JP7512008B2 - Anti-glycation agents - Google Patents
Anti-glycation agents Download PDFInfo
- Publication number
- JP7512008B2 JP7512008B2 JP2018103252A JP2018103252A JP7512008B2 JP 7512008 B2 JP7512008 B2 JP 7512008B2 JP 2018103252 A JP2018103252 A JP 2018103252A JP 2018103252 A JP2018103252 A JP 2018103252A JP 7512008 B2 JP7512008 B2 JP 7512008B2
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- Prior art keywords
- bagasse
- decomposition
- extract
- glycation
- treatment
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Description
本発明は、抗糖化剤に関する。 The present invention relates to an anti-glycation agent.
糖化とはメイラード反応とも呼ばれ、１９１２年にフランスの科学者L.C. Maillardによって発見されたアミノ酸・タンパク質と還元糖の非酵素的な化学反応である。糖化は食品の加熱中におこる着色、香り・風味の変化等食品化学の分野で注目されてきた。 Glycation, also known as the Maillard reaction, is a non-enzymatic chemical reaction between amino acids, proteins and reducing sugars that was discovered in 1912 by French scientist L.C. Maillard. Glycation has attracted attention in the field of food chemistry due to the changes in color, aroma and flavor that occur during heating of food.
生体における糖化は、グルコースなどの還元糖のカルボニル基とタンパク質とが非酵素的に反応し、シッフ塩基（schiff base）の形成を経てアマドリ転移により不可逆的な物質である糖化タンパク質となり、3-デオキシグルコソン（３ＤＧ）、グリオキサール、メチルグリオキサール、グリセルアルデヒド、グルタールアルデヒドなどのカルボニル化合物を中心とする反応中間体生成を経て、糖化最終生成物（advanced glycation endproducts:ＡＧＥｓ）の生成に至る反応である。 Glycation in the living body occurs when the carbonyl group of reducing sugars such as glucose reacts nonenzymatically with proteins to form a Schiff base, which then undergoes Amadori rearrangement to turn into glycated proteins, which are irreversible substances, and then through the production of reactive intermediates centered on carbonyl compounds such as 3-deoxyglucosone (3DG), glyoxal, methylglyoxal, glyceraldehyde, and glutaraldehyde, to produce advanced glycation endproducts (AGEs).
近年、ＡＧＥｓと、人の皮膚の老化、動脈硬化、糖尿病疾病、糖尿病の三大合併症（神経障害、網膜症、腎症）、成人病疾患等との関係性について種々の研究がなされており、これらの疾患の治療・改善及び老化防止・予防には、抗糖化剤が用いられる。そして、これまでにも、種々の抗糖化剤が提案されている。例えば、特許文献１には、焼酎残渣もろみの濃縮エキスを有効成分として含有する、抗糖化剤が開示されている。
In recent years, various studies have been conducted on the relationship between AGEs and human skin aging, arteriosclerosis, diabetic diseases, the three major complications of diabetes (neuropathy, retinopathy, nephropathy), adult diseases, etc., and anti-glycation agents are used to treat and improve these diseases and to prevent and prevent aging. Various anti-glycation agents have also been proposed to date. For example,
本発明は、新規な抗糖化剤を提供することを目的とする。 The present invention aims to provide a novel anti-glycation agent.
本発明は、バガスの分解抽出物を有効成分として含む抗糖化剤に関する。本発明の抗糖化剤は、バガスの分解抽出物を有効成分として含むため、抗糖化活性に優れている。 The present invention relates to an anti-glycation agent containing a decomposition extract of bagasse as an active ingredient. The anti-glycation agent of the present invention has excellent anti-glycation activity because it contains a decomposition extract of bagasse as an active ingredient.
バガスの分解抽出物は、水熱処理、酸処理、アルカリ処理、亜臨界水処理、微粉砕処理及び爆砕処理からなる群より選ばれる少なくとも１種の分解処理により得られる分解処理液であってよい。 The decomposition extract of bagasse may be a decomposition treatment liquid obtained by at least one decomposition treatment selected from the group consisting of hydrothermal treatment, acid treatment, alkali treatment, subcritical water treatment, pulverization treatment, and explosion treatment.
バガスの分解抽出物は、分解処理液を、固定担体を充填したカラムに通液することより得られる画分であってもよい。固定担体は、好ましくは、合成吸着剤又はイオン交換樹脂である。 The decomposition extract of bagasse may be a fraction obtained by passing the decomposition treatment liquid through a column packed with a fixed carrier. The fixed carrier is preferably a synthetic adsorbent or an ion exchange resin.
固定担体が合成吸着剤である場合、バガスの分解抽出物は、該合成吸着剤に吸着された成分を、水、メタノール、エタノール及びこれらの混合物からなる群より選ばれる少なくとも１種の溶媒で溶出させることにより得られる画分であってもよい。 When the fixed carrier is a synthetic adsorbent, the decomposed extract of bagasse may be a fraction obtained by eluting the components adsorbed on the synthetic adsorbent with at least one solvent selected from the group consisting of water, methanol, ethanol, and mixtures thereof.
合成吸着剤は、好ましくは、芳香族系樹脂、アクリル酸系メタクリル樹脂、又はアクリロニトリル脂肪族系樹脂である。 The synthetic adsorbent is preferably an aromatic resin, an acrylic acid-based methacrylic resin, or an acrylonitrile-aliphatic resin.
バガスの分解抽出物は、分解処理液を、固定担体としての合成吸着剤を充填したカラムに通液し、該合成吸着剤に吸着された成分を、エタノール及び水の混合溶媒で溶出させて得られる画分であってよく、この場合、合成吸着剤は、無置換基型の芳香族系樹脂であり、カラムの温度は２０～６０℃であり、混合溶媒のエタノール及び水の体積比（エタノール／水）は５０／５０～６０／４０であってもよい。 The decomposition extract of bagasse may be a fraction obtained by passing the decomposition treatment liquid through a column packed with a synthetic adsorbent as a fixed carrier and eluting the components adsorbed by the synthetic adsorbent with a mixed solvent of ethanol and water. In this case, the synthetic adsorbent is an unsubstituted aromatic resin, the temperature of the column is 20 to 60°C, and the volume ratio of ethanol and water in the mixed solvent (ethanol/water) may be 50/50 to 60/40.
上記抗糖化剤は、抗糖化活性に優れているため、抗糖化用飲食品として好適に用いることができる。 The above anti-glycation agents have excellent anti-glycation activity and can therefore be suitably used as anti-glycation foods and beverages.
本発明によれば、新規な抗糖化剤を提供することが可能となる。 The present invention makes it possible to provide a novel anti-glycation agent.
以下、本発明を実施するための形態について詳細に説明する。なお、本発明は、以下の実施形態に限定されるものではない。 The following describes in detail the embodiments of the present invention. Note that the present invention is not limited to the following embodiments.
本明細書における抗糖化剤は、抗糖化活性を有するものであり、具体的には、糖化最終生成物（ＡＧＥｓ）の、生成抑制作用（糖化反応阻害作用）、蓄積抑制作用又は分解作用を有するものであってよい。言い換えれば、本実施形態の抗糖化剤は、例えば、糖化最終生成物の生成抑制剤（糖化反応阻害剤）、蓄積抑制剤又は分解剤（分解促進剤）であってよい。 The anti-glycation agent in this specification has anti-glycation activity, and specifically may have an effect of inhibiting the production (glycation reaction inhibitory effect), the accumulation inhibitory effect, or the decomposition effect of advanced glycation end products (AGEs). In other words, the anti-glycation agent in this embodiment may be, for example, an agent for inhibiting the production (glycation reaction inhibitor), an agent for inhibiting the accumulation, or an agent for decomposing (decomposition promoter) advanced glycation end products.
糖化最終生成物（終末糖化産物）は、糖化反応（メイラード反応）による生成物の総称である。糖化最終生成物としては、例えば、ＣＭＬ（Ｎε－（ｃａｒｂｏｘｙｍｅｔｈｙｌ）ｌｙｓｉｎｅ）、ペントシジン（ｐｅｎｔｏｓｉｄｉｎｅ）、ピラリン（ｐｙｒｒａｌｉｎｅ）、クロスリン（ｃｒｏｓｓｌｉｎｅ）が挙げられる。また、本実施形態の抗糖化剤は、糖化反応における反応中間体の、生成抑制作用、蓄積抑制作用又は分解促進作用を有することにより、結果として、上述の抗糖化活性を有するものであってよい。糖化反応における反応中間体としては、具体的には、グリオキサール（ＧＯ）、３－デオキシグルコソン（３ＤＧ）、メチルグリオキサール（ＭＧＯ）等であってよい。 Advanced glycation end products are a general term for products resulting from glycation reactions (Maillard reactions). Examples of advanced glycation end products include CML (N ε -(carboxymethyl)lysine), pentosidine, pyrraline, and crossline. The anti-glycation agent of the present embodiment may have an effect of inhibiting the production, inhibiting the accumulation, or promoting the decomposition of a reaction intermediate in a glycation reaction, and may thus have the above-mentioned anti-glycation activity. Specific examples of reaction intermediates in a glycation reaction include glyoxal (GO), 3-deoxyglucosone (3DG), methylglyoxal (MGO), and the like.
本実施形態の抗糖化剤は、バガスの分解抽出物を有効成分として含む。 The anti-glycation agent of this embodiment contains a decomposition extract of bagasse as an active ingredient.
抗糖化剤におけるバガスの分解抽出物の含有量は、抗糖化剤全量基準で、０．０１～１００質量％であってもよく、０．１～１００質量％であってもよい。 The content of the bagasse decomposition extract in the anti-glycation agent may be 0.01 to 100% by mass, or 0.1 to 100% by mass, based on the total amount of the anti-glycation agent.
一実施形態に係る抗糖化剤は、バガスの分解抽出物を有効成分として含有する。バガスの分解抽出物には、ｐ－クマル酸、フェルラ酸、カフェ酸及びバニリン等のフェニルプロパノイド、並びにリグニン及びその分解物からなる群より選ばれる少なくとも１種が含まれていることが好ましい。 An anti-glycation agent according to one embodiment contains a decomposition extract of bagasse as an active ingredient. The decomposition extract of bagasse preferably contains at least one selected from the group consisting of phenylpropanoids such as p-coumaric acid, ferulic acid, caffeic acid and vanillin, as well as lignin and its decomposition products.
