JP5095912B2 - Immune enhancer - Google Patents
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- JP5095912B2 JP5095912B2 JP2004258050A JP2004258050A JP5095912B2 JP 5095912 B2 JP5095912 B2 JP 5095912B2 JP 2004258050 A JP2004258050 A JP 2004258050A JP 2004258050 A JP2004258050 A JP 2004258050A JP 5095912 B2 JP5095912 B2 JP 5095912B2
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Description
本発明は、免疫力を増強し、種々の細菌、ウイルス感染やガンの発生を予防する作用を有するイネ科穀粒ならびに乳酸菌を有効成分として含有する免疫増強剤及びイネ科穀粒ならびに乳酸菌を配合した免疫増強用飲食品に関する。 The present invention comprises a gramineous grain having an action of enhancing immunity and preventing the development of various bacteria, viral infections and cancer, and an immunopotentiator containing lactic acid bacteria as an active ingredient, a gramineous grain and lactic acid bacteria The present invention relates to a food and drink for enhancing immunity.
免疫とは、細菌やウイルスあるいは体内で発生する腫瘍などから生体を守るためのシステムである。近年、この免疫システムを増強させる食品成分が注目されている。このような成分として、乳酸菌、麹カビあるいは酵母などの食用微生物やそれらの細胞壁成分、又は、シイタケやアガリクスに代表される担子菌類の多糖類、特にβグルカン類などが知られている。
これら成分の免疫増強効果は、生体内の様々な細胞に成分が作用し、腫瘍壊死因子(以下TNFと略記)、インターロイキン(以下ILと略記)類、インターフェロン(以下IFNと略記)類などのサイトカインと総称される物質の産生が活性化、誘導されることにより生じる。誘導されたこれらの物質は、免疫担当細胞に作用し免疫系を活性化する。 サイトカインのうち、TNFは、単球やマクロファージから放出され、細胞増殖作用や抗ウイルス作用を示すことが知られている。IL類としては、IL1〜IL18の存在が知られている。そのうちIL12は、感染、炎症、種々の免疫反応などに伴い、主として単球やマクロファージから産生されるペプチドホルモンである。IL12は単球やマクロファージが活性化すると産生量が増加し、さらにリンパ球に働いてIFNγ産生を誘導することが知られている。IFN類は、産生する細胞の種類によって名称が異なり、IFNα、IFNβ、IFNγの3つが知られている。IFNγは、主としてリンパ球が産生する、分子量が約2万の糖蛋白質であって、抗ウイルス作用、マクロファージやナチュラルキラー細胞などの免疫担当細胞の活性化や分化誘導に作用し免疫調節因子として注目されている。
免疫担当細胞の活性が弱くなることにより引き起こされる病態には、免疫失調、免疫系の種々の異常、膠原病や潰瘍性大腸炎などの自己免疫疾患、アレルギー疾患、動脈硬化、インスリン抵抗性、糖尿病などの代謝性疾患や、多発性硬化症、移植片対宿主症、細菌感染症、ウイルス感染症、ウイルス肝炎、HIV感染などの感染症などがあり、免疫担当細胞を活性化することは、これら病態の予防、治療、改善、再発防止に非常に有益となりうる。そのため、免疫担当細胞を活性化できるような免疫増強剤、さらには免疫担当細胞を活性化できるような飲食品が強く望まれていた。
Immunity is a system for protecting a living body from bacteria, viruses, or tumors that occur in the body. In recent years, food ingredients that enhance this immune system have attracted attention. Known as such components are edible microorganisms such as lactic acid bacteria, mold and yeast, cell wall components thereof, and polysaccharides of basidiomycetes represented by shiitake mushrooms and agaricus, particularly β-glucans.
These components enhance the immune effect of various components in the body, such as tumor necrosis factor (hereinafter abbreviated as TNF), interleukins (hereinafter abbreviated as IL), and interferons (hereinafter abbreviated as IFN). This is caused by the activation and induction of production of substances collectively called cytokines. These induced substances act on immunocompetent cells and activate the immune system. Among cytokines, TNF is released from monocytes and macrophages and is known to exhibit cell proliferation and antiviral effects. The presence of IL1 to IL18 is known as ILs. Among them, IL12 is a peptide hormone produced mainly from monocytes and macrophages due to infection, inflammation, various immune responses and the like. IL12 is known to increase in production when monocytes and macrophages are activated, and to act on lymphocytes to induce IFNγ production. The names of IFNs vary depending on the type of cells to be produced, and three types are known: IFNα, IFNβ, and IFNγ. IFNγ is a glycoprotein with a molecular weight of approximately 20,000 that is produced mainly by lymphocytes. It acts as an immune regulator by acting on antiviral activity, activation of immune cells such as macrophages and natural killer cells, and induction of differentiation. Has been.
The pathology caused by weaker immunocompetent cell activity includes immune dysfunction, various abnormalities of the immune system, autoimmune diseases such as collagen disease and ulcerative colitis, allergic diseases, arteriosclerosis, insulin resistance, diabetes There are metabolic diseases such as multiple sclerosis, graft-versus-host disease, bacterial infections, viral infections, viral hepatitis, HIV infections, etc. It can be very beneficial in preventing, treating, improving, and preventing relapses. Therefore, there has been a strong demand for an immunopotentiator that can activate immunocompetent cells, and a food or drink that can activate immunocompetent cells.
これらIL1やIL12あるいはIFNγの産生を増強させるものとして、微生物由来の多糖類、或いは細胞壁成分などでは酵母菌体、乳酸菌菌体などが細胞培養実験で知られている。また、シイタケ抽出多糖類であるレンチナン或いは担子菌類のβグルカン類もIL1やIL12あるいはIFNγの産生増強に有効であることが知られている。しかし、これら微生物や担子菌は、培養に手間がかかり、特殊な設備を必要とする。また、これら微生物や胆子菌類由来のβグルカン或いはその他多糖類の抽出は、操作が煩雑であると共に、精製工程も煩雑で、コスト及び操作時間が多大にかかり、得られる食品素材あるいは食品が非常に高価なものとなってしまうという問題がある。さらに、免疫増強作用があるイネ科植物由来βグルカンを酸加水分解や酵素分解により低分子化して水溶性を高める技術も知られているが(例えば、特許文献1参照)、食品、医薬品などの素材として使用する場合、加熱操作や長時間の撹拌操作などが必要になり、酸や熱による変性や分子修飾のためのコストが高くなるという問題がある。また、化学的処理をした食品に抵抗感を抱く消費者も多いという問題がある。ゆえに、化学的処理を施さない、天然の食品を用いた免疫増強成分が望まれていた。
本発明の目的は、オーツ麦、大麦、小麦、ライ麦、米、とうもろこしなどのイネ科穀粒と乳酸菌とを組み合わせた免疫増強剤、及び免疫増強用飲食品を提供することにある。 An object of the present invention is to provide an immunopotentiator combining a gramineous grain such as oat, barley, wheat, rye, rice, corn and lactic acid bacteria, and a food and drink for immune boost.
