JP2006213671A - Mucous membrane immunostimulation composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a highly safe new mucous membrane immunostimulation composition which does not have problems such as side effects and can reinforce the production of IgA and pIgR, while strong mucous membrane immunologic mechanisms consisting mainly of immunoglobulin A (IgA) for protecting outer pathogenic microorganisms (antigens) such as viruses and bacteria exist in the saliva, lacrymal fluid, pituita, respiratory tract mucus, digestive tract secretion, milk and intestinal mucous membrane of living bodies. <P>SOLUTION: This mucous membrane immunostimulation composition contains galactomannan. The mucous membrane immunostimulation composition has an IgA production-reinforcing action in intestinal mucous membranes. The mucous membrane immunostimulation composition has a polymeric Ig receptor (pIgR) production-reinforcing action in intestinal tract epitheliocytes. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

本発明は、新規な粘膜免疫賦活組成物に関する。さらに詳しくは、本発明は、ガラクトマンナンを含有する粘膜免疫賦活組成物に関するものである。   The present invention relates to a novel mucosal immunostimulatory composition. More specifically, the present invention relates to a mucosal immunostimulatory composition containing galactomannan.

生体の唾液、涙液、鼻汁、気道粘液、消化管分泌液、乳汁や腸管の粘膜面には、ウイルスや細菌などの外からの病原菌（抗原）に対して防御するために免疫グロブリンＡ（ＩｇＡ）を主体とする強力な粘膜免疫機構が存在している。ＩｇＡは分子量約３９万の糖蛋白で、糖質を８％含み、ｈｅａｖｙ ｃｈａｉｎが２種類（α１、α２）存在してＩｇＡ１、ＩｇＡ２の２つのサブクラスの区別がある。また、血清ＩｇＡと分泌型ＩｇＡに分けられるが、ほとんどが分泌型ＩｇＡで唾液、涙液、鼻汁、気道粘液、消化管分泌液や乳汁などの外分泌液中に高濃度に含まれており、それぞれの局所粘膜における防御機能を行っている。なお、分泌型ＩｇＡは、２量体の形で存在し、分泌成分とＪｏｉｎｉｎｇ ｃｈａｉｎ（Ｊ鎖）が結合している。また、ＩｇＡは、母乳の中にもたくさん含まれている。これを飲んだ子供は、のどや消化管の表面にＩｇＡ抗体を受取とることで外からの抗原に対して体を守ることができる。   In order to protect against pathogenic bacteria (antigens) such as viruses and bacteria, the immunoglobulin A (IgA) is applied to the saliva, tears, nasal discharge, airway mucus, digestive tract secretions, milk and intestinal mucosal surfaces of living organisms. ) Is a strong mucosal immune mechanism. IgA is a glycoprotein with a molecular weight of about 390,000, contains 8% of carbohydrates, and there are two types of heavy chains (α1, α2), and there is a distinction between two subclasses IgA1 and IgA2. Moreover, although it is divided into serum IgA and secretory IgA, most are secretory IgA and are contained in high concentrations in exocrine fluids such as saliva, tears, nasal discharge, airway mucus, gastrointestinal secretions and milk, It has a protective function in the local mucosa. Secretory IgA exists in the form of a dimer, and a secretory component and a joining chain (J chain) are bound to each other. IgA is also contained in a large amount in breast milk. Children who take this can protect themselves against antigens from outside by receiving IgA antibodies on the surface of their throat and digestive tract.

