JP4035481B2 - Skin preparation - Google Patents

Description

【００４０】
例２：細胞培養によるメラニン生成抑制および細胞生存率試験
マウス由来のB16メラノーマ培養細胞を使用した。２枚の６穴プレートに10％FBS含有MEM培地を適量とり、B16メラノーマ細胞を播種し、37℃、二酸化炭素濃度5vol%中にて静置した。翌日、例１より得られた抽出物２を、最終固形物濃度が0（対照）、0.001、0.01、0.1、1、10μg/mLとなるように検体調製液を添加して混和した。培養5日目に培地を交換し、再度検体調製液を添加した。翌日培地を除き、１枚のプレートについて、細胞をリン酸緩衝液（pH7）にて洗浄した後回収し、B16メラノーマ培養細胞の白色化度を以下の基準にて評価した。
【００４１】

【００４２】
さらに残りの１枚のプレートについて、細胞をホルマリン固定後、１％クリスタルバイオレット溶液を添加し染色した。各検体濃度に対する細胞生存率をモノセレーター（オリンパス社製）で測定した。
【００４３】
また比較品１としてイチヤクソウ抽出物、比較品２として既にメラニン生成抑制作用のあることが知られているヨクイニン抽出物について同様の試験を行って評価した。イチヤクソウ抽出物（比較品１）は、イチヤクソウ属イチヤクソウ科イチヤクソウ（Pyrola japonica Klenze ex Alef.）の葉および茎の混合物各100gに50vol%含水エチルアルコールを１L加え、室温にて一週間抽出を行ない、濾液を濾過して得た。この時、イチヤクソウ50vol%含水エチルアルコール抽出物の乾固形分は0.035％であった。ヨクイニン抽出物（比較品２）は、ヨクイニン（日局）10gに、70vol%含水エチルアルコール100mLを加え、室温にて３日間抽出を行った後、濾過して得た。この時、ヨクイニン抽出物の乾固形分は0.8%であった。
【００４４】
培養細胞の白色化度の評価および細胞生存率は表２に示したとおりである。この表２の結果から明らかなように、オオウメガサソウ抽出物２は比較品１および比較品２より、低濃度で高いメラニン生成抑制能を有し、かつB16メラノーマ培養細胞に対し毒性が低いことが認められた。以上のことから、オオウメガサソウ抽出物を含有する皮膚外用剤を肌に適用することにより、極めて優れたメラニン生成抑制作用を発揮し、日焼けによる肌の黒色化、シミ、ソバカスなどを効果的に抑制し、美白効果が期待できる。また、オオウメガサソウ抽出物1および３についてもほぼ同様の結果が得られた。
【００４５】
【表２】

【００４６】
例３：細胞培養による細胞賦活作用の評価
ヒト新生児由来の線維芽細胞NB1RGBを使用した。24穴プレートに培地を適量とり、線維芽細胞NB1RGBを播種し、37℃、二酸化炭素濃度5vol%中にて静置した。例１で得たオオウメガサソウ抽出物２について、それぞれ最終固形分濃度が0（対照）、1、10、100μg/mLとなるように検体調製液を添加し混和した。培養4日目に培地を交換し、再度検体調製液を添加した。翌日、培地を除き、細胞をリン酸緩衝液にて洗浄した後回収し、各検体調製液で生育させた線維芽細胞NB1RGBの細胞数を対照と比較した細胞増殖率として細胞賦活効果を評価した。細胞数は、血球計算盤を用いてカウントした。
【００４７】
また、細胞賦活効果があることが知られている大豆抽出物を比較品３として同様の試験を行った。この大豆抽出物（比較品３）は、大豆の種子10gに、70vol%含水エチルアルコール100mLを加えて、室温にて3日間抽出を行なった後濾過して得た。この時、大豆抽出物の乾燥固形分は0.5%であった。
【００４８】
結果は表３に示したとおりである。この表３の結果から明らかなごとく、オオウメガサソウ抽出物２は、ヒト新生児由来の線維芽細胞NB1RGBに対して比較品３より高い細胞賦活能を有していることが認められた。従って、オオウメガサソウ抽出物を細胞賦活成分として肌に適用することにより、加齢、紫外線曝露等により生じる皮膚のしわ、たるみや、ツヤ、ハリの低下等を予防改善することが期待できる。なお、オオウメガサソウ抽出物１および３についても同様に試験したが、ほぼ同様の結果が得られた。
【００４９】
【表３】

【００５０】
例４：クリームの製造
以下の成分を組み合わせ、25種のクリーム（本発明品2〜12、比較品4〜17）を調製した。
【００５１】

成分(1)〜(6)、(8)、(10)、(13)、(15)、(17)および(21)を混合し、加熱して70℃に維持した。この混合物に、70℃に維持した成分(23)の一部を加えて乳化した。この乳化物に、成分(7)、(9)、(11)、(12)、(14)、(16)、(18)、(19)、(20)および(22)を加えた後、冷却してクリームを得た。
【００５２】
次いで、各クリーム１品につき35〜59才の女性15名をパネルとし、毎日朝と夜の2回、12週間にわたって洗顔後に被験クリームの適量を顔面に塗布した。塗布によるくすみ改善効果を以下の基準によって評価し、各評価基準に該当する人数を表４に示した。
【００５３】
＜評価＞ ＜内 容＞
有 効 肌のくすみが目立たなくなった。
やや有効 肌のくすみがあまり目立たなくなった。
無 効 使用前と変化なし。
【００５４】
また、各クリーム１品につき35〜59才の女性15名をパネルとし、毎日朝と夜の2回、12週間にわたって洗顔後に被験クリームの適量を顔面に塗布した。塗布によるツヤ、ハリ改善効果を以下の基準によって評価し、各評価基準に該当する人数を表４に示した。
【００５５】
＜評価＞ ＜内 容＞
有 効 肌のツヤ、ハリがかなり改善された。
やや有効 肌のツヤ、ハリが改善された。
無 効 使用前と変化なし。
【００５６】
【表４】

