JP4336486B2 - Hyaluronic acid production promoter - Google Patents

Description

【００９５】
表１の通り、本発明のコラーゲンペプチドは、肌荒れ改善に有効であると認められた。
【００９６】
（試験３）安全性試験
（１）皮膚一次刺激性試験
製造例１で得られたコラーゲンペプチドを固形分濃度が約2.0％になるように調製し、これを背部を剪毛したハートレー系モルモット（雌性，１群３匹，体重300〜350g）の皮膚の2×2cm²の四角当たり0.03mLずつ塗布した。判定は、適用後24，48，72時間に一次刺激性の評点法により紅斑及び浮腫を指標として行った。その結果、全ての動物において、何等、紅斑及び浮腫を認めず陰性と判定された。
【００９７】
（試験４）安全性試験
（２）皮膚累積刺激性試験
製造例１で得られたコラーゲンペプチドを固形分濃度が約2.0％となるように調製し、これを側腹部を剪毛（2×4cm²）したハートレー系モルモット（雌性，１群３匹，体重320g前後）の皮膚に１日１回、週５回、0.5mL／動物当りを塗布した。塗布は２週にわたって、又、剪毛は各週の最終塗布日に行った。判定は、各塗布日及び最終塗布日の翌日に一次刺激性の評点法により紅斑及び浮腫を指標として行った。その結果、全ての動物において、塗布後２週間にわたって、何等、紅斑及び浮腫を認めず陰性と判断された。
【００９８】
（試験５）安全性試験
（３）単回投与毒性試験
製造例１得られたコラーゲンペプチドを12.5％濃度になるよう精製水にて調整し、一匹につき16mL／kg量を、試験前、16時間絶食させたddy系マウス（雄性及び雌性、１群５匹、５週齢）に経口にてゾンデを以て投与し、毒性症状の発現、程度等を経時的に観察した。その結果、全てのマウスにおいて14日間、何等異常を認めず、解剖の結果も異常がなかった。よって、LD₅₀は2,000mg／kg以上であり、安全な物質と判断した。
【００９９】
（処方例）ヒアルロン酸産生促進剤、皮膚外用剤及び飲食品の製造
上記の評価結果に従い、以下にその処方例を示すが、各処方例は各製品の製造における常法により製造したもので良く、含有量のみを示した。又、本発明はこれらに限定されるわけではない。
【０１００】

【０１０１】
（処方例２）乳液 質量％
1.スクワラン 8.0
2.ホホバ油 7.0
3.パラアミノ安息香酸グリセリル 1.0
4.ウロカニン酸エチル 1.0
5.ビタミンＣリン酸エステルマグネシウム塩 1.0
6.セチルアルコール 1.5
7.グリセリンモノステアレート 2.0
8.ポリオキシエチレン(20)セチルエーテル 3.0
9.ポリオキシエチレン(20)ソオルビタンモノオレート 2.0
10.1,3-ブチレングリコール 1.0
11.グリセリン 2.0
12.1,2-ペンタンジオール 3.0
13.製造例１のブタ由来コラーゲンペプチド 2.0
14.製造例１のサメ由来コラーゲンペプチド 2.0
15.豚プラセンタ水抽出液 1.0
16.防腐剤（パラオキシ安息香酸エステル） 適量
17.精製水 100とする残余
【０１０２】
（処方例３）化粧用オイル 質量％
1.流動パラフィン 30.0
2.スクワラン 20.0
3.オリーブ油 20.0
4.パルミチン酸イソプロピル 10.0
5.サメ由来コラーゲンペプチド 1.0
6.杜仲葉50％エタノール抽出液 1.0
7.大豆種子熱水抽出液 1.0
8.オリーブ油 1.0
9.シア脂 1.0
10.ブチルヒドロキシアニソール 0.1
11.ビタミンＥ誘導体 0.1
12.防腐剤（塩化ベンザルコニウム） 適量
13.香料（当帰水） 適量
14.精製水 100とする残余
【０１０３】

【０１０４】
（処方例５）収れん化粧水 質量％
1.ソルビット 2.0
2.ＰＯＥ(20)オレイルアルコール 1.0
3.エタノール 15.0
4.製造例１のブタ由来コラーゲンペプチド 3.0
5.センブリ全草50％1,3-ブチレングリコール抽出液 2.0
6.ゲンチアナ全草50％エタノール抽出液 2.0
7.セージ全草50％エタノール抽出液 2.0
8.酵母50％1,3-ブチレングリコール抽出液 1.0
9.アラントイン 0.2
10.収れん剤（スルホ石炭酸亜鉛） 0.2
11.抗菌・防腐剤（チアミンラウリル硫酸塩） 適量
12.香料（ラベンダー水） 適量
13.精製水 100とする残余
【０１０５】
（処方例６）２層式化粧水（液〜液型） 質量％
1.スクワラン 8.0
2.ＰＯＥソルビタンテトラオレイン酸エステル 0.3
3.ソルビット 1.0
4.エタノール 15.0
5.製造例１のサメ由来コラーゲンペプチド 1.0
6.セージ全草50％エタノール抽出液 1.0
7.アスコルビン酸 0.2
8.収れん剤（カラミン） 0.1
9.防腐剤（フェノキシエタノール） 適量
10.香料（レモン水） 適量
11.精製水 100とする残余
【０１０６】

【０１０７】
（処方例８）パック 質量％
1.ポリビニルアルコール 15.0
2.カルボキシメチルセルロースナトリウム 5.0
3.プロピレングリコール 3.0
4.エタノール 10.0
5.製造例１のブタ由来コラーゲンペプチド 1.0
6.水溶性β-1,3-グルカン誘導体 1.0
7.キイチゴ果実50％ジグリセリン抽出液 1.0
8.生姜果実又は根30％1,2-ペンタンジオール抽出液 1.0
9.防腐剤（パラオキシ安息香酸エステル） 適量
10.香料（バラ水） 適量
11.精製水 100とする残余
【０１０８】
（処方例９）ピールオフパック 質量％
1.グリセリン 5.0
2.プロピレングリコール 4.0
3.ポリビニルアルコール 15.0
4.エタノール 8.0
5.ポリオキシエチレングリコール 1.0
6.パントテニルエチルエーテル 1.0
7.製造例１サメ由来コラーゲンペプチド 2.0
8.オランダゼリ（パセリ）葉又は茎50％エタノール抽出液 2.0
9.ローヤルゼリー50％エタノール抽出液 1.0
10.トレハロース溶解液 1.0
11.防腐剤（パラオキシ安息香酸エステル） 適量
12.香料（カミツレ水） 適量
13.精製水 100とする残余
【０１０９】
（処方例１０）コールドクリーム 質量％
1.サラシミツロウ 11.0
2.流動パラフィン 22.0
3.ラノリン 10.0
4.オリーブ油 5.0
5.カミツレ油 5.0
6.パーム油 5.0
7.ホウ砂 0.5
8.製造例１のブタ由来コラーゲンペプチド 2.0
9.白樺樹皮抽出液 2.0
(エタノール:1,3-ブチレングリコール=1:1抽出溶媒)
10.オタネニンジン根50％プロピレングリコール抽出液 2.0
11.マツホド菌核50％1,2-ブチレングリコール抽出液 1.0
12.大豆種子水抽出液 1.0
13.液状シア脂 1.0
14.グリチルリチン酸ジカリウム 0.1
15.防腐剤（アクリノール） 0.1
16.香料（セージ水） 適量
17.精製水 100とする残余
【０１１０】

【０１１１】

【０１１２】
（処方例１３）洗顔クリーム 質量％
1.ステアリン酸 10.0
2.パルミチン酸 10.0
3.ミリスチン酸 12.0
4.ラウリン酸 4.0
5.オレイルアルコール 1.5
6.ラノリン誘導体（E.O.付加物） 1.0
7.グリセリン 18.0
8.水酸化カリウム 6.0
9.製造例１のサメ由来コラーゲンペプチド 3.0
10.製造例１のブタ由来コラーゲンペプチド 2.0
11.ローヤルゼリー抽出液 1.0
(エタノール:1,3-ブチレングリコール=1:1エキス)
12.グリチルレチン酸 0.5
13.防腐剤（サルチル酸） 0.1
14.香料（ヨモギ水） 適量
15.精製水 100とする残余
【０１１３】

【０１１４】
（処方例１５）サンスクリーン化粧品（Ｏ／Ｗ型） 質量％
1.オキシベンゾン 2.0
2.パラメトキシケイ皮酸オクチル 5.0
3.スクワラン 10.0
4.ワセリン 5.0
5.ステアリルアルコール 3.0
6.ステアリン酸 3.0
7.グリセリルモノステアレート 2.0
8.ポリアクリル酸エチル 1.0
9.1,3-ブチレングリコール 6.0
10.エデト酸二ナトリウム 0.1
11.トリエタノールアミン 1.0
12.二酸化チタン 5.0
13.製造例１のブタ由来コラーゲンペプチド 0.5
14.ヤグルマギク葉50％プロピレングリコール抽出液 0.5
15.ハトムギ種子50％プロピレングリコール抽出液 0.5
16.柚子果実50％ジプロピレングリコール抽出液 0.5
17.防腐剤（パラオキシ安息香酸ベンジル） 適量
18.香料（林檎水） 適量
19.精製水 100とする残余
【０１１５】

【０１１６】
（処方例１７）クリームファンデーション（Ｏ／Ｗ型） 質量％
1.ステアリン酸 4.0
2.モノステアリン酸グリセリン 3.0
3.セタノール 1.5
4.ミリスチン酸イソプロピル 7.0
5.流動パラフィン 10.0
6.サラシミツロウ 3.0
7.トリエタノールアミン 1.5
8.グリセリン 3.0
9.ベントナイト 1.0
10.酸化チタン 8.0
11.2,4-ジヒドロキシベンゾフェノン 8.0
12.カオリン 3.0
13.タルク 3.0
14.着色顔料（黄酸化鉄） 1.0
15.製造例１のサメ由来コラーゲンペプチド 0.2
16.ドクダミ葉熱水抽出液乾燥粉末 0.2
17.温州蜜柑果皮又は果実熱水抽出液乾燥粉末 0.2
18.ユキノシタ全草熱水抽出液乾燥粉末 0.2
19.昆布藻50％エタノール抽出液 0.2
20.丁字蕾50％ジグリセリン抽出液 0.2
21.温州蜜柑果皮50％1,3-ブチレングリコール抽出液 0.2
22.防腐剤（フェノキシエタノール） 0.1
23.香料（ローズ水） 適量
24.精製水 100とする残余
【０１１７】

【０１１８】

【０１１９】
（処方例２０）リンス 質量％
1.塩化ステアリルトリメチルアンモニウム 2.0
2.セトステアリルアルコール 2.0
3.ポリオキシエチレンラノリンエーテル 3.0
4.プロピレングリコール 5.0
5.エチレングリコール 3.0
6.製造例１のブタ由来コラーゲンペプチド 1.0
7.製造例１のサメ由来コラーゲンペプチド 1.0
8.緑茶葉熱水抽出液 1.0
9.マツホド菌核50％1,2-ブチレングリコール抽出液 1.0
10.枇杷葉50％エタノール抽出液 1.0
11.トレハロ−ス溶液 1.0
12.加水分解ケラチン溶液 1.0
13.抗菌・防腐剤（塩化ベンザルコニウム） 適量
14.香料（カミツレ水） 適量
15.精製水 100とする残余
【０１２０】

【０１２１】
（処方例２２）ヘアーリキッド 質量％
1.エタノール 29.0
2.ポリオキシプロピレンブチルエーテルリン酸 10.0
3.ポリオキシプロピレンモノブチルエーテル 5.0
4.トリエタノールアミン 1.0
5.トリメチレングリコール 5.0
6.製造例１のブタ由来コラーゲンペプチド 1.0
7.製造例１のサメ由来コラーゲンペプチド 1.0
8.オタネニンジン根熱水抽出液 1.0
9.レモン果実50％1,3-ブチレングリコール抽出液 0.5
10.リンゴ果実30％エタノール抽出液 1.0
11.白樺樹液 1.0
12.アズレン 1.0
13.抗菌・防腐剤（パラベン、塩化ベンザルコニウム） 適量
14.香料（オレンジ水） 適量
15.精製水 100とする残余
【０１２２】
（処方例２３）ヘアートニック 質量％
1.エタノール 40.0
2.オレイン酸エチル 1.0
3.ポリオキシエチレン(40)硬化ヒマシ油 2.0
4.製造例１のブタ由来コラーゲンペプチド 3.0
5.製造例１のサメ由来コラーゲンペプチド 3.0
6.防腐剤（パラベン） 適量
7.精製水 100とする残余
【０１２３】

【０１２４】

【０１２５】
（処方例２６）育毛・養毛剤 質量％
1.エタノール 60.0
2.製造例１サメ由来コラーゲンペプチド 1.0
3.製造例１のブタ由来コラーゲンペプチド 1.0
4.牡丹根茎又は根皮60％エタノール抽出液 1.0
5.ヨモギ葉又は茎50％1,3-ブチレングリコール抽出液 1.0
6.大豆種子納豆菌発酵液 1.0
7.カンタリスチンキ 0.5
8.パントテン酸誘導体 0.2
9.β−グリチルレチン酸 0.2
10.レゾルシン 0.2
11.サリチル酸 0.2
12.ヒドロキシエチルキトサン溶液 0.2
13.エラスチン加水分解液 0.2
14.抗菌・防腐剤（パラベン） 0.1
15.香料（ラベンダー水） 適量
16.精製水 100とする残余
【０１２６】
（処方例２７）顆粒浴用剤 質量％
1.炭酸水素ナトリウム 58.0
2.無水硫酸ナトリウム 30.0
3.ホウ砂 2.0
4.製造例１のブタ由来コラーゲンペプチド乾燥粉末 4.0
5.製造例１のサメ由来コラーゲンペプチド乾燥粉末 3.0
6.棗全草熱水抽出液乾燥粉末 3.0
7.色素（グンジョウ緑） 適量
【０１２７】

【０１２８】
（処方例２９）被覆保護剤
ガーゼ又はリニメント布に製造例１のブタ由来コラーゲンペプチド及びサメ由来コラーゲンペプチド、抗生物質、抗炎症剤等、適量を混合した処方液を含浸させ、外傷部に添付する。又、製造例１のブタ由来コラーゲンペプチド及びサメ由来コラーゲンペプチドを直接、局所に散布し、ガーゼ等で被覆しても良い。
【０１２９】

