JP3719951B2 - Skin preparation - Google Patents
Skin preparation Download PDFInfo
- Publication number
- JP3719951B2 JP3719951B2 JP2001173568A JP2001173568A JP3719951B2 JP 3719951 B2 JP3719951 B2 JP 3719951B2 JP 2001173568 A JP2001173568 A JP 2001173568A JP 2001173568 A JP2001173568 A JP 2001173568A JP 3719951 B2 JP3719951 B2 JP 3719951B2
- Authority
- JP
- Japan
- Prior art keywords
- extract
- skin
- radix
- added
- external preparation
- 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 - Lifetime
Links
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- 241000544061 Cuculus canorus Species 0.000 claims description 22
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- 241000411851 herbal medicine Species 0.000 claims description 2
- 238000005342 ion exchange Methods 0.000 claims description 2
- 244000299906 Cucumis sativus var. sativus Species 0.000 claims 1
- 238000001179 sorption measurement Methods 0.000 claims 1
- 210000003491 skin Anatomy 0.000 description 43
- 230000000052 comparative effect Effects 0.000 description 22
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- 229960000894 sulindac Drugs 0.000 description 1
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- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
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Description
【0001】
【発明の属する技術分野】
本発明は、肌荒れ及び皮膚の老化の防止,改善効果が相乗的に向上した皮膚外用剤に関する。さらに詳しくは、カッコンの抽出物及び抽出分画物より選択した1種又は2種以上、もしくはその有効成分である4',7-ジヒドロキシイソフラボンと、抗炎症剤とを併用して成る皮膚外用剤に関する。
【0002】
【従来の技術】
加齢や紫外線曝露,皮膚組織内において発生する活性酸素種等による酸化的ストレス、薬物や種々のアレルゲンとの接触などにより、皮膚の炎症反応や皮膚の老化が進行することが知られている。これまで皮膚外用剤の分野では、かかる皮膚の炎症や老化を防止するべく、活性酸素種消去剤や抗炎症剤,抗アレルギー剤等多くの生理活性成分の探索及び検討がなされてきた。また、加齢や前記ストレスにより、真皮マトリックス成分であるコラーゲンの架橋等修飾により皮膚の老化症状が進行することが明らかになるにつれ、皮膚組織内においてその産生を促進する作用を有する物質の検討もなされている。近年は、消費者の天然志向及び植物志向を反映してか、かかる成分を植物に求める傾向が強くなっている。
【0003】
しかしながら、すでに報告されている植物起源の上記成分の中には、活性が低いため、皮膚外用剤に配合して十分な作用効果を得るにはかなりの高濃度を要したり、安定性や安全性上問題があったり、皮膚外用剤に好ましくない色や臭いを付与してしまうものがあったりして、皮膚外用剤に配合した際に、製剤安定性及び安全性と、作用効果のすべての面で満足できるものは少ないのが現状であった。また皮膚の炎症反応や老化は、種々の要因が複雑に関与し合って進行するため、前記反応の一部の過程のみに作用する物質を用いても十分な効果は得られなかった。
【0004】
【発明が解決しようとする課題】
そこで本発明においては、複雑な皮膚の炎症性反応等を抑制し、肌荒れや皮膚の老化の防止,改善効果が相乗的に向上した皮膚外用剤を得ることを目的とした。
【0005】
【課題を解決するための手段】
上記課題を解決するべく種々検討したところ、本発明者らはカッコン(Puerariae Radix)の抽出物及び抽出分画物に高い線維芽細胞賦活作用及びコラーゲン産生促進作用を見いだし、さらにこれらより選択した1種又は2種以上と、抗炎症剤の1種又は2種以上とを併用して皮膚外用剤に含有させることにより、肌荒れ及び皮膚の老化の防止,改善効果の相乗的な向上が得られることを見いだし、本発明を完成するに至った。
【0006】
特に、カッコン抽出物及び抽出分画物として、4',7-ジヒドロキシイソフラボン(ダイゼイン)含有量の高いものを用いると、良好な効果が得られ、また4',7-ジヒドロキシイソフラボン自体と併用してもよい。
【0007】
なお、カッコン抽出物については、ムコ多糖断片化抑制,活性酸素消去,抗酸化作用(特開平6−24937)、脂肪合成促進作用(特開平11−199499)、毛乳頭活性化作用(特開平11−240823)が開示され、ヒアルロン酸産生促進作用も報告されている(日本薬学会第120年会講演要旨集2,第58ページ,2000年)が、I型コラーゲンの産生促進作用については全く知られていない。さらに、7-イソプロポキシイソフラボンの代謝物についてI型コラーゲンの合成促進作用が報告されている(Calcified Tissue International 55(5) 356-362 (1994))が、カッコン抽出物中の4',7-ジヒドロキシイソフラボンについては抗アセチルコリン作用を有することは周知であるものの、かかる報告はこれまでなされていない。
【0008】
また、抗炎症剤については、肌荒れ改善効果を期待して、古くから皮膚外用剤に配合されているが、カッコンの抽出物もしくは抽出分画物又は4',7-ジヒドロキシイソフラボンと、抗炎症剤とを併用することにより得られる本発明の効果は、これまで全く示唆すらされていない。
【0009】
【発明の実施の形態】
本発明において用いるカッコン(Puerariae Radix)は、マメ科(Leguminosae)に属する落葉藤本であるクズ(Pueraria lobata Ohwi)の周皮を除いた根であり、日本産,韓国産及び中国産の角カッコン,板カッコン及び粉カッコンを用いることができる。
【0010】
カッコン(Puerariae Radix)は、生のまま抽出に供してもよいが、抽出効率を考えると、細切,乾燥,粉砕等の処理を行った後に抽出を行うことが好ましい。抽出は、抽出溶媒に浸漬して行う。抽出効率を上げるため撹拌を行ったり、抽出溶媒中でホモジナイズしてもよい。抽出温度としては、5℃程度から抽出溶媒の沸点以下の温度とするのが適切である。抽出時間は抽出溶媒の種類や抽出温度によっても異なるが、4時間〜14日間程度とするのが適切である。
【0011】
抽出溶媒としては、水の他、メタノール,エタノール,プロパノール,イソプロパノール等の低級アルコール、1,3-ブチレングリコール,プロピレングリコール,ジプロピレングリコール,グリセリン等の多価アルコール、エチルエーテル,プロピルエーテル等のエーテル類、酢酸エチル,酢酸ブチル等のエステル類、アセトン,エチルメチルケトン等のケトン類などの極性有機溶媒を用いることができ、これらより1種又は2種以上を選択して用いる。また、生理食塩水,リン酸緩衝液,リン酸緩衝生理食塩水等を用いてもよい。
【0012】
