JP5041565B2 - Stable inclusion compound of astaxanthin and γ-cyclodextrin and method for producing the same, and liquid, food and drink, feed, pharmaceutical and cosmetic use - Google Patents
Stable inclusion compound of astaxanthin and γ-cyclodextrin and method for producing the same, and liquid, food and drink, feed, pharmaceutical and cosmetic use Download PDFInfo
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- JP5041565B2 JP5041565B2 JP2001157753A JP2001157753A JP5041565B2 JP 5041565 B2 JP5041565 B2 JP 5041565B2 JP 2001157753 A JP2001157753 A JP 2001157753A JP 2001157753 A JP2001157753 A JP 2001157753A JP 5041565 B2 JP5041565 B2 JP 5041565B2
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- Prior art keywords
- astaxanthin
- cyclodextrin
- weight
- water
- inclusion compound
- Prior art date
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- JEBFVOLFMLUKLF-IFPLVEIFSA-N Astaxanthin Natural products CC(=C/C=C/C(=C/C=C/C1=C(C)C(=O)C(O)CC1(C)C)/C)C=CC=C(/C)C=CC=C(/C)C=CC2=C(C)C(=O)C(O)CC2(C)C JEBFVOLFMLUKLF-IFPLVEIFSA-N 0.000 title claims description 115
- 235000013793 astaxanthin Nutrition 0.000 title claims description 115
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- 229940022405 astaxanthin Drugs 0.000 title claims description 115
- 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 title claims description 106
- 229920000858 Cyclodextrin Polymers 0.000 title claims description 77
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 title claims description 66
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- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 5
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Description
【０００１】
【発明の属する技術分野】
本発明は、アスタキサンチンに対し、γ−シクロデキストリンを特定の割合で配合することを特徴とする安定なアスタキサンチンとγ−シクロデキストリンとの包接化合物及びその製造方法、並びに該包接化合物を含有する液剤、飲食物、動物用飼料、医薬品及び化粧品の用途に関する。
【０００２】
【従来の技術】
アスタキサンチンは動植物に含まれる代表的なカロテノイドであり、オキアミ、エビ、カニ等の甲殻類、マダイの体表や、サケの筋肉、イクラ等の魚卵に、また酵母や藻類等に分布する赤色カロテノイドとして知られていて、養殖魚介類の色調改善剤、色揚げ剤、食品添加物、化粧品の着色剤として利用されている。最近、アスタキサンチンが抗酸化剤等の作用を有することが報告され(清水延寿、幹渉、海洋生物のカロテノイド、幹渉編、恒星社厚生閣、平成５年)、さらには食品添加物等への応用も報告されている。しかしながら、アスタキサンチンは、他のカロテノイド色素と同様に脂溶性物質であることから、水溶性溶媒への溶解性や水溶性化合物に添加しようとすると、溶解性が悪いという問題があった。最近、アスタキサンチンはアスタキサンチン産生ヘマトコッカス藻の大量培養により大量且つ安価に入手することが可能になった。ところが、ヘマトコッカス等天然由来の抽出物に含まれるアスタキサンチンは、アスタキサンチンの遊離体、アスタキサンチン脂肪酸モノエステル及びアスタキサンチン脂肪酸ジエステルの他に夾雑物として、さらにモノグリセリド、ジグリセリド及びトリグリセリド等のグリセリド、遊離脂肪酸、又は該遊離脂肪酸に由来するエステル類等を含むため、従来の方法で粉末化しても、室温ではアスタキサンチンの赤色が褪色してしまい商品価値が低下するという問題があった。カロテノイドとシクロデキストリンとの包接体を調製する方法は多々報告されている例えば、（１）特開平9-124470号公報にはアスタキサンチン及び／又はそのエステルをシクロ（環状）デキストリン（α−シクロデキストリン、β−シクロデキストリン、γ−シクロデキストリン）を用いて包接することにより、水に可溶な粉末状の包接化合物を得ることができること、（２）特開平10-155459号公報にはアスタキサンチンエチルエステル含有ドリンク剤、滋養強壮強精剤が、また（３）特開2001-2569号公報にはシクロ（環状）デキストリン（α−シクロデキストリン、β−シクロデキストリン、γ−シクロデキストリン）を用いて包接することにより水に可溶な粉末状の包接物を得ることができることが記載されている。
しかしながら、アスタキサンチンとシクロデキストリンを単に混合しても安定なアスタキサンチン−シクロデキストリン包接物が得られず、またアスタキサンチンをエタノールで溶解させ、水で希釈しただけでは安定なアスタキサンチンとγ−シクロデキストリンとの包接化合物は得られないことが分かった。安定なアスタキサンチンとγ−シクロデキストリンとの包接化合物及びその製造方法、並びに該包接化合物の液剤、特に該粉末を溶解させ安定且つ澄明な液剤を得る方法については未だ充分な方法がない。
【０００３】
【発明が解決しようとする課題】
本発明は、安定なアスタキサンチンとγ−シクロデキストリンとの包接化合物及びその製造方法、並びに該包接化合物を含有する液剤、飲食物、動物用飼料、医薬品及び化粧品の用途を提供することを目的とする。
【０００４】
【発明を解決するための手段】
本発明の（１）はアスタキサンチン及び／又はそのエステル１重量部とγ−シクロデキストリン０．５〜１００重量部の混合物に、γ−シクロデキストリン１重量部に対して、酢酸エチル、ジクロロメタン、クロロホルム、アセトン、エーテルからなる群から選ばれる少なくとも１種の有機溶媒とアルコール類の合計０．５〜１０重量部と水１〜２０重量部の存在下で、混合することを特徴とするアスタキサンチン及び／又はそのエステルとγ−シクロデキストリンとの包接化合物の製造方法、
