JP2021078495A - Composition comprising fermented soybean - Google Patents

Composition comprising fermented soybean Download PDF

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JP2021078495A
JP2021078495A JP2020189530A JP2020189530A JP2021078495A JP 2021078495 A JP2021078495 A JP 2021078495A JP 2020189530 A JP2020189530 A JP 2020189530A JP 2020189530 A JP2020189530 A JP 2020189530A JP 2021078495 A JP2021078495 A JP 2021078495A
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lactic acid
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soybean
hericiaceae
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郁美 沖中
Ikumi Okinaka
郁美 沖中
知子 馬場
Tomoko Baba
知子 馬場
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Kosmos
Kosmos Co Ltd
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Kosmos Co Ltd
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Abstract

To provide a composition for immune suppression, for allergy symptom alleviation, allergy prevention, and cancer treatment or prevention.SOLUTION: A composition contains lactic acid bacteria-fermented soybeans, Sparassidaceae basidiomycetes and Hericiaceae basidiomycetes.SELECTED DRAWING: None

Description

関連出願
この出願は、2019年11月15日に米国特許庁に出願された仮出願番号62/935723号の優先権の利益を主張する。優先権基礎出願はその全体について、出典明示により本明細書の一部とする。
Related Application This application claims the priority benefit of Provisional Application No. 62/935723 filed with the United States Patent Office on November 15, 2019. The priority basic application as a whole is made a part of this specification by specifying the source.

本発明は大豆の乳酸菌発酵物、ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類を含む組成物に関する。 The present invention relates to a composition containing a fermented lactic acid bacterium of soybean, a basidiomycete of the family Sparassis crispa, and a basidiomycete of the family Hericiaceae.

乳酸菌は、様々な生理的効果を有することが知られており、例えば、整腸作用や免疫力向上作用等の生理活性を奏することが知られている(特許文献1、2)。このような乳酸菌の効用は、近年、プロバイオティクス効果などへの期待から、広く関心を集めている。 Lactic acid bacteria are known to have various physiological effects, and are known to exhibit physiological activities such as intestinal regulation action and immunity improving action (Patent Documents 1 and 2). In recent years, the utility of such lactic acid bacteria has attracted widespread interest due to expectations for probiotic effects.

また、豆類、いちじく葉、およびハナビラタケ科またはサンゴハリタケ科の担子菌類を混合したものを乳酸菌で発酵させて得られる発酵組成物が開示されている(特許文献3)。この発酵組成物は、主に家畜の免疫力向上、肺炎予防、インフルエンザ等のウイルス性感染症の予防等に関するものである。 Further, there is disclosed a fermentation composition obtained by fermenting a mixture of beans, strawberry leaves, and basidiomycetes of the family Sparassis crispa or Hericiaceae with lactic acid bacteria (Patent Document 3). This fermentation composition is mainly related to improvement of livestock immunity, prevention of pneumonia, prevention of viral infectious diseases such as influenza, and the like.

乳酸菌を含むさまざまな組成物が検討されているが、さらなる有用な組成物が求められている。 Various compositions containing lactic acid bacteria have been studied, but more useful compositions are sought.

特開2019−116423号公報Japanese Unexamined Patent Publication No. 2019-116423 特開2015−177748号公報Japanese Unexamined Patent Publication No. 2015-177748 特開2019−182763号公報Japanese Unexamined Patent Publication No. 2019-182763

本発明の目的は、免疫抑制、アレルギー症状緩和、アレルギー予防、またはがん治療もしくは予防等の効果を有する組成物を提供することである。 An object of the present invention is to provide a composition having effects such as immunosuppression, allergic symptom relief, allergy prevention, or cancer treatment or prevention.

本発明者は、大豆の乳酸菌発酵物、ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類を含む組成物により、上記課題が解決されることを見出し、本発明を完成させた。 The present inventor has found that the above-mentioned problems can be solved by a composition containing a fermented lactic acid bacterium of soybean, a basidiomycete of Sparassis crispa, and a basidiomycete of Hericiaceae, and completed the present invention.

すなわち、本発明は、
(1)大豆の乳酸菌発酵物、ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類を含む、組成物、
(2)ハナビラタケ科の担子菌類がハナビラタケであり、サンゴハリタケ科の担子菌類がヤマブシタケである(1)の組成物、
(3)乳酸菌が、柿由来の乳酸菌である、(1)または(2)の組成物、
(4)乳酸菌が、ラクトバチルス・パラカゼイである、(1)〜(3)のいずれかの組成物、
(5)免疫抑制用、アレルギー症状緩和用、アレルギー予防用、またはがん治療もしくは予防用である、(1)〜(4)のいずれかの組成物、
(6)花粉症の症状緩和用である、(1)〜(4)のいずれかの組成物、
(7)がん治療または予防用である、(1)〜(4)のいずれかの組成物、
を提供するものである。
That is, the present invention
(1) A composition containing a fermented soybean lactic acid bacterium, a basidiomycete of the Sparassis crispa family, and a basidiomycete of the Hericiaceae family.
(2) The composition of (1), in which the basidiomycete of the family Sparassis crispa is Sparassis crispa and the basidiomycete of the family Hericiaceae is Lion's mane.
(3) The composition of (1) or (2), wherein the lactic acid bacterium is a persimmon-derived lactic acid bacterium.
(4) The composition according to any one of (1) to (3), wherein the lactic acid bacterium is Lactobacillus paracasei.
(5) The composition according to any one of (1) to (4), which is for immunosuppression, allergic symptom relief, allergy prevention, or cancer treatment or prevention.
(6) The composition according to any one of (1) to (4), which is used for alleviating the symptoms of pollinosis.
(7) The composition according to any one of (1) to (4), which is for cancer treatment or prevention.
Is to provide.

本発明の組成物を用いることにより、免疫抑制、アレルギー症状緩和、アレルギー予防、またはがん治療もしくは予防効果が得られる。また、さらなる効果として、本発明の組成物は、腸内フローラへの乳酸菌の定着を促進し、上記効果を持続的に発揮することが期待できる。 By using the composition of the present invention, immunosuppression, allergic symptom relief, allergy prevention, or cancer treatment or preventive effect can be obtained. Further, as a further effect, the composition of the present invention can be expected to promote the colonization of lactic acid bacteria in the intestinal flora and continuously exert the above effect.

図1は、本発明の組成物(液体)の典型的な製造工程を示したフロー図である。FIG. 1 is a flow chart showing a typical manufacturing process of the composition (liquid) of the present invention. 図2は、本発明の組成物(カプセル)の典型的な製造工程を示したフロー図である。FIG. 2 is a flow chart showing a typical manufacturing process of the composition (capsule) of the present invention. 図3は、スギ抗原およびアジュバントを投与したマウスに対して、本発明の組成物を投与した群と、真水を投与した群の37日後のIL−10量を測定した結果を示すグラフである。FIG. 3 is a graph showing the results of measuring the amount of IL-10 in the group to which the composition of the present invention was administered and the group to which fresh water was administered 37 days after the mice administered with the Sugi antigen and the adjuvant. 図4は、スギ抗原およびアジュバントを投与したマウスに対して、本発明の組成物を投与した群と、真水を投与した群の37日後のIL−4量を測定した結果を示すグラフである。FIG. 4 is a graph showing the results of measuring the amount of IL-4 after 37 days in the group to which the composition of the present invention was administered and the group to which fresh water was administered to the mice to which the Sugi antigen and the adjuvant were administered.