本発明者は免疫増強作用を有する食品素材について鋭意研究を重ねた結果、オーツ麦などのイネ科穀粒及びその加工物とラクトバチルスなどの乳酸菌とを組み合わせた組成物が、それぞれが単独のものよりも免疫増強効果が相乗的に高まることを見出し、本発明を完成させるに至った。
すなわち本発明は、腹腔マクロファージと脾臓細胞とを共培養し、免疫原としてオボアルブミンを加えた培地に、乳酸菌の添加、無添加とオートミールの添加、無添加を組み合わせた実験系でNO2 -イオン産生量、IL12量、IFNγ量を測定したところ、マクロファージ活性化を反映するNO2 -イオン量は、オートミール単独添加、乳酸菌単独添加でも産生が確認されたが、オートミールに乳酸菌を添加した場合は、産生量が飛躍的に増大した。
また、IL12、IFNγのサイトカイン産生量は、オートミール単独添加や乳酸菌単独添加でもサイトカイン産生が見られたが、オートミールに乳酸菌、特にラクトバチルス・ガセリ菌を添加した場合は、産生量が飛躍的に増大した。
このように、オーツ麦などのイネ科穀粒及びその加工物とラクトバチルスなどの乳酸菌とを組み合わせた組成物がマクロファージを活性化し、それぞれが単独のものよりも、NO2 -イオン産生量や、IL12、IFNγのサイトカイン産生量が相乗的に増大することを見出し、イネ科穀粒及びその加工物と乳酸菌とを組み合わせたものが格別の免疫増強効果を有することが判明した。
As a result of intensive research on food materials having an immune enhancing effect, the present inventors have found that each composition comprising a combination of gramineous grains such as oats and processed products thereof and lactic acid bacteria such as Lactobacillus is independent. As a result, the present inventors have found that the immunopotentiating effect is synergistically increased and has completed the present invention.
That is, the present invention is to co-cultured with peritoneal macrophages and spleen cells, the medium ovalbumin added as an immunogen, the addition of lactic acid bacteria, the addition of additive-free and oatmeal, in experimental systems that combine additive-free NO 2 - ions production amount, IL12 amount was measured for IFNγ amount, NO 2 reflects macrophage activation - ion amount, oatmeal added alone, although production in lactic acid bacteria added alone is confirmed, the case of adding lactic acid bacteria to oatmeal, Production increased dramatically.
In addition, cytokine production of IL12 and IFNγ was also observed when oatmeal alone or lactic acid bacteria were added alone, but when lactic acid bacteria, especially Lactobacillus gasseri bacteria were added to oatmeal, the production amount increased dramatically. did.
In this way, a composition comprising a combination of gramineous grains such as oats and processed products thereof and lactic acid bacteria such as Lactobacillus activates macrophages, each producing more NO 2 - ions than a single one, It was found that cytokine production of IL12 and IFNγ synergistically increased, and it was found that a combination of gramineous grains and processed products thereof and lactic acid bacteria has a special immune enhancing effect.
したがって、本発明は、
(1) イネ科穀粒及び/又はその加工物と乳酸菌とを含有する免疫増強剤
(2) イネ科穀粒及び/又はその加工物を乳酸菌で発酵させた前記(1)記載の免疫増強剤
(3) イネ科穀粒及び/又はその加工物と乳酸菌菌体又は発酵乳とを混合した前記(1)〜(2)のいずれかに記載の免疫増強剤
(4) イネ科穀粒が、オーツ麦、大麦類、小麦類、ライ麦類、とうもろこし類又は米類の穀粒である前記(1)〜(3)のいずれかに記載の免疫増強剤
(5) 乳酸菌がラクトバチルス・ガセリである前記(1)〜(4)のいずれかに記載の免疫増強剤
(6) イネ科穀粒及び/又はその加工物と乳酸菌とを配合した免疫増強用飲食品
(7) イネ科穀粒及び/又はその加工物を乳酸菌で発酵させた前記(6)記載の免疫増強用飲食品
(8) イネ科穀粒及び/又はその加工物と乳酸菌菌体又は発酵乳とを混合した前記(6)〜(7) のいずれかに記載の免疫増強用飲食品
(9) イネ科穀粒が、オーツ麦、大麦類、小麦類、ライ麦類、とうもろこし類又は米類の穀粒である前記(6)〜(8)のいずれかに記載の免疫増強用飲食品
(10)乳酸菌がラクトバチルス・ガセリである前記(6)〜(9)のいずれかに記載の免疫増強用飲食品
からなる。
Therefore, the present invention
(1) Immunity enhancing agent containing gramineous grain and / or processed product thereof and lactic acid bacteria
(2) The immunopotentiator according to (1) above, wherein the gramineous grain and / or processed product thereof is fermented with lactic acid bacteria.
(3) The immunopotentiator according to any one of (1) to (2) above, wherein a gramineous grain and / or processed product thereof and lactic acid bacteria or fermented milk are mixed.
(4) The immunopotentiator according to any one of (1) to (3), wherein the gramineous grain is oat, barley, wheat, rye, corn, or rice grain.
(5) The immune enhancer according to any one of (1) to (4), wherein the lactic acid bacterium is Lactobacillus gasseri
(6) Immunity-enhancing foods and drinks containing cereal grains and / or processed products thereof and lactic acid bacteria
(7) The immune enhancing food or drink according to (6) above, wherein the gramineous grain and / or processed product thereof is fermented with lactic acid bacteria.
(8) The food / drink for immune enhancement according to any one of (6) to (7) above, wherein a gramineous grain and / or processed product thereof and lactic acid bacteria or fermented milk are mixed.
(9) The immunity-enhancing food or drink according to any one of (6) to (8), wherein the gramineous grain is oat, barley, wheat, rye, corn, or rice grain (10) The immune enhancing food or drink according to any one of (6) to (9), wherein the lactic acid bacterium is Lactobacillus gasseri.
本発明のイネ科穀粒及びその加工物と乳酸菌の配合物は、体内におけるIL12をはじめとするサイトカインの産生を促進し、それぞれを単独で摂る場合に比べて、飛躍的に産生量が増大することで、免疫システム全体に作用し、感染症や腫瘍発生の予防に有用である。 The gramineous grain of the present invention and the processed product thereof and the combination of lactic acid bacteria promote the production of cytokines including IL12 in the body, and the production amount is dramatically increased as compared with the case where each is taken alone. Therefore, it acts on the entire immune system and is useful for preventing infections and tumors.
