JP2021138770A - Antiallergic agent, intestinal immunoenhancer, intestinal adhesiveness improver of lactic acid bacteria - Google Patents
Antiallergic agent, intestinal immunoenhancer, intestinal adhesiveness improver of lactic acid bacteria Download PDFInfo
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Abstract
Description
本発明は、抗アレルギー剤、腸管免疫増強剤及び乳酸菌の腸管接着性向上剤に関する。 The present invention relates to an antiallergic agent, an intestinal immunopotentiator, and an intestinal adhesiveness improving agent for lactic acid bacteria.
人の免疫システムは複数種のＴ細胞が司令塔の役割を果たしている。Ｔ細胞としては、主としてＩｇＡ抗体産生を促し細胞性免疫を活性化させるＴｈ１細胞と、Ｉ型アレルギーを引き起こすＩｇＥ抗体産生を促進させて液性免疫を活性化させるＴｈ２細胞とが知られている。このＴｈ１細胞とＴｈ２細胞とはお互いに抑制しあい、Ｔｈ１細胞よりＴｈ２細胞が優位に働くとアレルギー症状がおこりやすい。 In the human immune system, multiple types of T cells act as control towers. As T cells, Th1 cells that mainly promote IgA antibody production and activate cell-mediated immunity and Th2 cells that promote IgE antibody production that causes type I allergy and activate humoral immunity are known. The Th1 cells and Th2 cells suppress each other, and when Th2 cells act predominantly over Th1 cells, allergic symptoms are likely to occur.
腸管には体内の免疫細胞の７割が集中して存在しているとされ、体の免疫システムの主要な役割を果たしている。近年、乳酸菌が腸管免疫において重要な働きをすることが解明されてきている。例えば乳酸菌の菌体成分は、腸管においてマクロファージや樹状細胞のサイトカイン分泌を促進し、これによりＴｈ１細胞の働きを活発化することや、ＩｇＡ抗体産生を促すことが知られている。これによりＴｈ２細胞の働きが抑制されてＩｇＥ抗体産生が抑制され、アレルギーが改善されると考えられている。 It is said that 70% of the immune cells in the body are concentrated in the intestinal tract, and play a major role in the body's immune system. In recent years, it has been elucidated that lactic acid bacteria play an important role in intestinal immunity. For example, it is known that the bacterial cell component of lactic acid bacteria promotes cytokine secretion of macrophages and dendritic cells in the intestinal tract, thereby activating the function of Th1 cells and promoting IgA antibody production. It is believed that this suppresses the action of Th2 cells, suppresses IgE antibody production, and improves allergies.
乳酸菌（及びその菌体成分）の腸管への接着は、このような腸管免疫刺激作用やそれに伴う抗アレルギー作用を高めるために非常に重要と考えられている。乳酸菌の腸管接着性を向上させる経口剤を用い、乳酸菌の腸管接着を促すことができればアレルギーの予防や改善が期待できる。そのような経口剤には安全性が高いことや安価に入手できることが求められるが、その開発は進んでおらず、患者・消費者の多様なニーズに十分に答えられていない。 Adhesion of lactic acid bacteria (and their cell components) to the intestinal tract is considered to be very important for enhancing such intestinal immunostimulatory action and the associated antiallergic action. If an oral agent that improves the intestinal adhesion of lactic acid bacteria can be used to promote the intestinal adhesion of lactic acid bacteria, prevention and improvement of allergies can be expected. Such oral preparations are required to be highly safe and available at low cost, but their development has not progressed and they have not fully answered the diverse needs of patients and consumers.
一方青汁は、植物の茎及び／又は葉を乾燥粉末や搾汁粉末等の加工物を利用した製品であり、簡易に野菜成分を摂取できる健康食品として利用されている。青汁の素材として用いられる植物の茎及び／又は葉は安全に摂取でき安価な食品素材として知られており、これまで種々の作用が検討されているが（例えば特許文献１）、腸管免疫における乳酸菌の役割に着目した抗アレルギー作用の検討はなされてこなかった。 On the other hand, green juice is a product using processed products such as dried powder and squeezed powder of plant stems and / or leaves, and is used as a health food in which vegetable components can be easily ingested. The stems and / or leaves of plants used as a material for green juice are known as inexpensive food materials that can be safely ingested, and various actions have been studied so far (for example, Patent Document 1), but in intestinal immunity. The antiallergic action focusing on the role of lactic acid bacteria has not been investigated.
従って、本発明の課題は、新たな乳酸菌の腸管接着性向上剤、腸管免疫増強剤及び抗アレルギー剤を提供することにある。 Therefore, an object of the present invention is to provide a new lactic acid bacterium intestinal adhesiveness improver, intestinal immunopotentiator and antiallergic agent.
本発明者らは、乳酸菌の腸管接着性を高めることができる物質について鋭意検討した。その結果、安価且つ安全に入手可能な素材として、青汁素材である植物の茎及び／又は葉を用いることで乳酸菌の腸管接着性を高めることができることを見出した。 The present inventors have diligently studied substances capable of enhancing the intestinal adhesiveness of lactic acid bacteria. As a result, it was found that the intestinal adhesiveness of lactic acid bacteria can be enhanced by using the stem and / or leaf of a plant which is a green juice material as an inexpensive and safely available material.
本発明は前記知見に基づくものであり、青汁素材である植物の茎及び／又は葉を含有する抗アレルギー剤（但しインターロイキン４産生抑制による抗アレルギー剤を除く）を提供するものである。 The present invention is based on the above findings, and provides an antiallergic agent containing a stem and / or leaf of a plant which is a green juice material (excluding an antiallergic agent by suppressing the production of interleukin 4).
また本発明は、青汁素材である植物の茎及び／又は葉を含有する腸管免疫増強剤及び乳酸菌の腸管接着性向上剤を提供するものである。 The present invention also provides an intestinal immunopotentiator containing a plant stem and / or a leaf, which is a green juice material, and an intestinal adhesiveness improving agent for lactic acid bacteria.
本発明によれば、安全に摂取でき、安価に入手でき、且つ乳酸菌の腸管接着性向上作用に優れた抗アレルギー剤、腸管免疫増強剤及び乳酸菌の腸管接着性向上剤が提供される。 According to the present invention, there are provided an antiallergic agent, an intestinal immunopotentiator, and an intestinal adhesiveness improving agent for lactic acid bacteria, which can be safely ingested, can be obtained at low cost, and have an excellent effect of improving the intestinal adhesiveness of lactic acid bacteria.
以下、本発明をその好ましい実施形態に基づき説明する。本発明の剤は、青汁素材である植物の茎及び／又は葉（以下、単に「茎葉」とも記載する）を含有するものである。以下の説明は特に断らない限り、本発明の抗アレルギー剤、腸管免疫増強剤及び乳酸菌の腸管接着性向上剤のいずれにも当てはまる。茎葉は茎のみであってもよく葉のみであってもよく、その混合物であってもよいが、葉のみ、又は茎及び葉の混合物であることが好ましい。また本発明の剤は、青汁素材である植物として、茎葉に加えて、花や根などを含有していてもよく、茎葉以外の部位を非含有であってもよい。 Hereinafter, the present invention will be described based on the preferred embodiment thereof. The agent of the present invention contains a plant stem and / or leaf (hereinafter, also simply referred to as "stem and leaf") which is a green juice material. Unless otherwise specified, the following description applies to any of the antiallergic agent, the intestinal immunopotentiator, and the intestinal adhesiveness improving agent of lactic acid bacteria of the present invention. The stems and leaves may be stems only, leaves only, or a mixture thereof, but leaves alone or a mixture of stems and leaves is preferable. Further, the agent of the present invention may contain flowers, roots and the like in addition to the foliage as a plant which is a green juice material, and may not contain a part other than the foliage.