【００５７】
表４に示した結果から明らかなように、オオウメガサソウ抽出物２を配合したクリーム（本発明品2-12）は、肌のくすみ等の防止および改善効果を発揮した。さらにオオウメガサソウ抽出物２と表４に示す(8)〜(17)のいずれかの薬効成分を併用して配合した各クリーム（それぞれ本発明品3-12）は、肌のくすみ等の防止および改善効果を相乗的に発揮した。
【００５８】
また、表４に示した結果から明らかなように、オオウメガサソウ抽出物２を配合したクリーム（本発明品2-12）は肌のツヤ、ハリ等の低下の防止および改善効果を発揮した。さらにオオウメガサソウ抽出物２と表４に示す(8)〜(17)の薬効成分を併用して配合した各クリーム（それぞれ本発明品3-12）は、肌のツヤ、ハリ等の低下の防止および改善効果を相乗的に発揮した。
【００５９】
なお、オオウメガサソウ抽出物１および３についても同様にクリームを製造して試験したが、ほぼ同様の結果が得られた。
例５：化粧水の製造
下記成分(1)〜(7)を混合溶解した溶液と、下記成分(8)〜(11)を混合溶解した溶液とを混合して均一にし、化粧水を得た。
（成分） （％）
(1)グリセリン 10.0
(2)1,3-ブチレングリコール 6.0
(3)オオウメガサソウ抽出物1(*1) 0.001
(4)グリチルリチン酸ジカリウム(*2) 0.1
(5)クエン酸 0.1
(6)クエン酸ナトリウム 0.3
(7)精製水 残量
(8)ポリオキシエチレン硬化ヒマシ油（60E.O.） 0.5
(9)エチルアルコール 8.0
(10)防腐剤 適量
(11)香料 適量
(*1)例１で製造したもの
(*2)池田糖化工業社製
得られた化粧水を、例４と同様のパネルにより評価した結果、この化粧水は、ツヤ、ハリおよび透明感のある美しい肌にする効果に優れた化粧水であることが確認された。
例６：乳液の製造
下記成分(13)〜(17)を加熱混合し、70℃に維持した混合物に、下記成分(1)〜(12)を加熱混合し、70℃に維持した混合物を加えて混合し、均一に乳化した。この乳化物を冷却後、成分(18)〜(22)を加え、均一に混合して乳液を得た。
（成分） （％）
(1)モノステアリン酸ソルビタン 0.3
(2)モノオレイン酸ポリオキシエチレンソルビタン（２０E.O.） 0.1
(3)親油型モノステアリン酸グリセリル 0.2
(4)ステアリン酸 0.5
(5)セタノール 0.5
(6)スクワラン 3.0
(7)流動パラフィン 4.0
(8)トリ-2-エチルヘキサン酸グリセリル 2.0
(9)ジメチルポリシロキサン 1.0
(10)水素添加大豆リン脂質 0.1
(11)ニコチン酸dl-α-トコフェロール(*1) 0.05
(12)防腐剤 適量
(13)カルボキシビニルポリマー水溶液（1.0%） 10.0
(14)水酸化ナトリウム 0.05
(15)グリセリン 5.0
(16)1,3-ブチレングリコール 7.0
(17)精製水 残量
(18)エチルアルコール 5.0
(19)オオウメガサソウ抽出物３(*2) 0.0001
(20)リン酸-L-アスコルビルマグネシウム(*3) 0.1
(21)麻セルロース末 3.0
(22)香料 適量
(*1)エーザイ社製
(*2)例１で製造したもの
(*3)日光ケミカルズ社製
得られた乳液を、例４と同様のパネルにより評価した結果、この乳液は、ツヤ、ハリおよび透明感のある美しい肌にする効果に優れた乳液であることが確認された。
例７：パックの製造
下記成分(1)〜(6)を混合し、70℃に加熱して溶解した溶液に、下記成分(7)および(8)を混合して溶解した溶液を加え、混合した。この混合液を冷却した後、成分(9)〜(11)を混合して、パックを得た。
（成分） （％）
(1)ポリビニルアルコール 15.0
(2)無水ケイ酸 0.5
(3)ポリエチレングリコール 0.5
(4)ポリオキシプロピレンメチルグルコシド 5.0
(6)グリセリン 5.0
(6)精製水 残量
(7)エチルアルコール 20.0
(8)防腐剤 適量
(9)オオウメガサソウ抽出物１(*1) 0.01
(10)カンゾウ抽出物(*2) 0.5
(11)香料 適量
(*1)例１で製造したもの
(*2)丸善製薬社製
得られたパックを、例４と同様のパネルにより評価した結果、このパックは、ツヤ、ハリおよび透明感のある美しい肌にする効果に優れたパックであることが確認された。
例８：リキッドファンデーションの製造
下記成分(1)〜(8)および(23)を混合溶解した溶液に、成分(14)〜(21)を加え、均一に混合し、70℃に維持した。この混合物に、下記成分(9)〜(13)および(24)を均一に溶解し、70℃に維持した混合物に添加して、均一に乳化した。この乳化物を冷却後、成分(22)および(25)を添加してリキッドファンデーションを得た。
（成分） （％）
(1)ジペンタエリトリット脂肪酸エステル（*1） 2.0
(2)流動パラフィン 5.0
(3)ステアリン酸 2.0
(4)セタノール 1.0
(5)自己乳化型モノステアリン酸グリセリル 1.0
(6)パラメトキシケイ皮酸-2-エチルヘキシル 8.0
(7)4-tert-ブチル-4'-メトキシジベンゾイルメタン 2.0
(8)防腐剤 適量
(9)グリセリン 5.0
(10)トリエタノールアミン 1.0
(11)カルボキシメチルセルロース 0.2
(12)ベントナイト 0.5
(13)精製水 残量
(14)酸化チタン 6.0
(15)微粒子酸化チタン 2.0
(16)微粒子酸化亜鉛 5.0
(17)マイカ 2.0
(18)タルク 4.0
(19)黄酸化鉄 1.0
(20)黒酸化鉄 0.05
(21)ベンガラ 0.5
(22)オオウメガサソウ抽出物１(*2) 0.01
(23)酢酸dl-α-トコフェロール(*3) 0.5
(24)リン酸-L-アスコルビルマグネシウム(*4) 0.5
(25)香料 適量
(*1)コスモールＡＲ（日清オイリオ社製）
(*2)例１で製造したもの
(*3)エーザイ社製
(*4)日光ケミカルズ社製
得られたリキッドファンデーションを、例４と同様のパネルにより評価した結果、このリキッドファンデーションは、日焼けや加齢等によるシミやくすみのない肌にする効果に優れたリキッドファンデーションであることが確認された。
例９：油性ファンデーションの製造
下記成分(1)〜(7)および(13)〜(17)を80℃で加熱溶解した溶液に、成分(8)〜(12)を加えて均一に混合し、冷却固化して油性ファンデーションを得た。
（成分） （％）
(1)キャンデリラワックス 4.0
(2)パラフィンワックス 5.0
(3)ワセリン 5.0
(4)ジメチルポリシロキサン 15.0
(5)スクワラン 25.0
(6)トリイソステアリン酸ジグリセリル 残量
(7)有機変性ベントナイト 3.0
(8)グリセリン 0.5
(9)酸化チタン 10.0
(10)セリサイト 5.0
(11)ナイロンパウダー 5.0
(12)着色顔料 適量
(13)アルキル変性カルボキシビニルポリマー 0.5
(14)オオウメガサソウ抽出物３(*1) 0.02
(15)酢酸dl-α-トコフェロール(*2) 0.1
(16)グリチルレチン酸ステアリル(*3) 0.1
(17)香料 適量
(*1)例１で製造したもの
(*2)エーザイ社製
(*3)丸善製薬社製
得られた油性ファンデーションを、例４と同様のパネルにより評価した結果、この油性ファンデーションは、日焼けや加齢等によるシミやくすみのない肌にする効果に優れた油性ファンデーションであることが確認された。
【００６０】
【発明の効果】
以上詳しく説明したとおり、本発明によって、安定かつ優れた美白効果または細胞賦活効果を有する皮膚外用剤が提供される。この皮膚外用剤は、メラニン生成抑制作用または細胞賦活作用を有しており、肌のくすみ、日やけなどによる皮膚の黒化、シミ、ソバカスの防止及び改善、加齢、紫外線曝露等により生じる皮膚のしわ、たるみや、ツヤ、ハリの低下等の予防または改善等に有効である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a skin external preparation containing an extract of a plant belonging to the genus Chimaphila Pursh as a whitening component or a cell activation component.
[0002]
[Prior art]
Conventionally, skin external preparations such as emulsions, creams, lotions, packs, cleaning agents, dispersions, ointments, liquids, aerosols, patches, poultices, liniments, and the like have been given a prescribed medicinal effect. Various medicinal agents are added for the purpose.
[0003]
For example, whitening agents such as ascorbic acid and hydroquinone are used to prevent or improve darkening of the skin caused by sunburn and the like, spots and freckles caused by pigmentation (see Patent Documents 1 and 2). Moreover, it is known that the cosmetics containing the extract of a Ichyakuaceae plant have a whitening effect (refer patent document 3).
[0004]
In addition, cell activators such as α-hydroxy acid and seaweed extract are used in order to prevent or ameliorate skin wrinkles, sagging, gloss, reduction of elasticity, etc. caused by aging, ultraviolet exposure, etc. (For example, Patent Documents 4 and 5).
[0005]
[Patent Document 1]
Japanese Patent Publication No.44-31237
[Patent Document 2]
JP 60-56912 A
[Patent Document 3]
JP-A-4-279511
[Patent Document 4]
Japanese Unexamined Patent Publication No. 7-13317
[Patent Document 5]
JP 2000-169320 A
[0006]
[Problems to be solved by the invention]
However, with these medicinal agents, their effects may not be sufficient, or the desired medicinal properties may not be obtained due to alteration in the formulation, etc., and improvements and development of new medicinal agents are desired. It was rare.
[0007]
This invention is made | formed in view of the above situations, Comprising: It aims at providing the skin external preparation which has the stable and outstanding whitening effect or cell activation effect.
[0008]
[Means for Solving the Problems]
As a result of intensive studies on the components that can be used as medicinal components of the topical skin preparation, the present inventors have shown that extracts from plants belonging to the genus Chimaphila Pursh are particularly high in suppressing the production of melanin. It was found that it has an action and is excellent as a whitening component. At the same time, it was found that this extract has a high cell activation effect and is excellent as a cell activation component. And this extract was able to be blended into a skin external preparation as a whitening component or a cell activation component, and found that a better effect was obtained as a skin external preparation by combining with a specific medicinal component, and the present invention was completed. .
[0009]
The present invention has been made on the basis of the above-mentioned novel findings. As a first invention for solving the above-mentioned problems, an extract of a plant belonging to the genus Chimaphila Pursh is used as a whitening ingredient. The skin external preparation contained as is provided.
[0010]
As a second invention, there is provided an external preparation for skin containing an extract of a plant belonging to the genus Chimaphila Pursh as a cell activation component.
[0011]