本発明は、一の態様において、大豆の乳酸菌発酵物、ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類を含む、組成物を提供する。 The present invention provides, in one embodiment, a composition comprising a fermented soybean lactic acid bacterium, a basidiomycete of the family Sparassis crispa and a basidiomycete of the family Hericiaceae.

本態様において使用される乳酸菌の種類は特に限定されないが、好ましくはラクトバチルス属の乳酸菌である。好ましいラクトバチルス属の乳酸菌の例として、ラクトバチルス・アシドフィラス、ラクトバチルス・ブレビス、ラクトバチルス・ブクネリ、ラクトバチルス・ブルガリカス、ラクトバチルス・カゼイ、ラクトバチルス・デルブルエッキ、ラクトバチルス・ファーメンタム、ラクトバチルス・ガセリ、ラクトバチルス・ヘルベティカス、ラクトバチルス・ヒルガルディ、ラクトバチルス・ジョンソニィ、ラクトバチルス・レイクマニ、ラクトバチルス・ラクチス、ラクトバチルス・パラカゼイ、ラクトバチルス・プランタラム、ラクトバチルス・ラムノサス、ラクトバチルス・ロイテリ、ラクトバチルス・サリバリウス等が挙げられる。さらに好ましい例は、ラクトバチルス・パラカゼイ、ラクトバチルス・ファーメンタムである。最も好ましい例は、ラクトバチルス・パラカゼイである。これらの乳酸菌は、1種類を用いても良いし、複数種を用いてもよい。また、乳酸菌の由来は特に限定されず、腸管系乳酸菌、動物由来乳酸菌、植物由来乳酸菌、海洋乳酸菌等が例示される。好ましくは、本態様において使用される乳酸菌は植物由来である。由来となる植物は特に限定されず、キャベツ、すぐき、大根、ニンジン、キュウリ等の野菜;パイナップル、柿等の果物;米、麦等の穀類;アロエ、サボテン等の多肉植物等が例示される。本態様における最も好ましい例として、柿から単離された乳酸菌が挙げられる。 The type of lactic acid bacterium used in this embodiment is not particularly limited, but is preferably a lactic acid bacterium belonging to the genus Lactobacillus. Examples of preferred Lactobacillus lactic acid bacteria are Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus bukunelli, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus del Bruecki, Lactobacillus fermentum, Lactobacillus. Lactobacillus Herveticas, Lactobacillus hirugardi, Lactobacillus Johnsony, Lactobacillus Reikmani, Lactobacillus lactis, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus ramnosus, Lactobacillus reuteri, Lactobacillus・ Sullivarius etc. can be mentioned. More preferred examples are Lactobacillus paracasei and Lactobacillus fermentum. The most preferred example is Lactobacillus paracasei. One type of these lactic acid bacteria may be used, or a plurality of types may be used. The origin of the lactic acid bacterium is not particularly limited, and examples thereof include intestinal lactic acid bacteria, animal-derived lactic acid bacteria, plant-derived lactic acid bacteria, and marine lactic acid bacteria. Preferably, the lactic acid bacterium used in this embodiment is of plant origin. The plant from which it is derived is not particularly limited, and examples thereof include vegetables such as cabbage, suguki, radish, carrot, and cucumber; fruits such as pineapple and persimmon; grains such as rice and wheat; and succulent plants such as aloe and cactus. The most preferable example in this embodiment is a lactic acid bacterium isolated from a persimmon.

具体的な実施形態において、本態様における乳酸菌の例として、その16SrDNAが配列番号1に記載の配列を有する乳酸菌が挙げられる。より具体的な実施形態において、本態様における乳酸菌は、その16SrDNA配列が、配列番号1に記載の配列と少なくとも75%の配列同一性、例えば少なくとも80%、少なくとも85%、少なくとも87%、少なくとも90%、少なくとも91%、少なくとも92%、少なくとも93%、少なくとも94%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%、または少なくとも99%、より具体的に90%、91%、92%、93%、94%、95%、96%、97%、98%、99%、または100%の配列同一性を有する。 In a specific embodiment, an example of the lactic acid bacterium in this embodiment is a lactic acid bacterium whose 16S rDNA has the sequence shown in SEQ ID NO: 1. In a more specific embodiment, the lactic acid bacterium in this embodiment has a 16SrDNA sequence having at least 75% sequence identity with the sequence set forth in SEQ ID NO: 1, such as at least 80%, at least 85%, at least 87%, at least 90. %, At least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, more specifically 90%, 91%, 92 %, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity.

本態様において使用される乳酸菌は、ラクトバチルス属以外の菌を含んでもよいし、ラクトバチルス属の菌のみでもよい。また、発酵には乳酸菌のみを用いてもよいし、必要に応じて乳酸菌以外の菌を併用してもよい。 The lactic acid bacterium used in this embodiment may contain a bacterium other than the genus Lactobacillus, or may be only a bacterium of the genus Lactobacillus. In addition, only lactic acid bacteria may be used for fermentation, or bacteria other than lactic acid bacteria may be used in combination if necessary.

本態様において使用される乳酸菌の入手方法は特に限定されず、市販品を利用してもよい。例えば、株式会社ダイワ、カネカ株式会社、セティ株式会社、東亜薬品工業株式会社、株式会社東洋新薬等から入手可能である。好ましくは、V−LAB原液(株式会社ダイワ)の乳酸菌が利用できる。 The method for obtaining the lactic acid bacterium used in this embodiment is not particularly limited, and a commercially available product may be used. For example, it can be obtained from Daiwa Co., Ltd., Kaneka Corporation, Seti Co., Ltd., Toa Yakuhin Kogyo Co., Ltd., Toyo Shinyaku Co., Ltd., etc. Preferably, lactic acid bacteria of V-LAB stock solution (Daiwa Co., Ltd.) can be used.

本態様の組成物は、大豆を上記乳酸菌で発酵した大豆の乳酸菌発酵物を含む。使用される大豆原料は、特に限定されず、あらゆる品種の大豆を使用し得る。また、大豆は全脂大豆でもよく、部分的または完全に脱脂された大豆でもよい。本態様において用いられる大豆原料の形態は特に限定されず、例えば、丸大豆、半割れ大豆、グリッツ、粉末状であり得る。本態様において用いられる大豆原料は、脱皮、および/または脱胚軸したものでもよいし、脱皮、および/または脱胚軸を行わないものでもよい。 The composition of this embodiment contains a lactic acid bacterium fermented product of soybean obtained by fermenting soybean with the above lactic acid bacterium. The soybean raw material used is not particularly limited, and all varieties of soybean can be used. Further, the soybean may be a full-fat soybean or a partially or completely defatted soybean. The form of the soybean raw material used in this embodiment is not particularly limited, and may be, for example, whole soybean, half-cracked soybean, grits, or powder. The soybean raw material used in this embodiment may be molted and / or hypocotyled, or may not be molted and / or hypocotyled.