青汁素材である植物としては、（１）大麦、（２）甘藷、（３）ケール、（４）桑及び（５）ボタンボウフウが好ましく挙げられる。以下これらについて説明する。 Preferable examples of the plant as a green juice material include (1) barley, (2) sweet potato, (3) kale, (4) morus alba and (5) button siler. These will be described below.
（１）大麦（学名 Hordeum vulgare）としては、二条大麦、六条大麦、裸大麦などが挙げられ、これらは１種又は２種以上を組み合わせて用いることができる。大麦の茎葉は、成熟期前、すなわち、分けつ開始期から出穂開始前期に収穫されたものであることが好ましい。具体的には、品種の違いによっても異なるが、一般に、背丈が１０ｃｍ以上、好ましくは１０〜９０ｃｍ程度、特に好ましくは２０〜８０ｃｍ程度、とりわけ３０〜７０ｃｍ程度である大麦から、茎葉を収穫することが好ましいが、これらに限定されるものではない。本発明に用いられる大麦茎葉は、通常入手可能なものであれば特に限定されず、後述する加工方法により得られるものや、市販品を利用することができる。 (1) Examples of barley (scientific name: Hordeum vulgare) include two-row barley, six-row barley, and bare barley, and these can be used alone or in combination of two or more. The barley foliage is preferably harvested before the maturity stage, that is, from the start of division to the beginning of heading. Specifically, although it varies depending on the variety, generally, the foliage is harvested from barley having a height of 10 cm or more, preferably about 10 to 90 cm, particularly preferably about 20 to 80 cm, especially about 30 to 70 cm. Is preferable, but the present invention is not limited to these. The barley foliage used in the present invention is not particularly limited as long as it is usually available, and those obtained by the processing method described later or commercially available products can be used.
（２）甘藷（学名 Ipomoea batatas）としては、すいおう、ジョイホワイト、コガネセンガン、シロユタカ、サツマスターチ、アヤムラサキなどが挙げられ、これらは１種又は２種以上を組み合わせて用いることができる。甘藷の中では、ポリフェノール含有量が高いすいおうが好ましい。すいおうは、一度茎葉を収穫した後であっても、同じ茎の先端から甘藷の若茎葉が再生するという特徴があるため、生産性の点からも好適に用いられる。甘藷茎葉としては、甘藷の栽培時に、地面から外に出ている茎及び／又は葉を用いることが好ましい。好ましくは、地上から外へ、５ｃｍ以上、より好ましくは１０ｃｍ以上、更に好ましくは２０ｃｍ以上出て成長した甘藷茎葉が好ましい。また、甘藷の茎が地面から外に出ている位置から甘藷茎葉の先端までの長さは、好ましくは３００ｃｍ以下、より好ましくは２００ｃｍ以下、更に好ましくは１５０ｃｍ以下である。甘藷茎葉としては、甘藷茎葉の先端部分（「甘藷の若茎葉」）が好ましく、他の茎葉に比べて、黄味がかった緑色を保持している状態の甘藷の若茎葉が更に好ましい。甘藷の若茎葉としては、甘藷茎葉の先端から１００ｃｍ以内の部位の茎葉が好ましく用いられる。甘藷の若茎葉は、植物体自身がやわらかいため、加工が容易である。更に、甘藷の若茎葉は、乾燥粉末とした場合、舌触りがよく、様々な食品に利用しやすくなる。本発明に用いられる甘藷茎葉は、通常入手可能なものであれば特に限定されず、後述する加工方法により得られるものや、市販品を利用することができる。 (2) Examples of sweet potato (scientific name: Ipomoea batatas) include Suiou, Joy White, Koganesengan, Shiroyutaka, Satsumastarch, Ayamurasaki, and the like, and these can be used alone or in combination of two or more. Among sweet potatoes, sweet potatoes having a high polyphenol content are preferable. Suiou is preferably used from the viewpoint of productivity because it has a characteristic that young sweet potato leaves are regenerated from the tip of the same stem even after the stems and leaves are harvested once. As the sweet potato stalks and leaves, it is preferable to use stems and / or leaves that are exposed from the ground when cultivating sweet potatoes. Preferably, sweet potato foliage grown 5 cm or more, more preferably 10 cm or more, still more preferably 20 cm or more from the ground to the outside is preferable. The length from the position where the sweet potato stalk is outside the ground to the tip of the sweet potato foliage is preferably 300 cm or less, more preferably 200 cm or less, still more preferably 150 cm or less. As the sweet potato foliage, the tip portion of the sweet potato foliage (“sweet potato young foliage”) is preferable, and the sweet potato young foliage in a state of maintaining a yellowish green color is more preferable as compared with other foliage. As the young foliage of sweet potato, foliage within 100 cm from the tip of the foliage of sweet potato is preferably used. The young leaves of sweet potato are easy to process because the plant itself is soft. Furthermore, the young foliage of sweet potato, when made into a dry powder, has a good texture and is easy to use in various foods. The sweet potato foliage used in the present invention is not particularly limited as long as it is usually available, and those obtained by the processing method described later or commercially available products can be used.
（３）ケールはBrassica oleracea L.（アブラナ属の作物）である。ケールの具体例としては、キッチンケール、ツリーケール、ブッシュケール、マローケール、コラード、緑葉カンラン、ドリンクリーフ、ポルトガルケール、中国ケール、サウザンド・ヘッデッド・ケール、ジャージー・ケール等が挙げられ、これらは１種又は２種以上を組み合わせて用いることができる。本発明に用いられるケール茎葉は、通常入手可能なものであれば特に限定されず、後述する加工方法により得られるものや、市販品を利用することができる。 (3) Kale is Brassica oleracea L. (Crop of Brassica). Specific examples of kale include kitchen kale, tree kale, bush kale, mallow kale, corrado, green leaf kale, drink leaf, Portuguese kale, Chinese kale, thousand headed kale, jersey kale, etc. Alternatively, two or more types can be used in combination. The kale foliage used in the present invention is not particularly limited as long as it is usually available, and those obtained by the processing method described later or commercially available products can be used.
（４）桑はクワ科クワ属（学名Morus）の総称である。桑としては、カラヤマグワ、ヤ
マグワ、ログワ、シマグワ、チョウセンクワやこれらの交配種や交雑種などが挙げられる。これらは１種又は２種以上を組み合わせて用いることができる。本発明に用いられる桑の茎葉は、通常入手可能なものであれば特に限定されず、後述する加工方法により得られるものや、市販品を利用することができる。
(4) Morus alba is a general term for the genus Morus alba (scientific name: Morus). Examples of mulberry include morus alba, yamagwa, logwa, shimagwa, morus alba, and hybrids and hybrids thereof. These can be used alone or in combination of two or more. The mulberry foliage used in the present invention is not particularly limited as long as it is usually available, and those obtained by the processing method described later or commercially available products can be used.
（５）ボタンボウフウ（学名Ｐeucedanum japonicum）は、セリ科カワラボウフウ属の多年草である。別名として長命草とも呼ばれ、主に九州南部から沖縄に自生する。本発明に用いられるボタンボウフウの茎葉は、通常入手可能なものであれば特に限定されず、後述する加工方法により得られるものや、市販品を利用することができる。 (5) Peucedanum japonicum (scientific name: Peucedanum japonicum) is a perennial plant belonging to the genus Peucedanum terrestris in the Umbelliferae family. Also known as longevity grass, it grows naturally from southern Kyushu to Okinawa. The foliage of Siler used in the present invention is not particularly limited as long as it is usually available, and those obtained by the processing method described later or commercially available products can be used.