本発明の免疫増強剤は、免疫担当細胞活性化作用あるいはサイトカイン、特にIFNγの産生促進作用を有する免疫増強作用を有し、そのまま摂取するか、あるいは飲食品などの素材として適している。 The immunopotentiator of the present invention has an immunopotentiating effect that activates immunocompetent cells or promotes the production of cytokines, particularly IFNγ, and is suitable for use as a raw material for foods and beverages.
本発明の免疫増強剤はイネ科植物種子由来の穀粒及びその加工物を用いる。イネ科植物の例としては、米類、小麦類、トウモロコシ類、ヒエ類、アワ類、キビ類、大麦類、オーツ麦類(カラス麦類)、ライ麦類などが挙げられ、好ましくは、大麦類、オーツ麦類、さらに好ましくはオーツ麦類である。本発明でイネ科穀粒とは、イネ科植物種子の可食部分を指す。また、本発明のイネ科植物種子由来の穀粒の加工物は、穀粒を一般に食品として用いられるときに行われる処理を行ったもので、例えばオートミール、押し麦、小麦粉、ライ麦粉、とうもろこし粉、米、米粉、さらに発芽玄米など、食用に適したいかなる形態のものでも用いることができる。また、加工及び調理の形態はどのようなものでもよく、粥や炊飯米などに用いられる加水加熱、パンやビスケットなどに用いられる焙焼などの処理をしてもよい。 The immunopotentiator of the present invention uses a grain derived from a grass seed and a processed product thereof. Examples of gramineous plants include rice, wheat, corn, barnyard millet, millet, millet, barley, oats (crown), rye, etc., preferably barley Oats, more preferably oats. In the present invention, the gramineous grain refers to the edible part of the gramineous plant seed. Moreover, the processed product of the grain derived from the grass seed of the present invention is a processed product that is generally used when the grain is used as a food, such as oatmeal, pressed wheat, wheat flour, rye flour, corn flour, Any form suitable for food, such as rice, rice flour, and germinated brown rice can be used. Moreover, what kind of thing may be sufficient as a process and cooking, You may perform processes, such as the water heating used for rice cake, cooked rice, etc., and the roasting used for bread, a biscuits, etc.
本発明の乳酸菌はラクトバチルス属の乳酸菌が好ましく、さらに好ましくは、ラクトバチルス・ガセリが挙げられる。この他にもラクトコッカス属、ストレプトコッカス属、ロイコノストック属、エンテロコッカス属、サーモフィルス属、ビフィドバクテリウム属を用いることもできる。 The lactic acid bacterium of the present invention is preferably a lactic acid bacterium of the genus Lactobacillus, more preferably Lactobacillus gasseri. In addition, the genus Lactococcus, Streptococcus, Leuconostoc, Enterococcus, Thermofilus, and Bifidobacterium can also be used.
また、乳酸菌とイネ科穀粒及びその加工物との混合方法は、穀粒あるいはその穀粉などの加工物に、生菌を接種する、あるいはさらにそれを発酵させる、凍結乾燥品などの菌体を混合するか、あるいは発酵乳などの乳酸菌含有食品と混合するかのいずれでもよい。さらには、イネ科穀粒及びその加工物を加水加熱したものに、生菌を接種するか、あるいはさらにそれを発酵させる、凍結乾燥品などの菌体を混合する、あるいは発酵乳などの乳酸菌含有食品と混合するかのいずれであってもよい。 In addition, the method of mixing lactic acid bacteria with gramineous grains and processed products thereof is to inoculate viable microorganisms into processed products such as grains or flour thereof, or to ferment them, such as lyophilized products. Either mixing or mixing with food containing lactic acid bacteria such as fermented milk may be used. In addition, ingredients of gramineous grains and processed products thereof are hydrolyzed and inoculated with live bacteria or further fermented, mixed with cells such as freeze-dried products, or contain lactic acid bacteria such as fermented milk Any of mixing with food may be sufficient.
本発明の免疫増強剤の形態は、イネ科穀粒及びその加工物と乳酸菌を混合したものを、粉末状あるいは固形状の場合は、錠剤、カプセル剤、顆粒剤、散剤、粉剤などにすれば良く、経口的に投与することが望ましい。また、流動状の場合は、袋、パウチなどに充填する。これらの形態は、従来から知られている通常の方法で製造することができる。製剤上許可されている担体や賦型剤などと混合して成型しても良い。
また、本発明の免疫増強用飲食品は加工及び調理の形態はどのようなものでもよく、上記のイネ科穀粒及びその加工物と乳酸菌の混合物を、粥や炊飯米などに用いられる加水加熱、パンやビスケットなどに用いられる焙焼などの処理をしてもよく、飲料、発酵乳、麺類、ソーセージなどの飲食品、さらには、各種粉乳の他、乳幼児食品、栄養組成物などに配合することも可能である。
The form of the immunopotentiator of the present invention may be a tablet, capsule, granule, powder, powder, etc. in the case of a powdered or solid mixture of gramineous grains and processed products thereof and lactic acid bacteria. It is good and should be administered orally. In the case of a fluid state, it is filled in a bag, a pouch or the like. These forms can be produced by a conventionally known ordinary method. You may mix and shape | mold with the support | carrier etc. which are permitted on a formulation, an excipient | filler.
In addition, the food and drink for immune enhancement of the present invention may be processed and cooked in any form, and the above-mentioned gramineous grains and the mixture of the processed product and lactic acid bacteria are used for the heating and heating used in rice bran, cooked rice, etc. , Roasting used in breads and biscuits, etc., may be processed into beverages, fermented milk, noodles, sausages and other foods and drinks, as well as various types of powdered milk, infant foods, nutritional compositions, etc. It is also possible.
また、本発明の乳酸菌を、イネ科穀粒及びその加工物に配合して、免疫増強剤あるいは、免疫増強用飲食品などの素材又はそれら素材の加工品に含有させて使用する場合、イネ科穀粒及びその加工物と乳酸菌の混合物を0.01〜50重量%含有させることが好ましい。
これらの免疫増強剤及び免疫増強用飲食品などは、免疫増強能を有するので、前述した免疫の不調により引き起こされるさまざまな病態の予防、治療、改善、再発防止に非常に有益となりうる。
In addition, when the lactic acid bacterium of the present invention is blended in a gramineous grain and processed product thereof and used in an immunopotentiating agent, a material such as an immune enhancing food or drink, or a processed product of such a material, It is preferable to contain 0.01 to 50% by weight of a mixture of grains and processed products thereof and lactic acid bacteria.
