JP4780817B2 - Epidermis ceramide production promoter and epidermis moisturizing function improving agent containing the same - Google Patents
Epidermis ceramide production promoter and epidermis moisturizing function improving agent containing the same Download PDFInfo
- Publication number
- JP4780817B2 JP4780817B2 JP2000029319A JP2000029319A JP4780817B2 JP 4780817 B2 JP4780817 B2 JP 4780817B2 JP 2000029319 A JP2000029319 A JP 2000029319A JP 2000029319 A JP2000029319 A JP 2000029319A JP 4780817 B2 JP4780817 B2 JP 4780817B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- epidermis
- ceramide
- ceramide production
- production promoter
- 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
Links
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Description
【０００１】
【発明の属する技術分野】
本発明は、表皮セラミドの生成を促進し得る表皮セラミド生成促進剤、及びこれを含有して成る、表皮セラミドの充実を図り、表皮保湿機能を正常化し得る、表皮保湿機能改善剤に関する。
【０００２】
【従来の技術】
セラミドが、表皮細胞間脂質の構成成分として表皮の保護機能及び保湿機能に関与し、加齢や紫外線曝露，有機溶媒や界面活性剤との接触といった物理的及び化学的ストレスによりセラミドの減少や構造の乱れが生じることにより、表皮の前記機能が損なわれることが明らかになるにつれ、これを外用により補う試みがなされ（特開昭６１−２６０００８，同６３−１９２７０３）、さらには保湿機能，安定性，安全性等に優れ、コスト的にも安価なセラミド類似のアミド誘導体の使用も多く開示されるに至っている（特開昭６３−２１６８１２，同６３−２１８６０９，同６３−２２２１０７等）。
【０００３】
しかしながら、セラミド或いはその類似化合物を外用しても、これらが効率よく経皮吸収され、表皮内で細胞間脂質の再構築に利用されるとはいい難い状況であった。また本来であれば、表皮内のセラミドの生成自体を活性化することが好ましいのであるが、これまで有効なセラミド生成促進剤はあまり報告されていない。
【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、表皮のセラミドの生成を有効に促進して表皮の保湿機能自体を改善することのできる、表皮セラミド生成促進剤及び表皮保湿機能改善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、表皮セラミドの生成を促進し得る物質を検索したところ、脂肪酸及びその塩並びに誘導体より成る群から選択した１種又は２種以上と、L-カルニチン及びDL-カルニチン、並びにこれらの塩及び誘導体より成る群から選択した１種又は２種以上を併用して担体や基剤に含有させることにより、良好な結果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】
【発明の実施の形態】
本発明において用い得る脂肪酸としては、炭素数６〜３２程度の直鎖もしくは分岐鎖を有する飽和又は不飽和脂肪酸が好ましいものとして挙げられる。直鎖飽和脂肪酸としては、ヘキサン酸（カプロン酸），オクタン酸（カプリル酸），デカン酸（カプリン酸），ウンデカン酸，ドデカン酸（ラウリン酸），テトラデカン酸（ミリスチン酸），ペンタデカン酸，ヘキサデカン酸（パルミチン酸），オクタデカン酸（ステアリン酸），エイコサン酸（アラキン酸），ドコサン酸（ベヘン酸）等が、直鎖モノエン酸としては、9-デセン酸（カプロレイン酸），9-ウンデセン酸（9-ウンデシレン酸），10-ウンデセン酸（10-ウンデシレン酸），2-ドデセン酸（2-ラウロレイン酸），5-ドデセン酸（5-ラウロレイン酸），11-ドデセン酸（11-ラウロレイン酸），5-テトラデセン酸（5-ミリストレイン酸），9-テトラデセン酸（9-ミリストレイン酸），2-ヘキサデセン酸（2-パルミトレイン酸），7-ヘキサデセン酸（7-パルミトレイン酸），cis-6-オクタデセン酸（ペトロセリン酸），trans-6-オクタデセン酸（ペトロセエライジン酸），cis-9-オクタデセン酸（オレイン酸），trans-9-オクタデセン酸（エライジン酸），cis-11-エイコセン酸（ゴンドイン酸），cis-13-ドコセン酸（エルカ酸）等が、ジエン酸としては、2,4-ヘキサジエン酸（ソルビン酸），cis-9,cis-12-オクタデカジエン酸（リノール酸），cis-9,trans-12-オクタデカジエン酸（リノエライジン酸）等が、トリエン酸としては、cis-9,trans-11,trans-13-オクタデカトリエン酸（α-エレオステアリン酸），trans-9,trans-11,trans-13-オクタデカトリエン酸（β-エレオステアリン酸），cis-9,cis-12,cis-15-オクタデカトリエン酸（リノレン酸），trans-9,trans-12,trans-15-オクタデカトリエン酸（リノエライジン酸）等が、テトラエン酸としては、5,8,11,14-エイコサテトラエン酸（アラキドン酸）等が例示される。また、分岐鎖を有する飽和脂肪酸としては、2-エチルブタン酸，2-メチルペンタン酸，2-エチルヘキサン酸，2,2-ジメチルオクタン酸，14-メチルペンタデカン酸（イソパルミチン酸），16-メチルヘプタデカン酸（イソステアリン酸）等が例示される。さらに、12-ヒドロキシステアリン酸等のヒドロキシ脂肪酸や、ヤシ油脂肪酸，ラノリン脂肪酸等の天然混合脂肪酸も使用できる。