【０１３０】

【０１３１】
（処方例３２）めんつゆ 質量％
1.醤油 80.0
2.黒酢 2.0
3.ブドウ糖 13.0
4.グルタミン酸ソーダ 2.0
5.製造例１のブタ由来コラーゲンペプチド乾燥粉末 3.0
【０１３２】
（処方例３３）うどん又はそば 質量％
1.小麦粉又はそば粉 93.0
2.食塩 1.0
3.製造例１のブタ由来コラーゲンペプチド乾燥粉末 2.0
4.製造例１のサメ由来コラーゲンペプチド乾燥粉末 1.0
【０１３３】
（処方例３４）飲料 質量％
1.ブドウ糖液糖 30.0
2.グレープフルーツ果汁 45.0
3.製造例１のブタ由来コラーゲンペプチド乾燥粉末 2.0
4.イヨカン果汁 5.0
5.果糖 4.0
6.香料 適量
7.酸味料 適量
【０１３４】
（処方例３５）パン 質量％
1.小麦粉 80.0
2.食塩 1.0
3.ブドウ糖 7.0
4.製造例１のサメ由来コラーゲンペプチド乾燥粉末 3.0
5.製造例１のブタ由来コラーゲンペプチド乾燥粉末 2.0
6.安息香酸 0.03
7.カルボキシメチルキチン溶液 2.0
8.ビタミンＥ 1.0
9.ヘム鉄 1.0
【０１３５】
（処方例３６）ソーセージ 質量％
1.ひき肉 80.0
2.鶏卵 10.0
3.香辛料 2.0
4.調味料 2.0
5.製造例１のブタ由来コラーゲンペプチド乾燥粉末 2.0
6.トウガラシエキス 4.0
【０１３６】
（処方例３７）ガム 質量％
1.メントールミクロン 30.0
2.グレープフルーツフレーバー 50.0
3.レモンフレ−バー 14.0
4.製造例１のサメ由来コラーゲンペプチド乾燥粉末 3.0
5.サリチル酸 0.03
6.タンニン 2.0
【０１３７】
（処方例３８）みそ汁 質量％
1.豆腐 30.0
2.油揚げ 5.0
3.ニンジン 5.0
4.ゴボウ 5.0
5.白菜 5.0
6.赤味噌 20.0
7.製造例１のブタ由来コラーゲンペプチド乾燥粉末 2.0
8.かつおだし 100とする残余
【０１３８】

【０１３９】
（試験６）使用効果試験
本発明の皮膚外用剤を実際に使用した場合の効果について検討を行った。使用テストは健康な成人女性２５〜５０歳の１０名をパネラーとし、毎日、朝と夜の２回、洗顔後に処方例１の乳液の適量を顔面に３ヶ月に渡って塗布することにより行った。尚、対照には、乳液から本発明のコラーゲンペプチドを除いたものを同様な方法にて処方したものを用いた。又、評価方法は下記の基準にて行い、結果は表２の通りで表中の数値は人数を表す。尚、使用期間中に皮膚の異常を訴えた者はなかった。
【０１４０】
「肌の張り・ツヤ改善効果」
有 効：肌の張り・ツヤが増した。
やや有効：肌の張り・ツヤがやや増した。
無 効：使用前と変化なし。
【０１４１】
〈表２〉

【０１４２】
（試験結果）
表２の通り、本発明品を含有する乳液は、有意に肌の張り・ツヤを与え、又、肌のシワ軽減等の効果を有することが確認できた。
【０１４３】
（試験７）使用効果試験
本発明の食品を実際に使用した場合の効果について検討を行った。使用テストは健康な成人女性２５〜５０歳の１０名をパネラーとし、毎日、朝と夜の２回、処方例３９のクッキー３枚（１回約50g）を１ヶ月に渡って飲食してもらった。尚、対照には、クッキーから本発明のコラーゲンペプチドを除いたものを同様な方法にて処方したものを用いた。又、評価方法は下記の基準にて行い、結果は表３の通りで表中の数値は人数を表す。尚、使用期間中に皮膚の異常を訴えた者はなかった。
【０１４４】
「肌の張り・ツヤ改善効果」
有 効：肌の張り・ツヤが増した。
やや有効：肌の張り・ツヤがやや増した。
無 効：使用前と変化なし。
【０１４５】
〈表３〉