本発明では、青汁素材である植物の茎葉として、該茎葉から得られる各種の加工物を用いることができる。そのような加工物としては、例えば、茎葉を乾燥及び粉砕して得られる乾燥粉末（粉砕末と呼ばれる場合もある）、茎葉の細片化物及びその乾燥粉末、茎葉を搾汁して得られる搾汁液及びその乾燥粉末、茎葉を水、有機溶媒又はそれらの混合物で抽出することにより得られる抽出液、及びその乾燥粉末等が挙げられる。これらは、茎葉を発酵する過程を経て得られたもの（発酵物）であってもよく、発酵過程を経ずに得られたもの（非発酵物）であってもよい。 In the present invention, as the foliage of a plant which is a green juice material, various processed products obtained from the foliage can be used. Such processed products include, for example, dry powder obtained by drying and crushing foliage (sometimes called crushed powder), fragmented foliage and its dry powder, and squeezing obtained by squeezing foliage. Examples thereof include a juice and a dry powder thereof, an extract obtained by extracting foliage with water, an organic solvent or a mixture thereof, and a dry powder thereof. These may be those obtained through the process of fermenting the foliage (fermented product) or those obtained without undergoing the fermentation process (non-fermented product).
例えば、茎葉を乾燥粉末化する（粉砕末とする）には従来公知の方法を用いることができる。そのような方法としては、茎葉に対して、乾燥処理及び粉砕処理を組み合わせた方法を用いることができる。乾燥処理及び粉砕処理はいずれを先に行ってもよいが、乾燥処理を先に行うことが好ましい。乾燥粉末化は、この方法に、更に必要に応じブランチング処理、殺菌処理などの処理から選ばれる１種又は２種以上の処理を組み合わせてもよい。また、粉砕処理を行う回数は１回でも、２回以上の処理を組み合わせてもよいが、粗粉砕処理を行った後に、より細かく粉砕する微粉砕処理を組み合わせることが好ましい。 For example, a conventionally known method can be used to dry and powder the foliage (to be crushed powder). As such a method, a method in which a drying treatment and a crushing treatment are combined with respect to the foliage can be used. Either the drying treatment or the pulverization treatment may be performed first, but it is preferable to perform the drying treatment first. The dry powdering may be combined with this method, if necessary, with one or more treatments selected from treatments such as blanching treatment and sterilization treatment. Further, the number of times of the pulverization treatment may be one or two or more times, but it is preferable to combine the fine pulverization treatment of finer pulverization after the coarse pulverization treatment.
ブランチング処理とは、茎葉に由来する緑色を鮮やかに保つための処理であり、ブランチング処理の方法としては、熱水処理や蒸煮処理などが挙げられる。ブランチング処理における加熱温度は、好ましくは８０℃より高い温度、より好ましくは８５℃以上、更に好ましくは９０℃以上の温度とすることが好ましい。加熱温度は１００℃以下が好ましい。加熱処理における加熱時間は、好ましくは１０分以下、より好ましくは５分以下、更に好ましくは３分以下、特に好ましくは１０秒〜１分とする。また、ブランチング処理として熱水処理を行う場合、熱水中に炭酸マグネシウムなどの炭酸塩や炭酸水素ナトリウムなどの炭酸水素塩を溶解させておくことで、茎葉の緑色をより鮮やかにすることができるため、好ましい。この場合の熱水のｐＨとしては好ましくは５．４以上、より好ましくは５．６以上８．４以下、更に好ましくは５．６以上８．０以下である。また、蒸煮処理としては、常圧又は加圧下において、茎葉を水蒸気により蒸煮する処理と冷却する処理とを繰り返す間歇的蒸煮処理が好ましい。間歇的蒸煮処理において、水蒸気により蒸煮する処理は、好ましくは２０〜４０秒間、より好ましくは３０秒間行われる。蒸煮処理後の冷却処理は、直ちに行われることが好ましく、その方法は、特に制限しないが、冷水への浸漬、冷蔵、冷風による冷却、温風による気化冷却、温風と冷風を組み合わせた気化冷却などが用いられる。このうち温風と冷風を組み合わせた気化冷却が好ましい。このような冷却処理は、茎葉の品温が、好ましくは６０℃以下、より好ましくは５０℃以下、最も好ましくは４０℃以下となるように行われる。また、ビタミン、ミネラル類、葉緑素などの栄養成分に富んだ茎葉の粉末を製造するためには、間歇的蒸煮処理を２〜５回繰り返すことが好ましい。 The blanching treatment is a treatment for keeping the green color derived from the foliage vivid, and examples of the blanching treatment method include hot water treatment and steaming treatment. The heating temperature in the blanching treatment is preferably a temperature higher than 80 ° C., more preferably 85 ° C. or higher, still more preferably 90 ° C. or higher. The heating temperature is preferably 100 ° C. or lower. The heating time in the heat treatment is preferably 10 minutes or less, more preferably 5 minutes or less, still more preferably 3 minutes or less, and particularly preferably 10 seconds to 1 minute. In addition, when hot water treatment is performed as a branching treatment, the green color of the foliage can be made more vivid by dissolving carbonate such as magnesium carbonate and hydrogen carbonate such as sodium hydrogen carbonate in hot water. It is preferable because it can be done. The pH of the hot water in this case is preferably 5.4 or more, more preferably 5.6 or more and 8.4 or less, and further preferably 5.6 or more and 8.0 or less. Further, as the steaming treatment, an intermittent steaming treatment in which the treatment of steaming the foliage with steam and the treatment of cooling under normal pressure or pressure is preferable. In the intermittent steaming treatment, the treatment of steaming with steam is preferably carried out for 20 to 40 seconds, more preferably 30 seconds. The cooling treatment after the steaming treatment is preferably performed immediately, and the method is not particularly limited, but is immersed in cold water, refrigerated, cooled by cold air, vaporized cooling by hot air, vaporized cooling by combining hot air and cold air. Etc. are used. Of these, vaporization cooling that combines hot air and cold air is preferable. Such a cooling treatment is carried out so that the product temperature of the foliage is preferably 60 ° C. or lower, more preferably 50 ° C. or lower, and most preferably 40 ° C. or lower. Further, in order to produce a foliage powder rich in nutrients such as vitamins, minerals and chlorophyll, it is preferable to repeat the intermittent steaming treatment 2 to 5 times.
また、殺菌処理とは、通常、温度・圧力・電磁波・薬剤等を用いて物理的・化学的に微生物細胞を殺滅させる処理である。これらの方法の中でも、加熱殺菌処理は、茎葉の香味を良好にすることができるため好ましい処理方法である。加熱処理の温度は、１１０℃以上で行うことが好ましく、具体的な機器としては、高圧殺菌機、加熱殺菌機、加圧蒸気殺菌機などを用いることができる。例えば、加圧蒸気殺菌による加熱処理の場合、粗粉砕された甘藷茎葉は、例えば、０．５ｋｇ／ｃｍ2以上１０ｋｇ／ｃｍ2以下の加圧下、１１０℃以上２００℃以下の飽和水蒸気により、２秒以上１０秒以下の間、加熱殺菌処理されることが好ましい。これらの殺菌処理の後で、必要に応じて、飽和水蒸気による加熱時に含んだ水分を更に乾燥することもできる。 The sterilization treatment is usually a treatment of physically and chemically killing microbial cells using temperature, pressure, electromagnetic waves, chemicals, or the like. Among these methods, the heat sterilization treatment is a preferable treatment method because it can improve the flavor of the foliage. The temperature of the heat treatment is preferably 110 ° C. or higher, and as specific equipment, a high-pressure sterilizer, a heat sterilizer, a pressurized steam sterilizer, or the like can be used. For example, in the case of heat treatment by pressure steam sterilization, the coarsely crushed sweet potato foliage is, for example, under pressure of 0.5 kg / cm 2 or more and 10 kg / cm 2 or less, with saturated steam of 110 ° C. or more and 200 ° C. or less. It is preferable that the heat sterilization treatment is performed for a period of seconds or more and 10 seconds or less. After these sterilization treatments, if necessary, the water contained during heating with saturated steam can be further dried.
