JP2016079186A - 皮膚化粧料、頭髪化粧料および飲食品 - Google Patents
皮膚化粧料、頭髪化粧料および飲食品 Download PDFInfo
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- JP2016079186A JP2016079186A JP2015206790A JP2015206790A JP2016079186A JP 2016079186 A JP2016079186 A JP 2016079186A JP 2015206790 A JP2015206790 A JP 2015206790A JP 2015206790 A JP2015206790 A JP 2015206790A JP 2016079186 A JP2016079186 A JP 2016079186A
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Abstract
【解決手段】本発明の抗肥満剤、サイクリックAMPホスホジエステラーゼ活性阻害剤、ジペプチジルペプチダーゼIV活性阻害剤、抗老化剤、育毛剤、抗男性ホルモン剤、美白剤、および抗炎症剤の有効成分として、ジヒドロフェルラ酸を含有させる。また、本発明の皮膚化粧料、頭髪化粧料、および飲食品に、ジヒドロフェルラ酸を配合する。
【選択図】なし
Description
本実施形態の抗肥満剤、サイクリックAMPホスホジエステラーゼ活性阻害剤、ジペプチジルペプチダーゼIV活性阻害剤、抗老化剤、育毛剤、抗男性ホルモン剤、美白剤、および抗炎症剤は、ジヒドロフェルラ酸を有効成分として含有するものである。また、本実施形態の皮膚化粧料、頭髪化粧料および飲食品は、ジヒドロフェルラ酸が配合されるものである。
以上のようにして得られるジヒドロフェルラ酸は、優れた抗肥満作用、サイクリックAMP(cAMP)ホスホジエステラーゼ活性阻害作用、ジペプチジルペプチダーゼIV(DPPIV)活性阻害作用、抗老化作用、育毛作用、抗男性ホルモン作用、美白作用、および抗炎症作用を有しているため、抗肥満剤、cAMPホスホジエステラーゼ活性阻害剤、DPPIV活性阻害剤、抗老化剤、育毛剤、抗男性ホルモン剤、美白剤、および抗炎症剤の有効成分として用いることができる。本実施形態の抗肥満剤、cAMPホスホジエステラーゼ活性阻害剤、DPPIV活性阻害剤、抗老化剤、育毛剤、抗男性ホルモン剤、美白剤、および抗炎症剤は、医薬品、医薬部外品、化粧品等の幅広い用途に使用することができる。
ジヒドロフェルラ酸は、優れた抗老化作用、育毛作用、抗男性ホルモン作用、美白作用、抗炎症作用、cAMPホスホジエステラーゼ活性阻害作用、DPPIV活性阻害作用、および抗肥満作用を有しているため、皮膚化粧料または頭髪化粧料に配合するのに好適である。この場合、ジヒドロフェルラ酸またはジヒドロフェルラ酸を含有する組成物をそのまま配合してもよいし、ジヒドロフェルラ酸またはジヒドロフェルラ酸を含有する組成物から製剤化した抗老化剤、育毛剤、抗男性ホルモン剤、美白剤、抗炎症剤、cAMPホスホジエステラーゼ活性阻害剤、DPPIV活性阻害剤、または抗肥満剤を配合してもよい。
ジヒドロフェルラ酸は、優れた抗肥満作用、cAMPホスホジエステラーゼ活性阻害作用、DPPIV活性阻害作用、抗老化作用、育毛作用、抗男性ホルモン作用、美白作用、および抗炎症作用を有しているため、飲食品に配合するのに好適である。この場合、ジヒドロフェルラ酸をそのまま配合してもよいし、ジヒドロフェルラ酸から製剤化した抗肥満剤、cAMPホスホジエステラーゼ活性阻害剤、DPPIV活性阻害剤、抗老化剤、育毛剤、抗男性ホルモン剤、美白剤、および抗炎症剤を配合してもよい。
ジヒドロフェルラ酸(試料1)について、以下のようにしてサイクリックAMPホスホジエステラーゼ活性阻害作用を試験した。
製品名:Chromatocorder 12(SYSTEM INSTRUMENTS社製)
固定相:Wakosil C18−ODS 5μm(和光純薬工業社製)
カラム長:250mm
移動相:1mmol/L TBAP in 25mmol/L KH2PO4 :CH3CN=90:10