粘膜面には、腸管免疫系と言われる多くのリンパ組織があり、ＩｇＡ産生に強く関係している。腸管の断面図を見ると腸管の消化吸収をつかさどる器官の間に挟まって腸管独特のリンパ節がある。これがパイエル板（Ｐｅｙｅｒ’ｓ ｐａｔｃｈ）であり、腸管での免疫の中枢的存在となっており、消化管の中でも非常に発違した防御システムを完成している。ＩｇＡが産生される一連の流れは、抗原提示細胞が、抗原の情報を収集し、Ｔ細胞がその情報を受けて、その物質に対して抗体を産生すべきか判断する。そして、実際にＩｇＡを作る細胞がＢ細胞であり刺激を受けた活性化Ｂ細胞が、全身の血液循環により粘膜面に分布した後、ＩｇＡ産生細胞（形質細胞）であるＢ細胞に分化してＩｇＡを産生する。また、ポリメリックＩｇ受容体（ｐＩｇＲ）を介したＩｇＡの上皮内輸送粘膜免疫組織も分泌型ＩｇＡの産生に必要不可欠である。小胞体内でヒトｐＩｇＲはタンパク質として合成され、Ｇｏｌｇｉ装置と呼ばれるところで糖の添加を受けて糖タンパク質になる。その後、胃、腸、肝などの上皮細胞の基底側細胞膜上や涙腺、唾液腺、乳腺などの腺房細胞に分布する。粘膜固有層の形質細胞より産生・分泌されたＪ鎖を含む２量体のＩｇＡはｐＩｇＲに結合した後、細胞内を輸送され、管腔側細胞膜上で切断され、分泌型ＩｇＡとして放出される。このように、局所粘膜面でのＩｇＡの産生増強作用は、生体防御機構（獲得免疫）を増強することが期待される。したがって、効果的にＩｇＡとｐＩｇＲ産生を増強する方法が求められている。ＩｇＡとｐＩｇＲ産生を増強する方法としては、例えば、１）フラクトオリゴ糖及びその組成物の提案（例えば特許文献１参照）しかしながら、１）の方法では、オリゴ糖自体に甘味を有するため添加できる食品が限定される。また、その効果が完全ではない。そこで、ＩｇＡとｐＩｇＲ産生を増強する作用を有する新たな粘膜免疫賦活組成物の開発が望まれている。   On the mucosal surface, there are many lymphoid tissues called the intestinal tract immune system, which are strongly related to IgA production. Looking at the cross-sectional view of the intestine, there are lymph nodes unique to the intestine that are sandwiched between the organs that control digestive absorption of the intestine. This is the Peyer's patch, which is a center of immunity in the intestinal tract, and completes a very different defense system in the digestive tract. The sequence of IgA production is such that the antigen-presenting cell collects antigen information and the T cell receives that information to determine if it should produce antibodies against the substance. Then, the activated B cells that are actually stimulated B cells are the B cells and are distributed on the mucosal surface by whole body blood circulation, and then differentiated into B cells that are IgA producing cells (plasma cells). IgA is produced. In addition, mucosal immune tissue that transports IgA in the epithelium via a polymeric Ig receptor (pIgR) is also essential for the production of secretory IgA. Human pIgR is synthesized as a protein in the endoplasmic reticulum, and is converted to a glycoprotein upon addition of sugar at what is called a Golgi apparatus. Thereafter, it is distributed on the basal cell membrane of epithelial cells such as stomach, intestine and liver and acinar cells such as lacrimal gland, salivary gland and mammary gland. Dimer IgA containing J chain produced and secreted by plasma cells in the lamina propria is bound to pIgR, then transported inside the cell, cleaved on the luminal cell membrane, and released as secretory IgA . Thus, the IgA production enhancing action on the local mucosal surface is expected to enhance the biological defense mechanism (acquired immunity). Therefore, there is a need for a method that effectively enhances IgA and pIgR production. Examples of methods for enhancing the production of IgA and pIgR include 1) Proposal of fructooligosaccharide and its composition (see, for example, Patent Document 1) However, in the method of 1), there is a food that can be added because the oligosaccharide itself has sweetness. Limited. Also, the effect is not perfect. Therefore, development of a new mucosal immunostimulatory composition having an effect of enhancing IgA and pIgR production is desired.