カッコン(Puerariae Radix)の上記溶媒による抽出物は、そのままでも本発明に係る皮膚外用剤に含有させることができるが、濃縮,乾固したものを水や極性溶媒に再度溶解したり、或いはこれらの生理作用を損なわない範囲で脱色,脱臭,脱塩等の精製処理を行ったり、カラムクロマトグラフィー等による分画処理を行った後に用いてもよい。特に、イオン交換吸着樹脂に吸着させた後、水・エタノール混合溶媒にて順次溶出した際、50容量%〜99.5容量%エタノール水溶液により溶出される画分が4',7-ジヒドロキシイソフラボンを最も多く含有し、コラーゲン産生促進作用の点から最も好ましく用いられる。イオン交換樹脂としては、DIAION MCIゲル HP-20(三菱化学株式会社製)等が好ましく用いられる。カッコンの前記抽出物やその処理物及び分画物は、各処理及び分画の後凍結乾燥し、用時に溶媒に溶解して用いることもできる。また、リポソーム等のベシクルやマイクロカプセル等に内包させて用いることもできる。
【0013】
また本発明においては、上記したカッコンの抽出物又はその分画物の替わりに、精製した4',7-ジヒドロキシイソフラボンを用いてもよい。
【0014】
本発明において、上記カッコン(Puerariae Radix)の抽出物及び抽出分画物の1種又は2種以上、もしくは4',7-ジヒドロキシイソフラボンと併用する抗炎症剤としては、コルチゾン,ヒドロコルチゾン,プレドニゾロン,メチルプレドニゾロン,デキサメタゾン,ベタメタゾン,トリアムシノロン,トリアムシノロンアセトニド,フルオシノロンアセトニド,フルオシノニド,ベクロメタゾン及びこれらのリン酸塩,プロピオン酸塩,酢酸塩,コハク酸塩等のステロイド性抗炎症剤、サリチル酸及びアスピリン,サリチルアミド,エテンザミド,サリチル酸メチル等のサリチル酸誘導体、インドメタシン,スリンダク等のインドール酢酸誘導体、フェニルブタゾン,オキシフェンブタゾン等のピラゾリジンジオン誘導体、メフェナム酸,フルフェナム酸等のアントラニル酸誘導体、イブプロフェン,ケトプロフェン,ナプロキセン等のプロピオン酸誘導体、ジクロフェナック,フェンブフェン,ブフェキサマク等のフェニル酢酸誘導体、ピロキシカム等のベンゾチアジン誘導体といった非ステロイド性抗炎症剤、グリチルリチン酸及びグリチルリチン酸ジカリウム,グリチルリチン酸モノアンモニウム等のグリチルリチン酸の塩並びに誘導体、グリチルレチン酸及びグリチルレチン酸ステアリル,ステアリン酸グリチルレチニル,3-サクシニルオキシグリチルレチン酸二ナトリウム等のグリチルレチン酸の塩並びに誘導体、グアイアズレン,グアイアズレンスルホン酸エチル,グアイアズレンスルホン酸ナトリウム,カマズレン等のアズレン誘導体、アラントイン、アロイン、アロエエモジン、シコニン及びイソブチルシコニン,アセチルシコニン,イソバレリルシコニン等のシコニン誘導体、ギンセノシドRa1,ギンセノシドRa2,ギンセノシドRb1等のギンセノシド、及び20-グルコギンセノシドRf等のギンセノシド誘導体、ペオニフロリン、ペオノール及びペオノシド,ペオノリド等のペオノール誘導体などが挙げられる。
【0015】
また本発明においては抗炎症剤として、オウゴン(Scutellariae Radix),カンゾウ(Glycyrrhizae Radix),クジン(Sophorae Radix),サイコ(Bupleuri Radix),シャクヤク(Paeoniae Radix),ショウマ(Cimicifugae Rhizoma),タイソウ(Zizyphi Fructus),チモ(Anemarrhenae Rhizoma),ボタンピ(Moutan Cortex),リュウタン(Gentianae Scabrae Radix),レンギョウ(Forsythiae Fructus)等、抗炎症剤として用いられる生薬又はその抽出物を用いることもできる。本発明に係る皮膚外用剤には、これら抗炎症剤より1種又は2種以上を選択して用いる。
【0016】
本発明においては、カッコン(Puerariae Radix)の抽出物及び抽出分画物の1種又は2種以上、もしくは4',7-ジヒドロキシイソフラボンと、抗炎症剤の1種又は2種以上とを皮膚外用剤基剤に含有させる。皮膚外用剤全量あたりの配合量としては、カッコン(Puerariae Radix)の抽出物又は抽出分画物についてはその調製方法により異なるが、0.0001〜5.0重量%程度、4',7-ジヒドロキシイソフラボンについては0.00001〜0.1重量%程度、抗炎症剤についてはその種類により異なるが、0.0001〜5.0重量%程度とするのが適切である。
【0017】
本発明に係る皮膚外用剤は、ローション剤,乳剤,ゲル剤,クリーム剤,軟膏剤,粉末剤,顆粒剤等、種々の剤型で提供することができる。また、化粧水,乳液,クリーム,美容液,パック等の皮膚化粧料、メイクアップベースローション,メイクアップベースクリーム等の下地化粧料、乳液状,油性,固形状等の各剤型のファンデーション,アイカラー,チークカラー等のメイクアップ化粧料、ハンドクリーム,レッグクリーム,ネッククリーム,ボディローション等の身体用化粧料等として提供することができる。
【0018】
なお本発明に係る皮膚外用剤には、カッコン(Puerariae Radix)抽出物等及び抗炎症剤の他に、油性成分,界面活性剤,保湿剤,顔料,紫外線吸収剤,抗酸化剤,香料,防菌防黴剤等の一般的な医薬品及び化粧料用原料や、皮膚細胞賦活剤,美白剤等の生理活性成分を含有させることができる。
【0019】
【実施例】
さらに本発明の特徴について、実施例により詳細に説明する。
【0020】
まず、本発明に係る皮膚外用剤に含有させるカッコン(Puerariae Radix)の抽出物及び抽出分画物の調製について示す。
【0021】
[カッコン抽出物1]
カッコンの乾燥粉末200gをエタノール1リットル中に浸漬し、20℃で7日間静置して抽出し、抽出液をろ過して回収した後濃縮,乾固し、凍結乾燥して、標記カッコン抽出物とした。
【0022】
[カッコン抽出物2]
カッコン500gを細切し、エタノール2リットル中にて20℃で3日間撹拌抽出し、抽出液をろ過して回収した後濃縮,乾固し、グリセリン1リットルに溶解して、標記カッコン抽出物とした。
【0023】
[カッコン抽出物3]
カッコン250gを乾燥,粉砕し、50容量%エタノール水溶液2リットル中にて20℃で7日間浸漬した後、ろ過してろ液を回収して、カッコン抽出物3とした。
【0024】
[カッコン抽出分画物1〜4]
カッコン(Puerariae Radix)500gを乾燥,粉砕し、エタノール2リットル中に浸漬して、20℃で7日間静置して抽出した後、ろ過してろ液を回収し、次いで濃縮,乾固して凍結乾燥する。この乾燥粉末36.0gをエタノール500mlに溶解し、さらに精製水1500mlを加え、600mlのDIAIONMCIゲル HP-20(三菱化学株式会社製)を添加して1時間撹拌した後、ろ過して前記樹脂を回収してカラムに充填し、水・エタノールの混合溶媒にて順次段階的に溶出した。その際、50容量%エタノール水溶液,70容量%エタノール水溶液,90容量%エタノール水溶液及び99.5容量%エタノール水溶液にて溶出される画分を回収し、それぞれ凍結乾燥して、標記抽出分画物1〜4とした。
【0025】
また、以下の本発明の実施例において配合した抗炎症剤は、医薬品又は化粧料用として市販されているものを用いた。抗炎症性生薬の抽出物の調製については、次に示す。
【0026】
[オウゴン抽出物]
オウゴン(Scutellariae Radix)300gを乾燥,粉砕し、エタノール500ml中に加えて20℃で10日間静置して抽出し、ろ過してろ液を回収した。このろ液を減圧濃縮し、凍結乾燥したものを標記抽出物とした。
【0027】
[カンゾウ抽出物]
カンゾウ(Glycyrrhizae Radix)500gを乾燥,粉砕し、熱水1リットル中にて2時間抽出した。ろ過してろ液を回収し、次いで減圧濃縮した後凍結乾燥して、標記抽出物とした。
【0028】
[クジン抽出物]
クジン(Sophorae Radix)500gを乾燥,粉砕し、50容量%エタノール水溶液1リットル中に浸漬して、25℃で7日間抽出した。ろ過してろ液を回収し、標記抽出物とした。
【0029】
[シャクヤク抽出物]
シャクヤク(Paeoniae Radix)550gを乾燥,粉砕し、50容量%エタノール水溶液1リットル中に浸漬して、撹拌しながら20℃で10日間抽出した。次いでろ過してろ液を回収し、減圧濃縮した後凍結乾燥して、標記抽出物とした。
【0030】
[タイソウ抽出物]
タイソウ(Zizyphi Fructus)600gを乾燥,粉砕し、50容量%エタノール水溶液1リットル中に浸漬して、25℃で7日間抽出した。ろ過してろ液を回収し、標記抽出物とした。
【0031】
[ボタンピ抽出物]
ボタンピ(Moutan Cortex)520gを乾燥,粉砕し、エタノール1リットル中に浸漬して10℃で14日間静置し、抽出した。ろ過してろ液を回収し、標記抽出物とした。
【0032】
[リュウタン抽出物]
