
米国特許第3,551,554号公報
【特許文献2】
特開昭51−32724号公報
【特許文献3】
特開昭52−83914号公報
【特許文献4】
特開昭52−1035号公報
【特許文献5】
特開平2−193932号公報
【特許文献6】
特開平2−207024号公報
【特許文献7】
特開2001−58961号公報
【特許文献8】
特公昭47−670号公報
【特許文献9】
特開平3−2523206号公報
【0006】
【発明が解決しようとする課題】
そこで本発明においては、美白剤、特に水溶性アスコルビン酸誘導体のような親水性薬剤に対する経皮吸収促進効果に優れ、かつ安全性に優れた皮膚外用剤を提供することを課題とした。
【0007】
【課題を解決するための手段】
本発明者等は上記課題を解決するために鋭意研究を行った結果、N−アセチルグルタミンに美白剤に対する優れた経皮吸収性があり、かつ皮膚刺激性が低く、安全性に優れており、N−アセチルグルタミンを美白効果を有する薬剤とともに皮膚外用剤に配合することにより上記課題が解決されることを見出し、本発明を完成するに至った。
【0008】
すなわち、本発明は、N−アセチルグルタミンと、美白剤から選択される1種又は2種以上を含有することを特徴とする皮膚外用剤である。
【0009】
本発明に用いる美白剤としては、水溶性の薬剤であることが好ましく、その中でもL−アスコルビン酸及びその塩又はその誘導体、ハイドロキノン及びその誘導体、システイン及びその誘導体、グルコサミン及びその誘導体、アゼライン酸及びその誘導体、リポ酸及びその誘導体並びにそれらの塩、レゾルシン及びその誘導体、グラブリジン、グラブレン、リクイリチン、イソリクイリチン、グルタチオン、ヒノキチオール及びその配糖体並びにそれらの塩、エラグ酸及びその誘導体並びにそれらの塩、胎盤抽出物、マンサク属,ジンコウ属,ツバキ属,タデ属,セイヨウヤマハッカ属,イブキジャコウソウ属,ヨモギ属,ノコギリソウ属,ヒヨドリバナ属,シナノキ属,イワユキノシタ属,ジンチョウゲ属,ガンピ属,ミツマタ属,ボタン属,カンゾウ属,クワ属,エンジュ属,バラ属,アロエ属,ニワトコ属,ユキノシタ属,ドクダミ属,カンアオイ属,タツナミソウ属,ヒマワリ属,アマドコロ属,アマ属,カントウ属,ワレモコウ属,ハッカ属,ハウチワマメ属に属する1種又は2種以上の植物の抽出物及び、カイメンソウ属,サンゴモ属,ヤハズグサ属,アミジグサ属,ヒジキ属,ソゾ属,フシツナギ属,イワヒゲ属,ダルス属,ホンダワラ属,モヅク属,ナガマツモ属,イシモヅク属,フトモヅク属,オキナワモヅク属に属する1種又は2種以上の藻類の抽出物から成る群から選択される1種又は2種以上、特に水溶性アスコルビン酸誘導体が好ましい。
【0010】
【発明の実施の形態】
以下、本発明の実施形態について詳述する。
【0011】
本発明で用いるN−アセチルグルタミンは、発酵法、合成法など、どのような製造方法でつくられたものでもよい。たとえば、発酵法による製造方法としては特公昭52−41211号公報、特公昭57−1994号公報に記載された方法がある。
【0012】
かかるN−アセチルグルタミンは、N−アセチルグルタミンの塩の形で使用してもよく、また遊離型と塩とを混合して使用してもよい。N−アセチルグルタミンの塩としては、ナトリウム、カリウム、リチウムなどのアルカリ金属塩、カルシウム、マグネシウムなどのアルカリ土類金属塩、アンモニウム塩およびモノエタノールアミン、トリエタノールアミン、トリイソプロパノールアミンなどのアミン類との塩などがあげられ、これらのアルカリ性成分は単独または混合物の形で使用される。これらのN−アセチルグルタミンの塩は、N−アセチルグルタミンから公知の方法で製造することができる。
【0013】
N−アセチルグルタミンおよび/またはその塩は、皮膚外用剤全量中に0.001〜5重量%、好ましくは0.005〜3重量%の割合で配合する。0.001重量%未満の配合では、経皮吸収促進効果が発揮できず、また5重量%を超えて配合しても、経皮吸収促進効果にそれ以上の向上が認められない。
【0014】
本発明においてN−アセチルグルタミンは、美白剤の経皮吸収を促進するために用いる。かかる美白剤としては、皮膚外用剤に配合できる美白薬剤であれば特に制限されないが、水溶性の美白薬剤が好ましい。美白剤としては例えば、L−アスコルビン酸及びその塩又はその誘導体、ハイドロキノン及びその誘導体、システイン及びその誘導体、グルコサミン及びその誘導体、アゼライン酸及びその誘導体、リポ酸及びその誘導体並びにそれらの塩、レゾルシン及びその誘導体、グラブリジン、グラブレン、リクイリチン、イソリクイリチン、グルタチオン、ヒノキチオール及びその配糖体並びにそれらの塩、エラグ酸及びその誘導体並びにそれらの塩、胎盤抽出物、マンサク属,ジンコウ属,ツバキ属,タデ属,セイヨウヤマハッカ属,イブキジャコウソウ属,ヨモギ属,ノコギリソウ属,ヒヨドリバナ属,シナノキ属,イワユキノシタ属,ジンチョウゲ属,ガンピ属,ミツマタ属,ボタン属,カンゾウ属,クワ属,エンジュ属,バラ属,アロエ属,ニワトコ属,ユキノシタ属,ドクダミ属,カンアオイ属,タツナミソウ属,ヒマワリ属,アマドコロ属,アマ属,カントウ属,ワレモコウ属,ハッカ属,ハウチワマメ属に属する1種又は2種以上の植物の抽出物及び、カイメンソウ属,サンゴモ属,ヤハズグサ属,アミジグサ属,ヒジキ属,ソゾ属,フシツナギ属,イワヒゲ属,ダルス属,ホンダワラ属,モヅク属,ナガマツモ属,イシモヅク属,フトモヅク属,オキナワモヅク属に属する1種又は2種以上の藻類の抽出物等が挙げられる。
【0015】
本発明で使用するL−アスコルビン酸及びその塩又はその誘導体としては、例えばL−アスコルビン酸モノステアレート,L−アスコルビン酸モノパルミテート,L−アスコルビン酸モノオレエート等のアスコルビン酸モノ脂肪酸エステル類、L−アスコルビン酸モノリン酸エステル,L−アスコルビン酸-2-硫酸エステル等のアスコルビン酸モノエステル誘導体、L−アスコルビン酸ジステアレート,L−アスコルビン酸ジパルミテート,L−アスコルビン酸ジオレエート等のL−アスコルビン酸ジ脂肪酸エステル誘導体、L−アスコルビン酸トリステアレート,L−アスコルビン酸トリパルミテート,L−アスコルビン酸トリオレエート等のL−アスコルビン酸トリ脂肪酸エステル誘導体、L−アスコルビン酸トリリン酸エステル等のL−アスコルビン酸トリエステル誘導体等を挙げることができる。これらのL−アスコルビン酸及びその塩又はその誘導体のうち、特に好ましいものは、L−アスコルビン酸,L−アスコルビン酸リン酸エステル及びこれらの塩である。
【0016】
本発明で使用するハイドロキノン及びその誘導体としては、特に限定されないが、ハイドロキノン配糖体が好ましく用いられ、例えば、ハイドロキノン−α−D−グルコース,ハイドロキノン−β−D−グルコース,ハイドロキノン−α−L−グルコース,ハイドロキノン−β−L−グルコース,ハイドロキノン−α−D−ガラクトース,ハイドロキノン−β−D−ガラクトース,ハイドロキノン−α−L−ガラクトース,ハイドロキノン−β−L−ガラクトース等の六炭糖配糖体、ハイドロキノン−α−D−リボース,ハイドロキノン−β−D−リボース,ハイドロキノン−α−L−リボース,ハイドロキノン−β−L−リボース,ハイドロキノン−α−D−アラビノース,ハイドロキノン−β−D−アラビノース,ハイドロキノン−α−L−アラビノース,ハイドロキノン−β−L−アラビノース等の五炭糖配糖体、ハイドロキノン−α−D−グルコサミン,ハイドロキノン−β−D−グルコサミン,ハイドロキノン−α−L−グルコサミン,ハイドロキノン−β−L−グルコサミン,ハイドロキノン−α−D−ガラクトサミン,ハイドロキノン−β−D−ガラクトサミン,ハイドロキノン−α−L−ガラクトサミン,ハイドロキノン−β−L−ガラクトサミン等のアミノ糖配糖体、ハイドロキノン−α−D−グルクロン酸,ハイドロキノン−β−D−グルクロン酸,ハイドロキノン−α−L−グルクロン酸,ハイドロキノン−β−L−グルクロン酸,ハイドロキノン−α−D−ガラクツロン酸,ハイドロキノン−β−D−ガラクツロン酸,ハイドロキノン−α−L−ガラクツロン酸,ハイドロキノン−β−L−ガラクツロン酸等のウロン酸配糖体等を挙げることができる。またその誘導体としては、アセチル化物等のエステル体、メチル化物などのエーテル体等を挙げることができ、これらの中でもハイドロキノン−β−D−グルコースが本発明の効果の面から最も好ましい。
【0017】
本発明で使用するシステイン及びその誘導体としては、特に限定されないが、例えばシステイン、システインのリン脂質エステル、スフィンゴシン及びその誘導体のエステル、糖脂質エステル、糖エステル、ステロールエステル及び炭素数8から20のアルキル若しくはアルケニルエステル等が挙げられる。
【0018】
本発明で使用するグルコサミン及びその誘導体としては、特に限定されないが、例えばグルコサミン、アセチルグルコサミン等のグルコサミンエステル類、グルコサミンメチルエーテル等のグルコサミンエーテル類等が挙げられる。
【0019】
本発明で使用するアゼライン酸及びその誘導体としては、特に限定されないが、例えばアゼライン酸、アゼライン酸モノアルキルエステル等のアゼライン酸モノエステル類、アゼライン酸ジアルキルエステル等のアゼライン酸ジエステル類等が挙げられる。
【0020】
本発明で使用するリポ酸及びその誘導体並びにそれらの塩としては、特に限定されないが、例えはリポ酸、リポ酸のナトリウム塩、カリウム塩、アルキルエステル、アルケニルエステル、アミド類、及び還元体のジヒドロリポ酸、ジヒドロリポアミド等が挙げられる。
【0021】
本発明で使用するレゾルシン及びその誘導体は、従来より抗菌剤として認知されており、また、メラニン産生抑制作用や色素沈着症改善効果を有することも確認されている(特開平4−1116号公報、特開平10−194951号公報)。本発明では、特に限定されないが、例えば、レゾルシン若しくはその配糖体を用いることが好ましい。
【0022】
本発明で使用するグラブリジン、グラブレンは、天然には、カンゾウの一種であるロシアカンゾウ(Glycyrrhiza glabra Lin.)に微量含まれている。グラブリジンについては、抗菌作用、抗酸化作用、抗う蝕作用、抗プラスミン作用等の薬理作用を有することが確認されており、さらに、メラニン生成抑制作用を有することも知られている(特開平1−311011号公報等)。本発明においては、カンゾウから精製したグラブリジン若しくはグラブレンを用いることが好ましい。
【0023】
本発明で使用するリクイリチンやイソリクイリチンは、カンゾウ中に含まれる成分である。含有される化合物である。本発明においては、カンゾウから精製したリクイリチン若しくはイソリクイリチンを用いることが好ましい。
【0024】
本発明で使用するグルタチオン及びその誘導体は、特にその基原を問わず、通常の化粧料,医薬部外品に配合されるものを使用する。
【0025】
本発明で使用するヒノキチオール及びその誘導体としては、特に限定されず、ヒノキチオール,ヒノキチオール亜鉛錯体,ヒノキチオール配糖体等が例示される。ヒノキチオールの配糖体は、下記一般式(1)若しくは一般式(2)で示される化合物であり、これらから1種を単独で、若しくは2種以上を混合して用いる。
【0026】
【化1】
【0027】
【化2】
【0028】
(式中Gは、下記一般式(3)若しくは一般式(4)で示される)
【0029】
【化3】
【0030】
【化4】
【0031】
(式中R1〜R4は、H若しくはCOCH3を示す)
【0032】
本発明で使用するヒノキチオール配糖体は、グルコースを下記一般式(5)
CH3COX (5)
(式中Xは、F,Cl,Br,OCH3,イミダゾリル基から選択される基を示す)で示されるアセチル化試薬等を用いて修飾した後、脱水縮合など既知の方法により製造される(例えば特開平7−17993号公報,特開平7−82288号公報)。また配糖体には、α結合及びβ結合を有する異性体が存在するが、そのいずれを用いてもよく、またそれらの混合物を用いることもでき、通常は混合物を用いる。
【0033】
本発明で使用するエラグ酸は、ポリフェノールの一種で、植物体内に含まれるエラグタンニンを加水分解して得られる。本発明においては、エラグ酸、及びその誘導体並びにそれらの塩を使用する。
【0034】
本発明で使用する胎盤抽出物としては、通常の皮膚外用剤に用いられるものであれば、特にその基原は問わない。
【0035】
本発明においては、マンサク属,ジンコウ属,ツバキ属,タデ属,セイヨウヤマハッカ属,イブキジャコウソウ属,ヨモギ属,ノコギリソウ属,ヒヨドリバナ属,シナノキ属,イワユキノシタ属,ジンチョウゲ属,ガンピ属,ミツマタ属,ボタン属,カンゾウ属,クワ属,エンジュ属,バラ属,アロエ属,ニワトコ属,ユキノシタ属,ドクダミ属,カンアオイ属,タツナミソウ属,ヒマワリ属,アマドコロ属,アマ属,カントウ属,ワレモコウ属,ハッカ属,ハウチワマメ属に属する1種又は2種以上の植物の抽出物及び、カイメンソウ属,サンゴモ属,ヤハズグサ属,アミジグサ属,ヒジキ属,ソゾ属,フシツナギ属,イワヒゲ属,ダルス属,ホンダワラ属,モヅク属,ナガマツモ属,イシモヅク属,フトモヅク属,オキナワモヅク属に属する1種又は2種以上の藻類の抽出物から選択される1種又は2種以上の抽出物を美白剤として用いてもよい。
【0036】
マンサク属(Hamamelis L.)は、マンサク科に属する落葉の木本であり、マンサク(Hamamelis japonica Sieb. et Zucc.),シナマンサク(Hamamelis mollis Oliv.),ハマメリス(Hamamelis virginiana L.)等が例示される。これらの植物の中でも、ハマメリス、特にハマメリスの樹皮を用いることが、美白効果の点から好ましい。
【0037】
ジンコウ属(Aquilaria Lam.)は、ジンチョウゲ科に属する常緑の高木で、十数種が知られている。本発明においては、その美白効果からジンコウ(Aquilaria agallocha Roxb.)を用いることが好ましい。
【0038】
ツバキ属(Camellia L.)は、ツバキ科に属する常緑の草本で約200種が知られている。本発明においては、その美白効果からツバキ(Camellia japonica L.)及びその変種、チャ(Camellia sinensis (L.) O. Kuntze)及びその変種を用いることが好ましい。
【0039】
タデ属(Polygonum L.)植物は、タデ科に属する草本で、約300種が知られている。本発明においては、その美白効果から、イタドリ(Polygonum cuspidatum Sieb. et Zucc.),ハチジョウイタドリ(Polygonum cuspidatum Sieb. et Zucc. var. hachidyoense Ohwi),オオイタドリ(Polygonum sachalinense Fr. Schm.)から選択される1種又は2種以上の植物を用いることが好ましい。
【0040】
セイヨウヤマハッカ属(Melissa L.)植物は,シソ科(Labiatae)に属する多年草であり、中でも、メリッサ(Melissa officinalis L.)の抽出物が、その美白効果から多く用いられる。
【0041】
イブキジャコウソウ属(Thymus L.)植物は、シソ科に属する低木であり、その美白効果の点からイブキジャコウソウ(Thymus serphyllum L. subsp. quinquecostatus (Aelak.) Kitamura),タイム(Thymus vulgaris L.)から選択される1種または2種以上を用いることが好ましい。
【0042】
ヨモギ属(Artemisia L.)植物は、キク科に属する双子葉植物で、ニガヨモギ(Artemisia absinthium L.),クソニンジン(Artemisia annua L.),カワラニンジン(Artemisia apiacea Hance),カワラヨモギ(Artemisia capillaris Thunb.),シナヨモギ(Artemisia cina Berg.),タラゴン(Artemisia dracunculus L.),オトコヨモギ(Artemisia japonica Thunb.),ミブヨモギ(Artemisia maritima L.),ヨモギ(Artemisia princeps Pamp.)から選択される1種又は2種以上を用いることが、美白効果の点から好ましい。