In these 1st invention and 2nd invention, it is set as the preferable aspect that the plant which belongs to the genus Euchymeaceae is the giant dragonfly (Chimaphila umbellata (L.) WPC Barton). In these inventions, licorice extract containing at least one of grabrizine, glabrene, liquiritin, and isolyquiritin, arbutin, ellagic acid, chamomile extract, vitamin C and its derivatives, vitamin E and its derivatives, glycyrrhizic acid and Another preferred embodiment is to contain one or two or more medicinal components selected from the group consisting of the derivatives, glycyrrhetinic acid and derivatives thereof, linoleic acid, tranexamic acid, and zinc oxide.
[0012]
The external preparation for skin in the present invention has an excellent medicinal effect, particularly a whitening effect and / or a cell activation effect, by containing an extract of a plant belonging to the genus Uchizoenaceae. In the present invention, the “whitening effect” means in vitro melanin production inhibitory effect; aging, blackening of skin (including scalp, lips, mucous membrane) caused by exposure to ultraviolet rays, and spots and freckles caused by pigmentation It is to be interpreted in the broadest sense including the action of preventing and improving the above and preventing and improving the dullness of the skin. Further, in the present invention, the “cell activation effect” means an in vitro cell proliferation promoting effect; an action to prevent and improve skin wrinkles, sagging caused by aging, UV exposure, etc., and reduction of elasticity, gloss, etc. Etc., and so on.
[0013]
Hereinafter, the present invention will be described in more detail with reference to embodiments.
[0014]
DETAILED DESCRIPTION OF THE INVENTION
Examples of the plant belonging to the genus Umegasaosou, which is used in the present invention, include persica and umesas.
[0015]
Giant scorpion (scientific name is Chimaphila umbellata (L.) WPC Barton; revised primary color Makino Botanical Encyclopedia, published by Hokuryukan, 1996) is widely distributed in the temperate zone of the northern hemisphere, and in Japan from north to north of Hokkaido and Kanto Tohoku. It grows in a dry forest near the coast of the sea (Asahi Encyclopedia, World of Asahi Shimbun, 1997).
[0016]
Umegasou (scientific name is Chimaphila japonica Miq .; revised primary color Makino Botanical Encyclopedia, published by Hokuryukan, 1996) is distributed in southern Sakhalin, the Korean Peninsula, China and Taiwan, and in Japan, Minami Kuril Island and Hokkaido It grows widely from coastal pine forests in Kyushu to coniferous forests in sub-alpine mountains (Asahi Encyclopedia World, published by Asahi Shimbun, 1997).
[0017]
The topical skin preparation of the present invention can contain, as an active ingredient, the above-mentioned Euglena, Umegasao, or a mixture of Euglena and Umegasao extract (hereinafter, these may be referred to as “plant extracts”). However, the extract of Persian butterfly is more preferable.
[0018]
The plant extract in the present invention can be prepared by a conventional extraction method using an appropriate solvent. For example, one or more whole plants or roots, stems, stems, leaves, branches, bark, fruits, flowers, seeds, etc. of the plant are immersed in a solvent at room temperature, low temperature or warm for a predetermined time. However, it can be prepared by eluting plant components in a solvent.
[0019]
The extraction solvent is not particularly limited. For example, water; lower monohydric alcohols such as methyl alcohol and ethyl alcohol; liquid polyhydric alcohols such as glycerin, propylene glycol and 1,3-butylene glycol; ketones such as acetone; One or more of ethers such as ether; esters such as ethyl acetate; and the like can be used.
[0020]
The plant extract in the present invention may be used as it is in a skin external preparation, or may be used after being left to mature for an appropriate period. If necessary, it can be used after being subjected to a purification treatment such as deodorization and decolorization by filtration or ion exchange resin within a range that does not affect the effect of the present invention. Further, a fraction having high activity can be taken out and used by using a separation means such as liquid chromatography.
[0021]
There is no restriction | limiting in particular about the form of the plant extract in this invention. It can be used in any form such as liquid, paste or gel. Alternatively, a liquid extract or the like can be dried and solidified, or dried by spray drying or the like and used as a powder.
[0022]
The blending amount of the plant extract in the external preparation for skin of the present invention is preferably 0.0001 to 10% by mass (hereinafter simply referred to as “%”), more preferably 0.0001 to 5%. When the extract is used as an extract, it may be in this range as a dry solid content. If it is this range, the skin external preparation which shows the more excellent whitening and / or cell activation effect, and has the favorable usability | use_condition will be obtained.
[0023]
The skin external preparation of the present invention may contain the above plant extract substantially alone or may be a mixture with other medicinal ingredients. Such medicinal ingredients include licorice extract containing at least one of glabrizine, glabrene, liquiritin, isoliquiritin, arbutin, ellagic acid, chamomile extract, vitamin C and its derivatives, vitamin E and its derivatives, glycyrrhizic acid and its derivatives Glycyrrhetinic acid and its derivatives, linoleic acid, tranexamic acid, and zinc oxide, as appropriate. As the licorice extract, Ural licorice belonging to the genus Lizoaceae (scientific name is Glycyrrhiza uralensis Fisch; primary color Makino Wakahan herb, published by Kitatakakan, 1988), Glycyrrhiza glabra L .; Examples include substances extracted by the conventional method from the Herbal University Encyclopedia, published by Hokuryukan, 1988). Arbutin is, for example, arbutin manufactured by Nacalai Tesque. The ellagic acid is ellagic acid manufactured by Sigma. The chamomile extract is a substance extracted by a conventional method from chamomile (Scientific name: Matricaria chamomilla L .; primary color Makino Wakahan herbaceous encyclopedia, published by Hokuryukan, 1988). Vitamin C and its derivatives are, for example, phosphate-L-ascorbyl magnesium (for example, phosphate-L-ascorbyl magnesium manufactured by Nippon Surfactant). Vitamin E and its derivatives are, for example, dl-α-tocopherol acetate (for example, tocopherol acetate manufactured by Eisai). Examples of the glycyrrhizic acid and derivatives thereof include dipotassium glycyrrhizinate (for example, dipotassium glycyrrhizinate manufactured by Ikeda Sakuka Kogyo Co., Ltd.). Examples of glycyrrhetinic acid and derivatives thereof include stearyl glycyrrhetinate (for example, manufactured by Maruzen Pharmaceutical Co., Ltd.). Linoleic acid is, for example, linoleic acid manufactured by Sigma. Tranexamic acid is, for example, tranexamic acid manufactured by Sigma. The zinc oxide is, for example, zinc oxide manufactured by Sakai Chemical.