移動相流速:1.0mL/min
検出:260nm
被験試料添加での標準品の分解率(D,%)=(1−B2/A)×100
cAMPホスホジエステラーゼ活性阻害率(%)=(1−D/C)×100
結果を表1に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにして血中脂質低減作用を試験した。
結果を表2に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにしてジペプチジルペプチダーゼIV(DPPIV)阻害作用を試験した。
式中の各項はそれぞれ以下を表す。
A:試料無添加・酵素添加での波長415nmにおける吸光度
B:試料無添加・酵素無添加での波長415nmにおける吸光度
C:被験試料添加・酵素添加での波長415nmにおける吸光度
D:被験試料添加・酵素無添加での波長415nmにおける吸光度
結果を表3に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにしてラミニン5産生促進作用を試験した。
式中の各項はそれぞれ以下を表す。
A:被験試料添加時の波長405nmにおける吸光度
B:試料無添加時の波長405nmにおける吸光度
結果を表4に示す。
MMP−2は、特開2007−217352号公報に記載の方法により調製したものを用いた。すなわち、MMP−2タンパク質を、C末端にヒスチジン6残基を持つ組換え体proMMPタンパク質として大腸菌遺伝子発現系を用い大量発現させ、Ni−NTA樹脂を用いた精製およびリフォールディングを行った後、活性型へ移行させた。これを酵素標品とし、適宜希釈し酵素溶液を調製した。
得られた酵素溶液を用い、ジヒドロフェルラ酸(試料1)について、以下のようにしてMMP−2活性阻害作用を試験した。
式中の各項はそれぞれ以下を表す。
A:試料無添加での基質添加120分後の420nmにおける蛍光強度
B:試料無添加での基質添加直後の420nmにおける蛍光強度
C:被験試料添加での基質添加120分後の420nmにおける蛍光強度
D:被験試料添加での基質添加直後の420nmにおける蛍光強度
結果を表5に示す。
ヒト正常皮膚線維芽細胞(NB1RGB)を、10%FBS含有α−MEM培地を用いて培養した後、トリプシン処理により細胞を回収した。回収した細胞を1.6×105 cells/mLの細胞密度になるよう0.5%FBS含有α−MEM培地で希釈した後、96ウェルプレートに1ウェル当たり100μLずつ播種し、一晩培養した。
式中の各項はそれぞれ以下を表す。
A:被験試料添加時のヒアルロン酸量
B:被験試料無添加時のヒアルロン酸量
結果を表6に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにして表皮角化細胞増殖促進作用を試験した。
式中の各項はそれぞれ以下を表す。
St:被験試料を添加した細胞でのブルーホルマザン生成量
Ct:試料無添加の細胞でのブルーホルマザン生成量
結果を表7に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにしてエラスチン産生促進作用を試験した。
式中の各項はそれぞれ以下を表す。
A:被験試料添加時のエラスチン量
B:試料無添加時のエラスチン量
結果を表8に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにしてMMP−1活性阻害作用を試験した。
式中の各項はそれぞれ以下を表す。
A:試料無添加・酵素添加での波長320nmにおける吸光度
B:試料無添加・酵素無添加での波長320nmにおける吸光度
C:試料添加・酵素添加での波長320nmにおける吸光度
D:試料添加・酵素無添加での波長320nmにおける吸光度
結果を表9に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにして皮膚線維芽細胞増殖促進作用を試験した。
式中の各項はそれぞれ以下を表す。
St:被験試料添加でのブルーホルマザン生成量
Ct:試料無添加でのブルーホルマザン生成量