These immunity enhancing agents and immunity-enhancing foods and drinks have immunity-enhancing ability and can be very useful for prevention, treatment, improvement, and prevention of recurrence of various pathological conditions caused by the above-mentioned immunity disorder.
本発明の免疫増強能を発揮させるためには、成人の場合、乳酸菌が菌体重量で10〜1,000mgイネ科穀粒及びその加工物が乾燥重量で1〜100g摂取することが望ましく、このように配合量を調整すれば良い。 In order to exert the immunopotentiating ability of the present invention, in the case of adults, it is desirable that lactic acid bacteria ingest 10 to 1,000 mg of gramineous grains and their processed products 1 to 100 g by dry weight. What is necessary is just to adjust a compounding quantity.
以下に、実施例及び試験例を示し、本発明についてより詳細に説明するが、これらは単に例示するのみであり、本発明はこれらによって何ら限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples. However, these are merely illustrative and the present invention is not limited thereto.
[試験例1]
腹腔マクロファージと脾臓細胞とを共培養し、免疫原としてオボアルブミンを加えた培地に、乳酸菌とオートミールの添加、無添加を組み合わせた実験系でマクロファージ活性化とサイトカイン産生を調べるために、NO2 -イオン産生量、IL12量、IFNγ量を測定した。
(試料の調製)
市販のオートミール10gを粉砕し、水0.09Lを加えて撹拌し、オートミール懸濁液を得た。次に、その懸濁液を加熱し、αアミラーゼを作用させて可溶性画分を採取し、さらにエタノールを接触させて沈殿させた画分を回収し、オーツβグルカンを得た。
MRS培地(DIFCO社製)1Lを滅菌し、ラクトバチルス・ガセリ(Lactobacillus gasseri) SBT2055(FERM P-15535)株の生菌10mgを接種し、37℃で一晩培養した。これを1700×gで25分間遠心分離し、乳酸菌の沈殿を得た。これに滅菌水を加えて懸濁し、菌体を洗浄するために遠心分離を3回繰り返した。これを100℃で30分間加熱してから凍結乾燥して乳酸菌体乾燥物1.0gを得た。この手法を用いてラクトバチルス・カゼイ(Lactobacillus casei) ATCC 393株ならびにビフィドバクテリウム・ロンガム(Bifidobacterium longum) SBT2928(FERM P-10657)株の菌体乾燥物を得た。
[Test Example 1]
The peritoneal macrophages and splenic cells were cocultured in medium ovalbumin added as an immunogen, the addition of lactic acid bacteria and oatmeal, in order to examine the macrophage activation and cytokine production in experimental systems that combine additive-free, NO 2 - The amount of ion production, the amount of IL12, and the amount of IFNγ were measured.
(Sample preparation)
10 g of commercially available oatmeal was pulverized, 0.09 L of water was added and stirred to obtain an oatmeal suspension. Next, the suspension was heated, α-amylase was allowed to act to collect a soluble fraction, and the fraction precipitated by contact with ethanol was collected to obtain oat β-glucan.
1 L of MRS medium (manufactured by DIFCO) was sterilized, inoculated with 10 mg of live bacteria of Lactobacillus gasseri SBT2055 (FERM P-15535) strain, and cultured at 37 ° C. overnight. This was centrifuged at 1700 × g for 25 minutes to obtain a precipitate of lactic acid bacteria. This was suspended in sterilized water and centrifuged three times to wash the cells. This was heated at 100 ° C. for 30 minutes and then lyophilized to obtain 1.0 g of a dried lactic acid bacterium. Lactobacillus casei ATCC 393 strain and Bifidobacterium longum SBT2928 (FERM P-10657) strain were obtained using this technique.
(腹腔マクロファージの誘導と調製)
上記オートミール懸濁液0.1ml、あるいは同量のβグルカン懸濁液(固形濃度1%)、あるいは生理食塩水をBALB/cマウスの腹腔に投与した。3日後にハンクス塩類緩衝液5mlを腹腔に投与し、腹部をマッサージして緩衝液を回収し、洗浄し、培養プレートに培養し、1時間後に浮遊細胞を除去して、腹腔マクロファージが接着した培養プレートを得た。
(Induction and preparation of peritoneal macrophages)
0.1 ml of the above oatmeal suspension or the same amount of β-glucan suspension (solid concentration 1%) or physiological saline was administered into the peritoneal cavity of BALB / c mice. After 3 days, Hank's salt buffer 5ml was administered to the abdominal cavity, the abdomen was massaged, the buffer was collected, washed, cultured on a culture plate, and suspended cells were removed after 1 hour, and the peritoneal macrophages adhered A plate was obtained.
(マウス脾臓細胞の調製)
BALB/cマウスに一匹当たり0.05mgのオボアルブミンと1mgの水酸化アルミニウムを混合したエマルジョンを、腹腔に投与した。10日後に解剖し、脾臓を摘出し、培養液中で脾臓を磨砕し、リンホプレップ(比重1.077)で密度勾配遠心を行い、脾臓細胞浮遊液を得た。
(Preparation of mouse spleen cells)
BALB / c mice were administered intraperitoneally with an emulsion containing 0.05 mg ovalbumin and 1 mg aluminum hydroxide per mouse. The spleen was excised 10 days later, the spleen was excised, the spleen was ground in a culture solution, and density gradient centrifugation was performed with a lymphoprep (specific gravity 1.077) to obtain a spleen cell suspension.
(腹腔マクロファージとの共培養)
マクロファージが接着した培養プレートに、脾臓細胞浮遊液を添加した。ブランクには細胞を含まない培地を添加した。さらに、培養液中に免疫原であるオボアルブミンを0.1mg/mlになるように加えた。さらに、ラクトバチルス・ガセリ(Lactobacillus gasseri) SBT2055(FERM P-15535)株、ラクトバチルス・カゼイ(Lactobacillus casei) ATCC 393株、及びビフィドバクテリウム・ロンガム(Bifidobacterium longum) SBT2928(FERM P-10657)株の菌体乾燥物をそれぞれ0.01mg/mlになるように添加して、37℃で3日間培養した。ブランクには菌体を含まない生理食塩水を添加した。
(Co-culture with peritoneal macrophages)
Spleen cell suspension was added to the culture plate to which the macrophages had adhered. Medium without cells was added to the blank. Further, ovalbumin, which is an immunogen, was added to the culture solution so as to be 0.1 mg / ml. Furthermore, Lactobacillus gasseri SBT2055 (FERM P-15535) strain, Lactobacillus casei (Lactobacillus casei) ATCC 393 strain, and Bifidobacterium longum SBT2928 (FERM P-10657) strain Were added at 0.01 mg / ml, and cultured at 37 ° C. for 3 days. Saline containing no bacterial cells was added to the blank.
