JPWO2009008503A1 - テアフラビンの選択的製造方法 - Google Patents
テアフラビンの選択的製造方法 Download PDFInfo
- Publication number
- JPWO2009008503A1 JPWO2009008503A1 JP2009522685A JP2009522685A JPWO2009008503A1 JP WO2009008503 A1 JPWO2009008503 A1 JP WO2009008503A1 JP 2009522685 A JP2009522685 A JP 2009522685A JP 2009522685 A JP2009522685 A JP 2009522685A JP WO2009008503 A1 JPWO2009008503 A1 JP WO2009008503A1
- Authority
- JP
- Japan
- Prior art keywords
- theaflavin
- epicatechin
- extract
- epigallocatechin
- gallate
- 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.)
- Granted
Links
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- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/16—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing two or more hetero rings
- C12P17/162—Heterorings having oxygen atoms as the only ring heteroatoms, e.g. Lasalocid
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Abstract
Description
(1)エピカテキン、エピガロカテキン、エピカテキン−3−O−ガレートおよびエピガロカテキン−3−O−ガレートを含有する加工した植物の抽出物と、ペルオキシダーゼ活性を有する植物細胞培養物を混合して選択的にテアフラビンを製造する、テアフラビンの製造方法。
(2)植物が、茶の葉および/または茎である、上記(1)記載のテアフラビンの製造方法。
(3)加工した植物の抽出物が、不発酵茶の抽出物である、上記(1)記載のテアフラビンの製造方法。
(4)植物細胞培養物が、茶細胞の培養物である、上記(1)〜(3)のいずれか1つに記載のテアフラビンの製造方法。
(5)さらに、過酸化水素を加えることを特徴とする、上記(1)〜(4)のいずれか1つに記載のテアフラビンの製造方法。
(6)さらに、エピカテキンを加えることを特徴とする、上記(1)〜(5)のいずれか1つに記載のテアフラビンの製造方法。
(7)上記(1)〜(6)のいずれか1つに記載のテアフラビンの製造方法のための、培養植物細胞。
本発明で用いられる、エピカテキン、エピガロカテキン、エピカテキン−3−O−ガレートおよびエピガロカテキン−3−O−ガレートとは、以下に示す化合物を意味する。
ここで、処理は、植物中の酸化酵素を失活させることができる処理であれば、方法や条件は限定されないが、蒸すおよび/または炒る等が好ましい。
ここで、酸化酵素とは、ECとEGCからTFを、ECとEGCGからTF3−Gを、ECGとEGCからTF3’−Gを、ECGとEGCGからTFDGを合成する酵素を意味し、限定されないが、好ましくはポリフェノールオキシダーゼおよび/ポリフェノールオキシダーゼ又はペルオキシダーゼを意味する。
例えば、日本で煎茶と呼ばれる緑茶は、摘み取った1番茶葉と2番茶葉のみを、茶葉中の酸化酵素が失活するまで蒸し、次いで茶葉を冷やし、茶葉を揉み、茶葉を乾燥させて作られる。日本で番茶と呼ばれる緑茶は、煎茶と同様な手順で製造されるが、原料に1番茶葉と2番茶葉以外の茶葉や茎なども用いるので、酸化酵素を失活させるための蒸しが煎茶のそれより強くなる(蒸し時間が長くなる)。なお、酸化酵素を失活させるための蒸し時間は、使用する茶の質(すなわち、新芽、若葉、成長した葉や茎)や量によって左右されるので、特に限定されない。
