JP2005145824A - Method for producing nobiletin - Google Patents
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本発明は、ノビレチンの製造方法に関する。 The present invention relates to a method for producing nobiletin.
柑橘類には、ノビレチン、タンゲレチン、ペンタメトキシフラボン、テトラメトキシフラボン、ヘプタメトキシフラボン等のポリアルコキシフラボノイドが含まれており、柑橘類に含まれているポリアルコシキフラボノイドは、マトリックスメタロプロテアーゼ産生阻害活性（特許文献１参照）、神経突起伸長活性（特許文献２参照）、プロスタグランジンＥ２産生抑制活性（特許文献３参照）等を有することが知られている。 Citrus includes polyalkoxyflavonoids such as nobiletin, tangeretin, pentamethoxyflavone, tetramethoxyflavone and heptamethoxyflavone. Polyalkoxyflavonoids contained in citrus have matrix metalloprotease production inhibitory activity (patent references 1), neurite outgrowth activity (see Patent Document 2), it is known to have a prostaglandin E 2 production inhibitory activity (see Patent Document 3) or the like.
柑橘類からのポリアルコシキフラボノイドの製造方法としては、柑橘類の果皮をアセトン中に液浸し、粗フラボノイド抽出液を得た後、オクタデシルシリカゲルを担体とする逆相系カラムで精製する方法（特許文献１、３参照）、柑橘類の果皮を９０（ｖ／ｖ）％エタノールで抽出した後、酢酸エチル−水で分液し、酢酸エチル層を減圧濃縮する方法（特許文献２参照）が知られている。
本発明は、工業的生産に適したノビレチンの製造方法を提供することを目的とする。 An object of this invention is to provide the manufacturing method of nobiletin suitable for industrial production.
上記目的を達成するために、本発明は、以下のノビレチンの製造方法を提供する。
（１）下記工程（ａ）〜（ｃ）を含むノビレチンの製造方法。
（ａ）柑橘類をエタノール濃度が０〜４０容量％のエタノール水溶液で抽出する工程
（ｂ）前記工程（ａ）で得られた抽出液を多孔性吸着樹脂に通液する工程
（ｃ）前記多孔性吸着樹脂に吸着したノビレチンを溶出する工程
（２）前記柑橘類がポンカンである前記（１）記載の製造方法。
（３）前記工程（ａ）において、前記柑橘類を前記エタノールで抽出する前又は抽出した後に、前記柑橘類を熱水で抽出する前記（１）又は（２）記載の製造方法。
（４）前記工程（ｂ）において、前記抽出液を濃縮した後、前記多孔性吸着樹脂に通液する前記（１）〜（３）のいずれかに記載の製造方法。
（５）前記工程（ｂ）において、前記抽出液の空間速度が０．８〜１．５である前記（１）〜（４）のいずれかに記載の製造方法。
（６）前記工程（ｃ）において、前記多孔性吸着樹脂に吸着したノビレチンをエタノール濃度が６０〜９０容量％のエタノール水溶液で溶出する前記（１）〜（５）のいずれかに記載の製造方法。
（７）前記多孔性吸着樹脂に吸着したノビレチンをエタノール濃度が６０〜９０容量％のエタノール水溶液で溶出する前に、前記前記多孔性吸着樹脂をエタノール濃度が３０〜５０容量％のエタノール水溶液で洗浄する前記（６）記載の製造方法。
In order to achieve the above object, the present invention provides the following method for producing nobiletin.
(1) A method for producing nobiletin, comprising the following steps (a) to (c).
(A) A step of extracting citrus fruits with an aqueous ethanol solution having an ethanol concentration of 0 to 40% by volume (b) A step of passing the extract obtained in the step (a) through a porous adsorption resin (c) The porosity The step of eluting nobiletin adsorbed on the adsorption resin (2) The production method according to (1), wherein the citrus fruit is Ponkan.
(3) In the said process (a), before extracting the said citrus fruits with the ethanol or after extracting, the said citrus fruits are extracted with hot water, The manufacturing method of the said (1) or (2) description.
(4) The manufacturing method according to any one of (1) to (3), wherein in the step (b), the extract is concentrated and then passed through the porous adsorption resin.
(5) The manufacturing method according to any one of (1) to (4), wherein a space velocity of the extract is 0.8 to 1.5 in the step (b).
(6) The production method according to any one of (1) to (5), wherein, in the step (c), nobiletin adsorbed on the porous adsorption resin is eluted with an ethanol aqueous solution having an ethanol concentration of 60 to 90% by volume. .
(7) Before eluting nobiletin adsorbed on the porous adsorption resin with an ethanol aqueous solution having an ethanol concentration of 60 to 90% by volume, the porous adsorption resin is washed with an ethanol aqueous solution having an ethanol concentration of 30 to 50% by volume. The manufacturing method according to (6) above.