また、乾燥処理としては、乾燥後の茎葉の水分含量が１０％以下、特に５％以下となるように乾燥する処理であることが、風味が良く、色鮮やかな茎葉の乾燥粉末を得られるため、好ましい。この乾燥処理は、例えば、熱風乾燥、高圧蒸気乾燥、電磁波乾燥、凍結乾燥などの当業者に公知の任意の方法により行われ得る。加熱による乾燥は、加温により茎葉が変色しない温度及び時間で行われ得る。風味が良く、色鮮やかな茎葉の乾燥粉末を得られる点において、６０℃以上１５０℃以下、好ましくは７０℃以上１００℃以下で乾燥処理を行うことが好ましい。茎葉をそのまま乾燥する場合は、２段階で乾燥を行うことが好ましい。２段乾燥は、例えば、熱風乾燥機などを用いて行うことができる。２段階乾燥は、まず、水分含有量が２５質量％以下となるまで、６０℃以上８０℃以下の温度で一次乾燥する。次いで、一次乾燥した茎葉の水分含有量が５質量％以下となるまで、一次乾燥よりも高い温度、好ましくは７０℃以上９０℃以下で二次乾燥する。 Further, as the drying treatment, the treatment of drying the foliage so that the water content of the foliage after drying is 10% or less, particularly 5% or less is performed because a dry powder of the foliage having a good flavor and a colorful color can be obtained. ,preferable. This drying process can be performed by any method known to those skilled in the art, such as hot air drying, high pressure steam drying, electromagnetic wave drying, and freeze drying. Drying by heating can be performed at a temperature and time at which the foliage does not discolor due to heating. It is preferable to carry out the drying treatment at 60 ° C. or higher and 150 ° C. or lower, preferably 70 ° C. or higher and 100 ° C. or lower, from the viewpoint of obtaining a dry powder of foliage having a good flavor and vivid color. When the foliage is dried as it is, it is preferable to dry it in two steps. The two-stage drying can be performed using, for example, a hot air dryer or the like. In the two-step drying, first, the primary drying is performed at a temperature of 60 ° C. or higher and 80 ° C. or lower until the water content becomes 25% by mass or less. Then, the primary dried foliage is secondarily dried at a temperature higher than the primary drying, preferably 70 ° C. or higher and 90 ° C. or lower, until the water content of the foliage is 5% by mass or less.
また、粉砕処理としては、クラッシャー、ミル、ブレンダー、石臼などを用いて当業者が通常使用する任意の方法により粉砕する処理が挙げられる。粉砕された茎葉は必要に応じて篩にかけられる。 Further, examples of the crushing treatment include a treatment of crushing by an arbitrary method usually used by those skilled in the art using a crusher, a mill, a blender, a stone mill or the like. The crushed foliage is sieved as needed.
乾燥処理及び粉砕処理に追加してブランチング処理を行う場合、ブランチング処理は乾燥処理の前に行われることが好ましい。また乾燥処理及び粉砕処理に追加して殺菌処理を行う場合、殺菌処理は、乾燥処理の後か、粉砕処理の前又は後に行われることが好ましい。 When the blanching treatment is performed in addition to the drying treatment and the crushing treatment, the blanching treatment is preferably performed before the drying treatment. When the sterilization treatment is performed in addition to the drying treatment and the crushing treatment, the sterilizing treatment is preferably performed after the drying treatment or before or after the crushing treatment.
具体的な乾燥粉末化の方法としては、例えば、茎葉を切断した後、ブランチング処理を行い、次いで水分含量が１０質量％以下、好ましくは５質量％以下となるように乾燥し、その後粉砕する方法が挙げられる（特開２００４−０００２１０号公報を参照）。また例えば、茎葉を切断した後、ブランチング処理を行い、次いで揉捻し、その後、乾燥し、粉砕する方法（特開２００２−０６５２０４号公報を参照）も挙げられる。また例えば、茎葉を乾燥し、粗粉砕した後、１１０℃以上で加熱し、更に微粉砕する方法（特開２００３−０３３１５１号公報を参照）も挙げられる。粉末の粒径としては、５０質量％以上、特に７０質量％以上が２００メッシュを通過することが好ましい。 As a specific method of dry powdering, for example, after cutting the foliage, blanching treatment is performed, then the mixture is dried so that the water content is 10% by mass or less, preferably 5% by mass or less, and then pulverized. A method can be mentioned (see JP-A-2004-000210). Further, for example, a method in which the foliage is cut, then blanched, then kneaded, then dried and pulverized (see JP-A-2002-065204) can also be mentioned. Further, for example, a method in which the foliage is dried, roughly pulverized, heated at 110 ° C. or higher, and further pulverized (see Japanese Patent Application Laid-Open No. 2003-033151) can also be mentioned. As the particle size of the powder, it is preferable that 50% by mass or more, particularly 70% by mass or more, passes through the 200 mesh.
茎葉を細片化する方法としては、スライス、破砕、細断等、当業者が植物体を細片化する際に通常使用する方法を用いることができる。細片化の一例として、スラリー化してもよい。スラリー化は、茎葉をミキサー、ジューサー、ブレンダー、マスコロイダーなどにかけ、茎葉をどろどろした粥状（液体と固体の懸濁液）にすることにより行う。このようにスラリー化することにより、茎葉は、細片の８０質量％以上が好ましくは平均径１ｍｍ以下、より好ましくは０.５ｍｍ以下、一層好ましくは０.１ｍｍ以下、最も好ましくは０．０５ｍｍ以下となるように細片化され、流動性を有するようになる。 As a method for shredding the foliage, a method usually used by those skilled in the art for shredding plants, such as slicing, crushing, and shredding, can be used. As an example of fragmentation, it may be made into a slurry. Slurry is performed by subjecting the foliage to a mixer, juicer, blender, mascoroider, etc. to make the foliage into a thick porridge (a suspension of liquid and solid). By slurrying in this way, the foliage is preferably 80% by mass or more of the strips, preferably having an average diameter of 1 mm or less, more preferably 0.5 mm or less, still more preferably 0.1 mm or less, and most preferably 0.05 mm or less. It will be fragmented so that it will have fluidity.
茎葉を搾汁する方法としては、茎葉又はその細片化物を圧搾するか、又は、茎葉の細片化物を遠心又はろ過する方法を挙げることができる。代表的な例としては、ミキサー、ジューサー等の機械的破砕手段によって搾汁し、必要に応じて、篩別、濾過等の手段によって粗固形分を除去することにより搾汁液を得る方法が挙げられ、具体的には、特開平０８−２４５４０８号公報や特開平０９−０４７２５２号公報に記載の方法が挙げられる。
また、茎葉の抽出物を得る方法としては、茎葉又はその細片化物に、エタノール、水、含水エタノールなどの当業者が通常用いる抽出溶媒を加え、必要に応じて加温して抽出する方法を挙げることができる。抽出物は、必要に応じて濃縮してもよい。
Examples of the method for squeezing the foliage include squeezing the foliage or its fragment, or centrifuging or filtering the foliage fragment. A typical example is a method of obtaining a juice by squeezing the juice by a mechanical crushing means such as a mixer or a juicer and, if necessary, removing the crude solid content by a means such as sieving or filtering. Specifically, the methods described in JP-A-08-245408 and JP-A-09-047252 can be mentioned.
In addition, as a method for obtaining an extract of foliage, a method of adding an extraction solvent usually used by those skilled in the art such as ethanol, water, hydrous ethanol, etc. to the foliage or its fragment is added and heated as necessary for extraction. Can be mentioned. The extract may be concentrated if necessary.
茎葉の加工物のうち、特に、茎葉の粉砕物（粉砕末等）、又は、搾汁（搾汁末等）を用いることが、本発明の剤をより一層色が鮮やかで風味が良好なものとできる点や、食物繊維の豊富なものとできる点等から好ましい。加工物としては市販されているものを使用できる。例えば大麦であれば、市販の大麦茎葉の粉砕末（商品名「大麦若葉末」等）や搾汁粉末（商品名「大麦若葉エキス」等）を使用でき、甘藷であれば例えば市販の甘藷茎葉の粉砕末（商品名「すいおう」等）を使用することができる。 Among the processed products of foliage, in particular, the use of crushed foliage (crushed powder, etc.) or squeezed juice (squeezed powder, etc.) makes the agent of the present invention even more vivid in color and has a good flavor. It is preferable because it can be made and that it can be rich in dietary fiber. As the processed product, a commercially available product can be used. For example, in the case of barley, commercially available crushed barley foliage powder (trade name "barley young leaf powder", etc.) or juice powder (trade name "barley young leaf extract", etc.) can be used, and in the case of sweet potato, for example, commercially available sweet potato foliage. Crushed powder (trade name "Suiou" etc.) can be used.