【０１４６】
（試験結果）
表３の通り、本発明品を含有するクッキーは、有意に肌の張り・ツヤを与え、又、肌のタルミも軽減することが確認できた。
【０１４７】
【発明の効果】
本発明のコラーゲン又はゼラチンのコラゲナーゼによる分解物であり、そのアミノ酸配列が、（Ｇｌｙ−Ｘ−Ｙ）（式中、Ｇｌｙは、グリシン残基を表し、Ｘ，Ｙはアミノ酸残基を表し、互いにＸ，Ｙは同一であっても、異なってもよい）で表されるコラーゲントリペプチドからなるコラーゲンペプチド（Ｇｌｙ−Ｘ−Ｙ）n（ｎは、正の整数を表す）は、安全性が高く、ヒアルロン酸産生を有意に促進し、肌荒れ改善作用を有することが確認された。更に、これらを含有する皮膚外用剤や飲食品は肌に対して、張りやツヤの付与、又はシワやタルミの改善といった皮膚老化防止効果を有する。
【図面の簡単な説明】
【図１】本発明のブタ由来コラーゲンペプチド（「サメ由来ＣＰ」と表す）並びにサメ由来コラーゲンペプチド（「ブタ由来ＣＰ」と表す）のヒアルロン酸産生促進率を示す図である。[0001]
BACKGROUND OF THE INVENTION
This invention provides the hyaluronic acid production promoter which uses the specific collagen peptide which is a decomposition product by collagenase of collagen or gelatin as an active ingredient, and the skin external preparation or food / beverage products containing the same.
[0002]
[Prior art]
Typical changes in the aging of human skin are wrinkles and tarmi, which is one of the major skin problems for older people and women. However, at present, there are few effective treatments for skin wrinkles and tarmi, and various studies on aging have been conducted in the aging society.
[0003]
At present, the formation of wrinkles and tarmi on human skin is thought to be caused by a decrease in skin elasticity, which includes aging, drying, oxidation, and the effects of sunlight (ultraviolet rays). Specific histological phenomena include changes in extracellular matrix components such as collagen, elastin, and glycosaminoglycans in the dermis. Among these glycosaminoglycans, hyaluronic acid is widely distributed in connective tissues. It is known as a high molecular weight polysaccharide that retains a large amount of moisture in the skin and has a gel-like form. Therefore, qualitative and quantitative reduction of hyaluronic acid is considered to be important in skin aging.
[0004]
[Problems to be solved by the invention]
Therefore, the present invention promotes the production of hyaluronic acid, develops a hyaluronic acid production promoter effective for preventing skin aging such as improvement of rough skin, imparting elasticity, tension and gloss of the skin, and improving wrinkles and talmi. An object of the present invention is to provide a composition that leads to beauty and maintenance of homeostasis by utilizing the natural action of the living body.
[0005]
[Means for Solving the Problems]
In view of these circumstances, the present inventors set a theme of development of a useful naturally-derived component having a hyaluronic acid production promoting action, and as a result, it is a degradation product of collagen or gelatin by collagenase, and its amino acid sequence is (Gly- XY) (wherein Gly represents a glycine residue, X and Y represent amino acid residues, and X and Y may be the same or different from each other). It was confirmed that the collagen peptide (Gly-XY) n (n is a positive integer) consisting of significantly promotes hyaluronic acid production. In addition, by increasing hyaluronic acid distributed in the connective tissue, it has an effect of improving skin roughness, and the skin external preparations and foods and beverages containing these have the application of tension and gloss, or the improvement of wrinkles and tarmi It was also confirmed to have an effect of preventing skin aging. Therefore, the present invention has been completed by providing a novel and safe hyaluronic acid production promoter, skin external preparation, and food and drink.
[0006]
DETAILED DESCRIPTION OF THE INVENTION
Collagen, which is an active ingredient of the present invention and is a starting material for collagen peptide, is not particularly limited, and any type I to XIII type collagen can be used. Collagen can also be used. In reality, it is assumed that collagen is a mixed type collagen obtained from various animals and fish. The source of this collagen is animal (for example, cattle, pigs, birds, whales, etc.). And fish (eg, flounder, salmon, sardines, tuna, sharks, etc.). Of these, pigs and sharks are particularly preferred.
[0007]
Extraction and purification of collagen from these components can be carried out using generally known methods. Specifically, for example, after pulverizing a tissue containing collagen such as bone, skin, tendon, meat, duck, scale, etc., washing with water, extraction with a dilute salt solution, extraction with an acid or alkali solution, pepsin, trypsin or hyaluronidase It can be obtained by purifying collagen by extraction with an enzyme such as salt, and applying known purification means such as salting out and dialysis. It can also be obtained as “regenerated collagen” by a generally known method. Commercially available collagen can also be used as a starting material for collagen peptides.
[0008]
Gelatin is a water-soluble protein obtained by heating and extracting the aforementioned collagen with water. In the present invention, gelatin produced by a generally known method can be used as a starting material for the above-described collagen peptide, and a commercially available product can also be used.
[0009]
The collagen peptide which is an active ingredient of the present invention can be produced by allowing collagenase to act on collagen or gelatin obtained as described above.
[0010]
The collagenase used here is not particularly limited, but is derived from bacteria such as Clostridium histolyticum Streptomyces parvulus, actinomycetes or fungi, and has a unique amino acid sequence [(Gly-XY) n (where Gly is a glycine residue). And X and Y represent amino acid residues, which may be the same or different from each other, and n represents a positive integer). Hereinafter, this amino acid sequence is also referred to as “specific amino acid sequence”. It is preferable to use collagenase that specifically cleaves the amino group terminal side of the glycine residue of)] because it is possible to obtain a collagen peptide rich in peptides of this unique amino acid sequence.
[0011]
Further, the collagenase used here may be a collagenase obtained as a natural product, for example, a modified collagenase having the above-mentioned specificity obtained by modification by a protein engineering technique.
[0012]
The types of amino acid residues that can be taken by the above X and Y are not particularly limited, and are usually amino acid residues of naturally occurring amino acids, specifically alanine residues, valine residues, leucine residues. Group, isoleucine residue, proline residue, hydroxyproline residue, phenylalanine residue, tryptophan residue, methionine residue, serine residue, threonine residue, cysteine residue, glutamine residue, glycine residue, asparagine residue , Tyrosine residue, lysine residue, arginine residue, histidine residue, aspartic acid residue, glutamic acid residue can be used (in this specification, unless otherwise specified, amino acid Residue means an L-form amino acid residue).
[0013]
The collagen peptide that can be used in the present invention is a collagenase immobilized on an immobilization carrier such as free or chitobar according to a generally known method, for example, a method described in JP-A-7-82299. Can be produced by a batch method, a column method or a combination of these methods, preferably by setting the reaction temperature to 40 to 45 ° C.
[0014]
Peptides having a unique amino acid sequence that can be produced in this way, most preferably collagen peptides rich in the above-described collagen tripeptides whose positive integer n is 1 (in order to exert the desired effects of the present invention) The positive integer n is preferably as small as possible), and the antigenicity peculiar to gelatin and collagen is remarkably suppressed, and these allergic reactions can be caused by containing this in a skin external preparation or food and drink. Etc. can be further improved.
[0015]
In addition, the collagen peptide containing a peptide having a specific amino acid sequence has a positive integer n of 1 to 7, that is, an average molecular weight of 280 to 3000 can express the effect of the product of the present invention, and collagen and the like. It is preferable in that the antigenicity derived from it can be eliminated and the safety to the skin can be maintained at a higher level. 280 which is the minimum value of the average molecular weight is a molecular weight assuming the above-described tripeptide having a positive integer n of 1, and as described above, it is preferable to take a value as small as possible around 280.
[0016]
Furthermore, the content of the collagen tripeptide having a specific amino acid sequence (positive integer n is 1) in the collagen peptide is preferably 25 to 100% with respect to the collagen peptide.
[0017]
The above-described fractionation of a degradation product having a specific average molecular weight of a collagen peptide, or the degradation product having a specific amino acid sequence collagen tripeptide (a positive integer n is 1) content in a specific range is usually used. A well-known fractionation method, for example, a gel filtration method, a reverse phase chromatography method, or the like can be used alone or in some cases in combination.
[0018]
Collagen peptides can be produced according to the above-described method and contained in the present product, but commercially available products such as the collagen name tripeptide series (manufactured by Miyagi Chemical Co., Ltd.) can also be used. Is possible.
[0019]
The collagen peptide in the present invention can be contained as it is in skin external preparations and foods and drinks, but its content varies somewhat depending on the type of applied dosage form, method of use, and expected action, but is usually 0.001 as a solid content. % Or more, and particularly preferably 0.01 to 20.0%.
[0020]
If this content is less than 0.001% with respect to the entire composition, it is difficult to sufficiently exert the hyaluronic acid production promoting effect, and conversely, even if it contains more than 20.0%, Not only is the tendency that the enhancement of the effect cannot be expected in proportion to the increase in the content, but this is not preferable, and there may be a problem in the preparation in terms of safety.
[0021]
The dosage form and form of the hyaluronic acid production promoter or skin external preparation of the present invention and food and drink are arbitrary, such as capsules, powders, granules, solids, liquids, gels, bubbles, emulsions, creams, ointments, sheets, etc. It can mix | blend and use with a form.
[0022]
The field of use can be used in various internal and external preparations (including preparations used for animals) in general, and specifically, ampoules, capsules, pills, tablets, powders, granules, solids, liquids 1) Pharmaceuticals, 2) Quasi-drugs, 3) Topical or systemic skin cosmetics (eg lotion) , Basic cosmetics such as emulsion, cream, ointment, lotion, oil, pack, facial cleanser and skin cleanser, massage agent, cleansing agent, hair remover, hair remover, shaving treatment, after shave lotion, pre-shave Makeup cosmetics such as lotion, shaving cream, foundation, lipstick, blusher, eye shadow, eyeliner, mascara, perfume, nail preparation, beauty nail enamel, beauty nail ena Removers, poultices, plasters, tapes, sheets, patches, aerosols, etc.), 4) medicinal or / and cosmetic preparations applied to the scalp and hair (eg shampoos, rinses, Hair treatment agent, pre-hair treatment agent, permanent solution, hair dye, hair styling agent, hair styling agent, hair growth / hair nourishing agent, poultice agent, plaster agent, tape agent, sheet agent, patch, aerosol agent, etc.), 5) bath Bathing agents used in hot water, 6) Other anti-smell and deodorants, deodorants, antiperspirants, hygiene products, sanitary cotton, wet tissue, toothpastes, mouth fresheners, gargles, etc. It is done.
[0023]
Furthermore, as foods and beverages, oral compositions (gum, candy, etc.), processed fishery products such as kamaboko and chikuwa, livestock products such as sausages and ham, Western confectionery, Japanese confectionery, raw noodles, Chinese noodles, boiled noodles, buckwheat etc. Seasonings such as noodles, sauce, soy sauce, sauce, sugar, honey, powdered candy, syrup, etc., spices such as curry powder, mustard powder, pepper powder, jam, marmalade, chocolate spread, pickles, red vegetables, sprinkles, or Processed vegetables and fruits such as canned and bottled vegetables, dairy products such as cheese, butter, yogurt, miso soup, soup, fruit juice, vegetable juice, whey drink, soft drink, alcoholic beverages, etc. Use for general foods and drinks such as health foods and health supplements.
[0024]
The hyaluronic acid production promoter or external preparation for skin and foods and beverages according to the present invention are optional components and additives exemplified below within the range that does not impair the effects of the present invention in addition to the essential components. The content in the preparation is not particularly specified, but is usually preferably 0.0001 to 50%.
[0025]
(1) Various fats and oils
Avocado oil, almond oil, fennel oil, egoma oil, olive oil, orange oil, orange rafa oil, sesame oil, cacao butter, chamomile oil, carrot oil, cucumber oil, beef tallow fatty acid, kukui nut oil, safflower oil, shea butter, liquid shea Fat, soybean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg yolk oil, palm oil, palm kernel oil, owl, coconut oil, beef tallow, lard , Squalene, squalane, pristane or hydrogenated products of these oils and fats (hardened oil, etc.).
[0026]
(2) Wax
Beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax, montan wax, shellac wax, rice wax, etc.
[0027]
(3) Mineral oil
Liquid paraffin, petrolatum, paraffin, ozokelide, ceresin, microcrystalline wax, etc.
[0028]
(4) Fatty acids
Natural fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, 12-hydroxystearic acid, undecylenic acid, tall oil, lanolin fatty acid, Synthetic fatty acids such as isononanoic acid, caproic acid, 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid and isopentanoic acid.
[0029]
(5) Alcohols
Natural alcohols such as ethanol, isopyropanol, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, phytosterol, phenoxyethanol, and synthetic alcohols such as 2-hexyldecanol, isostearyl alcohol, 2-octyldodecanol.
[0030]
(6) Polyhydric alcohols
Ethylene oxide, ethylene glycol, diethylene glycol, triethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, polyethylene glycol, propylene oxide, propylene glycol, polypropylene glycol, 1,3-butylene glycol Pentyl glycol, glycerin, pentaerythritol, threitol, arabitol, xylitol, ribitol, galactitol, sorbitol, mannitol, lactitol, maltitol and the like.
[0031]
(7) Esters
Isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, diethyl phthalate, phthalate Dibutyl acid, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, propylene glycol dioleate, and the like.
[0032]
(8) Metal soap
Aluminum stearate, magnesium stearate, zinc stearate, calcium stearate, zinc palmitate, magnesium myristate, zinc laurate, zinc undecylenate, etc.
[0033]
(9) Gums, sugars or water-soluble polymer compounds
Gum arabic, benzoin gum, danmar gum, guaiac gum, Irish moss, Karaya gum, tragacanth gum, carob gum, quinseed, agar, casein, lactose, fructose, sucrose or esters thereof, trehalose or derivatives thereof, dextrin, gelatin, pectin, starch, Carrageenan, carboxymethyl chitin or chitosan, hydroxyalkyl (C2-C4) chitin or chitosan to which alkylene (C2-C4) oxide such as ethylene oxide is added, low molecular chitin or chitosan, chitosan salt, sulfated chitin or chitosan, phosphorus Oxidized chitin or chitosan, alginic acid or salt thereof, hyaluronic acid or salt thereof, chondroitin sulfate or salt thereof, heparin, ethylcellulose, methylcellulose, carboxymethylcellulose, carboxy Siethyl cellulose, sodium carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, crystalline cellulose, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylate, polyalkylene oxide such as polyethylene oxide and polypropylene oxide, or The cross-linked polymer, carboxyvinyl polymer, polyethyleneimine, etc.
[0034]
(10) Surfactant
Anionic surfactant (alkyl carboxylate, alkyl sulfonate, alkyl sulfate ester salt, alkyl phosphate ester salt), cationic surfactant (alkylamine salt, alkyl quaternary ammonium salt), amphoteric surfactant: carboxylic acid Type amphoteric surfactant (amino type, betaine type), sulfate ester type amphoteric surfactant, sulfonic acid type amphoteric surfactant, phosphate ester type amphoteric surfactant, nonionic surfactant (ether type nonionic surfactant) Agent, ether ester type nonionic surfactant, ester type nonionic surfactant, block polymer type nonionic surfactant, nitrogen-containing type nonionic surfactant), other surfactants (natural surfactant, protein Hydrolyzed derivatives, polymer surfactants, surfactants containing titanium and silicon, fluorocarbon surfactants Etc..
[0035]
(11) Various vitamins
Vitamin A group: retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene, lycopene (provitamin A), vitamin B group: thiamine hydrochloride, thiamine sulfate (vitamin B1), riboflavin (vitamin B2), Pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folic acid, nicotinic acids, pantothenic acids, biotins, choline, inositols, vitamin C group: vitamin C acid or derivatives thereof, vitamin D group: ergocalciferol (vitamin D2 ), Cholecalciferol (vitamin D3), dihydrotaxosterol, vitamin E group: vitamin E or derivatives thereof, ubiquinones, vitamin K group: phytonadione (vitamin K1), menaquinone (vitamin K2), menadione (vitamin 3), menadiol (vitamin K4), other essential fatty acids (vitamin F), carnitine, ferulic acid, .gamma.-oryzanol, orotic acid, vitamin P such (rutin, eriocitrin, hesperidin), vitamin U and the like.
[0036]
(12) Various amino acids
Valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine, arginine, ornithine, histidine And amino acid derivatives such as sulfate, phosphate, nitrate, citrate, or pyrrolidone carboxylic acid.
[0037]
(13) Various additives derived from plant or animal materials
These are processed in a conventional manner according to the product type and form to be added (for example, pulverization, milling, washing, hydrolysis, fermentation, purification, pressing, extraction, fractionation, filtration, drying, pulverization) , Granulation, dissolution, sterilization, pH adjustment, deodorization, decolorization and the like are arbitrarily selected and combined), and may be arbitrarily selected from various materials.
[0038]
The solvent used for extraction may be selected in consideration of the intended purpose and type of the product to be provided or the processing to be performed later. Usually, water, methanol, ethanol, propyl alcohol, isopropyl alcohol, butanol 1 type selected from various organic solvents such as lower alcohols such as isobutanol or hydrous lower alcohols, polyhydric alcohols such as propylene glycol, 1,3-butylene glycol and glycerin or hydrous polyhydric alcohols, acetone and ethyl acetate Alternatively, it is desirable to use a mixture of two or more. However, when it is not preferable to contain an organic solvent depending on the application, it is sufficient to use only water or ethanol that can be easily removed after extraction, and it may be used alone or in any mixture with water. The thing extracted and extracted may be sufficient.
[0039]
In addition, when using additives derived from plant or animal-based ingredients for systemic or topical external preparations and cosmetics, it protects skin and hair, moisturizes, improves touch and texture, imparts flexibility, and stimulates Relaxation, stress relief by fragrance, cell activation (cell aging prevention), suppression of inflammation, improvement of skin and hair quality, prevention of rough skin and its improvement, hair growth, hair growth, hair loss prevention, imparting gloss, cleansing effect, In addition to cosmetic effects such as fatigue relief, blood flow promotion, and warm bath effects, effects such as flavoring, deodorization, thickening, antiseptic, and buffering can also be expected.
[0040]
In addition, in food and drink, nutritional supplementation, fatigue recovery, tonicity, cell activation (cell aging prevention) and other healthy and cosmetic effects, as well as improved taste, color tone, aroma, gloss, stabilization, thickening, It can be used for antiseptic purposes. In addition to this, various cosmetic and pharmaceutical effects of each of the known raw materials are expected, and by combining these, the intended effect can be promoted or multifunctional. It is also possible to make the product expected to be effective.
[0041]
Specific plants (herbal medicines) as raw materials include, for example, almonds (toen), ai (indigo leaves), aokazura (Keifu Fuji), Aoki (Aoki), Aogiri or Kenashia Ogiri (Ao Tung), Aotsu Samurai (wooden candy) , Aotenma, acacia, red ginseng, red spruce `` fruit '', red clover, red grapes, red ginseng (logwood), red wrinkles (red buds), red crested or red crested or reddish (root), red crested or reddish (ground yellow), Agi (Aki), Aki larch, Akinire (crusted skin), Aguay Guassou, Aguahe (Omiten coconut palm), Akebi (Kitsu), Asa (Asakojin), Maruba morning glory or morning glory (Chicken), Hydrangea (hydrangea), Ashitaba (Tomorrow), Azuki (Red Azuki), Asunaro, Acerola, Asenyaku (Asenyaku), Athira (Shokuyokanna), Anise, Abiyu, A Biurana, oilseed rape, Abemaki `` fruit '', avocado, ama, achacha (Amacha), Achacharu, Amadokoro (Jade bamboo), Amana (a light-hearted), amaranth (Hyuyu, Hagatetou, Himogeito, Senninkoku, Sugimorigateto, Hosoaogeito, Hasoagoito (Aozzuran, Amaranthus Hypochondriacus), Amiga Sayuri or Baimo (shellfish mother), Aristolomeria (Yurizuisen), Arcana (Arkana), Argarovo (Cabbage), Altea, Arnica, Alpinia or Katsumadai (Suzukuku), Angelica, Apricot or Honzu (Apricot kernel), Ansokkou (benzoic acid), Yellow support, Igakouzolina (Gallhead), Ikarisou or Yachima Taikoshi (Inyokaku), Rabbits (Kinshin Grass), Japanese knotweed (Tiger root), Yew (first place), Strawberry, Fig ( fig" Fruit, leaves ''), Ichihatsu (first), Ichibi (winter lion), Ichiyakusou (one medicinal herb), Ginkgo (Ginkgo `` seeds, leaves ''), Itohimehagi (distant), locust bean, Inazuna (Taileki), Inubiyu (Honagainubiyu) ), Rice `` Seeds, Seed coat '', Inondo `` Seeds '', Ibuki Sou Sou, Nettle, Iran Iran, Iwa Tobacco (Iwabuchi), Iwahiba or Iwamatsu (Maki), kidney bean, oolong tea, fennel (mud), wheat (Chibusano), Ukiyagara (Sanryo), Uguisukagura `` fruit '', Japanese cypress, turmeric (depressed gold), duckweed (float), usba saishin or keirin saishin or okasai saishin (spicy), usbenia oyster, usbenitachaoi oyster orchid orchid Summer hay), Udo or Shishido (Aki, Aki, Tang Dynasty), Unyadegato (Uncaria, Cat's Claw), Uva , Japanese apricot (seed `` seed, flesh ''), Japanese white beetle, Japanese eelfish (Kusako-kemo), Unshiu mikan (Chen), Unboku, Estragon, Ezoukogi (Tomogoka), Ezo-suzuran, Echinashi (Hosomuramurabareniku), Enishida, Enokitake , Ebisu or Cassia Tora (Keriko), El Campre, Elderberry `` fruit '', Elemi, Elingi or Prerotus eringi, Enju (Safflower, Camellia rice), Pea, Ogi or Kibanaougi (Yellow), Narcoli or Key Carbanarukoyuri (Yellow spirit), Ohisasanoyuki or Sasanoyuki, Auren (Yelen), Ogata Houken, Okarasuuri (Karokon), Oguruma (Civil fragrance), Otsura Rafuji (self-protection), Psyllium (pre-cargo, front-cursed grass), Japanese thistle State leakage, bald eagle), toucan (lion), toucan , Ovana okera or Okera (white birch), Ovanasasuberi (Banaba), Obayayashabushi "fruit", Steller's beetle (cereal sperm), Omia catechu, Hawthorn or Hawthorn (Yamako), Omi palm, Barley (barley), Oka, Okaze Serpentine), Oguruma (turnover), Oguri higotai (Zhengzhou leakage, indigo sashimi), Panax ginseng or Echirea ginseng (Ginseng), Hypericum pertussis or L. pertussis or Hypericum pertussis (broken grass), Odorikosou (continuous), Onamomi Sprouts, Onigurumi, Onikoro or Tokoro or Nagadokoro (Hikai), Oni Yagara (Tempa), Onyuri or Sasayuri or Hakatayuri (Yuri), Onoelan, Ononis, Halibut (Kiribana), Ominaeshi (losing sauce), Oyuko, Netherlands Mustard (watercress), Dutch jellies, Dutch ville, Dutch honey bees, Oh -"Fruits, Seeds, Leaves", Oregano, Orange "Fruits, Peels", Silkworms (Mature Yellow), Cacao "Fruits, Peels, Seeds", Oysters (Powder "Leaf"), Kagi Kazura (Tsukado) , Kakidooshi or Kantori (Lotus herb), Kakiran, Gaku hydrangea, Cassia, Casino oyster (fruit `` fruit ''), Gadju (莪 朮), Kashiwa (Bamboo shoot, Kashiwa leaf), Cascarilla, Cascaraca, Gypsophila, Gypsophila, Crab (Kinshato), Kaniwa, Carnation, Valerian (Valentine Root), Hippopotamus, Birch or Weeping Birch (White Birch), Gerbera, Pumpkin, Kapok'Noki "Seeds", Kahoku Salamander (Garden), Gama (Camellia), Chamomile or Roman Chamomile, chamomile (weed), cam cam (camo duck), carraguwa or yamaguwa (mulberry camellia), color, chrysanthemum salmon, crow cucumber or cinnamon crow (king moth), crow bisha (Half-summer), oats, guarana `` seed '', calahoo (kokubaku), karaya, garyu, karin (garden), garcinia, kawamidori, kawara-cho (commissioned greens, white-billed grass), kawajisha, kawaratake, kawaranadeshiko (stone bamboo) ) Or Ezokawaranadeshiko (buckwheat, buckwheat), Chinese carrot (blue potato), Chinese mugwort (bamboo chin mackerel), kansui (sweet candy), licorice (licorice), kantarasa, candelilla, kanto, canna, kanran, raspberry (ezo strawberry, Dutch Strawberry, Shrimp Strawberry, Narrow White Strawberry, Momiji Strawberry, European Yellow Strawberry), Kiwi `` Fruits, Leaves '', Kikarasuuri (Gurone), Chrysanthemum (Kikyo, Kikyo Root), Chrysanthemum (Chrysanthemum, Zebra Flower, Ginseng), Kikutaniku, Kisage ( (Fruit), scallop (sheep), pheasant (fruit), kizuta, yellow aloe, yellow mint, kina, quinano Ki (Cinchona, Red quince), Quinua (Quinoa), Yellowfin (Yellow), Kimame, Gymnema sylvesta, Kimenkaku, Cabbage, Cabbage `` Immature fruit '', Caraway, Cucumber, Gyory (Nishikawa willow, Tail willow), Kiraja saponaria , Kiraya, Kiranso (Kinza Kosaku), Kumquat “Fruits”, Kinkiju, Ginsekai, Kimbusen, Kinma, Kimihihiki (Sentsukusa), Kinran, Ginlan, Kinryohen, Guapeba Vermelha, Guava “Fruits”, Guayule, Quercus Infectria (Garlic), kukui nuts, kugenumaran, wolfberry (bamboo shoots, coconut leaves, cocoon leaves, ground bark), cedar kazura (tenmon winter), kudu (kudzu), camphor tree, gooseberry `` fruit '', ginseng (yellow flower bud), kudu Titi River, Gardenia (Mountain Lion), Kunugi (Mountain Saw), Kupuas, Kubeba, Mazasa, pine moth (horse whip grass), clara (bitter), cranberry "fruit", chestnut "seed, fruit, astringent skin", curk crifo latifolia "fruit", grapefruit "fruit and leaf", buckthorn, black moth (rescue necessity) , Kamebahikokoshi or kurobanahikikoshi or hikikoshi (prolongation grass), clove (clove, clove), gumba nazuna (sekimei, budgerigar), keigai (butterfly, cocoon), celosia (chicken flower, henko), gekkavidin, bay bay (laurel tree), Kenashi Sartorii rose (earthen soil, mountain return), Gentiana, Gennoshouko (Oldgrass grass), Kemponashi (Kigushi), Kokisekoku, Kushimikan (Koji, Tachibana, Obenimikan, Fuclican, Sagamikouji, Ponkan, Santara (Tachibana bark)), Koshinbara (Moon season flowers), Kousui mint, Kozo `` fruit '', Kocha (Tea), kohone (river bone), koh hong (Tsubakimoto, Karamoto), Koryang, Kouryokyo (Koryo), cilantro `` fruit '', Kouren (Huo Ren), Koganebana (Yellow Gon), cowberry (Etsutachibana), coconut `` Fruit '', Goshuyu (Kurean), Gosho Strawberry (Pepper), Pepper (Pepper), Cosmos, Copaiba Balsam, Coffee `` Seeds, Leaves '', Kobushi or Mokuren (Spicy Pepper), Burdock (Beef Bowl, Beef Bowl), Kobotanru, Sesame (sesame seeds), sesame seeds (genus ginseng), trash (seed), sakanekazura or binankazura or matsubusa, wheat (wheat), rice or rice bran "red rice cake, birch", rice oil, cola acminata "seed", cola vera `` Seeds '', Coleus Forskohlii, Colonyella, Koroha `` Fruits '', Colombo, Conzurango, Kombu, Konjac, Comfrey (Chang Zhang grass), Sisal (Sisal Asa), Sa Highland, Sakaneran (Ezosakaneran), Sasima button eel or cinnamon bud or Senacens (weikensen), Sakura (Oshima cherry, Yamazakura, Oyamazakura, Edohashi, Bean cherry, Miyazakura, Yoshino cherry, Takanezakura, Kanzakura, Kozakura, Kokura, Leaf Flowers, fruit, bark (cherry bark) ''), cherries, pomegranate, Sasa, Sasabagin orchid, sasanqua, Sadamodaka (Sawaka), sweet potato, sugar cane, sugar beet, sunflower jujube, saffron (bancho flower, west safflower), sapodilla , Sapotea mariyo, pomelo `` fruit '', savonso, salmon berry `` fruit '', salamander (sasma), salamander (sand sashimi), salvia (sage), ragweed (bamboo rape), sawagurumi (wild walnuts), sankaku cactus The Sangre Grado (croton), Cinnamon carrot, Sancini carrot (Ginseng ginseng), Sanshuyu (Yamamuro), Sansho (Yamamuro), Sandskon (Yamadone), Shia (Kalite), Cyano `` fruit '', Shiitake mushroom (Shiitake) , Zion, Shikakuameme, Dikitarisu, Shikunshi (Ashikiko), Perilla or Aojiso or Chiri-Mendiso or Catameniso (Shiyoha, Shiso-ko), Rosewood, Shinanoki, Shiraho-noki, Shinalen-gyo (ream), Shimeji (Himushiji, Shakashimeji, Hatakeshiji) , Oshiroi shimeji, beech shimeji, honjimeshi, shirotamogitake), shimokren (hot pepper), shimotsuso, potato, peonies (glaze), shajin (shasan), jasmine (matsurika), janohige (bare winter), juroxusage, shukukon Gypsophila, Shukushamitsu (sand seed, shrunk sand), Juzdama, Shuro "fruit", Shun , Zouenashi, Ginger (Ginger), Zozan Hydrangea (Tsuneyama), Shobu (Koji, Sone), Shozu `` Fruit '', Shirakashi `` Seeds '', Silane (Bikkyu), Shirogoricho `` Seeds '', White clover (Clover), White cherry (Chicken bone grass), white squirrels (scented squirrels), white squirrel “flowers”, white sage lupine, shirominanten (southern tenm), cinchona sylbula, ginkgo biloba (mizuka, sika flower, shenzhen), cinnamon, cinnamum cassia , Watermelon (Saijo), honeysuckle (gold and silver flowers, Shinobu), sorrel (Acid), swim berry `` fruit '', star apple, stevia, strawberry `` fruit '', tin-seed coconut (Sugar), sugina (question), purslane (horse teeth) (Skin, horse tooth tender), plum "fruit", sulgaran (oran), red pine "ball cone", caladium Tsutsu, Kizota, Gurmi, Hawthorn, Sunflower, Dandelion, Horse Chestnut (Maroni), Pear `` Fruit '', Prunus serrata, Elderberry (Elder), Prunus (Juniper, Juniper), Millefoil (Milfoil) ), Rose, pearl butterfly, mistletoe, yellow mint or wild mint Nosekoku) (Dendrobium, sarcophagus), Cedron (Boushuboku), Zeni Mallow, Hiroha Senega, Senega, Seri, Celery, Senkyu (river cucumber), Senshinren (Puncture ream) Dandan, sennin cactus, senna `` fruits, leaves '', senninsou (Otsuka), senburi (medicated), senboku, soka (grass), elephant shoots, prunus, buckwheat `` seed '', some mono-potato, broad bean, daiou (large yellow), Daikon radish, soybean, Daidai (orange peel, fruit), Takasago Gurihigotai (Southeast indigo sashimi), Takasaburo (Cirrus), Takatodai (daikon), Takaharabi (Kashiwaji), dark sweet cherry `` fruit '', hollyhock, Tachi musk (thyme, perilla), tachidokoro (hikai), tachiyanagi, tamarind `` seed '', onion, ramshiba (hot pepper), taranoki `` fruit, leaves, root bark '', tarayou (large leaf winter blue, one leaf tea, bitter tea, bitterness (Tea), Dahlia (Tenji button), Tarwi, Tankimi, Tanshichiwa, Tanjin, Dandelion, Shirobana Dandelion or Mouko Dandelion , Dammar, cherry `` fruit '', chigaya `` fruit, root, bud '', chixetsu carrot (bamboo ginseng), chicory, champa piedra (tulips), tulip, choco no stay, datura (artichoke), datura ), Korean senile (蕪 夷), Korean mugwort (艾艾), Choreimaitake (猪苓), Chorogi, camellia, tsukushikananeran, Tsukutake (mushroom), azalea, camellia, camellia, clover (lacquered licorice), camellia (duck) (Crop grass), vine azuki (red azuki beans), tsurutsuchiakebi, tsurudukudami (what's neck rice), tsuruna (apricot), tsuru carrot (four leaf ginseng), tsurumame, tsuwabuki, daiko, teuchigurumi, duberry `` fruit '', tengusa, tencha (bamboo tea), tendai oyakaku (Glaze), red pepper (winter lion), red pepper, red pepper (banban), Toki (Toyori), Tokinsenka (Marigold), Tosykachichi, Tounabena (river cut), Corn or Corn hair (Minami Kashiwa), Toshikomochi (Sadako), Torindo or Kyousen Lindou (Ryuboku), Toksa (wood bandit) , Dokudami (ten drugs), tokon (root), toshishi or bean pod or pear root, eucommia (Tatsunaka `` bark, leaf, root ''), ash (skin), tomato, tragacanth, triacanthus `` seed '', Turkish Kyo, Torumentilla, Doronoki, Toro-aoi, Tonkame, Niseria berry `` fruit '', Chinese yam or wild yam (Yakuyaku), Nagii Kada (Butcher Bloom), Naginata Koju, Nazuna, Rapeseed, Natsume or Vertical oyster (Sword bean), Natsumikan, Jujube Naniwaibara (Kanasakurako), Navena (repeated), Nameko, peanut (peanut), Nanten (nanten) Fruit), Namban Karamushi (Cannabis), Niosumire, Nigaki (Nakiki), Nigamugigi (Anniversary), Nikuzuku, Kay or Nikkei or Ceylon Nikkei or Yabu Nikkei (Cinnamon) or Keishi (Katsura Branch), Nyo-bachidori, Chile ), Elderberry (bone, `` fruit, flower, stem, leaf ''), garlic (large cocoon), nurde (pentose), leek, nemkin or nebu or nembi or nemkinoki or zigokubana (community), noami (large cocoon), noibara ( (Fruit), Nozenkazura (Lingen flower), Nogateto, Yarrow, Nodake (Mae-hu), Novara, Peach, Pineapple `` Fruit '', Hibiscus (Busouge, Furibususouge, Roselle), Hirindou, Gauchiwa, Pau Doce, Hakama Labosi Supplement), Hakkayumatou, Chinese cabbagebird, Hakusen (white ring skin), Hakulberry `` fruit '', Japanese chickweed (breeding), Hazel (coconut), Shiridokoro (roth root), basil, lotus (lotus, lotus meat, lotus root), parsley (holland jellied), hadakamigi, batata, wasp or mushroom (bamboo bamboo), patchouli, mint (thin load, light load leaf), yellow bean, pearl barley ( (Yokuinin), Hanasuge (knowing mother), banana, Hanahaku, Hanabishi (Sitoshi, Shishitsuri), vanilla bins, papaya, scallops, Pahalobo, hub "whole grass, stem, leaf", paprika, Hamakakiran, Hamago or Mitsuba Hamago (Vulgaris), Hamasuge (Katsukiko), Habibishi (Shitsuko), Hamanasu (Maikai Flower), Hamaboufu (Hamaboshi), Hamamelis, Palm, Rose (Rose), Balata, Balata Rubber, Agaric, Agaric ), Haran, Pariurus (Haricus japonica), Parietalia, Harkanran, Balsamina (Tsurure) (Ishi, bitter gourd), harimille (crusted skin, cinnabar white skin, cocoon leaf), Barbasco, Harlindow, HANDAI kai (胖胖 大海), breadfruit, giant eagle (shooting), lizard carrot (participant), pecan nuts, ganbanana (stone carp, (Vulture Shahua), Higurmadaria, Higotai, Hishitai, Pistachio, Beet, Hitsuba (Ishizuchi), Hitsubei Nishida, Daisies (Daisy), Hinata Taikozuchi (cow knee), Japanese cypress, Japanese cypress, Japanese cypress, hiba, castor, Sunflower, Bell Pepper, Himeuzu (Tempo), Himegama (Kaori), Himematsutake (Kawariharatake, Hiromatsutake), Himemuyoran, Pimenta `` Fruit '', Bikushi, Beakkyu, Hiyu `` Fruit '', Chickpea, Hiramame, Bellow Aoy, Hirohao Bald eagle), loquat `` fruits, leaves, stems '', betel nuts (large clothes, coconut), puer tea, sweet pods (south rattan), Japanese cypress, Japanese cypress poppy (Fuji winter flower, Japanese winter leaf), Fujibakama (Orchid), Japanese bean (Tsuname), Fujimodoki (Chujizakura, Spike), grapes `` fruit, pericarp, seeds, leaves '', beech, Fuyumushinatsusatake (Chinese insect summer grass), Brazilian licorice, Brazilian carrot, Brazilian palm, Brazilian elephant coconut, black currant `` fruit '', blackberry, buranyen, plum `` fruit '', fullcellaria, blueberry (Prunus japonica), prunes, floral blanka, blond psyllium, bundo ( Mung beans), hazelnuts, loofah, hetsukaran, safflower (safflower), heneken, belladonna, berries `` fruit '', persair, pervianburg, pereschia grandifolia, crabs or duckweed (scenic sky), boysenberry `` fruit '', scallop or narcissus Or nendo Hahagigi ・ Kokia (Golden eel), Hausairan, Blossoms (Akansen, Acute pupa, Radioceae), Pouteria sapota, Pouteria lucuma, Honoki, Spinach, Physalis (Torone), Hononoki (Wat Kobak, Park), Bokeh (Kiso), Hosoba Aragiku (bitter york), Hosobaa Guruma, Hosobanaokera (Amber), Hosoba Kirinso (Keiten 37), Hosobabareniku, Bodaiju (Ogi), Buttons (peony `` flowers, leaves, stems, bark '') , Buttonpi (peony skin), hop, jojoba, borage (borage), Bordeaux, howler berry `` fruit '', hononiku (meat juju, large art), honsekkok (iron skin stone, sparrow mountain stone potato), mizuru tennansho (Tennan star), Maitake (maiko), Maou (mao), maca, macadamia nuts, margaret (mokushungiku), macri (marine grass), mugwa (mulberry bark `` bark, leaf ''), magnolia Sprengeri, Masalan Suva, Masalan Suba de Ceara, Masheira de Boi, Mashua (Tamanousen Hallen, Kyukonkinrenka), Matatabi (Mushroom), Matsukasa, Pine "Leaf, Bark, Root", Matta Oryo, Matsuhodo (茯苓), Matico (Cordon Sillo), Mayoram (Hanahakka), Malvano Jazine (Bitter), Mulberry `` Fruit '', Quince, Malene (Bilaud Muzuka), Mango, Mangosteen, Manzanya (Andesca Mitsule), Manshugurumi, Mandarin `` `` Fruit '', Mannentake (Reishi), pheasant (fruit `` fruit ''), Mishima Psycho (Shibahu), Mizuoobako or Mizuasagao (Dragongrass), Mizokakushi (half-sided lotus), Misohagi (Chinese vegetable), Michiyanagi or Niwayanagi ( Henshu), Mitsuwashi, Mitsuba, Midori Zapote, Midori Hakka, Mimosa, Myo Moth, miracle fruit `` fruit '', myrrh, mirobaran, wheat straw, mugwort (mushroom), myrtle, mukuroji (life-prolonging skin), munya, purple (purple), purple saxkib (purple pearl), purple corn, purple sasafuji ( Kunming chicken blood wisteria, Megakansa opuntica, Mehajiki (beneficial mother grass), Mebougi, Japanese evening primrose (Evening primrose), Melaroica, Melissa, Melilot, Melon `` fruit '', Moukomugi, Mosouchiku, Mokkirin, Moje (Pepper), Mochinoki, Mochinoki Incense), Japanese maple peach, Peach (peach `` leaves, seeds, flowers, fruit ''), coconut palm, Morello cherry `` fruit '', Morohaya (burlap), Yakawamuraimo, Yakuchi (Michichi), cornflower (cornflower), Cornflower mint, yacon, yaba santa, yashabushi Fruit or persimmon `` fruit, pericarp, fruit ear '', willow willow, starfish (octagonal gold plate), mistletoe (willow infestation), willow (kawayanagi, tachiyanagi, weeping willow), red willow, cat willow, incolyanagi, kinuyanagi, miryana, unrya Palms, willows, giant willows, foxtail willows, fox willows, dronoks), willow tree `` leaves, stems '', jabgarashi, yabukouji (purple gold beef), yab tobacco (crane tsumugi, Tenmeisei), pokeweed (commercial land), yamahanoki (yamabuki) ), Japanese yam, Japanese sagebrush, Eucalyptus, Yukinoshita (tiger ear grass), Yucca or flavifolia, Yuzu `` fruit '', Lily, Yorusa, mugwort (birch leaves), Ligan (Raimaru), Lime `` fruit '', rye, Lacanca "fruit", raspberry "leaves, fruit", latania (chlamelia), latte Leopard or shallot (palm white), lavender, longan (long-eyed meat), agave (Aon agave, fuchlin agave), ryocha (green tea), apple `` fruit, seeds, leaves, roots '', gentian, lubas or suabisimus (cool), Ruritama Thistle (Vulgaria chintai, Xinjiang indigo sashimi), Reishi (toothpick, toothpick core), lettuce (chisha), red currant `` fruit '', red pitaya, lemon `` fruit '', lemongrass, forsythia or Chinese forsythia (ream), Astragalus, waxy, wax palm, locon (Yoshi, Sone), Loganberry "fruit", rosemary (Mannenrou), rosehip (Nobara), wasabi, cotton wisteria (Mong Monflower), Waremokkou (earthen) Etc.
[0042]
As seaweeds, seaweed [Green algae: Chlorella vulgaris, Chlorella pyrenoidosa, Chlorella ellipsoidia, Aonori (Usba aonori, Sugiaonori, Hiraaoori, Boaonori, Hosoeda Aonori), Anaaoosa (Aosa)] (Macombu, Resilibu, Hosocome, Mitsuishi Kombu), Wakame, Hirome, Aowakame, Giant Kelp (Macrocystis Integrifolia, Neocitus Ruetkeana), Hijiki, Hibamata, Umiuchiwa, Usubaumiuchiwa Umiuchiwa, Akaba Umiuchiwa, Konami Uchiwa, Okinawa Uchiwa, Usuki Uchiwa, Etsumi Uchiwa], seaweed [Red algae: Hijirimen, Maca (Tengusa), Hiraksa, Syria, Oaxa Caterpillar, Yatabegusa, Yuukiri, Shimatengusa, Tosakanori, Togekirinsai, Amakusakirinsai, Giraffe, Juniper ginkgo rhinoceros, Tsunomata, Totsuka (Yahazutsu notamata), Ezotsunotamata, Togetu no Takita , Yaleus banori, Kagius banori, Susius banori, Haius banori, Akamo mizunori] and the like.
[0043]
In addition, other algae such as green algae (Chlamydomonas: Chlamydomonas, Akayukimo, Dunaliella: Dunaliella, Chlorococcus: Chlorococcus, Kuwanomimo: Kuwanomimo, Volboxa: Ougemawari, Volbox, Palmera, Yotsumeo, Aomido: Chrysanthemum, Aoumidro, Tirguimidro, Hibidoro: Hibidoro, Aosa: Anaaaosa, Amiaosa, Nagaaosa, Kawanori: Kawanori, Friccella, Shiogusa Magama genus: Magamata, Iwagata: Fusaikawa, Surichogata, Heraiwata, Kurokita, Hanemo, Genus: Mill, Chromel, Sakibutimil, Nagamil, Hira Lemon, Casanori genus: Casanori, Jusmo genus: Jujusmo, Tamajusmo, Mizojuzumo, Mika ヅ kimo, Korekaete, Tsutsumimo genus: Kyukougusa, Hitogususa genus: Humanegusa, Hirohatohigususa, Umushihimoe, Sakikimoe Sumiremo: Sumiremo, Hoshimamidro, Fushinashimidoro etc.).
[0044]
Cyanobacteria (Suizenjinori: Suizinori, Aoko, Nenju: Kawatake, Ishijelly, Hassai, Yuremo, Rasenmo (Spirulina): Spirulina, Trichodesmium (Iaciasio), etc.
[0045]
Brown alga Sanadagusa: Sanadagusa, Fukurimamiji, Commongusa: Commongusa, Yahazugusa: Ezoyahaz, Yahazugusa, Uraboshiyahaz, Jigamusa: Jigmygusa, Umichiwagusa, Umamisakugakua, Hakusou : Navarimo, Chasomen genus: Motsuki Chasomen, Matsumo genus: Matsumo, Nagamatsumo genus: Nagamatsumo, Okinawa mozuku: Okinawa mozuku, fake Tomozuku: Niseft Mozuku, Futomozuku: Futomozuku, Ishimozuku: Ishimozuku, Kuromo: Kuromo, Nisemozuku: Nisemozuku, Mozuku: Mozuku, Ishige: Ishige, Iroro, Ichimegasa: Ichimegasa Umibosu, Urushigusu: Urushigusa, Keurushigusa, Tobaccogusa, Composita: Composita, Haberodomo: Haberodoki, Havanori: Habanori, Habanori: Habanori, Commonbukuro, Ezobukuro, Ezobukuro Chishima fukuronori genus: Chishima fukuronori, Kagomenori genus: Kagomenori, Muraridori genus: Murachidori, shark genus: shark zusa, genus genus: lobster, genus genus: yokojimamanori, Ganoderma genus: cynomolgus, fennel spider: fennel spider, vine genus: turmo, turtle genus: sea turtle, scorpion genus: sujime, misji kumbu genus: misji kumbu, atsuba misji kumbu, kumbu genus: tsutsugara kumbu, oyster kumbu, onikombu, gakonbubu Barracuda, Trollocombu: Trollocombu, Antokume: Antokume, Kajime: Kajime, Tsuruarame, Kurome, Kikuishikombu: Kikuishicombu, Nejikcombu: Nejicombu, Kuroshiome: Kuroshiome, Nekoshikonbu, Aramei Genus: Ainuwakame, Chigaiso, Oniwakame Ezoi Shige: Ezoi Shige, Yabane Moku: Yabane Moku, Rappa Moku: Rappa Moku, Joromoku: Ugano Moku, Jo Lomoku, Hiemoku, Honda Walla: Tamanashimoku, Isomoku, Nagashimamoku, Akamoku, Shidamoku, Honda Walla, Nejimoku, Narasamo, Mametawala, Tatsukuri, Yatsumata Moku, Umitora no Moku, Fushishimoku, Mohmokumoku, Hahamokumoku , Ukimo: Ouokimo, Burukimo: Burukimo, Kayamonori: Kayamonori, etc.).
[0046]
Red algae Genus: Sea urchins, Tsukumonori, Anemone crickets, Astragalus, Amaranthus, Amaranthus, Agaricata Genus: Tamaitadaki, Kaikekenori Genus: Kaginori, Kaikekenori, Tengusa: Himetengususa, Hytengususa, Oobusa, Nambugu , Kohira, Yohira, Kinukusa, Hibirodo: Hibirodo, Himebiro, Isomumedo: Isommedo, Aedes: Rhizome, Ryumons: Ryumon, Ranunculaceae, Nisekare Naminohana: Hosobanaminohana, Naminohana, Sangomodoki: Ragaramomodoki, Shiogusagoromo: Shiogusagoromo, Iwanokawa: Etsukiiwanawa, Kinokawa: Kinokawa, Kanonote, Sangori Kyono Shiro, Sakuranori, Nikumukade, Tambanori, Tsurutsuru, Fudarak, Marubahdarak, Isonohana: Nurakusa, Ronulaksa, Oomkadenori, Hirakintoki: Hirakintoki, Matabou: Matabou, Kintoki: Chabokintoki, Kintoki, Matsunori, Rice, Tokamatsu, Hitomatsu, Fushikintoki, Tsunomude, Nagakinito, Crayfish Nagaobane: Naganobane, Funori genus: Hanafonori, Fukurofunori, Mafunori, Karekigusa: Karekigusa, Tosakamodoki: Hosobanatosakamodoki, Hironotosakamodoki, Yatsudegatatosakamodoki, Kurotosakamodokisane, Zotosofomoza Tosakamodoki, Nankaitosakamodoki, Himetosakamodoki, Kinuhada: Kinuhada, Ezotosaka: Ezotosaka, Tsukasanori: Enashikarimenia, Otsukasanori, Hana Tacarimenia, Hoonoo: Honoo, Hikagenoit: Hikagenoit, Usuginu, Nikuhounoo: Nikuhounoo, Venus nago, Venus nago, Susca veni: Suscabeni, Okarugusa: Yamadagusa, Mirin: Mirin, Hosokamiso , Isomocca genus: Isomocca, Yukari genus: Yukari, Hosoyukari, Ibaranori genus: Ibaranori, Saidaibara, Tachiibara, Kagibaranori, Kojinoo: Kizino-o, Isodantsu: Isodantsu, Atsubanori: Atsubanori, Ogonori, Ogonori, Ogori Mizo-okonori, birch, beniogonori, fukureshinori, purple birch, shinkaibanori, spruce birch, kataogonori, ryukyuogono Li, Atlantic scorpion, Ivy genus, Yumigataonori, Kubireogonori, Mosagogonori, Kinubanori, Amanita genus: Hachijotensamodoki, Fushikenori genus: Fushikenori, Namiiwatake, Nymphalanthus Itagususa, Saimi, Hari, Lotus Jigusa: Lotus Jigusa, Sugi nori: Ikanoashi, Hosoibonori, Nobonori, Black Haginansou Genus: gourd, cherries, octopus: octopus, sedge, genus: genus, genus: goat, dals : Dulse, Scorpionus, Anadalus, Weibusa: Uebusca, Benifronori: Benifuronori, Fusunagi: Futsutsunagi, Himefusunagi, Hirohafushitsugi, Otsunagisou, Hirawatagigi, Usuwasugi , Egonori: Egonori, Futogigi, Saeda: Saeda, Chirimomiji: Chirimomiji, Konohori family: Habutaenori, Konohori, Suzuronori, Usubeni: Genus: Kagios banori, Yareus banori, Susius banori, Heius banori, Usubanorimodoki: Usubanorimodoki, Ayanishiki genus: Ayani Genus: Aeginu, Dadia: Enasidadia, Shimadadia: Isohagi, Shimadadia, Dajimodoki: Dajimodoki, Euglena: Morayogusa, Fuyugusa, Makuri: Makri, Yanaginogi, Yuna, Yukinagina , Sasabayanaginori, Sozo genus: Kurosozo, Kobsozo, Hanesozo, Sozonohana, Hanegusa genus: Hananegusa, Hananegusa, Kozanemo genus: Kozanemo, Isomurasaki, Hosozozanemo, Himegoshigusu, Giant genus Isomagusa, Suginasugusa: Suginasusa, Isobashou: Isobasho, Fujimatsumo: Fujimatsumo, Sawweed: Haeshinosakiba, Kawamoku : Kawamoku, Aokawa Mozuku, Himekawa Mozuku, Ideyugogome: Ideyugogome, Okichimozuku: Okimozu, Otosa, Chinomo: Chinomo, Chisujinori, Chisujinori, etc.).
[0047]
Axial algae (Shajikumo, Shiratamamo, Hoshitsurimo: Hoshitsurimo, Rikunotumusu, Flaskmo: Himebumo, Chaboflasmo, Tripera, etc.), yellow algae (Hikarimo: Hikarimo, etc.), etc.
[0048]
In addition, the materials derived from animal materials include chicken crown extract, cow or pig, human placenta extract, cow or pig stomach, duodenum, intestine, spleen extract or decomposition product thereof, cow or pig brain tissue Extracts, cattle / pigs / fish collagen hydrolyzate (acid, alkali, enzyme etc.) degradation products, water-soluble collagen or collagen derivatives such as acylated collagen, cattle / pigs / fish elastin or elastin hydrolyzate (acid, Alkaline, enzyme, etc.) or water-soluble elastin derivative, keratin and its degradation product or their derivatives, silk protein and its degradation product or their derivatives, pig or cow blood cell protein degradation product (globin peptide), cow or pig hemoglobin Degradation products (hemin, hematin, heme, protoheme, heme iron, etc.), milk, casein and its degradation products or derivatives thereof, skim milk powder and its degradation products or it Derivatives, lactoferrin or decomposed product thereof, egg ingredients, fish hydrolyzate, nucleic acid-related substance (ribonucleic acid, deoxyribonucleic acid), or the like.
[0049]
In addition, as a material derived from a plant or animal material, any site, cell, tissue, organ, metabolite, etc. derived from a gene recombinant or a cell fusion can be used. Furthermore, for example, an undifferentiated cell group, a cell group in the middle of differentiation, or the like obtained by culturing an arbitrary site, cell, tissue, organ or the like can also be used.
[0050]
(14) Marine components
Seawater such as deep sea water, for example, sea salt, dried seawater, dead sea or Atlantic or Pacific sea water (sodium chloride, magnesium chloride, potassium chloride, etc.), sea mud or mud (fango), for example Sea mud or mud from various locations such as Italy, Fango, German Fango, Eifel Fango, Freiburg Fango, etc. (Ingredients: silicon dioxide, titanium dioxide, aluminum oxide, iron oxide, manganese oxide, sodium oxide, potassium oxide, magnesium oxide, calcium oxide Strontium oxide, sodium, potassium, magnesium, calcium, chromium, iron, copper, nickel, zinc, lead, manganese, arsenic, water), saintoku stone, black meteorite, etc.
[0051]
(15) Microbial culture metabolites
Yeast metabolite, yeast extract, bacterial metabolite, bacterial extract, mold or actinomycete metabolite, mold or actinomycete extract, natto metabolite, natto extract, rice fermented extract, rice bran (red rice cake, birch ) Fermented extract, Euglena extract or decomposition product thereof or water-soluble derivative thereof, trehalose or derivative thereof, lactic acid fermentation product of raw milk or skim milk powder, lactic acid bacteria fermentation product of legumes, lactic acid bacteria fermentation product of coconut genus plant, etc.
[0052]
(16) α-hydroxy acids
Glycolic acid, citric acid, malic acid, tartaric acid, lactic acid, etc.
[0053]
(17) Inorganic pigment
Silica, magnesium silicate, talc, kaolin, bentonite, mica, mica titanium, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, calcium carbonate, magnesium carbonate, yellow iron oxide, red iron oxide, black iron oxide , Gunjo, chromium oxide, chromium hydroxide, carbon black, calamine, etc.
[0054]
(18) UV absorption / blocking agent
Benzophenone derivatives (2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate, dihydroxydimethoxybenzophenone, dihydroxydimethoxybenzophenone-sulfone Acid sodium, 2,4-dihydroxybenzophenone, tetrahydroxybenzophenone, etc.), paraaminobenzoic acid derivatives (paraaminobenzoic acid, ethyl paraaminobenzoate, glyceryl paraaminobenzoate, amyl paradimethylaminobenzoate, octyl paradimethylaminobenzoate, etc.) , Methoxycinnamate derivatives (ethyl paramethoxycinnamate, isopropyl paramethoxycinnamate, octyl paramethoxycinnamate, 2-ethoxyethyl paramethoxycinnamate, paramethoxycinnamate Acid sodium, potassium paramethoxycinnamate, glyceryl diparamethoxycinnamate mono-2-ethylhexanoate, etc.), salicylic acid derivatives (octyl salicylate, phenyl salicylate, homomenthyl salicylate, dipropylene glycol salicylate, ethylene glycol salicylate, myristyl salicylate, methyl salicylate, etc.) , Anthranilic acid derivatives (such as methyl anthranilate), urocanic acid derivatives (such as urocanic acid, ethyl urocanate), coumarin derivatives, amino acid compounds, benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives, camphor derivatives, Furan derivatives, pyrone derivatives, nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives, vitamin B6 derivatives, umbelliferone Esculin, benzyl cinnamate, cinoxate, oxybenzone, dioxybenzone, Okutabenzon, sulisobenzone, benzo resorcinol, arbutin, guaiazulene, shikonin, baicalin, baicalein, berberine, Neo Heliopan, ESCA rolls, zinc oxide, talc, kaolin.
[0055]
(19) Whitening agent
Paraaminobenzoic acid derivatives, salicylic acid derivatives, anthranilic acid derivatives, coumarin derivatives, amino acid compounds, benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives, camphor derivatives, furan derivatives, pyrone derivatives, nucleic acid derivatives, allantoin derivatives Nicotinic acid derivatives, vitamin C or derivatives thereof (vitamin C phosphate magnesium salt, vitamin C glucoside, etc.), vitamin E or derivatives thereof, kojic acid or derivatives thereof, oxybenzone, benzophenone, arbutin, guaiazulene, shikonin, baicalin, baicalein , Berberine, placenta extract, ellagic acid, lucinol etc.
[0056]
(20) Tyrosinase activity inhibitor
Vitamin C or a derivative thereof (vitamin C phosphate magnesium salt, vitamin C glucoside, etc.), hydroquinone or a derivative thereof (hydroquinone benzyl ether, etc.), kojic acid or a derivative thereof, vitamin E or a derivative thereof, N-acetyltyrosine or a derivative thereof , Glutathione, hydrogen peroxide, zinc peroxide, placenta extract, ellagic acid, arbutin, lucinol, silk extract, plant extract (camille, mulberry, gardenia, touki, firewood, clara, mugwort, honeysuckle, yellowfin, dokudami, matsuhod, Pearl barley, nettle, hops, hawthorn, eucalyptus, yarrow, altea, keihi, mankei, hamamelis, carraguwa or yamagwa, life-grass, bellflower, toshishi, sequel, shooting dry, mao, senkyu, dokatsu, psycho, Ufuu, littoralis, Scutellaria, peony bark, peony, cranesbill, kudzu root, licorice, Fushi aloe, Cimicifuga, safflower, green tea, black tea, Ali elixir), and the like.
[0057]
(21) Melanin pigment reduction / degradation substances
Phenylmercury hexachlorophene, mercuric oxide, mercuric chloride, hydrogen peroxide, zinc peroxide, hydroquinone or its derivatives (hydroquinone benzyl ether).
[0058]
(22) Turnover promotion / cell activator
Hydroquinone, Lactic acid bacteria extract, Placenta extract, Ganoderma extract, Vitamin A, Vitamin E, Allantoin, Spleen extract, Thymus extract, Yeast extract, Fermented milk extract, Plant extract (Aloe, Ogon, Horsetail, Gentian, Burdock, Shikon, Carrot, Hamamelis, Hop, Yokuinin, Odori Sou, Assembly, Toki, Toki Senko, Achacha, Hypericum, Cucumber, Ginger, Mannenrou, Parsley).
[0059]
(23) Astringent
Succinic acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc paraphenol sulfonate, potassium aluminum sulfate, resorcin, ferric chloride, tannic acid (including catechin compounds), etc.
[0060]
(24) Active oxygen scavenger
SOD, catalase, glutathione peroxidase and the like.
[0061]
(25) Antioxidants
Vitamin C or a salt thereof, stearic acid ester, vitamin E or a derivative thereof, nordihydrogua ceretenoic acid, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), hydroxytyrosol, parahydroxyanisole, propyl gallate, sesamol , Sesamorin, gossypol, propolis, etc.
[0062]
(26) Lipid peroxide production inhibitor
β-carotene, plant extract (sesame cultured cells, amacha, hypericum, clams, clove, melissa, enamel, birch, salvia, mannenrou, nanzenji, ages, ginkgo, green tea).
[0063]
(27) Anti-inflammatory agent
Ictamol, indomethacin, kaolin, salicylic acid, sodium salicylate, methyl salicylate, acetylsalicylic acid, diphenhydramine hydrochloride, d-camphor, dl-camphor, hydrocortisone, guaiazulene, camazulene, chlorpheniramine maleate, glycyrrhizic acid or its salt, glycyrrhetinic acid or its Salt, licorice extract, sicon extract, age extract, propolis, etc.
[0064]
(28) Antibacterial / disinfectant / disinfectant
Acrinol, sulfur, calcium gluconate, chlorhexidine gluconate, sulfamine, mercurochrome, lactoferrin or its hydrolyzate, alkyldiaminoethylglycine chloride solution, triclosan, sodium hypochlorite, chloramine T, salicy powder, iodine compound, iodoform, sorbin Acid or salt thereof, propionic acid or salt thereof, salicylic acid, dehydroacetic acid, parahydroxybenzoic acid esters, undecylenic acid, thiamine lauryl sulfate, thiamine lauryl nitrate, phenol, cresol, p-chlorophenol, p-chloro-m -Xylenol, p-chloro-m-cresol, thymol, phenethyl alcohol, O-phenylphenol, Irgasan CH3565, halocarban, hexachlorophene, chlorohexidine, ethanol, methanol Isopropyl alcohol, benzyl alcohol, ethylene glycol, propylene glycol, 2-phenoxyethanol, 1,2-pentanediol, zinc pyridione, chlorobutanol, isopropylmethylphenol, nonionic surfactant (polyoxyethylene lauryl ether, polyoxyethylene nonyl) Phenyl ether, polyoxyethylene octyl phenyl ether, etc.), amphoteric surfactant, anionic surfactant (sodium lauryl sulfate, lauroyl sarcosine potassium, etc.), cationic surfactant (cetyltrimethylammonium bromide, benzalkonium chloride, benzethonium chloride) , Methylrosaniline chloride), formaldehyde, hexamine, brilliant green, malachite green, crystal violet, jarmal, feeling Photoelement 101, Photosensitive element 201, Photosensitive element 401, N-long chain acyl basic amino acid derivatives and acid addition salts thereof, zinc oxide, hinokitiol, kudin, propolis, and the like.
[0065]
(29) Moisturizer
Glycerin, propylene glycol, 1,3-butylene glycol, polyethylene glycol, glycerin tricaprycapric acid, glycolic acid (α-hydroxy acid), hyaluronic acid or its salt, chondroitin sulfate or its salt, water-soluble chitin or its derivative or chitosan derivative Pyrrolidonecarboxylic acid or a salt thereof, sodium lactate, urea, sorbitol, amino acid or derivative thereof (valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, Tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine, arginine, ornithine, histidine and their sulfates and phosphates Nitrate, citrate, or pyrrolidone carboxylic acid), fats and oils “Avocado oil, almond oil, fennel oil, sesame oil, olive oil, orange oil, orange rafa oil, sesame oil, cacao butter, chamomile oil, carrot oil, cucumber oil, Beef tallow fatty acid, quince seed oil, cucumber nut oil, safflower oil, shea fat, liquid shea fat, soybean oil, camellia oil, corn oil, rapeseed oil, jojoba oil, persic oil, castor oil, sunflower oil, cottonseed oil, peanut oil, Turtle oil, tea tree oil, mink oil, egg yolk oil, palm oil, palm kernel oil, molasses, palm oil, eucalyptus oil, beef tallow, lard, squalene, squalane, pristane or hydrogenated products of these oils (cured oil) , Waxes (beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, Lanolin, candelilla wax, montan wax, shellac wax, rice wax), mineral oil (liquid paraffin, petrolatum, paraffin, ozokelide, ceresin, microcristan wax), natto bacteria metabolites, natto extract, silk fiber extract, plant extract (Akamatsu) Sap, aloe, kudzu, chamomile, licorice, cucumber, licorice, rice or rice bran, purple root, birch or white birch sap, assembly, mulberry white bark, maple leaf, loofah, peony skin, persimmon), etc.
[0066]
(30) Elastase activity inhibitor
Fluorophosphate diisopropyl, plant extract (Ogon, Hypericum, Clara, Mulberry leaves, Keihi, Gennosho, Comfrey, Salvia, Elderberry, Bodaige, Buttonpi), seaweed extract, etc.
[0067]
(31) Hair preparation
Selenium disulfide, alkylisoquinolinium bromide solution, zinc pyrithione, biphenamine, thianthol, castari tincture, pepper tincture, red pepper tincture, quinine hydrochloride, strong aqueous ammonia, potassium bromate, sodium bromate, thioglycolic acid and the like.
[0068]
(32) Antiandrogen
Follicular hormone (estrone, estradiol, ethinyl estradiol, etc.), isoflavone, oxendron, etc.
[0069]
(33) Peripheral blood flow promoter
Vitamin E or its derivatives, assembly extract, garlic extract, carrot extract, aloe extract, gentian extract, toki extract, cephalanthin, carpronium chloride, minoxidil and the like.
[0070]
(34) Stimulant
Pepper tincture, nonyl acid vanillamide, cantalis tincture, ginger tincture, peppermint oil, l-menthol, camphor, benzyl nicotinate, etc.
[0071]
(35) Metabolic active agent
Photosensitizer 301, hinokitiol, pantothenic acid or derivatives thereof, allantoin, placenta extract, biotin, pentadecanoic acid glyceride and the like.
[0072]
(36) Antiseborrheic agent
Pyridoxine or its derivatives, sulfur, vitamin B6 and the like.
[0073]
(37) Keratolytic agent
Resorcin, salicylic acid, lactic acid, urea, etc.
[0074]
(38) Oxidizing agent
Hydrogen peroxide solution, sodium persulfate, ammonium persulfate, sodium perborate, urea peroxide, sodium percarbonate, sodium tripolyphosphate, sodium bromate, potassium bromate, sodium pyrophosphate, sodium orthophosphate Sodium silicate hydrogen peroxide adduct, sodium sulfate hydrogen peroxide adduct, sodium chloride hydrogen peroxide adduct, β-tyrosinase enzyme solution, mushroom extract, etc.
[0075]
(39) Hair remover
Inorganic reducing agents such as strontium sulfate, sodium sulfide, barium sulfide, calcium sulfide, thioglycolic acid or its salts (calcium thioglycolate, sodium thioglycolate, lithium thioglycolate, magnesium thioglycolate, strontium thioglycolate) etc.
[0076]
(40) Hair swelling agent
Ethanolamine, urea, guanidine, etc.
[0077]
(41) Dye agent
5-aminoorthocresol, 2-amino-4-nitrophenol, 2-amino-5-nitrophenol, 1-amino-4-methylaminoanthraquinone, 3,3'-iminodiphenol, 2,4-diaminophenoxyethanol hydrochloride 2,4-diaminophenol hydrochloride, toluene-2,5-diamine hydrochloride, nitroparaphenylenediamine hydrochloride, paraphenylenediamine hydrochloride, N-phenylparaphenylenediamine hydrochloride, metaphenylenediamine hydrochloride, orthoaminophenol, N-phenyl acetate Paraphenylenediamine, 1,4-diaminoanthraquinone, 2,6-diaminopyridine, 1,5-dihydroxynaphthalene, toluene-2,5-diamine, toluene-3,4-diamine, nitroparaphenylenediamine, paraaminophenol, para Nitroorthophenylenediamine, paraphenylenediamine, paramethylamino Phenol, picramic acid, sodium picramate, N, N'-bis (4-aminophenyl) -2,5-diamino-1,4-quinonediimine, 5- (2-hydroxyethylamino) -2-methylphenol, N -Phenylparaphenylenediamine, metaaminophenol, metaphenylenediamine, 5-aminoorthocresol sulfate, 2-amino-5-nitrophenol sulfate, orthoaminophenol sulfate, orthochloroparaphenylenediamine sulfate, 4,4'-diamino sulfate Diphenylamine, 2,4-diaminophenol sulfate, toluene-2,5-diamine sulfate, nitroparaphenylenediamine sulfate, paraaminophenol sulfate, paranitroorthophenylenediamine sulfate, paranitrometaphenylenediamine sulfate, paraphenylenediamine sulfate, parasulfate sulfate Methylaminophenol, metaaminosulfate Diol, metaphenylenediamine sulfate, catechol, diphenylamine, α-naphthol, hydroquinone, pyrogallol, phloroglucin, gallic acid, resorcin, tannic acid, 2-hydroxy-5-nitro-2 ', 4'-diaminoazobenzene-5'-sulfone Sodium acid, hematein, etc.
[0078]
(42) Fragrance
Natural animal fragrances such as musk, civet, castrium, ambergris, anise essential oil, angelica essential oil, ylang ylang essential oil, iris essential oil, fennel essential oil, orange essential oil, cananga essential oil, caraway essential oil, cardamom essential oil, guayakwood essential oil, cumin essential oil, black letter Essential oil, cinnamon essential oil, cinnamon essential oil, geranium essential oil, copaiba balsam essential oil, coriander essential oil, perilla essential oil, cedarwood essential oil, citronella essential oil, jasmine essential oil, gingergrass essential oil, cedar essential oil, spearmint essential oil, western peppermint essential oil, dairy perfume essential oil, Tuberose essential oil, clove essential oil, orange flower essential oil, winter green essential oil, troubalsum essential oil, buttery essential oil, rose essential oil, palmarosa essential oil, cocoon essential oil, hiba essential oil, sandalwood essential oil, petit gren essential oil, bay essential oil, vetiva essential oil, bergamot essential oil, pel Plant flavors such as balsam essential oil, boad rose essential oil, melamine essential oil, mandarin essential oil, eucalyptus essential oil, lime essential oil, lavender essential oil, linaloe essential oil, lemongrass essential oil, lemon essential oil, rosemary (mannenrou) essential oil, Japanese mint mint essential oil, etc. Synthetic fragrance etc.
[0079]
(43) Dyes / colorants
Red cabbage dye, red rice dye, red dye, anato dye, scum dye, turmeric dye, enju dye, krill dye, amber dye, caramel, gold, silver, gardenia dye, corn dye, onion dye, tamarind dye, spirulina dye, Buckwheat whole pigment, cherry pigment, laver pigment, hibiscus pigment, grape juice pigment, marigold pigment, purple potato pigment, purple yam pigment, lac pigment, rutin etc.
[0080]
(44) Sweetener
Sugar, sweet tea, fructose, arabinose, galactose, xylose, stevia, mannose, maltose, honey, glucose, miraculin, monelin, licorice extract, etc.
[0081]
(45) Nutrition enhancer
Shell-calcined calcium, cyanocolabamine, yeast, wheat germ, egg yolk powder, hemicellulose, heme iron, etc.
[0082]
(46) Dairy products
Milk, cheese, fresh cream, butter, margarine, powdered milk, whey, condensed milk, etc.
[0083]
(44) Other
Hormones, sequestering agents, pH adjusters, chelating agents, antiseptic and antibacterial agents, fresheners, stabilizers, emulsifiers, animal and vegetable proteins and their degradation products, animal and vegetable polysaccharides and their degradation products , Animal / plant glycoproteins and their degradation products, blood flow promoters, anti-inflammatory agents / anti-inflammatory agents / anti-allergic agents, wound treatment agents, foam enhancers, thickeners, enzymes, purified water (electronic water, small clusters) ), Oral preparations, deodorants / deodorants, bitterings, seasonings, etc., and the combined use with these is expected to provide additive or synergistic improvements to the effects of the present invention or other cosmetic effects. it can.
[0084]
The hyaluronic acid production promoter or external preparation for skin of the present invention, and the method of addition to foods and drinks, may be added in advance or during the production, if appropriate considering the workability good.
[0085]
【Example】
Hereinafter, production examples, test examples, and formulation examples will be described, but the present invention is not limited thereto.
[0086]
(Production Example 1)
50 g of high-purity gelatin (Miyagi Chemical Co., Ltd.) was dissolved in 1,000 mL of 20 mM Tris-HCl buffer (pH 7.4) /0.1 M NaCl while heating, and then cooled to 50 ° C. The immobilized enzyme for enzymatic degradation was prepared by binding 100 mg of collagenase enzyme (manufactured by Washington, high-purity product purified from type IV) to 50 g of particle carrier. The amount bound to the carrier was calculated by measuring the change in absorbance at 280 nm before and after the binding, and the binding rate was 99% or more. During use, this immobilized enzyme is packed in a double column bioreactor with a pH sensor installed between the columns, and 20 mM Tris-HCl buffer (pH 7.4) /0.1 M NaCl buffer is used. Washing and equilibration were performed. The pH measurement is a system in which a concentrated Tris buffer solution flows from a connected tube when a change is detected by a pH sensor installed between the columns of the double column.
[0087]
The high-purity collagen obtained in the above step was applied to the vertical double collagenase enzyme-immobilized column prepared in the above step, and enzymatic degradation was performed by the column method. During this time, the flow rate was controlled at 20-60 mL per minute and the column temperature was controlled at 39 ± 1 ° C. The enzyme reaction completed solution that came out from the final (second column) was collected and filtered through a 0.45 μm filter.
[0088]
After the filtrate is pulverized by spray drying (spray dryer), a collagen peptide having a tripeptide content of at least 10% or more is obtained by gel filtration using a gel filter (trade name: Superdex 30pg, manufactured by Pharmacia). Was purified. The purified collagen peptide showed a peak with a molecular weight of about 280 due to the tripeptide. The tripeptide content can be increased by purification, and a collagen peptide having a tripeptide content of 80% or more can be obtained.
[0089]
After freeze-drying the collagen peptide obtained in the above step, that is, a collagen peptide having a tripeptide content of 10% or more, each NH ₂ Terminal amino acids and NH ₂ The second amino acid from the end was assayed by Edman degradation. As a result, NH ₂ It was proved that 97.5% of each terminal amino acid was glycine, and it was proved to retain the (Gly-XY) n structure, which is a characteristic amino acid sequence.
[0090]
(Test 1) Hyaluronic acid production promoting action test
"Test method and evaluation method"
5 x 10 in each well of 24-hole plate (Corning 3526) ^Four 1 mL of (cell / mL) normal human newborn foreskin dermal fibroblasts NHDF (NF) was seeded. Using DMEM medium (Kurabo) containing 5% FCS (fetal calf serum), 37 ° C, 5% CO ₂ After culturing for 3 days, the medium was replaced with a DMEM medium containing 0.5% FCS and the sample was added. Furthermore, the amount of hyaluronic acid (HA) was measured by ELISA using the culture supernatant after 24 hours of culture as a sample. At the same time, the number of cells was counted and evaluated as the amount of hyaluronic acid per cell. Purified water was used as a blank and N-acetylglucosamine was used as a positive control, and added to a test container to a final concentration of 0.1 mM. The collagen peptide of the present invention was added to a test container to a final concentration of 10 ppm. The results are shown in FIG.
"sample"
The test sample was prepared by adjusting the porcine-derived collagen peptide and the shark-derived collagen peptide obtained in Production Example 1 of the present invention to a solid content of 0.1%.
[0091]
(Test results)
As shown in FIG. 1, it was confirmed that the porcine-derived collagen peptide and shark-derived collagen peptide of the present invention have an action of significantly promoting the production of hyaluronic acid.
[0092]
(Test 2) Skin roughness improvement test
In order to evaluate the improvement effect on the rough skin of the product of the present invention, a sample application test was performed using a guinea pig for which a rough skin model was created. The sample was prepared by drying the porcine-derived collagen peptide and the shark-derived collagen peptide obtained in Production Example 1, and re-dissolving the obtained solid in purified water to a solid content concentration of 0.1%. Moreover, it implemented also only about the purified water as a comparison object.
[0093]
"Method"
Hartley guinea pigs (female, 5 weeks old, 3 per group) with hair removed on the back were coated with white petrolatum adjusted to 3% by weight sodium lauryl sulfate (0.2g) for 3 days to create rough skin. did. The skin roughness preparation site was divided into 4 minutes, each sample (1.0 mL) was applied 3 times / day, and the degree of skin roughness was evaluated according to the criteria (score) determined by observation after 3 days. The results are shown in Table 1.
"Criteria" 1 point that almost no erythema or desquamation is seen
2 mild desquamation without erythema
3 moderate desquamation without erythema
4 pieces of desquamation with weak erythema
5 desquamation with moderate erythema
6 debris with significant erythema
[0094]
<Table 1>