【０００７】
上記脂肪酸の塩としては、ナトリウム塩，カリウム塩等のアルカリ金属塩、トリエタノールアミン塩等のアミン塩等が、また誘導体としては、上記脂肪酸のアルキルエステル，アルケニルエステル，グリセリルエステル等各種エステル、及びアミドが挙げられる。本発明においては、これら脂肪酸及びその塩並びに誘導体より１種又は２種以上を選択して用いる。本発明に係る表皮セラミド生成促進剤においては、０．０００１〜５．０重量％程度担体等に含有させるのが適切である。
【０００８】
次いで、本発明において上記脂肪酸類の１種又は２種以上と併用するカルニチンは、4-トリメチルアミノ-3-ヒドロキシ酪酸のことであり、公知の物質である。カルニチン及びその塩並びに誘導体の皮膚化粧料への配合についてもすでに開示されており（特開昭５１−１４８０２）、また塩化カルニチンが表皮の透過バリア強度を強化させることも知られている（特開平１１−３０２１４３）が、本発明におけるように、脂肪酸類の１種又は２種以上と併用することにより、表皮のセラミドの生成を促進することはこれまで全く示されていない。
【０００９】
本発明においては、L-カルニチン及びDL-カルニチン及びこれらの塩並びに誘導体より１種又は２種以上を選択して用いる。これらの塩としては、塩酸塩，酢酸塩，硫酸塩等が挙げられ、誘導体としては、アルキルエステル，アルケニルエステル，グリセリルエステル等の各種エステル、及びアミド等が挙げられる。本発明に係る表皮セラミド生成促進剤においては、担体等に０．０００１〜５．０重量％程度含有させるのが適切である。
【００１０】
本発明に係る表皮セラミド生成促進剤は、上記脂肪酸及びその塩並びに誘導体より選択した１種又は２種以上と、L-カルニチン及びDL-カルニチン及びこれらの塩並びに誘導体より選択した１種又は２種以上とを、水，生理食塩水，リン酸緩衝生理食塩水といった水性担体や、ローション基剤，乳剤，ゲル剤，クリーム基剤，軟膏基剤等の皮膚外用剤用基剤に可溶化もしくは分散させて調製することができる。また、マイクロカプセルやリポソーム等に内包させてもよい。なお本発明に係る表皮セラミド生成促進剤には、製剤の安定化を図るため、界面活性剤，抗酸化剤，防菌防黴剤等を添加することができる。
【００１１】
さらに本発明においては、上記表皮セラミド生成促進剤の１種又は２種以上をそのまま、もしくは各種基剤に含有させて、表皮保湿機能改善剤とすることができる。かかる表皮保湿機能改善剤には、さらに保湿剤，皮膚細胞賦活剤，抗酸化剤，防菌防黴剤，香料等を添加することができる。
【００１２】
【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。
【００１３】
［実施例１］ 表皮セラミド生成促進剤１
（１）アラキドン酸 ０．１５２ｇ
（２）L-カルニチン １．６２２ｇ
（３）大豆レシチン １．０００ｇ
（４）精製水 全量を１．０リットルとする量
製法：(1)〜(3)を順次(4)に添加して混合，可溶化し、(4)で全体を１．０リットルとする。本実施例中のアラキドン酸濃度は５．０×１０-4Ｍ，L-カルニチン濃度は０．０１Ｍである。
【００１４】
上記の実施例１について、表皮のセラミド生成促進作用を評価した。その際、実施例１においてアラキドン酸を添加しないで同様に調製したものを比較例１、L-カルニチンを添加しないでアラキドン酸を倍量添加して同様に調製したものを比較例２として、同時に評価を行った。
【００１５】
表皮のセラミド生成促進作用は、正常ヒト表皮ケラチノサイトを用いて次のようにして評価した。まず、３５ｍｍ径のディッシュに正常ヒト表皮ケラチノサイトを５，０００個／ディッシュとなるように播種し、正常ヒト表皮角化細胞増殖用無血清液体培地（クラボウ社製）にて３７℃で９０％コンフルエントに達するまで培養する。次いで培地を上記実施例及び比較例のそれぞれを１．０ｍｌ添加し、全量を１００ｍｌとして調製した細胞分化用培地（１０容量％ウシ胎仔血清，１０μｇ／ｍｌインシュリン，０．４μｇ／ｍｌハイドロコルチゾンを添加したダルベッコ修正基礎培地（日研生物医学研究所製）と、Ｈａｍ’ｓ Ｆ-12培地（極東製薬工業製）の３：１混合培地）に交換し、２日ごとに培地を交換しながら培養して、１０日目にディッシュより回収したケラチノサイトよりクロロホルム・メタノール混合溶媒（容量比＝２：１）で脂質を抽出した。抽出した脂質は乾固した後前記混合溶媒２００μｌに溶解し、薄層クロマトグラフィーによりセラミドの定量を行った。なお、実施例及び比較例を添加せず、細胞分化用培地にて同様に培地交換した系を対照とした。実験はそれぞれの系について２回ずつ行い、平均値を算出して表１に示した。
【００１６】
【表１】
表１より明らかなように、本発明の実施例１を添加した系では、対照に比べて有意にセラミド含有量が上昇しており、セラミド生成の促進が認められていた。これに対し、L-カルニチンのみを含有する比較例１を添加した系では、対照に比べてセラミド含有量の上昇は認められず、アラキドン酸のみを倍量含有する比較例２を添加した系では、わずかなセラミド含有量の上昇が見られたのみであり、脂肪酸又はL-カルニチンのみでは、有効なセラミド生成の促進効果が得られないことが示された。
【００１８】
続いて、本発明に係る表皮セラミド生成促進剤についての他の実施例を示す。
【００１９】
［実施例２］ 表皮セラミド生成促進剤２（ローション剤型）
（１）エタノール １０．００ｇ
（２）ポリオキシエチレン(60E.O.)硬化ヒマシ油 ０．５０ｇ
（３）イソステアリン酸 ０．０５ｇ
（４）L-カルニチン塩酸塩 ０．２０ｇ
（５）パラオキシ安息香酸メチル ０．１０ｇ
（６）精製水 全量を１００ｍｌとする量
製法：(1)〜(5)を順次(6)に添加し、均一に溶解した後、全量を１００ｍｌとする。
【００２０】
［実施例３］ 表皮セラミド生成促進剤３（乳剤型）
（１）ステアリン酸 ０．２０（重量％）
（２）セタノール １．５０
（３）ワセリン ３．００
（４）流動パラフィン ７．００
（５）ポリオキシエチレン(10E.O.)モノオレイン酸 １．５０