（２）はアスタキサンチン及び／又はそのエステル１重量部と、γ−シクロデキストリン０．５〜１００重量部の混合物に、γ−シクロデキストリン１重量部に対して、酢酸エチル、ジクロロメタン、クロロホルム、アセトン、エーテルからなる群から選ばれる少なくとも１種の有機溶媒とアルコール類の合計０．５〜１０重量部と水１〜２０重量部の存在下で、混合し、生成した包接化合物を上記有機溶媒からなる群から選ばれる少なくとも１種の有機溶媒で洗浄し、乾燥し、さらに少量の水で洗浄後、乾燥することを特徴とする安定性が向上したアスタキサンチン及び／又はそのエステルとγ−シクロデキストリンとの包接化合物の製造方法、
（３）はアスタキサンチン及び／又はそのエステル１重量部に対し、γ−シクロデキストリン０．５〜１００重量部の割合で配合するアスタキサンチン及び／又はそのエステルとγ−シクロデキストリンとの包接化合物を形成することを特徴とするアスタキサンチン及び／又はそのエステルを安定化する方法である。
【０００５】
この明細書において、アスタキサンチンとは、アスタキサンチンの遊離体、アスタキサンチン脂肪酸モノエステル、アスタキサンチン脂肪酸ジエステルの群から選ばれる少なくとも１種からなるものである。脂肪酸エステルとは、炭素数が２個以上の飽和脂肪酸又は不飽和脂肪酸の群から選ばれる少なくとも１種以上からなるものである。
【０００６】
アスタキサンチンは、合成品及び／又は天然品であっても良いが、生体の安全性を考慮すると天然由来品、例えばヘマトコッカス藻体、ファフィア酵母又はオキアミ等から抽出されるアスタキサンチンが好ましく、さらに好ましくは工業的に大量且つ安定に入手できるヘマトコッカス藻体からの抽出アスタキサンチンである。
【０００７】
アスタキサンチンとして、ヘマトコッカス由来のアスタキサンチンオイルを使用するときは、オイル中のアスタキサンチンの含量とその他の夾雑物（主な成分は、モノ、ジ、トリグリセリド）の成分の重量に基づいてγ−シクロデキストリンの使用量を設定することができる。具体的には、アスタキサンチン１重量部に対し、γ−シクロデキストリン０．５〜１００重量部の範囲であり、好ましくは０．５〜５０重量部の範囲、より好ましくは１〜５０重量部の範囲である。
【０００８】
本発明においては上記γ−シクロデキストリン以外にアスタキサンチンとγ−シクロデキストリンとの包接化合物の安定性と、水への溶解性を妨げない範囲でα−シクロデキストリン、β−シクロデキストリン、δ−シクロデキストリン及び公知の水溶性のシクロデキストリン誘導体を添加しても良い。
【０００９】
水溶性のシクロデキストリン誘導体としては、例えば、ヒドロキシプロピル−β−シクロデキストリン、メチル−β−シクロデキストリン、モノアセチル−β−シクロデキストリン、トリアセチル−β−シクロデキストリン、モノクロロトリアジル−β−シクロデキストリン、スルホブチルエーテル−β−シクロデキストリン、ジ−Ｏ−メチル−β−シクロデキストリン、マルトシル−β−シクロデキストリン等を挙げることができる。
【００１０】
本発明の安定なアスタキサンチンとシクロデキストリンとの包接化合物は、アスタキサンチンとγ−シクロデキストリンとの混合物に水と少なくとも１種以上の有機溶媒を特定割合で配合することにより製造することができる。
【００１１】
用いる有機溶剤は、アスタキサンチン、アスタキサンチンオイルが溶解するものであれば特に制限はないが、好ましくは粉末化の最終段階で除去しやすいものであり、例えば、メタノール、エタノール、ブタノール、プロパノール等のアルコール類、酢酸エチル等のエステル類、ジクロロメタン、クロロホルム等のハロゲン化炭素水素、アセトン、エーテル等から選ばれる少なくとも１種である。より好ましくは短時間で包接化処理することができるエタノールとジクロロメタン又はクロロホルムの組合せである。
【００１２】
包接化の方法としては、混練法、液相混合法、溶媒蒸発法、共沈法、凍結乾燥法等を例示することができる。好ましくは取扱が容易である混練法、液相混合法、溶媒蒸発法である。
【００１３】
混練法は、例えば、混練機、乳鉢等を用いて、アスタキサンチン又はアスタキサンチンオイルとγ−シクロデキストリンとの混合物に水と前記有機溶媒の適量を加えて、すりつぶしながら、ペースト状になるまで練り混ぜる方法である。
【００１４】
液相混合法は、例えばフラスコ、反応釜等の容器内にアスタキサンチン又はアスタキサンチンオイルとγ−シクロデキストリンとを前記有機溶媒及び水を加え水相中で激しく攪拌混合する方法である。
【００１５】
溶媒蒸発法は、例えばロータリーエバポレーター等減圧可能な装置を用いて、アスタキサンチン又はアスタキサンチンオイルとγ−シクロデキストリンとの混合物に前記有機溶媒と水を添加した後、減圧下溶媒を留去する方法である。
【００１６】
共沈法は、アスタキサンチン又はアスタキサンチンオイルを前記有機溶媒に溶解した溶液を、所望の濃度に調製したγ−シクロデキストリンの水溶液に、攪拌しながら、滴下する方法である。
【００１７】
凍結乾燥法は、アスタキサンチン又はアスタキサンチンオイルとγ−シクロデキストリンに前記有機溶媒と水を添加し、混合後、凍結乾燥することにより、溶媒を留去する方法である。
【００１８】
アスタキサンチンとγ−シクロデキストリンとの包接化合物の製造中にアスタキサンチンが分解及び／又は褪色するのを防ぐため、包接化合物を調製する温度範囲は８０℃以下が好ましい。より好ましくは６０℃以下、さらに好ましくは室温付近である。
【００１９】
本発明の製法で得られた包接化合物は、充分に溶媒を除去した方がより安定な粉末として得られる。
【００２０】
本発明の製法において、γ−シクロデキストリンを、予めγ−シクロデキストリン１重量部に対して水０．５〜１０重量部を添加したものを用いるとより安定なアスタキサンチンとγ−シクロデキストリンとの包接化合物が得られる。
【００２１】
アスタキサンチンオイルを用いて包接化合物を調製するときに、以下の方法で行うと、さらに安定性の高い粉末が得られる。具体的には、アスタキサンチンオイルに含まれるアスタキサンチン１重量部と、γ−シクロデキストリン０．５〜１００重量部の混合物に、γ−シクロデキストリン１重量部に対して、メタノール、エタノール、プロパノール、ブタノール、アセトン、エーテル、酢酸エチル、ジクロロメタン、クロロホルムからなる群から選ばれる少なくとも１種の有機溶媒０．５〜１０重量部と水１〜２０重量部を添加し、生成した包接化合物を上記有機溶媒からなる群から選ばれる少なくとも１種の有機溶媒で洗浄し、乾燥し、さらに少量の水で洗浄後、乾燥する方法である。上記有機溶媒、水での洗浄により、アスタキサンチンの安定性に影響する微量成分が除去されるためと考えられる。
【００２２】
本発明のアスタキサンチンとγ−シクロデキストリンの包接化合物には、安定な包接化合物の形成を阻害しない範囲で、粉体製造において、慣用の水溶性の甘味料、香料、着色料、でんぷん、アルギン酸ソーダ等の崩壊剤、ラクトース、グリコース、シュクロース、マニトール、エリスリトール等の賦形剤、ヒドロキシプロピルセルロース、ゼラチン等の結合剤、グリセリン等の可塑剤等を用いることができる。
【００２３】
本発明の安定なアスタキサンチンとγ−シクロデキストリンとの包接化合物には、アスタキサンチン及び／又はそのエステルが空中で酸化分解されるのを防止するために、ブチルハイドキシトルエン、ブチルハイドロキシアニソール、ビタミンＥ類（トコフェロール及び、トコトリエノール又はその誘導体）、アスコルビン酸、Ｌ−アスコルビン酸パルミチン酸エステル、Ｌ−アスコルビン酸ステアリン酸エステル、アスコルビン酸ナトリウム、没食子酸、エトキシキン、グルタチオン、フィチン酸、カテキン類、ポリフェノール類、フラボノイド類、カロテノイド類、キサントフィル類、ゴマ抽出物、ローズマリー抽出物等の天然及び合成抗酸化剤を添加しても良い。