[0095]
As shown in Table 1, the collagen peptide of the present invention was recognized to be effective in improving rough skin.
[0096]
(Test 3) Safety test
(1) Skin primary irritation test
The collagen peptide obtained in Production Example 1 was prepared so as to have a solid content of about 2.0%, and this was obtained from the skin of a Hartley guinea pig (female, 3 mice per group, body weight 300 to 350 g) with the back shaved. × 2cm ² 0.03 mL per square was applied. Judgment was performed 24, 48, and 72 hours after application using the primary irritation scoring method with erythema and edema as indicators. As a result, in all animals, no erythema and edema were observed, and it was judged negative.
[0097]
(Test 4) Safety test
(2) Cumulative skin irritation test
The collagen peptide obtained in Production Example 1 was prepared so that the solid concentration was about 2.0%, and this was shaved on the flank (2 × 4 cm ² ) Hartley guinea pigs (female, 3 mice per group, body weight around 320 g) were applied once a day, 5 times a week, 0.5 mL / per animal. Application was for 2 weeks, and shaving was performed on the last application day of each week. Judgment was made on the day of each application and the day after the last application by the scoring method of primary irritation using erythema and edema as indices. As a result, in all animals, no erythema and edema were observed for 2 weeks after application, and it was judged negative.
[0098]
(Test 5) Safety test
(3) Single dose toxicity study
Production Example 1 A ddy mouse (male and female, 1 group 5) prepared by adjusting the obtained collagen peptide with purified water to a concentration of 12.5% and fasting 16 ml / kg per animal for 16 hours before the test. Mice, 5 weeks of age) were orally administered with a sonde, and the onset, degree, etc. of toxic symptoms were observed over time. As a result, no abnormalities were observed in all mice for 14 days, and no abnormalities were found in the anatomical results. Therefore, LD ₅₀ Was 2,000 mg / kg or more, and judged to be a safe substance.
[0099]
(Prescription example) Production of hyaluronic acid production promoter, external preparation for skin and food and drink
According to said evaluation result, the formulation example is shown below, but each formulation example may be what was manufactured by the conventional method in manufacture of each product, and showed only content. The present invention is not limited to these.
[0100]