特開２００３−２０１２３９JP 2003-201239 A

本発明は、副作用などの問題が無く、ＩｇＡとｐＩｇＲの産生増強することのできる安全性の高い新規な粘膜免疫賦活組成物を提供することを目的としてなされたものである。   The present invention has been made for the purpose of providing a highly safe mucosal immunostimulatory composition that is free from problems such as side effects and can enhance the production of IgA and pIgR.

本発明者らは、副作用や摂取困難などの問題が無く、生体防御機構を増強することが期待されるＩｇＡとｐＩｇＲの産生増強のできる安全性の高い新規な粘膜免疫賦活組成物を開発すべく鋭意研究を重ねた結果、ガラクトマンナンを有効成分とするものは、ＩｇＡとｐＩｇＲの産生をより効果的に増強することを新規に見いだし、この知見に基づいて本発明を完成するに至った。すなわち、本発明は、ガラクトマンナンを有効成分として含有することを特徴とする粘膜免疫賦活組成物を提供するものである。   The present inventors are to develop a novel highly safe mucosal immunostimulatory composition that can enhance the production of IgA and pIgR, which are expected to enhance the biological defense mechanism without problems such as side effects and difficulty in ingestion. As a result of intensive studies, it has been found that a substance containing galactomannan as an active ingredient can effectively enhance the production of IgA and pIgR, and the present invention has been completed based on this finding. That is, the present invention provides a mucosal immunostimulatory composition comprising galactomannan as an active ingredient.

本発明の粘膜免疫賦活組成物は、ＩｇＡとｐＩｇＲの産生を効果的に増強することができる。   The mucosal immunostimulatory composition of the present invention can effectively enhance the production of IgA and pIgR.

本発明における前記ガラクトマンナンとしては、ガラクトマンナンを主成分とするグァーガム、ローカストビーンガム、タラガム、カシアガム、セスバニアガム、フェニグリーク、ガラクトマンナン分解物等の天然粘質物があげられる。粘度の面から特に好ましくはガラクトマンナン分解物である。ガラクトマンナン分解物は、前記のガラクトマンナンを加水分解し低分子化することにより得られるものである。加水分解の方法としては、酵素分解法、酸分解法等、特に限定するものではないが、分解物の分子量が揃い易い点から酵素分解法が好ましい。酵素分解法に用いられる酵素は、マンノース直鎖を加水分解する酵素であれば市販のものでも天然由来のものでも特に限定されるものではないが、アスペルギルス属菌やリゾープス属菌等に由来するβ−マンナナーゼが好ましい。   Examples of the galactomannan in the present invention include natural gums such as guar gum, locust bean gum, tara gum, cassia gum, sesbania gum, fenigreek, and galactomannan degradation products mainly composed of galactomannan. Particularly preferred from the viewpoint of viscosity is a galactomannan decomposition product. The galactomannan degradation product is obtained by hydrolyzing the galactomannan and reducing the molecular weight. The hydrolysis method is not particularly limited, such as an enzymatic decomposition method or an acid decomposition method, but the enzymatic decomposition method is preferred because the molecular weights of the decomposed products are easily uniform. The enzyme used in the enzymatic degradation method is not particularly limited as long as it is an enzyme that hydrolyzes mannose straight chain, and it is not particularly limited, but it may be β derived from Aspergillus or Rhizopus. -Mannanase is preferred.