結果を表10に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにしてAQP3mRNA発現促進作用を試験した。
式中の各項はそれぞれ以下を表す。
A:被験試料添加時の補正値
B:試料無添加時の補正値
結果を表11に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにして最終糖化生成物(AGEs)の形成抑制作用を試験した。
式中の各項はそれぞれ以下を表す。
A:陰性対照での波長405nmにおける吸光度
B:陽性対照での波長405nmにおける吸光度
C:被験試料添加での波長405nmにおける吸光度
結果を表12に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにしてテストステロン5α−レダクターゼ阻害作用を試験した。
使用装置:Shimadzu GC-2010(島津製作所社製)
カラム:DB−1701(内径:0.53mm,長さ:30m,膜厚:1.0μm,J&W Scientific社製)
カラム温度:240℃
注入口温度:300℃
検出器:FID
試料注入量:1μL
スプリット比:1:2
キャリアガス:窒素ガス
キャリアガス流速:3mL/min
3α−アンドロスタンジオール、5α−DHTおよびテストステロンの標準品を塩化メチレンに溶解し、当該溶液をガスクロマトグラフィー分析に供し、これらの化合物の濃度(μg/mL)およびピーク面積から、ピーク面積と化合物の濃度との対応関係を予め求めておいた。そして、テストステロンとS−9との反応後の3α−アンドロスタンジオール、5α−DHTおよびテストステロンのそれぞれのピーク面積あたりの濃度を、予め求めておいた対応関係を利用して、下記式(1)に基づいて求めた。
式中の各項はそれぞれ以下を表す。
A:3α−アンドロスタンジオール、5α−DHTまたはテストステロンの濃度
B:3α−アンドロスタンジオール、5α−DHTまたはテストステロンのピーク面積
C:標準品の濃度
D:標準品のピーク面積
式中の各項はそれぞれ以下を表す。
E:3α−アンドロスタンジオールの濃度(μg/mL)
F:5α−DHTの濃度(μg/mL)
G:テストステロンの濃度(μg/mL)
テストステロン5α−レダクターゼ阻害率(%)=(1−H/I)×100・・・(3)
式中の各項はそれぞれ以下を表す。
H:被検試料添加での変換率
I:試料無添加での変換率
結果を表13に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにして毛乳頭細胞増殖促進作用を試験した。
式中の各項はそれぞれ以下を表す。
A:被験試料添加でのブルーホルマザン生成量
B:試料無添加でのブルーホルマザン生成量
結果を表14に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにしてB16メラノーマ細胞に対するメラニン産生抑制作用を試験した。
式中の各項はそれぞれ以下を表す。
A:試料無添加におけるメラニン量
B:被験試料添加におけるメラニン量
C:試料無添加における540nmの吸光度
D:被験試料添加における540nmの吸光度
結果を表15に示す。
0.1mol/L酢酸緩衝液(pH3.5)に溶解した被験試料(試料1,試料濃度は下記表14を参照)0.2mLに、ヒアルロニダーゼ溶液(Type IV-S(from bovine testes),400 NF units/mL,SIGMA社製)0.1mLを加え、37℃で20分間静置した。さらに、活性化剤として2.5mmol/L塩化カルシウム0.2mLを加え、37℃で20分間静置した。これに0.8mg/mLヒアルロン酸ナトリウム溶液(from rooster comb)0.5mLを加え、37℃で40分間反応した。その後、0.4mol/L水酸化ナトリウム0.2mLを加えて反応を止め冷却した後、各反応溶液にホウ酸溶液0.2mLを加え、3分間煮沸した。氷冷後、p−DABA試薬6mLを加え、37℃で20分間反応した。その後、波長585nmにおける吸光度を測定した。