【0043】
ノコギリソウ属(Achillea L.)植物は、キク科に属する双子葉植物で、ノコギリソウ(Achillea alpina L.),セイヨウノコギリソウ(Achillea milleifolium L.),ジャコウノコギリソウ(Achillea moschata Jacq.)等のノコギリソウ属ノコギリソウ(Achillea alpina L.),セイヨウノコギリソウ(Achillea milleifolium L.),ジャコウノコギリソウ(Achillea moschata Jacq.)から選択される1種又は2種以上を用いることが、美白効果の点から好ましい。
【0044】
ヒヨドリバナ属(Eupatorium L.)植物は、キク科に属する双子葉植物で、フジバカマ(Eupatorium japonicum Thunb.),サワヒヨドリ(Eupatorium lindleyanum DC.),ヒヨドリバナ(Eupatorium chinense L. var. oppositifolium (Koidz.) Murata et H. Koyama)から選択される1種又は2種以上を用いることが、美白効果の点から好ましい。
【0045】
シナノキ属(Tilia L.)植物は、シナノキ科(Tiliaceae)に属する植物であり、アメリカシナノキ(Tilia americana L.)、フユボダイジュ(Tilia cordata Mill.)、セイヨウシナノキ(Tilia europaea L.)、シナノキ(Tilia japonica Simonk.)、ヘラノキ(Tilia kiusiana Makino et Shiras.)、オオバオダイジュ(Tilia maximowicziana Shiras.)、ナツボダイジュ(Tilia platyphyllos Scop.),ボダイジュ(Tilia miqueliana Maxim.)から選択される1種又は2種以上を用いることが、美白効果の点から好ましい。
【0046】
イワユキノシタ属(Tanakaea Fr. et Sav.)植物は、ユキノシタ科に属する常緑の多年草で、その美白効果の点からイワユキノシタ(Tanakaea radicans Fr. et Sav.)を用いることが好ましい。
【0047】
ジンチョウゲ属(Daphne L.)植物は、ジンチョウゲ科に属する低木であり、サツマフジ(Daphne genkwa Sieb. et Zucc.),コショウノキ(Daphne kiusiana Miq.),コウシュジンチョウゲ(Daphne mezereum L.),ジンチョウゲ(Daphne odora Thunb.),オニシバリ(Daphne opseud-mezereum A. Gray),ナニワズ(Daphne kamtchatica Maxim. var. yezoensis Ohwi),カラスシキミ(Daphne miyabeana Makino)から選択される1種又は2種以上を用いることが、美白効果の点から好ましい。
【0048】
ガンピ属(Diplomorpha Meissn. ex C. A. Mey.)植物は、ジンチョウゲ科に属する低木であり、オオシマガンピ(Diplomorpha phymatoglossa (Koidz.) Nakai),ガンピ(Diplomorpha sikokiana (Fr. et Sav.) Honda ),キガンピ(Diplomorpha trichotoma (Thunb.) Nakai)から選択される1種又は2種以上を用いることが、美白効果の点から好ましい。
【0049】
ミツマタ属(Edgeworthia Meissn.)植物は、ジンチョウゲ科に属する低木であり、その入手のしやすさの点から、ミツマタ(Edgeworthia chrysantha Lindl.)を用いることが好ましい。
【0050】
本発明で用いるボタン属(Paeonia L.)植物は、キンポウゲ科に属する低木で、美白効果の点からボタン(Paeonia suffruticosa Andr.)及びシャクヤク(Paeonia lactiflora Pall.)から選択される1種又は2種が好ましい例として挙げられる。
【0051】
カンゾウ属(Glycyrrhiza L.)植物は、マメ科に属する草本であり、その入手のしやすさから、スペインカンゾウ(Glycyrrhiza glabra L.),キカンゾウ(G lycyrrhiza kansuensis Chang et peng),カンゾウ(Glycyrrhiza urarensis Fisch.)から選択される1種又は2種以上を用いることが好ましい。
【0052】
クワ属(Morus L.)植物は、クワ科に属する低木であり、その入手のしやすさからクワ(Morus alba L.)を用いることが好ましい。
【0053】
エンジュ属(Sophora L.)植物は、マメ科に属する高木であり、その美白効果の点からクララ(Sophora flavescens Ait.),エンジュ(Sophora japonica L.)から選択される1種又は2種を用いることが好ましい。
【0054】
バラ属(Rosa L.)植物は、バラ科(Rosaceae)に属する植物である。中でも,ノイバラ(Rosa multiflora Thunb.)は、わが国に自生するバラ科(Rosaceae)の蔓性落葉低木であり、生薬「エイジツ」(Rosae Fructus)の基原植物であり、高い美白効果を発揮する。また、この近縁植物である、テリハノイバラ(Rosa wichuraiana Crepin var. ampullicarpa Honda)、フジイバラ(Rosa fujisanensis Makino)においても、高い美白効果が得られる。
【0055】
アロエ属(Aloe L.)植物は、ユリ科(Liliaceae)に属する木本性多肉植物で、生薬「アロエ」(Aloe)の基原植物として用いられる。アロエ属に属する植物としては、生薬「アロエ」の基原植物であるアロエフェロックス(Aloe ferox Mill.)、アロエアフリカーナ(Aloe africana Mill.)、アロエスピカータ(Aloe spicata Baker)、アロエアルボレッセンス(Aloe arborescens Mill.)アロエスコトリナ(Aloe succotrina Lam.)アロエプリカティリス(Aloe plicatilis Mill.)、アロエバイネシー(Aloe bainesii Th. Dyer.)、アロエペリー(Aloe perryi Baker)、アロエベラ(Aloe vera L.)等の他に、キダチアロエ(Aloe arborescens Mill.var. natalensis Berg.)も用いることができる。これらより1種又は2種以上を選択して用いることが好ましい。
【0056】
ニワトコ属(Sambucus L.)植物は、スイカズラ科(Caprifoliaceae)に属する植物であり、その入手しやすさから、セイヨウニワトコ(Sambucus nigra L.),アメリカニワトコ(Sambucus canadensis L.),ソクズ(Sambucus javanica Reinw. ex Bl. subsp. chinensis)から選択される1種又は2種以上を用いることが好ましい。
【0057】
ユキノシタ属(Saxifraga L.)植物は、ユキノシタ科に属する多年草であり、ホシツヅリ(Saxifraga aizoon Jacq.),シコタンソウ(Saxifraga cherlerioides D. Don var. rebunshirensis (Engl. et Irmsch) Hara),ジンジソウ(Saxifraga cortusaefolia Sieb. et Zucc.),ダイモンジソウ(Saxifraga fortunei Hook. f. var. incisolobata (Engl. et Irmsch.) Nakai),ハルユキノシタ(Saxifraga nipponica Makino),センダイソウ(Saxifraga sendaica Maxim.),ユキノシタ(Saxifraga stolonifera Meerb.),フキユキノシタ(Saxifraga japonica Boiss.),クロクモソウ(Saxifraga fusca Maxim.),クモマグサ(Saxifraga merkii Fish. var. laciniata Nakai),クモマユキノシタ(Saxifraga laciniata Nakai et Takeda),シコタンソウ(Saxifraga bronchialalis L.),ムカゴユキノシタ(Saxifraga cernua L.),ヤマハナソウ(Saxifraga sachalinensis Fr.Schm.)から選択される1種又は2種以上を用いることが、その美白効果の点から好ましい。
【0058】
ドクダミ属(Houttuynia Thunb.)植物は、ドクダミ科(Saururaceae)に属する、1属1種ドクダミ(Houttuynia cordata Thunb.)のみからなる属である。ドクダミ(Houttuynia cordata Thunb.)の全草は、「ジュウヤク」(Houttuyniae Herba)または重薬「ジュウヤク」ともよばれる生薬であり、かかる生薬を用いることが、美白作用の点から好ましい。
【0059】
カンアオイ属(Heterotropa Morr. et Decne)植物は,ウマノスズクサ科(Aristolochiaceae)に属する植物で、最近の研究では,フタバアオイ属(Asarum L.)やアメリカカンアオイ属(Hexastylis L.)、ウスバサイシン属(Asiasarum L.)等も含めて扱われる。中でも、ウスバサイシン属(Asiasarum L.)は、生薬「サイシン」(Asiasari Radix)の基原植物であり、美白有効性の観点からは、ウスバサイシン(Asiasarum sieboldii F. Maekawa)またはケイリンサイシン(Asiasarum heterotropoides var. mandshuricum F. Maekawa)、その近縁植物であるクロフネサイシン(Asiasarum dimidiatum F. Maekawa)、オクエゾサイシン(Asiasarum heterotropoides F. Maekawa)、ウスゲサイシン(Asiasarum heterotropoides var. seoulense F. Maekawa)、石南七(Asarum himalaicum Hook. f. et Thoms. ex Klotzch)などが好ましく用いられる。
【0060】
タツナミソウ属(Scutellaria L.)植物は、シソ科(Labiatae)に属する草本、あるいは半低木である。タツナミソウ属植物としては、コガネバナ(Scutellaria baicalensis Georgi),オカタツナミソウ(Scutellaria brachyspica Nakai et Hara),タツナミソウ(Scutellaria indica L.),シソバタツナミ(Scutellaria laeteviolacea Koidz.),スクテラリア ラテリフォリア(Scutellaria laterifolia L.),ホナガタツナミ(Scutellaria maekawae Hara),ヤマタツナミウソウ(Scutellaria pekinensis Maxim. var. transitra (Makino) Hara),ナミキソウ(Scutellaria strigillosa Hemsl.)等が例示される。このなかでも、生薬オウゴン(Scutellariae Radix)の基原植物である、コガネバナ(Scutellaria baicalensis Georgi)を用いることが好ましい。
【0061】
ヒマワリ属(Helianthus L.)植物は、キク科(Compositae)に属する双子葉植物の一種であり、中でも、ヒマワリ(Helianthus annuus L.)の抽出物が多く用いられる。本発明においてヒマワリ(Helianthus annuus L.)は、花、種子、茎、葉、根を用いることが出来るが、花又は種子を用いることが好ましい。また、種子からヒマワリ油を搾油した残渣であるヒマワリ油粕を用いてもよい。
【0062】
アマドコロ属(Polygonatum Adans.)植物は、ユリ科(Liliaceae)に属する一年草で、生薬「オウセイ」(Polygonati Rhizoma)の基原植物であるナルコユリ(Polygonatum falcatum A. Gray),オオナルコユリ(Polygonatum macranthum Koidzumi),及び近縁植物であるカギクルマバナルコユリ(Polygonatum sib ricum Red.),クルマバナルコユリ(Polygonatum stenophyllum Maxim.)などがあり、これらより1種又は2種以上を選択して用いることが、美白効果の点から好ましい。
【0063】
アマ属(Linum L.)植物は、アマ科(Linaceae)の一年生、二年生、又は多年生草本で、繊維や種子、種子油が利用されている。本発明においては、その美白効果の点からアマ(Linum usitatissimum L.)の種子である生薬「アマニン」(Lini Semen)からの抽出物を用いることが好ましい。
【0064】
カントウ属(Tussilago L.)植物は、キク科(Compositae)に属する植物である。その入手のしやすさから、フキタンポポ(Tussilago farfara L.)を用いることが好ましい。
【0065】
ワレモコウ属(Sanguisorba L.)植物は,バラ科(Rosaceae)に属する植物であり、ワレモコウ(Sanguisorba officinalis L.),オランダワレモコウ(Sanguisorba minor Scop.)等が例示される。中でも,生薬「チユ」(Sanguisorba Radix)の基原植物であるワレモコウ(Sanguisorba officinalis L.)を用いることが、美白効果及び入手のしやすさの点から、好ましい。
【0066】
ハッカ属(Mentha L.)植物は、シソ科(Lamiaceae)の植物で、スペアミントと呼ばれるミドリハッカ(Mentha spicata Linne)や、セイヨウハッカ(Mentha piperita L.)及びその変種、あるいは、ハッカ(Mentha arvensis L. var. piperascens Malin.)などが例示される。
【0067】
ハウチワマメ属(Lupinus L.)植物は、マメ科(Leguminosae)の双子葉植物であり、シロバナルーピン(Lupinus albus L. ; Lupinus sativus Gaertn.),アオバナルーピン(Lupinus angustifolius L. ; Lupinus varius L. ; Lupinus linifolius Roth ; Lupinus reticulatus Desv.),カサバルーピン(Lupinus hirsutus L.),カバナハウチワマメ(Lupinus luteus L.),シュッコンルーピン(Lupinus polyphyllus Lindl.) ,エジプトルーピン(Lupinus termis Forsk. ; Lupinus graecus Boiss.)等が例示される。これらの植物の中でも、その美白効果の点からシロバナルーピン(Lupinus albus L. ; Lupinus sativus Gaertn.)が好ましく用いられる。またハウチワマメ属(Lupinus L.)植物の全草,葉,茎,根,宿根,花,種子を用いることが出来るが、種子を用いることが好ましい。
【0068】