大豆原料は、典型的には洗浄後、水または湯で浸漬し、蒸煮して粉砕したスラリーとして乳酸菌発酵に供される。浸漬時に、酢酸、クエン酸、塩酸などの酸、水酸化ナトリウム、重曹などのアルカリ、および/または塩化ナトリウム、塩化カリウムなどの塩を加えてもよい。 The soybean raw material is typically washed, soaked in water or hot water, steamed and pulverized, and subjected to lactic acid bacteria fermentation. At the time of immersion, acids such as acetic acid, citric acid and hydrochloric acid, alkalis such as sodium hydroxide and baking soda, and / or salts such as sodium chloride and potassium chloride may be added.

本態様において使用される大豆の乳酸菌発酵物は、大豆のみから得られた原料を乳酸菌発酵したものでもよいし、大豆由来以外の原料を混合した混合物を乳酸菌発酵したものでもよい。場合により、発酵の補助のための資化性糖類を1種類または2種類以上含んでいてもよいし、含んでいなくてもよい。資化性糖類の例として、グルコース、フラクトース、スクロース、マルトース、ガラクトース、ラクトース、ラフィノース、トレハロース、大豆オリゴ糖、フラクトオリゴ糖、キシロオリゴ糖等が挙げられる。大豆由来以外の原料の例として、甘味料、酸味料、調味料、着色料、香料、食物繊維、安定剤、酸化防止剤、増粘剤、ゲル化剤、乳化剤、界面活性剤、キレート剤、ビタミン、香辛料等が挙げられる。他の原料の添加量は特に限定されず、当業者が適宜調整できるが、本態様の組成物の効果を妨げない限度であることが好ましい。 The fermented lactic acid bacterium of soybean used in this embodiment may be a lactic acid bacterium fermented raw material obtained only from soybean, or a lactic acid bacterium fermented mixture of a mixture of raw materials other than soybean derived. In some cases, one or more assimilating sugars for assisting fermentation may or may not be contained. Examples of assimilating saccharides include glucose, fructooligo, sucrose, maltose, galactose, lactose, raffinose, trehalose, soybean oligosaccharide, fructooligosaccharide, xylooligosaccharide and the like. Examples of non-soy-derived ingredients include sweeteners, acidulants, seasonings, colorants, flavors, dietary fibers, stabilizers, antioxidants, thickeners, gelling agents, emulsifiers, surfactants, chelating agents, Examples include vitamins and spices. The amount of other raw materials added is not particularly limited and can be appropriately adjusted by those skilled in the art, but is preferably limited to a limit that does not interfere with the effects of the composition of this embodiment.

得られた大豆の乳酸菌発酵物は、そのまま組成物の原料として用いてもよいし、いったん乾燥させてから用いてもよい。乾燥させる場合は、加熱を行わない、例えば凍結乾燥による、ことが好ましい。 The obtained fermented soybean lactic acid bacterium may be used as it is as a raw material for the composition, or may be used after being dried once. When it is dried, it is preferable that it is not heated, for example, by freeze-drying.

本態様の組成物は、ハナビラタケ科の担子菌類を含む。本態様におけるハナビラタケ科の担子菌類は特に限定されず、例えば、ハナビラタケ(Sparassis crispa)、Sparassis cystidiosa、Sparassis miniensis、Sparassis spathulata、Sparassis radicataが挙げられる。一実施形態では、本態様におけるハナビラタケ科の担子菌類はハナビラタケである。 The composition of this embodiment contains basidiomycetes of the family Sparassis crispa. The basidiomycetes of the family Sparassis crispa in this embodiment are not particularly limited, and examples thereof include Sparassis crispa, Sparassis cystidiosa, Sparassis miniensis, Sparassis spathulata, and Sparassis radicata. In one embodiment, the basidiomycete of the family Sparassis crispa in this embodiment is Sparassis crispa.

本態様の組成物は、サンゴハリタケ科の担子菌類を含む。本態様におけるサンゴハリタケ科の担子菌類は特に限定されず、例えば、ウラジロウロコタケ、サンゴハリタケ、サンゴハリタケモドキ、ハナヤマブシタケ、ハナレハリタケ、ハナレハリタケモドキ、フサハリタケ、ヤマブシタケ等が挙げられる。一実施形態では、本態様におけるサンゴハリタケ科の担子菌類はヤマブシタケである。 The composition of this embodiment contains basidiomycetes of the family Hericiaceae. The basidiomycetes of the Hericiaceae family in this embodiment are not particularly limited, and examples thereof include Hericiaceae, Hericiaceae, Hericiaceae, Hericiaceae, Hericiaceae, Hericiaceae, Hericiaceae, and Lion's mane. In one embodiment, the basidiomycete of the Hericium family in this embodiment is Lion's mane.

本態様の組成物に使用される担子菌類の形態は特に限定されず、菌体、刻んだもの、粉末、エキス等適宜選択できる。また、生でも乾燥品でもよい。 The form of the basidiomycete used in the composition of this embodiment is not particularly limited, and cells, chopped ones, powders, extracts and the like can be appropriately selected. Moreover, it may be a raw product or a dried product.

本態様の組成物中の、上記の成分の含有量は特に限定されず、適宜調整できる。一例として、組成物中に、固形分換算で、大豆が5〜85重量%、より好ましくは10〜80重量%、ハナビラタケ科の担子菌類が1〜30重量%、より好ましくは5〜25重量%、サンゴハリタケ科の担子菌類が1〜30重量%、より好ましくは5〜25重量%含まれる。 The content of the above-mentioned components in the composition of this embodiment is not particularly limited and can be appropriately adjusted. As an example, in terms of solid content, 5 to 85% by weight of soybean, more preferably 10 to 80% by weight, and 1 to 30% by weight of basidiomycetes of Hericiaceae, more preferably 5 to 25% by weight, are contained in the composition. , Basidiomycetes of the Hericiaceae family are contained in an amount of 1 to 30% by weight, more preferably 5 to 25% by weight.

本態様の組成物の形態は特に限定されず、液状、ペースト状、粉状、顆粒状、固形状、ゲル状、等が例示される。なお、乳酸菌自体の作用が期待されるため、乾燥させる場合は加熱を行わない、例えば凍結乾燥による、ことが好ましい。 The form of the composition of this embodiment is not particularly limited, and examples thereof include liquid, paste, powder, granular, solid, and gel. Since the action of the lactic acid bacterium itself is expected, it is preferable not to heat the lactic acid bacterium when it is dried, for example, by freeze-drying.