本発明に使用されるガラクトマンナンは、５，０００〜３００，０００の平均分子量を持つことが望ましい。平均分子量５，０００以上であれば本発明の好適なＩｇＡとｐＩｇＲの産生増強効果を有するが、一方、平均分子量が３００，０００を超えると、粘度が高く食品に加工する場合に不都合が生じる場合が多いため、ガラクトマンナンの平均分子量は、５，０００〜３００，０００である事が望ましい。特に好ましくは８，０００〜２０，０００である。平均分子量の測定方法は、特に限定するものではないが、ポリエチレングリコール（分子量；２，０００、２０，０００、２００，０００）をマーカーに高速液体クロマトグラフ法（カラム；ＹＭＣ−Ｐａｃｋ Ｄｉｏｌ−１２０（株）ワイエムシィ）を用いて、分子量分布を測定する方法等を用いることにより求めることができる。   The galactomannan used in the present invention desirably has an average molecular weight of 5,000 to 300,000. If the average molecular weight is 5,000 or more, the present invention has a preferable IgA and pIgR production enhancing effect. On the other hand, if the average molecular weight exceeds 300,000, the viscosity is high and inconvenience occurs when processed into food. Therefore, the average molecular weight of galactomannan is desirably 5,000 to 300,000. Especially preferably, it is 8,000-20,000. The method for measuring the average molecular weight is not particularly limited, but high-performance liquid chromatographic method (column: YMC-Pack Diol-120) using polyethylene glycol (molecular weight; 2,000, 20,000, 200,000) as a marker. It can be determined by using a method for measuring the molecular weight distribution, etc. using YMC).

ガラクトマンナンは、種々の工業製品に好ましい物性を付与することが知られているが、このものがＩｇＡとｐＩｇＲの産生増強効果を有することは従来知られていなかった。しかし、本発明者らの研究によると、上述のようなガラクトマンナンを食品組成物として摂取をつづけるとき、ＩｇＡとｐＩｇＲの産生増強効果が認められることが見出された。   Galactomannan is known to impart favorable physical properties to various industrial products, but it has not been previously known that this has an effect of enhancing production of IgA and pIgR. However, according to the study by the present inventors, it has been found that when galactomannan as described above is continuously ingested as a food composition, an effect of enhancing production of IgA and pIgR is observed.

本発明では、ガラクトマンナンと配合する食品材料は特に限定されるものではなく、他の糖類、食物繊維、脂質、アミノ酸、蛋白質、さらにこれらに必要に応じて、乳酸菌、ビタミン、ミネラルのようなその他の機能性を有する物質を添加して粘膜免疫賦活組成物とすることができる。このようなガラクトマンナンの摂取方法としては、例えば、飲料、クッキー、スナック菓子、乳製品などの種々の食品とすることができるほか、例えば適当な増量剤、賦形剤などを用いて錠剤状、液状、シロップ状、顆粒状などの医薬品や健康食品の形態にすることもできる。ガラクトマンナンは、種々な食品に添加することが可能であることから容易に摂取することが可能であり、効果的にＩｇＡとｐＩｇＲの産生を増強することができる。本発明におけるガラクトマンナンのＩｇＡとｐＩｇＲの産生増強効果を試験例に基づいて詳しく説明する。   In the present invention, the food material to be blended with galactomannan is not particularly limited, and other sugars, dietary fibers, lipids, amino acids, proteins, and other such as lactic acid bacteria, vitamins, and minerals as necessary. It is possible to obtain a mucosal immunity stimulating composition by adding a substance having the above functionality. As a method for ingesting such galactomannan, for example, various foods such as beverages, cookies, snacks and dairy products can be used, and for example, tablets or liquids can be used using appropriate bulking agents and excipients. It can also be in the form of syrups, granules and other medicines and health foods. Galactomannan can be easily ingested because it can be added to various foods, and can effectively enhance the production of IgA and pIgR. The production enhancement effect of galactomannan in the present invention on IgA and pIgR will be described in detail based on test examples.

以下、調製例及び試験例をあげて本発明を更に詳しく説明するが、本発明はこれら実施例に何ら制約されるものではない。 Hereinafter, the present invention will be described in more detail with reference to Preparation Examples and Test Examples, but the present invention is not limited to these Examples.