リュウタン(Gentianae Scabrae Radix)650gを乾燥,粉砕し、熱水1リットル中にて4時間抽出した。ろ過してろ液を回収し、減圧濃縮した後凍結乾燥して、標記抽出物とした。
【0033】
[レンギョウ抽出物]
レンギョウ(Forsythiae Fructus)750gを粉砕し、1,3-ブチレングリコール1.2リットル中に浸漬して、撹拌しながら15℃で10日間抽出した。ろ過してろ液を回収し、標記抽出物とした。
【0034】
続いて、本発明に係る皮膚外用剤についての実施例の処方を示す。
【0035】
[実施例1] ローション剤
(1)エタノール 20.00(重量%)
(2)ポリオキシエチレン(60E.O.)硬化ヒマシ油 1.00
(3)カッコン抽出物1 0.05
(4)ジプロピレングリコール 5.00
(5)1,3-ブチレングリコール 10.00
(6)グアイアズレンスルホン酸ナトリウム 0.20
(7)パラオキシ安息香酸メチル 0.10
(8)精製水 63.65
製法:(1)に(2),(3)を添加して溶解し、アルコール相とする。一方、(8)に(4)〜(7)を順次溶解して水相とする。水相にアルコール相を添加し、撹拌,混合する。
【0036】
[実施例2] 乳剤
(1)セタノール 1.00(重量%)
(2)ミツロウ 0.50
(3)ワセリン 2.00
(4)スクワラン 6.00
(5)ジメチルポリシロキサン 2.00
(6)ポリオキシエチレン(20E.O.)ソルビタン 1.00
モノステアリン酸エステル
(7)グリセリルモノステアリン酸エステル 1.00
(8)グリセリン 4.00
(9)1,3-ブチレングリコール 4.00
(10)パラオキシ安息香酸メチル 0.10
(11)精製水 62.18
(12)カルボキシビニルポリマー 10.00
(1.0重量%水溶液)
(13)水酸化カリウム(10.0重量%水溶液) 1.00
(14)アラントイン 0.20
(15)エタノール 5.00
(16)カッコン抽出分画物1 0.02
製法:(1)〜(7)の油相成分を混合し、加熱溶解して75℃とする。一方、(8)〜(11)の水相成分を混合,溶解して75℃とする。これに前記油相を加えて予備乳化した後、(12)を添加してホモミキサーにて均一に乳化し、次いで(13)を加えて増粘させた後冷却し、40℃で(14)を添加,混合し、次いで(16)を(15)に溶解して加え、混合する。
【0037】
[実施例3] 乳剤
(1)セタノール 1.0(重量%)
(2)ミツロウ 0.5
(3)ワセリン 2.0
(4)スクワラン 6.0
(5)ジメチルポリシロキサン 2.0
(6)ポリオキシエチレン(20E.O.)ソルビタン 1.0
モノステアリン酸エステル
(7)グリセリルモノステアリン酸エステル 1.0
(8)グリチルレチン酸ステアリル 0.2
(9)グリセリン 4.0
(10)1,3-ブチレングリコール 4.0
(11)パラオキシ安息香酸メチル 0.1
(12)精製水 61.9
(13)カルボキシビニルポリマー 10.0
(1.0重量%水溶液)
(14)水酸化カリウム(10.0重量%水溶液) 1.0
(15)エタノール 5.0
(16)カッコン抽出物1 0.1
(17)オウゴン抽出物 0.2
製法:(1)〜(8)の油相成分を混合し、加熱溶解して75℃とする。一方、(9)〜(12)の水相成分を混合,溶解して75℃とする。これに前記油相を加えて予備乳化した後、(13)を添加してホモミキサーにて均一に乳化し、次いで(14)を加えて増粘させた後冷却し、40℃で(16),(17)を(15)に溶解して加え、混合する。
【0038】
[実施例4] 水中油型クリーム剤
(1)ミツロウ 6.00(重量%)
(2)セタノール 5.00
(3)還元ラノリン 8.00
(4)スクワラン 27.50
(5)グリセリル脂肪酸エステル 4.00
(6)親油型グリセリルモノステアリン酸エステル 2.00
(7)ポリオキシエチレン(20E.O.)ソルビタン 5.00
モノラウリン酸エステル
(8)グリチルレチン酸ステアリル 0.25
(9)プロピレングリコール 5.00
(10)パラオキシ安息香酸メチル 0.10
(11)カッコン抽出分画物2 0.02
(12)精製水 36.93
(13)クジン抽出物 0.20
製法:(1)〜(8)の油相成分を混合,溶解して75℃とする。一方、(10),(11)を(9)に溶解して(12)に加えて混合,溶解し、75℃に加熱する。次いで、この水相成分に前記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し、冷却後40℃にて(13)を添加,混合する。
【0039】
[実施例5] 水中油型クリーム剤
(1)ミツロウ 6.00(重量%)
(2)セタノール 5.00
(3)還元ラノリン 8.00
(4)スクワラン 27.50
(5)グリセリル脂肪酸エステル 4.00
(6)親油型グリセリルモノステアリン酸エステル 2.00
(7)ポリオキシエチレン(20E.O.)ソルビタン 5.00
モノラウリン酸エステル
(8)プロピレングリコール 5.00
(9)パラオキシ安息香酸メチル 0.10
(10)カッコン抽出分画物3 0.02
(11)精製水 36.38
(12)ブフェキサマク 1.00
製法:(1)〜(7)の油相成分を混合,溶解して75℃とする。一方、(9),(10)を(8)に溶解して(11)に加えて混合,溶解し、75℃に加熱する。次いで、この水相成分に前記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し、冷却後40℃にて(12)を添加,混合する。
【0040】
[実施例6] ゲル剤
(1)ジプロピレングリコール 10.00(重量%)
(2)カルボキシビニルポリマー 0.50
(3)水酸化カリウム(10.0重量%水溶液) 1.00
(4)パラオキシ安息香酸メチル 0.10
(5)カッコン抽出分画物3 0.02
(6)カンゾウ抽出物 0.30
(7)精製水 88.08
製法:(7)に(2),(6)を均一に溶解した後、(1)に(4),(5)を溶解して添加し、次いで(3)を加えて増粘させる。
【0041】
[実施例7] 水中油型乳剤型軟膏
(1)白色ワセリン 25.0(重量%)
(2)ステアリルアルコール 25.0
(3)グリセリン 12.0
(4)ラウリル硫酸ナトリウム 1.0
(5)パラオキシ安息香酸メチル 0.1
(6)精製水 34.4
(7)カッコン抽出分画物4の1.0(w/v)% 1.5
エタノール溶液
(8)ボタンピ抽出物 1.0
製法:(1)〜(4)の油相成分を混合,加熱して均一に溶解し、75℃とする。一方、(5),(6)の水相成分を混合,加熱して75℃とする。この水相成分に前記油相成分を撹拌しながら徐々に添加して乳化し、冷却した後、40℃にて(7),(8)を添加,混合する。
【0042】
[実施例8] リポソーム剤
(1)グリセリン 2.0(重量%)
(2)1,3-ブチレングリコール 3.0
(3)ポリオキシエチレン(25E.O.)オレイルエーテル 0.2
(4)エタノール 10.0
(5)パラオキシ安息香酸メチル 0.1
(6)精製水 79.7
(7)4',7-ジヒドロキシイソフラボン,シャクヤク 5.0
抽出物内包リポソーム
製法:(5)を(4)に溶解し、(1)〜(3)とともに(6)に添加して均一に混合し、これに(7)を加えて分散する。なお、(7)の4',7-ジヒドロキシイソフラボン,シャクヤク抽出物内包リポソームは、4',7-ジヒドロキシイソフラボン1.0(w/v)%及びシャクヤク抽出物2.0(w/v)%を含有する50容量%エタノール水溶液100mlに、大豆レシチン80gを添加して55℃で懸濁し、次いで超音波処理してリポソームを調製し、遠心分離により回収して得た。
【0043】
[実施例9] 油中水型エモリエントクリーム
(1)流動パラフィン 30.0(重量%)
(2)マイクロクリスタリンワックス 2.0
(3)ワセリン 5.0
(4)ジグリセリルジオレイン酸エステル 5.0
(5)L-グルタミン酸ナトリウム 1.6
(6)L-セリン 0.4
(7)プロピレングリコール 3.0
(8)パラオキシ安息香酸メチル 0.1
(9)カッコン抽出物2 0.5
(10)レンギョウ抽出物 1.5
(11)精製水 50.8
(12)香料 0.1
製法:(5),(6)を(11)の一部に溶解して50℃とし、あらかじめ50℃に加温した(4)に撹拌しながら徐々に添加する。これをあらかじめ混合し、70℃に加熱溶解した(1)〜(3)に均一に分散する。これに、(7)〜(10)を(11)の残部に添加し、70℃に加熱したものを撹拌しながら加え、ホモミキサーにて乳化する。冷却後、40℃にて(12)を添加,混合する。
【0044】
[実施例10] メイクアップベースクリーム