本発明の剤は、乳酸菌の腸管接着作用が高まる点から、青汁素材である植物が、前記（１）大麦、（２）甘藷、（３）ケール、（４）桑及び（５）ボタンボウフウのうち、２種以上を含むことが更に好ましい。とりわけ青汁素材である植物が、（１）大麦と、（２）甘藷、（３）ケール、（４）桑及び（５）ボタンボウフウから選ばれる少なくとも１種とを含むことが好ましい。より好ましくは（１）大麦と、（２）甘藷、（３）ケール、（４）桑及び（５）ボタンボウフウから選ばれる２種以上とを含むことが好ましい。（１）と、（２）〜（５）から選ばれる２種以上とを含有する場合は特に（１）大麦と、（３）ケールと、（５）ボタンボウフウとを含むことが好ましい。最も好ましいのは、（１）大麦、（２）甘藷、（３）ケール、（４）桑及び（５）ボタンボウフウを全て含有することである。 In the agent of the present invention, since the intestinal adhesive action of lactic acid bacteria is enhanced, the plants used as the green juice material are the above-mentioned (1) barley, (2) sweet potato, (3) kale, (4) mulberry and (5) button siler. Of these, it is more preferable to include two or more of them. In particular, it is preferable that the plant which is a green juice material contains (1) barley and at least one selected from (2) sweet potato, (3) kale, (4) morus alba and (5) button siler. More preferably, it contains (1) barley and two or more kinds selected from (2) sweet potato, (3) kale, (4) morus alba and (5) button siler. When (1) and two or more kinds selected from (2) to (5) are contained, it is particularly preferable to contain (1) barley, (3) kale, and (5) button siler. Most preferably, it contains all of (1) barley, (2) sweet potato, (3) kale, (4) morus alba and (5) button siler.
本発明の剤における青汁素材である植物の茎葉の合計量は、本発明の剤中、乾燥質量で０．０１質量％以上９０質量％以下であることが好ましく、０．０５質量％以上８０質量％以下であることがより好ましく、０．１質量％以上７０質量％以下であることが特に好ましい。ここでいう合計量とは、本発明の剤が青汁素材である植物として１種のみしか含有していない場合はその含有量である。本発明の剤が前記（１）〜（５）のいずれかの植物の茎葉を含有する場合、本発明の剤における（１）〜（５）の植物の茎葉の合計量の好ましい範囲は、前記青汁素材である植物の茎葉の合計量と同様である。 The total amount of the stems and leaves of the plant which is the green juice material in the agent of the present invention is preferably 0.01% by mass or more and 90% by mass or less, and 0.05% by mass or more and 80% by mass or less in terms of dry mass in the agent of the present invention. It is more preferably 0.1% by mass or less, and particularly preferably 0.1% by mass or more and 70% by mass or less. The total amount referred to here is the content of the agent of the present invention when it contains only one type of plant as a green juice material. When the agent of the present invention contains the foliage of any of the plants (1) to (5), the preferable range of the total amount of the foliage of the plants of (1) to (5) in the agent of the present invention is as described above. It is the same as the total amount of stems and leaves of plants that are green juice materials.
特に、本発明の剤による乳酸菌の腸管接着効果を高める点から、前記（１）〜（５）のいずれかの植物の茎葉を含有する場合、（１）〜（５）の各植物の茎葉は、本発明の剤中、乾燥質量で０．０１質量％以上８０質量％以下含まれることが好ましく、０．０５質量％以上７０質量％以下含まれることがより好ましく、０．１質量％以上５０質量％以下含まれることが特に好ましい。 In particular, from the viewpoint of enhancing the intestinal adhesion effect of the lactic acid bacterium by the agent of the present invention, when the foliage of any of the plants (1) to (5) is contained, the foliage of each of the plants (1) to (5) The agent of the present invention preferably contains 0.01% by mass or more and 80% by mass or less, more preferably 0.05% by mass or more and 70% by mass or less, and 0.1% by mass or more and 50% by mass or less in terms of dry mass. It is particularly preferable that it is contained in an amount of% by mass or less.
本発明の剤が、前記（１）と、（２）〜（５）のいずれか１種以上とを含有する場合は、（１）の乾燥質量１００質量部に対して（２）〜（５）の合計乾燥質量が０．１質量部以上１０００質量部以下であることが好ましく、０．５質量部以上８００質量部以下であることがより好ましく、１質量部以上５００質量部以下であることが特に好ましい。 When the agent of the present invention contains any one or more of (1) and (2) to (5), (2) to (5) with respect to 100 parts by mass of the dry mass of (1). ) Is preferably 0.1 part by mass or more and 1000 part by mass or less, more preferably 0.5 part by mass or more and 800 part by mass or less, and 1 part by mass or more and 500 part by mass or less. Is particularly preferable.
本発明の剤は、植物由来成分として、実質的に（１）〜（５）のみからなるものであってもよく、その他の植物由来成分を有していてもよい。例えば、本発明の剤における（１）〜（５）以外の植物由来成分は、例えば本発明の剤中、７０質量％以下であることが好ましく、５０質量％以下であることがより好ましい。 The agent of the present invention may be substantially composed of only (1) to (5) as a plant-derived component, or may have other plant-derived components. For example, the plant-derived components other than (1) to (5) in the agent of the present invention are preferably 70% by mass or less, more preferably 50% by mass or less, in the agent of the present invention, for example.
本発明の剤は、乳酸菌を非含有であってもよいが、乳酸菌を含有していることが、乳酸菌の腸管接着効果をより高める点から好ましい。乳酸菌は生菌であっても死菌であってもよい。生菌である場合は、腸内環境改善の点から好ましいが、死菌であってもよい。これは生菌のみならず死菌の菌体成分も、腸管免疫を刺激するものとされていることに基づく。本発明で使用される乳酸菌としては、代謝産物として乳酸を産生するものであれば特に限定されず、ヒトなどの動物において従来経口摂取されているものが挙げられ、例えば、Bifidobacterium属、Lactbacillus属、Enterococcus属、Leuconostoc属、Pediococcus属、Staphylococcus属、Tetragenococcus属、Bacillus属のものが挙げられる。
Bifidobacterium属としては、Bifidobacterium bifidum、Bifidobacterium breve、Bifidobacterium infantis、Bifidobacterium lactis、Bifidobacterium longum、Bifidobacterium adolescentis、Bifidobacterium mongolienseが挙げられる。
Lactbacillus属としては、Lactbacillus brevis、Lactbacillus gasseri、Lactobacillus acidophilus、Lactobacillus buchneri、Lactobacillus bulgaricus、Lactobacillus delburvecki、Lactobacillus casei、Lactobacillus crispatus、Lactobacillus curvatus、Lactobacillus halivaticus、Lactobacillus pentosus、Lactobacillus plantarum、Lactobacilus paracasei、Lactobacillus rhamnosus、Lactobacillus salivarius、Lactobacillus sporogenes、Lactobacillus sakei、Lactobacillus fructivorans、Lactobacillus hilgardii、Lactobacillus reuteri、Lactobacillus fermentumが挙げられる。
Enterococcusとしては、Enterococcus faecalis(Streptococcus faecalis と称されることもある)、Enterococcus faesium（Streptococcus faesiumと称されることもある)、Streptococcus thermophilus、Lactococcus lactis(Streptococcus lactisと称されることもある) が挙げられる。
Leuconostoc属としては、Leuconostoc mesenteroides、Leuconostoc oenos が挙げられる。
Pediococcus属としては、Pediococcus acidilactici、Pediococcus pentosaceusが挙げられる。
Staphylococcus属としては、Staphylococcus carnosus、Staphylococcus xylosusが挙げられる。
Tetragenococcus属としては、Tetragenococcus halophilusが挙げられる。Bacillus属としては、Bacillus coagulans、及びBacillus mesentericusなどが挙げられる。
とりわけ、Bacillus coagulans、Enterococcus faecalis、Bifidobacterium bifidum、Enterococcus faesium、Lactobacillus acidophilusが好ましい。これらは、１種を単独で使用してもよいし、２種以上を併用してもよい。
The agent of the present invention may not contain lactic acid bacteria, but it is preferable that the agent contains lactic acid bacteria from the viewpoint of further enhancing the intestinal adhesive effect of lactic acid bacteria. Lactic acid bacteria may be live or dead. When it is a live bacterium, it is preferable from the viewpoint of improving the intestinal environment, but it may be a dead bacterium. This is based on the fact that not only live bacteria but also killed bacterial cell components are supposed to stimulate intestinal immunity. The lactic acid bacterium used in the present invention is not particularly limited as long as it produces lactic acid as a metabolite, and examples thereof include those conventionally orally ingested in animals such as humans, for example, Bifidobacterium genus, Lactbacillus genus, Examples include those of the genera Enterococcus, Leuconostoc, Pediococcus, Staphylococcus, Tetragenococcus, and Bacillus.