（調製例１）
水９００ｇに０．１Ｎ塩酸を加えてｐＨ４．５に調整し、これにアスペルギルス属由来のβ−マンナナーゼ（阪急バイオインダストリー製）０．２ｇとグァーガム粉末（Ｌｕｃｉｄ製）１００ｇを添加混合して４０〜４５℃で２１時間酵素を作用させた。反応後９０℃、１５分間加熱して酵素を失活させた。濾過分離（吸引濾過）して、不溶物を除去して得られた透明な溶液を減圧濃縮（エバポレーター；Ｙａｍａｔｏ製）した後（固形分２０％）、噴霧乾燥（大川原化工機（株））し、本発明品の粘膜免疫賦活組成物であるガラクトマンナン分解物（平均分子量 約３０，０００）６５ｇが得られた。 (Preparation Example 1)
0.1N hydrochloric acid is added to 900 g of water to adjust the pH to 4.5, and 0.2 g of Aspergillus genus β-mannanase (Hankyu Bioindustry) and 100 g of guar gum powder (Lucid) are added and mixed. The enzyme was allowed to act at 45 ° C for 21 hours. After the reaction, the enzyme was inactivated by heating at 90 ° C. for 15 minutes. The transparent solution obtained by filtration separation (suction filtration) to remove insolubles was concentrated under reduced pressure (evaporator; manufactured by Yamato) (solid content 20%), and then spray-dried (Okawara Kako Co., Ltd.). As a result, 65 g of a galactomannan degradation product (average molecular weight of about 30,000), which is a mucosal immunostimulatory composition of the present invention, was obtained.

（調製例２）
水９００ｇに０．１Ｎ塩酸を加えてｐＨ３．０に調整し、これにアスペルギルス属由来のβ−マンナナーゼ（阪急バイオインダストリー製）０．１５ｇとグァーガム粉末（Ｌｕｃｉｄ製）１００ｇを添加混合して４０〜４５℃で２３時間酵素を作用させた。反応後９０℃、１５分間加熱して酵素を失活させた。濾過分離（吸引濾過）して、不溶物を除去して得られた透明な溶液を減圧濃縮（エバポレーター；Ｙａｍａｔｏ製）した後（固形分２０％）、噴霧乾燥（大川原化工機（株））し、本発明品の粘膜免疫賦活組成物であるガラクトマンナン分解物（平均分子量 約２０，０００）６８ｇが得られた。 (Preparation Example 2)
0.1N hydrochloric acid is added to 900 g of water to adjust the pH to 3.0, and 0.15 g of β-mannanase derived from Aspergillus genus (manufactured by Hankyu Bioindustry) and 100 g of guar gum powder (manufactured by Lucid) are added and mixed. The enzyme was allowed to act for 23 hours at 45 ° C. After the reaction, the enzyme was inactivated by heating at 90 ° C. for 15 minutes. The transparent solution obtained by filtration separation (suction filtration) to remove insolubles was concentrated under reduced pressure (evaporator; manufactured by Yamato) (solid content 20%), and then spray-dried (Okawara Kako Co., Ltd.). Thus, 68 g of a galactomannan degradation product (average molecular weight of about 20,000), which is a mucosal immunostimulatory composition of the present invention, was obtained.

（調製例３）
水９００ｇに０．１Ｎ塩酸を加えてｐＨ４．０に調整した。これにバチルス属由来のβ−マンナナーゼ（阪急バイオインダストリー製）０．２５ｇとグァーガム粉末（Ｌｕｃｉｄ製）１００ｇを添加混合して５０〜５５℃で１８時間酵素を作用させた。反応後９０℃、１５分間加熱して酵素を失活させた。濾過分離（吸引濾過）して、不溶物を除去して得られた透明な溶液を減圧濃縮（エバポレーター；Ｙａｍａｔｏ製）した後（固形分２０％）、噴霧乾燥（大川原化工機（株））し、本発明品の粘膜免疫賦活組成物であるガラクトマンナン分解物（平均分子量 約８，０００）６５ｇが得られた。 (Preparation Example 3)
The pH was adjusted to 4.0 by adding 0.1N hydrochloric acid to 900 g of water. 0.25 g of β-mannanase derived from Bacillus genus (manufactured by Hankyu Bioindustry) and 100 g of guar gum powder (manufactured by Lucid) were added and mixed, and the enzyme was allowed to act at 50 to 55 ° C. for 18 hours. After the reaction, the enzyme was inactivated by heating at 90 ° C. for 15 minutes. The transparent solution obtained by filtration separation (suction filtration) to remove insolubles was concentrated under reduced pressure (evaporator; manufactured by Yamato) (solid content 20%), and then spray-dried (Okawara Kako Co., Ltd.). As a result, 65 g of a galactomannan degradation product (average molecular weight of about 8,000), which is a mucosal immunostimulatory composition of the present invention, was obtained.

