JP2012041292A - 抗酸化性ポリヒドロキシベンゼン誘導体および抗炎症用皮膚外用剤 - Google Patents
抗酸化性ポリヒドロキシベンゼン誘導体および抗炎症用皮膚外用剤 Download PDFInfo
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- JP2012041292A JP2012041292A JP2010182951A JP2010182951A JP2012041292A JP 2012041292 A JP2012041292 A JP 2012041292A JP 2010182951 A JP2010182951 A JP 2010182951A JP 2010182951 A JP2010182951 A JP 2010182951A JP 2012041292 A JP2012041292 A JP 2012041292A
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- Prior art keywords
- polyhydroxybenzene
- skin
- astaxanthin
- derivative
- antioxidative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 235000013793 astaxanthin Nutrition 0.000 claims abstract description 32
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 claims abstract description 32
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Abstract
【解決手段】
アスタキサンチン、トコフェロールまたはトコトリエノールからなる抗酸化性物質の水酸基にリン酸をエステル結合させ、このリン酸エステルをポリヒドロキシベンゼンの1以上の水酸基とジエステル結合させたポリヒドロキシフェニルフォスフェートまたはその塩からなる抗酸化性ポリヒドロキシベンゼン誘導体とする。抗酸化性ポリヒドロキシベンゼン誘導体は、適度な脂溶性があって細胞内に取り込まれやすく、皮膚浸透性にも適した特性を有する。細胞に取り込まれた抗酸化性ポリヒドロキシベンゼン誘導体は、生体内組織に分布しているフォスファターゼ他の酵素等によってヒドロキシフェノールやアスタキサンチン、トコフェロールもしくはトコトリエノールに加水分解され、有用な効果を生体に及ぼす。
【選択図】なし
Description
さらに、美白効果の認められるハイドロキノンは、皮膚に紅斑が生じる場合があるなどの感作性があるため、一般には使用が制限され、充分に安全なものとはいえない。
したがって、これらの基を有するこの発明の抗酸化性ポリヒドロキシベンゼン誘導体は、適度な脂溶性があって細胞内に取り込まれやすく、皮膚浸透性にも適した特性を有する。
これらのポリヒドロキシベンゼンを用いたこの発明の抗酸化性ポリヒドロキシベンゼン誘導体には、前記した作用効果が充分に得られる。
先ず、トルエン、クロロベンゼン、ジクロロベンゼンなどから選ばれる非極性溶媒を用いて、トリメチルアミン、トリエチルアミン、N,N−ジメチルアニリンなどから選ばれる塩基の存在下で、化4で示されるアスタキサンチン、すなわち3,3'−ジヒドロキシ−β,β−カロテン−4,4'−ジオン、化5で示されるトコフェロールもしくは化6で示されるトコトリエノールに対して、オキシ塩化リンを−20〜20℃で反応させ、化7の式で示される1分子のアスタキサンチン残基、トコフェロール残基もしくはトコトリエノール残基を有するジクロロフォスフェート、または化8の式で示される2分子のアスタキサンチン残基、トコフェロール残基もしくはトコトリエノール残基を有するモノクロロフォスフェートを製造する。
これらを取り出す必要のある場合は、蒸留により単離できるが、上記の非極性溶媒の溶液として次工程へ進んでも良い。
アスタキサンチンとオキシ塩化リンを反応させ、1分子のアスタキサンチン残基を有するジクロロフォスフェートであるアスタキサンチンジクロロフォスフェートを合成した。
以下に、製造方法をその合成工程毎に詳細に説明する。
窒素置換下、フェニル酢酸1307.1g(9.6モル)を−5℃に冷却し、28%発煙硫酸54.3g(0.2モル)を滴下し、p−ヒドロキシフェノール110.1g(1.0モル)を仕込む。同温度で17時間反応させ、濾過、冷アセトンにより洗浄し、210.5gのp−フェニル酢酸フェノール(純度85.4%)をwetケーキとして得た。
窒素置換下、トルエン540mL及びオキシ塩化リン138.0g(0.9モル)を仕込み、−10℃に冷却する。そこに、アスタキサンチン537.1g(0.9モル、1.0モル比)とトリエチルアミン91.1g(0.9モル)の溶液を滴下し、0℃で12時間反応させた。25℃に昇温した後、濾過によりトリエチルアミンの塩酸塩を除去し、116.8gのアスタキサンチンジクロロフォスフェートのトルエン溶液(濃度34.7%)を得た。
窒素置換下、トルエン2000mLに上記のp−フェニル酢酸フェノール198.4g(1.0モル)を仕込み、室温でトリエチルアミン202.4gを滴下し、1時間攪拌する。その後、−10℃に冷却し、上記のアスタキサンチンジクロロフォスフェートのトルエン溶液1945.5g(0.9モル)を1時間かけて滴下し、同温度で14時間攪拌する。得られた反応マスに6.7%の塩酸水溶液15047gを加え、35℃で4時間加水分解を行い、トルエン層を10%塩酸/7.1%塩化ナトリウム水溶液1000gで2回洗浄した後、更に20%塩化ナトリウム水溶液で1回洗浄した。
これにより得られた化合物が、所期した分子構造のポリヒドロキシベンゼン誘導体である[2−(1,3,3−トリメチル−n−ブチル)−5,7,7−オクチル]−p−ヒドロキシフェニルフォスフェートであることが確認された。
実施例1において、アスタキサンチンの代わりにα−トコフェロールを用いたこと以外は実施例1と全く同様の方法で化合物を得た。