本態様の組成物は、大豆の乳酸菌発酵物、ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類のみから調製されてもよい。場合により、発酵の補助のための資化性糖類を1種類または2種類以上含んでいてもよいし、含んでいなくてもよい。資化性糖類の例として、グルコース、フラクトース、スクロース、マルトース、ガラクトース、ラクトース、ラフィノース、トレハロース、大豆オリゴ糖、フラクトオリゴ糖、キシロオリゴ糖等が挙げられる。また、本態様の組成物は、さらに他の原料が添加されていてもよいし、添加されていなくてもよい。他の原料の例として、甘味料、酸味料、調味料、着色料、香料、食物繊維、安定剤、酸化防止剤、増粘剤、ゲル化剤、乳化剤、界面活性剤、キレート剤、ビタミン、香辛料等が挙げられる。他の原料の添加量は特に限定されず、当業者が適宜調整できるが、本態様の組成物の効果を妨げない限度であることが好ましい。 The composition of this embodiment may be prepared only from a fermented lactic acid bacterium of soybean, a basidiomycete of the family Sparassis crispa, and a basidiomycete of the family Hericiaceae. In some cases, one or more assimilating sugars for assisting fermentation may or may not be contained. Examples of assimilating saccharides include glucose, fructooligo, sucrose, maltose, galactose, lactose, raffinose, trehalose, soybean oligosaccharide, fructooligosaccharide, xylooligosaccharide and the like. Further, in the composition of this embodiment, other raw materials may or may not be added. Examples of other ingredients include sweeteners, acidulants, seasonings, colorants, flavors, dietary fibers, stabilizers, antioxidants, thickeners, gelling agents, emulsifiers, surfactants, chelating agents, vitamins, Examples include spices. The amount of other raw materials added is not particularly limited and can be appropriately adjusted by those skilled in the art, but is preferably limited to a limit that does not interfere with the effects of the composition of this embodiment.

本態様の組成物は、大豆、ハナビラタケ科の担子菌類、およびサンゴハリタケ科の担子菌類の作用により、乳酸菌密度を少なくとも1×10cfu/mL、好ましくは少なくとも1×10cfu/mL、より好ましくは少なくとも1×1010cfu/mL、さらにより好ましくは少なくとも1×1011cfu/mLとすることができる。 The composition of this embodiment has a lactic acid bacterium density of at least 1 × 10 8 cfu / mL, preferably at least 1 × 10 9 cfu / mL, more preferably by the action of soybeans, basidiomycetes of the family Hericiaceae, and basidiomycetes of the family Hericiaceae. Can be at least 1 × 10 10 cfu / mL, and even more preferably at least 1 × 10 11 cfu / mL.

本発明は、他の態様において、大豆の乳酸菌発酵物、ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類を含む組成物の製造方法を提供する。 In another aspect, the present invention provides a method for producing a composition containing a fermented lactic acid bacterium of soybean, a basidiomycete of the family Sparassis crispa, and a basidiomycete of the family Hericiaceae.

本態様の方法において使用される乳酸菌、大豆、ハナビラタケ科の担子菌類、およびサンゴハリタケ科の担子菌類についての説明は上述のとおりである。 The description of lactic acid bacteria, soybeans, basidiomycetes of the family Sparassis crispa, and basidiomycetes of the family Hericiaceae used in the method of this embodiment is as described above.

本態様の方法では、発酵原料の一つとして大豆の溶液またはスラリーを調製する。スラリーを得る方法の1つの例として、原料大豆に水または温水を加えて10〜30時間浸漬した後、グラインダー等で粉砕する方法が挙げられる。この際、粉砕する前に液体部分を分離して、粉砕後に再度液体部分を混合してもよい。他の例として、パルベライザー等で粉砕した豆類を水または温水に分散する方法が挙げられる。豆類の殺菌、酵素失活のために、浸漬段階および/またはスラリーの段階で加熱処理を行うことが好ましい。加熱処理の条件は特に限定されず、当業者が適宜調整できる。具体例として、例えば90〜120℃、1〜5時間で行うことができる。得られたスラリーをそのまま発酵原料としてもよいし、スラリーを遠心分離、濾過等の固液分離に供して液体成分のみを回収して発酵原料としてもよい。場合により、浸漬または分散に用いる水または湯に、酢酸、クエン酸、塩酸などの酸、水酸化ナトリウム、重曹などのアルカリ、および/または塩化ナトリウム、塩化カリウムなどの塩を加えてもよいし、加えなくてもよい。 In the method of this embodiment, a soybean solution or slurry is prepared as one of the fermentation raw materials. As an example of a method for obtaining a slurry, there is a method in which water or warm water is added to raw soybeans, soaked for 10 to 30 hours, and then pulverized with a grinder or the like. At this time, the liquid portion may be separated before pulverization, and the liquid portion may be mixed again after pulverization. As another example, there is a method of dispersing beans crushed by a parvelizer or the like in water or warm water. For sterilization and enzyme inactivation of beans, it is preferable to perform heat treatment at the immersion stage and / or the slurry stage. The conditions of the heat treatment are not particularly limited and can be appropriately adjusted by those skilled in the art. As a specific example, it can be carried out at 90 to 120 ° C. for 1 to 5 hours, for example. The obtained slurry may be used as a fermentation raw material as it is, or the slurry may be subjected to solid-liquid separation such as centrifugation or filtration to recover only the liquid component and used as a fermentation raw material. In some cases, acids such as acetic acid, citric acid and hydrochloric acid, alkalis such as sodium hydroxide and baking soda, and / or salts such as sodium chloride and potassium chloride may be added to the water or hot water used for immersion or dispersion. It does not have to be added.

本態様の方法における、乳酸菌の添加量、発酵温度、発酵時間等の発酵条件は特に限定されず、当業者が適宜調整できる。具体例として、例えば10〜50℃で3〜144時間、15〜45℃で24〜120時間、20〜40℃で48〜96時間等が挙げられる。発酵の前に、乳酸菌の栄養源として、必要に応じて資化性糖類を加えてもよい。資化性糖類の例は、上述のとおりである。資化性糖類の添加量は特に限定されず、当業者が適宜調整できる。例えば、発酵原料全体に対して1〜20重量%、5〜10重量%等が挙げられる。また、資化性糖類を加えなくてもよい。 Fermentation conditions such as the amount of lactic acid bacteria added, the fermentation temperature, and the fermentation time in the method of this embodiment are not particularly limited and can be appropriately adjusted by those skilled in the art. Specific examples include, for example, 3 to 144 hours at 10 to 50 ° C., 24 to 120 hours at 15 to 45 ° C., 48 to 96 hours at 20 to 40 ° C., and the like. Prior to fermentation, assimilating sugars may be added as a nutrient source for lactic acid bacteria, if necessary. Examples of assimilating sugars are as described above. The amount of the assimilating sugar added is not particularly limited and can be appropriately adjusted by those skilled in the art. For example, 1 to 20% by weight, 5 to 10% by weight, etc. are mentioned with respect to the whole fermentation raw material. Moreover, it is not necessary to add the assimilating sugar.

本態様の方法において、得られた発酵物は、そのまま大豆の乳酸菌発酵物として用いてもよい。また、希釈、濃縮、乾燥等を行ってもよい。乾燥させる場合は加熱を行わない、例えば凍結乾燥による、ことが好ましい。 In the method of this embodiment, the obtained fermented product may be used as it is as a fermented product of lactic acid bacteria of soybean. Further, dilution, concentration, drying and the like may be performed. When it is dried, it is preferably not heated, for example, by freeze-drying.