「バガス」とは、典型的には原料糖製造工程における製糖過程で排出されるバガスをいう。原料糖工場における製糖過程で排出されるバガスには、最終圧搾機を出た最終バガスだけではなく、第１圧搾機を含む以降の圧搾機に食い込まれた細裂甘蔗をも含む。好適なバガスは、原料糖工場において圧搾工程により糖汁を圧搾した後に排出されるバガスである。当該バガスは、甘蔗の種類、収穫時期等により、その含まれる水分、糖分及びそれらの組成比が異なるが、本発明においては、これらのバガスを任意に用いることができる。さらに、本実施形態では、原料のバガスとして、原料糖工場と同様に、例えば黒糖製造工場において排出される甘蔗圧搾後に残るバガス、又は実験室レベルの小規模な実施により甘蔗から糖液を圧搾した後のバガスも用いることができる。 "Bagasse" typically refers to bagasse discharged during the sugar manufacturing process in the raw sugar manufacturing process. The bagasse discharged during the sugar manufacturing process in a raw sugar factory includes not only the final bagasse that leaves the final press, but also shredded sugarcane that is eaten into the subsequent presses, including the first press. A suitable bagasse is bagasse discharged after the sugar juice is compressed in the compression process in a raw sugar factory. The moisture, sugar content, and composition ratio of the bagasse vary depending on the type of sugarcane, harvest time, etc., but in the present invention, any of these bagasses can be used. Furthermore, in this embodiment, as in the raw sugar factory, bagasse remaining after sugarcane compression discharged from, for example, a brown sugar manufacturing factory, or bagasse after sugar juice is compressed from sugarcane in a small-scale laboratory-level implementation can also be used as the raw bagasse.
バガスの分解抽出物は、一実施形態において、バガス（及び／又はその加工物）の分解処理液であってよい。分解処理液は、アルカリ処理、水熱処理、酸処理、亜臨界水処理、微粉砕処理及び爆砕処理からなる群から選ばれる少なくとも１種以上の分解処理により得ることができる。分解処理は、バガスの分解抽出物を得やすい観点から、好ましくはアルカリ処理又は水熱処理である。 In one embodiment, the decomposition extract of bagasse may be a decomposition treatment liquid of bagasse (and/or a processed product thereof). The decomposition treatment liquid can be obtained by at least one decomposition treatment selected from the group consisting of an alkali treatment, a hydrothermal treatment, an acid treatment, a subcritical water treatment, a fine pulverization treatment, and an explosion treatment. From the viewpoint of facilitating the production of a decomposition extract of bagasse, the decomposition treatment is preferably an alkali treatment or a hydrothermal treatment.
アルカリ処理は、バガスにアルカリ性溶液を接触させる処理であってよい。アルカリ性溶液を接触させる方法としては、例えば、アルカリ性溶液をバガスに振りかける方法、バガスをアルカリ性溶液に浸漬させる方法等が挙げられる。バガスをアルカリ性溶液に浸漬させる方法においては、バガス及びアルカリ性溶液の混合物を撹拌しながら浸漬させてもよい。 The alkaline treatment may be a treatment in which the bagasse is brought into contact with an alkaline solution. Examples of methods for bringing the bagasse into contact with the alkaline solution include a method in which the bagasse is sprinkled with the alkaline solution, and a method in which the bagasse is immersed in the alkaline solution. In the method in which the bagasse is immersed in the alkaline solution, the bagasse may be immersed in a mixture of the bagasse and the alkaline solution while being stirred.
アルカリ性溶液としては、水酸化ナトリウム水溶液、水酸化カリウム水溶液、アンモニア水溶液等が挙げられる。アルカリ性溶液は、これらの溶液を１種単独で又は２種以上を混合して用いられてよい。アルカリ性溶液は、安価であり、食品製造工程で容易に用いられる観点から、好ましくは水酸化ナトリウム水溶液である。 Examples of alkaline solutions include aqueous sodium hydroxide solutions, aqueous potassium hydroxide solutions, and aqueous ammonia solutions. The alkaline solution may be one of these solutions alone or a mixture of two or more of them. From the viewpoints of being inexpensive and easily usable in food manufacturing processes, the alkaline solution is preferably an aqueous sodium hydroxide solution.
アルカリ性溶液の温度（液温）は、分解処理の処理時間を短縮する観点から、好ましくは４０℃以上であり、より好ましくは１００℃以上であり、更に好ましくは１３０℃以上である。アルカリ性溶液の温度は、分解処理液に多糖類を残存させないようにする観点から、好ましくは２５０℃以下であり、より好ましくは２００℃以下であり、更に好ましくは１５０℃以下である。 The temperature of the alkaline solution (liquid temperature) is preferably 40°C or higher, more preferably 100°C or higher, and even more preferably 130°C or higher, from the viewpoint of shortening the processing time of the decomposition process. The temperature of the alkaline solution is preferably 250°C or lower, more preferably 200°C or lower, and even more preferably 150°C or lower, from the viewpoint of not leaving polysaccharides in the decomposition process liquid.
アルカリ処理は、常圧下で行われてよく、加圧して行われてもよい。加圧する場合、圧力は、０．１ＭＰａ以上、０．２ＭＰａ以上であってよく、４．０ＭＰａ以下、１．６ＭＰａ以下、又は０．５ＭＰａ以下であってよい。 The alkali treatment may be carried out under normal pressure or under pressure. When pressure is applied, the pressure may be 0.1 MPa or more, 0.2 MPa or more, and 4.0 MPa or less, 1.6 MPa or less, or 0.5 MPa or less.
水熱処理は、バガスに高温の水又は水蒸気を高圧下で接触させる処理であってよい。水熱処理は、より具体的には、例えば、バガスの固形物濃度が０．１～５０％となるように水を加え、高温・高圧条件下で分解処理を行う方法であってもよい。水又は水蒸気の温度は１３０～２５０℃であることが好ましく、加える圧力は、各温度の水の飽和水蒸気圧に、更に０．１～０．５ＭＰa高い圧力であることが好ましい。 Hydrothermal treatment may be a process in which bagasse is brought into contact with high-temperature water or steam under high pressure. More specifically, hydrothermal treatment may be a method in which water is added so that the solids concentration of the bagasse is 0.1 to 50%, and decomposition treatment is carried out under high-temperature and high-pressure conditions. The temperature of the water or steam is preferably 130 to 250°C, and the applied pressure is preferably 0.1 to 0.5 MPa higher than the saturated steam pressure of water at each temperature.
酸処理は、バガスに酸性溶液を接触させる処理であってよい。酸性溶液としては、希硫酸等が挙げられる。バガスに酸性溶液を接触させる方法、酸処理における酸溶液の温度、酸処理における圧力条件は、上述したアルカリ処理における方法又は条件と同様であってよい。 The acid treatment may be a treatment in which the bagasse is brought into contact with an acidic solution. Examples of the acidic solution include dilute sulfuric acid. The method of bringing the bagasse into contact with the acidic solution, the temperature of the acidic solution in the acid treatment, and the pressure conditions in the acid treatment may be the same as the method or conditions in the alkali treatment described above.
亜臨界水処理は、バガスに亜臨界水を接触させる処理であってよい。バガスに亜臨界水を接触させる方法は、上述したアルカリ処理における方法と同様であってよい。亜臨界水処理の条件は特に制限されないが、亜臨界水の温度を１６０～２４０℃とし、処理時間を１～９０分間とすることが好ましい。 The subcritical water treatment may be a treatment in which subcritical water is brought into contact with bagasse. The method for bringing subcritical water into contact with bagasse may be the same as the method for the alkaline treatment described above. There are no particular limitations on the conditions for the subcritical water treatment, but it is preferable that the temperature of the subcritical water is 160 to 240°C and the treatment time is 1 to 90 minutes.
微粉砕処理は、圧縮、衝撃、せん断、摩擦などによりバガスを数μｍ～数百μｍに粉砕する処理であってよい。爆砕処理は、水熱処理によりバガスに含まれる不溶性キシランをある程度分解させた後、耐圧反応容器に設けられたバルブを一気に開放すること等によって、瞬間的に大気圧に放出することによりバガスを粉砕する処理であってよい。 The fine pulverization process may be a process in which bagasse is pulverized to a size of several μm to several hundred μm by compression, impact, shear, friction, etc. The explosion process may be a process in which the insoluble xylan contained in the bagasse is decomposed to a certain extent by hydrothermal treatment, and then the bagasse is pulverized by instantly releasing it to atmospheric pressure by suddenly opening a valve installed in a pressure-resistant reaction vessel, for example.
分解処理液においては、上述した分解処理の後、固形分及び液分を分離する処理がなされてもよい。この場合、分離後に得られた液分を分解処理液とすることができる。固形分及び液分を分離する方法は、ストレーナー、ろ過、遠心分離、デカンテーション等による分離であってよい。 After the above-mentioned decomposition process, the decomposition liquid may be subjected to a process for separating the solid and liquid components. In this case, the liquid obtained after the separation may be used as the decomposition liquid. The method for separating the solid and liquid components may be separation using a strainer, filtration, centrifugation, decantation, etc.
分解処理液においては、膜分離により多糖類等の高分子成分が除去されてもよい。この場合、膜分離後の液分を分解処理液とすることができる。分離膜は、限外濾過膜（ＵＦ膜）であれば特に限定されない。限外濾過膜の分画分子量は、好ましくは２，５００～５０，０００であり、より好ましくは２，５００～５，０００である。 In the decomposition treatment liquid, polymeric components such as polysaccharides may be removed by membrane separation. In this case, the liquid after membrane separation can be used as the decomposition treatment liquid. There are no particular limitations on the separation membrane as long as it is an ultrafiltration membrane (UF membrane). The molecular weight cutoff of the ultrafiltration membrane is preferably 2,500 to 50,000, and more preferably 2,500 to 5,000.
限外濾過膜の素材としては、ポリイミド、ポリエーテルスルホン（ＰＥＳ）、ポリスルホン（ＰＳ）、ポリアクリロニトリル（ＰＡＮ）、ポリフッ化ビニルデン（ＰＶＤＦ）、再生セルロース、セルロース、セルロースエステル、スルホン化ポリスルホン、スルホン化ポリエーテルスルホン、ポリオレフィン、ポリビニルアルコール、ポリメチルメタクリレート、ポリ四フッ化エチレン等を使用することができる。 Materials that can be used for the ultrafiltration membrane include polyimide, polyethersulfone (PES), polysulfone (PS), polyacrylonitrile (PAN), polyvinylidene fluoride (PVDF), regenerated cellulose, cellulose, cellulose ester, sulfonated polysulfone, sulfonated polyethersulfone, polyolefin, polyvinyl alcohol, polymethyl methacrylate, and polytetrafluoroethylene.
限外濾過膜の濾過方式は、デッドエンド濾過、クロスフロー濾過であってよいが、膜ファウリング抑制の観点から、クロスフロー濾過であることが好ましい。 The filtration method of the ultrafiltration membrane may be dead-end filtration or cross-flow filtration, but cross-flow filtration is preferred from the viewpoint of suppressing membrane fouling.