エステル
（６）酢酸トコフェロール ０．５０
（７）グリセリン ５．００
（８）パラオキシ安息香酸メチル ０．１０
（９）水酸化カリウム ０．０２
（10）DL-カルニチン ０．５０
（11）精製水 ８０．６８
製法：(1)〜(6)の油相成分を混合，加熱して均一に溶解し、７０℃とする。一方、(7)〜(11)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、冷却する。
【００２１】
［実施例４］ 表皮セラミド生成促進剤４（ゲル剤型）
（１）モノステアリン酸プロピレングリコール ０．０２（重量％）
（２）ジプロピレングリコール １０．００
（３）カルボキシビニルポリマー ０．５０
（４）水酸化カリウム ０．１０
（５）パラオキシ安息香酸メチル ０．１０
（６）精製水 ８８．９３
（７）L-カルニチン塩酸塩 ０．３５
製法：(6)に(3)を均一に溶解した後、(2)に(1)，(5)を溶解して添加し、次いで(4)を加えて増粘させ、(7)を添加，溶解する。
【００２２】
［実施例５］ 表皮セラミド生成促進剤５（クリーム剤型）
（１）ミツロウ ６．０（重量％）
（２）セタノール ５．０
（３）還元ラノリン ８．０
（４）スクワラン ２７．５
（５）9-ウンデシレン酸，10-ウンデシレン酸混合物 ０．１
（６）グリセリル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 ５．０
モノラウリン酸エステル
（８）プロピレングリコール ５．０
（９）パラオキシ安息香酸メチル ０．１
（10）L-カルニチン酢酸塩 ０．５
（11）精製水 ４０．３
製法：(1)〜(7)の油相成分を混合，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℃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、冷却する。
【００２３】
［実施例６］ 表皮セラミド生成促進剤６（軟膏剤型）
（１）白色ワセリン ２５．００（重量％）
（２）ステアリルアルコール ２５．００
（３）パルミチン酸 ０．０１
（４）ベヘン酸 ０．０１
（５）グリセリン １２．００
（６）ラウリル硫酸ナトリウム １．００
（７）パラオキシ安息香酸メチル ０．１０
（８）精製水 ３６．５８
（９）L-カルニチン ０．１５
（10）DL-カルニチン塩酸塩 ０．１５
製法：(1)〜(6)の油相成分を混合，加熱して均一に溶解し、７５℃とする。一方、(7)，(8)の水相成分を混合，加熱して均一とし、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(9)，(10)を添加，溶解する。
【００２４】
［実施例７］ 表皮セラミド生成促進剤７（リポソーム）
（１）大豆レシチン ８０．００（ｇ）
（２）イソパルミチン酸 ０．０５
（３）リノレン酸 ０．０２
（４）酢酸トコフェロール ０．５０
（５）L-カルニチン ０．５０
（６）精製水 １００．００
製法：(5)を(6)に添加して溶解する。これに、(1)に(2)〜(4)を添加，混合して添加し、６５℃で懸濁した後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する。
【００２５】
［実施例８］ 表皮セラミド生成促進剤８（マイクロカプセル）
（１）オリーブ油 １０．０（重量％）
（２）ミリスチン酸オクチルドデシル ０．２
（３）アルギン酸ナトリウム ０．６
（４）ポリビニルアルコール １２．０
（５）グリセリン １２．０
（６）L-カルニチン ０．２
（７）精製水 ６５．０
製法：(1)に(2)を混合，溶解し、(3)〜(6)を(7)に加えて溶解した水溶液に撹拌しながら添加，分散する。この分散液を撹拌しながら２０重量％の塩化カルシウム水溶液中に滴下し、生じたマイクロカプセルを遠心分離にて回収する。
【００２６】
次に、本発明に係る表皮保湿機能改善剤についての実施例を示す。
【００２７】
［実施例９］ 表皮保湿機能改善剤１
（１）流動パラフィン １０．０（重量％）
（２）白色ワセリン ５．０
（３）セタノール ６．０
（４）ポリオキシエチレン(30E.O.)セチルエーテル ２．０
（５）自己乳化型グリセリルモノステアリン酸 １０．０
エステル
（６）プロピレングリコール １０．０
（７）パラオキシ安息香酸メチル ０．１
（８）表皮セラミド生成促進剤１ ２．０
（９）精製水 ５４．９
製法：(1)〜(5)の油相成分を混合，加熱溶解し、７５℃とする。一方(6)〜(9)の水相成分を混合，加熱溶解して７５℃とし、これに前記油相を撹拌しながら徐々に添加した後、ホモミキサーにて乳化し、冷却する。
【００２８】
［実施例１０］ 表皮保湿機能改善剤２
（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）表皮セラミド生成促進剤２ １．０
（９）パラオキシ安息香酸メチル ０．１
（10）精製水 ５１．８
（11）香料 ０．１
製法：(5)，(6)を(10)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)に均一に分散し、次いで(7)〜(9)を(10)の残部に溶解して７０℃に加熱したものを撹拌しながら添加し、ホモミキサーにて乳化する。冷却後、５０℃にて(11)を添加，混合する。
【００２９】
［実施例１１］ 表皮保湿機能改善剤３
（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）香料 ０．１
（７）精製水 ７４．６
（８）表皮セラミド生成促進剤７ １０．０
製法：(5)，(6)を(4)に溶解し、(1)〜(3)とともに(7)に添加して均一に混合し、これに(8)を加えて分散する。
【００３０】
［実施例１２］ 表皮保湿機能改善剤４
（１）ジプロピレングリコール １０．０（重量％）
（２）カルボキシビニルポリマー ０．５
（３）水酸化カリウム ０．１
（４）パラオキシ安息香酸メチル ０．１
（５）精製水 ８６．８
（６）表皮セラミド生成促進剤８ ２．５