大豆の乳酸菌発酵物に、ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類を添加、混合することにより、本発明の組成物が得られる。ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類を添加するタイミングは特に限定されず、発酵前、発酵中、発酵後のいずれでもよい。例えば、大豆の発酵液に添加し、発酵を継続してもよい。また他の例では、ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類は発酵前に大豆の溶液またはスラリーと混合されてもよい。 The composition of the present invention can be obtained by adding and mixing basidiomycetes of the family Sparassis crispa and basidiomycetes of the family Hericiaceae to the fermented lactic acid bacteria of soybean. The timing of adding the basidiomycetes of Sparassis crispa and the basidiomycetes of Hericiaceae is not particularly limited, and may be any of pre-fermentation, during fermentation, and after fermentation. For example, it may be added to the fermentation broth of soybean to continue the fermentation. In other examples, Sparassis crispa basidiomycetes and Hericiaceae basidiomycetes may be mixed with soybean solution or slurry prior to fermentation.

本態様の方法において、大豆、ハナビラタケ科の担子菌類、サンゴハリタケ科の担子菌類、乳酸菌、資化性糖類以外に、上述した他の原料を添加してもよいし、しなくてもよい。添加量、添加のタイミングは当業者が適宜調整できる。 In the method of this embodiment, in addition to soybean, basidiomycete of Sparassis crispa, basidiomycete of Hericiaceae, lactic acid bacterium, and assimilating saccharide, other raw materials described above may or may not be added. Those skilled in the art can appropriately adjust the amount of addition and the timing of addition.

乾燥させた大豆の乳酸菌発酵物に、ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類を添加、混合したものを、そのまま本発明の組成物とすることができる。また、大豆にハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類を添加してから乳酸菌発酵する場合に、得られた発酵物をそのまま用いる場合は、速やかに冷却することが好ましい。冷却温度は、10℃以下、例えば−2〜10℃が挙げられる。本態様の方法において得られた組成物は、冷蔵保存することが好ましい。また、希釈、濃縮、乾燥等を行ってもよい。乾燥させる場合は加熱を行わない、例えば凍結乾燥による、ことが好ましい。 The composition of the present invention can be obtained by adding and mixing the basidiomycetes of Sparassis crispa and the basidiomycetes of Hericiaceae to the fermented lactic acid bacteria of dried soybean. Further, in the case of adding basidiomycetes of Sparassis crispa and basidiomycetes of Hericiaceae to soybean and then fermenting with lactic acid bacteria, when the obtained fermented product is used as it is, it is preferable to cool it quickly. The cooling temperature is 10 ° C. or lower, for example, -2 to 10 ° C. The composition obtained by the method of this embodiment is preferably stored in a refrigerator. Further, dilution, concentration, drying and the like may be performed. When it is dried, it is preferably not heated, for example, by freeze-drying.

本発明は、他の態様において、大豆の乳酸菌発酵物、ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類を有効成分として含む医薬組成物を提供する。また他の態様において、当該医薬組成物の製造方法を提供する。 In another aspect, the present invention provides a pharmaceutical composition containing a fermented soybean lactic acid bacterium, a basidiomycete of the family Sparassis crispa, and a basidiomycete of the family Hericiaceae as active ingredients. In another aspect, a method for producing the pharmaceutical composition is provided.

本態様では、上記の組成物をそのまま医薬組成物として用いてもよい。または、上記の組成物を常法に従って製剤化してもよく(例えば、Remington's Pharmaceutical Science, latest edition, Mark Publishing Company, Easton, U.S.A参照)、医薬的に許容される担体や添加物を共に含むものであってもよい。例えば界面活性剤、賦形剤、着色料、着香料、保存料、安定剤、緩衝剤、懸濁剤、等張化剤、結合剤、崩壊剤、滑沢剤、流動性促進剤、矯味剤等が挙げられるが、これらに制限されず、その他常用の担体が適宜使用できる。具体的には、軽質無水ケイ酸、乳糖、結晶セルロース、マンニトール、デンプン、カルメロースカルシウム、カルメロースナトリウム、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポリビニルアセタールジエチルアミノアセテート、ポリビニルピロリドン、ゼラチン、中鎖脂肪酸トリグリセライド、ポリオキシエチレン硬化ヒマシ油60、白糖、カルボキシメチルセルロース、コーンスターチ、無機塩類等を挙げることができる。 In this embodiment, the above composition may be used as it is as a pharmaceutical composition. Alternatively, the above composition may be formulated according to a conventional method (see, for example, Remington's Pharmaceutical Science, latest edition, Mark Publishing Company, Easton, USA), including both pharmaceutically acceptable carriers and additives. There may be. For example, surfactants, excipients, colorants, flavoring agents, preservatives, stabilizers, buffers, suspending agents, tonicity agents, binders, disintegrants, lubricants, fluidity promoters, flavoring agents. However, the present invention is not limited to these, and other commonly used carriers can be appropriately used. Specifically, light anhydrous silicic acid, lactose, crystalline cellulose, mannitol, starch, carmellose calcium, carmellose sodium, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinyl acetal diethylaminoacetate, polyvinyl pyrrolidone, gelatin, medium chain fatty acid triglyceride, Examples thereof include polyoxyethylene hydrogenated castor oil 60, sucrose, carboxymethyl cellulose, corn starch, and inorganic salts.

本態様の医薬組成物の投与方法として、経口投与または非経口投与が挙げられ、係る投与方法としては具体的には、注射投与、経鼻投与、経肺投与、経皮投与などが挙げられる。注射投与の例としては、例えば、静脈内注射、筋肉内注射、腹腔内注射、皮下注射などによって本態様の医薬組成物を全身または局部的に投与できる。好ましくは、本態様の医薬組成物の投与方法は経口投与である。本態様の医薬組成物の形態は特に限定されず、例えば濃縮液、粉末、顆粒、錠剤、タブレット、カプセル剤、ドリンク剤等が挙げられる。 Examples of the method for administering the pharmaceutical composition of this embodiment include oral administration and parenteral administration, and specific examples of such administration methods include injection administration, nasal administration, pulmonary administration, and transdermal administration. As an example of injection administration, the pharmaceutical composition of this embodiment can be administered systemically or locally, for example, by intravenous injection, intramuscular injection, intraperitoneal injection, subcutaneous injection, or the like. Preferably, the method of administration of the pharmaceutical composition of this embodiment is oral administration. The form of the pharmaceutical composition of this embodiment is not particularly limited, and examples thereof include concentrates, powders, granules, tablets, tablets, capsules, and drinks.

本態様の医薬組成物の投与対象は、ヒト、ヒトを含む動物、またはヒトを含まない動物が挙げられ、例えば、ヒト、マウス、ラット、サル、ブタ、ウシ、ウマ、ヤギ、ヒツジ、ロバ、イヌ、ネコ、ウサギ、ハムスター、モルモット、ニワトリ、その他家畜、家禽、愛玩動物などが例示できるが、これらに制限されない。 The subject of administration of the pharmaceutical composition of this embodiment includes humans, animals including humans, and animals not containing humans, for example, humans, mice, rats, monkeys, pigs, cows, horses, goats, sheep, donkeys, etc. Examples include, but are not limited to, dogs, cats, rabbits, hamsters, guinea pigs, chickens, and other livestock, poultry, and pet animals.