限外濾過膜の膜形態としては、平膜型、スパイラル型、チューブラー型、中空糸型等、適宜の形態のものが使用できる。より具体的には、ＧＥ Ｐｏｗｅｒ＆ＷａｔｅｒのＧＥシリーズ、ＧＨシリーズ、ＧＫシリーズ、ＤＥＳＡＬ社のＧ－５タイプ、Ｇ－１０タイプ、Ｇ－２０タイプ、Ｇ－５０タイプ、ＰＷタイプ、ＨＷＳＵＦタイプ、ＫＯＣＨ社のＨＦＭ－１８０、ＨＦＭ－１８３、ＨＦＭ－２５１、ＨＦＭ－３００、ＨＦＫ－１３１、ＨＦＫ－３２８、ＭＰＴ－Ｕ２０、ＭＰＳ－Ｕ２０Ｐ、ＭＰＳ－Ｕ２０Ｓ、Ｓｙｎｄｅｒ社のＳＰＥ１、ＳＰＥ３、ＳＰＥ５、ＳＰＥ１０、ＳＰＥ３０、ＳＰＶ５、ＳＰＶ５０、ＳＯＷ３０、旭化成株式会社製のマイクローザ（登録商標）ＵＦシリーズの分画分子量３，０００から１０，０００に相当するもの、日東電工株式会社製のＮＴＲ７４１０、ＮＴＲ７４５０等が挙げられる。 The ultrafiltration membrane may be of any suitable type, such as flat membrane, spiral, tubular, hollow fiber, etc. More specifically, examples include the GE series, GH series, and GK series from GE Power & Water, the G-5 type, G-10 type, G-20 type, G-50 type, PW type, and HWSUF type from DESAL, the HFM-180, HFM-183, HFM-251, HFM-300, HFK-131, HFK-328, MPT-U20, MPS-U20P, and MPS-U20S from KOCH, the SPE1, SPE3, SPE5, SPE10, SPE30, SPV5, SPV50, and SOW30 from Synder, the Microza (registered trademark) UF series from Asahi Kasei Corporation that has a molecular weight cutoff of 3,000 to 10,000, and the NTR7410 and NTR7450 from Nitto Denko Corporation.
バガスの分解抽出物は、他の実施形態において、上述した分解処理液を、固定担体を充填したカラムに通液することより得られる画分であってもよい。分解処理液をカラムに通液することにより、分解処理液中の抗糖化活性を有する成分（有効成分）が固定担体に吸着され、糖類及び無機塩類の大部分がそのまま流出する。 In another embodiment, the decomposition extract of bagasse may be a fraction obtained by passing the above-mentioned decomposition treatment liquid through a column packed with a fixed carrier. By passing the decomposition treatment liquid through the column, the components having anti-glycation activity (active components) in the decomposition treatment liquid are adsorbed onto the fixed carrier, and most of the sugars and inorganic salts flow out as they are.
上述した分解処理液は、直接又は水で任意の濃度に調整して、カラムに通液することができる。分解処理液においては、カラムの通液前にｐＨを調整してもよい。吸着率を向上させる観点から、分解処理液は、ｐＨ６以下に調整されていることが好ましい。分解処理液のｐＨは、４．５を超え６以下であってもよい。 The above-mentioned decomposition treatment liquid can be passed through the column directly or after adjusting the concentration with water to any desired concentration. The pH of the decomposition treatment liquid may be adjusted before passing through the column. From the viewpoint of improving the adsorption rate, it is preferable that the decomposition treatment liquid is adjusted to a pH of 6 or less. The pH of the decomposition treatment liquid may be more than 4.5 and 6 or less.
固定担体は、好ましくは、合成吸着剤又はイオン交換樹脂のいずれかである。 The fixed support is preferably either a synthetic adsorbent or an ion exchange resin.
合成吸着剤は、好ましくは合成多孔質吸着剤である。合成吸着剤（合成多孔質吸着剤）としては、好ましくは有機系樹脂が用いられる。有機系樹脂は、好ましくは、芳香族系樹脂、アクリル酸系メタクリル樹脂、又はアクリロニトリル脂肪族系樹脂である。 The synthetic adsorbent is preferably a synthetic porous adsorbent. As the synthetic adsorbent (synthetic porous adsorbent), an organic resin is preferably used. The organic resin is preferably an aromatic resin, an acrylic acid-based methacrylic resin, or an acrylonitrile aliphatic resin.
芳香族系樹脂としては、例えば、スチレン－ジビニルベンゼン系樹脂が挙げられる。芳香族系樹脂としては、疎水性置換基を有する芳香族系樹脂、無置換基型の芳香族系樹脂、無置換基型に特殊処理をした芳香族系樹脂等の多孔質性樹脂も挙げられ、このうち、無置換基型の芳香族系樹脂又は無置換基型に特殊処理をした芳香族系樹脂が好ましい。 Examples of aromatic resins include styrene-divinylbenzene resins. Examples of aromatic resins include porous resins such as aromatic resins with hydrophobic substituents, unsubstituted aromatic resins, and aromatic resins that have been specially treated to be unsubstituted. Of these, unsubstituted aromatic resins and aromatic resins that have been specially treated to be unsubstituted are preferred.
合成吸着剤で市販のものとしては、ダイヤイオン（商標）ＨＰ－１０、ＨＰ－２０、ＨＰ－２１、ＨＰ－３０、ＨＰ－４０、ＨＰ－５０（以上、無置換基型の芳香族系樹脂、いずれも商品名、三菱ケミカル株式会社製）；ＳＰ－８２５、ＳＰ－８００、ＳＰ－８５０、ＳＰ－８７５、ＳＰ－７０、ＳＰ－７００（以上、無置換基型に特殊処理を施した芳香族系樹脂、いずれも商品名、三菱ケミカル株式会社製）；ＳＰ－９００（芳香族系樹脂、商品名、三菱ケミカル株式会社製）；アンバーライト（商標）ＸＡＤ－２、ＸＡＤ－４、ＸＡＤ－１６、ＸＡＤ－２０００（以上、芳香族系樹脂、いずれも商品名、株式会社オルガノ製）；ダイヤイオン（商標）ＳＰ－２０５、ＳＰ－２０６、ＳＰ－２０７（以上、疎水性置換基を有する芳香族系樹脂、いずれも商品名、三菱ケミカル株式会社製）；ＨＰ－２ＭＧ、ＥＸ－００２１（以上、疎水性置換基を有する芳香族系樹脂、いずれも商品名、三菱ケミカル株式会社製）；アンバーライト（商標）ＸＡＤ－７、ＸＡＤ－８（以上、アクリル酸エステル樹脂、いずれも商品名、株式会社オルガノ製）；ダイヤイオン（商標）ＨＰ１ＭＧ、ＨＰ２ＭＧ（以上、アクリル酸メタクリル樹脂、いずれも商品名、三菱ケミカル株式会社製）；セファデックス（商標）ＬＨ２０、ＬＨ６０（以上、架橋デキストランの誘導体、いずれも商品名、ファルマシア バイオテク株式会社製）等が挙げられる。中でも、無置換基型の芳香族系樹脂（例えば、ＨＰ－２０）又は無置換基型に特殊処理を施した芳香族系樹脂（例えば、ＳＰ－８５０）が好ましい。 Synthetic adsorbents that are commercially available include Diaion (trademark) HP-10, HP-20, HP-21, HP-30, HP-40, HP-50 (all unsubstituted aromatic resins, all trade names, manufactured by Mitsubishi Chemical Corporation); SP-825, SP-800, SP-850, SP-875, SP-70, SP-700 (all unsubstituted aromatic resins that have been specially treated, all trade names, manufactured by Mitsubishi Chemical Corporation); SP-900 (aromatic resin, trade name, manufactured by Mitsubishi Chemical Corporation); Amberlite (trademark) XAD-2, XAD-4, XAD-16, XAD-2000 (aromatic resins, all trade names, manufactured by Organo Corporation); Diaion Examples of such resins include POLY(TM) SP-205, SP-206, and SP-207 (aromatic resins having hydrophobic substituents, all trade names, manufactured by Mitsubishi Chemical Corporation); HP-2MG and EX-0021 (aromatic resins having hydrophobic substituents, all trade names, manufactured by Mitsubishi Chemical Corporation); Amberlite(TM) XAD-7 and XAD-8 (acrylic ester resins, all trade names, manufactured by Organo Corporation); Diaion(TM) HP1MG and HP2MG (methacrylic acrylate resins, all trade names, manufactured by Mitsubishi Chemical Corporation); Sephadex(TM) LH20 and LH60 (crosslinked dextran derivatives, all trade names, manufactured by Pharmacia Biotech Co., Ltd.). Among these, aromatic resins without substituents (e.g., HP-20) or aromatic resins that have been specially treated with an unsubstituted type (e.g., SP-850) are preferred.
カラムに充填する合成吸着剤の量は、カラムの大きさ、合成吸着剤の種類等によって適宜決定することができる。 The amount of synthetic adsorbent to be packed into the column can be determined appropriately depending on the size of the column, the type of synthetic adsorbent, etc.
固定担体として合成吸着剤を用いる場合、分解処理液を通液するときの通液速度は、カラムの大きさ、溶出溶媒の種類、合成吸着剤の種類等によって適宜変更が可能であるが、好ましくは、ＳＶ＝１～３０時間－１である。なお、ＳＶ（Ｓｐａｃｅ Ｖｅｌｏｃｉｔｙ、空間速度）は、１時間当たり樹脂容量の何倍量の液体を通液するかという単位である。
When a synthetic adsorbent is used as the fixed carrier, the flow rate of the decomposition treatment liquid can be appropriately changed depending on the size of the column, the type of elution solvent, the type of synthetic adsorbent, etc., but is preferably SV = 1 to 30
合成吸着剤に吸着された吸着成分（有効成分）は、溶媒（溶出溶媒）により溶出させることができる。吸着成分をより効率よく回収する観点から、吸着成分を溶出させる前に、カラムに残留する糖類及び無機塩類を水洗により洗い流すことが好ましい。この場合、溶出させた成分をバガスの分解抽出物とすることができる。 The adsorbed components (active ingredients) adsorbed to the synthetic adsorbent can be eluted with a solvent (elution solvent). From the viewpoint of recovering the adsorbed components more efficiently, it is preferable to wash away the sugars and inorganic salts remaining in the column with water before eluting the adsorbed components. In this case, the eluted components can be used as a decomposition extract of bagasse.
固定担体として合成吸着剤を用いる場合、溶出溶媒は、水、メタノール、エタノール及びこれらの混合物からなる群より選ばれる少なくとも１種であってよい。溶出溶媒は、アルコール及び水の混合溶媒が好ましく、エタノール及び水の混合溶媒がより好ましく、吸着成分が室温においてより効率よく溶出可能となる観点から、体積比が５０／５０～６０／４０（エタノール／水）であるエタノール及び水の混合溶媒が更に好ましい。 When a synthetic adsorbent is used as the fixed carrier, the elution solvent may be at least one selected from the group consisting of water, methanol, ethanol, and mixtures thereof. The elution solvent is preferably a mixed solvent of alcohol and water, more preferably a mixed solvent of ethanol and water, and even more preferably a mixed solvent of ethanol and water with a volume ratio of 50/50 to 60/40 (ethanol/water) from the viewpoint of enabling the adsorbed components to be eluted more efficiently at room temperature.