製法：(5)に(2)を均一に溶解した後、(1)に(4)を溶解して添加し、次いで(3)を加えて増粘させ、(6)を添加，分散する。
【００３１】
上記本発明の実施例９〜実施例１２について使用試験を行い、表皮保湿機能の改善状況を評価した。その際、実施例９，実施例１１において、表皮セラミド生成促進剤１及び表皮セラミド生成促進剤７について脂肪酸を添加せずに同様に調製したものを添加して比較例３，比較例５とし、実施例１０，実施例１２において、表皮セラミド生成促進剤２及び表皮セラミド生成促進剤８についてL-カルニチン又はその塩を添加せずに同様に調製したものを添加して比較例４，比較例６とし、同時に使用試験に供した。
【００３２】
使用試験は、顕著な肌荒れ症状を呈する１０才代〜６０才代の男女パネラー２０名を１群とし、各群に実施例９〜実施例１２及び比較例３〜比較例６のそれぞれをブラインドにて１日２回、２週間使用させ、使用試験開始前と使用試験終了後の各パネラーの皮膚の状態を観察し、同時に皮膚表面のコンダクタンスを測定して行った。皮膚の状態は、表２に示す評価基準に従って評価して点数化した。皮膚の状態及び皮膚表面コンダクタンスの測定値について２０名の平均値を求め、使用試験開始前と使用試験終了後を比較して表３に示した。
【００３３】
【表２】
【表３】
表３より明らかなように、本発明の実施例９〜実施例１２使用群では皮膚の状態はほぼ良好な状態まで改善しており、表皮水分量を示す皮膚表面のコンダクタンス値は有意に上昇していた。これに対し比較例３〜比較例６使用群では、皮膚の状態の改善は不十分で、皮膚表面のコンダクタンス値の上昇も、使用試験開始前に比べて認められるものの、その程度は各対応する実施例使用群に比べてはるかに小さいものであった。
【００３６】
【発明の効果】
以上詳述したように本発明により、表皮のセラミドの生成を有効に促進して表皮の保湿機能を改善することのできる、表皮セラミド生成促進剤及び表皮保湿機能改善剤を得ることができた。[0001]
BACKGROUND OF THE INVENTION
TECHNICAL FIELD The present invention relates to an epidermis ceramide production promoter that can promote the production of epidermis ceramide, and an epidermis moisturizing function improving agent that contains this and can enhance the epidermis ceramide and normalize the epidermis moisturizing function.
[0002]
[Prior art]
Ceramide is involved in the protective and moisturizing functions of the epidermis as a constituent of the epidermal intercellular lipid, and the decrease and structure of ceramide due to physical and chemical stresses such as aging, UV exposure, contact with organic solvents and surfactants. As it becomes clear that the above-mentioned function of the epidermis is impaired due to the disturbance of the skin, attempts have been made to compensate for this by external application (Japanese Patent Laid-Open No. 61-260008, 63-192703), and further, the moisture retention function and stability. Many ceramide-like amide derivatives, which are excellent in safety and the like and inexpensive in cost, have been disclosed (Japanese Patent Laid-Open Nos. 63-216812, 63-218609, 63-222107, etc.).
[0003]
However, even if ceramide or a similar compound is applied externally, it is difficult to efficiently transdermally absorb these and use them to reconstruct intercellular lipids in the epidermis. Moreover, originally, it is preferable to activate the production of ceramide in the epidermis, but no effective ceramide production promoter has been reported so far.
[0004]
[Problems to be solved by the invention]
Therefore, an object of the present invention is to obtain an epidermis ceramide production promoter and an epidermis moisturizing function improving agent that can effectively promote the production of ceramide in the epidermis and improve the moisturizing function itself of the epidermis.