Examples of the genus Bifidobacterium include Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium adolescentis, and Bifidobacterium mongoliense.
The Lactbacillus genus, Lactbacillus brevis, Lactbacillus gasseri, Lactobacillus acidophilus, Lactobacillus buchneri, Lactobacillus bulgaricus, Lactobacillus delburvecki, Lactobacillus casei, Lactobacillus crispatus, Lactobacillus curvatus, Lactobacillus halivaticus, Lactobacillus pentosus, Lactobacillus plantarum, Lactobacilus paracasei, Lactobacillus rhamnosus, Lactobacillus salivarius, Lactobacillus sporogenes, Lactobacillus sakei, Lactobacillus fructivorans, Lactobacillus hilgardii, Lactobacillus reuteri, Lactobacillus fermentum.
Enterococcus includes Enterococcus faecalis (sometimes called Streptococcus faecalis), Enterococcus faesium (sometimes called Streptococcus faesium), Streptococcus thermophilus, and Lactococcus lactis (sometimes called Streptococcus lactis). Be done.
Examples of the genus Leuconostoc include Leuconostoc mesenteroides and Leuconostoc oenos.
Examples of the genus Pediococcus include Pediococcus acidilactici and Pediococcus pentosaceus.
Examples of the genus Staphylococcus include Staphylococcus carnosus and Staphylococcus xylosus.
Examples of the genus Tetragenococcus include Tetragenococcus halophilus. Examples of the genus Bacillus include Bacillus coagulans and Bacillus mesentericus.
In particular, Bacillus coagulans, Enterococcus faecalis, Bifidobacterium bifidum, Enterococcus faesium, and Lactobacillus acidophilus are preferable. These may be used alone or in combination of two or more.
本発明の剤が乳酸菌を含有する場合、乳酸菌の含有量は特に限定されないが、例えば菌体数として、本発明の剤中、1×103個以上、好ましくは1×105個以上1×1020個以下、更に好ましくは1×107個以上1×1015個以下とすることが、製剤の容易性及び乳酸菌の腸管付着効果を高める点から好ましい。 When the agent of the present invention contains lactic acid bacteria, the content of the lactic acid bacteria is not particularly limited. For example, the number of cells in the agent of the present invention is 1 × 10 3 or more, preferably 1 × 10 5 or more 1 ×. 10 20 or less, more preferably 1 × 10 7 or more and 1 × 10 15 or less are preferable from the viewpoint of easiness of preparation and enhancing the intestinal adhesion effect of lactic acid bacteria.
本発明の剤は乳酸菌を含有する場合、乳酸菌と前記植物の茎葉とが同一剤に含まれていてもよく別々の剤に含まれていてもよい。別々の剤に含まれている場合は、本発明の剤は２剤以上の多剤型となる。同一剤に含まれている場合、本発明の剤は、１剤型であっても多剤型であってもよいが１剤型であることが摂取の簡便性等の点で好ましい。本発明の剤の剤形は、１剤型及び多剤型のいずれに関わらず、固体状、液状、ペースト状、ゲル状などが挙げられる。例えば、固体状としては、粉末状、粒状、顆粒状、錠状、棒状、板状、ブロック状、固形状、ハードカプセルやソフトカプセルのようなカプセル状、カプレット状、タブレット状、チュアブル状、スティック状等の各形態が挙げられる。液状としては例えば流動状、シロップ状等が挙げられる。これらは薬学的に許容される基材や担体を添加して、公知の製剤方法によって、各種の剤形に製剤可能である。 When the agent of the present invention contains lactic acid bacteria, the lactic acid bacteria and the foliage of the plant may be contained in the same agent or in different agents. When contained in separate agents, the agent of the present invention is a multi-dose form of two or more agents. When contained in the same agent, the agent of the present invention may be a one-drug type or a multi-drug type, but the one-drug type is preferable in terms of ease of ingestion and the like. The dosage form of the agent of the present invention may be solid, liquid, paste, gel or the like regardless of whether it is a one-agent type or a multi-agent type. For example, solids include powder, granules, granules, tablets, rods, plates, blocks, solids, capsules such as hard capsules and soft capsules, caplets, tablets, chewables, sticks, etc. Each form of is mentioned. Examples of the liquid include a fluid and a syrup. These can be formulated into various dosage forms by a known formulation method by adding a pharmaceutically acceptable base material or carrier.
例えば、乳酸菌を含有する本発明の剤の好ましい剤型としては、乳酸菌と前記植物の茎葉とを含み、粉末状、細粒状、顆粒状、錠状、ソフトカプセルやハードカプセル等のカプセル状、液状のいずれかである１剤型の形態や、前記植物の茎葉を含み、粉末状、細粒状、顆粒状、錠状、ソフトカプセルやハードカプセル等のカプセル状、液状である第１剤と、乳酸菌を含み、粉末状、細粒状、顆粒状、錠状、ソフトカプセルやハードカプセル等のカプセル状、液状のいずれかである第２剤とを有する２剤型の形態などが挙げられる。なお、本発明においては前記植物の茎葉を含む第１剤を単独で使用することにより、腸内に存在する乳酸菌やビフィズス菌の腸管接着性を向上させることもできる。 For example, the preferred dosage form of the agent of the present invention containing lactic acid bacteria includes lactic acid bacteria and the foliage of the plant, and may be powdery, finely granular, granular, tableted, capsule-like such as soft capsule or hard capsule, or liquid. The first dosage form, which is a one-dosage form, contains the foliage of the plant, and contains powder, fine granules, granules, tablets, capsules such as soft capsules and hard capsules, and a liquid first agent, and powder containing lactic acid bacteria. Examples thereof include a two-dosage form having a second agent which is either in the form of a fine granule, a granule, a tablet, a capsule such as a soft capsule or a hard capsule, or a liquid. In the present invention, the intestinal adhesiveness of lactic acid bacteria and bifidobacteria existing in the intestine can be improved by using the first agent containing the foliage of the plant alone.