[0024]
The compounding amount of the medicinal ingredient in the external preparation for skin of the present invention varies depending on the kind of medicinal ingredient, but is preferably in the range shown below. That is, licorice extract, arbutin, ellagic acid, chamomile extract, phosphoric acid-L-ascorbyl magnesium, linoleic acid, tranexamic acid, dl-α-tocopherol acetate, dipotassium glycyrrhetinate, stearyl glycyrrhetinate in the external preparation for skin of the present invention Is preferably 0.00001 to 10%, more preferably 0.0001 to 5%. When the extract is used as an extract, it may be in this range as a dry solid content. If it is this range, when combined with a plant extract, the temporal stability of the plant extract is not affected, which is preferable. Moreover, if it is this range, the skin external preparation which shows the more excellent whitening and / or cell activation effect, and has the favorable usability | use_condition will be obtained.
[0025]
As a compounding quantity of the zinc oxide in the skin external preparation of this invention, Preferably it is 0.001-30%, More preferably, it is the range of 0.01-25%. If it is in this range, it exhibits a better UV protection effect, or an UV protection effect together with other medicinal ingredients, and prevents wrinkles and sagging due to UV rays, resulting in a better whitening and / or cell activation effect. The skin external preparation shown is obtained.
[0026]
These other medicinal ingredients can be used alone or in combination.
[0027]
The form of the external preparation for skin of the present invention is not particularly limited, for example, emulsion, cream, lotion, cosmetic liquid, pack, cleaning agent, makeup cosmetic, dispersion liquid, ointment, liquid agent, aerosol, patch, cataplasm, It may be any form of cosmetic such as liniment, quasi-drug or topical medicine.
[0028]
In addition to the above-mentioned components, various components usually used in cosmetics, quasi-drugs, external medicines and the like can be appropriately added to the skin external preparation of the present invention as long as the effects of the present invention are not impaired. . Examples of such components include water, alcohol, oil agent, surfactant, thickener, powder, chelating agent, pH adjuster, various medicinal agents, extracts from animals, plants and microorganisms, and fragrances. Examples of such things are as follows (in parentheses after the plant name are the names of plants, names of herbal medicines, etc.).
[0029]
As the alcohol, a monohydric alcohol or a polyhydric alcohol such as ethyl alcohol can be used for the purpose of dissolution, refreshing feeling, antiseptic, moisturizing and the like, as long as it does not overlap with essential components.
[0030]
The oil agent can be used regardless of its origin or property as an agent that improves usability and usability. For example, liquid paraffin, squalane, triglyceride oil, ester oil, waxes, fatty acids, higher alcohol, silicone oil, fluorine oil, various waxes and the like.
[0031]
Surfactants are used for emulsification and solubilization of oils and the like, and anionic, cationic, nonionic and amphoteric active agents can be used.
[0032]
As a thickener, carboxyvinyl polymer, carrageenan, agar, xanthan gum, dextrin fatty acid ester, organically modified clay mineral, etc. can be used regardless of the origin of chemical synthesis products or natural products as long as they do not overlap with essential components. . These components can be used not only for adjusting the viscosity of the external preparation for skin but also for purposes such as gelation, moisturization, and film formation.
[0033]
The powder may be composite or surface-treated for the purpose of improving usability and usability regardless of the shape, particle size, porosity, crystal structure, and the like. Inorganic powders such as talc, mica, sericite, silicic anhydride, organic powders such as nylon powder, pearl pigments such as fish scale foil, bismuth oxychloride, inorganic pigments such as iron oxide, carbon black, ultramarine, tar dyes and The lake, natural pigments and the like are used depending on the application.
[0034]
For the purpose of preventing deterioration of the quality of components in the drug, a chelating agent such as EDTA and a pH adjuster using a buffer such as lactic acid-sodium lactate can also be used.
[0035]
As preservatives and fungicides, benzoic acid, sodium benzoate, paraoxybenzoic acid ester, parachlormetacresol, benzalkonium chloride, phenoxyethanol, isopropylmethylphenol and the like are used for the purpose of preventing and improving acne and the like.
[0036]
Examples of the anti-inflammatory agent include sulfur and its derivatives, nettle extract, inchinkou extract, turmeric extract, elder extract, larva extract, mugwort extract and the like. By blending an anti-inflammatory agent, effects such as suppression of skin pigmentation caused by inflammation and prevention of wrinkles and sagging can be further enhanced or imparted.
[0037]
Blood circulation promoters are used for the purpose of preventing wrinkles and decreased elasticity by promoting blood flow in the skin. Examples include red pepper tincture and γ-oryzanol. Examples of enzymes include lipase and papain. By blending these, the effect of preventing wrinkles and sagging can be further enhanced or imparted.
[0038]
【Example】
EXAMPLES The present invention will be described in more detail with reference to examples and test examples below, but the scope of the present invention is not limited to the following examples.
Example 1: Production of persica extract
1 L of purified water, 50 vol% hydrous ethyl alcohol or ethyl alcohol was separately added to 100 g of a mixture of leaves and stems of Chimaphila umbellata (L.) WPC Barton, followed by extraction at room temperature for 4 hours. The filtrate obtained after filtration was used as the following extract.
・ Extract 1: Purified water extract
・ Extract 2: 50vol% hydrous ethyl alcohol extract
・ Extract 3: Ethyl alcohol extract
Further, the solvent of each extract was distilled off to dryness, and the weight (g) of the obtained solid content is shown in Table 1.
[0039]
[Table 1]