【００２４】
本発明のアスタキサンチンとγ−シクロデキストリンとの包接化合物を含有する均一且つ透明な液剤は、該包接化合物を水に溶解させることにより、又は懸濁させた後不溶物を所望の孔径のフィルターを用いてろ過することにより、調製することができる。
【００２５】
上記液剤には、さらに液剤の調製において、通常用いられる界面活性剤、溶解補助剤等を、包接化合物の溶解性に影響しない量を添加しても良い。界面活性剤としては、ショ糖脂肪酸エステル、プロピレングリコールエステル、グリセリン脂肪酸エステル、ソルビタン脂肪酸エステル、デキストリン、還元デキストリン等を挙げることができる。
【００２６】
本発明の包接化合物を、飲食物、栄養補助食品又は機能性食品として用いる場合の形態は、通常の薬剤で用いられる形態に準拠したものであり、例えば、錠剤、散剤、顆粒剤、カプセル剤、ドリンク剤の形態が例示できる。栄養のバランスをとるため、常法に従って一般に使用されている賦形剤、増量剤、ビタミン類、繊維質、タンパク質、アミノ酸、ミネラル類、動植物性抽出エキス、甘味料、香料、安定化剤、色素等を添加することができる。
【００２７】
飲食物の形態としては、加工乳、チーズ、バター、マーガリン、生クリーム、アイスクリーム、氷菓子、プリン、乳製品、ゼリー、キャンディー、ドロップ、飴、キャラメル、チューインガム、カステラ、ケーキ、ドーナッツ、ビスケット、クラッカー、スナック菓子、フライドポテト、ポテトチップ、ポップコーン、もち、団子、大福、スープ、ソーセージ、ハム、ベーコン、肉製品、カマボコ、チクワ、ハンペン、魚製品、スパッゲッティ、パスタ、グラタン、パエリア、カレー、ソース、ケチャップ、ドレッシング、漬け物、炭酸系飲料、果汁飲料、スポーツ飲料、茶、コーヒー、ココア、ビール、リキュール、カクテル、薬用酒等の一般食品の形態を上げることができる。また、安定で均一かつ澄明な赤色系の液剤として清涼感のある飲料として利用することができる。
【００２８】
飼料として用いる場合は、そのまま飼料として用いてもよいが、一般に用いられる動物用、魚類用配合飼料の配合原料、例えば、トウモロコシ、マイロ、魚粉、ふすま、食塩、炭酸カルシウム、リン酸カルシウム、アミノ酸類、ビタミン類、微量ミネラル、既存の抗酸化剤等を配合しても良い。
【００２９】
医薬品として用いるには、常法に従って、例えば、錠剤及び粉末のような固形投与形態、あるいはシロップのような液体投与形態で経口投与される。また非経口投与的に、例えば、貼付薬、軟膏、注射剤、座薬としても使用可能である。薬剤の調製自体は常法に従って行うことができる。
【００３０】
化粧品の形態としては、特に限定されず、例えば、乳液、クリーム、化粧水、パック、洗浄料等のスキンケア化粧料、ファンデーション、アイシャドウ、マスカラ、口紅等のメーキャップ化粧料、分散液、軟膏、外用液剤、クリーム剤等の化粧料とすることができる。また、通常化粧品や医薬品等の皮膚外用剤に用いられる成分、例えば、水（アルカリ単純温泉水、深層水、精製水等を含む）、低級アルコール、多価アルコール、油脂、ロウ、鉱物油、脂肪酸、粉体、金属セッケン、pH調整剤、界面活性剤、増粘剤、色素、植物又は動物系原料由来の抽出物、ビタミン類、アミノ酸類、ホルモン類、殺菌・消毒剤、角質溶解剤、酵素、清涼剤、安定化剤、金属イオンキレート剤、血行促進剤、精油、消臭剤、保湿剤、収斂剤、抗脂漏剤、細胞賦活剤、香料等を添加しても良い。
【００３１】
【実施例】
本発明を以下の参考例、実施例、比較例により詳細に説明する。
参考例１ ヘマトコッカス藻からのアスタキサンチンオイルの調製：
【００３２】
公知の方法によりヘマトコッカス藻を培養し、アスタキサンチン含有ヘマトコッカス藻体を得た。藻体を培養液から分離、乾燥した後、アセトン抽出し、必要ならば不溶物を除去した後、エバポレーターで減圧下アセトンを留去することによりアスタキサンチン抽出物（以下アスタキサンチンオイル）を得た。このアスタキサンチンオイル中のアスタキサンチン含量は吸光度法（測定波長４７５nm、溶媒アセトン）にて定量した。オイル中の遊離体スタキサンチンとアスタキサンチン脂肪酸モノエステル及びアスタキサンチン脂肪酸ジエステルの合計の量はオイル全量に対して１５重量％であった。アスタキサンチンオイル中のアスタキサンチンの組成は、遊離体アスタキサンチン（６重量％）、アスタキサンチン脂肪酸モノエステル（８２重量％）及びアスタキサンチン脂肪酸ジエステル（１２重量％）であった。その他の成分としてモノ−、ジ−、トリ−グリセリド類が５０重量％であった。
ただし、本発明に用いるアスタキサンチンオイルの組成、脂肪酸の種類は特にに限定されるものではない。
【００３３】
実施例１
アスタキサンチン（合成品、シグマ製）１．０ｇ、粉末状のγ−シクロデキストリン（商品名デキシパールγ−１００、塩水港精糖製）４．０ｇ、エタノール−ジクロロメタン（容量比＝１：１）混合溶液４ｍｌ及びイオン交換水４ｍｌを乳鉢に入れ、乳棒でよく混合した。有機溶媒が揮発した後、再びエタノール−ジクロロメタン（容量比＝１：１）混合溶液４ｍｌを加え、再びよく混合し、この操作を３回繰り返しペースト状とした。最終段階で添加した溶媒を殆ど揮発させ、湿った粉体状物の残分を真空乾燥機にて減圧下１晩乾燥した。
【００３４】
実施例２
参考例１で得られたアスタキサンチンオイル１．０ｇ、上記γ−シクロデキストリン２．０ｇ、エタノール−ジクロロメタン（容量比＝１：１）混合溶液２ｍｌ及びイオン交換水２ｍｌを乳鉢に入れ、乳棒でよく混合した。有機溶媒が揮発した後、再びエタノール−ジクロロメタン（容量比＝１：１）混合溶液２ｍｌを加え、再びよく混合し、この操作を３回繰り返しペースト状とした。最終段階で添加した溶媒を殆ど揮発させ、湿った粉体状物の残分を真空乾燥機にて減圧下１晩乾燥した。
【００３５】
実施例３
上記γ−シクロデキストリン４．０ｇと水４．０ｍｌを乳鉢に加え、良く混練した後、参考例１で得られたアスタキサンチンオイル１．０ｇとエタノール−ジクロロメタン（様良否＝１：１）混合溶液４．０ｍｌを加え、良く混練した。有機溶媒が揮発した後、再びエタノール−ジクロロメタン（容量比＝１：１）混合溶液４ｍｌを加え、再びよく混合し、この操作を３回繰り返しペースト状とした。最終段階で添加した溶媒を殆ど揮発させ、湿った粉体状物の残分を真空乾燥機にて減圧下１晩乾燥した。
【００３６】
実施例４
参考例１で得られたアスタキサンチンオイル１．０ｇ、上記γ−シクロデキストリン４．０ｇ、水１０ｍｌ及びエタノール−ジクロロメタン（容量比＝１：１）混合溶液１０ｍｌをナス型フラスコに入れ、６０℃に加温してロータリーエバポレーターで減圧下有機溶媒を留去した。溶媒を留去した後再びエタノール−ジクロロメタン（容量比＝１：１）混合溶液１０ｍｌを加え、６０℃に加温して減圧下で有機溶媒を留去した。この操作を４回繰り返し、最後に水も完全に留去した後、真空乾燥機にて減圧下１晩乾燥した。
【００３７】
実施例５
参考例１で得られたアスタキサンチンオイル１．０ｇ、上記γ−シクロデキストリン５．０ｇ、水１０ｍｌ及びエタノール−ジクロロメタン（容量比＝１：１）混合溶液１０ｍｌをナス型フラスコに入れ、６０℃に加温して、３時間還流した。遠心分離し、残分（固形分）をとり出し、真空乾燥機にて減圧下１晩乾燥した。
【００３８】
実施例６
参考例１で得られたアスタキサンチンオイル１．０ｇ、上記γ−シクロデキストリン５．０ｇ、水１０ｍｌ及びエタノール−ジクロロメタン（容量比＝１：１）混合溶液１０ｍｌをナス型フラスコに入れ、６０℃に加温して、３時間還流した。エタノール１０ｍｌを添加後、遠心分離し、残分（固形分）をとり出した。この操作を２回繰り返した後、真空乾燥機にて減圧下１晩乾燥した。１０ｍｌの水を加え３０分間振とうし、遠心分離した。再び同じ操作を行った後、真空乾燥機で減圧下１晩乾燥した。
【００３９】
比較例１