本願発明で使用する藻類としては、カイメンソウ(Ceratodictyon spongiosum)に代表されるカイメンソウ属(Ceratodictyon)藻類、無節サンゴモ(Corallina sp.),サンゴモ(Corallina officinalis),ピリヒバ(Corallina pilurifera)等のサンゴモ属(Corallina)藻類、ヤハズグサ(Dictyopteris latiuscula),シワヤハズ(Dictyopteris undulata),ヘラヤハズ(Dictyopteris prolifera),スジヤハズ(Dictyopteris plagiogramma),ヒメヤハズ(Dictyopteris repens),エゾヤハズ(Dictyopteris divaricata),ウラボシヤハズ(Dictyopteris polypodioides)等のヤハズグサ属(Dictyopteris)藻類、ハリアミジ(Dictyota spinulosa)に代表されるアミジグサ属(Dictyota)藻類、ヒジキ(Hizikia fusiformis)に代表されるヒジキ属(Hizikia)藻類、ソゾsp.(Laurencia sp.),クロソゾ(Laurencia intermedia),ミツデソゾ(Laurencia okamurai),ソゾノハナ(Laurencia grevilleana),オオソゾ(Laurencia glandulifera),ハネソゾ(Laurencia pinnata),コブソゾ(Laurencia undulata)等のソゾ属(Laurencia)藻類、フシツナギ(Lomentaria catenata),コスジフシツナギ(Lomentaria hakodatensis)等のフシツナギ属(Lomentaria)藻類、イワヒゲ(Myelophycus caespitosus)に代表されるイワヒゲ属(Myelophycus)藻類、ダルス(Palmaria palmata)に代表されるダルス属(Rhodymenia)藻類、ホンダワラ(Sargassum fulvellum),エンドウモク(Sargassum yendoi),マメタワラ(Sargassum piluriferum),ヤツマタモク(Sargassum patens),アカモク(Sargassum horneri),ノコギリモク(Sargassum serratifolium),オオバノコギリモク(Sargassum giganteifolium),ヨレモク(Sargassum tortile),ヤナギモク(オオバモク:Sargassum ringgoldianum),ネジモク(Sargassum sagamianum),ハハキモク(Sargassum kjellmanianum),ウミトラノオ(Sargassum thunbergii),フシスジモク(Sargassum confusum),イソモク(Sargassum hemiphyllum),ナラサモ(Sargassum nigrifolium),トゲモク(Sargassum micracanthum),タマナシモク(Sargassum nipponicum),ジンメソウ(Sargassum vulgare),フタエモク(ヒイラギモク:Sargassum duplicatum),エゾノネジモク(Sargassum yezoense)等のホンダワラ属(Sargassum)藻類、モヅク(Nemacystus decipieus)に代表されるモヅク属(Nemacystus)藻類、ナガマツモ(Chordaria flagelliformis),イシモヅクダマシ(Chordaria firma)等のナガマツモ属(Chordaria)藻類、イシモヅク(Sphaerotrichia divaricata)に代表されるイシモヅク属(Sphaerotrichia)藻類、フトモヅク(Tinocladia crassa ( Suringar) Kylin)に代表される、フトモヅク属(Tinocladia Kylin)属藻類、オキナワモヅク(Cladosiphon okamuranus)に代表されるオキナワモヅク属(Cladosiphon)藻類等が例示される。
【0069】
これらの植物及び藻類からの抽出物は、各種の全草又はその葉,樹皮,根,花,枝等の1又は2以上の箇所を生のまま若しくは乾燥させて使用する。抽出溶媒としては特に限定されず、水、エタノール,メタノール,イソプロパノール,イソブタノール,n-ヘキサノール,メチルアミルアルコール,2-エチルブタノール,n-オクチルアルコール等の1価アルコール類、グリセリン,エチレングリコール,エチレングリコールモノメチルエーテル,プロピレングリコール,プロピレングリコールモノメチルエーテル,プロピレングリコールモノエチルエーテル,トリエチレングリコール,1,3-ブチレングリコール,へキシレングリコール等の多価アルコール又はその誘導体、アセトン,メチルエチルケトン,メチルイソブチルケトン,メチル-n-プロピルケトン等のケトン類、酢酸エチル,酢酸イソプロピル等のエステル類、エチルエーテル,イソプロピルエーテル,n-ブチルエーテル等のエーテル類、スクワラン,ワセリン,パラフィンワックス,パラフィン油などの炭化水素類、オリーブ油,小麦胚芽油,米油,ゴマ油,マカダミアンナッツ油,アルモンド油,ヤシ油等の植物油脂、牛脂,豚脂,鯨油等の動物油脂などが例示される。また、リン酸緩衝生理食塩水等の無機塩類を添加した極性溶媒、界面活性剤を添加した溶媒を用いることもでき、特に限定されない。
【0070】
更に、抽出方法としては、室温,冷却又は加熱した状態で含浸させて抽出する方法、水蒸気蒸留などの蒸留法を用いて抽出する方法、植物又は藻類を圧搾して抽出物を得る圧搾法などが例示され、これらの方法を単独で、又は2種以上を組み合わせて抽出を行う。
【0071】
抽出の際の植物又は藻類と溶媒との比率は特に限定されないが、植物又は藻類1に対して溶媒0.1〜1000重量倍、特に抽出操作,効率の点で、0.5〜100重量倍が好ましい。また抽出圧力及び抽出温度は常圧下で0℃から溶媒の沸点以下の範囲とするのが便利であり、抽出時間は抽出温度などにより異なるが2時間〜2週間の範囲とするのが好ましい。
【0072】
このようにして得られた植物又は藻類の抽出物は、抽出物をそのまま用いることもできるが、その効果を失わない範囲で、脱臭,脱色,濃縮などの精製操作を加えたり、さらにはカラムクロマトグラフィーなどを用いて分画物として用いてもよい。これらの抽出物や精製物,分画物は、これらから溶媒を除去することによって乾固物とすることもでき、さらに、アルコールなどの溶媒に可溶化した形態、或いは乳剤の形態で用いることができる。
【0073】
これらの美白剤の皮膚外用剤への配合量は、その効果や添加した際の臭い,色調の点から考え、0.0001〜10重量%の濃度範囲とすることが望ましい。
【0074】
これらの美白剤の中でも、水溶性のアスコルビン酸誘導体が特にその経皮吸収促進効果の点から好ましい。
【0075】
なお、本発明に係る皮膚外用剤には、上述の成分の他に、通常医薬品,医薬部外品,化粧料に配合される、油性成分,粉体,色素,乳化剤,可溶化剤,薬剤,香料,樹脂,アルコールなどを本発明の効果,特徴を損なわない範囲において適宜配合することができる。
【0076】
【実施例】
以下実施例を挙げて本発明を具体的に説明する。なお、特に断らない限り、実施例中の量目は、重量%で示した。実施例の説明に先立ち本発明で用いた効果試験方法について説明する。
【0077】
(1) 薬剤皮膚透過性試験
美白剤に対する経皮吸収促進効果を評価するため、ヘアレスマウス皮膚透過試験を行った。試験は、ヘアレスマウスの剥離した皮膚を、0.785cm2の拡散有効面積を持つ拡散セルに、角質層側がドナー相、真皮側がレセプター相になるように装着し、試料を塗布することにより行った。レセプター相にはPH7.4のリン酸緩衝溶液5mlをレセプター液として入れた。24時間後にレセプター液をサンプリングし、高速液体クロマトグラフィーにより美白剤の透過量を求めた。結果は薬剤透過率(%)として表した。
【0078】
[実施例1〜3、比較例1]
表1に示す処方の皮膚外用剤を、(3)に(1)、(2)を溶解して調製した。
【0079】
【表1】
【0080】
実施例1〜実施例3、比較例1の薬剤皮膚透過性試験結果は、表1に示したとおり、N−アセチルグルタミンを配合していない比較例1と比べて、美白剤(アスコルビン酸グルコシド)とN−アセチルグルタミンを組み合わせて配合した実施例の皮膚外用剤は、薬剤透過率が高く、N−アセチルグルタミンが美白剤の経皮吸収を顕著に促進していることは明らかである。
【0081】
続いて、美白剤として配合する植物,藻類抽出物の調製例を示す。
【0082】
[イタドリ抽出物]
イタドリ(Polygonum cuspidatum Sieb. et Zucc.)の根茎550gを乾燥,粉砕し、50容量%エタノール水溶液1,500mL中にて25℃で5日間撹拌抽出した。次いで、抽出液をろ過し、ろ液をイタドリ抽出物とした。
【0083】
[イタドリ抽出分画物]
イタドリ(Polygonum cuspidatum Sieb. et Zucc.)の根茎の乾燥粉末200gを50容量%エタノール水溶液2,000mL中に浸漬し、室温で7日間抽出した。次いで、抽出液をろ過し、ろ液を減圧濃縮し、30容量%エタノール水溶液800mLに溶解して、DIAION MCI Gel HP−20カラム(三菱化成株式会社製)にかけ、40容量%エタノール水溶液にて溶出される画分を回収した。次いで前記画分をシリカゲル薄層クロマトグラフィーにてクロロホルム・メタノール混合物(容量比=5:1)を展開溶媒として用いて分画した。得られた画分のうち、(-)-エピカテキンを含む画分を掻き取り、50容量%エタノール50mLに溶解したろ液をイタドリ抽出分画物とした。
【0084】
[ハマメリス抽出物]
ハマメリス(Hamamelis virginiana L.)の葉500gを乾燥,粉砕し、50容量%エタノール水溶液1,000mL中にて25℃で5日間撹拌抽出した。次いで抽出液をろ過し、ろ液を回収してハマメリス抽出物とした。
【0085】
[ハマメリス抽出分画物]
ハマメリス(Hamamelis virginiana L.)の葉及び樹皮計500gを細切し、熱水1,500mL中にて5時間撹拌抽出した。次いで抽出液をろ過し、ろ液をDIAION MCI Gel HP−20カラム(三菱化成株式会社製)にかけ、エタノール・水混合溶媒で溶出し、ハマメリタンニン含量が50重量%以上の画分を回収してハマメリス抽出分画物とした。
【0086】
[メリッサ抽出物]
メリッサ(Melissa officinalis L.)の開花期の全草350gを細切し、オリーブ油1,000ml中にて20℃で7日間浸漬して抽出した。抽出液をろ過してろ液を回収してセイヨウオトギリソウ抽出物とした。
【0087】
[甘草抽出物]
カンゾウ(Glycyrrhiza urarensis Fisch.)の根及び根茎500gを乾燥,粉砕し、無水エタノール水溶液1,000mL中にて25℃で24時間撹拌抽出した。抽出液をろ過してろ液を回収し、減圧濃縮した後、凍結乾燥により乾固させる。乾固物を酢酸エチル1,000mL中にて20℃で2日間撹拌抽出した。抽出後、減圧乾燥して甘草エキスとした。
【0088】
[ジンコウ抽出物]
ジンコウ(Aquillaria agallocha Roxb.)の枝及び幹,計300gを乾燥,粉砕し、エタノール1,000中にて20℃で10日間浸漬した。次いで、抽出液をろ過し、ろ液を1/10容量まで濃縮してジンコウ抽出物とした。
【0089】
[ウーロン茶抽出物]
ウーロン茶(Thea sinensis L. var. viridis Szkzyl.)の葉440gを乾燥,粉砕し、精製水1,000mL中にて50℃で24時間撹拌抽出した。抽出液をろ過し、ろ液を1/5容量まで濃縮してウーロン茶抽出物とした。
【0090】
[カワラヨモギ抽出物]
カワラヨモギ(Artemisia capillaris Thunb.)の葉300gを粉砕し、1,3-ブチレングリコール1,000mL中にて25℃で5日間撹拌抽出した。抽出液をろ過し、ろ液を回収してカワラヨモギ抽出物とした。
【0091】
[タイム抽出物]
タイム(Thymus vulgaris L.)の全草450gを乾燥,粉砕し、50容量%グリセリン水溶液1,500mL中にて25℃で5日間撹拌抽出した。抽出液をろ過し、ろ液を回収してタイム抽出物とした。
【0092】
[ボタン抽出物]
ボタン(Paeonia suffruticosa Andr.)の根皮300gを乾燥,粉砕し、95容量%エタノール水溶液1,000mL中にて25℃で5日間撹拌抽出した。抽出液をろ過し、ろ液を回収してボタン抽出物とした。
【0093】
[クワ抽出物]
クワ(Morus alba L.)の根皮350gを細切し、1,3-ブチレングリコール1,000mL中にて20℃で7日間浸漬して抽出した。抽出液をろ過してろ液を回収してクワ抽出物とした。
【0094】
[セイヨウノコギリソウ抽出物]
セイヨウノコギリソウ(Achillea milleifolium L.)の花320gを生理食塩水2,000mL中10℃にてホモジナイズし、更に4時間撹拌抽出した。抽出液をろ過し、ろ液を回収してセイヨウノコギリソウ抽出物とした。
【0095】
[ユズ抽出物]
ユズ(Citrus junos Sieb. et Tanaka)の乾燥果実450gを粉砕し、50容量%エタノール水溶液1,500mL中にて25℃で5日間撹拌抽出した。抽出液をろ過し、ろ液を回収してユズ抽出物とした。
【0096】
[ヘラヤハズ抽出物],[紅藻抽出物]
海から採取した、ヘラヤハズ,紅藻の全藻を水洗した後細切し、等量のリン酸緩衝生理食塩水(pH7.4)に分散後、ブレンダーミルで3時間撹拌抽出した。抽出液をろ過し、ろ液を回収して上記各抽出物とした。
【0097】
[シャクヤク抽出物]
シャクヤク(Paeonia lactiflora Pall.)の乾燥根450gを粉砕し、50容量%エタノール水溶液1,500mL中にて25℃で5日間撹拌抽出した。抽出液をろ過し、ろ液を回収してシャクヤク抽出物とした。
【0098】
つづいて、本発明に係る他の実施例の処方を示す。
【0099】
[実施例4〜実施例12] 美容液
(1)1,3-ブチレングリコール 30.0
(2)N−アセチルグルタミン 1.0
(3)精製水 全量を100とする量
(4)表2に示す美白剤 表2に示す配合量
製法:(1)〜(4)の成分を混合,均一化する。
【0100】
【表2】
【0101】
上記処方にて調製した本発明の実施例4〜実施例12及び、実施例1においてN−アセチルグルタミンを精製水に代替して調製した比較例1について、色素沈着症状の改善効果の評価を行った。色素沈着症状の改善効果は、顕著なしみ,ソバカス等の色素沈着症状を有する女性パネラー20名を一群とし、各群に実施例又は比較例をそれぞれブラインドにて1日2回ずつ1ヶ月間使用させ、1ヶ月後の皮膚の色素沈着の状態を観察して使用前と比較して評価した。色素沈着の状態は、表3に示す判定基準にしたがって評価し、20名の平均値を算出して表4に示した。
【0102】
【表3】
【0103】
【表4】
【0104】
表4から明らかなように、本発明に係る実施例使用群では、全群で顕著な色素沈着症状の改善が認められており、使用試験終了後には、軽度若しくはわずかな色素沈着が認められるにすぎない程度まで症状が改善されていた。特に、N−アセチルグルタミンと、L−アスコルビン酸リン酸エステルマグネシウム塩を併用した実施例4,イタドリ抽出分画物を併用した実施例11,ハマメリス抽出分画物を併用した実施例12使用群において、良好な改善が見られていた。これに対し、美白剤を単独で配合した比較例使用群においては、色素沈着症状の改善は認められるものの、それぞれ対応する実施例使用群に比べ、改善の程度は明らかに小さいものであった。
【0105】
なお、本発明の実施例4〜実施例12については、上記使用試験期間中に含有成分の析出,分離,凝集,変臭,変色といった製剤の状態変化は全く見られなかった。また、各実施例使用群において、皮膚刺激性反応や皮膚感作性反応を示したパネラーは存在しなかった。
【0106】
本発明のそのほかの実施例を示す。
【0107】
[実施例13] 美白用クリーム
(1)1,3-ブチレングリコール 10.00
(2)パラオキシ安息香酸メチル 0.10
(3)ショ糖ステアリン酸エステル 0.35
(4)N−ステアロイル−L−グルタミン酸ナトリウム 0.35
(5)カルボキシビニルポリマー(1重量%水溶液) 2.00
(6)2−メタクリロイルオキシエチルホスホリルコリン・
メタクリル酸ブチル共重合体液モノラウリン酸ポリグリセリル 0.50
(7)精製水 65.70
(8)スクワラン 3.00
(9)ミリスチン酸オクチルドデシル 3.00
(10)親油型モノステアリン酸グリセリン 3.00
(11)ミツロウ 1.00
(12)ステアリン酸 1.00