[0040]
Example 2: Suppression of melanin production by cell culture and cell viability test
Mouse-derived B16 melanoma cultured cells were used. Appropriate amounts of 10% FBS-containing MEM medium were taken in two 6-well plates, B16 melanoma cells were seeded, and allowed to stand at 37 ° C. in a carbon dioxide concentration of 5 vol%. On the next day, the extract 2 obtained from Example 1 was mixed with the sample preparation solution added so that the final solid concentration was 0 (control), 0.001, 0.01, 0.1, 1, 10 μg / mL. On day 5 of the culture, the medium was changed, and the sample preparation solution was added again. The medium was removed the next day, and the cells were collected after washing with phosphate buffer (pH 7) on one plate, and the whiteness of the cultured B16 melanoma cells was evaluated according to the following criteria.
[0041]

[0042]
Further, the remaining one plate was stained with formalin-fixed cells after adding 1% crystal violet solution. The cell viability for each sample concentration was measured with a monocerator (Olympus).
[0043]
Moreover, the same test was performed and evaluated on the yakuin extract as comparative product 1 and the yokuinin extract already known to have a melanin production inhibitory effect as comparative product 2. Ichiyakuso extract (Comparative product 1) is a weekly mixture of 100 g of leaves and stems of Pyrola japonica Klenze ex Alef. The filtrate was obtained by filtration. At this time, the dry solid content of the 50 vol% water-containing ethyl alcohol extract was 0.035%. Yokuinin extract (Comparative product 2) was obtained by adding 100 mL of 70vol% hydrated ethyl alcohol to 10g of Yokuinin (Japan Pharmacopoeia), performing extraction at room temperature for 3 days, and then filtering. At this time, the dry solid content of the Yokuinin extract was 0.8%.
[0044]
The evaluation of the degree of whitening of the cultured cells and the cell viability are as shown in Table 2. As is apparent from the results in Table 2, Euphorbia extract 2 has a higher ability to suppress melanin production at a lower concentration than Comparative product 1 and Comparative product 2, and is less toxic to B16 melanoma cultured cells. Admitted. Based on the above, by applying to the skin a topical skin preparation containing the extract of Euglena sp., It exhibits an extremely excellent melanin production inhibitory effect, effectively suppressing skin blackening, spots, buckwheat, etc. due to sunburn. And whitening effect can be expected. In addition, almost the same results were obtained with the extracts of Persica serrata 1 and 3.
[0045]
[Table 2]