柑橘類の抽出溶媒としてエタノール濃度が０〜４０容量％のエタノール水溶液を使用することにより、柑橘類から高収率でノビレチンを抽出することができる。
また、柑橘類の抽出溶媒としてエタノール濃度が０〜４０容量％のエタノール水溶液を使用することにより、柑橘類抽出液の濃縮時に析出物の発生を防止することができ、析出物により柑橘類抽出液の多孔性吸着樹脂への通液が阻害されることを防止することができる。
したがって、柑橘類の抽出溶媒としてエタノール濃度が０〜４０容量％のエタノール水溶液を使用することにより、ノビレチンの工業的生産が可能となる。
Nobiletin can be extracted from citrus fruits with a high yield by using an ethanol aqueous solution having an ethanol concentration of 0 to 40% by volume as an extraction solvent for citrus fruits.
In addition, by using an ethanol aqueous solution having an ethanol concentration of 0 to 40% by volume as a citrus extraction solvent, it is possible to prevent the generation of precipitates when the citrus extract is concentrated, and the precipitates make the citrus extract porous. It is possible to prevent the liquid passing through the adsorption resin from being inhibited.
Therefore, industrial production of nobiletin becomes possible by using an ethanol aqueous solution having an ethanol concentration of 0 to 40% by volume as an extraction solvent for citrus fruits.
工程（ａ）
工程（ａ）は、柑橘類をエタノール濃度が０〜４０容量％のエタノール水溶液で抽出する工程である。
柑橘類としては、ミカン科に属するシークワーシャー（Citrus depressa）、タチバナ（C.tachibana）、コウジ（C.leiocarpa）、ギリミカン（C.tardiva）、ジミカン（C.succosa）、キシュウ（C.kinokuni）、コベニミカン（C.erythrosa）、スンキ（C.sunki）、チチュウカイマンダリン（C.deliciosa）、キング（C.nobilis）、ポンカン（C.retuculata）、ダンシータンジェリン（C.tangerina）；ユズ区に属するハナユ（C.hanayu）、コウライタチバナ（C.nippokoreana）等が挙げられ、これらのうち１種又は２種以上の柑橘類を抽出原料として使用することができるが、ポンカンを抽出原料として使用することが好ましい。
Step (a)
Step (a) is a step of extracting citrus fruits with an aqueous ethanol solution having an ethanol concentration of 0 to 40% by volume.
Citrus fruits include Citrus depressa, C.tachibana, Koji (C.leiocarpa), C.tardiva, C.succosa, and C.kinokuni. , C.erythrosa, C.sunki, C. deliciosa, C. nobilis, C. retuculata, Dancy tangerine (C. tangerina); C. hanayu, C. nippokoreana, etc. can be mentioned. Among these, one or more citrus fruits can be used as the extraction raw material, but Ponkan can be used as the extraction raw material. preferable.
抽出原料として使用できる柑橘類の部位としては、例えば、果実、果皮、葉等が挙げられ、これらのうち１種又は２種以上を抽出原料として使用することができるが、果実又は果皮を抽出原料として使用することが好ましい。果実としては、果皮を含む果実全体を使用することが好ましい。果実又は果皮としては、未熟な果実（摘果果実）又はその果皮及び成熟した果実又はその果皮のいずれを使用してもよい。抽出原料には、切断、破砕、乾燥等の前処理を行うことができる。 Examples of citrus parts that can be used as an extraction raw material include fruits, pericarps, leaves, and the like, and one or more of these can be used as the extraction raw material, but the fruit or pericarp is used as the extraction raw material. It is preferable to use it. As the fruit, it is preferable to use the whole fruit including the skin. As the fruit or pericarp, any of immature fruit (plucked fruit) or pericarp and mature fruit or pericarp may be used. The extraction raw material can be subjected to pretreatment such as cutting, crushing, and drying.
エタノール水溶液におけるエタノール濃度は０〜４０容量％の範囲内で適宜変更することができる。なお、エタノール濃度が０容量％のエタノール水溶液とは、水を意味する。水には、純水、水道水、井戸水、鉱泉水、鉱水、温泉水、湧水、淡水等の他、これらに各種処理を施したものが含まれる。水に施す処理としては、例えば、精製、加熱、殺菌、滅菌、ろ過、イオン交換、浸透圧の調整、緩衝化等が含まれる。 The ethanol concentration in the aqueous ethanol solution can be appropriately changed within the range of 0 to 40% by volume. The ethanol aqueous solution having an ethanol concentration of 0% by volume means water. The water includes pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, as well as those subjected to various treatments. Examples of the treatment applied to water include purification, heating, sterilization, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, and the like.