[0005]
[Means for Solving the Problems]
In order to solve the above problems, a search for a substance capable of promoting the production of epidermal ceramide was conducted. As a result, one or more selected from the group consisting of fatty acids and salts and derivatives thereof, L-carnitine and DL-carnitine, and It has been found that good results can be obtained by using one or more selected from the group consisting of these salts and derivatives in combination in a carrier or base, and the present invention has been completed.
[0006]
DETAILED DESCRIPTION OF THE INVENTION
The fatty acid that can be used in the present invention is preferably a saturated or unsaturated fatty acid having a straight chain or branched chain having about 6 to 32 carbon atoms. Linear saturated fatty acids include hexanoic acid (caproic acid), octanoic acid (caprylic acid), decanoic acid (capric acid), undecanoic acid, dodecanoic acid (lauric acid), tetradecanoic acid (myristic acid), pentadecanoic acid, hexadecanoic acid (Palmitic acid), octadecanoic acid (stearic acid), eicosanoic acid (arachinic acid), docosanoic acid (behenic acid), etc., as linear monoenoic acid, 9-decenoic acid (caproleic acid), 9-undecenoic acid (9 -Undecylenic acid), 10-Undecenoic acid (10-undecylenic acid), 2-dodecenoic acid (2-laurolenic acid), 5-dodecenoic acid (5-laurolenic acid), 11-dodecenoic acid (11-laurolenic acid), 5 -Tetradecenoic acid (5-myristoleic acid), 9-tetradecenoic acid (9-myristoleic acid), 2-hexadecenoic acid (2-palmitoleic acid), 7-hexadecenoic acid (7- Lumitoleic acid), cis-6-octadecenoic acid (petroceric acid), trans-6-octadecenoic acid (petroceleic acid), cis-9-octadecenoic acid (oleic acid), trans-9-octadecenoic acid (elaidic acid) , Cis-11-eicosenoic acid (gondoic acid), cis-13-docosenoic acid (erucic acid), etc., as dienoic acid, 2,4-hexadienoic acid (sorbic acid), cis-9, cis-12-octa Decadienoic acid (linoleic acid), cis-9, trans-12-octadecadienoic acid (linoleidic acid), etc., as the trienoic acid, cis-9, trans-11, trans-13-octadecatrienoic acid ( α-eleostearic acid), trans-9, trans-11, trans-13-octadecatrienoic acid (β-eleostearic acid), cis-9, cis-12, cis-15-octadecatrienoic acid ( Linolenic acid), trans-9, trans-12, trans-15-octadecatrienoic acid (linoleidic acid), etc. 5,8,11,14-eicosatetraenoic acid (arachidonic acid) and the like. Examples of branched saturated fatty acids include 2-ethylbutanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid, 2,2-dimethyloctanoic acid, 14-methylpentadecanoic acid (isopalmitic acid), 16-methyl Examples include heptadecanoic acid (isostearic acid). Further, hydroxy fatty acids such as 12-hydroxystearic acid and natural mixed fatty acids such as coconut oil fatty acid and lanolin fatty acid can be used.
[0007]
Examples of the fatty acid salts include alkali metal salts such as sodium salts and potassium salts, amine salts such as triethanolamine salts, and derivatives such as various esters such as alkyl esters, alkenyl esters, and glyceryl esters of the above fatty acids, and Amides are mentioned. In the present invention, one or more of these fatty acids and salts and derivatives thereof are selected and used. In the epidermis ceramide production promoter according to the present invention, it is appropriate to contain it in a carrier or the like in an amount of about 0.0001 to 5.0% by weight.
[0008]
Next, carnitine used in combination with one or more of the above fatty acids in the present invention is 4-trimethylamino-3-hydroxybutyric acid, which is a known substance. The formulation of carnitine and its salts and derivatives into skin cosmetics has already been disclosed (Japanese Patent Laid-Open No. 51-14802), and it is also known that carnitine chloride enhances the permeation barrier strength of the epidermis (Japanese Patent Laid-Open No. Hei 5). 11-302143), as in the present invention, has never been shown to promote the production of ceramides in the epidermis by using in combination with one or more fatty acids.
[0009]
In the present invention, one or more of L-carnitine, DL-carnitine and their salts and derivatives are selected and used. These salts include hydrochlorides, acetates, sulfates, etc., and derivatives include various esters such as alkyl esters, alkenyl esters, glyceryl esters, and amides. In the epidermis ceramide production promoter according to the present invention, it is appropriate to contain about 0.0001 to 5.0% by weight in a carrier or the like.
[0010]
The epidermis ceramide production promoter according to the present invention is one or more selected from the above fatty acids and salts and derivatives thereof, and one or two selected from L-carnitine, DL-carnitine and salts and derivatives thereof. The above is solubilized or dispersed in an aqueous carrier such as water, physiological saline or phosphate buffered saline, or a base for external preparations such as a lotion base, emulsion, gel, cream base or ointment base. Can be prepared. Further, it may be encapsulated in microcapsules or liposomes. In addition, a surfactant, an antioxidant, a fungicide, an antifungal agent and the like can be added to the epidermis ceramide production promoter according to the present invention in order to stabilize the preparation.
[0011]
Furthermore, in this invention, 1 type, or 2 or more types of the said skin ceramide production | generation promoter can be used as it is or it is made to contain in various bases, and it can be set as a skin moisturizing function improving agent. A moisturizing agent, skin cell activator, antioxidant, antibacterial and antifungal agent, fragrance and the like can be further added to the skin moisturizing function improving agent.
[0012]
【Example】
Further, the features of the present invention will be described in detail with reference to examples.