(13)ベヘニルアルコール 2.50
(14)パーム硬化油 2.00
(15)ホホバ油 0.10
(16)グリチルレチン酸ステアリル 0.05
(17)ジメチルシロキサン/ビニルジメチルシロキサン共重合体液 1.00
(18)ボタン抽出物 0.05
(19)メリッサ抽出物 0.05
(20)シャクヤク抽出物 0.05
(21)水酸化ナトリウム(10重量%水溶液) 1.00
(22)ポリグルタミン酸 0.05
(23)ユズ抽出物 0.20
(24)N−アセチルグルタミン 0.50
(25)アスコルビン酸リン酸エステルナトリウム塩 1.00
(26)クエン酸ナトリウム 0.20
(27)ジエチレントリアミン五酢酸五ナトリウム(40重量%水溶液) 0.20
(28)精製水 1.00
(29)香料 0.05
製法:(1)〜(7)の油性成分、及び(8)〜(17)の水性成分をそれぞれ混合均一化して75℃に加熱する。水性成分に油性成分を添加して乳化後、(18)〜(29)の成分を順次添加する。
【0108】
[実施例14] 美容液
(1)アジピン酸ジ−2−ヘプチルウンデシル 2.00
(2)トリ2−エチルヘキサン酸グリセリル 4.00
(3)ジメチルポリシロキサン 2.00
(4)ベヘニルアルコール 1.00
(5)自己乳化型モノステアリン酸グリセリル 1.30
(6)水素添加大豆リン脂質 0.20
(7)モノステアリン酸ポリエチレングリコール 0.20
(8)ミツロウ 0.10
(9)ステアリン酸 0.10
(10)ホホバ油 0.10
(11)スクワラン 0.10
(12)グリチルレチン酸ステアリル 0.05
(13)1,3-ブチレングリコール 6.00
(14)精製水 57.34
(15)ヒドロキシエチルセルロール(1重量%水溶液) 6.00
(16)キサンタンガム(1重量%水溶液) 3.00
(17)アスコルビン酸リン酸エステルマグネシウム塩 2.00
(18)ジエチレントリアミン五酢酸五ナトリウム(40重量%水溶液) 0.20
(19)水酸化ナトリウム(10重量%水溶液) 2.00
(20)クエン酸ナトリウム(10重量%水溶液) 5.00
(21)ボタン抽出物 0.02
(22)メリッサ抽出物 0.02
(23)シャクヤク抽出物 0.02
(24)ユズ抽出物 0.02
(25)N−アセチルグルタミン 0.10
(26)エタノール 7.00
(27)香料 0.08
(28)パラオキシ安息香酸メチル 0.05
製法:(1)〜(12)の油性成分、及び(13)〜(16)の水性成分をそれぞれ混合均一化して75℃に加熱する。水性成分に油性成分を添加して乳化後、(17)〜(28)の成分を順次添加する。
【0109】
[実施例15] 皮膚用ローション
(1)精製水 86.19
(2)グリチルリチン酸ジカリウム 0.05
(3)ポリエチレングリコール(4000) 1.00
(4)トリメチルグリシン 1.00
(5)紅藻抽出物 1.60
(6)アスコルビン酸リン酸エステルナトリウム塩 2.00
(7)水酸化ナトリウム(10重量%水溶液) 2.20
(8)クエン酸ナトリウム 0.30
(9)ジエチレントリアミン五酢酸五ナトリウム(40重量%水溶液) 0.20
(10)N−アセチルグルタミン 0.30
(11)ボタン抽出物 0.02
(12)シャクヤク抽出物 0.02
(13)メリッサ抽出物 0.02
(14)ユズ抽出物 0.02
(15)エタノール 5.00
(16)ポリオキシエチレン(60EO)硬化ヒマシ油 0.02
(17)香料 0.01
(18)パラオキシ安息香酸メチル 0.05
製法:(1)〜(18)を混合し、均一とする。
【0110】
[実施例16] 皮膚用乳剤
(1)ステアリン酸 0.2
(2)セタノール 1.5
(3)ワセリン 3.0
(4)流動パラフィン 7.0
(5)ポリオキシエチレン(10E.O.)モノオレイン酸エステル 1.5
(6)グリセリン 5.0
(7)トリエタノールアミン 1.0
(8)N−アセチルグルタミン 0.5
(9)精製水 79.5
(10)乳酸菌抽出物 0.5
(11)胎盤抽出物 0.3
製法:(1)〜(5)の油相成分を混合,加熱して均一に溶解し、70℃に保つ。一方、(6)〜(9)の水相成分を混合,加熱して均一とし、70℃とする。この水相成分に油相成分を撹拌しながら徐々に添加して乳化した後冷却し、40℃で(10),(11)の成分を添加する。
【0111】
[実施例17] 皮膚用ゲル剤
(1)精製水 90.5
(2)カルボキシビニルポリマー 0.5
(3)N−アセチルグルタミン 0.7
(4)ジプロピレングリコール 8.0
(5)水酸化カリウム 0.1
(6)メリッサ抽出物 0.2
製法:(1)に(2)及び(3)を均一に溶解した後、(4)を添加し、次いで(5)を加えて増粘させ、(6)を添加して均一に混合する。
【0112】
[実施例18] 皮膚用クリーム
(1)ミツロウ 6.0
(2)セタノール 5.0
(3)還元ラノリン 8.0
(4)スクワラン 29.5
(5)親油型グリセリンモノステアリン酸エステル 4.0
(6)ポリオキシエチレン(20E.O.)
ソルビタンモノラウリン酸エステル 5.0
(7)プロピレングリコール 5.0
(8)N−アセチルグルタミン 1.0
(9)ウーロン茶抽出物 0.2
(10)精製水 36.3
製法:(1)〜(6)の油相成分を混合,溶解して75℃に加熱する。一方、(7)〜(10)の水相成分を混合,溶解して75℃に加熱する。次いで、上記水相成分に油相成分を添加して予備乳化した後、ホモミキサーにて均一に乳化する。
【0113】
[実施例19] 水中油型乳剤性軟膏
(1)白色ワセリン 25.0
(2)ステアリルアルコール 25.0
(3)グリセリン 10.0
(4)ラウリル硫酸ナトリウム 1.0
(5)N−アセチルグルタミン 0.3
(6)カワラヨモギ抽出物 0.2
(7)精製水 38.5
製法:(1)〜(4)の油相成分を混合,溶解して均一とし、75℃に加熱する。一方、(5),(6)を(7)に溶解して75℃にて加熱溶解し、これに前記油相成分を添加して乳化する。
【0114】
[実施例20] メイクアップベースクリーム
(1)ステアリン酸 12.0
(2)セタノール 2.0
(3)グリセリントリ-2-エチルヘキサン酸エステル 2.5
(4)自己乳化型グリセリンモノステアリン酸エステル 2.0
(5)プロピレングリコール 10.0
(6)水酸化カリウム 0.3
(7)N−アセチルグルタミン 1.5
(8)精製水 68.0
(9)酸化チタン 1.0
(10)ベンガラ 0.1
(11)黄酸化鉄 0.4
(12)香料 0.1
(13)ボタン抽出物 0.1
製法:(1)〜(4)の油相成分を混合し、75℃に加熱して均一とする。一方、(5)〜(8)の成分を混合し、75℃に加熱,溶解して均一とし、これに(9)〜(11)の顔料を添加し、ホモミキサーにて均一に分散させ水相成分とする。この水相成分に前記油相成分を添加し、ホモミキサーにて乳化した後冷却し、40℃にて(12),(13)の成分を添加,混合する。
【0115】
[実施例21] 乳液状ファンデーション
(1)ステアリン酸 2.0
(2)スクワラン 5.0
(3)ミリスチン酸オクチルドデシル 5.0
(4)セタノール 1.0
(5)デカグリセリンモノイソパルミチン酸エステル 9.0
(6)1,3-ブチレングリコール 8.0
(7)水酸化カリウム 0.1
(8)N−アセチルグルタミン 0.5
(9)精製水 51.0
(10)酸化チタン 9.0
(11)タルク 7.4
(12)ベンガラ 0.5
(13)黄酸化鉄 1.1
(14)黒酸化鉄 0.1
(15)香料 0.1
(16)クワ抽出物 0.2
製法:(1)〜(5)の油相成分を混合し、75℃に加熱して均一とする。一方、(6)〜(9)の水相成分を混合し、75℃に加熱,溶解して均一とし、これに(10)〜(14)の顔料を添加し、ホモミキサーにて均一に分散させる。油相成分を添加して乳化した後冷却し、40℃にて(15),(16)の成分を添加,混合する。
【0116】
[実施例22] ハンドクリーム
(1)セタノール 4.0
(2)ワセリン 2.0
(3)流動パラフィン 10.0
(4)グリセリンモノステアリン酸エステル 1.5
(5)ポリオキシエチレン(60E.O.)
グリセリンイソステアリン酸エステル 2.5
(6)酢酸トコフェロール 0.5
(7)グリセリン 20.0
(8)パラオキシ安息香酸メチル 0.1
(9)N−アセチルグルタミン 2.5
(10)ハイドロキノン-β-D-グルコース 1.0
(11)精製水 55.9
製法:(1)〜(6)の油相成分を混合,溶解して75℃に加熱する。一方、(7)〜(11)の水相成分を混合,溶解して75℃に加熱する。次いで、水相成分に油相成分を添加して予備乳化した後、ホモミキサーにて均一に乳化する。
【0117】
[実施例23] ゼリー状ピールオフパック
(1)ポリビニルアルコール 15.0
(2)カルボキシメチルセルロース 5.0
(3)1,3-ブチレングリコール 3.0
(4)エタノール 6.0
(5)ポリオキシエチレン(20E.O.)オレイルエーテル 0.5
(6)N−アセチルグルタミン 3.0
(7)セイヨウノコギリソウ抽出物 0.1
(8)精製水 67.4
製法:(8)に(3)を加えて75℃に加熱する。これに(1),(2)を添加して溶解させ、(4)〜(7)を添加して可溶化する。
【0118】
[実施例24] マッサージゲル
(1)ジプロピレングリコール 7.0
(2)グリセリン 8.0
(3)ポリオキシエチレン(15E.O.)オレイルエーテル 1.0
(4)カルボキシビニルポリマー 0.4
(5)メチルセルロース 0.2
(6)N−アセチルグルタミン 0.5
(7)シャクヤク抽出物 0.2
(8)水酸化カリウム 0.1
(9)精製水 82.6
製法:75℃に加熱した(9)に、(1)〜(8)の成分を順次添加,溶解,均一化する。
【0119】
[実施例25] 洗顔料
(1)ステアリン酸 2.0
(2)セタノール 3.0
(3)ワセリン 10.0
(4)流動パラフィン 33.0
(5)ミリスチン酸イソプロピル 7.5
(6)グリセリンモノステアリン酸エステル 2.5
(7)ポリオキシエチレン(20E.O.)ソルビタン
モノステアリン酸エステル 2.5
(8)グリセリン 5.0
(9)水酸化カリウム 0.1
(10)精製水 31.2
(11)ヘラヤハズ抽出物 0.2
(12)N−アセチルグルタミン 3.0
製法:(1)〜(7)の油相成分を混合,加熱溶解し、70℃とする。一方、(8)〜(10)の水相成分を混合して加熱溶解し、70℃とする。この水相成分に油相成分を徐々に添加して予備乳化し、次いでホモミキサーにて均一に乳化後冷却し、40℃で(11),(12)の成分を添加する。
【0120】
[実施例26] クレンジングクリーム
(1)精製水 16.65
(2)ポリオキシエチレンヤシ油脂肪酸ソルビタン(20EO) 2.40
(3)1,3-ブチレングリコール 8.00
(4)水素添加大豆リン脂質 0.10
(5)カルボキシビニルポリマー(1重量%水溶液) 20.00
(6)グリチルレチン酸ステアリル 0.05
(7)ベヘニルアルコール 1.20
(8)ステアリン酸 0.10
(9)ミツロウ 0.10
(10)硬化油 0.10
(11)ホホバ油 0.10
(12)トコフェロール 0.05
(13)モノステアリン酸ソルビタン 1.60
(14)2−エチルヘキサン酸セチル 5.00
(15)スクワラン 40.00
(16)L−アルギニン(10重量%水溶液) 1.50
(17)パラオキシ安息香酸メチル 0.10
(18)1,3-ブチレングリコール 2.00
(19)アスコルビン酸リン酸エステルマグネシウム塩 0.50
(20)ボタン抽出物 0.02
(21)シャクヤク抽出物 0.02
(22)メリッサ抽出物 0.02
(23)ユズ抽出物 0.02
(24)N−アセチルグルタミン 0.30
(25)香料 0.07
製法:(1)〜(5)の水相成分を混合,加熱溶解し、70℃とする。一方、(6)〜(15)の油相成分を混合して加熱溶解し、70℃とする。水相成分に油相成分を徐々に添加して予備乳化し、次いでホモミキサーにて均一に乳化後冷却し、40℃で(16)〜(25)の成分を順次添加する。
【0121】
[実施例27] 洗顔料
(1)ミリスチン酸 30.00
(2)親油型モノステアリン酸グリセリル 6.00
(3)ステアリン酸 2.80
(4)(ヒドロキシステアリン酸/イソステアリン酸)
ジペンタエリトリットエステル 1.00
(5)グリセリン 17.00
(6)水酸化カリウム 8.00
(7)精製水 31.74
(8)N−ステアロイル−L−グルタミン酸ナトリウム 1.00
(9)1,3−ブチレングリコール 1.00
(10)パラオキシ安息香酸メチル 0.08
(11)水素添加大豆リン脂質 0.10
(12)塩化O−〔2−ヒドロキシ−3−(トリメチルアンモニオ)
プロピル〕ヒドロキシエチルセルロース液 0.05
(13)グリチルリチン酸ジカリウム 0.05
(14)アスコルビン酸リン酸エステルマグネシウム塩 0.50
(15)ボタン抽出物 0.02
(16)シャクヤク抽出物 0.02
(17)メリッサ抽出物 0.02
(18)ユズ抽出物 0.02
(19)N−アセチルグルタミン 0.10
(20)香料 0.50
製法:(1)〜(5)の油相成分を混合,加熱溶解し、70℃とする。一方、(6)〜(12)の水相成分を混合して加熱溶解し、70℃とする。水相成分に油相成分を徐々に添加して予備乳化し、次いでホモミキサーにて均一に乳化後冷却し、40℃で(13)〜(20)の成分を順次添加する。
【0122】
[実施例28] マスク剤
(1)N−ステアロイル−L−グルタミン酸ナトリウム 1.00
(2)精製水 48.14
(3)モノステアリン酸ポリエチレングリコール 2.00
(4)モノパルミチン酸ポリオキシエチレンソルビタン(20EO) 1.00
(5)ジエチレントリアミン五酢酸五ナトリウム(40重量%水溶液) 0.20
(6)L−アルギニン 0.03
(7)1,3−ブチレングリコール 3.00
(8)酸化チタン 4.00
(9)ベヘニルアルコール 3.50
(10)親油型モノステアリン酸グリセリン 3.50
(11)ミリスチン酸オクチルドデシル 15.00
(12)スクワラン 12.00
(13)セスキオレイン酸ソルビタン 1.00
(14)ステアリン酸 0.10
(15)ミツロウ 0.10
(16)ホホバ油 0.10
(17)硬化油 0.10
(18)グリチルレチン酸ステアリル 0.05
(19)アルコール 2.00
(20)パラオキシ安息香酸メチル 0.10
(21)香料 0.07
(22)アスコルビン酸リン酸エステルマグネシウム塩 0.50
(23)クエン酸ナトリウム(10重量%水溶液) 2.00
(24)ボタン抽出物 0.02
(25)シャクヤク抽出物 0.02
(26)メリッサ抽出物 0.02
(27)ユズ抽出物 0.10
(28)N−アセチルグルタミン 0.35
製法:(1)〜(8)の水相成分を混合し、ホモミキサーにて均質に分散させ、70℃に加熱する。一方、(6)〜(18)の油相成分を混合して加熱溶解し、70℃とする。水相成分に油相成分を徐々に添加し、ホモミキサーにて均一に乳化後冷却し、40℃で(19)〜(28)の成分を順次添加する。
【0123】
上述の実施例13〜実施例28について、色素沈着症状の改善効果の評価を行ったところ、全ての実施例において、良好な色素沈着症状の改善効果が認められた。
【0124】
実施例4〜実施例28について、24時間閉塞貼付試験、皮膚刺激性試験を行ったところ、高い安全性を示した。
【0125】
【発明の効果】
以上詳述したように、美白剤、特に水溶性アスコルビン酸誘導体のような親水性薬剤に対する経皮吸収促進効果が良好で、優れた美白効果を発揮する皮膚外用剤を提供することができた。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an external preparation for skin. More specifically, the present invention relates to a skin external preparation that can promote percutaneous absorption of a whitening agent and can effectively exert a whitening effect.