[0101]
(Formulation Example 2) Milk Mass%
1. Squalane 8.0
2. Jojoba oil 7.0
3.Glyceryl paraaminobenzoate 1.0
4.ethyl urocanate 1.0
5. Vitamin C phosphate magnesium salt 1.0
6.Cetyl alcohol 1.5
7. Glycerin monostearate 2.0
8.Polyoxyethylene (20) cetyl ether 3.0
9.Polyoxyethylene (20) soorbitan monooleate 2.0
10.1,3-Butylene glycol 1.0
11.Glycerin 2.0
12.1,2-Pentanediol 3.0
13. Pig-derived collagen peptide 2.0 of Production Example 1
14. Shark-derived collagen peptide of Production Example 1 2.0
15.Pig placenta water extract 1.0
16. Preservative (paraoxybenzoic acid ester) appropriate amount
17.Residue with 100 purified water
[0102]
(Formulation Example 3) Cosmetic Oil Mass%
1.liquid paraffin 30.0
2.Squalane 20.0
3.Olive oil 20.0
4.Isopropyl palmitate 10.0
5. Shark-derived collagen peptide 1.0
6. Tochu Naka 50% ethanol extract 1.0
7. Soybean seed hot water extract 1.0
8.Olive oil 1.0
9. Shea fat 1.0
10.Butylhydroxyanisole 0.1
11. Vitamin E derivative 0.1
12. Preservative (benzalkonium chloride) appropriate amount
13. Perfume (today water) appropriate amount
14. Residue with 100 purified water
[0103]