(1)ステアリン酸 12.00(重量%)
(2)セタノール 2.00
(3)グリセリルトリ2-エチルヘキサン酸エステル 2.50
(4)自己乳化型グリセリルモノステアリン酸 2.00
エステル
(5)プロピレングリコール 10.00
(6)カッコン抽出物1 0.02
(7)パラオキシ安息香酸メチル 0.10
(8)リュウタン抽出物 0.05
(9)水酸化カリウム 0.30
(10)精製水 68.43
(11)酸化チタン 2.00
(12)ベンガラ 0.40
(13)黄酸化鉄 0.10
(14)香料 0.10
製法:(1)〜(4)の油相成分を混合,溶解して75℃とする。一方、(5)に(6),(7)を溶解して(8),(9)とともに(10)に加えて混合,加熱溶解し、これに(11)〜(13)の顔料成分を添加してホモミキサーにて均一に分散して75℃とする。次いで、この水相成分に前記油相成分を添加してホモミキサーにて均一に乳化し、冷却後40℃にて(14)を添加,混合する。
【0045】
[実施例11] 乳液状ファンデーション
(1)ステアリン酸 2.00(重量%)
(2)スクワラン 5.00
(3)ミリスチン酸オクチルドデシル 5.00
(4)セタノール 1.00
(5)デカグリセリルモノイソパルミチン酸エステル 9.00
(6)1,3-ブチレンクリコール 6.00
(7)パラオキシ安息香酸メチル 0.10
(8)水酸化カリウム 0.08
(9)精製水 51.57
(10)酸化チタン 9.00
(11)タルク 7.40
(12)ベンガラ 0.50
(13)黄酸化鉄 1.10
(14)黒酸化鉄 0.10
(15)カッコン抽出物3 1.00
(16)タイソウ抽出物 1.00
(17)香料 0.15
製法:(1)〜(5)の油相成分を混合,溶解して75℃とする。一方、(6)〜(9)の水相成分を混合,加熱溶解し、これに(10)〜(14)の顔料成分を添加してホモミキサーにて均一に分散して75℃とする。次いで、この水相成分に前記油相成分を添加してホモミキサーにて均一に乳化し、冷却後40℃にて(15)〜(17)を添加,混合する。
【0046】
[実施例12] ハンドクリーム
(1)セタノール 4.00(重量%)
(2)ワセリン 2.00
(3)流動パラフィン 10.00
(4)グリセリルモノステアリン酸エステル 1.50
(5)ポリオキシエチレン(60E.O.)グリセリル 2.50
イソステアリン酸エステル
(6)酢酸トコフェロール 0.25
(7)グリセリン 20.00
(8)パラオキシ安息香酸メチル 0.10
(9)カッコン抽出分画物1 0.01
(10)グリチルリチン酸ジカリウム 0.02
(11)精製水 59.62
製法:(1)〜(6)の油相成分を混合,溶解して75℃とする。一方、(8),(9)を(7)に溶解して(10)とともに(11)に加えて混合,溶解し、75℃とする。次いで、この水相成分に前記油相成分を添加してホモミキサーにて均一に乳化し、冷却する。
【0047】
上記した本発明に係る実施例のうち、実施例1〜実施例8について、中波長紫外線(UVB)による皮膚のしわ形成に対する抑制効果を評価した。その際実施例1〜実施例8において、それぞれ配合したカッコン抽出物又は分画物及び抗炎症剤、或いは4',7-ジヒドロキシイソフラボン,シャクヤク抽出物内包リポソームを、表1に示すように代替して比較例1〜比較例8とし、同時に評価を行った。評価は、ヘアレスマウス5匹を1群とし、各群について実施例及び比較例をそれぞれ0.2gずつ1日1回背部に塗布し、100mJ/cm2/回のUVBを1週間に3回、20週間照射し、ヘアレスマウス皮膚におけるしわの形成状況を観察し、表2に示す判定基準に従って点数化して評価した。この際、精製水のみを塗布した群を対照とした。結果は各群の平均値を算出し、UVB照射日数との関係により表3に示した。
【0048】
【表1】
【0049】
【表2】
【0050】
【表3】
【0051】
表3より明らかなように、対照においては、UVB照射日数が10週を越える頃には皮膚に形成されたしわの深さは中程度にまで達し、20週後には深いしわの形成が認められていた。有効成分として、カッコン抽出物又は抽出分画物のみを含有する比較例1及び比較例6塗布群では、20週後に軽微なしわの形成が認められる程度で、しわの形成は良好に抑制されており、また抗炎症剤を含有し、カッコン抽出物又は抽出分画物もしくは4',7-ジヒドロキシイソフラボンを含有しない他の比較例塗布群でも、対照に比べてしわ形成に対する抑制効果は認められていたが、それぞれ対応する実施例塗布群では、いずれも20週後に微小なしわの形成が認められた程度で、それぞれ対応する比較例塗布群に比べて、しわ形成に対する抑制効果は有意に向上していた。
【0052】
続いて、本発明の実施例1〜実施例12について使用試験を行い、皮膚の老化症状の改善効果を評価した。その際、実施例9〜実施例12において、配合したカッコン抽出物又は抽出分画物及び抗炎症剤を表4に示すように代替して比較例9〜比較例12とし、上記比較例1〜比較例8とともに同時に使用試験に供した。
【0053】
【表4】
【0054】
皮膚の老化症状の改善効果は、小じわ形成及び皮膚弾性の低下が顕著に認められる40才代〜60才代の女性パネラー20名を1群とし、各群に実施例及び比較例のそれぞれをブラインドにて1日2回、2カ月間連続して使用させて評価した。小じわの程度については肉眼観察及び写真撮影により評価し、皮膚弾性についてはキュートメーターにより測定して、それぞれ使用試験開始前及び終了後の状態を比較し、「改善」,「やや改善」,「変化なし」の3段階で評価した。結果は、各評価を得たパネラー数にて表5に示した。
【0055】
【表5】
【0056】
表5より明らかなように、有効成分として抗炎症剤を含有するがカッコン抽出物等を含有しない比較例2〜比較例5,比較例7,比較例8及び比較例10〜比較例12の各使用群においては、小じわ及び皮膚弾性の改善傾向は認められるものの、明確な改善を認めたパネラーはさほど多くなかった。カッコンの抽出物又は抽出分画物のみを含有する比較例1,比較例6,及び比較例9の各使用群のそれぞれにおいては、かなり良好な小じわ及び皮膚弾性の改善傾向が認められていたが、実施例使用群においては、それぞれ対応する比較例使用群に比べて、明確な改善を認めたパネラーは有意に多くなっていた。
【0057】
また、本発明の実施例1〜実施例12及び比較例1〜比較例12について、肌荒れ症状の改善効果を評価した。肌荒れ症状の改善効果は、顕著な肌荒れ症状を呈する20才代〜60才代の女性パネラー20名を1群とし、各群に実施例及び比較例のそれぞれをブラインドにて1日2回、2カ月間連続して使用させて評価した。使用試験開始前及び終了後の皮膚の状態を、表6に示す評価基準に従って評価,点数化し、20名の平均値を算出して表7に示した。
【0058】
【表6】
【0059】
【表7】
【0060】
表7より明らかなように、本発明の実施例使用群ではいずれにおいても顕著な肌荒れの改善が認められ、使用試験終了後において、皮膚の状態はほぼ良好〜良好な状態にまで改善されていた。これに対し比較例使用群においても、かなり良好な肌荒れの改善が認められていたが、その程度はそれぞれ対応する実施例使用群に比べて小さいものであった。
【0061】
なお実施例1〜実施例12については、25℃で6カ月間保存した場合において状態の変化は全く認められず、男性パネラー30名による48時間の背部閉塞貼付試験においても、問題となる皮膚刺激性反応は認められなかった。
【0062】
【発明の効果】
以上詳述したように、本発明により、安定性及び安全性が良好で、肌荒れ及び皮膚の老化の防止,改善効果が相乗的に向上した皮膚外用剤を得ることができた。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an external preparation for skin which synergistically improves the effect of preventing and improving rough skin and aging of the skin. More specifically, an external preparation for skin comprising a combination of one or more selected from an extract and extract of cuckoo, or 4 ', 7-dihydroxyisoflavone, which is an active ingredient thereof, and an anti-inflammatory agent. About.