[0002]
[Prior art]
Conventionally, in skin external preparations such as lotions, ointments, creams, and poultices, ingredients that exhibit various medicinal effects by transdermal absorption are blended. However, since the skin originally has a function to prevent the invasion of foreign substances from outside the body, sufficient transdermal absorption cannot be obtained only by blending medicinal ingredients in a normal external preparation base. In many cases, sufficient medicinal effects cannot be obtained.
[0003]
Therefore, in order to improve percutaneous absorption of medicinal components, aprotic solvents such as dimethyl sulfoxide and N, N-dimethylformylamide (see Patent Document 1), anionic or amphoteric surfactants (Patent Document 2, Patent Document) 3), 1-dodecylazacycloheptan-2-one (see Patent Document 4), terpene ketones such as l-carvone, menthone and piperiton (see Patent Document 5), d-limonene (see Patent Document 6), N -Mono- or di-substituted-p-menthane-3-carboxamide (see Patent Document 7) and the like are disclosed. However, even if these transdermal absorption enhancers are used, sufficient transdermal absorbability of the drug may not be obtained, and particularly effective percutaneous absorption promotion for hydrophilic drugs such as water-soluble ascorbic acid derivatives. Little drug has been found. In addition, many of the above-mentioned transdermal absorption enhancers have strong skin irritation, and by applying a formulation containing the same, erythema is produced on the skin, and a transdermal absorption enhancer that is satisfactory in terms of safety is obtained. The current situation is not.
[0004]
N-acetylglutamine is an N-acetylated derivative of glutamine and is superior in thermal stability to glutamine (see Patent Document 8), and increases moisture retention of the stratum corneum by applying to the skin (Patent Document) 9) is known.
[0005]
[Patent Document 1]
U.S. Pat. No. 3,551,554
[Patent Document 2]
JP-A-51-32724
[Patent Document 3]
JP 52-83914 A
[Patent Document 4]
JP 52-1035 A
[Patent Document 5]
JP-A-2-193932
[Patent Document 6]
JP-A-2-207024
[Patent Document 7]
JP 2001-58961 A
[Patent Document 8]
Japanese Patent Publication No. 47-670
[Patent Document 9]
Japanese Patent Laid-Open No. 3-2523206
[0006]
[Problems to be solved by the invention]
Accordingly, an object of the present invention is to provide a skin external preparation that is excellent in the effect of promoting percutaneous absorption of a whitening agent, particularly a hydrophilic drug such as a water-soluble ascorbic acid derivative, and is excellent in safety.
[0007]
[Means for Solving the Problems]
As a result of diligent research to solve the above problems, the inventors of the present invention have excellent transdermal absorbability of N-acetylglutamine with respect to whitening agents, low skin irritation, and excellent safety. It has been found that the above-mentioned problems can be solved by blending N-acetylglutamine into a skin external preparation together with a drug having a whitening effect, and the present invention has been completed.
[0008]
That is, this invention is N-acetylglutamine and the skin external preparation characterized by containing 1 type, or 2 or more types selected from a whitening agent.
[0009]
The whitening agent used in the present invention is preferably a water-soluble drug, among which L-ascorbic acid and its salts or derivatives thereof, hydroquinone and its derivatives, cysteine and its derivatives, glucosamine and its derivatives, azelaic acid and Derivatives thereof, lipoic acid and derivatives thereof and salts thereof, resorcin and derivatives thereof, grabrizine, grabrene, liquiritin, isoliquiritin, glutathione, hinokitiol and glycosides thereof, salts thereof, ellagic acid and derivatives thereof and salts thereof, placenta Extract, witch genus, zinc genus, camellia genus, genus genus, genus genus genus, genus genus genus, mugwort, genus yarrow, genus genus, genus genus, genus genus, genus genus, genus genus, button , Licorice, mulberry genus, enju genus, rose genus, aloe genus, elderberry genus, saxifraga genus, dokudami genus, canaoi genus, seaweed genus, sunflower genus, genus coral genus, flax genus, canton genus, genus genus Extracts of one or more plants belonging to the genus and genus Caenus, coral spruce, cirrus, amygusa, hijiki, sozo, fushitsunagi, iwahige, dalus, hondawala, moss One or two or more selected from the group consisting of extracts of one or more algae belonging to the genus, genus Ishimo, genus Futomo, and Okinawa, particularly preferred are water-soluble ascorbic acid derivatives.
[0010]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, embodiments of the present invention will be described in detail.
[0011]
N-acetylglutamine used in the present invention may be produced by any production method such as a fermentation method or a synthesis method. For example, as a production method by a fermentation method, there are methods described in JP-B-52-41211 and JP-B-57-1994.
[0012]
Such N-acetylglutamine may be used in the form of a salt of N-acetylglutamine, or a free form and a salt may be mixed and used. Examples of the salt of N-acetylglutamine include alkali metal salts such as sodium, potassium and lithium, alkaline earth metal salts such as calcium and magnesium, ammonium salts and amines such as monoethanolamine, triethanolamine and triisopropanolamine. These alkaline components are used alone or in the form of a mixture. These salts of N-acetylglutamine can be produced from N-acetylglutamine by a known method.
[0013]
N-acetylglutamine and / or a salt thereof is blended in an amount of 0.001 to 5% by weight, preferably 0.005 to 3% by weight, in the total amount of the external preparation for skin. When the amount is less than 0.001% by weight, the effect of promoting percutaneous absorption cannot be exhibited. Even when the amount exceeds 5% by weight, no further improvement is observed in the effect of promoting percutaneous absorption.
[0014]
In the present invention, N-acetylglutamine is used to promote transdermal absorption of a whitening agent. Such a whitening agent is not particularly limited as long as it is a whitening agent that can be blended in a skin external preparation, but a water-soluble whitening agent is preferable. Examples of whitening agents include L-ascorbic acid and its salts or derivatives thereof, hydroquinone and its derivatives, cysteine and its derivatives, glucosamine and its derivatives, azelaic acid and its derivatives, lipoic acid and its derivatives and their salts, resorcin and Derivatives thereof, glabrizine, glabrene, liquiritin, isoliquiritin, glutathione, hinokitiol and glycosides thereof, salts thereof, ellagic acid and derivatives thereof, salts thereof, placenta extract, witch genus, ginseng, camellia, genus Genus genus genus, genus euglena, mugwort, yarrow, genus genus, linden genus, genus genus genus, genus genus, gimpi, mitsumata, button genus, licorice, mulberry genus, rose genus, aloe genus Extract of one or more kinds of plants belonging to the genus Elder, Genus, Dromedary, Ganoderma, Gypsophila, Sunflower, Sunflower, Amadokoroma, Ama, Gancho, Valeriana, Hakka, Ganoderma, and One or two species belonging to the genus Spirium, Coralum, Spiraea, Amijigusa, Hijiki, Sozo, Fushitsunagi, Iwahigenus, Darus, Hondara, Mokaku, Nagamatsumo, Ishimokushi, Futomokushi, Okinawamoku Examples include extracts of algae over species.
[0015]
Examples of L-ascorbic acid and salts thereof or derivatives thereof used in the present invention include ascorbic acid monofatty acid esters such as L-ascorbic acid monostearate, L-ascorbic acid monopalmitate, L-ascorbic acid monooleate, L -Ascorbic acid monophosphate ester, L-ascorbic acid monoester derivative such as L-ascorbic acid-2-sulfate ester, L-ascorbic acid difatty acid ester such as L-ascorbic acid distearate, L-ascorbic acid dipalmitate, L-ascorbic acid dioleate L-ascorbic acid trifatty acid derivatives such as L-ascorbic acid tristearate, L-ascorbic acid tripalmitate, L-ascorbic acid trioleate, L-ascorbic acid triphosphate Ascorbic acid triester derivatives and the like. Of these L-ascorbic acid and salts thereof or derivatives thereof, particularly preferred are L-ascorbic acid, L-ascorbic acid phosphate and salts thereof.
[0016]
Although it does not specifically limit as hydroquinone and its derivative used by this invention, Hydroquinone glycoside is used preferably, for example, hydroquinone-alpha-D-glucose, hydroquinone-beta-D-glucose, hydroquinone-alpha-L-. Hexose sugar glycosides such as glucose, hydroquinone-β-L-glucose, hydroquinone-α-D-galactose, hydroquinone-β-D-galactose, hydroquinone-α-L-galactose, hydroquinone-β-L-galactose, Hydroquinone-α-D-ribose, hydroquinone-β-D-ribose, hydroquinone-α-L-ribose, hydroquinone-β-L-ribose, hydroquinone-α-D-arabinose, hydroquinone-β-D-arabinose, hydroquinone- α-L-Arabi Pentoses, hydroquinone-β-L-arabinose, etc., hydroquinone-α-D-glucosamine, hydroquinone-β-D-glucosamine, hydroquinone-α-L-glucosamine, hydroquinone-β-L-glucosamine , Hydroquinone-α-D-galactosamine, hydroquinone-β-D-galactosamine, hydroquinone-α-L-galactosamine, hydroquinone-β-L-galactosamine, etc. amino sugar glycosides, hydroquinone-α-D-glucuronic acid, hydroquinone -Β-D-glucuronic acid, hydroquinone-α-L-glucuronic acid, hydroquinone-β-L-glucuronic acid, hydroquinone-α-D-galacturonic acid, hydroquinone-β-D-galacturonic acid, hydroquinone-α-L- Galacturonic acid, hydroquinone Examples thereof include uronic acid glycosides such as -β-L-galacturonic acid. Examples of the derivatives include ester bodies such as acetylated substances and ether bodies such as methylated substances. Among these derivatives, hydroquinone-β-D-glucose is most preferable from the viewpoint of the effects of the present invention.
[0017]
Cysteine and derivatives thereof used in the present invention are not particularly limited, and examples thereof include cysteine, phospholipid esters of cysteine, esters of sphingosine and derivatives thereof, glycolipid esters, sugar esters, sterol esters, and alkyl having 8 to 20 carbon atoms. Or an alkenyl ester etc. are mentioned.
[0018]
The glucosamine and derivatives thereof used in the present invention are not particularly limited, and examples thereof include glucosamine esters such as glucosamine and acetylglucosamine, and glucosamine ethers such as glucosamine methyl ether.
[0019]
The azelaic acid and derivatives thereof used in the present invention are not particularly limited, and examples thereof include azelaic acid monoesters such as azelaic acid and azelaic acid monoalkyl ester, and azelaic acid diesters such as azelaic acid dialkyl ester.
[0020]
Lipoic acid and its derivatives and salts thereof used in the present invention are not particularly limited. For example, lipoic acid, sodium salt of lipoic acid, potassium salt, alkyl ester, alkenyl ester, amides, and reduced dihydrolipolipid. Examples include acids and dihydrolipoamide.
[0021]
Resorcin and its derivatives used in the present invention have been conventionally recognized as antibacterial agents, and have also been confirmed to have an inhibitory effect on melanin production and an effect of improving pigmentation (Japanese Patent Laid-Open No. 4-1116, JP-A-10-194951). Although it does not specifically limit in this invention, For example, it is preferable to use resorcinol or its glycoside.
[0022]
Gravulidine and grabrene used in the present invention are naturally a kind of licorice, Russian licorice (Glycyrrhiza glabra Lin.) Contains a trace amount. Grabludin has been confirmed to have pharmacological actions such as antibacterial action, antioxidant action, anti-cariogenic action, and anti-plasmin action, and is also known to have melanin production-inhibiting action (JP-A-1- 311011 publication etc.). In the present invention, it is preferable to use grabrizine or grabrene purified from licorice.
[0023]
The liquiritin and isoliquiritin used in the present invention are components contained in licorice. It is a contained compound. In the present invention, it is preferable to use liquiritin or isoliquiritin purified from licorice.
[0024]
Glutathione and derivatives thereof used in the present invention are those blended in ordinary cosmetics and quasi drugs, regardless of their bases.
[0025]
The hinokitiol and its derivative used in the present invention are not particularly limited, and examples thereof include hinokitiol, hinokitiol zinc complex, hinokitiol glycoside and the like. The glycoside of hinokitiol is a compound represented by the following general formula (1) or general formula (2), and one of these is used alone or a mixture of two or more.
[0026]
[Chemical 1]
[0027]
[Chemical 2]
[0028]
(In the formula, G is represented by the following general formula (3) or general formula (4))
[0029]
[Chemical Formula 3]
[0030]
[Formula 4]
[0031]
(Where R1~ RFourIs H or COCHThreeIndicate)
[0032]
The hinokitiol glycoside used in the present invention is glucose represented by the following general formula (5).
CHThreeCOX (5)
(Where X is F, Cl, Br, OCHThree, Which represents a group selected from imidazolyl groups) and the like, and then produced by a known method such as dehydration condensation (for example, JP-A-7-17993, JP-A-7-82288). Issue gazette). In addition, there are isomers having an α bond and a β bond in glycosides, any of which may be used, and a mixture thereof may be used, and usually a mixture is used.
[0033]
Ellagic acid used in the present invention is a kind of polyphenol, and is obtained by hydrolyzing ellagitannins contained in plants. In the present invention, ellagic acid, its derivatives and salts thereof are used.
[0034]
The placenta extract used in the present invention is not particularly limited as long as it is used for normal skin external preparations.
[0035]
In the present invention, witch genus, genus genus, camellia, genus genus, genus genus genus, genus genus genus, mugwort, genus yarrow, genus genus, genus genus, genus genus genus, genus genus, genus mitsumata, Button genus, daylily genus, mulberry genus, rose genus, aloe genus, elderberry genus, saxifrage genus, dokudami genus, kanaoi genus, seaweed genus, sunflower genus, amadokorogen genus, genus genus, kanto genus, moth genus, mint genus , Extracts of one or more plants belonging to the genus Hauchiwama, and the genus Caenopus, Coralus, Copella, Ajigusa, Hijiki, Sozo, Fusunagi, Iwagenu, Darus, Hondara, Mocha , Genus Nagamatsu, Imomo, Futomoku, Okinawa One or one or more extracts selected from extracts of two or more algae may be used as a whitening agent that.