固定担体として合成吸着剤を用いる場合、溶出する際のカラムの温度（カラム温度）は室温であってよいが、室温よりもカラム温度を高温にすることにより、エタノール及び水の混合溶媒においてエタノールの混合割合を減らすことができ、吸着成分をより効率的に溶出させることができる。温度は、好ましくは２０～６０℃であり、より好ましくは４０～６０℃である。カラム内は常圧条件下であっても、加圧条件下であってもよい。 When a synthetic adsorbent is used as the fixed carrier, the temperature of the column during elution (column temperature) may be room temperature, but by setting the column temperature higher than room temperature, the mixing ratio of ethanol in the mixed solvent of ethanol and water can be reduced, and the adsorbed components can be eluted more efficiently. The temperature is preferably 20 to 60°C, and more preferably 40 to 60°C. The inside of the column may be under normal pressure or under pressurized conditions.
固定担体として合成吸着剤を用いる場合、溶出速度は、カラムの大きさ、溶出溶媒の種類、合成吸着剤の種類等によって適宜設定することが可能であるが、好ましくは、ＳＶ＝０．１～１０時間－１である。 When a synthetic adsorbent is used as the fixed carrier, the elution rate can be appropriately set depending on the size of the column, the type of elution solvent, the type of synthetic adsorbent, etc., but is preferably SV=0.1 to 10 h -1 .
イオン交換樹脂は、樹脂の形態に基づいて、ゲル型樹脂と、ポーラス型、マイクロポーラス型又はハイポーラス型等の多孔性樹脂とに分類されるが、特に制限はない。イオン交換樹脂は、好ましくは陰イオン交換樹脂である。陰イオン交換樹脂としては、強塩基性陰イオン交換樹脂又は弱塩基性陰イオン交換樹脂が用いられてよい。アルカリ処理液を原料として使用する場合、好ましくは、強塩基性陰イオン交換樹脂が用いられるが、その他の処理による分解処理液を原料とする場合は特に制限はない。 Ion exchange resins are classified into gel-type resins and porous resins such as porous, microporous, or highly porous resins based on the form of the resin, but there are no particular limitations. The ion exchange resin is preferably an anion exchange resin. As the anion exchange resin, a strong basic anion exchange resin or a weak basic anion exchange resin may be used. When an alkaline processing liquid is used as a raw material, a strong basic anion exchange resin is preferably used, but there are no particular limitations when a decomposition processing liquid from other processes is used as a raw material.
市販の強塩基性陰イオン交換樹脂としては、ダイヤイオン（商標）ＰＡ３０６、ＰＡ３０８、ＰＡ３１２、ＰＡ３１６、ＰＡ３１８Ｌ、ＨＰＡ２５、ＳＡ１０Ａ、ＳＡ１２Ａ、ＳＡ１１Ａ、ＳＡ２０Ａ、ＵＢＡ１２０（以上、三菱ケミカル株式会社製）、アンバーライト（商標）ＩＲＡ４００Ｊ、ＩＲＡ４０２Ｂｌ、ＩＲＡ４０４Ｊ、ＩＲＡ９００Ｊ、ＩＲＡ９０４、ＩＲＡ４５８ＲＦ、ＩＲＡ９５８、ＩＲＡ４１０Ｊ、ＩＲＡ４１１、ＩＲＡ９１０ＣＴ（以上、オルガノ株式会社製）、ダウエックス（商標）マラソンＡ、マラソンＭＳＡ、ＭＯＮＯＳＰＨＥＲＥ５５０Ａ、マラソンＡ２（以上、ダウケミカル日本株式会社製）等が挙げられる。 Commercially available strong basic anion exchange resins include Diaion (trademark) PA306, PA308, PA312, PA316, PA318L, HPA25, SA10A, SA12A, SA11A, SA20A, and UBA120 (all manufactured by Mitsubishi Chemical Corporation), Amberlite (trademark) IRA400J, IRA402B1, IRA404J, IRA900J, IRA904, IRA458RF, IRA958, IRA410J, IRA411, and IRA910CT (all manufactured by Organo Corporation), and Dowex (trademark) Marathon A, Marathon MSA, MONOSPHERE550A, and Marathon A2 (all manufactured by Dow Chemical Japan).
市販の弱塩基性陰イオン交換樹脂としては、ダイヤイオン（商標）ＷＡ１０、ＷＡ２０、ＷＡ２１Ｊ、ＷＡ３０（以上、三菱ケミカル株式会社製）、アンバーライト（商標）ＩＲＡ４７８ＲＦ、ＩＲＡ６７、ＩＲＡ９６ＳＢ、ＩＲＡ９８、ＸＥ５８３（以上、オルガノ株式会社製）、ダウエックス（商標）マラソンＷＢＡ、６６、ＭＯＮＯＳＰＨＥＲＥ６６、ＭＯＮＯＳＰＨＥＲＥ７７（以上、ダウケミカル日本株式会社製）等が挙げられる。 Commercially available weakly basic anion exchange resins include Diaion (trademark) WA10, WA20, WA21J, and WA30 (all manufactured by Mitsubishi Chemical Corporation), Amberlite (trademark) IRA478RF, IRA67, IRA96SB, IRA98, and XE583 (all manufactured by Organo Corporation), and Dowex (trademark) Marathon WBA, 66, MONOSPHERE 66, and MONOSPHERE 77 (all manufactured by Dow Chemical Japan Ltd.).
カラムに充填するイオン交換樹脂の量は、カラムの大きさ、イオン交換樹脂の種類などによって適宜決定できるが、分解処理液の固形分に対して２～１０，０００倍湿潤体積量が好ましく、５～５００倍湿潤体積量がより好ましい。 The amount of ion exchange resin to be packed in the column can be determined appropriately depending on the size of the column, the type of ion exchange resin, etc., but a wet volume of 2 to 10,000 times the solid content of the decomposition treatment liquid is preferable, and a wet volume of 5 to 500 times is more preferable.
通液条件は、前処理液の種類、イオン交換樹脂の種類等により適宜設定することが可能である。好ましくは、流速はＳＶ＝０．３～３０時間－１であり、通液する液量はイオン交換樹脂の１００～３００％であり、カラム温度は４０～９０℃である。カラム内は常圧又は加圧された状態であってもよい。 The liquid passing conditions can be appropriately set depending on the type of pretreatment liquid, the type of ion exchange resin, etc. Preferably, the flow rate is SV=0.3 to 30 h -1 , the amount of liquid passing is 100 to 300% of the ion exchange resin, and the column temperature is 40 to 90° C. The inside of the column may be at normal pressure or under pressure.
固定担体としてイオン交換樹脂を用いる場合、バガスの分解抽出物は、イオン交換樹脂を充填したカラムに通液し、塩や酸、アルコール又はこれらの混合水溶液等の溶離液で溶出させることで得られる画分であってもよい。溶離液は脱気処理されていてもよい。 When an ion exchange resin is used as the fixed carrier, the decomposed extract of bagasse may be a fraction obtained by passing the extract through a column packed with an ion exchange resin and eluting it with an eluent such as a salt, an acid, an alcohol, or a mixed aqueous solution of these. The eluent may be degassed.
バガスの分解抽出物は、一実施形態においては、上述した分解処理液又は画分を濃縮した濃縮物であってもよい。濃縮方法は公知の方法であってよく、例えば、減圧下での溶媒留去、凍結乾燥等の方法であってよい。濃縮を行う場合、分解処理液又は画分を１５～３０倍に濃縮して、濃縮後の成分をバガスの分解抽出物とすることができる。 In one embodiment, the decomposition extract of bagasse may be a concentrate obtained by concentrating the above-mentioned decomposition treatment liquid or fraction. The concentration method may be a known method, such as distilling off the solvent under reduced pressure or freeze-drying. When concentration is performed, the decomposition treatment liquid or fraction may be concentrated 15 to 30 times, and the concentrated components may be used as the decomposition extract of bagasse.
バガスの分解抽出物は、例えば、次のようにして得ることができる。バガスに、固形物濃度が０．１～５０％となるように１質量％の水酸化ナトリウム水溶液を添加して１００℃で煮沸を行い、分解処理液（アルカリ処理液）を得る。分解処理液を分画分子量２５００～５０００のＵＦ膜にて限外濾過を行い、得られた濾過液を酸性に調整してから、無置換基型の芳香族系樹脂を充填したカラムに、カラム温度２０～６０℃にて通液する。その後、カラムに吸着された成分を、カラム温度２０～６０℃にて、体積比が５０／５０～６０／４０（エタノール／水）のエタノール及び水の混合溶媒（溶出溶媒）で溶出させ、エタノール及び水の混合溶媒での溶出開始時点から集めた溶出液の量が該芳香族系樹脂の４５倍湿潤体積量以内に溶出する画分を回収する。回収された画分（抗糖化活性を有する成分を含む画分）を集め、慣用の手段（減圧下での溶媒留去、凍結乾燥等）により濃縮して、バガスの分解抽出物を得ることができる。このようにして得られたバガスの分解抽出物は、固形分が３０質量％以上になるように濃縮した液状又は粉末状の抽出物として保存することができる。抽出物の保存は、当該抽出物が液状の場合、冷蔵で行うことが好ましい。 For example, the decomposition extract of bagasse can be obtained as follows. A 1% by mass aqueous solution of sodium hydroxide is added to the bagasse so that the solid concentration is 0.1 to 50%, and the bagasse is boiled at 100°C to obtain a decomposition treatment liquid (alkaline treatment liquid). The decomposition treatment liquid is ultrafiltered using a UF membrane with a molecular weight cutoff of 2500 to 5000, and the obtained filtrate is adjusted to be acidic and then passed through a column packed with an unsubstituted aromatic resin at a column temperature of 20 to 60°C. The components adsorbed in the column are then eluted with a mixed solvent of ethanol and water (elution solvent) with a volume ratio of 50/50 to 60/40 (ethanol/water) at a column temperature of 20 to 60°C, and the fraction eluted in an amount of elution liquid collected from the start of elution with the mixed solvent of ethanol and water within 45 times the wet volume of the aromatic resin is collected. The recovered fractions (fractions containing components with anti-glycation activity) can be collected and concentrated by conventional means (solvent distillation under reduced pressure, freeze-drying, etc.) to obtain a decomposition extract of bagasse. The decomposition extract of bagasse thus obtained can be stored as a liquid or powder extract concentrated to a solid content of 30% by mass or more. When the extract is in liquid form, it is preferably stored refrigerated.