抽出処理は、柑橘類に含まれるノビレチンを抽出できる限り特に限定されず、常法に従って行うことができる。例えば、抽出原料の１〜２０倍量（質量比）の抽出溶媒に抽出原料を浸漬し、常温又は還流加熱下で０．１〜３時間抽出した後、濾過して残渣を除去することにより、ノビレチンを含有する抽出液を得ることができる。得られた抽出液は、常法に従って濃縮してもよい。また、得られた抽出液は、脱色等を目的として活性炭処理してもよい。 The extraction treatment is not particularly limited as long as nobiletin contained in citrus can be extracted, and can be performed according to a conventional method. For example, by immersing the extraction raw material in an extraction solvent 1 to 20 times the mass of the extraction raw material (mass ratio), extracting for 0.1 to 3 hours at room temperature or under reflux heating, and then filtering to remove the residue, An extract containing nobiletin can be obtained. The obtained extract may be concentrated according to a conventional method. The obtained extract may be treated with activated carbon for the purpose of decolorization and the like.
柑橘類をエタノール濃度が０〜４０容量％のエタノール水溶液で抽出する前又は抽出した後に、柑橘類を熱水で抽出することが好ましい。これにより、柑橘類からのノビレチン収率を向上させることができる。熱水の温度は通常４０〜１００℃、好ましくは６０〜９０℃である。エタノール濃度が０〜４０容量％のエタノール水溶液で抽出する前に熱水で抽出する場合には、柑橘類を熱水で抽出し、濾過して、ノビレチンを含有する抽出液を得た後、残渣をエタノール濃度が０〜４０容量％のエタノール水溶液で抽出し、濾過して、ノビレチンを含有する抽出液を得、両抽出液を混合する。エタノール濃度が０〜４０容量％のエタノール水溶液で抽出した後に熱水で抽出する場合には、柑橘類をエタノール濃度が０〜４０容量％のエタノール水溶液で抽出し、濾過して、ノビレチンを含有する抽出液を得た後、残渣を熱水で抽出し、濾過して、ノビレチンを含有する抽出液を得、両抽出液を混合する。 It is preferable to extract the citrus fruits with hot water before or after extracting the citrus fruits with an aqueous ethanol solution having an ethanol concentration of 0 to 40% by volume. Thereby, the nobiletin yield from citrus can be improved. The temperature of the hot water is usually 40 to 100 ° C, preferably 60 to 90 ° C. When extracting with hot water before extraction with an aqueous ethanol solution having an ethanol concentration of 0 to 40% by volume, citrus fruits are extracted with hot water and filtered to obtain an extract containing nobiletin, and then the residue is removed. Extraction is performed with an aqueous ethanol solution having an ethanol concentration of 0 to 40% by volume, followed by filtration to obtain an extract containing nobiletin, and both extracts are mixed. When extracting with hot water after extracting with an aqueous ethanol solution with an ethanol concentration of 0 to 40% by volume, the citrus fruits are extracted with an aqueous ethanol solution with an ethanol concentration of 0 to 40% by volume, filtered, and extracted containing nobiletin. After obtaining the liquid, the residue is extracted with hot water and filtered to obtain an extract containing nobiletin, and the two extracts are mixed.
工程（ｂ）
工程（ｂ）は、工程（ａ）で得られた抽出液を多孔性吸着樹脂に通液する工程である。
工程（ａ）で得られた抽出液には、エタノール濃度が０〜４０容量％のエタノール水溶液を用いて得られた抽出液、及び該抽出液と熱水を用いて得られた抽出液との混合液が含まれる。
多孔性吸着樹脂は、ノビレチンを吸着し得る限り特に限定されるものではない。多孔性吸着樹脂としては、例えば、合成吸着樹脂、活性炭等が挙げられ、これらのうち１種類又は２種類以上を使用することができるが、合成吸着樹脂を使用することが好ましい。
Step (b)
Step (b) is a step of passing the extract obtained in step (a) through the porous adsorption resin.
The extract obtained in step (a) includes an extract obtained using an aqueous ethanol solution having an ethanol concentration of 0 to 40% by volume, and an extract obtained using the extract and hot water. A liquid mixture is included.
The porous adsorption resin is not particularly limited as long as it can adsorb nobiletin. Examples of the porous adsorption resin include synthetic adsorption resin, activated carbon, and the like. Among these, one type or two or more types can be used, and it is preferable to use a synthetic adsorption resin.