[0013]
[Example 1] Epidermal ceramide production promoter 1
(1) Arachidonic acid 0.152g
(2) L-carnitine 1.622g
(3) Soy lecithin 1.000 g
(4) Purified water Mass production method with a total volume of 1.0 liter: Add (1) to (3) to (4) in order and mix and solubilize. . In this example, the arachidonic acid concentration is 5.0 × 10 −4 M, and the L-carnitine concentration is 0.01M.
[0014]
About said Example 1, the ceramide production | generation promotion effect of the epidermis was evaluated. At that time, the same preparation without adding arachidonic acid in Example 1 was made as Comparative Example 1, and the same preparation with double addition of arachidonic acid without addition of L-carnitine was made as Comparative Example 2 at the same time. Evaluation was performed.
[0015]
The ceramide production promoting action of the epidermis was evaluated as follows using normal human epidermal keratinocytes. First, normal human epidermal keratinocytes were seeded at a density of 5,000 cells / dish in a 35 mm diameter dish, and 90% confluent at 37 ° C. in a serum-free liquid medium for proliferation of normal human epidermal keratinocytes (Kurabo). Incubate until reached. Next, 1.0 ml of each of the above Examples and Comparative Examples was added to the medium, and a medium for cell differentiation prepared with a total volume of 100 ml (10 vol% fetal calf serum, 10 μg / ml insulin, 0.4 μg / ml hydrocortisone was added) Dulbecco's modified basal medium (manufactured by Nikken Biomedical Research Institute) and Ham's F-12 medium (manufactured by Kyokuto Pharmaceutical Co., Ltd.), and the culture is performed while changing the medium every two days. Then, lipids were extracted from the keratinocytes recovered from the dish on the 10th day with a chloroform / methanol mixed solvent (volume ratio = 2: 1). The extracted lipid was dried and dissolved in 200 μl of the mixed solvent, and ceramide was quantified by thin layer chromatography. In addition, the system which did not add an Example and a comparative example but changed the culture medium similarly in the culture medium for cell differentiation was made into the control | contrast. The experiment was performed twice for each system, and the average value was calculated and shown in Table 1.
[0016]
[Table 1]
As is clear from Table 1, in the system to which Example 1 of the present invention was added, the ceramide content was significantly increased as compared with the control, and promotion of ceramide formation was recognized. In contrast, in the system to which Comparative Example 1 containing only L-carnitine was added, no increase in ceramide content was observed compared to the control, and in the system to which Comparative Example 2 containing only double amounts of arachidonic acid was added. Only a slight increase in the ceramide content was observed, and it was shown that only the fatty acid or L-carnitine cannot provide an effective ceramide production promoting effect.
[0018]
Subsequently, other examples of the epidermis ceramide production promoter according to the present invention will be shown.
[0019]
[Example 2] Epidermal ceramide production promoter 2 (lotion type)
(1) Ethanol 10.00g
(2) Polyoxyethylene (60E.O.) hydrogenated castor oil 0.50g
(3) 0.05 g of isostearic acid
(4) L-carnitine hydrochloride 0.20g
(5) Methyl paraoxybenzoate 0.10 g
(6) Purified water Mass production method with a total volume of 100 ml: (1) to (5) are sequentially added to (6) and dissolved uniformly, and then the total volume is 100 ml.
[0020]
[Example 3] Epidermal ceramide formation promoter 3 (emulsion type)
(1) Stearic acid 0.20 (wt%)
(2) Cetanol 1.50
(3) Petrolatum 3.00
(4) Liquid paraffin 7.00
(5) Polyoxyethylene (10E.O.) monooleic acid 1.50
Ester (6) Tocopherol acetate 0.50
(7) Glycerin 5.00
(8) Methyl paraoxybenzoate 0.10
(9) Potassium hydroxide 0.02
(10) DL-carnitine 0.50
(11) Purified water 80.68
Production method: The oil phase components (1) to (6) are mixed and heated to dissolve uniformly to 70 ° C. On the other hand, the aqueous phase components (7) to (11) are mixed and heated to be uniform, and set to 70 ° C. The oil phase component is gradually added to the aqueous phase component with stirring, emulsified, and cooled.
[0021]
[Example 4] Epidermal ceramide production promoter 4 (gel formulation)
(1) Propylene glycol monostearate 0.02 (wt%)
(2) Dipropylene glycol 10.00
(3) Carboxyvinyl polymer 0.50
(4) Potassium hydroxide 0.10
(5) Methyl paraoxybenzoate 0.10
(6) Purified water 88.93
(7) L-carnitine hydrochloride 0.35
Manufacturing method: (3) is uniformly dissolved in (6), then (1) and (5) are dissolved and added to (2), then (4) is added to increase the viscosity, and (7) is added , Dissolve.
[0022]
[Example 5] Epidermal ceramide production promoter 5 (cream type)
(1) Beeswaw 6.0 (wt%)
(2) Cetanol 5.0
(3) Reduced lanolin 8.0
(4) Squalane 27.5
(5) 9-undecylenic acid, 10-undecylenic acid mixture 0.1
(6) Glyceryl monostearate 2.5
(7) Polyoxyethylene (20E.O.) sorbitan 5.0
Monolaurate (8) Propylene glycol 5.0
(9) Methyl paraoxybenzoate 0.1
(10) L-carnitine acetate 0.5
(11) Purified water 40.3
Production method: The oil phase components (1) to (7) are mixed and dissolved to 75 ° C. On the other hand, the water phase components (8) to (11) are 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 and cooled.