(NO2 -イオンの定量)
培養上清を回収し、上清中の一酸化窒素産生量を反映するNO2 -イオンを定量し、マクロファージの活性化度合いを調べた。その結果を図1に示す。
図1に示されるように、生理食塩水のみを投与したブランク群では4±3μMであったのに対し、オートミール群で生理食塩水を投与した群は13±5μMであり、活性化が起こっていることが確認された。また、オートミール群で乳酸菌を添加した群は、さらなる活性化が認められた。乳酸菌の中で比較すると、ラクトバチルス・ガセリが30±5μMとなり最も高い活性化誘導能を有しており、ラクトバチルス・カゼイ、及びビフィドバクテリウム・ロンガムはそれぞれ、25±4μM、14±3μMであった。また、βグルカン群で生理食塩水を投与した群では6±3μMであり、ブランク群でラクトバチルス・ガセリを添加した群でも8±5μMであり、オートミール群よりは低いものであった。
(Quantitative determination of NO 2 - ions)
The culture supernatant was collected, and NO 2 − ions reflecting the amount of nitric oxide produced in the supernatant were quantified to examine the degree of macrophage activation. The results are shown in FIG.
As shown in Figure 1, the blank group administered only with saline was 4 ± 3 μM, whereas the oatmeal group administered with saline was 13 ± 5 μM, and activation occurred. It was confirmed that In the oatmeal group, the group added with lactic acid bacteria was further activated. Compared with lactic acid bacteria, Lactobacillus gasseri has 30 ± 5 μM and has the highest activation inducing ability, Lactobacillus casei and Bifidobacterium longum are 25 ± 4 μM, 14 ± 3 μM, respectively Met. In addition, the β-glucan group administered with saline was 6 ± 3 μM, and the blank group added with Lactobacillus gasseri was 8 ± 5 μM, which was lower than the oatmeal group.
(IL12の定量)
前記共培養上清中のIL12量を、マウスIL12ELISAキット(Endogen社製)を用いて定量し、IL12量の産生量を調べた。その結果を図2に示す。
図2に示されるように、生理食塩水のみを投与したブランク群では検出限界以下であったのに対し、オートミール群で生理食塩水を投与した群は19±5pg/mlとIL12産生量が高く、さらに乳酸菌、特にラクトバチルス・ガセリを添加した群では103±3pg/mlとなり、産生量が飛躍的に増大した。また、βグルカン群では13±4pg/mlであり、ブランク群でラクトバチルス・ガセリを添加した群でも15±2pg/mlであり、オートミール群よりは低いものであった。
(Quantification of IL12)
The amount of IL12 in the co-culture supernatant was quantified using a mouse IL12 ELISA kit (manufactured by Endogen), and the amount of IL12 produced was examined. The result is shown in FIG.
As shown in FIG. 2, the blank group administered with only saline was below the detection limit, whereas the group administered with saline in the oatmeal group had a high IL12 production of 19 ± 5 pg / ml. Furthermore, in the group to which lactic acid bacteria, particularly Lactobacillus gasseri was added, it became 103 ± 3 pg / ml, and the production amount increased dramatically. The β-glucan group was 13 ± 4 pg / ml, and the blank group to which Lactobacillus gasseri was added was 15 ± 2 pg / ml, which was lower than the oatmeal group.
(IFNγの定量)
前記共培養上清中のIFNγ量を、マウスIFNγELISAキット(Endogen社製)を用いて定量し、IFNγ量の産生量を調べた。その結果を図3に示す。
図3に示されるように、ブランク群では8±1ng/mlであったのに対し、乳酸菌添加群、特にラクトバチルス・ガセリを添加した群で22±3ng/mlと、産生量が増大した。ラクトバチルス・カゼイ、及びビフィドバクテリウム・ロンガム群はそれぞれ、20±4ng/ml、9±3ng/mlであった。さらにオートミールにより活性化されたと考えられるマクロファージが共存することでラクトバチルス・ガセリを添加したオートミール群が80±5ng/mlとなり、飛躍的に増大した。ラクトバチルス・カゼイ群、及びビフィドバクテリウム・ロンガム群はそれぞれ、70±7ng/ml、48±8ng/mlであった。また、βグルカン群では6±3ng/mlであり、オートミール群よりはずっと低いものであった。
以上に示したように、腹腔マクロファージと脾臓細胞とを共培養し、免疫原としてオボアルブミンを加えた培地に、乳酸菌とオートミールの添加、無添加を組み合わせた実験系でNO2 -イオン産生量、IL12量、IFNγ量を測定した試験の結果、マクロファージ活性化を反映するNO2 -イオン量は、オートミール単独添加、乳酸菌単独添加でも確認されたが、オートミールに乳酸菌を添加した場合は、産生量が飛躍的に増大した。
また、IL12、IFNγのサイトカイン産生量は、オートミール単独添加や乳酸菌単独添加でもサイトカイン産生が見られたが、オートミールに乳酸菌、特にラクトバチルス・ガセリを添加した場合は、産生量が飛躍的に増大した。
このように、オーツ麦などのイネ科穀粒及びその加工物と乳酸菌とを組み合わせた組成物がマクロファージを活性化し、それぞれが単独のものよりも、NO2 -イオン産生量や、IL12、IFNγのサイトカイン産生量が相乗的に増大することが判明した。
(Quantification of IFNγ)
The amount of IFNγ in the co-culture supernatant was quantified using a mouse IFNγ ELISA kit (manufactured by Endogen), and the amount of IFNγ produced was examined. The results are shown in FIG.
As shown in FIG. 3, the production amount was increased to 8 ± 1 ng / ml in the blank group, whereas it was 22 ± 3 ng / ml in the group added with lactic acid bacteria, particularly the group added with Lactobacillus gasseri. The Lactobacillus casei and Bifidobacterium longum groups were 20 ± 4 ng / ml and 9 ± 3 ng / ml, respectively. Furthermore, the coexistence of macrophages thought to have been activated by oatmeal increased the oatmeal group to which Lactobacillus gasseri was added to 80 ± 5 ng / ml, which increased dramatically. The Lactobacillus casei group and the Bifidobacterium longum group were 70 ± 7 ng / ml and 48 ± 8 ng / ml, respectively. In the β-glucan group, it was 6 ± 3 ng / ml, much lower than in the oatmeal group.
As shown above, peritoneal macrophages and spleen cells were co-cultured, and NO 2 - ion production in an experimental system in which lactic acid bacteria and oatmeal were added or not added to a medium supplemented with ovalbumin as an immunogen. IL12 amount, results of tests to measure IFNγ amount, NO 2 reflects macrophage activation - ion amount, oatmeal single addition, has been confirmed in lactic acid bacteria added alone, the case of adding lactic acid bacteria to oatmeal, production amount Increased dramatically.