α−トコトリエノール−p−ヒドロキシフェニルフォスフェートのナトリウム塩を以下の方法で製造した。
シミ、ソバカスや色黒等の悩みを持つ被験者を一群20名とし、各化粧料を毎日、朝と夜、3ヶ月間塗布して使用させ、3ヶ月後に累積塗布効果を以下の判定基準により自己判定させ、さらに判定結果を以下の基準で評価し、結果を表5中に示した。
有効:薄くなった。
やや有効:やや薄くなった。
無効:変化なし。
◎:被験者のうち著効、有効の示す割合(有効率)が80%以上。
○:被験者のうち著効、有効の示す割合(有効率)が60%以上80%未満。
△:被験者のうち著効、有効の示す割合(有効率)が40%以上60%未満。
×:被験者のうち著効、有効の示す割合(有効率)が40%未満。
シミ、ソバカスや色黒等の悩みを持つ被験者を一群20名とし、各化粧料を毎日、朝と夜、3ヶ月間塗布使用させ、3ヶ月後に累積塗布効果を以下の判定基準により自己判定させ、さらに判定結果を以下の基準で評価し、表5に示した。
有効:薬剤による紅斑がわずかしか確認されなかった。
やや有効:薬剤による紅斑が少し確認された。
無効:薬剤による紅斑が確認された。
◎:被験者のうち著効、有効の示す割合(有効率)が80%以上。
○:被験者のうち著効、有効の示す割合(有効率)が60%以上80%未満。
△:被験者のうち著効、有効の示す割合(有効率)が40%以上60%未満。
×:被験者のうち著効、有効の示す割合(有効率)が40%未満。
アスタキサンチン−p−ヒドロキシフェニルフォスフェートナトリウム塩 1.0
グリセリン 10.0
エタノール 5.0
水酸化ナトリウム 0.5
カルボキシビニルポリマー 0.8
香料 適量
防腐剤 適量
精製水 残余
α−トコフェロール−p−ヒドロキシフェニルフォスフェート 2.0
1,3−ブチレングリコール 10.0
カルボキシビニルポリマー 0.3
スクワラン 5.0
セタノール 0.8
L−アルギニン 0.3
香料 適量
防腐剤 適量
精製水 残余
α−トコトリエノール−p−ジヒドロキシフェニルフォスフェート 5.0
1,3−ブチレングリコール 10.0
カルボキシビニルポリマー 0.3
スクワラン 5.0
セタノール 2.0
ミツロウ 3.0
L−アルギニン 0.3
香料 適量
防腐剤 適量
精製水 残余
したがって、これらの基を有するこの発明の抗酸化性ポリヒドロキシベンゼン誘導体は、適度な脂溶性があって細胞内に取り込まれやすく、皮膚浸透性にも適した特性を有する。
Claims (5)
- アスタキサンチン、トコフェロールまたはトコトリエノールからなる抗酸化性物質の水酸基にリン酸をエステル結合させ、このリン酸エステルをポリヒドロキシベンゼンの1以上の水酸基とジエステル結合させることにより、ポリヒドロキシフェニルフォスフェートまたはその塩としたものからなる抗酸化性ポリヒドロキシベンゼン誘導体。
- ポリヒドロキシベンゼンが、ジヒドロキシベンゼン、トリヒドロキシベンゼン、テトラヒドロキシベンゼン、ペンタヒドロキシベンゼンまたはヘキサヒドロキシベンゼンである請求項1に記載の抗酸化性ポリヒドロキシベンゼン誘導体。
- ジヒドロキシベンゼンが、カテコール、レゾルシンまたはハイドロキノンである請求項2に記載の抗酸化性ポリヒドロキシベンゼン誘導体。
- 請求項1〜3のいずれかに記載の抗酸化性ポリヒドロキシベンゼン誘導体を有効成分として含有する抗炎症用皮膚外用剤。
- 請求項1〜3のいずれかに記載の抗酸化性ポリヒドロキシベンゼン誘導体を有効成分として含有する美白用化粧料。
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JPS59219295A (ja) * | 1983-05-30 | 1984-12-10 | Senjiyu Seiyaku Kk | リン酸ジエステルまたはその塩およびそれらの製造法 |
JPS62145019A (ja) * | 1985-12-19 | 1987-06-29 | Senjiyu Seiyaku Kk | 抗炎症剤 |
JPH0873312A (ja) * | 1994-09-02 | 1996-03-19 | Noevir Co Ltd | 皮膚外用剤 |
JPH0873311A (ja) * | 1994-09-02 | 1996-03-19 | Noevir Co Ltd | 皮膚外用剤 |
JPH09176173A (ja) * | 1995-12-25 | 1997-07-08 | Senju Pharmaceut Co Ltd | リン酸ジエステルの製造法およびその中間体 |
JP2006232768A (ja) * | 2005-02-28 | 2006-09-07 | Nippon Menaade Keshohin Kk | Atp産生促進剤 |
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JPS59219295A (ja) * | 1983-05-30 | 1984-12-10 | Senjiyu Seiyaku Kk | リン酸ジエステルまたはその塩およびそれらの製造法 |
JPS62145019A (ja) * | 1985-12-19 | 1987-06-29 | Senjiyu Seiyaku Kk | 抗炎症剤 |
JPH0873312A (ja) * | 1994-09-02 | 1996-03-19 | Noevir Co Ltd | 皮膚外用剤 |
JPH0873311A (ja) * | 1994-09-02 | 1996-03-19 | Noevir Co Ltd | 皮膚外用剤 |
JPH09176173A (ja) * | 1995-12-25 | 1997-07-08 | Senju Pharmaceut Co Ltd | リン酸ジエステルの製造法およびその中間体 |
JP2006232768A (ja) * | 2005-02-28 | 2006-09-07 | Nippon Menaade Keshohin Kk | Atp産生促進剤 |
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