[0023]
[Example 6] Epidermal ceramide formation promoter 6 (ointment type)
(1) White petrolatum 25.00 (wt%)
(2) Stearyl alcohol 25.00
(3) Palmitic acid 0.01
(4) Behenic acid 0.01
(5) Glycerin 12.00
(6) Sodium lauryl sulfate 1.00
(7) Methyl paraoxybenzoate 0.10
(8) Purified water 36.58
(9) L-carnitine 0.15
(10) DL-carnitine hydrochloride 0.15
Production method: The oil phase components (1) to (6) are mixed and heated to dissolve uniformly to 75 ° C. On the other hand, the water phase components (7) and (8) are mixed and heated to be uniform, and the temperature is set to 75 ° C. The oil phase component is gradually added to the aqueous phase component while stirring to emulsify, and after cooling, (9) and (10) are added and dissolved at 40 ° C.
[0024]
[Example 7] Epidermal ceramide production promoter 7 (liposome)
(1) Soy lecithin 80.00 (g)
(2) Isopalmitic acid 0.05
(3) Linolenic acid 0.02
(4) Tocopherol acetate 0.50
(5) L-carnitine 0.50
(6) Purified water 100.00
Manufacturing method: Add (5) to (6) and dissolve. To this, (2) to (4) are added to (1), mixed and added, suspended at 65 ° C. and then sonicated to prepare liposomes, which are collected by centrifugation.
[0025]
[Example 8] Epidermal ceramide production promoter 8 (microcapsule)
(1) Olive oil 10.0 (% by weight)
(2) Octyldodecyl myristate 0.2
(3) Sodium alginate 0.6
(4) Polyvinyl alcohol 12.0
(5) Glycerin 12.0
(6) L-carnitine 0.2
(7) Purified water 65.0
Production method: (2) is mixed and dissolved in (1), and (3) to (6) are added to (7) and dissolved in the dissolved aqueous solution with stirring. The dispersion is dropped into a 20% by weight calcium chloride aqueous solution while stirring, and the resulting microcapsules are collected by centrifugation.
[0026]
Next, the Example about the skin moisturizing function improving agent which concerns on this invention is shown.
[0027]
[Example 9] Skin moisturizing function improving agent 1
(1) Liquid paraffin 10.0 (% by weight)
(2) White petrolatum 5.0
(3) Cetanol 6.0
(4) Polyoxyethylene (30E.O.) cetyl ether 2.0
(5) Self-emulsifying glyceryl monostearic acid 10.0
Ester (6) Propylene glycol 10.0
(7) Methyl paraoxybenzoate 0.1
(8) Skin ceramide production promoter 1 2.0
(9) Purified water 54.9
Production method: The oil phase components (1) to (5) are mixed and dissolved by heating to 75 ° C. On the other hand, the aqueous phase components (6) to (9) are mixed, dissolved by heating to 75 ° C., and the oil phase is gradually added to this while stirring, then emulsified with a homomixer and cooled.
[0028]
[Example 10] Skin moisturizing function improving agent 2
(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) Epidermis ceramide production promoter 2 1.0
(9) Methyl paraoxybenzoate 0.1
(10) Purified water 51.8
(11) Fragrance 0.1
Production method: Dissolve (5) and (6) in a part of (10) to 50 ° C, and gradually add to (4) heated to 50 ° C in advance with stirring. This was mixed in advance and uniformly dispersed in (1) to (3) heated and dissolved at 70 ° C. Then, (7) to (9) were dissolved in the remainder of (10) and heated to 70 ° C. Add with stirring and emulsify with homomixer. After cooling, add and mix (11) at 50 ° C.
[0029]
[Example 11] Skin moisturizing function improving agent 3
(1) Glycerin 2.0 (% by weight)
(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) Fragrance 0.1
(7) Purified water 74.6
(8) Epidermal ceramide production promoter 7 10.0
Manufacturing method: Dissolve (5) and (6) in (4), add to (7) together with (1) to (3), mix uniformly, add (8) to this and disperse.
[0030]
[Example 12] Skin moisturizing function improving agent 4
(1) Dipropylene glycol 10.0 (% by weight)
(2) Carboxyvinyl polymer 0.5
(3) Potassium hydroxide 0.1
(4) Methyl paraoxybenzoate 0.1
(5) Purified water 86.8
(6) Epidermal ceramide production promoter 8 2.5
Manufacturing method: (2) is uniformly dissolved in (5), (4) is dissolved and added to (1), then (3) is added to increase the viscosity, and (6) is added and dispersed.
[0031]
A use test was conducted on Examples 9 to 12 of the present invention, and the improvement status of the skin moisturizing function was evaluated. In that case, in Example 9 and Example 11, what was prepared similarly without adding a fatty acid about the epidermis ceramide production | generation promoter 1 and the epidermis ceramide production | generation accelerator 7 was used as the comparative example 3 and the comparative example 5, In Example 10 and Example 12, the same preparation was made without adding L-carnitine or a salt thereof to the epidermal ceramide production accelerator 2 and the epidermal ceramide production accelerator 8, and Comparative Examples 4 and 6 At the same time, it was subjected to a use test.