In addition, cytokine production of IL12 and IFNγ was observed even when oatmeal alone or lactic acid bacteria were added alone, but when lactic acid bacteria, particularly Lactobacillus gasseri was added to oatmeal, the production amount increased dramatically. .
Thus, a composition comprising a combination of cereal grains such as oats and processed products thereof and lactic acid bacteria activates macrophages, each of which produces more NO 2 − ions, IL12, and IFNγ than those alone. It was found that cytokine production increases synergistically.
[試験例2]
(マウスでの経口摂取実験)
試験例1の結果、イネ科穀粒と乳酸菌とを組み合わせた組成物がマクロファージを活性化し、それぞれが単独のものよりも、NO2 -イオン産生量や、IL12、IFNγのサイトカイン産生量が相乗的に増大することが判明したが、このサイトカイン産生量の増大がマウス生体内でも立証されるかを確認した。
表1に示す割合でマウス用飼料を調製した。
[Test Example 2]
(Ingestion experiment in mice)
As a result of Test Example 1, a composition comprising a combination of gramineous grains and lactic acid bacteria activates macrophages, and each of them produces synergistic NO 2 − ion production and IL 12 and IFNγ cytokine production compared to a single one. However, it was confirmed whether this increase in cytokine production was also demonstrated in vivo in mice.
Mice feed was prepared at the ratio shown in Table 1.
BALB/cマウス(6週齢、雌性、日本クレア社)を12匹ずつ5群に分け、表2に示した飼料を、それぞれ自由摂取させた。試験開始7日目に、一匹あたり0.05mgのオボアルブミンと1mgの水酸化アルミニウムを混合したエマルジョンを腹腔に投与した。試験開始21日目に7日目と同様にオボアルブミンと水酸化アルミニウムの投与を行った。試験開始28日目に採血し、リンホプレップ(比重1.077)で密度勾配遠心を行い、末梢血単核球画分を調製した。免疫原であるオボアルブミンを0.1mg/mlになるように培養液中に加えて末梢血単核球画分を培養プレートに培養した。3日間培養し、培養上清中のIFNγ量を、マウスIFNγELISAキット(Endogen社製)を用いて定量した。 BALB / c mice (6 weeks old, female, Nippon Claire) were divided into 5 groups of 12 mice, and the feeds shown in Table 2 were fed freely. On the 7th day from the start of the test, an emulsion containing 0.05 mg of ovalbumin and 1 mg of aluminum hydroxide per mouse was administered into the abdominal cavity. On the 21st day from the start of the test, ovalbumin and aluminum hydroxide were administered as in the 7th day. On the 28th day from the start of the test, blood was collected and subjected to density gradient centrifugation with Lymphoprep (specific gravity 1.077) to prepare a peripheral blood mononuclear cell fraction. Ovalbumin, which is an immunogen, was added to the culture solution to a concentration of 0.1 mg / ml, and the peripheral blood mononuclear cell fraction was cultured on a culture plate. After culturing for 3 days, the amount of IFNγ in the culture supernatant was quantified using a mouse IFNγ ELISA kit (manufactured by Endogen).
(IFNγの定量)
IFNγ量の産生量を測定した結果を図4に示す。
図4に示されるように、実験動物飼料であるCE−2粉末のみを与えたE群では2.3±0.8ng/mlであったのに対し、オートミールを添加したA群では3.5±0.5ng/ml、菌体乾燥物を添加したB群では5.1±1.0ng/ml、となりIFNγ産生量が増加した。オートミールと乳酸菌を共に添加したC群では21±2.7ng/ml、オートミールの乳酸菌発酵物散剤を添加したD群では24±3.9ng/mlとなり、いずれも飛躍的に産生量が増大した。
この試験の結果、イネ科穀粒の加工物であるオートミールと乳酸菌とを組み合わせたものがマクロファージを活性化し、それぞれが単独のものよりもIFNγのサイトカイン産生量が相乗的に増大することが生体内でも確認された。
(Quantification of IFNγ)
The results of measuring the amount of IFNγ produced are shown in FIG.
As shown in FIG. 4, it was 2.3 ± 0.8 ng / ml in group E given only CE-2 powder as an experimental animal feed, whereas it was 3.5 ± 0.5 ng / ml in group A to which oatmeal was added. In the group B to which the dried microbial cell product was added, the amount of IFNγ was increased to 5.1 ± 1.0 ng / ml. In Group C to which both oatmeal and lactic acid bacteria were added, 21 ± 2.7 ng / ml, and in Group D to which oatmeal lactic acid bacteria fermented powder was added, the production amount increased dramatically.
As a result of this test, the combination of oatmeal, a processed product of gramineous grains, and lactic acid bacteria activates macrophages, and the amount of IFNγ cytokine produced synergistically increases in vivo compared to that of a single product. But it was confirmed.
市販のオートミール(雪印乳業社製、イギリス原産)を10gと試験例1で調製したラクトバチルス・ガセリSBT2055(FERM P-15535)株の菌体乾燥物0.05gとを混合して、本発明の免疫増強剤である散剤を製造した。 10 g of commercially available oatmeal (manufactured by Snow Brand Milk Products Co., Ltd., native to the United Kingdom) and 0.05 g of a dried bacterial cell product of Lactobacillus gasseri SBT2055 (FERM P-15535) strain prepared in Test Example 1 are mixed. A powder which is an enhancer was produced.
市販のオートミール(雪印乳業社製、イギリス原産)100gに水0.5lを加え加熱した。これにラクトバチルス・ガセリ(Lactobacillus gasseri) SBT2055(FERM P-15535)株の生菌108cfu(100mg)を無菌的に接種し、37℃で2日間発酵させた後、乾燥して破砕し、本発明の免疫増強剤である発酵物散剤を製造した。
同様にして、大麦由来の押麦(愛健社製)、小麦粉(日清製粉社製)、ライ麦粉(日清製粉社製)、発芽玄米(ファンケル社製)ならびにトウモロコシ粉(辻安全食品社製)についても同様の製造方法で行い、本発明の免疫増強剤であるそれぞれの発酵物散剤を製造した。
0.5 l of water was added to 100 g of commercially available oatmeal (manufactured by Snow Brand Milk Products Co., Ltd., UK) and heated. Lactobacillus gasseri (Lactobacillus gasseri) SBT2055 (FERM P-15535) strain
Similarly, barley-derived oats (manufactured by Aiken Co., Ltd.), wheat flour (manufactured by Nisshin Flour Mills Co., Ltd.), rye flour (manufactured by Nisshin Flour Mills Co., Ltd.), germinated brown rice (manufactured by Funkel Co., Ltd.), and corn flour (manufactured by Sakai Safety Foods Co., Ltd. ) Was also carried out by the same production method, and each fermented powder powder, which was an immune enhancer of the present invention, was produced.