工程（ａ）で得られた抽出液は、濃縮した後、多孔性吸着樹脂に通液することが好ましい。これにより、多孔性吸着樹脂への通液時間を短縮することができる。濃縮は、減圧濃縮等の常法に従って行うことができ、通常３〜１０倍、好ましくは４〜６倍に濃縮する。 The extract obtained in the step (a) is preferably passed through a porous adsorption resin after being concentrated. Thereby, the liquid passing time to porous adsorption resin can be shortened. Concentration can be carried out according to a conventional method such as vacuum concentration, and is usually concentrated 3 to 10 times, preferably 4 to 6 times.
抽出液の空間速度は通常０．１〜４、好ましくは０．８〜１．５である。なお、１時間当たり樹脂量の１倍量を通過させる速度を空間速度（Space Velocity，SV）＝１とする。 The space velocity of the extract is usually 0.1 to 4, preferably 0.8 to 1.5. In addition, the space velocity (Space Velocity, SV) = 1 is defined as the speed at which the amount of resin per hour passes.
工程（ａ）で得られた抽出液を多孔性吸着樹脂に通液し、多孔性吸着樹脂から流出してくる液には多孔性吸着樹脂に吸着しなかったノビレチンが含まれている可能性があるので、これを回収しておくことが好ましい。 The extract obtained in step (a) is passed through the porous adsorption resin, and the liquid flowing out of the porous adsorption resin may contain nobiletin that was not adsorbed on the porous adsorption resin. Since there is, it is preferable to collect this.
工程（ｃ）
工程（ｃ）は、多孔性吸着樹脂に吸着したノビレチンを溶出する工程である。
多孔性吸着樹脂に吸着したノビレチンを溶出させることができる溶媒としては、例えば、エタノール水溶液、メタノール水溶液、イソプロパノール水溶液等が挙げられるが、これらのうちエタノール水溶液を使用することが好ましい。ノビレチンの溶出に使用するエタノール水溶液のエタノール濃度は、通常５５〜９５容量％、好ましくは６０〜９０容量％である。
Step (c)
Step (c) is a step of eluting nobiletin adsorbed on the porous adsorption resin.
Examples of the solvent capable of eluting nobiletin adsorbed on the porous adsorption resin include an ethanol aqueous solution, a methanol aqueous solution, and an isopropanol aqueous solution. Among these, it is preferable to use an ethanol aqueous solution. The ethanol concentration of the aqueous ethanol solution used for elution of nobiletin is usually 55 to 95% by volume, preferably 60 to 90% by volume.
多孔性吸着樹脂に吸着したノビレチンを溶出させる前に、多孔性吸着樹脂を洗浄し、多孔性吸着樹脂に吸着したノビレチン以外の成分を溶出させることが好ましい。多孔性吸着樹脂の洗浄液としては、例えば、水、エタノール水溶液、メタノール水溶液、イソプロパノール水溶液、水酸化ナトリウム水溶液等が挙げられるが、これらのうちエタノール水溶液を使用することが好ましい。多孔性吸着樹脂の洗浄に使用するエタノール水溶液のエタノール濃度は、通常１０〜５０容量％、好ましくは３０〜５０容量％である。 Before eluting nobiletin adsorbed on the porous adsorption resin, it is preferable to wash the porous adsorption resin and elute components other than nobiletin adsorbed on the porous adsorption resin. Examples of the cleaning liquid for the porous adsorption resin include water, an aqueous ethanol solution, an aqueous methanol solution, an aqueous isopropanol solution, and an aqueous sodium hydroxide solution. Of these, an aqueous ethanol solution is preferably used. The ethanol concentration of the aqueous ethanol solution used for washing the porous adsorption resin is usually 10 to 50% by volume, preferably 30 to 50% by volume.
多孔性吸着樹脂からの溶出液を、減圧乾燥等の常法に従って乾燥することによりノビレチン粗精製物を得ることができる。多孔性吸着樹脂からの溶出液に、工程（ｃ）で得られる多孔性吸着樹脂洗浄液を混合し、この混合液を乾燥することによりノビレチン粗精製物を得ることもできる。
ノビレチン粗精製物には、通常、柑橘類に含まれるノビレチン以外のポリメトキシフラボノイド（例えば、タンゲレチン、ペンタメトキシフラボン、テトラメトキシフラボン、ヘプタメトキシフラボン）が含まれている。
A crude nobiletin product can be obtained by drying the eluate from the porous adsorption resin according to a conventional method such as drying under reduced pressure. It is also possible to obtain a nobiletin crude purified product by mixing the porous adsorbent resin washing liquid obtained in the step (c) with the eluate from the porous adsorbent resin and drying the mixed liquid.
The nobiletin crude product usually contains polymethoxyflavonoids other than nobiletin contained in citrus fruits (for example, tangeretin, pentamethoxyflavone, tetramethoxyflavone, heptamethoxyflavone).