本態様の医薬組成物は、1日3回、1日2回、あるいは1日1回投与してもよい。また例えば、対象に毎食時またはその前もしくは後に本態様の医薬組成物を投与してもよく、あるいは対象に1日1回、例えば、朝食時またはその前もしくは後、昼食時またはその前もしくは後、夕食時またはその前もしくは後に本態様の医薬組成物を投与してもよい。また、食間に本態様の医薬組成物を投与してもよい。 The pharmaceutical composition of this embodiment may be administered three times a day, twice a day, or once a day. Also, for example, the subject may be administered with the pharmaceutical composition of this embodiment at each meal or before or after, or once daily, for example, at breakfast or before or after, at lunch or before or after. , The pharmaceutical composition of this embodiment may be administered at or before or after dinner. Moreover, you may administer the pharmaceutical composition of this embodiment between meals.

本態様の医薬組成物の投与量は、疾患に応じて適宜調整でき、特に制限されない。投与量の例として、固形分換算で、成人1日あたり組成物として約0.3gまたはそれ以上、約1gまたはそれ以上等が挙げられる。 The dose of the pharmaceutical composition of this embodiment can be appropriately adjusted according to the disease and is not particularly limited. Examples of the dose include, in terms of solid content, about 0.3 g or more, about 1 g or more of the composition per adult per day, and the like.

本態様の医薬組成物は、免疫抑制、アレルギー症状緩和、アレルギー予防、またはがん治療に使用できる。アレルギーとして、例えばアトピー性皮膚炎、気管支ぜんそく、アレルギー性鼻炎、食物・薬物・金属アレルギー等が挙げられる。より具体的な例として、本組成物は花粉症症状緩和、予防用として使用できる。また、本態様の医薬組成物は、腸内フローラへの乳酸菌の定着を促進し、上記効果を持続的に発揮することが期待できる。 The pharmaceutical composition of this embodiment can be used for immunosuppression, allergic symptom relief, allergy prevention, or cancer treatment. Examples of allergies include atopic dermatitis, bronchial asthma, allergic rhinitis, food / drug / metal allergies, and the like. As a more specific example, this composition can be used for alleviating and preventing pollinosis symptoms. In addition, the pharmaceutical composition of this embodiment can be expected to promote the colonization of lactic acid bacteria in the intestinal flora and continuously exert the above effects.

本態様におけるがんの例として、悪性黒色腫(メラノーマ)、皮膚がん、肺がん、気管および気管支がん、口腔上皮がん、食道がん、胃がん、結腸がん、直腸がん、大腸がん、肝臓および肝内胆管がん、腎臓がん、膵臓がん、前立腺がん、乳がん、子宮がん、卵巣がん、脳腫瘍等の上皮細胞などが悪性化したがん・腫瘍や、筋肉腫、骨肉腫、ユーイング肉腫等の支持組織を構成する細胞である筋肉や骨が悪性化したがん・腫瘍や、白血病、悪性リンパ腫、骨髄腫、バーキットリンパ腫等の造血細胞由来のがん・腫瘍などを挙げることができる。 Examples of cancers in this embodiment are malignant melanoma, skin cancer, lung cancer, tracheal and bronchial cancer, oral epithelial cancer, esophageal cancer, gastric cancer, colon cancer, rectal cancer, colon cancer. , Liver and intrahepatic bile duct cancer, kidney cancer, pancreatic cancer, prostate cancer, breast cancer, uterine cancer, ovarian cancer, brain tumor and other cancers / tumors with malignant epithelial cells, myoma, Cancers / tumors in which muscles and bones that make up supporting tissues such as osteosarcoma and Ewing sarcoma have become malignant, and cancers / tumors derived from hematopoietic cells such as leukemia, malignant lymphoma, myeloma, and Berkit lymphoma Can be mentioned.

本発明は、他の態様において、大豆の乳酸菌発酵物、ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類を含む食品を提供する。また他の態様において、当該食品の製造方法を提供する。 In another aspect, the present invention provides a food containing a fermented soybean lactic acid bacterium, a basidiomycete of the family Sparassis crispa, and a basidiomycete of the family Hericiaceae. Further, in another aspect, a method for producing the food is provided.

本態様では、上記の組成物をそのまま食品として用いてもよい。また、上記医薬組成物で挙げた担体や添加物を含んでもよい。本態様の食品の形態は特に限定されず、例えば濃縮液、粉末、顆粒、タブレット、錠剤、ガム、キャンディー、カプセル、ペースト、ゼリー、ドリンク等が挙げられる。また、上記の組成物をそのまま、または濃縮液、粉末、顆粒、ペースト等の状態として他の食品に添加してもよい。また、上記の組成物をそのまま、または濃縮液、粉末、顆粒、ペースト等の状態とし、必要に応じて他の原料を添加して、食品添加物として利用してもよい。 In this embodiment, the above composition may be used as it is as a food. In addition, the carriers and additives mentioned in the above pharmaceutical compositions may be included. The form of the food of this embodiment is not particularly limited, and examples thereof include concentrates, powders, granules, tablets, tablets, gums, candies, capsules, pastes, jellies, and drinks. Further, the above composition may be added to other foods as it is or in the form of a concentrate, powder, granules, paste or the like. Further, the above composition may be used as it is, or in a state of a concentrate, powder, granule, paste or the like, and if necessary, other raw materials may be added and used as a food additive.

本態様の食品に含まれ得る、他の原料の例として、例えば砂糖、塩、醤油、味噌、酢等の調味料;蜂蜜、メープルシロップ、スクラロース登録商標、アセスルファムカリウム、アスパルテーム等の甘味料;クエン酸、リンゴ酸、酒石酸、酢酸等の酸味料;カフェイン、ナリンジン等の苦味料;オレガノ、コショウ、シナモン、ショウガ、ターメリック、唐辛子、バジル、パプリカ、わさび等の香辛料;サラダ油、ごま油、サフラワー油、ひまわり油、菜種油、魚油、牛脂、豚脂等の油;香味油;酵母エキス、魚介エキス、ビーフエキス、ポークエキス、チキンエキス等のエキス類;果汁;野菜汁;ビタミン;ミネラル;糖類;オリゴ糖類;多糖類;食物繊維;アミノ酸;ペプチド;脂肪酸;補酵素;香料;乳化剤;増粘剤;発色剤などが挙げられる。 Examples of other raw materials that may be contained in the food of this embodiment are seasonings such as sugar, salt, soy sauce, miso, vinegar; sweeteners such as honey, maple syrup, sclarose registered trademark , acesulfam potassium, aspartame; Acids such as acid, malic acid, tartaric acid, acetic acid; bitterness such as caffeine, narringine; spices such as oregano, pepper, cinnamon, ginger, turmeric, chili, basil, paprika, wasabi; salad oil, sesame oil, saflower oil , Sunflower oil, rapeseed oil, fish oil, beef fat, pork fat, etc .; flavor oil; yeast extract, seafood extract, beef extract, pork extract, chicken extract and other extracts; fruit juice; vegetable juice; vitamins; minerals; sugars; oligosaccharides ; Polysaccharides; dietary fiber; amino acids; peptides; fatty acids; coenzymes; flavors; emulsifiers; thickeners; color formers and the like.