バガスの分解抽出物は、他の例として、例えば、次のようにして得ることもできる。すなわち、バガスに固形物濃度が０．１～５０％となるように加水して１３０～２５０℃の水により、０．２～４．０Ｍｐａの圧力下で水熱処理を行い、濾過による固液分離で分解処理液（水熱処理液）を得る。得られた水熱処理液について、無置換基型に特殊処理を施した芳香族系樹脂を充填したカラムに、温度２０～６０℃にて通液した後、カラムに吸着された成分を、カラム温度２０～６０℃にて、体積比が５０／５０～６０／４０（エタノール／水）のエタノール及び水の混合溶媒（溶出溶媒）で溶出させ、エタノール及び水の混合溶媒での溶出開始時点から集めた溶出液の量が該芳香族系樹脂の５倍湿潤体積量以内に溶出する画分を回収する。回収された画分（抗糖化活性を有する成分を含む画分）を集め、慣用の手段（減圧下での溶媒留去、凍結乾燥等）により濃縮して、バガスの分解抽出物を得ることができる。このようにして得られたバガスの分解抽出物は、固形分が３０質量％以上になるように濃縮した液状又は粉末状の抽出物として保存することができる。抽出物の保存は、当該抽出物が液状の場合、冷蔵で行うことが好ましい。 As another example, the decomposition extract of bagasse can be obtained, for example, as follows. That is, water is added to bagasse so that the solid concentration is 0.1 to 50%, and the bagasse is hydrothermally treated with water at 130 to 250°C under a pressure of 0.2 to 4.0 MPa, and a decomposition treatment liquid (hydrothermally treated liquid) is obtained by solid-liquid separation by filtration. The obtained hydrothermally treated liquid is passed through a column packed with aromatic resin that has been specially treated to be unsubstituted at a temperature of 20 to 60°C, and the components adsorbed in the column are eluted with a mixed solvent of ethanol and water (elution solvent) with a volume ratio of 50/50 to 60/40 (ethanol/water) at a column temperature of 20 to 60°C, and the fraction eluted in an amount of elution liquid collected from the start of elution with the mixed solvent of ethanol and water within 5 times the wet volume of the aromatic resin is recovered. The recovered fractions (fractions containing components with anti-glycation activity) can be collected and concentrated by conventional means (solvent distillation under reduced pressure, freeze-drying, etc.) to obtain a decomposition extract of bagasse. The decomposition extract of bagasse thus obtained can be stored as a liquid or powder extract concentrated to a solid content of 30% by mass or more. When the extract is in liquid form, it is preferably stored refrigerated.
上述した各実施形態におけるバガスの分解抽出物は、液状又は粉末状であってよい。粉末状のバガスの分解抽出物は、例えば、液状のバガス分解抽出物を用いて、スプレードライ法、凍結乾燥法、流動層造粒法、又は賦形剤を用いた粉末化法等により製造することができる。 The bagasse decomposition extract in each of the above-mentioned embodiments may be in liquid or powder form. A powdered bagasse decomposition extract can be produced, for example, by using a liquid bagasse decomposition extract by a spray drying method, a freeze-drying method, a fluidized bed granulation method, or a powdering method using an excipient.
本実施形態の抗糖化剤は、バガスの分解抽出物以外に賦形剤などを含んでもよい。賦形剤として、抗糖化剤が動物用である場合、コーンスターチ、及び小麦デンプン等の各種デンプン、デキストリン、各種グルテン、小麦粉、ふすま、各種米糠、大豆かす、及び黄粉などの大豆類、グルコース又は乳糖などの糖類、植物・動物油等の油脂類、魚粉類、酵母類、ケイ素化合物類、各種リン酸塩、ケイソウ土又はベントナイトなどの鉱物類、飼料及び飼料添加物の製剤を製造する上で使用できる賦形剤が挙げられる。また、抗糖化剤がヒト用である場合、乳糖、デンプン及びマルトース等の糖類、その他ヒト用の製剤を製造する上で使用できる賦形剤が挙げられる。これらのうち、コーンスターチ、デキストリン及び脱脂米糠は、製剤用担体として用いることができ、これらと甘蔗由来の抽出物を混合することで、抗糖化剤を、例えば、粉末状、顆粒状、又は錠剤状の固形製剤とすることができる。 The anti-glycation agent of this embodiment may contain excipients in addition to the decomposition extract of bagasse. When the anti-glycation agent is for animals, the excipients include corn starch, various starches such as wheat starch, dextrin, various glutens, wheat flour, bran, various rice bran, soybeans such as soybean meal and yellow flour, sugars such as glucose or lactose, fats and oils such as vegetable and animal oils, fish meal, yeast, silicon compounds, various phosphates, minerals such as diatomaceous earth or bentonite, and excipients that can be used in producing formulations of feed and feed additives. When the anti-glycation agent is for humans, the excipients include sugars such as lactose, starch, and maltose, and other excipients that can be used in producing formulations for humans. Of these, corn starch, dextrin, and defatted rice bran can be used as formulation carriers, and by mixing these with an extract derived from sugar cane, the anti-glycation agent can be made into a solid formulation in the form of, for example, powder, granules, or tablets.
本実施形態の抗糖化剤は、ヒト又は動物に投与（経口投与又は非経口投与）することにより、抗糖化効果を奏するものであってよい。 The anti-glycation agent of this embodiment may exert an anti-glycation effect by being administered (orally or parenterally) to a human or animal.
抗糖化剤が非経口投与される場合、投与量としては、例えば、バガスの分解抽出物が体重１ｋｇ当たり１回に１００μｇ以上となるように投与されるのが好ましく、１５０μｇ以上となるように投与されるのがより好ましく、２００μｇ以上となるように投与されるのが更に好ましい。また、バガスの分解抽出物が体重１ｋｇ当たり１日に２００μｇ以上となるように投与されるのが好ましく、３００μｇ以上となるように投与されるのがより好ましく、４００μｇ以上となるように投与されるのが更に好ましい。また、バガスの分解抽出物が、体重１ｋｇ当たり１回に２０００ｍｇ以下となるように投与されるのが好ましく、１５００ｍｇ以下となるように投与されるのがより好ましく、１０００ｍｇ以下となるように投与されるのが更に好ましい。また、バガスの分解抽出物が体重１ｋｇ当たり１日に４０００ｍｇ以下となるように投与されるのが好ましく、３０００ｍｇ以下となるように投与されるのがより好ましく、２０００ｍｇ以下となるように投与されるのが更に好ましい。この範囲であれば、十分な血中濃度を達成することができ、抗糖化活性をよりよく発現することができる。 When the anti-glycation agent is administered parenterally, the dosage is, for example, preferably 100 μg or more of the decomposition extract of bagasse per kg of body weight, more preferably 150 μg or more, and even more preferably 200 μg or more. Also, preferably 200 μg or more of the decomposition extract of bagasse per kg of body weight per day, more preferably 300 μg or more, and even more preferably 400 μg or more. Also, preferably 2000 mg or less of the decomposition extract of bagasse per kg of body weight per day, more preferably 1500 mg or less, and even more preferably 1000 mg or less. In addition, the bagasse decomposition extract is preferably administered at 4000 mg or less per kg of body weight per day, more preferably at 3000 mg or less, and even more preferably at 2000 mg or less. Within this range, a sufficient blood concentration can be achieved and anti-glycation activity can be better expressed.
抗糖化剤が経口投与される場合、抗糖化剤の投与量は、バガスの分解抽出物の精製度、形態、対象とする動物の種類、健康状態、成長の度合い等により適宜決定し得る。特に投与の形態、例えば集中投与又は長期投与のいずれかであるかは、投与量を決定する上で重要な要因である。集中投与である場合、抗糖化剤の投与量は、バガスの分解抽出物の全量基準（固形分）で、体重１ｋｇ当たり１日に５０～３，０００ｍｇ、又は１００～２，０００ｍｇであってよい。また、集中投与の場合の投与期間は、１～２０日間であってよい。日常的に長期投与する場合、抗糖化剤の投与量は、バガスの分解抽出物の全量基準（固形分）で、体重１ｋｇ当たり１日に１～５００ｍｇ又は、１～１００ｍｇであってよい。長期投与の場合の投与期間は、例えば、数週間から数ヶ月間（例えば、２０～１８０日間）であってよい。この範囲であれば、十分な血中濃度を達成することができ、抗糖化活性をよりよく発現することができる。 When the anti-glycation agent is orally administered, the dosage of the anti-glycation agent may be appropriately determined depending on the degree of purification and form of the decomposition extract of bagasse, the type of the target animal, its health condition, the degree of growth, etc. In particular, the form of administration, for example, whether it is intensive administration or long-term administration, is an important factor in determining the dosage. When it is intensive administration, the dosage of the anti-glycation agent may be 50 to 3,000 mg or 100 to 2,000 mg per kg of body weight per day based on the total amount (solid content) of the decomposition extract of bagasse. In addition, the administration period in the case of intensive administration may be 1 to 20 days. When it is administered on a daily basis for a long period of time, the dosage of the anti-glycation agent may be 1 to 500 mg or 1 to 100 mg per kg of body weight per day based on the total amount (solid content) of the decomposition extract of bagasse. In the case of long-term administration, the administration period may be, for example, several weeks to several months (for example, 20 to 180 days). Within this range, sufficient blood concentrations can be achieved and anti-glycation activity can be better expressed.
本実施形態の抗糖化剤は、医薬品、医薬部外品、飲食品（食品組成物）、飼料、飼料添加物等の製品の成分として使用することができる。飲食品(飲料及び食品)としては、例えば、健康食品、機能性表示食品、特別用途食品、栄養補助食品、サプリメント又は特定保健用食品等が挙げられる。また、上記抗糖化剤は、調味料（醤油、味噌等）、菓子類等の食品、又は水、清涼飲料水、果汁飲料、アルコール飲料等の飲料における成分として使用することもできる。 The anti-glycation agent of this embodiment can be used as an ingredient in products such as medicines, quasi-drugs, food and beverages (food compositions), feed, and feed additives. Examples of food and beverages (drinks and foods) include health foods, functional foods, special purpose foods, nutritional supplements, supplements, and foods for specified health uses. The anti-glycation agent can also be used as an ingredient in foods such as seasonings (soy sauce, miso, etc.), confectioneries, and beverages such as water, soft drinks, fruit juice drinks, and alcoholic beverages.