[0002]
[Prior art]
It is known that inflammatory reaction of the skin and aging of the skin progress due to aging, exposure to ultraviolet rays, oxidative stress due to reactive oxygen species generated in the skin tissue, contact with drugs and various allergens, and the like. In the field of topical skin preparations, many physiologically active ingredients such as reactive oxygen species scavengers, anti-inflammatory agents, and antiallergic agents have been searched and examined in order to prevent inflammation and aging of the skin. In addition, as it becomes clear that aging symptoms of skin progress due to modification of collagen, which is a component of the dermis matrix, due to aging and stress, studies on substances that have the effect of promoting their production in skin tissue Has been made. In recent years, there has been an increasing tendency to demand such components from plants, reflecting the natural and plant orientation of consumers.
[0003]
However, among the above-mentioned ingredients of plant origin that have already been reported, the activity is low, so that a considerably high concentration is required to obtain a sufficient action effect when blended with an external preparation for skin, stability or safety. When there are problems with sexuality, or there are things that give unfavorable color or odor to the external preparation for skin, when blended with external preparation for skin, all of the stability and safety of the preparation, and the action effect There are few things that can be satisfied in terms of the situation. In addition, since the inflammatory reaction and aging of the skin proceed with various factors involved in a complicated manner, sufficient effects cannot be obtained even if a substance that acts only on a part of the reaction is used.
[0004]
[Problems to be solved by the invention]
Accordingly, an object of the present invention is to obtain an external preparation for skin that suppresses complex skin inflammatory reactions and the like, and synergistically improves the effect of preventing and improving rough skin and aging of the skin.
[0005]
[Means for Solving the Problems]
As a result of various studies to solve the above-mentioned problems, the present inventors have found a high fibroblast activation action and a collagen production promotion action in the extract and extract fraction of cucumber ( Puerariae Radix ), and further selected from these 1 The combination of seeds or two or more and one or more anti-inflammatory agents in the topical skin preparation can prevent skin roughness and skin aging, and provide a synergistic improvement in the improvement effect. As a result, the present invention has been completed.
[0006]
In particular, the use of an extract with a high content of 4 ′, 7-dihydroxyisoflavone (daidzein) as a cuckoo extract and extract fraction provides a good effect, and can also be used in combination with 4 ′, 7-dihydroxyisoflavone itself. May be.
[0007]
In addition, as for the cuckoo extract, mucopolysaccharide fragmentation suppression, active oxygen elimination, antioxidant action (JP-A-6-24937), fat synthesis promoting action (JP-A-11-199499), hair papilla activating action (JP-A-11) -240823) has been disclosed, and hyaluronic acid production promoting action has also been reported (Abstracts of the 120th Annual Meeting of the Pharmaceutical Society of Japan 2, page 58, 2000), but the production promotion action of type I collagen is completely known. It is not done. Furthermore, a metabolite of 7-isopropoxyisoflavone has been reported to promote type I collagen synthesis (Calcified Tissue International 55 (5) 356-362 (1994)). Although it is well known that dihydroxyisoflavone has an antiacetylcholine action, no such report has been made so far.
[0008]
In addition, anti-inflammatory agents have long been blended in topical skin preparations with the expectation of improving skin roughness. However, the extract or extract of cuckoo or 4 ', 7-dihydroxyisoflavone and anti-inflammatory agents The effect of the present invention obtained by using together is not even suggested so far.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
Cucon ( Puerariae Radix ) used in the present invention is a root excluding pericy of the deciduous Fujimoto ( Pueraria lobata Ohwi) belonging to the leguminosae ( Leguminosae ), Japanese, Korean and Chinese square brackets, Board brackets and powder brackets can be used.
[0010]
Cascon ( Puerariae Radix ) may be subjected to extraction as it is, but considering extraction efficiency, it is preferable to perform extraction after processing such as shredding, drying, and pulverization. Extraction is performed by immersing in an extraction solvent. In order to increase the extraction efficiency, stirring may be performed, or homogenization may be performed in an extraction solvent. The extraction temperature is suitably about 5 ° C. to the boiling point of the extraction solvent. The extraction time varies depending on the type of extraction solvent and the extraction temperature, but is suitably about 4 hours to 14 days.
[0011]
Extraction solvents include water, lower alcohols such as methanol, ethanol, propanol, and isopropanol, polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, dipropylene glycol, and glycerin, and ethers such as ethyl ether and propyl ether. , Polar organic solvents such as esters such as ethyl acetate and butyl acetate, and ketones such as acetone and ethyl methyl ketone can be used, and one or more of these are selected and used. Further, physiological saline, phosphate buffer, phosphate buffered saline, or the like may be used.
[0012]
The extract from the above-mentioned solvent of cucumber ( Puerariae Radix ) can be incorporated into the external preparation for skin according to the present invention as it is, but the concentrated and dried solid can be dissolved again in water or a polar solvent, or these It may be used after performing purification treatment such as decolorization, deodorization, desalting, etc. within the range that does not impair the physiological action, or after fractionation treatment by column chromatography or the like. In particular, when adsorbed on an ion-exchange adsorbing resin and then eluted sequentially with a mixed solvent of water and ethanol, the fraction eluted with an aqueous solution of 50% to 99.5% by volume of ethanol contains 4 ', 7-dihydroxyisoflavone. It is contained most and is most preferably used from the viewpoint of promoting collagen production. As the ion exchange resin, DIAION MCI gel HP-20 (manufactured by Mitsubishi Chemical Corporation) and the like are preferably used. The extract of Kacon and its processed products and fractions can be freeze-dried after each processing and fractionation and dissolved in a solvent before use. It can also be used by encapsulating in vesicles such as liposomes or microcapsules.
[0013]
In the present invention, purified 4 ′, 7-dihydroxyisoflavone may be used in place of the above-described extract of cuckoo or a fraction thereof.
[0014]
In the present invention, the anti-inflammatory agent used in combination with one or more of the extracts and extract fractions of the above-mentioned cuckon ( Puerariae Radix ), or 4 ′, 7-dihydroxyisoflavone is used as cortisone, hydrocortisone, prednisolone, methyl Prednisolone, dexamethasone, betamethasone, triamcinolone, triamcinolone acetonide, fluocinolone acetonide, fluocinonide, beclomethasone and steroidal anti-inflammatory agents such as phosphate, propionate, acetate, succinate, salicylic acid and aspirin, Salicylic acid derivatives such as salicylamide, etenzamide and methyl salicylate, indoleacetic acid derivatives such as indomethacin and sulindac, pyrazolidinedione derivatives such as phenylbutazone and oxyphenbutazone, mefenamic acid and flufe Non-steroidal anti-inflammatory agents such as anthranilic acid derivatives such as namic acid, propionic acid derivatives such as ibuprofen, ketoprofen and naproxen, phenylacetic acid derivatives such as diclofenac, fenbufen and bufexamac, and benzothiazine derivatives such as piroxicam, glycyrrhizic acid and dipotassium glycyrrhizinate, Glycyrrhizic acid salts and derivatives such as monoammonium glycyrrhizinate, glycyrrhetinic acid and stearyl glycyrrhetinate, glycyrrhetinyl stearate, 3-succinyloxyglycyrrhetinic acid disodium salt and derivatives, guaiazulene, ethyl guaiazulene sulfonate, guaiazulene sulfone Azulene derivatives such as sodium acid and camazulene, allantoin, aloin, aloe Jin, shikonin and isobutyl shikonin, acetyl shikonin, shikonin derivatives such isovaleryloxy shikonin, ginsenoside R a1, ginsenoside derivatives such as ginsenoside R a2, Ginsenoside such Ginsenoside R b1, and 20-glucoside Gin Seno glucoside R f, paeoniflorin, Examples include peonol and peonoside derivatives such as peonoside and peonolide.