[0104]
(Formulation Example 5) Astringent lotion
1.Sorbit 2.0
2. POE (20) oleyl alcohol 1.0
3.Ethanol 15.0
4. Pig-derived collagen peptide of Production Example 1 3.0
5. Whole plant 50% 1,3-butylene glycol extract 2.0
6. Gentian whole plant 50% ethanol extract 2.0
7. Sage whole plant 50% ethanol extract 2.0
8. Yeast 50% 1,3-butylene glycol extract 1.0
9.Allantoin 0.2
10. Astringent (Zinc Sulfocolate) 0.2
11. Antibacterial and antiseptic (thiamin lauryl sulfate) appropriate amount
12. Fragrance (lavender water) appropriate amount
13. Residue with 100 purified water
[0105]
(Prescription Example 6) Two-layer lotion (liquid to liquid type)
1. Squalane 8.0
2. POE sorbitan tetraoleate 0.3
3.Sorbit 1.0
4.Ethanol 15.0
5. Shark-derived collagen peptide of Production Example 1 1.0
6. Sage whole plant 50% ethanol extract 1.0
7.Ascorbic acid 0.2
8. Astringent (calamine) 0.1
9. Preservative (phenoxyethanol) appropriate amount
10. Perfume (lemon water) appropriate amount
11. Residue with 100 purified water
[0106]