本発明の剤の経口摂取方法は限定されず、そのまま摂取するのであってもよく、また剤を水やお湯、牛乳、ヨーグルトなどに分散又は溶解させたものを摂取するのであってもよい。また本発明の剤が多剤型である場合は、複数剤を同時に摂取してもよく、別のタイミングで摂取してもよい。別のタイミングで摂取する場合は、例えば乳酸菌含有剤と植物茎葉含有剤とでいずれを先に摂取してもよいが、両者の摂取の時間差としては２４時間以内が好ましく、１８時間以内がより好ましく、１５時間以内が特に好ましい。また２剤の摂取方法は、同じであっても異なっていてもよく、異なる場合は例えば、乳酸菌含有剤はそのまま摂取し、植物茎葉含有剤は水やお湯、牛乳、ヨーグルトなどに分散して摂取する、という例があげられ、これは逆であってもよい。 The oral ingestion method of the agent of the present invention is not limited, and the agent may be ingested as it is, or may be ingested by dispersing or dissolving the agent in water, hot water, milk, yogurt or the like. When the agent of the present invention is in a multi-dose form, a plurality of agents may be ingested at the same time, or may be ingested at different timings. When ingesting at different timings, for example, either the lactic acid bacterium-containing agent or the plant foliage-containing agent may be ingested first, but the time difference between the two intakes is preferably within 24 hours, more preferably within 18 hours. , 15 hours or less is particularly preferable. The method of ingesting the two agents may be the same or different. If they are different, for example, the lactic acid bacterium-containing agent should be ingested as it is, and the plant foliage-containing agent should be dispersed in water, hot water, milk, yogurt, etc. An example is given, which may be the other way around.
本発明の剤は前記植物の茎葉及び乳酸菌以外に、通常使用される他の成分を、本発明の効果を損なわない範囲で含有してもよい。このような成分としては、種々の賦形剤、結合剤、光沢剤、滑沢剤、安定剤、希釈剤、増量剤、増粘剤、乳化剤、酸化防止剤、ｐＨ調整剤、着色料、香料、添加剤などを挙げることができる。その他の成分の含有量は、本発明の剤の形態等に応じて適宜選択することができる。また本発明の剤が多剤型である場合、いずれの剤にいずれの他の成分を含有するかについても、その剤の形態に応じて適宜選択される。 In addition to the foliage and lactic acid bacteria of the plant, the agent of the present invention may contain other commonly used components as long as the effects of the present invention are not impaired. Such ingredients include various excipients, binders, brighteners, lubricants, stabilizers, diluents, bulking agents, thickeners, emulsifiers, antioxidants, pH regulators, colorants, fragrances. , Additives and the like. The content of other components can be appropriately selected depending on the form of the agent of the present invention and the like. Further, when the agent of the present invention is in a multi-dosage form, which agent contains which other component is appropriately selected according to the form of the agent.
本発明の剤の１日の経口投与量は前記植物の茎葉の乾燥質量として１０ｍｇ以上であることが好ましい。本発明の剤は、連続的に、例えば毎日でも投与でき、長期的、例えば１ヶ月以上の間投与を継続して差し支えない。 The daily oral dose of the agent of the present invention is preferably 10 mg or more as the dry mass of the foliage of the plant. The agent of the present invention can be administered continuously, for example daily, and may be continuously administered for a long period of time, for example, for one month or longer.
本発明の剤が乳酸菌を含有する場合もしない場合も、前記植物の茎葉の経口投与量を前提として、乳酸菌の１日の経口投与量は1×103個以上、特に1×105個以上1×1020個以下であることが好ましい。 Regardless of whether the agent of the present invention contains or does not contain lactic acid bacteria, the daily oral dose of lactic acid bacteria is 1 × 10 3 or more, particularly 1 × 10 5 or more, assuming the oral dose of the foliage of the plant. It is preferably 1 × 10 20 or less.
本発明の剤は、後述する実施例の記載から明らかな通り、前記植物の茎葉の作用により乳酸菌の腸管接着性を高めることができる。ここでいう腸管接着性とは、好ましくは腸管上皮（腸管上皮細胞）への接着性をいう。
このため、本発明の剤はこれを経口摂取することで、腸管における乳酸菌の作用を高めることができ、例えば腸管免疫増強剤として用いることができるほか、アトピー性皮膚炎、アレルギー性鼻炎、花粉症、湿疹、蕁麻疹等の発疹、下痢や嘔吐等のアレルギー症状の予防や改善を図ることができる。前記の腸管免疫増強剤の作用は、Ｔｈ１細胞の働きを活発化したり、ＩｇＡ抗体産生を促すことを含む。本発明の剤は、ヒトに対して好適に適用されるものであるが、それぞれの作用効果が奏される限り、ヒト以外の動物（例えば、マウス、ラット、ハムスター、イヌ、ネコ、ウシ、ブタ、サル等）に対して適用することもできる。本発明のアレルギー剤からは、インターロイキン４産生を抑制することにより抗アレルギー作用を発揮するものを除くものとする。
As is clear from the description of Examples described later, the agent of the present invention can enhance the intestinal adhesiveness of lactic acid bacteria by the action of the foliage of the plant. The term "intestinal adhesiveness" as used herein preferably refers to adhesiveness to intestinal epithelium (intestinal epithelial cells).
Therefore, the agent of the present invention can enhance the action of lactic acid bacteria in the intestinal tract by orally ingesting it, and can be used, for example, as an intestinal immunopotentiator, as well as atopic dermatitis, allergic rhinitis, and hay fever. , Eczema, urticaria and other rashes, and allergic symptoms such as diarrhea and vomiting can be prevented or ameliorated. The action of the intestinal immunopotentiator includes activating the function of Th1 cells and promoting IgA antibody production. The agent of the present invention is preferably applied to humans, but as long as the respective actions and effects are exhibited, non-human animals (for example, mice, rats, hamsters, dogs, cats, cows, pigs). , Monkey, etc.). From the allergic agents of the present invention, those exhibiting an antiallergic effect by suppressing the production of interleukin 4 are excluded.
本発明の剤により腸管接着（付着）性を高める対象となる乳酸菌としては、本発明の剤に含有されていてもよい乳酸菌として前記で上げたものと同様のものを挙げることができる。本発明は、本発明の剤を含有する食品又は医薬品、医薬部外品などを提供する。本発明は乳酸菌とともに本発明の剤を摂取して腸管における乳酸菌接着を促す方法（但し医療行為を除く）を提供する。 Examples of the lactic acid bacterium to be targeted for enhancing the intestinal adhesiveness (adhesion) by the agent of the present invention include the same lactic acid bacteria as those mentioned above as the lactic acid bacterium that may be contained in the agent of the present invention. The present invention provides foods or pharmaceuticals containing the agents of the present invention, quasi-drugs, and the like. The present invention provides a method (excluding medical practice) of ingesting the agent of the present invention together with lactic acid bacteria to promote adhesion of lactic acid bacteria in the intestinal tract.
以下、実施例を挙げて本発明を更に詳細に説明する。しかし本発明の範囲はかかる実施例に限定されない。以下、特に断らない場合「％」は質量％、「部」は質量部を表す。 Hereinafter, the present invention will be described in more detail with reference to examples. However, the scope of the present invention is not limited to such examples. Hereinafter, unless otherwise specified, "%" represents mass% and "parts" represents mass parts.
大麦茎葉として、出穂前に刈り取った茎及び葉を乾燥及び粉砕処理して得られた粉砕末（株式会社東洋新薬製）を用いた。甘藷茎葉として、茎葉の先端から３０〜８０ｃｍの長さで刈り取った甘藷の茎及び葉を乾燥及び粉砕処理して得られた粉砕末（同社製）を用いた。ケールとして、ケールの茎及び葉を乾燥及び粉砕処理して得られた粉砕末（同社製）を用いた。桑として、桑の茎及び葉を乾燥及び粉砕処理して得られた粉砕末（同社製）を用いた。ボタンボウフウとして、ボタンボウフウの茎及び葉を乾燥及び粉砕処理して得られた粉砕末（同社製）を用いた。これらの粉砕末は、いずれも２００メッシュ区分を９０質量％以上が通過するものであり、また水分量は５質量％以下であった。これらの粉砕末を被験物質として以下の接着能試験に供した。 As the barley stems and leaves, crushed powder (manufactured by Toyo Shinyaku Co., Ltd.) obtained by drying and crushing the stems and leaves cut before heading was used. As the sweet potato foliage, crushed powder (manufactured by the same company) obtained by drying and crushing the stalks and leaves of sweet potato cut to a length of 30 to 80 cm from the tip of the foliage was used. As the kale, crushed powder (manufactured by the same company) obtained by drying and crushing the stems and leaves of kale was used. As morus alba, crushed powder (manufactured by the same company) obtained by drying and crushing mulberry stems and leaves was used. As the button sill, crushed powder (manufactured by the same company) obtained by drying and crushing the stems and leaves of the button sill was used. In each of these pulverized powders, 90% by mass or more passed through the 200 mesh section, and the water content was 5% by mass or less. These pulverized powders were used as test substances for the following adhesive performance tests.