参考例１で得られたアスタキサンチンオイル１．０ｇと上記γ−シクロデキストリン２．０ｇを乳鉢に入れ、乳棒でよく混合した。
【００４０】
比較例２
参考例１で得られたアスタキサンチンオイル１．０ｇ、上記γ−シクロデキストリン２．０ｇ及び水２．０ｇを乳鉢に入れ、乳棒でよく混合した後、真空乾燥機にて減圧下１晩乾燥した。
【００４１】
比較例３
参考例１で得られたアスタキサンチンオイル１．０ｇ、上記γ−シクロデキストリン２．０ｇ、水２．０ｇ及びエタノール２．０ｍｌを乳鉢に入れ、乳棒でよく混合し、溶媒を殆ど揮発させた後、真空乾燥機にて減圧下１晩乾燥した。
【００４２】
比較例４
参考例１で得られたアスタキサンチンオイル１．０ｇ、上記γ−シクロデキストリン２．０ｇ、水２．０ｇ及びジクロロメタン２．０ｍｌを乳鉢に入れ、乳棒でよく混合し、溶媒を殆ど揮発させた後、真空乾燥機で減圧し１晩乾燥した。溶媒を変えて調製した。
【００４３】
下記表１に上記実施例１〜６と比較例１〜３の方法により得られるアスタキサンチンとγ−シクロデキストリンとの粉体の調製方法、溶媒の種類、アスタキサンチンに対するγ−シクロデキストリン配合量、安定性試験の結果（残存率）を示す。
なお、表中、γ−ＣＤはγ−シクロデキストリン、ＥＴはエタノール、ＤＭはジクロロメタンを意味し、添加量は重量で示す。
【００４４】
安定性比較試験は以下に示す方法で行った。
各被験物質１０ｍｇをキャップ付き試験管（１０ｍｌ）に入れ、酸素で置換し、封をした後、８０℃で加温し、２時間及び４時間後のアスタキサンチン含量を測定した。
なお、包接体中のアスタキサンチンの含量はクロロホルムで抽出後、吸光度法（測定長４８５ｎｍ、溶媒クロロホルム）にて測定した。
【００４５】
【表１】
上記表１の結果から本発明の製法で得られる包接化合物は、酸素置換下８０℃４時間の過酷試験後もアスタキサンチンが８３〜９９％も残存し、極めて安定なものであった。これに対し、比較例１〜４の従来法で調製した粉体ではアスタキサンチンの４時間後の含量は極めて低くなり、不安定なものであった。
【００４７】
本発明の包接化合物は、安定な粉末であり、又水に溶解し易い特長を有する。
以下に本発明の包接化合物の水に対する溶解性と透明性について述べる。
【００４８】
上記実施例１〜６で得られた包接化合物、及び比較例１〜４で得られた混合物の各試料の適量を所望の量の水に加え、攪拌機、超音波振とう機等で溶解させ、遠心分離後、上澄み液中のアスタキサンチン含量を測定し溶解性の比較試験を行った。
【００４９】
試験例Ｂ１〜Ｂ１０
各試料２０ｍｇを水５０ｍｌに加え、超音波振とうを５分間行い、遠心分離後、上澄み液中のアスタキサンチン含量を測定した。
その結果を表２に示す。表中、溶解性は、○は沈殿がない状態、△は少量沈殿が生じた状態、×は油滴が浮遊する状態であることを示す。
【００５０】
【表２】
上記表２の結果ら明らかな様に本発明の実施例１〜６の方法で得られたアスタキサンチンとγ−シクロデキストリンとの包接化合物は極めて容易に水に溶けることがわかる。これらの溶液を直射日光の当たらない場所に室温で１カ月放置したが褪色は見られなかった。
【００５２】
一方、比較例１〜４の従来法で得られる粉末は、水を添加するとアスタキサンチンオイルが浮遊し、γ−シクロデキストリンのみが水に溶けた。
【００５３】
以上の結果から本発明のアスタキサンチンに対し、γ−シクロデキストリンを特定の割合で配合することを特徴とする製法により得られるアスタキサンチンとγ−シクロデキストリンとの包接化合物は、熱に対し極めて安定であり、また該包接化合物が水に溶解し易いことがわかる。
【００５４】
製造例１ 錠剤
実施例６の包接化合物 １５ｇ
アビセル ３５ｇ
還元麦芽糖水飴 １５ｇ
部分α化デンプン １０ｇ
軽質無水ケイ酸 ２ｇ
噴霧乳糖 ２０ｇ
ショ糖脂肪酸エステル ３ｇ
上記各成分を常法に従って均一に混合し、１粒３００ｍｇの錠剤とした。
【００５５】
製造例２ カプセル剤
ゼラチン ７０ｇ
グリセリン ２３ｇ
パラオキシ安息香酸プロピル １ｇ
水 ６ｇ
上記成分からなるソフトカプセル剤皮の中に、実施例６の包接化合物３０重量％、ヤシ油７０重量％からなる内容物充填し３００ｍｇのカプセル剤とした。
【００５６】
製造例３ ドリンク剤
実施例６の包接化合物 ２ｇ
ＤＬ−酒石酸ナトリウム ０．１ｇ
液糖 ８００ｇ
クエン酸 １２ｇ
ビタミンＣ １０ｇ
ビタミンＥ ３０ｇ
香料 １．５ｇ
塩化カリウム ０．１ｇ
硫酸マグネシウム ０．５ｇ
上記の成分を配合し、水を加えて１０Ｌとし、常法に従ってドリンク剤を調製した。
【００５７】
製造例４ クリーム
実施例６の包接化合物 １ｇ
グリセリンモノステリン酸 ７ｇ
プロピレングリコール ５ｇ
スクワラン １５ｇ
メチルパラオキシベンゼン ０．１ｇ
プロピルパラオキシベンゼン ０．１ｇ
上記の成分に水を加えて１００ｇになるように配合し、常法に従って、クリームを調製した。
【００５８】
製造例５ 清涼飲料水
実施例６の包接化合物 ２ｇ
液糖 １０００ｇ
クエン酸 １６ｇ
アスコルビン酸 ２ｇ
香料 １５ｇ
上記の成分に水１０Ｌを配合し、常法に従って、透明な清涼飲料水を調製した。
【００５９】
製造例６ クッキー
実施例６の包接化合物 ２ｇ
牛乳 ６３０ｇ
砂糖 １３０ｇ
コーンスターチ １３０ｇ
食塩 １０ｇ
上記の成分を配合し、常法に従って、クッキーを焼いた。
【００６０】
製造例７
実施例６の包接化合物 ２ｇ
トウモロコシ粉 ３００ｇ
小麦粉 ３００ｇ
魚粉 ５０ｇ
アルファルファミール ５０ｇ
キャッサバミール ５０ｇ
フスマ ５０ｇ
大豆粉 ２００ｇ
上記の成分を配合し、常法に従って、ペレット状にしニワトリ用飼料とした。
【００６１】
【発明の効果】
本発明により安定なアスタキサンチンとシクロデキストリンとの包接化合物を提供できた。このものは加工が容易であり、飲食物、動物飼料、医薬品、健康食品等の分野での利用に有用である。また、本発明の包接化合物は水に容易に溶け易く且つ均一な溶液とすることができるので摂取又は服用する時に用時溶解して利用することができる。
【図面の簡単な説明】
【図１】 図中（Ａ）はアスタキサンチン（遊離体、合成品）、（Ｂ）はγ−シクロデキストリン、（Ｃ）はアスタキサンチンとγ−シクロデキストリンをモル比１：３で混練処理した粉末、（Ｄ）はアスタキサンチンとγ−シクロデキストリンをモル比１：３で混合した粉末のＸＲＤスペクトルである。上記（Ｃ）は包接化合物を形成している。
【図２】 図中、（Ｅ）はアスタキサンチンとα−シクロデキストリンをモル比１：３で混練した粉末、（Ｆ）アスタキサンチンとα−シクロデキストリンをモル比１：３で混合した粉末、（Ｇ）はアスタキサンチンとβ−シクロデキストリンをモル比１：３で混練した粉末、（Ｆ）アスタキサンチンとβ−シクロデキストリンをモル比１：３で混合した粉末のＸＲＤスペクトルである。包接化合物が形成されていないことを示す。[0001]
BACKGROUND OF THE INVENTION
The present invention comprises a stable inclusion compound of astaxanthin and γ-cyclodextrin, characterized in that γ-cyclodextrin is blended at a specific ratio with astaxanthin, and a method for producing the same, and the inclusion compound The present invention relates to the use of liquids, foods and drinks, animal feeds, pharmaceuticals and cosmetics.