[0046]
Example 3: Evaluation of cell activation by cell culture
Human neonatal fibroblast NB1RGB was used. An appropriate amount of medium was taken in a 24-well plate, seeded with fibroblasts NB1RGB, and allowed to stand at 37 ° C. in a carbon dioxide concentration of 5 vol%. The sample preparation solution was added to and mixed with the cassava extract 2 obtained in Example 1 so that the final solid concentration was 0 (control), 1, 10, and 100 μg / mL, respectively. On day 4 of the culture, the medium was changed, and the sample preparation solution was added again. The next day, the medium was removed, and the cells were washed after washing with phosphate buffer and collected, and the cell activation effect was evaluated as the cell proliferation rate compared to the control by the number of fibroblasts NB1RGB grown in each sample preparation solution . The number of cells was counted using a hemocytometer.
[0047]
Moreover, the same test was done by making the soybean extract known to have a cell activation effect into the comparative product 3. This soybean extract (Comparative Product 3) was obtained by adding 100 mL of 70 vol% hydrous ethyl alcohol to 10 g of soybean seeds, performing extraction at room temperature for 3 days, and then filtering. At this time, the dry solid content of the soybean extract was 0.5%.
[0048]
The results are as shown in Table 3. As is apparent from the results of Table 3, it was confirmed that Euphorbia suso extract 2 has a higher cell activation ability than that of Comparative product 3 against human neonatal fibroblast NB1RGB. Therefore, it can be expected that the wrinkle, sagging, gloss, and reduction in skin caused by aging, ultraviolet exposure, etc. can be prevented and improved by applying the extract of Euglena as a cell activating component. In addition, although the same test was carried out also about the persian extract 1 and 3, the similar result was obtained.
[0049]
[Table 3]