（接着能試験）
（１）96well plateを用いたmonolayer作製
37℃、5体積%CO2インキュベーター内で、75cm2フラスコを用いて、通常培地にて腸管上皮細胞株Caco-2細胞を培養した。この通常培地は、44.5 mL DMEM（1%ペニシリン−ストレプトマイシン含有）へ5mL FBS（Japan Bio Serum社）及び0.5 mL NEAA（Non-Essential Amino Acids、SIGMA社）を加えて調製した。トリプシン処理により浮遊させた細胞を、75 cm2フラスコから96well clear plateに4.0×104cells/wellの細胞密度で播種した。37℃、5体積%CO2インキュベーター内で72時間培養し、monolayerを作製した。
(Adhesiveness test)
(1) Monolayer production using 96 well plate
Intestinal epithelial cell line Caco-2 cells were cultured in normal medium using a 75 cm 2 flask in a 5 volume% CO 2 incubator at 37 ° C. This normal medium was prepared by adding 5 mL FBS (Japan Bio Serum) and 0.5 mL NEAA (Non-Essential Amino Acids, SIGMA) to 44.5 mL DMEM (containing 1% penicillin-streptomycin). Cells suspended by trypsin treatment were seeded from a 75 cm 2 flask onto a 96 well clear plate at a cell density of 4.0 × 10 4 cells / well. A monolayer was prepared by culturing in a 5 volume% CO 2 incubator at 37 ° C for 72 hours.
（２）B coagulansの蛍光標識
−80℃でグリセロールストックされたBacillus coagulansを室温（25℃）にもどし、37℃に温めたMRS液体培地に播種した。37℃で24時間培養したものを試験に用いた。
前培養したB.coagulansを採取し、室温・1000gで3分間遠心した。上清を除いて得たペレットを1mＬのリン酸緩衝生理食塩液（PBS）へ懸濁し、室温・1000gで3分間遠心した。同様の懸濁及び遠心をもう1度繰り返し、上清を取り除いてペレットを1mＬのPBSへ懸濁し、carboxyfluorescein diacetate（CFDA、同仁化学研究所社製）を15μL添加した。遮光し室温で30分間インキュベートした後、室温・1000gで3分間遠心した。上清を除き1mＬのPBSへ懸濁し、室温・1000gで3分間遠心する操作を２回繰り返した。その後、上清を除き試験培地へ懸濁した。なおblankとしてCFDAを添加しない以外は同様の操作を行ったものを用意した。試験培地としては45 mL RPMI1640培地（1%ペニシリン−ストレプトマイシン含有）へ5 mL のFBS（Japan Bio Serum社）を加えたものを用いた。
前記懸濁液をBlackplateへ100μＬ移し蛍光強度を測定した。励起波長は495nm、蛍光波長515nmとした。測定した蛍光強度からblankの値を差し引き、蛍光強度が200になるよう試験培地を用いて希釈しこれをB.coagulansサンプルとした。
(2) Fluorescent label of B coagulans Bacillus coagulans stocked in glycerol at -80 ° C was returned to room temperature (25 ° C) and seeded in MRS liquid medium warmed to 37 ° C. Those cultured at 37 ° C. for 24 hours were used for the test.
Pre-cultured B. coagulans were collected and centrifuged at room temperature and 1000 g for 3 minutes. The pellet obtained by removing the supernatant was suspended in 1 mL of phosphate buffered saline (PBS) and centrifuged at room temperature of 1000 g for 3 minutes. The same suspension and centrifugation were repeated once more, the supernatant was removed, the pellet was suspended in 1 mL of PBS, and 15 μL of carboxyfluorescein diacetate (CFDA, manufactured by Dojin Chemical Laboratory) was added. After incubating at room temperature for 30 minutes in the dark, the mixture was centrifuged at room temperature and 1000 g for 3 minutes. The supernatant was removed, suspended in 1 mL of PBS, and centrifuged at room temperature and 1000 g for 3 minutes, and the operation was repeated twice. Then, the supernatant was removed and suspended in the test medium. A blank was prepared by performing the same operation except that CFDA was not added. As the test medium, 45 mL RPMI1640 medium (containing 1% penicillin-streptomycin) to which 5 mL of FBS (Japan Bio Serum) was added was used.
The suspension was transferred to a Black plate in an amount of 100 μL, and the fluorescence intensity was measured. The excitation wavelength was 495 nm and the fluorescence wavelength was 515 nm. The blank value was subtracted from the measured fluorescence intensity, diluted with a test medium so that the fluorescence intensity became 200, and this was used as a B. coagulans sample.
（３）蛍光強度測定によるB.coagulans接着能評価
（１）で作製したCaco-2細胞のmonolayerの培地を通常培地から前記試験培地へ置換した。培地を除き、被験物質を試験培地に分散させた分散液、及び（２）で調製したB.coagulansサンプルを100μＬずつ96wellplateへ添加した（B.coagulans最終蛍光強度100）。37℃の5体積%CO2インキュベーター内で2時間培養後、各wellにホルマリン150μｌ添加し、遮光して4℃で30分間固定した。PBSで3回洗浄し、PBSを100μｌ添加したのちvarioskanで蛍光強度を測定した（励起波長495nm、蛍光波長515nm)。測定値に基づき、乳酸菌のみを添加したサンプル蛍光強度に対する相対値（％）を算出し、これを乳酸菌の腸管細胞monolayerへの接着率とした。結果を図1に示す。なお、被験物質のインキュベート時のCaco-2細胞培養液中の濃度は、下記表１に記載の通りである（表１の数値の単位はμｇ／ｍＬ）。
(3) Evaluation of B. coagulans adhesive ability by measuring fluorescence intensity The medium of the monolayer of Caco-2 cells prepared in (1) was replaced with the test medium from the normal medium. The medium was removed, and 100 μL of the dispersion liquid in which the test substance was dispersed in the test medium and the B. coagulans sample prepared in (2) were added to a 96-well plate (B. coagulans final fluorescence intensity 100). After culturing in a 5 volume% CO 2 incubator at 37 ° C. for 2 hours, 150 μl of formalin was added to each well, and the cells were fixed at 4 ° C. for 30 minutes in the dark. After washing 3 times with PBS and adding 100 μl of PBS, the fluorescence intensity was measured with varioskan (excitation wavelength 495 nm, fluorescence wavelength 515 nm). Based on the measured values, a relative value (%) with respect to the fluorescence intensity of the sample to which only lactic acid bacteria were added was calculated, and this was used as the adhesion rate of lactic acid bacteria to the intestinal cell monolayer. The results are shown in Figure 1. The concentration of the test substance in the Caco-2 cell culture solution at the time of incubation is as shown in Table 1 below (the numerical unit in Table 1 is μg / mL).
図１の結果から、青汁素材である植物の茎葉は、乳酸菌の腸管接着率を高めることが判る。更に、大麦茎葉を含む２種以上の植物の茎葉を用いると、更に乳酸菌の腸管接着率が高くなることが判る。 From the results of FIG. 1, it can be seen that the stems and leaves of plants, which are green juice materials, increase the intestinal adhesion rate of lactic acid bacteria. Furthermore, it can be seen that the intestinal adhesion rate of lactic acid bacteria is further increased by using the foliage of two or more kinds of plants including barley foliage.
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