[0002]
[Prior art]
Astaxanthin is a typical carotenoid contained in animals and plants. Red carotenoids are distributed in crustaceans such as krill, shrimp and crabs, body surface of red sea bream, salmon muscles, salmon muscles, and fish eggs such as salmon roe, yeast and algae. And is used as a color improver, a deep-fried agent, a food additive, and a cosmetic colorant for cultured seafood. Recently, it has been reported that astaxanthin has an anti-oxidant action (Nobuto Shimizu, Miki Wataru, Marine Carotenoid, Miki Wataru, Hoshiseisha Koseikaku, 1993), and further to food additives, etc. Applications have also been reported. However, since astaxanthin is a fat-soluble substance like other carotenoid pigments, there is a problem that solubility in a water-soluble solvent or addition to a water-soluble compound is poor. Recently, astaxanthin has become available in large quantities and at low cost by mass culture of astaxanthin-producing Haematococcus algae. However, astaxanthin contained in naturally derived extracts such as Haematococcus, astaxanthin free form, astaxanthin fatty acid monoester and astaxanthin fatty acid diester, in addition to impurities, glycerides such as monoglyceride, diglyceride and triglyceride, free fatty acid, or Since the ester derived from the free fatty acid is included, there is a problem that even when powdered by the conventional method, the red color of astaxanthin is faded at room temperature and the commercial value is lowered. For example, (1) JP-A-9-124470 discloses astaxanthin and / or an ester thereof as cyclo (cyclic) dextrin (α-cyclodextrin). , Β-cyclodextrin, γ-cyclodextrin) can be used to obtain a water-soluble powdered inclusion compound, (2) JP-A-10-155459 discloses astaxanthin ethyl Ester-containing drinks, nourishing tonics, and (3) Japanese Patent Application Laid-Open No. 2001-2569 include a cyclo (cyclic) dextrin (α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin). It is described that a powdery clathrate soluble in water can be obtained.
However, a simple astaxanthin-cyclodextrin inclusion product cannot be obtained by simply mixing astaxanthin and cyclodextrin, and astaxanthin and γ-cyclodextrin can only be obtained by dissolving astaxanthin in ethanol and diluting with water. It was found that no inclusion compound was obtained. There is still no sufficient method for a stable inclusion compound of astaxanthin and γ-cyclodextrin and a method for producing the same, and a solution for the inclusion compound, particularly a method for obtaining a stable and clear solution by dissolving the powder.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to provide a stable inclusion compound of astaxanthin and γ-cyclodextrin and a method for producing the same, and a liquid agent, food and drink, animal feed, pharmaceuticals and cosmetics containing the inclusion compound. And
[0004]
[Means for Solving the Invention]
Of the present invention(1) is a mixture of 1 part by weight of astaxanthin and / or its ester and 0.5 to 100 parts by weight of γ-cyclodextrin, 1 part by weight of γ-cyclodextrin, ethyl acetate, dichloromethane, chloroform, acetone, ether Astaxanthin and / or an ester thereof mixed in the presence of a total of 0.5 to 10 parts by weight of at least one organic solvent selected from the group consisting of alcohols and 1 to 20 parts by weight of water a method for producing an inclusion compound with γ-cyclodextrin,
(2) is a mixture of 1 part by weight of astaxanthin and / or its ester and 0.5 to 100 parts by weight of γ-cyclodextrin, 1 part by weight of γ-cyclodextrin, ethyl acetate, dichloromethane, chloroform, acetone, In the presence of a total of 0.5 to 10 parts by weight of an alcohol selected from at least one organic solvent selected from the group consisting of ethers and 1 to 20 parts by weight of water, the resulting clathrate was mixed from the organic solvent. Washed with at least one organic solvent selected from the group consisting of: Astaxanthin and / or an ester thereof and γ-cyclodextrin with improved stability, characterized by drying after washing with a small amount of water A method for producing an inclusion compound of
(3) forms an inclusion compound of astaxanthin and / or an ester thereof and γ-cyclodextrin blended at a ratio of 0.5 to 100 parts by weight of γ-cyclodextrin to 1 part by weight of astaxanthin and / or its ester To stabilize astaxanthin and / or its esterIt is.
[0005]
In this specification, astaxanthin is composed of at least one selected from the group of astaxanthin free form, astaxanthin fatty acid monoester, and astaxanthin fatty acid diester. The fatty acid ester is composed of at least one selected from the group of saturated fatty acids or unsaturated fatty acids having 2 or more carbon atoms.
[0006]
Astaxanthin may be a synthetic product and / or a natural product, but considering the safety of the living body, a natural product such as astaxanthin extracted from Haematococcus alga, Phaffia yeast or krill is preferred, and more preferably It is an astaxanthin extracted from Haematococcus alga bodies that are industrially available in large quantities and stably.
[0007]
When using astaxanthin oil derived from Haematococcus as astaxanthin, the content of γ-cyclodextrin is based on the content of astaxanthin in the oil and the weight of other impurities (main components are mono, di, and triglycerides). Usage can be set. Specifically, it is in the range of 0.5 to 100 parts by weight of γ-cyclodextrin with respect to 1 part by weight of astaxanthin, preferably in the range of 0.5 to 50 parts by weight, more preferably in the range of 1 to 50 parts by weight. It is.
[0008]
In the present invention, in addition to the above-described γ-cyclodextrin, α-cyclodextrin, β-cyclodextrin, δ-cyclodextrin as long as the stability of the inclusion compound of astaxanthin and γ-cyclodextrin and the solubility in water are not hindered. Dextrin and a known water-soluble cyclodextrin derivative may be added.
[0009]
Examples of water-soluble cyclodextrin derivatives include hydroxypropyl-β-cyclodextrin, methyl-β-cyclodextrin, monoacetyl-β-cyclodextrin, triacetyl-β-cyclodextrin, monochlorotriazyl-β-cyclodextrin And sulfobutyl ether-β-cyclodextrin, di-O-methyl-β-cyclodextrin, maltosyl-β-cyclodextrin and the like.
[0010]
The stable inclusion compound of astaxanthin and cyclodextrin of the present invention can be produced by blending water and at least one organic solvent at a specific ratio in a mixture of astaxanthin and γ-cyclodextrin.