（調製例４）
水９００ｇに０．１Ｎ塩酸を加えてｐＨ４．０に調整した。これにバチルス属由来のβ−マンナナーゼ（阪急バイオインダストリー製）０．２５ｇとグァーガム粉末（Ｌｕｃｉｄ製）１００ｇを添加混合して５０〜５５℃で２０時間酵素を作用させた。反応後９０℃、１５分間加熱して酵素を失活させた。濾過分離（吸引濾過）して、不溶物を除去して得られた透明な溶液を減圧濃縮（エバポレーター；Ｙａｍａｔｏ製）した後（固形分２０％）、噴霧乾燥（大川原化工機（株））し、本発明品の粘膜免疫賦活組成物であるガラクトマンナン分解物（平均分子量 約７，０００）７０ｇが得られた。 (Preparation Example 4)
The pH was adjusted to 4.0 by adding 0.1N hydrochloric acid to 900 g of water. To this, 0.25 g of β-mannanase derived from Bacillus genus (manufactured by Hankyu Bioindustry) and 100 g of guar gum powder (manufactured by Lucid) were added and mixed, and the enzyme was allowed to act at 50 to 55 ° C. for 20 hours. After the reaction, the enzyme was inactivated by heating at 90 ° C. for 15 minutes. The transparent solution obtained by filtration separation (suction filtration) to remove insolubles was concentrated under reduced pressure (evaporator; manufactured by Yamato) (solid content 20%), and then spray-dried (Okawara Kako Co., Ltd.). As a result, 70 g of a galactomannan degradation product (average molecular weight of about 7,000), which is a mucosal immunostimulatory composition of the present invention, was obtained.

実験動物は、３０匹の３週齢の雄性ＢＡＬＢ／ｃマウスを日本クレア社より購入した。ガラクトマンナンは、実施例１〜４を用いた。オリゴ糖群はフラクトオリゴ糖を用いた。   As experimental animals, 30 male 3-week-old BALB / c mice were purchased from CLEA Japan. Examples 1 to 4 were used as galactomannans. As the oligosaccharide group, fructooligosaccharides were used.

動物は対照群およびガラクトマンナン群（４群）とオリゴ糖群の計６群（１群５匹）に分けた。購入した日から試験終了日（摂取期間２８日間）まで、対照群には基本飼料（表１）を、ガラクトマンナン群には基本飼料にガラクトマンナンを５％（ｗ／ｗ）、オリゴ糖群には、基本飼料にフラクトオリゴ糖を５％（ｗ／ｗ）添加した実験飼料を自由摂取させた。摂取終了後、腸組織よりパイエル板を摘出し、パイエル板リンパ球の分離培養（ＣＯ_２存在下３７℃で７日間）を行った後、培養上清を回収し酵素免疫測定法によりＩｇＡ含量を測定した。また、大腸組織中のｐＩｇＲ量もウェスタンブロッティング法により測定した。 The animals were divided into a total of 6 groups (5 per group): a control group, a galactomannan group (4 groups), and an oligosaccharide group. From the date of purchase to the end of the test (intake period 28 days), the basic feed (Table 1) was used for the control group, 5% (w / w) galactomannan for the galactomannan group, and the oligosaccharide group Were allowed to freely ingest an experimental diet in which 5% (w / w) fructooligosaccharide was added to the basic diet. After ingestion, the Peyer's patch was removed from the intestinal tissue, and Peyer's patch lymphocytes were separated and cultured (7 days at 37 ° C in the presence of CO ₂ ), and the culture supernatant was collected and IgA content was determined by enzyme immunoassay. It was measured. Further, the amount of pIgR in the large intestine tissue was also measured by Western blotting.