[0015]
As anti-inflammatory agent in the present invention, scutellaria root (Scutellariae Radix), licorice (Glycyrrhizae Radix), Sophora root (Sophorae Radix), Psycho (Bupleuri Radix), peony (Paeoniae Radix), Cimicifuga (Cimicifugae Rhizoma), gymnastics (Zizyphi Fructus ), Chimo ( Anemarrhenae Rhizoma ), Buttonpi ( Moutan Cortex ), Ryutan ( Gentianae Scabrae Radix ), Forsythiae Fructus, and other herbal medicines used as anti-inflammatory agents or extracts thereof can also be used. For the external preparation for skin according to the present invention, one or more of these anti-inflammatory agents are selected and used.
[0016]
In the present invention, one or more kinds of extracts and extracted fractions of cucumber ( Puerariae Radix ), or 4 ', 7-dihydroxyisoflavone and one or more kinds of anti-inflammatory agents are applied to the skin. Included in the base. The blending amount per total amount of the external preparation for skin is about 0.0001 to 5.0% by weight, 4 ′, 7-dihydroxy, although it depends on the preparation method of the extract or extract fraction of cucumber ( Puerariae Radix ). For isoflavones, about 0.00001 to 0.1% by weight, and for anti-inflammatory agents, depending on the type, it is appropriate to set them to about 0.0001 to 5.0% by weight.
[0017]
The external preparation for skin according to the present invention can be provided in various dosage forms such as lotions, emulsions, gels, creams, ointments, powders, granules and the like. In addition, skin cosmetics such as lotion, milky lotion, cream, beauty essence, packs, foundation cosmetics such as makeup base lotion and makeup base cream, foundations for each dosage form such as emulsion, oily, solid, etc. It can be provided as makeup cosmetics such as color and teak color, and body cosmetics such as hand cream, leg cream, neck cream and body lotion.
[0018]
In addition, skin external preparations according to the present invention include oil components, surfactants, moisturizers, pigments, UV absorbers, antioxidants, perfumes, anti-inflammatory agents, in addition to extracts such as Cucon ( Puerariae Radix ) and anti-inflammatory agents. General pharmaceutical ingredients such as antifungal agents and cosmetic raw materials, and physiologically active ingredients such as skin cell activators and whitening agents can be included.
[0019]
【Example】
Further, the features of the present invention will be described in detail with reference to examples.
[0020]
First, preparation of an extract and extract fraction of cucumber ( Puerariae Radix ) to be included in the external preparation for skin according to the present invention will be described.
[0021]
[Cuckoo extract 1]
200g of dried powder of cocoon is immersed in 1 liter of ethanol, left to stand at 20 ° C for 7 days and extracted. The extract is collected by filtration, concentrated, dried and freeze-dried. It was.
[0022]
[Cuckoo extract 2]
Chop 500 g, chop and extract in 2 liters of ethanol at 20 ° C. for 3 days, collect the extract by filtration, concentrate, dry, dissolve in 1 liter of glycerin, did.
[0023]
[Cuckoo extract 3]
250 g of the cocoon was dried and pulverized, immersed in 2 liters of a 50% by volume ethanol aqueous solution at 20 ° C. for 7 days, filtered, and the filtrate was recovered to obtain the cocoon extract 3.
[0024]
[Cracoon extract fractions 1-4]
500 g of cucumber ( Puerariae Radix ) is dried, ground, immersed in 2 liters of ethanol, left to stand at 20 ° C. for 7 days, extracted, filtered to collect the filtrate, then concentrated, dried and frozen dry. 36.0 g of this dry powder is dissolved in 500 ml of ethanol, 1500 ml of purified water is further added, 600 ml of DIAIONMCI gel HP-20 (manufactured by Mitsubishi Chemical Corporation) is added and stirred for 1 hour, and then filtered to remove the resin. It was collected and packed in a column, and eluted stepwise in a mixed solvent of water and ethanol. At that time, fractions eluted with 50% by volume ethanol aqueous solution, 70% by volume ethanol aqueous solution, 90% by volume ethanol aqueous solution and 99.5% by volume ethanol aqueous solution were collected and lyophilized, respectively, and the extracted fractions were extracted. 1-4.
[0025]
Moreover, what was marketed as a pharmaceutical or cosmetics was used for the anti-inflammatory agent mix | blended in the following Example of this invention. The preparation of the anti-inflammatory crude drug extract is described below.
[0026]
[Ougon extract]
300 g of Ogon ( Scutellariae Radix ) was dried, pulverized, added to 500 ml of ethanol, left standing at 20 ° C. for 10 days for extraction, and filtered to collect the filtrate. The filtrate was concentrated under reduced pressure and lyophilized to give the title extract.
[0027]
[Licorice extract]
500 g of licorice ( Glycyrrhizae Radix ) was dried, ground, and extracted in 1 liter of hot water for 2 hours. The filtrate was collected by filtration, then concentrated under reduced pressure and then lyophilized to obtain the title extract.
[0028]
[Cuzin extract]
500 g of kujin ( Sophorae Radix ) was dried, pulverized, immersed in 1 liter of 50 vol% ethanol aqueous solution, and extracted at 25 ° C. for 7 days. The filtrate was collected by filtration and used as the title extract.
[0029]
[Peonies extract]
550 g of peony ( Paeoniae Radix ) was dried, pulverized, immersed in 1 liter of 50% by volume ethanol aqueous solution, and extracted at 20 ° C. for 10 days with stirring. The filtrate was then collected by filtration, concentrated under reduced pressure, and lyophilized to give the title extract.
[0030]
[Tithus extract]
600 g of Taisou ( Zizyphi Fructus ) was dried, pulverized, immersed in 1 liter of a 50% by volume ethanol aqueous solution, and extracted at 25 ° C. for 7 days. The filtrate was collected by filtration and used as the title extract.
[0031]
[Button pi extract]
520 g of button pin ( Moutan Cortex ) was dried, pulverized, immersed in 1 liter of ethanol, allowed to stand at 10 ° C. for 14 days, and extracted. The filtrate was collected by filtration and used as the title extract.
[0032]
[Ryutan extract]
650 g of Ryutan ( Gentianae Scabrae Radix ) was dried, ground and extracted in 1 liter of hot water for 4 hours. The filtrate was collected by filtration, concentrated under reduced pressure, and lyophilized to give the title extract.
[0033]
[Forsythia extract]
Forsythiae Fructus (750 g) was pulverized, immersed in 1.2 liters of 1,3-butylene glycol, and extracted for 10 days at 15 ° C. with stirring. The filtrate was collected by filtration and used as the title extract.
[0034]
Then, the prescription of the Example about the skin external preparation which concerns on this invention is shown.
[0035]
[Example 1] Lotion agent (1) Ethanol 20.00 (wt%)
(2) Polyoxyethylene (60E.O.) hydrogenated castor oil 1.00
(3) Cuckoo extract 1 0.05
(4) Dipropylene glycol 5.00
(5) 1,3-butylene glycol 10.00
(6) Sodium guaiazulene sulfonate 0.20
(7) Methyl paraoxybenzoate 0.10
(8) Purified water 63.65
Manufacturing method: Add (2) and (3) to (1) and dissolve to make the alcohol phase. On the other hand, (4) to (7) are sequentially dissolved in (8) to obtain an aqueous phase. Add the alcohol phase to the water phase and stir and mix.
[0036]
[Example 2] Emulsion (1) Cetanol 1.00 (wt%)
(2) Beeswax 0.50
(3) Petrolatum 2.00
(4) Squalane 6.00
(5) Dimethylpolysiloxane 2.00
(6) Polyoxyethylene (20E.O.) sorbitan 1.00
Monostearate (7) Glyceryl monostearate 1.00
(8) Glycerin 4.00
(9) 1,3-butylene glycol 4.00
(10) Methyl paraoxybenzoate 0.10
(11) Purified water 62.18
(12) Carboxyvinyl polymer 10.00
(1.0 wt% aqueous solution)
(13) Potassium hydroxide (10.0 wt% aqueous solution) 1.00
(14) Allantoin 0.20
(15) Ethanol 5.00
(16) Cuckoo extract fraction 1 0.02
Production method: The oil phase components (1) to (7) are mixed and dissolved by heating to 75 ° C. On the other hand, the water phase components (8) to (11) are mixed and dissolved to 75 ° C. After preliminarily emulsifying by adding the oil phase to this, (12) was added and uniformly emulsified with a homomixer, and then (13) was added to increase the viscosity, followed by cooling at 40 ° C. (14) Are added and mixed, then (16) is dissolved in (15) and added and mixed.