[0011]
The organic solvent to be used is not particularly limited as long as it dissolves astaxanthin and astaxanthin oil, but is preferably easy to remove at the final stage of pulverization, for example, alcohols such as methanol, ethanol, butanol, and propanol , At least one selected from esters such as ethyl acetate, halogenated carbon hydrogen such as dichloromethane and chloroform, acetone, ether and the like. More preferably, it is a combination of ethanol and dichloromethane or chloroform which can be included in a short time.
[0012]
Examples of the inclusion method include a kneading method, a liquid phase mixing method, a solvent evaporation method, a coprecipitation method, and a freeze drying method. A kneading method, a liquid phase mixing method, and a solvent evaporation method that are easy to handle are preferable.
[0013]
The kneading method is, for example, using a kneader, a mortar, etc., adding water and the appropriate amount of the organic solvent to a mixture of astaxanthin or astaxanthin oil and γ-cyclodextrin, and kneading and mixing until a paste is obtained. It is.
[0014]
The liquid phase mixing method is a method in which astaxanthin or astaxanthin oil and γ-cyclodextrin are added to the organic solvent and water in a container such as a flask or a reaction kettle and vigorously stirred and mixed in the aqueous phase.
[0015]
The solvent evaporation method is a method of adding the organic solvent and water to astaxanthin or a mixture of astaxanthin oil and γ-cyclodextrin, and then distilling off the solvent under reduced pressure, using an apparatus capable of reducing pressure, such as a rotary evaporator. .
[0016]
The coprecipitation method is a method in which a solution obtained by dissolving astaxanthin or astaxanthin oil in the organic solvent is dropped into an aqueous solution of γ-cyclodextrin prepared to a desired concentration while stirring.
[0017]
The freeze-drying method is a method in which the organic solvent and water are added to astaxanthin or astaxanthin oil and γ-cyclodextrin, mixed and then freeze-dried to distill off the solvent.
[0018]
In order to prevent astaxanthin from decomposing and / or fading during the production of the inclusion compound of astaxanthin and γ-cyclodextrin, the temperature range for preparing the inclusion compound is preferably 80 ° C. or less. More preferably, it is 60 degrees C or less, More preferably, it is room temperature vicinity.
[0019]
The clathrate compound obtained by the production method of the present invention can be obtained as a more stable powder when the solvent is sufficiently removed.
[0020]
In the production method of the present invention, a more stable package of astaxanthin and γ-cyclodextrin is obtained by using γ-cyclodextrin in which 0.5 to 10 parts by weight of water is previously added to 1 part by weight of γ-cyclodextrin. A contact compound is obtained.
[0021]
When the clathrate compound is prepared using astaxanthin oil, a powder having higher stability can be obtained by the following method. Specifically, in a mixture of 1 part by weight of astaxanthin contained in astaxanthin oil and 0.5 to 100 parts by weight of γ-cyclodextrin, 1 part by weight of γ-cyclodextrin, methanol, ethanol, propanol, butanol, 0.5 to 10 parts by weight of at least one organic solvent selected from the group consisting of acetone, ether, ethyl acetate, dichloromethane and chloroform and 1 to 20 parts by weight of water are added, and the resulting clathrate is added from the organic solvent. This is a method of washing with at least one organic solvent selected from the group consisting of drying, drying, washing with a small amount of water, and drying. This is probably because the trace components that affect the stability of astaxanthin are removed by washing with the organic solvent and water.
[0022]
The inclusion compound of astaxanthin and γ-cyclodextrin according to the present invention includes conventional water-soluble sweeteners, fragrances, coloring agents, starches, alginic acid in powder production as long as they do not inhibit the formation of stable inclusion compounds. Disintegrants such as soda, excipients such as lactose, glycolose, sucrose, mannitol, erythritol, binders such as hydroxypropylcellulose and gelatin, plasticizers such as glycerin, and the like can be used.
[0023]
The stable inclusion compound of astaxanthin and γ-cyclodextrin of the present invention includes butylhydridotoluene, butylhydroxyanisole, vitamin E to prevent astaxanthin and / or its ester from being oxidatively decomposed in the air. (Tocopherol and tocotrienol or derivatives thereof), ascorbic acid, L-ascorbyl palmitate, L-ascorbate stearate, sodium ascorbate, gallic acid, ethoxyquin, glutathione, phytic acid, catechins, polyphenols, Natural and synthetic antioxidants such as flavonoids, carotenoids, xanthophylls, sesame extract, rosemary extract and the like may be added.
[0024]
The uniform and transparent liquid preparation containing the inclusion compound of astaxanthin and γ-cyclodextrin according to the present invention can be obtained by dissolving the inclusion compound in water or suspending the insoluble matter after the suspension. It can prepare by filtering using.
[0025]
In the liquid preparation, surfactants, dissolution aids and the like that are usually used in preparation of the liquid preparation may be added in an amount that does not affect the solubility of the clathrate compound. Examples of the surfactant include sucrose fatty acid ester, propylene glycol ester, glycerin fatty acid ester, sorbitan fatty acid ester, dextrin, and reduced dextrin.
[0026]
When the inclusion compound of the present invention is used as a food, drink, nutritional supplement, or functional food, the form conforms to the form used in ordinary drugs, such as tablets, powders, granules, capsules. The form of a drink agent can be illustrated. In order to balance nutrition, commonly used excipients, extenders, vitamins, fibers, proteins, amino acids, minerals, animal and plant extracts, sweeteners, flavors, stabilizers, pigments Etc. can be added.
[0027]
As the form of food and drink, processed milk, cheese, butter, margarine, fresh cream, ice cream, ice confectionery, pudding, dairy products, jelly, candy, drop, rice cake, caramel, chewing gum, castella, cake, donuts, biscuits, Crackers, snacks, french fries, potato chips, popcorn, rice cakes, dumplings, daifuku, soup, sausage, ham, bacon, meat products, seaweed, chikuwa, hanpen, fish products, spaghetti, pasta, gratin, paella, curry, sauce , Ketchup, dressing, pickles, carbonated drinks, fruit juice drinks, sports drinks, tea, coffee, cocoa, beer, liqueur, cocktail, medicinal liquor, etc. Further, it can be used as a refreshing beverage as a stable, uniform and clear red liquid.
[0028]
When used as a feed, it may be used as it is, but it is used as a raw material for commonly used animal and fish feeds such as corn, milo, fish meal, bran, salt, calcium carbonate, calcium phosphate, amino acids, vitamins. , Trace minerals, existing antioxidants, etc. may be blended.
[0029]
For use as a pharmaceutical, it is orally administered in a conventional manner, for example, in solid dosage forms such as tablets and powders, or liquid dosage forms such as syrups. It can also be used parenterally, for example, as a patch, ointment, injection, or suppository. The preparation of the drug itself can be performed according to a conventional method.
[0030]
The form of the cosmetic is not particularly limited. For example, skin care cosmetics such as emulsions, creams, lotions, packs, cleaning agents, makeup cosmetics such as foundations, eye shadows, mascaras, and lipsticks, dispersions, ointments, and external use. Cosmetics such as liquids and creams can be obtained. In addition, ingredients commonly used in skin preparations such as cosmetics and pharmaceuticals, such as water (including alkaline simple hot spring water, deep water, purified water, etc.), lower alcohols, polyhydric alcohols, fats and oils, waxes, mineral oils, fatty acids , Powder, metal soap, pH adjuster, surfactant, thickener, pigment, extract derived from plant or animal materials, vitamins, amino acids, hormones, bactericidal / disinfectant, keratolytic agent, enzyme , Refreshing agents, stabilizers, metal ion chelating agents, blood circulation promoters, essential oils, deodorants, moisturizers, astringents, antiseborrheic agents, cell activators, fragrances, and the like may be added.