[0107]
(Formulation example 8) Pack mass%
1.Polyvinyl alcohol 15.0
2.Carboxymethylcellulose sodium 5.0
3.Propylene glycol 3.0
4.Ethanol 10.0
5. Pig-derived collagen peptide of Production Example 1 1.0
6. Water-soluble β-1,3-glucan derivative 1.0
7. Raspberry fruit 50% diglycerin extract 1.0
8. Ginger fruit or root 30% 1,2-pentanediol extract 1.0
9. Preservative (paraoxybenzoic acid ester) appropriate amount
10. Perfume (rose water) appropriate amount
11. Residue with 100 purified water
[0108]
(Formulation example 9) Peel-off pack mass%
1.Glycerin 5.0
2.Propylene glycol 4.0
3.Polyvinyl alcohol 15.0
4.Ethanol 8.0
5.Polyoxyethylene glycol 1.0
6. Pantothenyl ethyl ether 1.0
7. Production Example 1 Shark-derived collagen peptide 2.0
8. Dutch Jelly (Parsley) Leaf or Stem 50% Ethanol Extract 2.0
9. Royal jelly 50% ethanol extract 1.0
10. Trehalose solution 1.0
11. Preservative (paraoxybenzoic acid ester) appropriate amount
12. Fragrance (camomile water) appropriate amount
13. Residue with 100 purified water
[0109]
(Prescription Example 10) Cold cream mass%
1. Sarah Beeswax 11.0
2.liquid paraffin 22.0
3.Lanoline 10.0
4.Olive oil 5.0
5. Chamomile oil 5.0
6. Palm oil 5.0
7.borax 0.5
8. Pig-derived collagen peptide 2.0 of Production Example 1
9. Birch bark extract 2.0
(Ethanol: 1,3-butylene glycol = 1: 1 extraction solvent)
10. Ginseng root 50% propylene glycol extract 2.0
11. Matsuhodo nuclei 50% 1,2-butylene glycol extract 1.0
12. Soybean seed water extract 1.0
13.Liquid shea fat 1.0
14.Dipotassium glycyrrhizinate 0.1
15. Preservative (Acrinol) 0.1
16. Fragrance (sage water) appropriate amount
17.Residue with 100 purified water
[0110]