[試験例3]
(マウスでの経口摂取実験)
ゲッ歯目用実験動物飼料CE‐2粉末(日本クレア社製)90重量%と表2に示す試料10重量%を混合してマウス用飼料を調製した。
[Test Example 3]
(Ingestion experiment in mice)
Rodent experimental animal feed CE-2 powder (manufactured by CLEA Japan) 90% by weight and 10% by weight of the sample shown in Table 2 were mixed to prepare a mouse feed.
BALB/cマウス(6週齢、雌性、日本クレア社)を10匹ずつ14群に分け、上記飼料を、それぞれに自由摂取させた。試験開始7日目に、一匹あたり0.05mgのオボアルブミンと1mgの水酸化アルミニウムを混合したエマルジョンを腹腔に投与した。試験開始21日目に7日目と同様にオボアルブミンと水酸化アルミニウムの腹腔内投与を行った。試験開始28日目に採血し、リンホプレップ(比重1.077)で密度勾配遠心を行って末梢血単核球画分を調製した。免疫原であるオボアルブミンを0.1mg/mlになるように培養液中に加えて末梢血単核球画分を培養プレートに培養した。3日間培養し、培養上清中のIFNγ量を、マウスIFNγELISAキット(Endogen社製)を用いて定量した。IFNγ量を定量した結果を図5に示す。 BALB / c mice (6 weeks old, female, Nippon Claire) were divided into 14 groups of 10 animals, and each of the above-mentioned feeds was freely fed. On the 7th day from the start of the test, an emulsion containing 0.05 mg of ovalbumin and 1 mg of aluminum hydroxide was administered to the peritoneal cavity per animal. Ovalbumin and aluminum hydroxide were intraperitoneally administered on the 21st day of the test on the 7th day. Blood was collected on the 28th day from the start of the test, and a peripheral blood mononuclear cell fraction was prepared by performing density gradient centrifugation with Lymphoprep (specific gravity 1.077). Ovalbumin, which is an immunogen, was added to the culture solution to a concentration of 0.1 mg / ml, and the peripheral blood mononuclear cell fraction was cultured on a culture plate. After culturing for 3 days, the amount of IFNγ in the culture supernatant was quantified using a mouse IFNγ ELISA kit (manufactured by Endogen). The results of quantifying the amount of IFNγ are shown in FIG.
図5に示されるように、飼料のみを与えたN群では2.9±0.9ng/mlであったのに対し、各種イネ科穀粒を乳酸菌で発酵させた群については、A群で23±4ng/ml、B群で15±3ng/ml、C群で10±2ng/ml、D群で11±3ng/ml、E群で18±4ng/ml、F群で11±2ng/mlとなり、IFNγ産生量が増大した。対照である飼料のみを与えたN群に比べていずれも飛躍的に産生量が増大した。なお、各種イネ科穀粒を、発酵させずに粉砕したものを飼料に添加した群については、G群で3.5±1.2ng/ml、H群で3.0±0.6ng/ml、I群で2.5±0.8ng/ml、J群で2.8±0.8ng/ml、K群で2.9±1.0ng/ml、L群で2.6±0.9ng/mlとなり、IFNγ産生量は対照であるN群に比べて同等のものであった。また、菌体乾燥物のみを飼料に添加したM群では5.1±1.0ng/mlとなり、発酵物散剤を添加した各群のIFNγ産生量の増大は、乳酸菌の効果ではないことが分かる。 As shown in FIG. 5, the N group given only feed was 2.9 ± 0.9 ng / ml, whereas the group in which various gramineous grains were fermented with lactic acid bacteria was 23 ± 4 ng in the A group. / Ml, 15 ± 3 ng / ml in Group B, 10 ± 2 ng / ml in Group C, 11 ± 3 ng / ml in Group D, 18 ± 4 ng / ml in Group E, 11 ± 2 ng / ml in Group F, IFNγ Production increased. Compared with the N group to which only the feed as a control was given, the production amount dramatically increased. In addition, about the group which grind | pulverized various gramineous grains without fermenting and added to feed, it is 3.5 ± 1.2 ng / ml in the G group, 3.0 ± 0.6 ng / ml in the H group, and 2.5 ± in the I group. 0.8 ng / ml, 2.8 ± 0.8 ng / ml in the J group, 2.9 ± 1.0 ng / ml in the K group, 2.6 ± 0.9 ng / ml in the L group, and IFNγ production is equivalent to that of the control N group It was a thing. Moreover, it becomes 5.1 +/- 1.0 ng / ml in the M group which added only the microbial cell dry matter to the feed, and it turns out that the increase in IFNγ production amount of each group to which the fermented powder is added is not an effect of lactic acid bacteria.
この試験の結果、各種イネ科穀粒及びその加工物と乳酸菌とを組み合わせたものがマクロファージを活性化し、それぞれが単独のものよりもIFNγのサイトカイン産生量が相乗的に増大することが生体内でも確認された。
各種イネ科植物種子の中ではオートミール発酵物散剤のIFNγ産生量が最も多かった。
As a result of this test, the combination of various gramineous grains and processed products thereof with lactic acid bacteria activates macrophages, and each of them also synergistically increases the amount of IFNγ cytokine production compared to a single one in vivo. confirmed.
Among various grass seeds, the amount of IFNγ produced by oatmeal fermented powder was the highest.
生乳に脱脂粉乳を2%添加して溶解し、ホモジナイザーで均質化して100℃、10分加熱した後、41℃まで冷却したヨーグルトミックス200gを調製した。一方、市販のオートミール(雪印乳業社製、イギリス原産)200gに水0.5lを加え加熱したオートミール加水加熱物を調製した。ヨーグルトミックス200gとオートミール加水加熱物300gを混和し、この混和物にラクトバチルス・ガセリSBT2055(FERM P-15535)株を5重量%接種して混合し、100gずつカップに分注した後、37〜40℃にて発酵させた。乳酸酸度が0.7%になった時点で発酵を終了し、10℃以下で1晩冷却して本発明の免疫増強用発酵乳を製造した。 2% skim milk powder was added to raw milk to dissolve it, homogenized with a homogenizer, heated at 100 ° C. for 10 minutes, and then 200 g of yogurt mix cooled to 41 ° C. was prepared. Meanwhile, a heated oatmeal hydrolyzate was prepared by adding 0.5 l of water to 200 g of a commercially available oatmeal (manufactured by Snow Brand Milk Products Co., Ltd., native to the United Kingdom). Mix 200g of yogurt mix and 300g of heated oatmeal mixture, inoculate 5% by weight of Lactobacillus gasseri SBT2055 (FERM P-15535) strain into this blend, mix and dispense 100g at a time, 37 ~ Fermented at 40 ° C. When the lactic acid acidity reached 0.7%, the fermentation was terminated and cooled overnight at 10 ° C. or lower to produce the fermented milk for immune enhancement of the present invention.