[0032]
In the use test, 20 male and female panelists in their 10's to 60's who exhibit remarkable rough skin symptoms are grouped together, and each of Examples 9 to 12 and Comparative Examples 3 to 6 is blinded to each group. It was used twice a day for 2 weeks, and the skin condition of each paneler was observed before and after the use test was started, and at the same time, the conductance of the skin surface was measured. The skin condition was evaluated according to the evaluation criteria shown in Table 2 and scored. The average value of 20 persons was calculated | required about the measured value of a skin state and skin surface conductance, and it showed in Table 3 by comparing before the use test start and after the use test end.
[0033]
[Table 2]
[Table 3]
As is apparent from Table 3, the skin condition in the use group of Examples 9 to 12 of the present invention was improved to a substantially good state, and the conductance value on the skin surface indicating the amount of water in the epidermis increased significantly. It was. On the other hand, in the use groups of Comparative Examples 3 to 6, the improvement of the skin condition is insufficient, and an increase in the conductance value of the skin surface is also observed compared to before the start of the use test, but the degree corresponds to each. It was much smaller than the example use group.
[0036]
【The invention's effect】
As described above in detail, according to the present invention, it was possible to obtain an epidermis ceramide production promoter and an epidermis moisturizing function improving agent that can effectively promote the production of ceramide in the epidermis and improve the moisturizing function of the epidermis.
Claims (1)
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| Application Number | Priority Date | Filing Date | Title |
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| JP2000029319A JP4780817B2 (en) | 2000-02-07 | 2000-02-07 | Epidermis ceramide production promoter and epidermis moisturizing function improving agent containing the same |
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| JP2000029319A JP4780817B2 (en) | 2000-02-07 | 2000-02-07 | Epidermis ceramide production promoter and epidermis moisturizing function improving agent containing the same |
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| JP4780817B2 true JP4780817B2 (en) | 2011-09-28 |
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Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10129502A1 (en) * | 2001-06-19 | 2003-01-09 | Beiersdorf Ag | Use of carnitine and / or one or more acyl-carnitines for the production of cosmetic or dermatological preparations to increase ceramide biosynthesis |
| DE10133200A1 (en) * | 2001-07-07 | 2003-01-23 | Beiersdorf Ag | Use of topical compositions containing carnitine and its precursors, derivatives or metabolites to, e.g. improve skin condition or to treat or prevent skin disorders, abnormal lipid peroxidation, reduced cell-cell communication or dandruff |
| JP4787461B2 (en) * | 2003-05-15 | 2011-10-05 | 花王株式会社 | Skin cosmetics |
| ITMI20041603A1 (en) * | 2004-08-04 | 2004-11-04 | Vama Farmacosmetica S R L | 1-CARNITINE COSMETIC RAW MATERIAL FOR LONG-LASTING MOISTURIZING PREPARATION AND COSMETIC PREPARATION OBTAINED WITH THIS RAW MATERIAL |
| CN101296684B (en) * | 2005-08-25 | 2012-10-10 | 高露洁-棕榄公司 | moisturizing composition |
| KR20090103869A (en) * | 2006-11-02 | 2009-10-01 | 메루샹가부시키가이샤 | Ceramide synthesis accelerators, cosmetic preparation, skin preparation for external use, method of preventing aging, and method of diminishing wrinkle |
| JP2014221748A (en) * | 2013-05-14 | 2014-11-27 | 昭和電工株式会社 | Epidermis-related factor activator |
| CN106265123A (en) * | 2016-08-22 | 2017-01-04 | 欧诗漫生物股份有限公司 | A kind of cosmetics cream containing Cer NS & carnosine submicron liposome and preparation method thereof |
| JP2020203862A (en) * | 2019-06-18 | 2020-12-24 | 小林製薬株式会社 | External composition for improving skin barrier function |
| JP7833254B2 (en) * | 2019-06-18 | 2026-03-19 | 小林製薬株式会社 | External composition |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS51148042A (en) * | 1975-06-14 | 1976-12-18 | Kanebo Ltd | Skin toiletry |
| JPS63192703A (en) * | 1987-02-04 | 1988-08-10 | Kao Corp | External agent for skin |
| JPH1129457A (en) * | 1997-07-04 | 1999-02-02 | Kanebo Ltd | Skin cosmetic |
| JPH11180851A (en) * | 1997-12-22 | 1999-07-06 | Kanebo Ltd | Skin cosmetic |
| DE19806946A1 (en) * | 1998-02-19 | 1999-09-09 | Beiersdorf Ag | Combination of (acyl) carnitine and retinoid for use in skin care, effective e.g. against light-induced damage and inflammation |
| DE19806947A1 (en) * | 1998-02-19 | 1999-08-26 | Beiersdorf Ag | Combination of (acyl) carnitine and (hydro)quinone for use in skin care, effective e.g. against light-induced damage and inflammation |
| DE19806890A1 (en) * | 1998-02-19 | 1999-08-26 | Beiersdorf Ag | Combination of (acyl) carnitine and oxidant for use in skin care, effective e.g. against light-induced damage and inflammation |
| DE19806889A1 (en) * | 1998-02-19 | 1999-08-26 | Beiersdorf Ag | Treatment or prevention of skin aging using acyl carnitine, effective e.g. against light-induced damage, dry skin and inflammation |
| JPH11302143A (en) * | 1998-02-20 | 1999-11-02 | Kanebo Ltd | Enhancer of barrier strength against permeation through skin, and cosmetic |
| US6149924A (en) * | 1998-07-20 | 2000-11-21 | Biomed Research & Technologies, Inc. | Composition for enhancing lipid production, barrier function, hydrogen peroxide neutralization, and moisturization of the skin |
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