[0031]
【Example】
The present invention will be described in detail with reference to the following reference examples, examples and comparative examples.
Reference Example 1 Preparation of astaxanthin oil from Haematococcus algae:
[0032]
Hematococcus algae were cultured by a known method to obtain an astaxanthin-containing hematococcus alga body. The alga bodies were separated from the culture broth and dried, then extracted with acetone. If necessary, insolubles were removed, and then acetone was distilled off under reduced pressure with an evaporator to obtain an astaxanthin extract (hereinafter referred to as astaxanthin oil). The astaxanthin content in the astaxanthin oil was quantified by an absorbance method (measurement wavelength: 475 nm, solvent acetone). The total amount of free staxanthin, astaxanthin fatty acid monoester and astaxanthin fatty acid diester in the oil was 15% by weight based on the total amount of oil. The composition of astaxanthin in the astaxanthin oil was free astaxanthin (6% by weight), astaxanthin fatty acid monoester (82% by weight) and astaxanthin fatty acid diester (12% by weight). The other components were 50% by weight of mono-, di- and triglycerides.
However, the composition of the astaxanthin oil used in the present invention and the type of fatty acid are not particularly limited.
[0033]
Example 1
1.0 g of astaxanthin (synthetic product, manufactured by Sigma), 4.0 g of powdery γ-cyclodextrin (trade name DEXIPARL γ-100, manufactured by Shimizu Minato Sugar Co., Ltd.), 4 ml of ethanol-dichloromethane (volume ratio = 1: 1) mixed solution And 4 ml of ion exchange water was put in a mortar and mixed well with a pestle. After the organic solvent was volatilized, 4 ml of a mixed solution of ethanol-dichloromethane (volume ratio = 1: 1) was added again and mixed well. This operation was repeated three times to obtain a paste. The solvent added in the final stage was almost volatilized, and the residue of the wet powder was dried overnight under reduced pressure in a vacuum dryer.
[0034]
Example 2
Place 1.0 g of astaxanthin oil obtained in Reference Example 1, 2.0 g of the above γ-cyclodextrin, 2 ml of ethanol-dichloromethane (volume ratio = 1: 1) mixed solution and 2 ml of ion-exchanged water in a mortar and mix well with a pestle. did. After the organic solvent was volatilized, 2 ml of a mixed solution of ethanol-dichloromethane (volume ratio = 1: 1) was added again and mixed well. This operation was repeated three times to obtain a paste. The solvent added in the final stage was almost volatilized, and the residue of the wet powder was dried overnight under reduced pressure in a vacuum dryer.
[0035]
Example 3
After adding 4.0 g of the above γ-cyclodextrin and 4.0 ml of water to a mortar and kneading well, a mixed solution 4 of 1.0 g of astaxanthin oil obtained in Reference Example 1 and ethanol-dichloromethane (like quality = 1: 1). 0.0 ml was added and kneaded well. After the organic solvent was volatilized, 4 ml of a mixed solution of ethanol-dichloromethane (volume ratio = 1: 1) was added again and mixed well. This operation was repeated three times to obtain a paste. The solvent added in the final stage was almost volatilized, and the residue of the wet powder was dried overnight under reduced pressure in a vacuum dryer.
[0036]
Example 4
1.0 g of astaxanthin oil obtained in Reference Example 1, 4.0 g of the above-mentioned γ-cyclodextrin, 10 ml of water and 10 ml of a mixed solution of ethanol-dichloromethane (volume ratio = 1: 1) are placed in an eggplant type flask and heated to 60 ° C. The organic solvent was distilled off under reduced pressure using a rotary evaporator. After the solvent was distilled off, 10 ml of a mixed solution of ethanol-dichloromethane (volume ratio = 1: 1) was added again, and the mixture was heated to 60 ° C. and the organic solvent was distilled off under reduced pressure. This operation was repeated 4 times. Finally, water was completely distilled off, followed by drying overnight under reduced pressure in a vacuum dryer.
[0037]
Example 5
1.0 g of astaxanthin oil obtained in Reference Example 1, 5.0 g of the above-mentioned γ-cyclodextrin, 10 ml of water and 10 ml of a mixed solution of ethanol-dichloromethane (volume ratio = 1: 1) are placed in an eggplant type flask and heated to 60 ° C. Warmed and refluxed for 3 hours. Centrifugation was performed, and the residue (solid content) was taken out and dried overnight in a vacuum dryer under reduced pressure.
[0038]
Example 6
1.0 g of astaxanthin oil obtained in Reference Example 1, 5.0 g of the above-mentioned γ-cyclodextrin, 10 ml of water and 10 ml of a mixed solution of ethanol-dichloromethane (volume ratio = 1: 1) are placed in an eggplant type flask and heated to 60 ° C. Warmed and refluxed for 3 hours. After adding 10 ml of ethanol, the mixture was centrifuged, and the residue (solid content) was taken out. After this operation was repeated twice, it was dried overnight under reduced pressure in a vacuum dryer. 10 ml of water was added and the mixture was shaken for 30 minutes and centrifuged. After performing the same operation again, it was dried overnight in a vacuum dryer under reduced pressure.
[0039]
Comparative Example 1
1.0 g of astaxanthin oil obtained in Reference Example 1 and 2.0 g of the above γ-cyclodextrin were put in a mortar and mixed well with a pestle.
[0040]
Comparative Example 2
1.0 g of astaxanthin oil obtained in Reference Example 1, 2.0 g of the above-mentioned γ-cyclodextrin and 2.0 g of water were put in a mortar, mixed well with a pestle, and then dried overnight under reduced pressure in a vacuum dryer.
[0041]
Comparative Example 3
Astaxanthin oil 1.0 g obtained in Reference Example 1, 2.0 g of the above γ-cyclodextrin, 2.0 g of water and 2.0 ml of ethanol were put in a mortar, mixed well with a pestle, and the solvent was almost volatilized. It was dried overnight under reduced pressure in a vacuum dryer.
[0042]
Comparative Example 4
After 1.0 g of astaxanthin oil obtained in Reference Example 1, 2.0 g of the above γ-cyclodextrin, 2.0 g of water and 2.0 ml of dichloromethane were mixed in a mortar and mixed well with a pestle, the solvent was almost volatilized. The pressure was reduced with a vacuum drier and dried overnight. Prepared with different solvents.
[0043]
Table 1 below shows a method for preparing powders of astaxanthin and γ-cyclodextrin obtained by the methods of Examples 1 to 6 and Comparative Examples 1 to 3, types of solvents, blending amount of γ-cyclodextrin with respect to astaxanthin, and stability. The result (residual rate) of the test is shown.
In the table, γ-CD means γ-cyclodextrin, ET means ethanol, DM means dichloromethane, and the addition amount is shown by weight.
[0044]
The stability comparison test was performed by the method shown below.
10 mg of each test substance was placed in a capped test tube (10 ml), replaced with oxygen, sealed, heated at 80 ° C., and the astaxanthin content after 2 hours and 4 hours was measured.
The content of astaxanthin in the clathrate was measured by an absorbance method (measurement length: 485 nm, solvent chloroform) after extraction with chloroform.
[0045]
[Table 1]
From the results shown in Table 1, the clathrate compound obtained by the production method of the present invention was extremely stable with 83 to 99% of astaxanthin remaining after a severe test at 80 ° C. for 4 hours under oxygen substitution. On the other hand, in the powders prepared by the conventional methods of Comparative Examples 1 to 4, the content of astaxanthin after 4 hours was extremely low and unstable.