[0036]
Witch Hazel (Hamamelis L.) is a deciduous wooden book belonging to the witch hazel family.Hamamelis japonica Sieb. Et Zucc.), Sinamansaku (Hamamelis mollis Oliv.), Hamelis (Hamamelis virginiana L.) etc. are exemplified. Among these plants, it is preferable from the viewpoint of whitening effect to use bark of Hamelis, particularly Hamelis.
[0037]
Gentian (Aquilaria Lam.) Is an evergreen tree that belongs to the genus family, and more than a dozen species are known. In the present invention, zinc white (Aquilaria agallocha Roxb.) Is preferred.
[0038]
Camellia (Camellia L.) is an evergreen herb belonging to the camellia family and about 200 species are known. In the present invention, camellia (Camellia japonica L.) and its variants, Cha (Camellia sinensis (L.) O. Kuntze) and its variants are preferably used.
[0039]
Tade genus (Polygonum L.) The plant is a herb belonging to the family Taceae, and about 300 species are known. In the present invention, the whitening effect (Itadori (Polygonum cuspidatum Sieb. Et Zucc.), Honeybird (Polygonum cuspidatum Sieb. Et Zucc. Var.hachidyoense Ohwi)Polygonum sachalinense It is preferable to use one or more plants selected from Fr. Schm.).
[0040]
Genus genus (Melissa L.) Plants are Labiatae (Labiatae) Perennials, among them Melissa (Melissa officinalis L.) extract is often used because of its whitening effect.
[0041]
Genus genusThymus L.) The plant is a shrub belonging to the family Lamiaceae.Thymus serphyllum L. subsp.quinquecostatus (Aelak.) Kitamura), Time (Thymus vulgaris It is preferable to use one or more selected from L.).
[0042]
Artemisia (Artemisia L.) The plant is a dicotyledonous plant belonging to the family Asteraceae.Artemisia absinthium L.), ginseng (Artemisia annua L.), Chinese carrot (Artemisia apiacea Hance)Artemisia capillaris Thunb.)Artemisia cina Berg.), Tarragon (Artemisia dracunculus L.), Mugwort (Artemisia japonica Thunb.), Mibu mugwort (Artemisia maritima L.), Artemisia (Artemisia princeps It is preferable from the viewpoint of the whitening effect to use one or more selected from Pamp.).
[0043]
Yarrow (genus Yarrow)Achillea L.) The plant is a dicotyledonous plant belonging to the family Asteraceae.Achillea alpina L.), Achillea millefolium (Achillea milleifolium L.), musk millet (Achillea moschata Jacq.) Achillea spp.Achillea alpina L.), Achillea millefolium (Achillea milleifolium L.), musk millet (Achillea moschata From the viewpoint of the whitening effect, it is preferable to use one or more selected from Jacq.).
[0044]
Chrysanthemum (genusEupatorium L.) The plant is a dicotyledonous plant belonging to the family Asteraceae.Eupatorium japonicum Thunb.)Eupatorium lindleyanum DC.), Hydrangea (Eupatorium chinense L. var.oppositifolium From the viewpoint of the whitening effect, it is preferable to use one or more selected from (Koidz.) Murata et H. Koyama).
[0045]
The genus Tilia L. is a plant belonging to the family Tiliaceae.Tilia americana L.), Fuyubodaiju (Tilia cordata Mill.), Linden tree (Tilia europaea L.), linden (Tilia japonica Simonk.)Tilia kiusiana Makino et Shiras.)Tilia maximowicziana Shiras.)Tilia platyphyllos Scop.), Bodaige (Tilia miqueliana From the viewpoint of the whitening effect, it is preferable to use one or more selected from Maxim.
[0046]
Iwayukinoshita (Tanakaea Fr. et Sav.) Is an evergreen perennial plant belonging to the family of the family Saxifragaceae.Tanakaea radicans Fr. et Sav.) Is preferably used.
[0047]
Genus genus (Daphne L.) The plant is a shrub belonging to the genus family, Satsuma Fuji (Daphne genkwa Sieb. Et Zucc.), Pepper (Daphne kiusiana Miq.)Daphne mezereum L.)Daphne odora Thunb.), Onishi Bali (Daphne opseud-mezereum A. Gray), Naniwazu (Daphne kamtchatica Maxim.var.yezoensis Ohwi), Crow Shikimi (Daphne miyabeana From the viewpoint of the whitening effect, it is preferable to use one or more selected from Makino).
[0048]
Gamppi (Diplomorpha Meissn. Ex C. A. Mey.) The plant is a shrub belonging to the family Zinaceae.Diplomorpha phymatoglossa (Koidz.) Nakai), Ganpi (Diplomorpha sikokiana (Fr. et Sav.) Honda), Kiganpi (Diplomorpha trichotoma Use of one or more selected from (Thunb.) Nakai) is preferable in terms of whitening effect.
[0049]
Mitsumata (Edgeworthia Meissn.) The plant is a shrub belonging to the family Genraceae, and from the point of availability,Edgeworthia chrysantha Lindl.) Is preferably used.
[0050]
The button genus (Paeonia L.) plant used in the present invention is a shrub belonging to the family Ranunculaceae, and from the point of whitening effect, buttons (Paeonia suffruticosa Andr.) And peonies (Paeonia Preferred examples include one or two selected from lactiflora Pall.).
[0051]
Daylily (Glycyrrhiza L.) The plant is a herb belonging to the leguminous family.Glycyrrhiza glabra L.), licorice (G lycyrrhiza kansuensis Chang et peng), daylily (Glycyrrhiza urarensis It is preferable to use one or more selected from Fisch.).
[0052]
Mulberry (Morus L.) The plant is a shrub belonging to the mulberry family, and mulberry (Morus alba L.) is preferably used.
[0053]
Enju (Sophora L.) The plant is a tree belonging to the leguminous family, and Clara (Sophora flavescens Ait.), Enju (Sophora japonica It is preferable to use one or two selected from L.).
[0054]
Rosa L. plants are from the family Rosaceae (Rosaceae) Belonging to the plant. Among them, Neubara (Rosa multiflora Thunb.) Is a rose family that grows naturally in Japan (Rosaceae) Vine deciduous shrub, herbal medicine "AGES" (Rosae Fructus) Is a basic plant and exhibits a high whitening effect. In addition, this related plant, Teri Hanoi rose (Rosa wichuraiana Crepin var.ampullicarpa Honda), Fujiibara (Rosa fujisanensis Makino) also provides a high whitening effect.
[0055]
Aloe L. plants are lily family (Liliaceae) A woody succulent plant belonging toAloe) Used as a base plant. As plants belonging to the genus Aloe, Aloe Ferrox, the original plant of the herbal medicine "Aloe" (Aloe ferox Mill.), Aloe Africana (Aloe africana Mill.), Aloe Spicata (Aloe spicata Baker), Aloe Alborescens (Aloe arborescens Mill.) Aloescotrina (Aloe succotrina Lam.) Aloe Pricatiris (Aloe plicatilis Mill.), Aloe Vennessy (Aloe bainesii Th. Dyer.), Aloe Perry (Aloe perryi Baker), aloe vera (Aloe vera L.) etc., Kidachi Aloe (Aloe arborescens Mill.var.natalensis Berg.) Can also be used. It is preferable to use one or more selected from these.
[0056]
Elderflower (Sambucus L.) plants are honeysuckle (Caprifoliaceae), And because of its availability, elderberry (Sambucus nigra L.), American elderberry (Sambucus canadensis L.), Sokuzu (Sambucus javanica Reinw.ex Bl.subsp.chinensisIt is preferable to use 1 type, or 2 or more types selected from.
[0057]
The genus Yukinoshita (Saxifraga L.) The plant is a perennial plant belonging to the family Chironomidae,Saxifraga aizoon Jacq.)Saxifraga cherlerioides D. Don var.rebunshirensis (Engl. Et Irmsch) Hara)Saxifraga cortusaefolia Sieb. Et Zucc.)Saxifraga fortunei Hook.f.var.incisolobata (Engl. Et Irmsch.) Nakai), Harukinoshita (Saxifraga nipponica Makino)Saxifraga sendaica Maxim.), Yukinoshita (Saxifraga stolonifera Meerb.), Fukuyukishinoshita (Saxifraga japonica Boiss.), Black spider (Saxifraga fusca Maxim.), Spider Mosa (Saxifraga merkii Fish.var.laciniata Nakai), Kumoma Yukinoshita (Saxifraga laciniata Nakai et Takeda)Saxifraga bronchialalis L.), Mukago Yukinoshita (Saxifraga cernua L.)Saxifraga sachalinensis Fr. Schm.) Is preferably used from the viewpoint of the whitening effect.
[0058]
The plant of the genus Houttuynia Thunb. Belongs to the family Saururaceae and consists of only one genus, Houttuynia cordata Thunb. The entire herb of Houttuynia cordata Thunb. Is a herbal medicine called “Houttuyniae Herba” or a heavy medicine “Zyuyaku”, and it is preferable to use such herbal medicine from the viewpoint of whitening action.
[0059]
Heterotropa Morr. Et Decne is a plant belonging to the family Aristolochiaceae, and recent research has shown that it belongs to the genus Asarum L., Hexastylis L., and Asasarum L. .) Etc. are treated. Among them, the genus Usasasairum (Asiasarum L.) is the base plant of the herbal medicine “Asiasari Radix”. From the viewpoint of whitening effectiveness,Asiasarum sieboldii F. Maekawa) or Keirin Saishin (Asiasarum heterotropoides var.mandshuricum F. Maekawa), its related plants, kurofunesaicin (Asiasarum dimidiatum F. Maekawa), okuezosaicin (Asiasarum heterotropoides F. Maekawa), Usgesaicin (Asiasarum heterotropoides var.seoulense F. Maekawa) and Shinan Minami (Asarum himalaicum Hook. F. Et Thoms. Ex Klotzch) are preferably used.
[0060]
The plant of the genus Scutellaria L.Labiatae) Herb or semi-shrub. As the plant belonging to the genus Capillaris,Scutellaria baicalensis Georgi)Scutellaria brachyspica Nakai et Hara)Scutellaria indica L.), Natsumi Shisobata (Scutellaria laeteviolacea Koidz.), Scutellaria Laterifolia (Scutellaria laterifolia L.), Hanagatatsunami (Scutellaria maekawae Hara), Yamagata Natsou (Scutellaria pekinensis Maxim.var.transitra (Makino) Hara), Namikisou (Scutellaria strigillosa Hemsl.) Etc. Among them, herbal medicine Ogon (Scutellariae Radix), The root plant,Scutellaria baicalensis Georgi) is preferred.
[0061]
Sunflower (Helianthus L.) plants are Asteraceae (Compositae) Is a kind of dicotyledonous plant, among which sunflower (Helianthus annuus L.) extract is often used. In the present invention, sunflower (Helianthus annuus L.) can use flowers, seeds, stems, leaves, and roots, but preferably uses flowers or seeds. Moreover, you may use the sunflower oil cake which is the residue which squeezed the sunflower oil from the seed.
[0062]
The plant of the genus Polygonatum Adans.Liliaceae) Narukoyuri (Polygonati Rhizoma), the original plant of the herbal medicinePolygonatum falcatum A. Gray)Polygonatum macranthum Koidzumi)Polygonatum sib ricum Red.), Carba Narukoyuri (Polygonatum stenophyllum Maxim.), Etc., and it is preferable to use one or more selected from these in view of the whitening effect.
[0063]
The plant of the genus Linum L.Linaceae) Annual, biennial, or perennial herbs that use fiber, seeds, or seed oil. In the present invention, from the point of the whitening effect,Linum usitatissimum It is preferred to use an extract from the herbal medicine "Amanin" (Lini Semen), which is the seed of L.).
[0064]
Tussilago L. plants are Asteraceae (Compositae) Belonging to the plant. Because of its easy availability,Tussilago farfara L.) is preferably used.
[0065]
The plant of the genus Sanguisorba L.Rosaceae) Is a plant belonging to)Sanguisorba officinalis L.), Dutch remocow (Sanguisorba minor Scop.) Etc. Among them, herbal medicine "Chiyu" (Sanguisorba Radix)Sanguisorba officinalis L.) is preferred from the viewpoint of whitening effect and availability.
[0066]
Mentha L. is a plant belonging to the family Lamiaceae and is a green mint called spearmint (Mentha spicata Linne)Mentha piperita L.) and its variants, or mint (Mentha arvensis L. var.piperascens Malin.).
[0067]
Giant bean genus (Lupinus L.) Plants are legumes (Leguminosae) Dicotyledonous plant, white lopin (Lupinus albus L.;Lupinus sativus Gaertn.), Aobanarupin (Lupinus angustifolius L.;Lupinus varius L.;Lupinus linifolius Roth;Lupinus reticulatus Desv.), Casa Balupin (Lupinus hirsutus L.)Lupinus luteus L.), Shukon Lupine (Lupinus polyphyllus Lindl.), Egyptian Lupine (Lupinus termis Forsk.Lupinus graecus Boiss.) Etc. Among these plants, white-spotted lupine (Lupinus albus L.;Lupinus sativus Gaertn.) Is preferably used. In addition,Lupinus L.) Whole plants, leaves, stems, roots, perennials, flowers and seeds can be used, but seeds are preferred.
[0068]
As the algae used in the present invention,Ceratodictyon spongiosum)Ceratodictyon) Algae, Innocent Coral (Corallina sp.), coral (Corallina officinalis), Pirihiba (Corallina pilurifera) Coral spider genus (Corallina) Algae, Yakuzusa (Dictyopteris latiuscula), Siwayahaz (Dictyopteris undulata), Herayahaz (Dictyopteris prolifera), Sujiyahaz (Dictyopteris plagiogramma), Himeyahaz (Dictyopteris repens), Ezoyahaz (Dictyopteris divaricata), Uraboshahaz (Dictyopteris polypodioides), Etc.Dictyopteris) Algae, Harajidae (Dictyota spinulosaAmidigusa represented by ()DictyotaAlgae, hijiki (Hizikia fusiformis)Hizikia) Algae, Sozo sp.Laurencia sp.), Kurosozo (Laurencia intermedia), Mitsudezozo (Laurencia okamurai), Sozonohana (Laurencia grevilleana), Osozo (Laurencia glandulifera), Hanesoso (Laurencia pinnata), Kobusoso (Laurencia undulata), etc.Laurencia) Algae, Fushitsunagi (Lomentaria catenata), Kosuji Fushitsugi (Lomentaria hakodatensis)Lomentaria) Algae, sardine (Myelophycus caespitosus)Myelophycus) Algae, genus Darus represented by Dulse (Palmaria palmata)Rhodymenia) Algae, Honda Walla (Sargassum fulvellum), Pea (Sargassum yendoi), Mametawala (Sargassum piluriferum), Yatsuma Tamoku (Sargassum patens), Akamoku (Sargassum horneri), Sawtooth Moku (Sargassum serratifolium), Sawworm (Sargassum giganteifolium), Yoremoku (Sargassum tortile), Willow Moku (Obermoku:Sargassum ringgoldianum), Nejimok (Sargassum sagamianum), Haha Moku (Sargassum kjellmanianum), Umitorano (Sargassum thunbergii)Sargassum confusum), Isomoc (Sargassum hemiphyllum), Narasamo (Sargassum nigrifolium), Togemoku (Sargassum micracanthum), Tamanashimoku (Sargassum nipponicum), Ginseng (Sargassum vulgare), Futaemoku (Holly Moku:Sargassum duplicatum), Esononezmok (Sargassum yezoense), Etc.SargassumAlgae, mok (Nemacystus decipieus) Genus represented by ()Nemacystus) Algae, Nagamatsumo (Chordaria flagelliformis), Ishimo Kudamashi (Chordaria firma)Chordaria) Algae, Isimo (Sphaerotrichia divaricata)Sphaerotrichia) Algae, ftmok (Tinocladia crassa (Suringar) The genus Futomoku (represented by Kylin)Tinocladia Kylin) Algae, OkinawaCladosiphon okamuranus)Cladosiphon) Algae and the like are exemplified.