ヒアルロニダーゼ活性阻害率(%)={1−(St−Sb)/(Ct−Cb)}×100
式中の各項はそれぞれ以下を表す。
St:被験試料溶液の波長585nmにおける吸光度
Sb:被験試料溶液ブランクの波長585nmにおける吸光度
Ct:コントロール溶液の波長585nmにおける吸光度
Cb:コントロール溶液ブランクの波長585nmにおける吸光度
結果を表16に示す。
ジヒドロフェルラ酸(試料1)について、以下のようにしてヘキソサミニダーゼ遊離抑制作用を試験した。
式中の各項はそれぞれ以下を表す。
A:試料無添加での補正値
B:被験試料添加での補正値
C:被験試料添加・p−NAG無添加での補正値
結果を表17に示す。
マウスマクロファージ細胞(RAW264.7)を、10%FBS含有ダルベッコMEM培地を用いて培養した後、セルスクレーパーにより細胞を回収した。回収した細胞を2.0×105 cells/mLの濃度になるように10%FBS含有ダルベッコMEM培地で希釈した後、96ウェルプレートに1ウェル当たり100μLずつ播種し、18時間培養した。
式中の各項はそれぞれ以下を表す。
A:被験試料添加・LPS刺激時のプロスタグランジンE2 量
B:試料無添加・LPS刺激時のプロスタグランジンE2 量
C:試料無添加・LPS無刺激時のプロスタグランジンE2 量
結果を表18に示す。
下記組成の乳液を常法により製造した。
ジヒドロフェルラ酸 0.01g
ホホバオイル 4.00g
1,3−ブチレングリコール 3.00g
アルブチン 3.00g
ポリオキシエチレンセチルエーテル(20E.O.) 2.50g
オリーブオイル 2.00g
スクワラン 2.00g
セタノール 2.00g
モノステアリン酸グリセリル 2.00g
オレイン酸ポリオキシエチレンソルビタン(20E.O.) 2.00g
パラオキシ安息香酸メチル 0.15g
グリチルリチン酸ステアリル 0.10g
黄杞エキス 0.10g
グリチルリチン酸ジカリウム 0.10g
イチョウ葉エキス 0.10g
コンキオリン 0.10g
オウバクエキス 0.10g
カミツレエキス 0.10g
香料 0.05g
精製水 残部(全量を100gとする)
下記組成のクリームを常法により製造した。
ジヒドロフェルラ酸 0.05g
クジンエキス 0.1g
オウゴンエキス 0.1g
流動パラフィン 5.0g
サラシミツロウ 4.0g
スクワラン 10.0g
セタノール 3.0g
ラノリン 2.0g
ステアリン酸 1.0g
オレイン酸ポリオキシエチレンソルビタン(20E.O.) 1.5g
モノステアリン酸グリセリル 3.0g
油溶性甘草エキス 0.1g
1,3−ブチレングリコール 6.0g
パラオキシ安息香酸メチル 1.5g
香料 0.1g
精製水 残部(全量を100gとする)
下記組成の美容液を常法により製造した。
ジヒドロフェルラ酸 0.01g
カミツレエキス 0.1g
ニンジンエキス 0.1g
キサンタンガム 0.3g
ヒドロキシエチルセルロース 0.1g
カルボキシビニルポリマー 0.1g
1,3−ブチレングリコール 4.0g
グリチルリチン酸ジカリウム 0.1g
グリセリン 2.0g
水酸化カリウム 0.25g
香料 0.01g
防腐剤(パラオキシ安息香酸メチル) 0.15g
エタノール 2.0g
精製水 残部(全量を100gとする)
下記組成のヘアトニックを常法により製造した。
ジヒドロフェルラ酸 0.4g
酢酸トコフェロール 適量
セファラチン 0.002g
イソプロピルメチルフェノール 0.1g
ヒアルロン酸ナトリウム 0.15g
グリセリン 15.0g
エタノール 15.0g
香料 適量
キレート剤(エデト酸ナトリウム) 適量
防腐剤(ヒノキチオール) 適量
可溶化剤(ポリオキシエチレンセチルエーテル) 適量
精製水 残部(全量を100gとする)
下記組成のシャンプーを常法により製造した。
ジヒドロフェルラ酸 0.5g
マジョラム抽出物 1.0g
ウメ果実部抽出物 0.2g
ヤシ油脂肪酸メチルタウリンナトリウム 10.0g
ヤシ油脂肪酸アミドプロピルベタイン 10.0g
ポリオキシエチレンアルキルエーテル硫酸ナトリウム 20.0g