[0047]
The clathrate compound of the present invention is a stable powder and has the feature of being easily dissolved in water.
The solubility and transparency of the clathrate compound of the present invention in water will be described below.
[0048]
Appropriate amount of each sample of the clathrate compound obtained in Examples 1-6 and the mixture obtained in Comparative Examples 1-4 is added to a desired amount of water and dissolved with a stirrer, ultrasonic shaker, etc. After centrifugation, the astaxanthin content in the supernatant was measured, and a solubility comparison test was performed.
[0049]
Test examples B1 to B10
20 mg of each sample was added to 50 ml of water, subjected to ultrasonic shaking for 5 minutes, centrifuged, and the astaxanthin content in the supernatant was measured.
The results are shown in Table 2. In the table, solubility means that ◯ is a state without precipitation, Δ is a state where a small amount of precipitation is generated, and X is a state where oil droplets are floating.
[0050]
[Table 2]
As is apparent from the results in Table 2 above, it can be seen that the inclusion compound of astaxanthin and γ-cyclodextrin obtained by the methods of Examples 1 to 6 of the present invention is very easily soluble in water. These solutions were left in a place not exposed to direct sunlight for 1 month at room temperature, but no fading was observed.
[0052]
On the other hand, powders obtained by the conventional methods of Comparative Examples 1 to 4 floated astaxanthin oil when only water was added, and only γ-cyclodextrin was dissolved in water.
[0053]
From the above results, the inclusion compound of astaxanthin and γ-cyclodextrin obtained by the production method characterized by blending γ-cyclodextrin at a specific ratio with the astaxanthin of the present invention is extremely stable against heat. It can also be seen that the inclusion compound is easily dissolved in water.
[0054]
Production Example 1 Tablet
15 g of the inclusion compound of Example 6
Avicel 35g
Reduced maltose starch syrup 15g
Partially pregelatinized starch 10g
Light anhydrous silicic acid 2g
20g sprayed lactose
Sucrose fatty acid ester 3g
Each of the above components was uniformly mixed according to a conventional method to prepare a tablet of 300 mg per tablet.
[0055]
Production Example 2 Capsule
70g gelatin
Glycerin 23g
1 g propyl paraoxybenzoate
6g of water
A soft capsule skin made of the above components was filled with a content of 30% by weight of the clathrate compound of Example 6 and 70% by weight of coconut oil to give a 300 mg capsule.
[0056]
Production Example 3 Drink
2g of inclusion compound of Example 6
DL-sodium tartrate 0.1g
800g liquid sugar
Citric acid 12g
Vitamin C 10g
Vitamin E 30g
Fragrance 1.5g
Potassium chloride 0.1g
Magnesium sulfate 0.5g
The above ingredients were blended, water was added to make 10 L, and a drink was prepared according to a conventional method.
[0057]
Production Example 4 Cream
1 g of inclusion compound of Example 6
Glycerol monosteric acid 7g
5g propylene glycol
Squalane 15g
Methyl paraoxybenzene 0.1g
Propylparaoxybenzene 0.1g
Water was added to the above ingredients and blended to 100 g, and a cream was prepared according to a conventional method.
[0058]
Production Example 5 Soft Drink
2g of inclusion compound of Example 6
Liquid sugar 1000g
Citric acid 16g
Ascorbic acid 2g
Fragrance 15g
10 L of water was mixed with the above components, and a transparent soft drink was prepared according to a conventional method.
[0059]
Production Example 6 Cookie
2g of inclusion compound of Example 6
630 g of milk
130g sugar
Cornstarch 130g
10g of salt
The above ingredients were blended, and cookies were baked according to a conventional method.
[0060]
Production Example 7
2g of inclusion compound of Example 6
300g corn flour
300g flour
50g fish meal
Alfalfa meal 50g
Cassava meal 50g
50g bran
200g soy flour
The above ingredients were blended and pelletized according to a conventional method to prepare a chicken feed.
[0061]
【The invention's effect】
According to the present invention, a stable inclusion compound of astaxanthin and cyclodextrin could be provided. This product is easy to process and is useful for use in fields such as foods and drinks, animal feeds, pharmaceuticals, and health foods. In addition, since the inclusion compound of the present invention is easily dissolved in water and can be made into a uniform solution, it can be dissolved and used at the time of use or ingestion.
[Brief description of the drawings]
FIG. 1 (A) is astaxanthin (free form, synthetic product), (B) is γ-cyclodextrin, (C) is a powder obtained by kneading astaxanthin and γ-cyclodextrin at a molar ratio of 1: 3, (D) is an XRD spectrum of a powder in which astaxanthin and γ-cyclodextrin are mixed at a molar ratio of 1: 3. The above (C) forms an inclusion compound.
In the figure, (E) is a powder obtained by kneading astaxanthin and α-cyclodextrin at a molar ratio of 1: 3, (F) a powder obtained by mixing astaxanthin and α-cyclodextrin at a molar ratio of 1: 3, (G ) Is an XRD spectrum of a powder obtained by kneading astaxanthin and β-cyclodextrin at a molar ratio of 1: 3, and (F) a powder obtained by mixing astaxanthin and β-cyclodextrin at a molar ratio of 1: 3. It indicates that no inclusion compound is formed.
Claims (3)
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| JP2001157753A JP5041565B2 (en) | 2001-05-25 | 2001-05-25 | Stable inclusion compound of astaxanthin and γ-cyclodextrin and method for producing the same, and liquid, food and drink, feed, pharmaceutical and cosmetic use |
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| JP4666932B2 (en) * | 2004-02-27 | 2011-04-06 | 株式会社スギヨ | Method for producing carbohydrate-carotenoid pigment fat solution and / or solid solution |
| JP4934272B2 (en) * | 2004-08-31 | 2012-05-16 | 富士化学工業株式会社 | Method for producing astaxanthin-containing extract and astaxanthin-containing extract obtained by the method |
| WO2006104610A2 (en) | 2005-02-24 | 2006-10-05 | Diffusion Pharmaceuticals Llc | Trans carotenoids, their synthesis, formulation and uses |
| JP2008291150A (en) * | 2007-05-25 | 2008-12-04 | Cyclochem:Kk | Astaxanthin-cyclodextrin inclusion compound |
| JP2009184947A (en) * | 2008-02-05 | 2009-08-20 | Unitika Ltd | Cyclic dextrin clathrate compound |
| NO339201B1 (en) * | 2009-06-25 | 2016-11-14 | Trouw Int Bv | Fish feed with a water-soluble antioxidant and carotenoid pigment and method for increasing pigment retention in fish meat |
| JP6414895B2 (en) * | 2015-06-30 | 2018-10-31 | 株式会社 伊藤園 | Fruit juice-containing beverage containing astaxanthin and method for producing the same |
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| JPS62267261A (en) * | 1986-05-14 | 1987-11-19 | Ichimaru Pharcos Co Ltd | Beta-carotene clathrate |
| JPH02135070A (en) * | 1988-11-15 | 1990-05-23 | San Ei Chem Ind Ltd | Method for stabilizing carotenoid dye |
| US5221735A (en) * | 1991-02-25 | 1993-06-22 | Hoffmann-La Roche Inc. | Cyclodextrin-polyene inclusion complexes |
| JP2838051B2 (en) * | 1995-03-27 | 1998-12-16 | カゴメ株式会社 | Water-soluble lycopene preparation |
| JPH09124470A (en) * | 1995-10-26 | 1997-05-13 | Suntory Ltd | Antistress composition |
| JP2001002569A (en) * | 1999-06-18 | 2001-01-09 | Itano Refrigerated Food Co Ltd | Composition for improving memory |
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