飼料としては、ドッグフード、キャットフード等のコンパニオン・アニマル用飼料、家畜用飼料、家禽用飼料、養殖魚介類用飼料等が挙げられる。「飼料」には、動物が栄養目的で経口的に摂取するもの全てが含まれる。具体的には、養分含量の面から分類すると、粗飼料、濃厚飼料、無機物飼料、特殊飼料の全てを包含し、また公的規格の面から分類すると、配合飼料、混合飼料、単体飼料の全てを包含する。また、給餌方法の面から分類すると、直接給餌する飼料、他の飼料と混合して給餌する飼料、または飲料水に添加し栄養分を補給するための飼料の全てを包含する。 Examples of feed include companion animal feed such as dog food and cat food, livestock feed, poultry feed, and farmed fish and shellfish feed. "Feed" includes anything that animals take orally for nutritional purposes. Specifically, when classified in terms of nutrient content, it includes roughage, concentrated feed, inorganic feed, and special feed, and when classified in terms of official standards, it includes compound feed, mixed feed, and single feed. When classified in terms of feeding method, it includes all feed that is fed directly, mixed with other feed, or added to drinking water to supplement nutrients.
本実施形態の抗糖化剤からなる、又は抗糖化剤を含む上記製品（例えば、飲食品）は、抗糖化用であってよい。すなわち、本実施形態の抗糖化剤を含有する飲食品は、抗糖化用飲食品として好適に用いることができる。上記抗糖化剤を含有する、上記製品の形状は、固形又は液体のいずれの形状であってもよい。 The above-mentioned product (e.g., food and drink) consisting of or containing the anti-glycation agent of this embodiment may be for anti-glycation purposes. In other words, food and drink containing the anti-glycation agent of this embodiment can be suitably used as anti-glycation food and drink. The product containing the anti-glycation agent may be in the form of either a solid or liquid.
上記製品に含まれる抗糖化剤の含有量は、上記製品の種類及び摂取方法に応じて、適宜決定してよい。抗糖化効果をより一層有効に発揮する観点から、上記製品は、固形分として０．００１質量％以上となるような量のバガスの分解抽出物を含むことが好ましい。抗糖化剤を含有する、上記製品を集中的に摂取する場合、上記製品の摂取量（１日当たりの摂取量）は、バガスの分解抽出物の全量基準（固形分）で、好ましくは５０～３，０００ｍｇ／ｋｇ（体重）であり、より好ましくは１００～２，０００ｍｇ／ｋｇ（体重）である。日常的に長期摂取する場合、上記製品の摂取量（１日当たりの摂取量）は、バガスの分解抽出物の全量基準（固形分）で、好ましくは１～５００ｍｇ／ｋｇ（体重）である。 The content of the anti-glycation agent contained in the product may be appropriately determined depending on the type of the product and the method of ingestion. From the viewpoint of more effectively exerting the anti-glycation effect, it is preferable that the product contains a bagasse decomposition extract in an amount of 0.001% by mass or more in terms of solid content. When the product containing the anti-glycation agent is ingested intensively, the intake amount of the product (intake amount per day) is preferably 50 to 3,000 mg/kg (body weight) and more preferably 100 to 2,000 mg/kg (body weight) based on the total amount (solid content) of the bagasse decomposition extract. When ingested daily for a long period of time, the intake amount of the product (intake amount per day) is preferably 1 to 500 mg/kg (body weight) based on the total amount (solid content) of the bagasse decomposition extract.
以下、実施例に基づいて本発明をより具体的に説明する。ただし、本発明は、以下の実施例により限定されるものではない。バガスの分解抽出物は、以下、単に「抽出物」と表現することがある。 The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to the following examples. The decomposition extract of bagasse may be referred to simply as the "extract" below.
＜バガスの分解抽出物の製造＞
［製造例１］
サトウキビの搾りかすであるバガス１５ｋｇ（含水率５０質量％）及び０．５％（ｗ／ｗ）水酸化ナトリウム水溶液１００Ｌを混合し、１５０℃の条件でアルカリ処理を行った。アルカリ処理後の混合液を固形分と液分に分離して、液分を約１００Ｌ得た。分画分子量２５００のＵＦ膜（ＧＥウォーター＆プロセス・テクノロジー社、ＧＨ８０４０Ｆ３０）を用いて限外濾過を行い、濾過液８０Ｌを得た。合成吸着剤（三菱ケミカル株式会社製、ＨＰ－２０）１リットルを樹脂塔（内径８０ｍｍ、高さ４００ｍｍ）に充填し、これに上記の濾過液を、ｐＨを６に調整してから流速１０リットル／時間（ＳＶ＝１０．０（時間－１））で通液した。
<Production of bagasse decomposition extract>
[Production Example 1]
15 kg of bagasse (water content 50% by mass), which is sugarcane pomace, and 100 L of 0.5% (w/w) aqueous sodium hydroxide solution were mixed and subjected to an alkali treatment under the condition of 150 ° C. The mixture after the alkali treatment was separated into a solid portion and a liquid portion, and about 100 L of the liquid portion was obtained. Ultrafiltration was performed using a UF membrane (GE Water & Process Technology, GH8040F30) with a molecular weight cutoff of 2500, and 80 L of filtrate was obtained. 1 liter of synthetic adsorbent (manufactured by Mitsubishi Chemical Corporation, HP-20) was filled in a resin tower (
続いて、５リットルの精製水を、流速１０リットル／時間（ＳＶ＝１０．０（時間－１））で樹脂塔に通液して洗浄した。次に、溶出溶媒として６０％エタノール水溶液（エタノール／水＝６０／４０（体積／体積））２リットルを、流速２リットル／時間（ＳＶ＝２．０（時間－１））で樹脂塔に通液した。続けて、２リットルの精製水を流速２リットル／時間（ＳＶ＝２．０（時間－１））で樹脂塔に通液し、合成吸着剤に吸着した成分を溶出させた。樹脂塔から溶出した画分を、ロータリーエバポレーターにて約１０倍の濃度に減圧濃縮したのち、一晩凍結乾燥して、バガスの分解抽出物として、茶褐色の粉末２０ｇを得た。これを抽出物Ａとした。 Subsequently, 5 liters of purified water was passed through the resin tower at a flow rate of 10 liters/hour (SV=10.0 (hour - 1 )) to wash the resin tower. Next, 2 liters of 60% aqueous ethanol solution (ethanol/water=60/40 (volume/volume)) was passed through the resin tower at a flow rate of 2 liters/hour (SV=2.0 (hour-1)) as an elution solvent. Subsequently, 2 liters of purified water was passed through the resin tower at a flow rate of 2 liters/hour (SV=2.0 (hour -1 )) to elute the components adsorbed to the synthetic adsorbent. The fraction eluted from the resin tower was concentrated under reduced pressure to about 10 times the concentration using a rotary evaporator, and then freeze-dried overnight to obtain 20 g of a brownish-red powder as a decomposition extract of bagasse. This was designated as Extract A.
［製造例２］
サトウキビの搾りかすであるバガス３０ｋｇ（含水率５０質量％）を、２００℃の熱水１００Ｌで水熱処理を行った。前処理後の混合液を固形分と液分に分離して、液分を約８８Ｌ得た。分画分子量２５００のＵＦ膜（ＧＥウォーター＆プロセス・テクノロジー社、ＧＨ８０４０Ｆ３０）を用いて限外濾過を行い、濾過液７０Ｌを得た。合成吸着剤（三菱ケミカル株式会社製、ＳＰ－８５０）１リットルを樹脂塔（内径８０ｍｍ、高さ４００ｍｍ）に充填し、これに上記の濾過液のうち２５Ｌを、流速２０リットル／時間（ＳＶ＝２０．０（時間－１））で通液した。
[Production Example 2]
30 kg of bagasse (water content 50% by mass), which is sugarcane pomace, was hydrothermally treated with 100 L of hot water at 200 ° C. The pretreated mixed liquid was separated into a solid and a liquid, and about 88 L of the liquid was obtained. Ultrafiltration was performed using a UF membrane (GE Water & Process Technology, GH8040F30) with a molecular weight cutoff of 2500, and 70 L of filtrate was obtained. 1 L of synthetic adsorbent (Mitsubishi Chemical Corporation, SP-850) was packed in a resin tower (
続いて、３．３リットルの精製水を、流速２０リットル／時間（ＳＶ＝２０．０（時間－１））で樹脂塔に通液して洗浄した。次に、溶出溶媒として６０％エタノール水溶液（エタノール／水＝６０／４０（体積／体積））２リットルを、流速２リットル／時間（ＳＶ＝２．０（時間－１））で樹脂塔に通液した。続けて、２リットルの精製水を流速２リットル／時間（ＳＶ＝２．０（時間－１））で樹脂塔に通液し、合成吸着剤に吸着した成分を溶出させた。樹脂塔から溶出した画分を、ロータリーエバポレーターにて約１０倍の濃度に減圧濃縮したのち、一晩凍結乾燥して、バガスの分解抽出物として、茶褐色の粉末４０ｇを得た。これを抽出物Ｗとした。 Subsequently, 3.3 liters of purified water was passed through the resin tower at a flow rate of 20 liters/hour (SV=20.0 (hour - 1)) to wash the resin tower. Next, 2 liters of 60% aqueous ethanol solution (ethanol/water=60/40 (volume/volume)) was passed through the resin tower at a flow rate of 2 liters/hour (SV=2.0 (hour -1 )) as an elution solvent. Subsequently, 2 liters of purified water was passed through the resin tower at a flow rate of 2 liters/hour (SV=2.0 (hour -1 )) to elute the components adsorbed to the synthetic adsorbent. The fraction eluted from the resin tower was concentrated under reduced pressure to about 10 times the concentration using a rotary evaporator, and then freeze-dried overnight to obtain 40 g of a brown powder as a decomposition extract of bagasse. This was designated as Extract W.
＜抽出物Ａの抗糖化活性評価（試験例１～２）＞
試験例１：ヒト血清アルブミンモデルにおける抗糖化活性の評価
グルコース－ヒト血清アルブミン（ＨＳＡ）の反応により生成されるＡＧＥｓに対するバガスの分解抽出物（抽出物Ａ）の抗糖化活性（ＡＧＥｓ生成抑制作用）を調べた。
<Evaluation of Anti-Glycation Activity of Extract A (Test Examples 1 and 2)>
Test Example 1: Evaluation of anti-glycation activity in a human serum albumin model The anti-glycation activity (AGEs production inhibitory effect) of a bagasse decomposition extract (extract A) against AGEs produced by the reaction of glucose-human serum albumin (HSA) was investigated.
（サンプル調製）
バガスの分解抽出物である抽出物Ａを１００ｍｇ／ｍＬとなるように蒸留水で溶解し試験液原液を調製した。この試験原液を蒸留水で希釈して、０．０１～１００ｍｇ／ｍＬの溶液を調製した。これを試験用のサンプルとした。陽性対照として、糖化反応阻害剤であるアミノグアニジンの水溶液（濃度３．０ｍｇ／ｍＬ）を調製した。
Sample Preparation
Extract A, which is a decomposition extract of bagasse, was dissolved in distilled water to a concentration of 100 mg/mL to prepare a test stock solution. This test stock solution was diluted with distilled water to prepare a solution of 0.01 to 100 mg/mL. This was used as the test sample. As a positive control, an aqueous solution of aminoguanidine, a glycation reaction inhibitor (concentration 3.0 mg/mL), was prepared.