[0037]
[Example 3] Emulsion (1) Cetanol 1.0 (wt%)
(2) Beeswax 0.5
(3) Vaseline 2.0
(4) Squalane 6.0
(5) Dimethylpolysiloxane 2.0
(6) Polyoxyethylene (20E.O.) sorbitan 1.0
Monostearate (7) Glyceryl monostearate 1.0
(8) Stearyl glycyrrhetinate 0.2
(9) Glycerin 4.0
(10) 1,3-butylene glycol 4.0
(11) Methyl paraoxybenzoate 0.1
(12) Purified water 61.9
(13) Carboxyvinyl polymer 10.0
(1.0 wt% aqueous solution)
(14) Potassium hydroxide (10.0 wt% aqueous solution) 1.0
(15) Ethanol 5.0
(16) Cuckoo extract 1 0.1
(17) Ogon extract 0.2
Production method: The oil phase components (1) to (8) are mixed and dissolved by heating to 75 ° C. On the other hand, the aqueous phase components (9) to (12) are mixed and dissolved to 75 ° C. After preliminarily emulsifying by adding the oil phase to this, (13) was added and uniformly emulsified with a homomixer, and then (14) was added to increase the viscosity, followed by cooling at 40 ° C. (16) , (17) are dissolved in (15) and added.
[0038]
[Example 4] Oil-in-water cream (1) Beeswax 6.00 (wt%)
(2) Cetanol 5.00
(3) Reduced lanolin 8.00
(4) Squalane 27.50
(5) Glyceryl fatty acid ester 4.00
(6) Lipophilic glyceryl monostearate 2.00
(7) Polyoxyethylene (20E.O.) sorbitan 5.00
Monolaurate (8) Stearyl glycyrrhetinate 0.25
(9) Propylene glycol 5.00
(10) Methyl paraoxybenzoate 0.10
(11) Cuckoo extract fraction 2 0.02
(12) Purified water 36.93
(13) Kujin extract 0.20
Manufacturing method: The oil phase components (1) to (8) are mixed and dissolved to 75 ° C. On the other hand, (10) and (11) are dissolved in (9), added to (12), mixed and dissolved, and heated to 75 ° C. Next, the oil phase component is added to the aqueous phase component and pre-emulsified, and then uniformly emulsified with a homomixer. After cooling, (13) is added and mixed at 40 ° C.
[0039]
[Example 5] Oil-in-water cream (1) Beeswax 6.00 (wt%)
(2) Cetanol 5.00
(3) Reduced lanolin 8.00
(4) Squalane 27.50
(5) Glyceryl fatty acid ester 4.00
(6) Lipophilic glyceryl monostearate 2.00
(7) Polyoxyethylene (20E.O.) sorbitan 5.00
Monolaurate (8) Propylene glycol 5.00
(9) Methyl paraoxybenzoate 0.10
(10) Cuckoo extract fraction 3 0.02
(11) Purified water 36.38
(12) Bufexamac 1.00
Production method: The oil phase components (1) to (7) are mixed and dissolved to 75 ° C. On the other hand, (9) and (10) are dissolved in (8), mixed and dissolved in (11), and heated to 75 ° C. Next, the oil phase component is added to the aqueous phase component and pre-emulsified, and then uniformly emulsified with a homomixer. After cooling, (12) is added and mixed at 40 ° C.
[0040]
[Example 6] Gel agent (1) Dipropylene glycol 10.00 (wt%)
(2) Carboxyvinyl polymer 0.50
(3) Potassium hydroxide (10.0 wt% aqueous solution) 1.00
(4) Methyl paraoxybenzoate 0.10
(5) Cuckoo extract fraction 3 0.02
(6) Licorice extract 0.30
(7) Purified water 88.08
Production method: (2) and (6) are uniformly dissolved in (7), (4) and (5) are dissolved and added to (1), and then (3) is added to increase the viscosity.
[0041]
[Example 7] Oil-in-water emulsion type ointment (1) White petrolatum 25.0 (% by weight)
(2) Stearyl alcohol 25.0
(3) Glycerin 12.0
(4) Sodium lauryl sulfate 1.0
(5) Methyl paraoxybenzoate 0.1
(6) Purified water 34.4
(7) 1.0 (w / v)% of parentheses extracted fraction 4 1.5
Ethanol solution (8) Buttonpi extract 1.0
Production method: The oil phase components (1) to (4) are mixed and heated to dissolve uniformly to 75 ° C. On the other hand, the aqueous phase components (5) and (6) are mixed and heated to 75 ° C. The oil phase component is gradually added to the aqueous phase component while stirring to emulsify, and after cooling, (7) and (8) are added and mixed at 40 ° C.
[0042]
[Example 8] Liposome agent (1) Glycerin 2.0 (wt%)
(2) 1,3-butylene glycol 3.0
(3) Polyoxyethylene (25E.O.) oleyl ether 0.2
(4) Ethanol 10.0
(5) Methyl paraoxybenzoate 0.1
(6) Purified water 79.7
(7) 4 ', 7-dihydroxyisoflavone, peony 5.0
Extract encapsulated liposome production method: Dissolve (5) in (4), add to (6) together with (1) to (3), mix uniformly, add (7) to this and disperse. The liposome encapsulating 4 ', 7-dihydroxyisoflavone and peony extract of (7) is 1.0 (w / v)% of 4', 7-dihydroxyisoflavone and 2.0 (w / v)% of peony extract. 80 g of soybean lecithin was added to 100 ml of a 50 vol% ethanol aqueous solution containing and suspended at 55 ° C., followed by sonication to prepare liposomes, which were collected by centrifugation.
[0043]
[Example 9] Water-in-oil emollient cream (1) Liquid paraffin 30.0 (wt%)
(2) Microcrystalline wax 2.0
(3) Vaseline 5.0
(4) Diglyceryl dioleate 5.0
(5) Sodium L-glutamate 1.6
(6) L-serine 0.4
(7) Propylene glycol 3.0
(8) Methyl paraoxybenzoate 0.1
(9) Cuckoo extract 2 0.5
(10) Forsythia extract 1.5
(11) Purified water 50.8
(12) Fragrance 0.1
Production method: Dissolve (5) and (6) in a part of (11) to 50 ° C, and gradually add to (4) heated to 50 ° C in advance with stirring. These are mixed in advance and uniformly dispersed in (1) to (3) heated and dissolved at 70 ° C. (7) to (10) are added to the remainder of (11), and the mixture heated to 70 ° C. is added with stirring and emulsified with a homomixer. After cooling, add and mix (12) at 40 ° C.
[0044]
[Example 10] Make-up base cream (1) Stearic acid 12.00 (wt%)
(2) Cetanol 2.00
(3) Glyceryl tri-2-ethylhexanoate 2.50
(4) Self-emulsifying glyceryl monostearic acid 2.00
Ester (5) Propylene glycol 10.00
(6) Cuckoo extract 1 0.02
(7) Methyl paraoxybenzoate 0.10
(8) Ryutan extract 0.05
(9) Potassium hydroxide 0.30
(10) Purified water 68.43
(11) Titanium oxide 2.00
(12) Bengala 0.40
(13) Yellow iron oxide 0.10
(14) Fragrance 0.10
Manufacturing method: The oil phase components (1) to (4) are mixed and dissolved to 75 ° C. On the other hand, (6) and (7) are dissolved in (5) and added to (10) together with (8) and (9), mixed and heated to dissolve, and the pigment components (11) to (13) are added to this. Add and disperse uniformly with homomixer to 75 ° C. Next, the oil phase component is added to the water phase component, and the mixture is uniformly emulsified with a homomixer. After cooling, (14) is added and mixed at 40 ° C.