[0069]
Extracts from these plants and algae are used raw or dried at one or more sites such as various whole plants or their leaves, bark, roots, flowers, branches and the like. The extraction solvent is not particularly limited, and monohydric alcohols such as water, ethanol, methanol, isopropanol, isobutanol, n-hexanol, methylamyl alcohol, 2-ethylbutanol, n-octyl alcohol, glycerin, ethylene glycol, ethylene Glycol monomethyl ether, propylene glycol, propylene glycol monomethyl ether, propylene glycol monoethyl ether, triethylene glycol, 1,3-butylene glycol, hexylene glycol and other polyhydric alcohols or derivatives thereof, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl -Ketones such as n-propyl ketone, esters such as ethyl acetate and isopropyl acetate, ethers such as ethyl ether, isopropyl ether and n-butyl ether , Hydrocarbons such as squalane, petrolatum, paraffin wax, paraffin oil, olive oil, wheat germ oil, rice oil, sesame oil, macadamian nut oil, almond oil, coconut oil and other vegetable oils, beef fat, pork fat, whale oil, etc. Animal fats and oils are exemplified. Moreover, the polar solvent which added inorganic salts, such as phosphate buffered saline, and the solvent which added surfactant can also be used, It does not specifically limit.
[0070]
Furthermore, as extraction methods, there are a method of impregnating and extracting at room temperature, in a cooled or heated state, a method of extracting using a distillation method such as steam distillation, a pressing method of pressing plants or algae to obtain an extract, and the like. Exemplified, these methods are extracted alone or in combination of two or more.
[0071]
The ratio of the plant or algae and the solvent during the extraction is not particularly limited, but the solvent is 0.1 to 1000 times by weight with respect to the plant or algae 1, especially 0.5 to 100 times by weight in terms of extraction operation and efficiency. Is preferred. The extraction pressure and extraction temperature are conveniently in the range of 0 ° C. to the boiling point of the solvent under normal pressure, and the extraction time is preferably in the range of 2 hours to 2 weeks, although it varies depending on the extraction temperature.
[0072]
The plant or algae extract thus obtained can be used as it is. However, purification operations such as deodorization, decolorization, and concentration are added to the extent that the effects are not lost. It may be used as a fraction using a graphic or the like. These extracts, purified products, and fractions can be dried by removing the solvent from them, and can also be used in a form solubilized in a solvent such as alcohol, or in the form of an emulsion. it can.
[0073]
The amount of these whitening agents to be added to the external preparation for skin is preferably in a concentration range of 0.0001 to 10% by weight in view of the effect, odor and color tone when added.
[0074]
Among these whitening agents, a water-soluble ascorbic acid derivative is particularly preferable from the viewpoint of the effect of promoting transdermal absorption.
[0075]
In addition, in the skin external preparation according to the present invention, in addition to the above-described components, oily ingredients, powders, pigments, emulsifiers, solubilizers, drugs, and the like, which are usually blended in pharmaceuticals, quasi drugs, and cosmetics A fragrance, a resin, alcohol, or the like can be appropriately blended within a range that does not impair the effects and features of the present invention.
[0076]
【Example】
Hereinafter, the present invention will be specifically described with reference to examples. In addition, unless otherwise indicated, the quantity in an Example was shown by weight%. Prior to the description of the examples, the effect test method used in the present invention will be described.
[0077]
(1) Drug skin permeability test
A hairless mouse skin permeation test was conducted to evaluate the effect of promoting transdermal absorption on a whitening agent. In the test, the peeled skin of a hairless mouse was measured at 0.785 cm.2The sample was applied to a diffusion cell having a diffusion effective area of 1 cm so that the stratum corneum side was the donor phase and the dermis side was the receptor phase. In the receptor phase, 5 ml of a phosphate buffer solution of PH 7.4 was added as a receptor solution. The receptor solution was sampled after 24 hours, and the amount of whitening agent permeated was determined by high performance liquid chromatography. The results were expressed as drug permeability (%).
[0078]
[Examples 1 to 3, Comparative Example 1]
An external preparation for skin having the formulation shown in Table 1 was prepared by dissolving (1) and (2) in (3).
[0079]
[Table 1]
[0080]
The drug skin permeability test results of Examples 1 to 3 and Comparative Example 1 are as shown in Table 1. Compared with Comparative Example 1 in which N-acetylglutamine was not blended, whitening agent (ascorbic acid glucoside) It is clear that the topical skin preparations of Examples in which N-acetylglutamine is combined with N-acetylglutamine have high drug permeability, and N-acetylglutamine significantly promotes the transdermal absorption of the whitening agent.
[0081]
Then, the preparation example of the plant and algae extract mix | blended as a whitening agent is shown.
[0082]
[Itadori extract]
Itadori (Polygonum cuspidatum Sieb. Et Zucc.) 550 g of rhizome was dried, pulverized, and extracted by stirring in 1,500 mL of 50 vol% ethanol aqueous solution at 25 ° C. for 5 days. Subsequently, the extract was filtered, and the filtrate was used as the itadori extract.
[0083]
[Itadori extract fraction]
Itadori (Polygonum cuspidatum 200 g of dried rhizome powder of Sieb. Et Zucc.) Was immersed in 2,000 mL of 50 vol% ethanol aqueous solution and extracted at room temperature for 7 days. Next, the extract was filtered, the filtrate was concentrated under reduced pressure, dissolved in 800 mL of a 30% by volume ethanol aqueous solution, applied to a DIAION MCI Gel HP-20 column (manufactured by Mitsubishi Kasei Co., Ltd.), and eluted with a 40% by volume ethanol aqueous solution. The fractions to be collected were collected. Subsequently, the fraction was fractionated by silica gel thin layer chromatography using a chloroform / methanol mixture (volume ratio = 5: 1) as a developing solvent. Among the obtained fractions, a fraction containing (−)-epicatechin was scraped, and a filtrate dissolved in 50 mL of 50% by volume ethanol was used as an itadori extract fraction.
[0084]
[Hamamelis extract]
Hamelis (Hamamelis virginiana L.) Leaves (500 g) were dried, pulverized and extracted with stirring in 1,000 mL of 50% by volume ethanol aqueous solution at 25 ° C. for 5 days. Subsequently, the extract was filtered, and the filtrate was collected to obtain a Hamelis extract.
[0085]
[Hamamelis extract fraction]
Hamelis (Hamamelis virginiana L.) A total of 500 g of leaves and bark were chopped and extracted in 1,500 mL of hot water with stirring for 5 hours. Next, the extract is filtered, and the filtrate is applied to a DIAION MCI Gel HP-20 column (manufactured by Mitsubishi Kasei Co., Ltd.) and eluted with a mixed solvent of ethanol and water, and a fraction having a Hamelian tannin content of 50% by weight or more is recovered. Was used as a Hamelis extract fraction.
[0086]
[Melissa extract]
Melissa (Melissa officinalis L.) 350 g of the whole flowering plant was chopped and extracted by dipping in 1,000 ml of olive oil at 20 ° C. for 7 days. The extract was filtered and the filtrate was collected to obtain a Hypericum perforatum extract.
[0087]
[Licorice extract]
Daylily (Glycyrrhiza urarensis Fisch.) Roots and rhizomes (500 g) were dried, ground, and extracted in 1,000 mL of an absolute ethanol aqueous solution at 25 ° C. for 24 hours. The extract is filtered to collect the filtrate, concentrated under reduced pressure, and then dried by lyophilization. The dried product was extracted by stirring in 1,000 mL of ethyl acetate at 20 ° C. for 2 days. After extraction, the extract was dried under reduced pressure to obtain a licorice extract.
[0088]
[Ginkgo extract]
Zincou (Aquillaria agallocha Roxb.) Branches and trunks, 300 g in total, were dried, ground and immersed in ethanol 1,000 at 20 ° C. for 10 days. Next, the extract was filtered, and the filtrate was concentrated to 1/10 volume to obtain a ginkgo extract.
[0089]
[Oolong tea extract]
Oolong Tea(Thea sinensis L. var.viridis Szkzyl.) Leaves (440 g) were dried, ground, and extracted in 1,000 mL of purified water with stirring at 50 ° C. for 24 hours. The extract was filtered, and the filtrate was concentrated to 1/5 volume to obtain a oolong tea extract.
[0090]
[Kawara mugwort extract]
Chinese mugwort (Artemisia capillaris Thunb.) Leaves were pulverized and extracted with stirring in 1,000 mL of 1,3-butylene glycol at 25 ° C. for 5 days. The extract was filtered, and the filtrate was collected to obtain a Kawamomogi extract.
[0091]
[Time extract]
time(Thymus vulgaris 450 g of the whole plant of L.) was dried, pulverized, and extracted by stirring in 1,500 mL of 50% by volume glycerin aqueous solution at 25 ° C. for 5 days. The extract was filtered and the filtrate was collected to obtain a thyme extract.
[0092]
[Button extract]
button(Paeonia suffruticosa Andr.) Root bark (300 g) was dried, pulverized, and extracted by stirring in 1,000 mL of 95% by volume ethanol aqueous solution at 25 ° C. for 5 days. The extract was filtered, and the filtrate was collected to obtain a button extract.
[0093]
[Mulberry extract]
Mulberry (Morus alba L.) root bark (350 g) was minced and extracted by immersion in 1,000 mL of 1,3-butylene glycol at 20 ° C. for 7 days. The extract was filtered and the filtrate was collected to obtain a mulberry extract.
[0094]
[Achillea millefolium extract]
Achillea millefolium (Achillea milleifolium L.) 320 g of flowers were homogenized in 2,000 mL of physiological saline at 10 ° C., and further extracted with stirring for 4 hours. The extract was filtered, and the filtrate was collected to obtain a yarrow extract.
[0095]
[Yuzu extract]
Yuzu (Citrus junos 450 g of dried fruits of Sieb. Et Tanaka) were pulverized and extracted with stirring in 1,500 mL of 50 vol% ethanol aqueous solution at 25 ° C. for 5 days. The extract was filtered, and the filtrate was collected to obtain a yuzu extract.
[0096]
[Herayahaz extract], [Red algae extract]
All the algae of Herayahaz and red algae collected from the sea were washed with water and then chopped, dispersed in an equal amount of phosphate buffered saline (pH 7.4), and then extracted by stirring with a blender mill for 3 hours. The extract was filtered, and the filtrate was collected to obtain the above extracts.
[0097]
[Peonies extract]
Peonies (Paeonia 450 g of dry roots of lactiflora Pall.) were pulverized and extracted with stirring in 1,500 mL of 50% by volume ethanol aqueous solution at 25 ° C. for 5 days. The extract was filtered, and the filtrate was collected to obtain a peony extract.
[0098]
It continues and the prescription of the other Example which concerns on this invention is shown.
[0099]
[Examples 4 to 12] Cosmetic liquid
(1) 1,3-butylene glycol 30.0
(2) N-acetylglutamine 1.0
(3) Purified water Amount that makes the total amount 100
(4) Whitening agent shown in Table 2
Production method: Components (1) to (4) are mixed and homogenized.
[0100]
[Table 2]
[0101]
With respect to Examples 4 to 12 of the present invention prepared according to the above formulation and Comparative Example 1 prepared by substituting N-acetylglutamine with purified water in Example 1, the effect of improving pigmentation symptoms was evaluated. It was. The effect of improving pigmentation symptoms is a group of 20 female panelists with pigmentation symptoms such as remarkable spots and buckwheat, and each group is used twice a day for one month for each example or comparative example for one month. In addition, the state of skin pigmentation after one month was observed and evaluated in comparison with before use. The pigmentation state was evaluated according to the criteria shown in Table 3, and the average value of 20 people was calculated and shown in Table 4.
[0102]
[Table 3]
[0103]
[Table 4]
[0104]
As is apparent from Table 4, in the group using the examples according to the present invention, marked improvement in pigmentation symptoms was observed in all groups, and mild or slight pigmentation was observed after the end of the use test. Symptoms were improved to the extent that it was not too much. In particular, in Example 4 in which N-acetylglutamine and L-ascorbic acid phosphate magnesium salt were used in combination, Example 11 in which itadori extract fraction was used in combination, and Example 12 in which Hamameris extract fraction was used in combination Good improvement was seen. On the other hand, although the improvement of the pigmentation symptom was observed in the comparative example use group in which the whitening agent was blended alone, the degree of improvement was clearly small compared to the corresponding example use group.
[0105]
In Examples 4 to 12 of the present invention, no change in the state of the preparation such as precipitation, separation, aggregation, odor change, and discoloration of the components was observed during the use test period. Moreover, in each Example use group, the paneler which showed skin irritation reaction and skin sensitization reaction did not exist.
[0106]
The other Example of this invention is shown.
[0107]
[Example 13] Cream for whitening
(1) 1,3-butylene glycol 10.00
(2) Methyl paraoxybenzoate 0.10
(3) Sucrose stearate 0.35
(4) Sodium N-stearoyl-L-glutamate 0.35
(5) Carboxyvinyl polymer (1 wt% aqueous solution) 2.00
(6) 2-Methacryloyloxyethyl phosphorylcholine
Butyl methacrylate copolymer liquid polyglyceryl monolaurate 0.50
(7) Purified water 65.70
(8) Squalane 3.00
(9) Octyldodecyl myristate 3.00
(10) Lipophilic glyceryl monostearate 3.00
(11) Beeslow 1.00
(12) Stearic acid 1.00
(13) Behenyl alcohol 2.50
(14) Hardened palm oil 2.00
(15) Jojoba oil 0.10
(16) Stearyl glycyrrhetinate 0.05
(17) Dimethylsiloxane / vinyldimethylsiloxane copolymer solution 1.00
(18) Button extract 0.05
(19) Melissa extract 0.05
(20) Peonies extract 0.05
(21) Sodium hydroxide (10% by weight aqueous solution) 1.00
(22) Polyglutamic acid 0.05
(23) Yuzu extract 0.20
(24) N-acetylglutamine 0.50
(25) Ascorbic acid phosphate sodium salt 1.00
(26) Sodium citrate 0.20
(27) Diethylenetriaminepentaacetic acid pentasodium (40% by weight aqueous solution) 0.20
(28) Purified water 1.00
(29) Fragrance 0.05
Production method: The oily components (1) to (7) and the aqueous components (8) to (17) are mixed and homogenized, and heated to 75 ° C. After the oil component is added to the aqueous component and emulsified, the components (18) to (29) are sequentially added.