多孔性吸着樹脂に吸着したノビレチンを溶出させる後、多孔性吸着樹脂を洗浄し、多孔性吸着樹脂に吸着している成分を溶出させることにより、多孔性吸着樹脂を繰り返し使用することができる。多孔性吸着樹脂の洗浄液としては、例えば、水、エタノール水溶液、メタノール水溶液、イソプロパノール水溶液、水酸化ナトリウム水溶液等が挙げられるが、これらのうちエタノール水溶液を使用することが好ましい。多孔性吸着樹脂の洗浄に使用するエタノール水溶液のエタノール濃度は、通常７０〜９９容量％である。 After eluting nobiletin adsorbed on the porous adsorption resin, the porous adsorption resin can be repeatedly used by washing the porous adsorption resin and eluting the components adsorbed on the porous adsorption resin. Examples of the cleaning liquid for the porous adsorption resin include water, an aqueous ethanol solution, an aqueous methanol solution, an aqueous isopropanol solution, and an aqueous sodium hydroxide solution. Of these, an aqueous ethanol solution is preferably used. The ethanol concentration of the aqueous ethanol solution used for washing the porous adsorption resin is usually 70 to 99% by volume.
以下、比較例及び実施例に基づき本発明をさらに詳細に説明するが、本発明はこれらの内容に限定されるものではない。なお、以下の比較例及び実施例において、「％」は容量％を表す。 Hereinafter, although this invention is demonstrated further in detail based on a comparative example and an Example, this invention is not limited to these content. In the following comparative examples and examples, “%” represents volume%.
〔比較例１〕
ポンカン摘果果実（果皮を含む果実全体）５５６．４ｇを９０％エタノール１５００ｍＬで還流下にて１時間抽出した後、濾過して、９０％エタノール１番抽出液を得た。次いで、残渣を再び９０％エタノール１５００ｍＬで還流下にて１時間抽出した後、濾過して、９０％エタノール２番抽出液を得た。次いで、残渣を９０℃の熱水１５００ｍＬで抽出した後、濾過して、熱水抽出液を得た。９０％エタノール１番抽出液及び９０％エタノール２番抽出液を合わせ、９０％エタノール総抽出液を得、これを活性炭（カルボラフィン（商品名、日本エンバイロケミカルズ株式会社製）５ｇ）処理して脱色した。
[Comparative Example 1]
556.4 g of Ponkan fruit (whole fruit including the pericarp) was extracted with 1500 mL of 90% ethanol under reflux for 1 hour and then filtered to obtain 90% ethanol No. 1 extract. Next, the residue was again extracted with 1500 mL of 90% ethanol for 1 hour under reflux, followed by filtration to obtain 90% ethanol No. 2 extract. Next, the residue was extracted with 1500 mL of hot water at 90 ° C. and then filtered to obtain a hot water extract. 90% ethanol No. 1 extract and 90% ethanol No. 2 extract are combined to obtain a 90% ethanol total extract, and this is treated with activated carbon (Carlabafine (trade name, manufactured by Nippon Environmental Chemicals Co., Ltd.) 5 g) for decolorization. did.
(i)９０％エタノール１番抽出液、(ii)９０％エタノール２番抽出液、(iii)９０％エタノール総抽出液、(iv)活性炭処理後の９０％エタノール総抽出液、(v)熱水抽出液、(vi)活性炭処理後の９０％エタノール総抽出液と熱水抽出液との混合液における固形分量、固形分中のノビレチン含量、原料に対するノビレチン収率を表１に示す。 (i) 90% ethanol No. 1 extract, (ii) 90% ethanol No. 2 extract, (iii) 90% ethanol total extract, (iv) 90% ethanol total extract after activated carbon treatment, (v) heat Table 1 shows the solid content, the nobiletin content in the solid content, and the nobiletin yield relative to the raw material in the aqueous extract, (vi) the mixture of the 90% ethanol total extract after the activated carbon treatment and the hot water extract.
９０％エタノール抽出液の活性炭処理時にノビレチンの損失が大きかった。
また、活性炭処理後の９０％エタノール総抽出液と熱水抽出液との混合液を減圧濃縮したところ、析出物が多かった。ノビレチン粗精製物を得るためには、抽出液を多孔性吸着樹脂に通液する必要があるが、抽出液中の析出物は通液の阻害物となる。
The loss of nobiletin was large when the 90% ethanol extract was treated with activated carbon.
Moreover, when the liquid mixture of 90% ethanol total extract and hot water extract after activated carbon treatment was concentrated under reduced pressure, there were many precipitates. In order to obtain a nobiletin crude purified product, it is necessary to pass the extract through the porous adsorption resin.