（糖化反応条件）
０．１ｍｏｌ／Ｌリン酸緩衝液（ｐＨ７．４）、８ｍｇ／ｍＬヒト血清アルブミン（ＨＳＡ、Ｓｉｇｍａ－Ａｌｄｒｉｃｈ社製）、及び０．２ｍｏｌ／Ｌグルコース水溶液からなる反応液中に、調製した各濃度のサンプルを１／１０濃度（反応終濃度）になるように添加し、６０℃で４０時間インキュベーションした。陰性対照としてサンプルの代わりに蒸留水を添加したものを用いた。陽性対照として上述のアミノグアニジン水溶液を用いた。なお、陽性対照に対するブランクとしてグルコースの代わりに蒸留水を添加したものを用いた。
(Saccharification reaction conditions)
The prepared samples of each concentration were added to a reaction solution consisting of 0.1 mol/L phosphate buffer (pH 7.4), 8 mg/mL human serum albumin (HSA, Sigma-Aldrich), and 0.2 mol/L glucose aqueous solution to give a concentration of 1/10 (final reaction concentration), and incubated at 60°C for 40 hours. As a negative control, a solution to which distilled water was added instead of the sample was used. As a positive control, the above-mentioned aminoguanidine aqueous solution was used. As a blank for the positive control, a solution to which distilled water was added instead of glucose was used.
（抗糖化活性の測定）
糖化反応終了後、反応液に生成した蛍光性ＡＧＥｓをマイクロプレートリーダー（ＳｐｅｃｔｒａＭａｘ ｉ３、モレキュラーデバイス社）で測定した（励起波長３７０ｎｍ、蛍光波長４４０ｎｍ）。ＡＧＥｓの生成阻害率（以下、単に「阻害率」ともいう）は、糖化反応においてサンプルを添加した反応液の蛍光強度をＦ１とし、グルコース水溶液の代わりに蒸留水を添加してインキュベーションした反応液の蛍光強度をＦ２とし、バガスの分解抽出物又はアミノグアニジンを添加せずにインキュベーションした反応液の蛍光強度をＦ３とし、ブランクとして、バガスの分解抽出物又はアミノグアニジンを添加せずに、グルコース水溶液の代わりに蒸留水を添加してインキュベーションした反応液の蛍光強度をＦ４として、下記の式に従って算出した。
蛍光性ＡＧＥｓ阻害率（％）＝（１－（Ｆ１－Ｆ２）／（Ｆ３－Ｆ４））×１００
(Measurement of anti-glycation activity)
After the saccharification reaction was completed, the fluorescent AGEs produced in the reaction solution were measured using a microplate reader (SpectraMax i3, Molecular Devices) (excitation wavelength 370 nm, fluorescence wavelength 440 nm). The inhibition rate of AGEs production (hereinafter also simply referred to as "inhibition rate") was calculated according to the following formula, where F1 is the fluorescence intensity of the reaction solution to which the sample was added in the saccharification reaction, F2 is the fluorescence intensity of the reaction solution to which distilled water was added instead of the glucose aqueous solution and incubated, F3 is the fluorescence intensity of the reaction solution to which the bagasse decomposition extract or aminoguanidine was not added, and F4 is the fluorescence intensity of the blank reaction solution to which the bagasse decomposition extract or aminoguanidine was not added and distilled water was added instead of the glucose aqueous solution.
Fluorescent AGEs inhibition rate (%) = (1 - (F 1 - F 2 ) / (F 3 - F 4 )) x 100
バガスの分解抽出物（抽出物Ａ）の各反応終濃度（０．１ｍｇ／ｍＬ、０．３ｍｇ／ｍＬ又は１ｍｇ／ｍＬ）における蛍光性ＡＧＥｓ（ＨＳＡ）の阻害率を図１に示す。図１のとおり、抽出物Ａは、濃度依存的に阻害率が増加し、抗糖化活性（蛍光性ＡＧＥｓ（ＨＳＡ）生成抑制作用）を示した。陽性対照であるアミノグアニジンの０．３ｍｇ／ｍＬにおける蛍光性ＡＧＥｓ（ＨＳＡ）の阻害率は８１．２±１．４％であった。アミノグアニジンは、抗糖化活性（蛍光性ＡＧＥｓ（ＨＳＡ）生成抑制作用）を有することが確認された。抽出物Ａの各濃度におけるサンプルの阻害率から算出したＩＣ５０（５０％生成阻害濃度）は、０．１９ｍｇ／ｍＬで、ヒト血清アルブミンモデルにおいて、抽出物Ａは抗糖化活性を有していることが示された。 The inhibition rate of fluorescent AGEs (HSA) at each final reaction concentration (0.1 mg/mL, 0.3 mg/mL, or 1 mg/mL) of the decomposed extract of bagasse (Extract A) is shown in FIG. 1. As shown in FIG. 1, Extract A showed an increase in the inhibition rate in a concentration-dependent manner, indicating anti-glycation activity (inhibitory effect on the production of fluorescent AGEs (HSA)). The inhibition rate of fluorescent AGEs (HSA) at 0.3 mg/mL of aminoguanidine, the positive control, was 81.2±1.4%. It was confirmed that aminoguanidine has anti-glycation activity (inhibitory effect on the production of fluorescent AGEs (HSA)). The IC 50 (50% inhibition concentration) calculated from the inhibition rate of the samples at each concentration of Extract A was 0.19 mg/mL, indicating that Extract A has anti-glycation activity in the human serum albumin model.
試験例２：ＡＧＥｓ架橋切断試験（ＡＧＥｓ分解活性の評価）
次に、ＡＧＥｓ架橋切断試験により、バガスの分解抽出物（抽出物Ａ）のＡＧＥｓ分解活性を評価した。ＡＧＥｓ分解活性（ＡＧＥｓ架橋切断作用）は、公知の方法（例えば、Ｇｌｙｃａｔｉｖｅ Ｓｔｒｅｓｓ Ｒｅｓｅａｒｃｈ ２０１５年，２巻（２号），ｐｐ．５８－６６）である、αジケトン構造を有する１－フェニルー１，２－プロパンジオン（ｌ－ｐｈｅｎｙｌ－１，２－ｐｒｏｐａｎｅｄｉｏｎｅ：ＰＰＤ）をモデル基質とした反応系を使用した方法で評価した。
Test Example 2: AGEs cross-link cleavage test (evaluation of AGEs decomposition activity)
Next, the AGEs decomposition activity of the bagasse decomposition extract (extract A) was evaluated by an AGEs cross-link cleavage test. The AGEs decomposition activity (AGEs cross-link cleavage activity) was evaluated by a known method (e.g., Glycative Stress Research 2015, Vol. 2 (No. 2), pp. 58-66) using a reaction system with 1-phenyl-1,2-propanedione (PPD) having an α-diketone structure as a model substrate.
（サンプル調製）
バガスの分解抽出物である抽出物Ａを２０ｍｇ／ｍＬとなるように蒸留水で溶解し、試験用のサンプルを調製した。
Sample Preparation
Extract A, which is a decomposed extract of bagasse, was dissolved in distilled water to a concentration of 20 mg/mL to prepare a test sample.
（架橋切断反応条件）
０．１６ｍｏｌ／Ｌのリン酸緩衝液（ｐＨ７．４）、２ｍｍｏｌ／ｍＬのＰＰＤの組成の反応液中に、上記で調製したサンプルを１／２濃度（１０ｍｇ／ｍＬ）になるように添加し、３７℃で８時間インキュベーションした。陰性対照としてはサンプルの代わりに蒸留水を添加したものを用いた。陽性対照としてＰＴＢ（Ｎ－ｐｈｅｎａｃｙｌｔｈｉａｚｏｌｉｕｍｂｒｏｍｉｄｅ）を用いた。反応液を２０℃、３０００×ｇで１０分間遠心分離し、上清を得た。上清中の安息香酸量を逆相ＨＰＬＣで分析した。反応液中の安息香酸量は、別途測定したサンプル中の安息香酸量を差し引いて求めた。１ｍｏｌのＰＰＤは１ｍｏｌの安息香酸を生成することから、以下の式で架橋切断率を算出した。
架橋切断率（％）＝｛（Ａ－Ｂ）／Ｃ｝×１００
Ａ：反応液中の安息香酸量
Ｂ：サンプル中の安息香酸量
Ｃ：反応に供したＰＰＤ量（基質量）
(Cross-linking cleavage reaction conditions)
The sample prepared above was added to a reaction solution with a composition of 0.16 mol/L phosphate buffer (pH 7.4) and 2 mmol/mL PPD to a concentration of 1/2 (10 mg/mL), and incubated at 37°C for 8 hours. As a negative control, a solution to which distilled water was added instead of the sample was used. As a positive control, PTB (N-phenacylthiazolium bromide) was used. The reaction solution was centrifuged at 20°C and 3000 x g for 10 minutes to obtain a supernatant. The amount of benzoic acid in the supernatant was analyzed by reverse phase HPLC. The amount of benzoic acid in the reaction solution was calculated by subtracting the amount of benzoic acid in a sample measured separately. Since 1 mol of PPD produces 1 mol of benzoic acid, the crosslink cleavage rate was calculated by the following formula.
Crosslink cleavage rate (%) = {(A - B) / C} x 100
A: Amount of benzoic acid in the reaction solution B: Amount of benzoic acid in the sample C: Amount of PPD (substrate amount) used in the reaction
（架橋切断試験結果）
サンプル及びＰＴＢ溶液（５ｍｍｏｌ／Ｌ）における架橋切断率と、ＰＴＢ（５ｍｍｏｌ／Ｌ）を１００％としたときのサンプルにおける架橋切断率の値（切断率相対値）を求めたところ、サンプルの架橋切断率は８．５０、ＰＴＢの架橋切断率は２０．１であり、サンプルの切断率相対値は４２．２９％であった。よって、抽出物ＡがＡＧＥｓの分解活性を有していることが示された。
(Cross-linking breakage test results)
The crosslink cleavage rates of the sample and PTB solution (5 mmol/L), and the crosslink cleavage rate of the sample when PTB (5 mmol/L) was taken as 100% (relative cleavage rate) were calculated, and the crosslink cleavage rate of the sample was 8.50, the crosslink cleavage rate of PTB was 20.1, and the relative cleavage rate of the sample was 42.29%, indicating that Extract A has AGEs decomposition activity.