[0050]
Example 4: Production of cream
The following ingredients were combined to prepare 25 types of creams (Products 2-12 of the present invention, Comparative products 4-17).
[0051]

Ingredients (1)-(6), (8), (10), (13), (15), (17) and (21) were mixed, heated and maintained at 70 ° C. To this mixture, a part of the component (23) maintained at 70 ° C. was added and emulsified. After adding components (7), (9), (11), (12), (14), (16), (18), (19), (20) and (22) to this emulsion, Cooled to obtain a cream.
[0052]
Next, 15 females aged 35 to 59 years for each cream were used as panels, and an appropriate amount of the test cream was applied to the face after face washing for 12 weeks twice a day in the morning and evening. The dullness improvement effect by application was evaluated according to the following criteria, and the number of people corresponding to each evaluation criterion is shown in Table 4.
[0053]
<Evaluation><Contents>
Effective Skin dullness is not noticeable.
Slightly effective Skin dullness is less noticeable.
Invalid No change before use.
[0054]
In addition, 15 women aged 35 to 59 years for each cream were used as a panel, and an appropriate amount of the test cream was applied to the face after washing for 12 weeks twice a day in the morning and every day. The gloss and elasticity improvement effect by application was evaluated according to the following criteria, and the number of people corresponding to each evaluation criteria is shown in Table 4.
[0055]
<Evaluation><Contents>
Effective Skin gloss and firmness have been considerably improved.
Slightly effective Skin gloss and firmness improved.
Invalid No change before use.
[0056]
[Table 4]