[0108]
[Example 14] Cosmetic liquid
(1) Di-2-heptylundecyl adipate 2.00
(2) Glyceryl tri-2-ethylhexanoate 4.00
(3) Dimethylpolysiloxane 2.00
(4) Behenyl alcohol 1.00
(5) Self-emulsifying glyceryl monostearate 1.30
(6) Hydrogenated soybean phospholipid 0.20
(7) Polyethylene glycol monostearate 0.20
(8) Beeslow 0.10
(9) Stearic acid 0.10
(10) Jojoba oil 0.10
(11) Squalane 0.10
(12) Stearyl glycyrrhetinate 0.05
(13) 1,3-Butylene glycol 6.00
(14) Purified water 57.34
(15) Hydroxyethyl cellulose (1% by weight aqueous solution) 6.00
(16) Xanthan gum (1 wt% aqueous solution) 3.00
(17) Ascorbic acid phosphate magnesium salt 2.00
(18) Diethylenetriaminepentaacetic acid pentasodium (40% by weight aqueous solution) 0.20
(19) Sodium hydroxide (10% by weight aqueous solution) 2.00
(20) Sodium citrate (10% by weight aqueous solution) 5.00
(21) Button extract 0.02
(22) Melissa extract 0.02
(23) Peonies extract 0.02
(24) Yuzu extract 0.02
(25) N-acetylglutamine 0.10
(26) Ethanol 7.00
(27) Perfume 0.08
(28) Methyl paraoxybenzoate 0.05
Production method: Oil components (1) to (12) and aqueous components (13) to (16) are mixed and homogenized, and heated to 75 ° C. After the oily component is added to the aqueous component and emulsified, the components (17) to (28) are sequentially added.
[0109]
[Example 15] Skin lotion
(1) Purified water 86.19
(2) Dipotassium glycyrrhizinate 0.05
(3) Polyethylene glycol (4000) 1.00
(4) Trimethylglycine 1.00
(5) Red algae extract 1.60
(6) Ascorbic acid phosphate sodium salt 2.00
(7) Sodium hydroxide (10 wt% aqueous solution) 2.20
(8) Sodium citrate 0.30
(9) Diethylenetriaminepentaacetic acid pentasodium (40% by weight aqueous solution) 0.20
(10) N-acetylglutamine 0.30
(11) Button extract 0.02
(12) Peony extract 0.02
(13) Melissa extract 0.02
(14) Yuzu extract 0.02
(15) Ethanol 5.00
(16) Polyoxyethylene (60EO) hydrogenated castor oil 0.02
(17) Fragrance 0.01
(18) Methyl paraoxybenzoate 0.05
Production method: (1) to (18) are mixed and made uniform.
[0110]
Example 16 Skin Emulsion
(1) Stearic acid 0.2
(2) Cetanol 1.5
(3) Vaseline 3.0
(4) Liquid paraffin 7.0
(5) Polyoxyethylene (10E.O.) monooleate 1.5
(6) Glycerin 5.0
(7) Triethanolamine 1.0
(8) N-acetylglutamine 0.5
(9) Purified water 79.5
(10) Lactic acid bacteria extract 0.5
(11) Placenta extract 0.3
Production method: The oil phase components (1) to (5) are mixed, heated and uniformly dissolved, and kept at 70 ° C. On the other hand, the aqueous phase components (6) to (9) are mixed and heated to be uniform, and set to 70 ° C. The oil phase component is gradually added to the water phase component with stirring and emulsified, and then cooled, and the components (10) and (11) are added at 40 ° C.
[0111]
[Example 17] Gel for skin
(1) Purified water 90.5
(2) Carboxyvinyl polymer 0.5
(3) N-acetylglutamine 0.7
(4) Dipropylene glycol 8.0
(5) Potassium hydroxide 0.1
(6) Melissa extract 0.2
Production method: (2) and (3) are uniformly dissolved in (1), then (4) is added, then (5) is added to increase the viscosity, and (6) is added and mixed uniformly.
[0112]
[Example 18] Skin cream
(1) Beeslow 6.0
(2) Cetanol 5.0
(3) Reduced lanolin 8.0
(4) Squalane 29.5
(5) Lipophilic glycerin monostearate 4.0
(6) Polyoxyethylene (20E.O.)
Sorbitan monolaurate 5.0
(7) Propylene glycol 5.0
(8) N-acetylglutamine 1.0
(9) Oolong tea extract 0.2
(10) Purified water 36.3
Production method: The oil phase components (1) to (6) are mixed, dissolved, and heated to 75 ° C. On the other hand, the aqueous phase components (7) to (10) are mixed and dissolved and heated to 75 ° C. Subsequently, after adding an oil phase component to the said water phase component and pre-emulsifying, it emulsifies uniformly with a homomixer.
[0113]
Example 19 Oil-in-water emulsion ointment
(1) White petrolatum 25.0
(2) Stearyl alcohol 25.0
(3) Glycerin 10.0
(4) Sodium lauryl sulfate 1.0
(5) N-acetylglutamine 0.3
(6) Kawara mugwort extract 0.2
(7) Purified water 38.5
Production method: The oil phase components (1) to (4) are mixed, dissolved and made uniform, and heated to 75 ° C. On the other hand, (5) and (6) are dissolved in (7) and heated and dissolved at 75 ° C., and the oil phase component is added to this and emulsified.
[0114]
[Example 20] Makeup base cream
(1) Stearic acid 12.0
(2) Cetanol 2.0
(3) Glycerin tri-2-ethylhexanoate 2.5
(4) Self-emulsifying glycerin monostearate 2.0
(5) Propylene glycol 10.0
(6) Potassium hydroxide 0.3
(7) N-acetylglutamine 1.5
(8) Purified water 68.0
(9) Titanium oxide 1.0
(10) Bengala 0.1
(11) Yellow iron oxide 0.4
(12) Fragrance 0.1
(13) Button extract 0.1
Production method: The oil phase components (1) to (4) are mixed and heated to 75 ° C. to be uniform. On the other hand, the components (5) to (8) are mixed, heated and dissolved at 75 ° C. to make it uniform, and the pigments (9) to (11) are added to this and dispersed uniformly with a homomixer. The phase component. The oil phase component is added to the aqueous phase component, emulsified with a homomixer, cooled, and the components (12) and (13) are added and mixed at 40 ° C.
[0115]
[Example 21] Emulsion foundation
(1) Stearic acid 2.0
(2) Squalane 5.0
(3) Octyldodecyl myristate 5.0
(4) Cetanol 1.0
(5) Decaglycerin monoisopalmitate 9.0
(6) 1,3-butylene glycol 8.0
(7) Potassium hydroxide 0.1
(8) N-acetylglutamine 0.5
(9) Purified water 51.0
(10) Titanium oxide 9.0
(11) Talc 7.4
(12) Bengala 0.5
(13) Yellow iron oxide 1.1
(14) Black iron oxide 0.1
(15) Fragrance 0.1
(16) Mulberry extract 0.2
Production method: The oil phase components (1) to (5) are mixed and heated to 75 ° C. to be uniform. On the other hand, the water phase components (6) to (9) are mixed, heated and dissolved at 75 ° C. to make it uniform, and the pigments (10) to (14) are added to this and dispersed uniformly with a homomixer. Let The oil phase component is added and emulsified, then cooled, and the components (15) and (16) are added and mixed at 40 ° C.
[0116]
[Example 22] Hand cream
(1) Cetanol 4.0
(2) Vaseline 2.0
(3) Liquid paraffin 10.0
(4) Glycerin monostearate 1.5
(5) Polyoxyethylene (60E.O.)
Glycerol isostearate 2.5
(6) Tocopherol acetate 0.5
(7) Glycerin 20.0
(8) Methyl paraoxybenzoate 0.1
(9) N-acetylglutamine 2.5
(10) Hydroquinone-β-D-glucose 1.0
(11) Purified water 55.9
Production method: The oil phase components (1) to (6) are mixed, dissolved, and heated to 75 ° C. On the other hand, the aqueous phase components (7) to (11) are mixed and dissolved and heated to 75 ° C. Subsequently, after adding an oil phase component to a water phase component and pre-emulsifying, it emulsifies uniformly with a homomixer.
[0117]
[Example 23] Jelly peel-off pack
(1) Polyvinyl alcohol 15.0
(2) Carboxymethylcellulose 5.0
(3) 1,3-butylene glycol 3.0
(4) Ethanol 6.0
(5) Polyoxyethylene (20E.O.) oleyl ether 0.5
(6) N-acetylglutamine 3.0
(7) Achillea millefolium extract 0.1
(8) Purified water 67.4
Production method: Add (3) to (8) and heat to 75 ° C. (1) and (2) are added and dissolved therein, and (4) to (7) are added and solubilized.
[0118]
[Example 24] Massage gel
(1) Dipropylene glycol 7.0
(2) Glycerin 8.0
(3) Polyoxyethylene (15E.O.) oleyl ether 1.0
(4) Carboxyvinyl polymer 0.4
(5) Methylcellulose 0.2
(6) N-acetylglutamine 0.5
(7) Peonies extract 0.2
(8) Potassium hydroxide 0.1
(9) Purified water 82.6
Production method: Components (1) to (8) are sequentially added, dissolved and homogenized to (9) heated to 75 ° C.
[0119]
[Example 25] Face wash
(1) Stearic acid 2.0
(2) Cetanol 3.0
(3) Vaseline 10.0
(4) Liquid paraffin 33.0
(5) Isopropyl myristate 7.5
(6) Glycerin monostearate 2.5
(7) Polyoxyethylene (20E.O.) sorbitan
Monostearic acid ester 2.5
(8) Glycerin 5.0
(9) Potassium hydroxide 0.1
(10) Purified water 31.2
(11) Herayahaz extract 0.2
(12) N-acetylglutamine 3.0
Production method: The oil phase components (1) to (7) are mixed and dissolved by heating to 70 ° C. On the other hand, the water phase components (8) to (10) are mixed and dissolved by heating to 70 ° C. The oil phase component is gradually added to this water phase component and pre-emulsified, then uniformly emulsified with a homomixer and cooled, and then the components (11) and (12) are added at 40 ° C.
[0120]
[Example 26] Cleansing cream
(1) Purified water 16.65
(2) Polyoxyethylene coconut oil fatty acid sorbitan (20EO) 2.40
(3) 1,3-butylene glycol 8.00
(4) Hydrogenated soybean phospholipid 0.10
(5) Carboxyvinyl polymer (1% by weight aqueous solution) 20.00
(6) Stearyl glycyrrhetinate 0.05
(7) Behenyl alcohol 1.20
(8) Stearic acid 0.10
(9) Beeswax 0.10
(10) Hardened oil 0.10
(11) Jojoba oil 0.10
(12) Tocopherol 0.05
(13) Sorbitan monostearate 1.60
(14) Cetyl 2-ethylhexanoate 5.00
(15) Squalane 40.00
(16) L-arginine (10% by weight aqueous solution) 1.50
(17) Methyl paraoxybenzoate 0.10
(18) 1,3-Butylene glycol 2.00
(19) Ascorbic acid phosphate magnesium salt 0.50
(20) Button extract 0.02
(21) Peonies extract 0.02
(22) Melissa extract 0.02
(23) Yuzu extract 0.02
(24) N-acetylglutamine 0.30
(25) Perfume 0.07
Production method: The aqueous phase components (1) to (5) are mixed and dissolved by heating to 70 ° C. On the other hand, the oil phase components (6) to (15) are mixed and dissolved by heating to 70 ° C. The oil phase component is gradually added to the water phase component and pre-emulsified, and then uniformly emulsified with a homomixer and cooled, and then the components (16) to (25) are sequentially added at 40 ° C.
[0121]
[Example 27] Face wash
(1) Myristic acid 30.00
(2) Lipophilic glyceryl monostearate 6.00
(3) Stearic acid 2.80
(4) (hydroxystearic acid / isostearic acid)
Dipentaerythritol ester 1.00
(5) Glycerin 17.00
(6) Potassium hydroxide 8.00
(7) Purified water 31.74
(8) N-stearoyl-L-glutamate sodium 1.00
(9) 1,3-butylene glycol 1.00
(10) Methyl paraoxybenzoate 0.08
(11) Hydrogenated soybean phospholipid 0.10
(12) O- [2-hydroxy-3- (trimethylammonio) chloride
Propyl) hydroxyethyl cellulose solution 0.05
(13) Dipotassium glycyrrhizinate 0.05
(14) Ascorbic acid phosphate magnesium salt 0.50
(15) Button extract 0.02
(16) Peonies extract 0.02
(17) Melissa extract 0.02
(18) Yuzu extract 0.02
(19) N-acetylglutamine 0.10
(20) Fragrance 0.50
Production method: The oil phase components (1) to (5) are mixed and dissolved by heating to 70 ° C. On the other hand, the aqueous phase components (6) to (12) are mixed and dissolved by heating to 70 ° C. The oil phase component is gradually added to the water phase component and pre-emulsified, then uniformly emulsified with a homomixer and cooled, and then the components (13) to (20) are sequentially added at 40 ° C.
[0122]
[Example 28] Masking agent
(1) Sodium N-stearoyl-L-glutamate 1.00
(2) Purified water 48.14
(3) Polyethylene glycol monostearate 2.00
(4) Polyoxyethylene sorbitan monopalmitate (20EO) 1.00
(5) Diethylenetriaminepentaacetic acid pentasodium (40% by weight aqueous solution) 0.20
(6) L-arginine 0.03
(7) 1,3-butylene glycol 3.00
(8) Titanium oxide 4.00
(9) Behenyl alcohol 3.50
(10) Lipophilic glyceryl monostearate 3.50
(11) Octyldodecyl myristate 15.00
(12) Squalane 12.00
(13) Sorbitan sesquioleate 1.00
(14) Stearic acid 0.10
(15) Beeswax 0.10
(16) Jojoba oil 0.10
(17) Hardened oil 0.10
(18) Stearyl glycyrrhetinate 0.05
(19) Alcohol 2.00
(20) Methyl paraoxybenzoate 0.10
(21) Fragrance 0.07
(22) Ascorbic acid phosphate magnesium salt 0.50
(23) Sodium citrate (10% by weight aqueous solution) 2.00
(24) Button extract 0.02
(25) Peonies extract 0.02
(26) Melissa extract 0.02
(27) Yuzu extract 0.10
(28) N-acetylglutamine 0.35
Production method: The aqueous phase components (1) to (8) are mixed, homogeneously dispersed with a homomixer, and heated to 70 ° C. On the other hand, the oil phase components (6) to (18) are mixed and dissolved by heating to 70 ° C. The oil phase component is gradually added to the water phase component, and the mixture is uniformly emulsified with a homomixer and cooled.
[0123]
When the improvement effect of the pigmentation symptom was evaluated about the above-mentioned Example 13-Example 28, the favorable improvement effect of the pigmentation symptom was recognized in all the Examples.
[0124]
About Example 4-Example 28, when the 24-hour obstruction | occlusion sticking test and the skin irritation test were done, high safety | security was shown.
[0125]
【The invention's effect】
As described above in detail, it was possible to provide a skin external preparation that has a good transdermal absorption promoting effect on a whitening agent, particularly a hydrophilic drug such as a water-soluble ascorbic acid derivative, and exhibits an excellent whitening effect.
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JP2006241009A (en) * | 2005-03-01 | 2006-09-14 | Dhc Co | Skin care preparation for external use for bleaching |
JP3747053B2 (en) * | 2005-07-12 | 2006-02-22 | 株式会社ノエビア | External preparation for skin and method for penetration of whitening agent using the same |
JP5423002B2 (en) * | 2006-06-23 | 2014-02-19 | 味の素株式会社 | Collagen synthesis promoter containing zinc as an active ingredient |
WO2007148832A1 (en) * | 2006-06-23 | 2007-12-27 | Ajinomoto Co., Inc. | Skin whitening agent containing zinc as active ingredient |
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JP2011105644A (en) * | 2009-11-17 | 2011-06-02 | Maruzen Pharmaceut Co Ltd | Melanin uptake inhibitor |
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