ヤシ油脂肪酸ジエタノールアミド 4.0g
プロピレングリコール 2.0g
香料 適量
精製水 残部(全量を100gとする)
常法により、以下の組成を有する錠剤を製造した。
ジヒドロフェルラ酸 5.0mg
ドロマイト(カルシウム20%、マグネシウム10%含有) 83.4mg
カゼインホスホペプチド 16.7mg
ビタミンC 33.4mg
マルチトール 136.8mg
コラーゲン 12.7mg
ショ糖脂肪酸エステル 12.0mg
常法により、以下の組成を有する経口液状製剤を製造した。
<1アンプル(1本100mL)中の組成>
ジヒドロフェルラ酸 0.3質量%
ソルビット 12.0質量%
安息香酸ナトリウム 0.1質量%
香料 1.0質量%
硫酸カルシウム 0.5質量%
精製水 残部(100質量%)
Claims (16)
- ジヒドロフェルラ酸を有効成分として含有することを特徴とする抗肥満剤。
- 前記ジヒドロフェルラ酸が、cAMPホスホジエステラーゼ活性阻害作用、血中コレステロール低減作用、血中遊離脂肪酸低減作用、およびジペプチジルペプチダーゼIV活性阻害作用からなる群より選択される1種または2種以上の作用を有することを特徴とする請求項1に記載の抗肥満剤。
- ジヒドロフェルラ酸を有効成分として含有することを特徴とするサイクリックAMPホスホジエステラーゼ活性阻害剤。
- ジヒドロフェルラ酸を有効成分として含有することを特徴とするジペプチジルペプチダーゼIV活性阻害剤。
- ジヒドロフェルラ酸を有効成分として含有することを特徴とする抗老化剤。
- 前記ジヒドロフェルラ酸が、ラミニン5産生促進作用、マトリックスメタロプロテアーゼ−2活性阻害作用、ヒアルロン酸産生促進作用、表皮角化細胞増殖促進作用、エラスチン産生促進作用、マトリックスメタロプロテアーゼ−1活性阻害作用、線維芽細胞増殖促進作用、アクアポリン3mRNA発現促進作用、および最終糖化産物形成抑制作用からなる群より選択される1種または2種以上の作用を有することを特徴とする請求項5に記載の抗老化剤。
- ジヒドロフェルラ酸を有効成分として含有することを特徴とする育毛剤。
- 前記ジヒドロフェルラ酸が、テストステロン5α−レダクターゼ活性阻害作用および/または毛乳頭細胞増殖促進作用からなる群より選択される1種または2種以上の作用を有することを特徴とする請求項7に記載の育毛剤。
- ジヒドロフェルラ酸を有効成分として含有することを特徴とする抗男性ホルモン剤。
- ジヒドロフェルラ酸を有効成分として含有することを特徴とする美白剤。
- 前記ジヒドロフェルラ酸が、メラニン産生抑制作用を有することを特徴とする請求項10に記載の美白剤。
- ジヒドロフェルラ酸を有効成分として含有することを特徴とする抗炎症剤。
- 前記ジヒドロフェルラ酸が、ヒアルロニダーゼ活性阻害作用、ヘキソサミニダーゼ遊離抑制作用、およびシクロオキシゲナーゼ−2活性阻害作用からなる群より選択される1種または2種以上の作用を有することを特徴とする請求項12に記載の抗炎症剤。
- ジヒドロフェルラ酸を配合したことを特徴とする皮膚化粧料。
- ジヒドロフェルラ酸を配合したことを特徴とする頭髪化粧料。
- ジヒドロフェルラ酸を配合したことを特徴とする飲食品。
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WO2022239837A1 (ja) * | 2021-05-12 | 2022-11-17 | 丸善製薬株式会社 | 経口組成物、皮膚化粧料および頭髪化粧料 |
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WO2023218869A1 (ja) * | 2022-05-13 | 2023-11-16 | 丸善製薬株式会社 | 副交感神経活性化剤及び副交感神経活性化用組成物 |
WO2023218868A1 (ja) * | 2022-05-13 | 2023-11-16 | 丸善製薬株式会社 | 交感神経活性化剤及び交感神経活性化用組成物 |
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