＜抽出物Ｗの抗糖化活性評価（試験例３～４）＞
試験例３：ヒト血清アルブミンモデルにおける抗糖化活性の評価
バガスの分解抽出物として上述の抽出物Ｗを用いたこと、サンプルの調製において蒸留水ではなくジメチルスルホキシド（ＤＭＳＯ）を用いたこと以外は、試験例１と同様にして、抗糖化活性を評価した。陽性対照としては、アミノグアニジンの水溶液（最終濃度０．３ｍｇ／ｍＬ）を用いた。陽性対照であるアミノグアニジンの０．３ｍｇ／ｍＬにおける蛍光性ＡＧＥｓ（ＨＳＡ）の阻害率は７４．６±０．８％であった。測定結果を図２に示す。また、抽出物Ｗの各濃度におけるサンプルの阻害率から算出したＩＣ５０（５０％生成阻害濃度）は、０．１４ｍｇ／ｍＬで、抽出物Ｗは、抗糖化活性を有していることが示された。
<Evaluation of anti-glycation activity of extract W (Test Examples 3 and 4)>
Test Example 3: Evaluation of anti-glycation activity in a human serum albumin model The anti-glycation activity was evaluated in the same manner as in Test Example 1, except that the above-mentioned Extract W was used as the decomposition extract of bagasse, and dimethyl sulfoxide (DMSO) was used instead of distilled water in preparing the samples. An aqueous solution of aminoguanidine (final concentration 0.3 mg/mL) was used as a positive control. The inhibition rate of fluorescent AGEs (HSA) at 0.3 mg/mL of aminoguanidine, the positive control, was 74.6±0.8%. The measurement results are shown in FIG. 2. In addition, the IC 50 (50% inhibition concentration) calculated from the inhibition rate of the samples at each concentration of Extract W was 0.14 mg/mL, indicating that Extract W has anti-glycation activity.
試験例４：ＡＧＥｓ架橋切断試験（ＡＧＥｓ分解活性の評価）
（サンプル調製）
バガスの分解抽出物である抽出物Ｗを５０％ＤＭＳＯで溶解し、２０ｍｇ／ｍＬ溶液を調製した。この溶液を５０％ＤＭＳＯで段階希釈して、試験用のサンプルとした。陽性対照としては、１０ｍｍｏｌ／ＬのＰＴＢ（Ｎ－ｐｈｅｎａｃｙｌｔｈｉａｚｏｌｉｕｍｂｒｏｍｉｄｅ）溶液を用いた。
Test Example 4: AGEs cross-link cleavage test (evaluation of AGEs decomposition activity)
Sample Preparation
Extract W, a decomposition extract of bagasse, was dissolved in 50% DMSO to prepare a 20 mg/mL solution. This solution was serially diluted with 50% DMSO to prepare a test sample. A 10 mmol/L PTB (N-phenacylthiazolium bromide) solution was used as a positive control.
（架橋切断反応条件）
試験溶液又はＰＴＢ溶液（１０ｍｍｏｌ／Ｌ）と、１０ｍｍｏｌ／ＬのＰＰＤ溶液と、０．２ｍｏｌ／Ｌリン酸緩衝液（ｐＨ７．４）と、を５：１：４の割合で混合し、３７℃で８時間反応させた（ｎ＝３）。反応終了後、塩酸を加えて反応停止させた。その後、反応液を２０℃で３，０００×ｇで１０分間遠心分離し、上清中の安息香酸量を逆相ＨＰＬＣで分析した。反応液中の安息香酸量は、別途測定したサンプル中の安息香酸量を差し引いて求めた。１ｍｏｌのＰＰＤは１ｍｏｌの安息香酸を生成することから、以下の式で架橋切断率を算出した。架橋切断の相対値（切断率相対値）はＰＴＢの架橋切断率を１００としたときの、各濃度の架橋切断率の値（％）である。なお、測定装置としては、島津超高速液体クロマトグラフＮｅｘｅｒａシステム（株式会社島津製作所製）を用いた。
架橋切断率（％）＝｛（Ａ－Ｂ）／Ｃ｝×１００
Ａ：反応液中の安息香酸量
Ｂ：サンプル中の安息香酸量
Ｃ：反応に供したＰＰＤ量（基質量）
(Cross-linking cleavage reaction conditions)
The test solution or PTB solution (10 mmol/L), 10 mmol/L PPD solution, and 0.2 mol/L phosphate buffer (pH 7.4) were mixed in a ratio of 5:1:4 and reacted at 37°C for 8 hours (n=3). After the reaction was completed, hydrochloric acid was added to stop the reaction. Then, the reaction solution was centrifuged at 20°C and 3,000 x g for 10 minutes, and the amount of benzoic acid in the supernatant was analyzed by reverse phase HPLC. The amount of benzoic acid in the reaction solution was calculated by subtracting the amount of benzoic acid in a sample measured separately. Since 1 mol of PPD produces 1 mol of benzoic acid, the crosslink cleavage rate was calculated by the following formula. The relative value of crosslink cleavage (relative cleavage rate) is the value (%) of the crosslink cleavage rate of each concentration when the crosslink cleavage rate of PTB is set to 100. In addition, a Shimadzu ultra-high performance liquid chromatograph Nexera system (manufactured by Shimadzu Corporation) was used as the measuring device.
Crosslink cleavage rate (%) = {(A - B) / C} x 100
A: Amount of benzoic acid in the reaction solution B: Amount of benzoic acid in the sample C: Amount of PPD (substrate amount) used in the reaction
（架橋切断試験結果）
サンプル及びＰＴＢ溶液（５ｍｍｏｌ／Ｌ）における架橋切断率と、ＰＴＢ（５ｍｍｏｌ／Ｌ）を１００％としたときのサンプルにおける架橋切断率の値（切断率相対値）を求めたところ、サンプルの架橋切断率は１０．０７、ＰＴＢの架橋切断率は２２．４であり、サンプルの切断率相対値は４４．８７％であった。よって、抽出物ＷがＡＧＥｓの分解活性を有していることが示された。
(Cross-linking breakage test results)
The crosslink cleavage rates of the sample and PTB solution (5 mmol/L), and the crosslink cleavage rate of the sample when PTB (5 mmol/L) was taken as 100% (relative cleavage rate) were calculated, and the crosslink cleavage rate of the sample was 10.07, the crosslink cleavage rate of PTB was 22.4, and the relative cleavage rate of the sample was 44.87%, indicating that Extract W has the activity of decomposing AGEs.
Claims (8)
前記合成吸着剤は、無置換基型の芳香族系樹脂であり、
前記カラムの温度は２０～６０℃であり、
前記混合溶媒のエタノール及び水の体積比（エタノール／水）は５０／５０～６０／４０である、請求項２に記載の抗糖化剤。 The bagasse decomposition extract is a fraction obtained by passing the decomposition treatment liquid through a column packed with a synthetic adsorbent as a fixed carrier, and eluting the components adsorbed by the synthetic adsorbent with a mixed solvent of ethanol and water,
The synthetic adsorbent is a non-substituted aromatic resin,
The temperature of the column is 20 to 60° C.
The anti-glycation agent according to claim 2, wherein the volume ratio of ethanol and water (ethanol/water) in the mixed solvent is 50/50 to 60/40.
An anti-glycation food or drink comprising the anti-glycation agent according to any one of claims 1 to 7.
Priority Applications (7)
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| JP2018103252A JP7512008B2 (en) | 2018-05-30 | 2018-05-30 | Anti-glycation agents |
| CN201980035152.6A CN112203672A (en) | 2018-05-30 | 2019-05-30 | Obesity inhibitor, anti-dementia agent, deodorant, anti-aging agent, anti-glycation agent, anti-type I allergy agent, anti-hypertensive agent, flavor improving agent, muscle enhancer and bone metabolism improving agent |
| US17/058,756 US12036311B2 (en) | 2018-05-30 | 2019-05-30 | Anti-obesity agent, anti-dementia agent, deodorant, anti-aging agent, anti-glycation agent, anti-type I allergy agent, hypotensive agent, flavor improving agent, muscle enhancing agent, and bone metabolism improving agent |
| AU2019277620A AU2019277620B2 (en) | 2018-05-30 | 2019-05-30 | Anti-obesity agent, anti-dementia agent, deodorant, anti-aging agent, anti-glycation agent, anti-type i allergy agent, hypotensive agent, flavor improving agent, muscle enhancing agent, and bone metabolism improving agent |
| PCT/JP2019/021592 WO2019230907A1 (en) | 2018-05-30 | 2019-05-30 | Anti-obesity agent, anti-dementia agent, deodorant, anti-aging agent, anti-glycation agent, anti-type i allergy agent, hypotensive agent, flavor improving agent, muscle enhancing agent, and bone metabolism improving agent |
| US17/222,343 US12102709B2 (en) | 2018-05-30 | 2021-04-05 | Anti-obesity agent, anti-dementia agent, deodorant, anti-aging agent, anti-glycation agent, anti-type I allergy agent, hypotensive agent, flavor improving agent, muscle enhancing agent, and bone metabolism improving agent |
| US18/757,769 US20240358627A1 (en) | 2018-05-30 | 2024-06-28 | Anti-Obesity Agent, Anti-Dementia Agent, Deodorant, Anti-Aging Agent, Anti-Glycation Agent, Anti-Type I Allergy Agent, Hypotensive Agent, Flavor Improving Agent, Muscle Enhancing Agent, and Bone Metabolism Improving Agent |
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| WO2013100105A1 (en) | 2011-12-27 | 2013-07-04 | 森下仁丹株式会社 | Maillard reaction inhibitor |
Non-Patent Citations (3)
| Title |
|---|
| Ｉｚａｂｅｌａ Ｓａｄｏｗｓｋａ－Ｂａｒｔｏｓｚ，Ｇｒｚｅｇｏｒｚ Ｂａｒｔｏｓｚ，Ｐｒｅｖｅｎｔｉｏｎ ｏｆ Ｐｒｏｔｅｉｎ Ｇｌｙｃａｔｉｏｎ ｂｙ Ｎａｔｕｒａｌ Ｃｏｍｐｏｕｎｄｓ，Ｍｏｌｅｃｕｌｅｓ，２０１５年，ｖｏｌ．２０，ｐ．３３０９－３３３４，Ａｂｓｔｒａｃｔ |
| 三菱ケミカル，合成吸着剤，［ｏｎｌｉｎｅ］，２０１７年４月４日，ｈｔｔｐｓ：／／ｗｅｂ．ａｒｃｈｉｖｅ．ｏｒｇ／ｗｅｂ／２０１７０４０７２５４７／ｈｔｔｐ：／／ｗｗｗ．ｄｉａｉｏｎ．ｃｏｍ／ｐｒｏｄｕｃｔｓ／ｓｙｎｔｈｅｓｉｓ＿０２０１．ｈｔｍｌ＃０１ |
| 古田到真，伊藤傑，水雅美，河合俊和，国内製糖工場廃棄物からの有価物製造におけるＧＨＧ削減技術実証，精糖技術研究会誌，２０１７年，ｖｏｌ．６３，ｐ．７－１０，実験方法 |
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