本発明には、煎茶や番茶と等価な緑茶も含まれる。また、本発明には、中国緑茶と等価な緑茶も含まれる。
本発明で用いる植物細胞培養物は、植物培養細胞を継体して用いるため、反応にいつでも供給することができて機動性に優れており、しかも安価であるという利点を有する。
さらに、必要に応じて寒天などを添加して構成したものを用いることもできる。
加工した植物の抽出物と植物細胞培養物の混合における水性溶媒は、ペルオキシダーゼが活性である水性溶媒であれば限定されないが、水、植物細胞培養用培地、植物細胞を培養した培養液、リン酸緩衝液、クエン酸緩衝液等が挙げられる。好ましくは、水、植物細胞培養用培地、植物細胞を培養した培養液、より好ましくは水である。水の場合、工業化において、廃液中のリン酸等の処理が不要となり廃液の処理が容易となるためである。なお、緩衝液の濃度は、0.3M〜0.001M、好ましくは0.2M〜0.01M、より好ましくは0.1M〜1/15M程度である。
本実験では、植物細胞として茶の成体細胞(茶の品種;さやまかおり、茶の使用部位;実生)を用い、以下のように茶細胞培養物を調製した。すなわち、寒天培地上で作成した茶培養細胞のカルスを、2,4−ジクロロフェノキシ酢酸及び蔗糖を含むGamborg's B5(B5)培地(フラスコ1個あたりに100mL)に移植した。次いで、培養細胞が均一になるまで25℃、暗条件下において約10日間、110rpmでふりまぜながら培養し、茶細胞培養物(Camellia sinensis cell culture)を調製した。この茶細胞培養物のペルオキシダーゼ活性は15.5unit/mLであった。
なお、これら細胞培養物のペルオキシダーゼ活性はタバコ(N. tabacum)=9.6unit/mL、にんじん(D. carota)=8.0unit/mLである。
5%(W/V)ピロガロール(和光純薬(株))2ml、H2O 14ml、0.5% H2O2 1.0ml、0.1M pH6.0リン酸緩衝液2.0mlに、酵素を含む試料1mlを、約25℃の雰囲気下で加え、20秒間激しく振とう後、2M H2SO4 1.0mlを加えて反応をとめる。反応液を、ジエチルエーテル25mlで2回抽出し、ジエチルエーテルで100mlにする。420nmで吸光度を測定する。プルプロガリンの生成量は、あらかじめ作成しておいたプルプロガリンの検量線より求めた。この条件下でプルプロガリン1mgを生成する酵素量が、ペルオキシダーゼ活性の1ユニットとして定義されるので、生成されたプルプロガリン量から試料1ml中のペルオキシダーゼ活性(ユニット)が計算される。
EC、ECG、EGC、EGCG、TFの分析には、HPLC装置(JASCO(株)、PU−980、UV−970)とODS120A(TOSHO、4.6mm×250mm)カラムを用いた。分析試料には、番茶水抽出液そのもの;番茶水抽出液の酢酸エチル抽出物;番茶の酢酸エチル抽出物;反応液そのもの;反応液の酢酸エチル抽出物;またはメタノール溶出フラクションを用いた。HPLCの条件は、溶媒;アセトニトリル:酢酸エチル:0.05%H3PO4=21:3:76、流速;1.0ml/min、温度;25℃である。検出は、UV280nmでおこなった。標準のEC(WAKO(株))、ECG(WAKO(株))、EGC(WAKO(株))、EGCG(WAKO(株))、TF(長良サイエンス(株))を用いて、検量線を作成し、検量線から、試料中のEC、ECG、EGC、EGCG、TFの量を計算により求めた。
乾燥番茶(お茶のミズイ園製の番茶)75gを1500mlの水に24時間浸して抽出後、茶葉を濾去した濾液を番茶抽出液として1840ml得た(なお、濾過の際、茶葉を洗う操作がはいったため、抽出液は1840mlとなった。)。この番茶抽出液中のEC量は488.5mg、ECG量は122.4mg、EGC量は556.5mg、EGCG量は610.5mgであった。この番茶抽出液中に、上記のように調製した茶細胞培養物45mlと3%過酸化水素水9mlを加え110rpmにて振とうしながら反応を開始した。反応開始4時間後にさらに茶細胞培養物25mlと3%過酸化水素水4.5ml、さらに反応開始5時間後に茶細胞培養物5mlと3%過酸化水素水1mlを加え、反応開始9時間後に反応を終了した。反応後酢酸エチルで3回抽出した。得られた酢酸エチル抽出液をロータリーエバポレーターレーターにて濃縮後、あらかじめメタノールで平衡化しているSepadexLH−20カラムクロマトグラフィー(GE healthcare Bio-Sciences AB)に添加してメタノールで溶出することにより、赤色のフラクションを集めた。テアフラビンは赤色しているので、肉眼によりテアフラビンのフラクションの回収が可能である。結果として、テアフラビン193mgを得た。