[0045]
[Example 11] Emulsion foundation (1) Stearic acid 2.00 (wt%)
(2) Squalane 5.00
(3) Octyl dodecyl myristate 5.00
(4) Cetanol 1.00
(5) Decaglyceryl monoisopalmitate 9.00
(6) 1,3-Butylenecricol 6.00
(7) Methyl paraoxybenzoate 0.10
(8) Potassium hydroxide 0.08
(9) Purified water 51.57
(10) Titanium oxide 9.00
(11) Talc 7.40
(12) Bengala 0.50
(13) Yellow iron oxide 1.10.
(14) Black iron oxide 0.10
(15) Cuckoo extract 3 1.00
(16) Isolate extract 1.00
(17) Fragrance 0.15
Manufacturing method: The oil phase components (1) to (5) are mixed and dissolved to 75 ° C. On the other hand, the aqueous phase components (6) to (9) are mixed, dissolved by heating, the pigment components (10) to (14) are added thereto, and the mixture is uniformly dispersed with a homomixer to 75 ° C. Next, the oil phase component is added to the aqueous phase component, and the mixture is uniformly emulsified with a homomixer. After cooling, (15) to (17) are added and mixed at 40 ° C.
[0046]
[Example 12] Hand cream (1) Cetanol 4.00 (wt%)
(2) Vaseline 2.00
(3) Liquid paraffin 10.00
(4) Glyceryl monostearate 1.50
(5) Polyoxyethylene (60E.O.) glyceryl 2.50
Isostearic acid ester (6) Tocopherol acetate 0.25
(7) Glycerin 20.00
(8) Methyl paraoxybenzoate 0.10
(9) Cuckoo extract fraction 1 0.01
(10) Dipotassium glycyrrhizinate 0.02
(11) Purified water 59.62
Production method: The oil phase components (1) to (6) are mixed and dissolved to 75 ° C. On the other hand, (8) and (9) are dissolved in (7) and added to (11) together with (10), and mixed and dissolved to obtain 75 ° C. Next, the oil phase component is added to the aqueous phase component, and the mixture is uniformly emulsified with a homomixer and cooled.
[0047]
Among the examples according to the present invention described above, Examples 1 to 8 were evaluated for the effect of suppressing wrinkle formation on the skin by medium wavelength ultraviolet rays (UVB). At that time, in Example 1 to Example 8, as shown in Table 1, the konkon extract or fraction and the anti-inflammatory agent, or 4 ′, 7-dihydroxyisoflavone and peony extract-encapsulating liposomes were replaced. Comparative Examples 1 to 8 were evaluated at the same time. The evaluation was performed by taking 5 hairless mice as a group, applying 0.2 g of each of the examples and comparative examples to the back part once a day for each group, and applying UVB of 100 mJ / cm 2 / times 3 times a week. Irradiated for 20 weeks, the state of wrinkle formation in the hairless mouse skin was observed, scored according to the criteria shown in Table 2, and evaluated. At this time, a group to which only purified water was applied was used as a control. As a result, the average value of each group was calculated and shown in Table 3 according to the relationship with the number of days of UVB irradiation.
[0048]
[Table 1]
[0049]
[Table 2]
[0050]
[Table 3]
[0051]
As is apparent from Table 3, in the control, when the UVB irradiation days exceeded 10 weeks, the depth of wrinkles formed in the skin reached a medium level, and after 20 weeks, formation of deep wrinkles was observed. It was. In the application group of Comparative Example 1 and Comparative Example 6 containing only the cool extract or extract fraction as an active ingredient, the formation of wrinkles was suppressed to the extent that slight wrinkle formation was observed after 20 weeks. In addition, an inhibitory effect on wrinkle formation was recognized in the other application group containing an anti-inflammatory agent and not containing a cuckoo extract or extract fraction or 4 ′, 7-dihydroxyisoflavone as compared with the control. However, in each of the corresponding example application groups, the formation of fine wrinkles was observed after 20 weeks, and the inhibitory effect on wrinkle formation was significantly improved compared to the corresponding comparative application group. It was.
[0052]
Then, the use test was done about Example 1-Example 12 of this invention, and the improvement effect of the skin aging symptom was evaluated. At that time, in Example 9 to Example 12, the blended cuckoo extract or extract fraction and the anti-inflammatory agent were replaced as shown in Table 4 to give Comparative Examples 9 to 12, and Comparative Examples 1 to Simultaneously with the comparative example 8, it used for the use test.
[0053]
[Table 4]
[0054]
The effect of improving skin aging symptoms is that 20 female panelists in their 40's to 60's in which fine wrinkle formation and skin elasticity are markedly reduced are considered as one group, and each of the examples and comparative examples is blinded in each group. And used continuously twice a day for 2 months. The degree of fine lines is evaluated by visual observation and photography, and the skin elasticity is measured by a cut meter, and the state before and after the use test is started and compared, respectively. “Improved”, “Slightly improved”, “Change” It was evaluated in three stages, “none”. The results are shown in Table 5 in terms of the number of panelists that obtained each evaluation.
[0055]
[Table 5]
[0056]
As is apparent from Table 5, each of Comparative Examples 2 to 5, Comparative Example 7, Comparative Example 8 and Comparative Example 10 to Comparative Example 12 containing an anti-inflammatory agent as an active ingredient but not containing a cuckoo extract or the like. In the use group, although there was a tendency to improve fine wrinkles and skin elasticity, there were not so many panelists that showed a clear improvement. In each of the use groups of Comparative Example 1, Comparative Example 6, and Comparative Example 9 containing only the extract of Kakkon or the extract fraction, a fairly good tendency to improve fine wrinkles and skin elasticity was observed. In the Example use group, the number of panelists who recognized a clear improvement was significantly greater than in the corresponding Comparative Example use group.
[0057]
Moreover, the improvement effect of the rough skin symptom was evaluated about Example 1- Example 12 and Comparative Example 1- Comparative Example 12 of this invention. The improvement effect of rough skin symptoms is a group of 20 female panelists in their 20s to 60s who show remarkable rough skin symptoms, and each of the examples and comparative examples is blinded twice a day. Evaluated by using continuously for months. The skin condition before and after the start of the use test was evaluated and scored according to the evaluation criteria shown in Table 6, and the average value of 20 people was calculated and shown in Table 7.
[0058]
[Table 6]
[0059]
[Table 7]
[0060]
As is clear from Table 7, in the examples using group of the present invention, remarkable improvement in rough skin was observed in any of the groups, and after completion of the use test, the skin condition was improved from almost good to good. . On the other hand, in the comparative example use group, a considerably good improvement in rough skin was observed, but the degree was smaller than the corresponding example use group.
[0061]
In Examples 1 to 12, no change in state was observed when stored at 25 ° C. for 6 months, and the skin irritation was problematic even in a 48-hour back obstruction test with 30 male panelists. Sexual reaction was not observed.
[0062]
【The invention's effect】
As described above in detail, according to the present invention, it was possible to obtain an external preparation for skin having excellent stability and safety, and synergistically improving effects of preventing and improving rough skin and aging of the skin.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001173568A JP3719951B2 (en) | 2001-06-08 | 2001-06-08 | Skin preparation |
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|---|---|---|---|
| JP2001173568A JP3719951B2 (en) | 2001-06-08 | 2001-06-08 | Skin preparation |
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| JP2002363091A JP2002363091A (en) | 2002-12-18 |
| JP3719951B2 true JP3719951B2 (en) | 2005-11-24 |
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| KR101640736B1 (en) * | 2010-03-09 | 2016-07-29 | 주식회사 엘지생활건강 | Composition for improving skin wrinkle |
| CN103784428B (en) * | 2013-10-11 | 2015-07-15 | 广东省农业科学院动物卫生研究所 | Application of paeonol in preparing medicine for resisting eimeria tenella |
| EP4072558A4 (en) * | 2019-12-13 | 2023-12-20 | Buzzelet Development And Technologies Ltd | COMPOSITIONS AND METHODS FOR TREATING INFLAMMATION WITH STEROIDS AND MODULATOR |
| CN115645425B (en) * | 2022-11-17 | 2024-02-20 | 云南中医药大学 | A kind of paeonol-glycyrrhizic acid solid dispersion with synergistic antibacterial effect and its preparation method and use |
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