[0057]
As can be seen from the results shown in Table 4, the cream (Product 2-12 of the present invention) formulated with Euglena extract 2 exhibited the effect of preventing and improving skin dullness. Furthermore, each cream (Product 3-12 of the present invention) formulated with combined use of Eucalyptus extract 2 and any of the medicinal components (8) to (17) shown in Table 4 prevents skin dullness and the like. The improvement effect was demonstrated synergistically.
[0058]
Further, as is apparent from the results shown in Table 4, the cream (Product 2-12 of the present invention) in which the extract of Euglena spp. 2 was effective in preventing and improving the reduction of skin gloss and firmness. Furthermore, each cream (invention product 3-12) formulated with combined use of Euglena extract 2 and the medicinal ingredients (8) to (17) shown in Table 4 prevents the reduction of skin gloss and firmness. And the improvement effect was demonstrated synergistically.
[0059]
In addition, although the cream was similarly manufactured and tested also about the perennial Sesame extract 1 and 3, the similar result was obtained.
Example 5: Production of lotion
A solution in which the following components (1) to (7) were mixed and dissolved and a solution in which the following components (8) to (11) were mixed and dissolved were mixed and made uniform to obtain a lotion.
(Ingredient) (%)
(1) Glycerin 10.0
(2) 1,3-Butylene glycol 6.0
(3) Capsicum extract 1 (* 1) 0.001
(4) Dipotassium glycyrrhizinate (* 2) 0.1
(5) Citric acid 0.1
(6) Sodium citrate 0.3
(7) Purified water remaining
(8) Polyoxyethylene hydrogenated castor oil (60E.O.) 0.5
(9) Ethyl alcohol 8.0
(10) Preservative appropriate amount
(11) Fragrance appropriate amount
(* 1) manufactured in Example 1
(* 2) Ikeda saccharification industry
As a result of evaluating the obtained lotion using the same panel as in Example 4, it was confirmed that this lotion was a lotion excellent in the effect of making glossy, firm and transparent beautiful skin.
Example 6: Production of emulsion
The following components (13) to (17) were heated and mixed, and the following components (1) to (12) were heated and mixed to the mixture maintained at 70 ° C., and the mixture maintained at 70 ° C. was added and mixed uniformly. Emulsified. After cooling this emulsion, components (18) to (22) were added and mixed uniformly to obtain an emulsion.
(Ingredient) (%)
(1) Sorbitan monostearate0.3
(2) Polyoxyethylene sorbitan monooleate (20E.O.) 0.1
(3) Lipophilic glyceryl monostearate 0.2
(4) Stearic acid 0.5
(5) Cetanol 0.5
(6) Squalane 3.0
(7) Liquid paraffin 4.0
(8) Glyceryl tri-2-ethylhexanoate 2.0
(9) Dimethylpolysiloxane 1.0
(10) Hydrogenated soybean phospholipid 0.1
(11) dl-α-tocopherol nicotinate (* 1) 0.05
(12) Preservative appropriate amount
(13) Carboxyvinyl polymer aqueous solution (1.0%) 10.0
(14) Sodium hydroxide 0.05
(15) Glycerin 5.0
(16) 1,3-Butylene glycol 7.0
(17) Purified water remaining
(18) Ethyl alcohol 5.0
(19) Coleoptera extract 3 (* 2) 0.0001
(20) Phosphate-L-ascorbyl magnesium (* 3) 0.1
(21) Hemp cellulose powder 3.0
(22) Perfume appropriate amount
(* 1) Eisai
(* 2) manufactured in Example 1
(* 3) Nikko Chemicals
As a result of evaluating the obtained emulsion using the same panel as in Example 4, it was confirmed that this emulsion was an emulsion excellent in the effect of making glossy, firm and transparent beautiful skin.
Example 7: Pack production
The following components (1) to (6) were mixed, and the solution in which the following components (7) and (8) were dissolved was added to the solution dissolved by heating to 70 ° C. and mixed. After cooling the mixed solution, the components (9) to (11) were mixed to obtain a pack.
(Ingredient) (%)
(1) Polyvinyl alcohol 15.0
(2) Silicic anhydride 0.5
(3) Polyethylene glycol 0.5
(4) Polyoxypropylene methyl glucoside 5.0
(6) Glycerin 5.0
(6) Remaining amount of purified water
(7) Ethyl alcohol 20.0
(8) Preservative appropriate amount
(9) Capsicum extract 1 (* 1) 0.01
(10) Daylily extract (* 2) 0.5
(11) Fragrance appropriate amount
(* 1) manufactured in Example 1
(* 2) Made by Maruzen Pharmaceutical Co., Ltd.
The obtained pack was evaluated by the same panel as in Example 4. As a result, it was confirmed that this pack was a pack excellent in the effect of making glossy, firm and transparent beautiful skin.
Example 8: Production of liquid foundation
Components (14) to (21) were added to a solution in which the following components (1) to (8) and (23) were mixed and dissolved, mixed uniformly, and maintained at 70 ° C. The following components (9) to (13) and (24) were uniformly dissolved in this mixture and added to the mixture maintained at 70 ° C. to uniformly emulsify. After cooling this emulsion, components (22) and (25) were added to obtain a liquid foundation.
(Ingredient) (%)
(1) Dipentaerythritol fatty acid ester (* 1) 2.0
(2) Liquid paraffin 5.0
(3) Stearic acid 2.0
(4) Cetanol 1.0
(5) Self-emulsifying glyceryl monostearate 1.0
(6) 2-methoxyhexyl paramethoxycinnamate 8.0
(7) 4-tert-Butyl-4'-methoxydibenzoylmethane 2.0
(8) Preservative appropriate amount
(9) Glycerin 5.0
(10) Triethanolamine 1.0
(11) Carboxymethylcellulose 0.2
(12) Bentonite 0.5
(13) Remaining amount of purified water
(14) Titanium oxide 6.0
(15) Fine particle titanium oxide 2.0
(16) Fine zinc oxide 5.0
(17) Mica 2.0
(18) Talc 4.0
(19) Yellow iron oxide 1.0
(20) Black iron oxide 0.05
(21) Bengala 0.5
(22) Capsicum extract 1 (* 2) 0.01
(23) dl-α-Tocopherol acetate (* 3) 0.5
(24) Phosphate-L-ascorbyl magnesium (* 4) 0.5
(25) Perfume appropriate amount
(* 1) Cosmall AR (Nisshin Oilio)
(* 2) manufactured in Example 1
(* 3) Eisai
(* 4) Nikko Chemicals
As a result of evaluating the obtained liquid foundation using the same panel as in Example 4, it was confirmed that this liquid foundation was a liquid foundation excellent in the effect of making the skin free from spots and dullness caused by sunburn or aging. .
Example 9: Production of oily foundation
Add components (8) to (12) to a solution in which the following components (1) to (7) and (13) to (17) are dissolved by heating at 80 ° C., mix uniformly, cool and solidify to obtain an oily foundation. Obtained.
(Ingredient) (%)
(1) Candelilla wax 4.0
(2) Paraffin wax 5.0
(3) Vaseline 5.0
(4) Dimethylpolysiloxane 15.0
(5) Squalane 25.0
(6) Diglyceryl triisostearate
(7) Organically modified bentonite 3.0
(8) Glycerin 0.5
(9) Titanium oxide 10.0
(10) Sericite 5.0
(11) Nylon powder 5.0
(12) Coloring pigment appropriate amount
(13) Alkyl-modified carboxyvinyl polymer 0.5
(14) Coleoptera extract 3 (* 1) 0.02
(15) dl-α-tocopherol acetate (* 2) 0.1
(16) Stearyl glycyrrhetinate (* 3) 0.1
(17) Perfume appropriate amount
(* 1) manufactured in Example 1
(* 2) Eisai
(* 3) Made by Maruzen Pharmaceutical Co., Ltd.
As a result of evaluating the obtained oily foundation using the same panel as in Example 4, it was confirmed that this oily foundation was an oily foundation excellent in the effect of making skin free from spots and dullness due to sunburn or aging. .
[0060]
【The invention's effect】
As explained in detail above, the present invention provides a skin external preparation having a stable and excellent whitening effect or cell activation effect. This external preparation for skin has a melanin production inhibitory action or a cell activation action, and it is caused by dull skin, darkening of skin due to sunburn, etc., prevention and improvement of spots and freckles, aging, exposure to ultraviolet rays, etc. It is effective for prevention or improvement of wrinkles, sagging, gloss, reduction of elasticity and the like.

Claims (3)

Pyrolaceae chimaphila Ooumegasasou (Chimaphila umbellata (L.) WPC Barton ) cell-activating skin external preparation comprising an extract of a plant belonging to. Furthermore, licorice extract containing at least one of grabrizine, glabrene, liquiritin, isoliquiritin, arbutin, ellagic acid, chamomile extract, vitamin C and its derivatives, vitamin E and its derivatives, glycyrrhizic acid and its derivatives, glycyrrhetinic acid and its derivatives, linoleic acid, tranexamic acid, and skin external preparation according to claim 1, further comprising one selected from the group consisting of zinc oxide, or two or more kinds. Hari skin, skin external preparation according to claim 1 or 2, wherein the for gloss improvement.