〔比較例２〕
ポンカン摘果果実（果皮を含む果実全体）５００．０ｇを９０％エタノール１５００ｍＬで還流下にて１時間抽出した後、濾過して、９０％エタノール抽出液を得た。次いで、残渣を９０℃の熱水１５００ｍＬで抽出した後、濾過して、熱水抽出液を得た。９０％エタノール抽出液を活性炭（カルボラフィン（商品名、日本エンバイロケミカルズ株式会社製）２ｇ）処理して脱色した。
[Comparative Example 2]
After extracting 500.0 g of Ponkan fruit (whole fruit including the skin) with 1,500 mL of 90% ethanol under reflux for 1 hour, the mixture was filtered to obtain a 90% ethanol extract. Next, the residue was extracted with 1500 mL of hot water at 90 ° C. and then filtered to obtain a hot water extract. The 90% ethanol extract was treated with activated carbon (Carlabafine (trade name, manufactured by Nippon Enviro Chemicals Co., Ltd.) 2 g) for decolorization.
(i)９０％エタノール抽出液、(ii)活性炭処理後の９０％エタノール抽出液、(iii)熱水抽出液、(iv)活性炭処理後の９０％エタノール抽出液と熱水抽出液との混合液における固形分量、固形分中のノビレチン含量、原料に対するノビレチン収率を表２に示す。 (i) 90% ethanol extract, (ii) 90% ethanol extract after activated carbon treatment, (iii) hot water extract, (iv) mixing of 90% ethanol extract and hot water extract after activated carbon treatment Table 2 shows the solid content, the nobiletin content in the solid, and the nobiletin yield relative to the raw material.
活性炭量を減少させることにより、９０％エタノール抽出液の活性炭処理時のノビレチンの損失は減少した。しかし、活性炭処理後の９０％エタノール抽出液と熱水抽出液との混合液を濃縮したところ、析出物は依然多かった。 By reducing the amount of activated carbon, the loss of nobiletin during the activated carbon treatment of the 90% ethanol extract was reduced. However, when the mixture of the 90% ethanol extract and the hot water extract after the activated carbon treatment was concentrated, there were still many precipitates.
〔実施例１〕
ポンカン摘果果実（果皮を含む果実全体）５００．０ｇを３０％エタノール１０００ｍＬで還流下にて１時間抽出した後、濾過して、３０％エタノール抽出液を得た。次いで、残渣を９０℃の熱水１０００ｍＬで抽出した後、濾過して、熱水抽出液を得た。
[Example 1]
After extracting 500.0 g of Ponkan fruit (whole fruit including the pericarp) under reflux with 1000 mL of 30% ethanol for 1 hour, it was filtered to obtain a 30% ethanol extract. Next, the residue was extracted with 1000 mL of hot water at 90 ° C. and then filtered to obtain a hot water extract.
(i)３０％エタノール抽出液、(ii)熱水抽出液、(iii)３０％エタノール抽出液と熱水抽出液との混合液における固形分量、固形分中のノビレチン含量、原料に対するノビレチン収率を表３に示す。 (i) 30% ethanol extract, (ii) hot water extract, (iii) solid content in mixed solution of 30% ethanol extract and hot water extract, nobiletin content in solid, nobiletin yield relative to raw material Is shown in Table 3.
３０％エタノールを用いる場合には、９０％エタノールを用いる場合によりもノビレチン収率が高かった。また、３０％エタノール抽出液と熱水抽出液との混合液を減圧濃縮したところ懸濁溶液となったが、多孔性吸着樹脂への通液は可能であった。 When 30% ethanol was used, the nobiletin yield was higher than when 90% ethanol was used. Moreover, when the liquid mixture of 30% ethanol extract and hot water extract was concentrated under reduced pressure, it became a suspension solution, but it was possible to pass through the porous adsorption resin.
〔実施例２〕
ポンカン摘果果実（果皮を含む果実全体）２７８．０ｇを９０℃の熱水１０００ｍＬで抽出した後、濾過して、熱水１番抽出液を得た。次いで、残渣を９０℃の熱水１０００ｍＬで抽出した後、濾過して、熱水２番抽出液を得た。熱水１番抽出液と２番抽出液とを合わせて熱水総抽出液を得た。
[Example 2]
After extracting 278.0 g of Ponkan fruit (whole fruit including the skin) with 1000 mL of hot water at 90 ° C., it was filtered to obtain No. 1 hot water extract. Next, the residue was extracted with 1000 mL of hot water at 90 ° C. and then filtered to obtain No. 2 hot water extract. The hot water No. 1 extract and No. 2 extract were combined to obtain a hot water total extract.