ビタミンCとクエン酸の等量混合物40g、グラニュー糖100g、コーンスターチと乳糖の等量混合物60gに、上記実施例1で得られたオートミールとラクトバチルス・ガセリSBT2055(FERM P-15535)株の菌体乾燥物からなる散剤800gを加えて混合した。混合物を1.5gずつ袋に詰め、本発明のスティック状免疫増強用栄養健康食品を製造した。 Bacteria of oatmeal and Lactobacillus gasseri SBT2055 (FERM P-15535) strain obtained in Example 1 above were added to 40 g of an equal mixture of vitamin C and citric acid, 100 g of granulated sugar, and 60 g of an equal mixture of corn starch and lactose. 800 g of a powder consisting of a dried product was added and mixed. Each 1.5 g of the mixture was packed in a bag to produce the stick-shaped immune health food for enhancing immunity of the present invention.
表3に示した配合で原料を混合してドウを作成した。表3の中で散剤と表示しているのは、上記実施例1で得られたオートミールとラクトバチルス・ガセリSBT2055(FERM P-15535)株の菌体乾燥物からなる散剤である。このドウを成型した後、焙焼して、本発明の免疫増強用ビスケットを製造した。 Raw materials were mixed with the formulation shown in Table 3 to prepare a dough. What is indicated as powder in Table 3 is a powder comprising the oatmeal obtained in Example 1 above and a dried cell product of Lactobacillus gasseri SBT2055 (FERM P-15535) strain. The dough was molded and then roasted to produce the immune enhancing biscuit of the present invention.
[表3]
小麦粉 30.4(重量%)
砂糖 20.0
食塩 0.5
マーガリン 12.5
卵 12.1
水 3.7
炭酸水素ナトリウム 0.1
重炭酸アンモニウム 0.2
炭酸カルシウム 0.5
散剤(実施例1) 20.0
[Table 3]
Flour 30.4 (wt%)
Sugar 20.0
Salt 0.5
Margarine 12.5
Egg 12.1
Water 3.7
Sodium bicarbonate 0.1
Ammonium bicarbonate 0.2
Calcium carbonate 0.5
Powder (Example 1) 20.0
Claims (3)
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JP2009203160A (en) * | 2006-05-25 | 2009-09-10 | Saihatsu Ko | Antiviral and antibacterial agent |
AU2007292786B2 (en) * | 2006-09-04 | 2013-02-14 | Megmilk Snow Brand Co., Ltd. | Agent for accelerating the increase in and/or preventing the decrease in blood adiponectin level, and visceral fat accumulation inhibitor |
JP5053667B2 (en) * | 2006-12-28 | 2012-10-17 | 日清ファルマ株式会社 | Novel lactic acid bacteria and lactic acid bacteria fermentation products for promoting adipocyte differentiation |
JP5220325B2 (en) * | 2007-02-28 | 2013-06-26 | 株式会社日清製粉グループ本社 | Antiallergic agent |
JP2008214253A (en) | 2007-03-02 | 2008-09-18 | Snow Brand Milk Prod Co Ltd | Visceral fat reduction agent |
JP5225652B2 (en) | 2007-10-29 | 2013-07-03 | 雪印メグミルク株式会社 | Adiponectin secretion promoter and / or suppressor |
AU2009220403B2 (en) | 2008-03-07 | 2015-02-26 | Megmilk Snow Brand Co., Ltd. | Agents for promoting secretion and/or suppressing decrease of adiponectin |
PL2515937T3 (en) * | 2009-12-22 | 2020-05-18 | Probi Ab | Non-fermented compositions comprising a cereal based fraction and a probiotic and uses thereof |
JP5937015B2 (en) * | 2010-12-16 | 2016-06-22 | 株式会社明治 | Delayed type hypersensitivity reducing agent |
JP6767157B2 (en) * | 2016-04-28 | 2020-10-14 | 雪印メグミルク株式会社 | Interferon λ inducer |
CN111011685A (en) * | 2019-12-30 | 2020-04-17 | 江南大学 | Fermented milk rich in probiotics and preparation method thereof |
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JP3510639B2 (en) * | 1991-06-28 | 2004-03-29 | カルピス株式会社 | Functional food or health food with a function to regulate interleukin production |
JPH0576272A (en) * | 1991-09-19 | 1993-03-30 | Lotte Co Ltd | Baked cake prepared by using wheat flour fermented with lactobacillus and production thereof |
JP2510924B2 (en) * | 1992-03-31 | 1996-06-26 | 雪印乳業株式会社 | Antioxidants for food additives |
JPH06303909A (en) * | 1993-04-23 | 1994-11-01 | Kameda Seika Kk | Round grain-treated rice cake and its production |
JP3004890B2 (en) * | 1995-03-28 | 2000-01-31 | 雪印乳業株式会社 | Pathogen infection protective agent |
JP4044975B2 (en) * | 1995-07-25 | 2008-02-06 | 株式会社叶匠壽庵 | Diabetes therapeutic agent consisting of fermented lactic acid bacteria |
JP4064481B2 (en) * | 1996-10-11 | 2008-03-19 | ハウスウェルネスフーズ株式会社 | Immunostimulator |
JP4601745B2 (en) * | 1999-08-23 | 2010-12-22 | ハウスウェルネスフーズ株式会社 | Formulation with synergistic enhancement of immunostimulatory effect |
JP4812157B2 (en) * | 2000-05-16 | 2011-11-09 | 株式会社Adeka | Pharmaceutical material containing low molecular weight β-glucan with immunopotentiating action |
JP2003250528A (en) * | 2002-03-06 | 2003-09-09 | Yakult Honsha Co Ltd | Survival-improving agent of bacterium belonging to the genus bifidobacterium, proliferation-promoting agent, or method for producing fermentation product containing the bacterium |
JP2003335695A (en) * | 2002-05-17 | 2003-11-25 | Nippon Bio Kk | Immunoenhancing agent composed of fermented soybean, antitumor agent, processed food, and method for producing fermented soybean |
JP2004154035A (en) * | 2002-11-06 | 2004-06-03 | Combi Corp | Method for producing lactobacillus fermented food product, lactobacillus fermented food product and defecation improver both obtained by the method |
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