[0111]

[0112]
(Prescription Example 13) Face-wash cream%
1.Stearic acid 10.0
2.palmitic acid 10.0
3.Myristic acid 12.0
4.Lauric acid 4.0
5.Oleyl alcohol 1.5
6. Lanolin derivative (EO adduct) 1.0
7.Glycerin 18.0
8.Potassium hydroxide 6.0
9. Shark-derived collagen peptide of Production Example 3.0
10. Pig-derived collagen peptide of Production Example 1 2.0
11. Royal Jelly Extract 1.0
(Ethanol: 1,3-butylene glycol = 1: 1 extract)
12.Glycyrrhetinic acid 0.5
13. Preservative (salicylic acid) 0.1
14. Fragrance (mugwort water) appropriate amount
15. Residue with 100 purified water
[0113]

[0114]
(Formulation Example 15) Sunscreen cosmetics (O / W type)
1.Oxybenzone 2.0
2.Octyl paramethoxycinnamate 5.0
3.Squalane 10.0
4.Vaseline 5.0
5. Stearyl alcohol 3.0
6.Stearic acid 3.0
7. Glyceryl monostearate 2.0
8.Polyethyl acrylate 1.0
9.1,3-Butylene glycol 6.0
10.Edetate disodium 0.1
11.Triethanolamine 1.0
12.Titanium dioxide 5.0
13. Pig-derived collagen peptide of Production Example 1 0.5
14. Cornflower leaf 50% propylene glycol extract 0.5
15. Barley seed 50% propylene glycol extract 0.5
16. Palm fruit 50% dipropylene glycol extract 0.5
17. Preservative (benzyl paraoxybenzoate) appropriate amount
18. Perfume (apple water) appropriate amount
19.Residue with 100 purified water
[0115]

[0116]
(Prescription example 17) Cream foundation (O / W type)
1.Stearic acid 4.0
2.Glycerol monostearate3.0
3.Cetanol 1.5
4.Isopropyl myristate 7.0
5. Liquid paraffin 10.0
6. Sarah Beeswax 3.0
7.Triethanolamine 1.5
8.Glycerin 3.0
9. Bentonite 1.0
10.Titanium oxide 8.0
11.2,4-Dihydroxybenzophenone 8.0
12.Kaolin 3.0
13. Talc 3.0
14. Colored pigment (yellow iron oxide) 1.0
15. Shark-derived collagen peptide of Production Example 1 0.2
16.Dokudami leaf hot water extract dry powder 0.2
17. Wenzhou citrus peel or fruit hot water extract dry powder 0.2
18.Yukinoshita Whole Grass Hot Water Extract Dry Powder 0.2
19. Kelp algae 50% ethanol extract 0.2
20. Dingyo 50% diglycerin extract 0.2
21. Wenzhou tangerine peel 50% 1,3-butylene glycol extract 0.2
22. Preservative (phenoxyethanol) 0.1
23. Perfume (rose water) appropriate amount
24. The balance of 100 purified water
[0117]

[0118]

[0119]
(Formulation example 20) Rinse mass%
1. Stearyltrimethylammonium chloride 2.0
2.Cetostearyl alcohol 2.0
3.Polyoxyethylene lanolin ether 3.0
4.Propylene glycol 5.0
5.Ethylene glycol 3.0
6. Pig-derived collagen peptide 1.0 of Production Example 1
7. Shark-derived collagen peptide of Production Example 1 1.0
8.Green tea leaf hot water extract 1.0
9. Matsuhodo nuclei 50% 1,2-butylene glycol extract 1.0
10. Persimmon leaf 50% ethanol extract 1.0
11. Trehalose solution 1.0
12. Hydrolyzed keratin solution 1.0
13. Antibacterial and antiseptic (benzalkonium chloride) appropriate amount
14. Fragrance (camomile water) appropriate amount
15. Residue with 100 purified water
[0120]

[0121]
(Formulation Example 22) Hair Liquid Mass%
1.Ethanol 29.0
2.Polyoxypropylene butyl ether phosphate 10.0
3.Polyoxypropylene monobutyl ether 5.0
4.Triethanolamine 1.0
5.Trimethylene glycol 5.0
6. Pig-derived collagen peptide 1.0 of Production Example 1
7. Shark-derived collagen peptide of Production Example 1 1.0
8. Panax ginseng root hot water extract 1.0
9. Lemon fruit 50% 1,3-butylene glycol extract 0.5
10. Apple fruit 30% ethanol extract 1.0
11. Birch sap 1.0
12.azulen 1.0
13. Antibacterial and antiseptic (paraben, benzalkonium chloride) appropriate amount
14. Fragrance (orange water) appropriate amount
15. Residue with 100 purified water
[0122]
(Prescription example 23) Hair artnic mass%
1.Ethanol 40.0
2.Ethyl oleate 1.0
3.Polyoxyethylene (40) hydrogenated castor oil 2.0
4. Pig-derived collagen peptide of Production Example 1 3.0
5. Shark-derived collagen peptide of Production Example 1 3.0
6. Preservative (paraben) appropriate amount
7. Residue with 100 purified water
[0123]

[0124]

[0125]
(Formulation Example 26) Hair growth / hair growth agent
1.Ethanol 60.0
2. Production Example 1 Shark-derived collagen peptide 1.0
3. Pig-derived collagen peptide of Production Example 1 1.0
4. Peony rhizome or root bark 60% ethanol extract 1.0
5. Artemisia leaf or stem 50% 1,3-butylene glycol extract 1.0
6. Soybean seed natto fermentation liquid 1.0
7. Cantalis tincture 0.5
8.Pantothenic acid derivative 0.2
9.β-Glycyrrhetinic acid 0.2
10.Resorcin 0.2
11.salicylic acid 0.2
12.Hydroxyethyl chitosan solution 0.2
13.Elastin hydrolyzate 0.2
14. Antibacterial and antiseptic (paraben) 0.1
15. Perfume (lavender water) appropriate amount
16.Residue with 100 purified water
[0126]
(Prescription Example 27) Granule bath agent
1.Sodium bicarbonate 58.0
2.Anhydrous sodium sulfate 30.0
3. Borax 2.0
4. Pig-derived collagen peptide dry powder of Production Example 1 4.0
5. Shark-derived collagen peptide dry powder of Production Example 1 3.0
6. Dried whole plant hot water extract dry powder 3.0
7. Pigment (Gungjo Green) appropriate amount
[0127]

[0128]
(Prescription Example 29) Coating protective agent
A gauze or liniment cloth is impregnated with a prescription solution in which an appropriate amount of a porcine-derived collagen peptide and a shark-derived collagen peptide, antibiotics, anti-inflammatory agents, etc. of Production Example 1 are mixed, and is attached to the wound. Alternatively, the porcine-derived collagen peptide and shark-derived collagen peptide of Production Example 1 may be directly applied locally and coated with gauze or the like.
[0129]

[0130]

[0131]
(Formulation example 32) Mentsuyu mass%
1. Soy sauce 80.0
2.Black vinegar 2.0
3.Glucose 13.0
4.Sodium glutamate 2.0
5. Pig-derived collagen peptide dry powder of Production Example 1 3.0
[0132]
(Prescription Example 33) Udon or buckwheat mass%
1. Wheat flour or buckwheat flour 93.0
2.Salt 1.0
3. Pig-derived collagen peptide dry powder of Production Example 1 2.0
4. Shark-derived collagen peptide dry powder of Production Example 1 1.0
[0133]
(Prescription Example 34) Beverage Mass%
1.Glucose liquid sugar 30.0
2.Grapefruit juice 45.0
3. Pig-derived collagen peptide dry powder of Production Example 1 2.0
4. Iyokan Juice 5.0
5.Fructose 4.0
6.Perfume appropriate amount
7. Acidity
[0134]
(Prescription Example 35) Bread Mass%
1. Flour 80.0
2.Salt 1.0
3.Glucose 7.0
4. Shark-derived collagen peptide dry powder of Production Example 1 3.0
5. Pig-derived collagen peptide dry powder of Production Example 1 2.0
6.benzoic acid 0.03
7.Carboxymethylchitin solution 2.0
8. Vitamin E 1.0
9. Heme Iron 1.0
[0135]
(Prescription Example 36) Sausage Mass%
1. Minced meat 80.0
2. Egg 10.0
3.Spice 2.0
4.Condiment 2.0
5. Pig-derived collagen peptide dry powder of Production Example 1 2.0
6.Pepper extract 4.0
[0136]
(Prescription Example 37) Gum mass%
1.Mentholmicron 30.0
2. Grapefruit flavor 50.0
3.Lemon flavor 14.0
4. Shark-derived collagen peptide dry powder of Production Example 1 3.0
5.Salicylic acid 0.03
6.Tannin 2.0
[0137]
(Prescription Example 38) Miso Soup Mass%
1.Tofu 30.0
2. Fried chicken 5.0
3.Carrot 5.0
4. Burdock 5.0
5.Chinese cabbage 5.0
6.Red miso 20.0
7. Pig-derived collagen peptide dry powder of Production Example 1 2.0
8.Remaining bonito stock 100
[0138]

[0139]
(Test 6) Use effect test
The effect when the external preparation for skin of the present invention was actually used was examined. The use test was conducted with 10 healthy adult females 25 to 50 years old as panelists, and each day, twice in the morning and at night, applying a suitable amount of the emulsion of Formulation Example 1 to the face for 3 months after face washing. . In addition, the thing which remove | excluded the collagen peptide of this invention from the emulsion by the same method was used for the control | contrast. The evaluation method is based on the following criteria, and the results are as shown in Table 2. The numerical values in the table represent the number of people. No one complained of skin abnormalities during the period of use.
[0140]
"Improve skin tension and gloss"
Effective: Increased skin tension and gloss.
Slightly effective: Slightly increased skin tension and gloss.
Invalid: No change before use.
[0141]
<Table 2>

[0142]
(Test results)
As shown in Table 2, it was confirmed that the emulsion containing the product of the present invention significantly gave skin tension and gloss and had effects such as reduction of skin wrinkles.
[0143]
(Test 7) Use effect test
The effect when the food of the present invention was actually used was examined. The use test was conducted by 10 healthy adult females 25 to 50 years old as panelists, and each day, twice a day in the morning and at night, and 3 cookies (about 50g each) of the prescription example 39 were eaten and consumed for 1 month. It was. In addition, what prepared the thing remove | excluding the collagen peptide of this invention from the cookie by the same method was used for the control | contrast. The evaluation method is based on the following criteria, and the results are as shown in Table 3. The numerical values in the table represent the number of people. No one complained of skin abnormalities during the period of use.
[0144]
"Improve skin tension and gloss"
Effective: Increased skin tension and gloss.
Slightly effective: Slightly increased skin tension and gloss.
Invalid: No change before use.
[0145]
<Table 3>

[0146]
(Test results)
As shown in Table 3, it was confirmed that the cookie containing the product of the present invention significantly gave skin tension and gloss, and also reduced the skin talmi.
[0147]
【The invention's effect】
Collagenase degradation product of collagen or gelatin of the present invention, the amino acid sequence of which is (Gly-XY) (wherein Gly represents a glycine residue, X and Y represent amino acid residues, A collagen peptide (Gly-XY) n (n represents a positive integer) represented by a collagen tripeptide represented by X and Y may be the same or different is highly safe. It was confirmed that hyaluronic acid production was significantly promoted and the skin roughening action was improved. Furthermore, the skin external preparations and foods and drinks containing these have the effect of preventing skin aging such as imparting tension or gloss to the skin, or improving wrinkles and tarmi.
[Brief description of the drawings]
FIG. 1 is a graph showing hyaluronic acid production promotion rates of a porcine-derived collagen peptide (represented as “shark-derived CP”) and a shark-derived collagen peptide (represented as “pig-derived CP”) of the present invention.

Claims (1)

Collagen or gelatin degradation product of collagenase having an amino acid sequence of (Gly-XY) (wherein Gly represents a glycine residue, X and Y represent amino acid residues, and X, Y Hyaluron comprising a collagen peptide (Gly-XY) n (n represents a positive integer) composed of a collagen tripeptide represented by the following formulas: Acid production promoter (excluding external preparations for skin) .

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