本態様の食品は、1日3回、1日2回、あるいは1日1回摂取してもよい。ある実施形態において、本態様の食品は機能性食品として、例えば、毎食時またはその前もしくは後に摂取してもよく、あるいは1日1回、例えば、朝食時またはその前もしくは後、昼食時またはその前もしくは後、夕食時またはその前もしくは後に摂取してもよい。また、食間に摂取してもよい。 The food of this embodiment may be ingested three times a day, twice a day, or once a day. In certain embodiments, the food of this embodiment may be ingested as a functional food, eg, at each meal or before or after, or once daily, eg, at breakfast or before or after, at lunch or above. It may be taken before or after, at dinner or before or after. It may also be taken between meals.

本態様の食品の摂取量は、商品設計に応じて適宜調整でき、特に制限されない。好ましい摂取量の例として、例えば成人一日あたり組成物として5〜100ml、10〜75ml、20〜60ml、40〜60ml等である。 The intake of the food of this embodiment can be appropriately adjusted according to the product design and is not particularly limited. Examples of preferred intakes are, for example, 5 to 100 ml, 10 to 75 ml, 20 to 60 ml, 40 to 60 ml, etc. of the composition per day for adults.

本態様の食品は、免疫抑制、アレルギー症状緩和、アレルギー予防等の効果が期待できる。アレルギーとして、例えばアトピー性皮膚炎、気管支ぜんそく、アレルギー性鼻炎、食物・薬物・金属アレルギー等が挙げられる。より具体的な例として、本組成物は花粉症症状緩和、予防用として使用できる。また、本態様の食品は、腸内フローラへのOTU520の乳酸菌の定着を促進し、上記効果を持続的に発揮することが期待できる。本態様の食品の摂取対象は特に制限されず、乳幼児、成人、高齢者等幅広く利用できる。 The food of this embodiment can be expected to have effects such as immunosuppression, allergic symptom relief, and allergy prevention. Examples of allergies include atopic dermatitis, bronchial asthma, allergic rhinitis, food / drug / metal allergies, and the like. As a more specific example, this composition can be used for alleviating and preventing pollinosis symptoms. In addition, the food of this embodiment can be expected to promote the colonization of lactic acid bacteria of OTU520 in the intestinal flora and continuously exert the above effects. The ingestion target of the food of this embodiment is not particularly limited, and can be widely used by infants, adults, the elderly and the like.

以下、実施例により本発明の実施形態についてより具体的に記載する。 Hereinafter, embodiments of the present invention will be described in more detail with reference to Examples.

実施例1:植物由来乳酸菌の同定
刀根早生種の柿から単離された乳酸菌について、16SrDNA解析を行った。得られた16SrDNAの配列を表1に示す。
Example 1: Identification of plant-derived lactic acid bacteria 16S rDNA analysis was performed on lactic acid bacteria isolated from persimmons of early-maturing sword roots. The sequence of the obtained 16SrDNA is shown in Table 1.

Figure 2021078495
Figure 2021078495

本配列は、Lactobacillus paracasei subsp. paracasei JCM8130株に100%の相動性を示しており、本乳酸菌はラクトバチルス・パラカゼイであると同定された。また、その塩基配列より、OTUの理論値が517bpとなるので、OTU520の範囲に含まれるものであった。OTU(Operational Taxonomic Unit)とは、T−RFLP解析における分類単位を意味し、菌の種類に相当するものをいう(特開2012−165716号公報参照)。OTU520の乳酸菌とは、ヒト腸内細菌分類群のうち、Lactobacillus、Streptococcus、Enterococcus等を含む、いわゆる善玉菌と呼ばれる乳酸菌群をいう(例えば、URL: https://www.tecsrg.co.jp/t-rflp/tree_html/lactobacillales_520.html参照)。 This sequence showed 100% compatibility with the Lactobacillus paracasei subsp. Paracasei JCM8130 strain, and this lactic acid bacterium was identified as Lactobacillus paracasei. Further, since the theoretical value of OTU is 517 bp from the base sequence, it is included in the range of OTU520. The OTU (Operational Taxonomic Unit) means a classification unit in T-RFLP analysis, and refers to a unit corresponding to the type of fungus (see JP-A-2012-165716). The lactic acid bacterium of OTU520 refers to a so-called good bacterium group including Lactobacillus, Streptococcus, Enterococcus, etc. in the human intestinal bacterium classification group (for example, URL: https://www.tecsrg.co.jp/). See t-rflp/tree_html/lactobacillales_520.html).

実施例2:組成物(液体)の調製
丸大豆を水で洗浄した後、3倍量の水を加えて15時間浸漬した後、100℃に加熱して3時間煮沸処理した。処理物をろ過し、ろ液にビタミンC、ヤマブシタケ、ハナビラタケを添加し、混合した。ろ過残渣をミルで粉砕し、大豆粕を分離した後、混合物に添加した。得られた混合物を121℃20分で高圧滅菌し、35℃に冷却した。実施例1で得た乳酸菌を添加し、30℃で24時間培養した後、容器に充填し本発明の組成物(液体)を得た。本組成物の配合を表2に示す。
Example 2: Preparation of composition (liquid) After washing the whole soybean with water, 3 times the amount of water was added, the mixture was immersed for 15 hours, and then heated to 100 ° C. and boiled for 3 hours. The treated product was filtered, and Vitamin C, Lion's mane, and Sparassis crispa were added to the filtrate and mixed. The filtration residue was milled to separate soybean meal and then added to the mixture. The resulting mixture was sterilized under high pressure at 121 ° C. for 20 minutes and cooled to 35 ° C. The lactic acid bacterium obtained in Example 1 was added, and the mixture was cultured at 30 ° C. for 24 hours and then filled in a container to obtain the composition (liquid) of the present invention. The composition of this composition is shown in Table 2.

Figure 2021078495
Figure 2021078495

実施例3:組成物(カプセル)の調製
丸大豆を水で洗浄した後、3倍量の水を加え、さらに酢酸をpH4.0になるように加えた後、冷蔵で一晩浸漬した。水切り後、蒸し器にて100℃1時間蒸煮した後、ミートチョッパー(φ5mm)にて粉砕し、35℃まで冷却した。実施例1で得た乳酸菌および糖質を添加し、30℃で24時間培養した後、フリーズドライ、粉砕して大豆の乳酸菌発酵物の粉末を得た。これにハナビラタケ末、ヤマブシタケ末、他の成分を配合し、カプセルに充填して本発明の組成物(カプセル)を得た。本組成物の配合を表3に示す。
Example 3: Preparation of composition (capsule) The whole soybean was washed with water, three times the amount of water was added, acetic acid was further added to pH 4.0, and the soybean was immersed in a refrigerator overnight. After draining, it was steamed at 100 ° C. for 1 hour in a steamer, pulverized with a meat chopper (φ5 mm), and cooled to 35 ° C. The lactic acid bacteria and sugars obtained in Example 1 were added, cultured at 30 ° C. for 24 hours, freeze-dried, and pulverized to obtain a powder of a fermented soybean lactic acid bacterium. Sparassis crispa powder, Lion's mane powder, and other ingredients were added thereto and filled into capsules to obtain the composition (capsule) of the present invention. The composition of this composition is shown in Table 3.