酢酸エチル抽出液を濃縮して、1.82gの番茶抽出物を得た。番茶抽出物24.1mg(この番茶抽出物24.1mg中のEC量は4.3mg、ECG量は1.1mg、EGC量は4.9mg、EGCG量は5.4mgであった)を水18.5mlに溶解後、3%過酸化水素0.3ml、茶培養細胞1.2mlを加え28分間反応させた。
反応開始9分後のHPLC分析において、テアフラビンのピークが認められた。これより、水抽出液ではなく酢酸エチル抽出物を用いても、合成反応は可能であることから、原料を濃縮することで反応容量を小さくできることが明らかとなった。また、テアフラビンの酸化により生じるテアナフトキノンのピークが、反応終了時(28分)のHPLC分析において認められた。これより、生成されたテアフラビンはさらに酸化され、テアナフトキノンに変換されることが明らかとなった。
実施例2で得られた番茶抽出物の241mg(この番茶抽出物241mg中のEC量は43mg、ECG量は11mg、EGC量は49mg、EGCG量は54mgであった)を水185mlに溶解後、3%過酸化水素3ml、茶細胞培養物24mlを加え9分間反応させた。反応後酢酸エチルで3回抽出した。SepadexLH−20カラムクロマトグラフィーにてメタノールで溶出してテアフラビン17.2mgを得た。
製造されたTFの量52.5mg÷(番茶抽出物中のEGCの含有量41.55mg÷EGCの分子量306×TFの分子量564)×100=68.6%
番茶抽出液700ml(乾燥番茶5gを600mlの水で24時間抽出後、茶葉を濾去した濾液である。濾過の際、茶葉を洗う操作がはいったため、抽出液は700mlとなった。)を酢酸エチルで3回抽出した。酢酸エチル抽出液を濃縮後、1.82gの番茶抽出物を得た。番茶抽出物24.1mg(この24.1mgの番茶抽出物中のEC量は4.3mg、ECG量は1.1mg、EGC量は4.9mg、EGCG量は5.4mgであった)、エピカテキン4mgを水18.5mlに溶解後、3%過酸化水素0.3ml、茶細胞培養物1.2mlを加え12分間反応させた。反応後酢酸エチルで3回抽出した。SepadexLH−20カラムクロマトグラフィーにてメタノールで溶出することによりテアフラビンを13.8mg得た。
製造されたTFの量13.75mg÷(番茶抽出物中のEGCの量4.9mg÷EGCの分子量306×TFの分子量564)×100)=収率152.2%
番茶抽出液中のEGCの含有量4.9mg÷EGCの分子量306=0.016mmol
番茶抽出液中のEGCGの含有量5.43mg÷EGCGの分子量458=0.01186mmol
製造されたTFの量13.75mg÷((番茶抽出液中のEGCの含有量0.016mmol+番茶抽出液中のEGCGの含有量0.01186mmol)×TFの分子量564)×100)=収率87.5%
Claims (7)
- エピカテキン、エピガロカテキン、エピカテキン−3−O−ガレートおよびエピガロカテキン−3−O−ガレートを含有する加工した植物の抽出物と、ペルオキシダーゼ活性を有する植物細胞培養物を混合して選択的にテアフラビンを製造する、テアフラビンの製造方法。
- 植物が、茶の葉および/または茎である、請求項1に記載のテアフラビンの製造方法。
- 加工した植物が、不発酵茶である、請求項1に記載のテアフラビンの製造方法。
- 植物細胞培養物が、茶細胞の培養物である、請求項1〜3のいずれか1項に記載のテアフラビンの製造方法。
- さらに、過酸化水素を加えることを特徴とする、請求項1〜4のいずれか1項に記載のテアフラビンの製造方法。
- さらに、エピカテキンを加えることを特徴とする、請求項1〜5のいずれか1項に記載のテアフラビンの製造方法。
- 請求項1〜6のいずれか1項に記載のテアフラビン製造方法のための、培養植物細胞。
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