(i)熱水１番抽出液、(ii)熱水２番抽出液、(iii)熱水総抽出液における固形分量、固形分中のノビレチン含量、原料に対するノビレチン収率を表４に示す。 Table 4 shows the solid content in (i) hot water No. 1 extract, (ii) hot water No. 2 extract, and (iii) total hot water extract, nobiletin content in the solid, and nobiletin yield relative to the raw material.
熱水を用いる場合には、９０％エタノールを用いる場合よりもノビレチン収率が高かった。また、熱水総抽出液を減圧濃縮したところ懸濁溶液となったが、多孔性吸着樹脂への通液は可能であった。 When hot water was used, the nobiletin yield was higher than when 90% ethanol was used. Moreover, when the hot water total extract was concentrated under reduced pressure, a suspension solution was obtained, but it was possible to pass through the porous adsorption resin.
〔実施例３〕
ポンカン摘果果実（果皮を含む果実全体）２５００ｋｇを３０％エタノール２８００Ｌで還流下にて１時間抽出した後、濾過して、３０％エタノール抽出液を得た。次いで、残渣を９０℃以上の熱水２３００ｍＬで１時間抽出した後、濾過して、熱水抽出液を得た。３０％エタノール抽出液と熱水抽出液とを合わせた後、減圧濃縮し、濃縮液５００Ｌを得た。減圧濃縮に用いた濃縮缶を７０％エタノール１００Ｌで洗浄し、洗浄液と濃縮液と合わせた。洗浄液と濃縮液との混合液を室温で２日間保管した後、デカントし、デカント上清５４０Ｌを得た。デカント上清をＳＶ＝１にて多孔性吸着樹脂（ダイヤイオンＨＰ−２０（三菱化学（株）製））５００Ｌに通液し、多孔性吸着樹脂通過液を回収した。
Example 3
Ponkan fruit (whole fruit including fruit) 2500 kg was extracted with 30% ethanol 2800 L under reflux for 1 hour and then filtered to obtain a 30% ethanol extract. Subsequently, the residue was extracted with 2300 mL of hot water at 90 ° C. or higher for 1 hour, and then filtered to obtain a hot water extract. A 30% ethanol extract and a hot water extract were combined and then concentrated under reduced pressure to obtain 500 L of a concentrate. The concentration can used for vacuum concentration was washed with 100 L of 70% ethanol, and the washing solution and the concentrated solution were combined. The mixture of the washing liquid and the concentrated liquid was stored at room temperature for 2 days and then decanted to obtain 540 L of decanted supernatant. The decant supernatant was passed through 500 L of porous adsorption resin (Diaion HP-20 (manufactured by Mitsubishi Chemical Corporation)) at SV = 1, and the porous adsorption resin passage liquid was collected.
デカント上清を通液した後の多孔性吸着樹脂に１５％エタノール５００Ｌ、５０％エタノール２０００Ｌ、７０％エタノール２５００Ｌ及び９０％エタノール１０００Ｌを順次通液し、１５％エタノール溶出液、５０％エタノール溶出液、７０％エタノール溶出液、９０％エタノール溶出液を得た。 After passing through the decant supernatant, 15% ethanol 500L, 50% ethanol 2000L, 70% ethanol 2500L and 90% ethanol 1000L are sequentially passed through the porous adsorption resin, 15% ethanol eluate, 50% ethanol eluate. 70% ethanol eluate and 90% ethanol eluate were obtained.
７０％エタノール溶出液を減圧濃縮し、濃縮液６０Ｌを得た。減圧濃縮に用いた濃縮缶を７０％エタノール１００Ｌで洗浄し、洗浄液と濃縮液とを合わせた。減圧濃縮時にクロロフィルを除去した。減圧濃縮後、減圧乾燥してポンカン粗精製物１．３０ｋｇを得た。 The 70% ethanol eluate was concentrated under reduced pressure to obtain 60 L of a concentrate. The concentration can used for vacuum concentration was washed with 100 L of 70% ethanol, and the washing solution and the concentrated solution were combined. Chlorophyll was removed during concentration under reduced pressure. After concentration under reduced pressure, the residue was dried under reduced pressure to obtain 1.30 kg of a crude Ponkan product.
(i)３０％エタノール抽出液、(ii)熱水抽出液、(iii)３０％エタノール抽出液と熱水抽出液との混合液の濃縮液、(iv)デカント上清、(v)多孔性吸着樹脂通過液、(vi)５０％エタノール溶出液、(vii)７０％エタノール溶出液、(viii)９０％エタノール溶出液における固形分量、固形分中のノビレチン含量、ノビレチン回収率を表５に示す。 (i) 30% ethanol extract, (ii) hot water extract, (iii) concentrated solution of a mixture of 30% ethanol extract and hot water extract, (iv) decant supernatant, (v) porosity Table 5 shows the adsorbent resin passing solution, (vi) 50% ethanol eluate, (vii) 70% ethanol eluate, (viii) 90% ethanol eluate solid content, nobiletin content in solid content, and nobiletin recovery. .