Figure 2021078495
Figure 2021078495

実施例4:アレルギー抑制作用の確認
マウスを2群に分け、一方の群は実施例2で得た組成物を、他方の群は真水を37日間摂取させた。双方の群に、腹腔内に精製スギ花粉抗原およびアジュバントを投与した(1μg、週1回×3回、およびくしゃみ検査のために0.2μg点鼻投与1日1回×7日)。摂取開始37日後にELISA法により血中のIL−10およびIL−4濃度を測定した。結果を図3、4に示す。本発明の組成物を摂取した群は、花粉症を抑制するサイトカインIL−10の量が有意に高く、また花粉症を悪化させるサイトカインIL−4の量が有意に低い結果となった。
Example 4: Confirmation of allergy-suppressing effect Mice were divided into two groups, one group was ingested with the composition obtained in Example 2, and the other group was ingested with fresh water for 37 days. Both groups received intraperitoneal purified cedar pollen antigen and adjuvant (1 μg, once weekly x 3 times, and 0.2 μg nasal drops once daily x 7 days for sneezing test). The IL-10 and IL-4 concentrations in the blood were measured by the ELISA method 37 days after the start of ingestion. The results are shown in FIGS. 3 and 4. In the group ingesting the composition of the present invention, the amount of cytokine IL-10 that suppresses pollinosis was significantly high, and the amount of cytokine IL-4 that exacerbated pollinosis was significantly low.

実施例5:本発明の組成物による腸内フローラの変化
マウスを3群に分け、通常飼育群として、滅菌MF飼料(オリエンタル酵母)を与えた群、投与群として、実施例3の組成物を、カプセルではなくタブレットにしたものを、5.5gタブレットを1日当たり8粒与えた群、コントロール群として、実施例3の組成物の発酵大豆粉末を大豆パウダーに置き換え、ハナビラタケ末およびヤマブシタケ末無添加のタブレットを作成し、1日当たり8粒与えた群とした。実験開始前(day0)および4週間経過時(day28)の時点で各マウスから糞飼料を採取し、T−RFLP法/Nagashima法による分析を行い、各実験群間およびday0とday28の間でヒト腸内細菌分類群の各OTUのピーク面積比を比較した。
Example 5: Changes in intestinal flora by the composition of the present invention The mice were divided into three groups, and the composition of Example 3 was used as a normal breeding group, a group fed with a sterilized MF feed (Oriental yeast), and an administration group. , The group in which 8 tablets of 5.5 g tablets were given per day instead of capsules, and as a control group, the fermented soybean powder of the composition of Example 3 was replaced with soybean powder, and Hanabira bamboo powder and Yamabushitake powder were not added. Tablets were prepared and used as a group in which 8 tablets were given per day. Fecal feed was collected from each mouse before the start of the experiment (day 0) and at the time when 4 weeks had passed (day 28), and analysis was performed by the T-RFLP method / Nagashima method. The peak area ratio of each OTU in the Gut microbiota taxon was compared.

マウス個体毎の各OTUピーク面積比を算出したところ、投与群のday28では、day0で検出されなかったOTU520 Lactobacillalesが10匹中8匹に検出された。この新たに検出されたOTU520の菌群は本発明の組成物に含まれている乳酸菌に該当し、本発明の組成物の摂取によってマウスに取り込まれたものと考えられた。本発明の組成物は、植物性乳酸菌が生きたまま腸に届き、効率よく乳酸菌を腸内フローラに定着させることができると考えられた。 When the peak area ratio of each OTU for each individual mouse was calculated, OTU520 Lactobacillales, which was not detected on day0, was detected in 8 out of 10 mice on day28 of the administration group. This newly detected bacterial group of OTU520 corresponds to the lactic acid bacterium contained in the composition of the present invention, and it is considered that it was taken up by the mouse by ingestion of the composition of the present invention. It was considered that the composition of the present invention allows plant-derived lactic acid bacteria to reach the intestine alive and efficiently colonize the intestinal flora.

実施例6:アレルギーインデックスおよび腫瘍マーカーへの影響
成人に対し、アレルギーインデックス(IgE、Viewアレルギー39項目)および腫瘍マーカー(CEA、TPA、CA15−3、CA19−9、CA125、HER2蛋白質量、ICTP、PSA)を検査し、アレルギー疾患を持つ、または腫瘍マーカーが基準値以上の被験者を選択し、3ヶ月に1回、実施例3の組成物を配布し、経過観察および検査を実施した。アレルギーインデックスの数値、および腫瘍マーカーの数値の改善は、それぞれアレルギー症状の緩和、およびがん治療効果を有することを示す。
Example 6: Effects on allergy index and tumor marker For adults, allergy index (IgE, View allergy 39 items) and tumor marker (CEA, TPA, CA15-3, CA19-9, CA125, HER2 protein mass, ICTP, PSA) was examined, subjects with allergic diseases or tumor markers above the reference value were selected, the composition of Example 3 was distributed once every three months, and follow-up and examination were performed. Improvements in allergy index values and tumor marker values indicate that they have allergic symptom relief and cancer therapeutic effects, respectively.

本発明の組成物は、免疫抑制、アレルギー症状緩和、アレルギー予防、またはがん治療もしくは予防効果を提供する。また、本発明の組成物は、腸内フローラへの乳酸菌の定着を促進し、上記効果を持続的に発揮することが期待できる。 The compositions of the present invention provide immunosuppressive, allergic symptom relief, allergy prevention, or cancer therapeutic or prophylactic effects. In addition, the composition of the present invention can be expected to promote the colonization of lactic acid bacteria in the intestinal flora and continuously exert the above effects.

Claims (7)

大豆の乳酸菌発酵物、ハナビラタケ科の担子菌類およびサンゴハリタケ科の担子菌類を含む、組成物。 A composition comprising a fermented soybean lactic acid bacterium, a basidiomycete of the Sparassis crispa family, and a basidiomycete of the Hericiaceae family. ハナビラタケ科の担子菌類がハナビラタケであり、サンゴハリタケ科の担子菌類がヤマブシタケである、請求項1に記載の組成物。 The composition according to claim 1, wherein the basidiomycete of the family Sparassis crispa is Sparassis crispa, and the basidiomycete of the family Hericiaceae is Lion's mane. 乳酸菌が、柿由来の乳酸菌である、請求項1または2に記載の組成物。 The composition according to claim 1 or 2, wherein the lactic acid bacterium is a persimmon-derived lactic acid bacterium. 乳酸菌が、ラクトバチルス・パラカゼイである、請求項1〜3のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 3, wherein the lactic acid bacterium is Lactobacillus paracasei. 免疫抑制用、アレルギー症状緩和用、アレルギー予防用、またはがん治療もしくは予防用である、請求項1〜4のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 4, which is for immunosuppression, for allergic symptom relief, for allergy prevention, or for cancer treatment or prevention. 花粉症の症状緩和用である、請求項1〜4のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 4, which is used for alleviating the symptoms of pollinosis. がん治療または予防用である、請求項1〜4のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 4, which is used for cancer treatment or prevention.
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