７０％エタノール溶出液におけるノビレチン回収率は７０％であったが、デカントでの損失部分及び９０％エタノール溶出液に含まれるノビレチンは回収が可能である。 The nobiletin recovery rate in the 70% ethanol eluate was 70%, but the lost part in the decant and the nobiletin contained in the 90% ethanol eluate can be recovered.
Claims (7)
（ａ）柑橘類をエタノール濃度が０〜４０容量％のエタノール水溶液で抽出する工程
（ｂ）前記工程（ａ）で得られた抽出液を多孔性吸着樹脂に通液する工程
（ｃ）前記多孔性吸着樹脂に吸着したノビレチンを溶出する工程 The manufacturing method of nobiletin including the following process (a)-(c).
(A) A step of extracting citrus fruits with an aqueous ethanol solution having an ethanol concentration of 0 to 40% by volume (b) A step of passing the extract obtained in the step (a) through a porous adsorption resin (c) The porosity Process for eluting nobiletin adsorbed on adsorbent resin
The porous adsorption resin is washed with an ethanol aqueous solution with an ethanol concentration of 30-50 vol% before eluting nobiletin adsorbed on the porous adsorption resin with an ethanol aqueous solution with an ethanol concentration of 60-90 vol%. 6. The production method according to 6.
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| JP2006327998A (en) * | 2005-05-27 | 2006-12-07 | Nakamura Gakuen | Citrus fruit extract and its production method |
| JP2008043840A (en) * | 2006-08-11 | 2008-02-28 | Tetsuro Asao | Method for extracting effective component |
| JP2010163363A (en) * | 2009-01-13 | 2010-07-29 | Kao Corp | Method for producing extract containing apigenin in high concentration |
| JP2012056938A (en) * | 2010-08-11 | 2012-03-22 | Japan Royal Jelly Co Ltd | Method for producing nobiletin, and nobiletin-containing extract |
| CN102875509A (en) * | 2012-11-02 | 2013-01-16 | 陕西慧科植物开发有限公司 | Method for extracting high-purity nobiletin from citrus peels |
| WO2014057727A1 (en) | 2012-10-12 | 2014-04-17 | 国立大学法人 琉球大学 | Method for manufacturing substance containing nobiletin and tangeretin derived from citrus fruits, and nobiletin- and tangeretin-containing substance obtained thereby |
| KR101727903B1 (en) * | 2014-09-23 | 2017-04-19 | 주식회사 비케이바이오 | Citrus peel fermentation extract for antimetastatic or anti-cancer activity, preparing method thereof and health functional food comprising the the same |
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| WO2002020112A1 (en) * | 2000-09-04 | 2002-03-14 | Queen Bioactives Pty Ltd | Process for selectively extracting bioactive components |
| JP2003292488A (en) * | 2002-04-02 | 2003-10-15 | Ogawa & Co Ltd | Method for separating polymethoxyflavones |
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| WO2002020112A1 (en) * | 2000-09-04 | 2002-03-14 | Queen Bioactives Pty Ltd | Process for selectively extracting bioactive components |
| JP2003292488A (en) * | 2002-04-02 | 2003-10-15 | Ogawa & Co Ltd | Method for separating polymethoxyflavones |
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| JP2006327998A (en) * | 2005-05-27 | 2006-12-07 | Nakamura Gakuen | Citrus fruit extract and its production method |
| JP4585913B2 (en) * | 2005-05-27 | 2010-11-24 | 学校法人中村学園 | Citrus extract and production method thereof |
| JP2008043840A (en) * | 2006-08-11 | 2008-02-28 | Tetsuro Asao | Method for extracting effective component |
| JP2010163363A (en) * | 2009-01-13 | 2010-07-29 | Kao Corp | Method for producing extract containing apigenin in high concentration |
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| JP2012056938A (en) * | 2010-08-11 | 2012-03-22 | Japan Royal Jelly Co Ltd | Method for producing nobiletin, and nobiletin-containing extract |
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| CN102875509A (en) * | 2012-11-02 | 2013-01-16 | 陕西慧科植物开发有限公司 | Method for extracting high-purity nobiletin from citrus peels |
| KR101727903B1 (en) * | 2014-09-23 | 2017-04-19 | 주식회사 비케이바이오 | Citrus peel fermentation extract for antimetastatic or anti-cancer activity, preparing method thereof and health functional food comprising the the same |
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