ガラクトマンナン摂取群では、パイエル板からのＩｇＡ産生量が対照群とオリゴ糖群に比較して有意に増加した（表２）。   In the galactomannan intake group, IgA production from Peyer's patch increased significantly compared to the control group and the oligosaccharide group (Table 2).

ガラクトマンナン摂取群では、大腸内のｐＩｇＲ産生量が対照群とオリゴ糖に比較して有意に増加した（図１）。   In the galactomannan intake group, the amount of pIgR produced in the large intestine increased significantly compared to the control group and the oligosaccharide (FIG. 1).

実験動物は、３０匹の４〜５週齢の雄性Ｓｐｒａｇｕｅ−Ｄａｗｌｅｙを日本クレア社より購入し。ガラクトマンナンは、実施例１〜４を用いた。オリゴ糖群はフラクトオリゴ糖（明治乳業（株）製）を用いた。動物は対照群およびガラクトマンナン群（４群）とオリゴ糖群の計６群（１群５匹）に分けた。購入した日から試験終了日（摂取期間１４日間）まで、対照群には基本飼料ＡＩＮ９３Ｇ（表３）を、ガラクトマンナン群には基本飼料にガラクトマンナンを５％（ｗ／ｗ）、オリゴ糖群には、基本飼料にフラクトオリゴ糖を５％（ｗ／ｗ）添加した。摂取終了後、腸組織よりパイエル板を摘出し、パイエル板リンパ球の分離培養（ＣＯ２存在下３７℃で７日間）を行った後、培養上清を回収し酵素免疫測定法によりＩｇＡ含量を測定した。また、大腸組織中のｐＩｇＲ量もウェスタンブロッティング法により測定した。   For experimental animals, 30 male Sprague-Dawleys 4 to 5 weeks old were purchased from Clea Japan. Examples 1 to 4 were used as galactomannans. As the oligosaccharide group, fructooligosaccharide (manufactured by Meiji Dairies) was used. The animals were divided into a total of 6 groups (5 per group): a control group, a galactomannan group (4 groups), and an oligosaccharide group. From the date of purchase to the end of the test (intake period 14 days), the control group was basic feed AIN93G (Table 3), the galactomannan group was galactomannan 5% (w / w), the oligosaccharide group In addition, 5% (w / w) of fructooligosaccharide was added to the basic feed. After ingestion, the Peyer's patch was removed from the intestinal tissue, and Peyer's patch lymphocytes were separated and cultured (7 days at 37 ° C. in the presence of CO 2), and the culture supernatant was collected and the IgA content was measured by enzyme immunoassay. did. Further, the amount of pIgR in the large intestine tissue was also measured by Western blotting.

ガラクトマンナン摂取群では、パイエル板からのＩｇＡ産生量が対照群とオリゴ糖群に比較して有意に増加した（表４）。   In the galactomannan intake group, IgA production from Peyer's patches increased significantly compared to the control group and the oligosaccharide group (Table 4).

ガラクトマンナン摂取群では、大腸内のｐＩｇＲ産生量が対照群とオリゴ糖群に比較して有意に増加した（図２）。   In the galactomannan intake group, pIgR production in the large intestine was significantly increased compared to the control group and the oligosaccharide group (FIG. 2).

（調製例５）
調製例１のガラクトマンナン分解物５ｇに粉糖９３．５ｇ、アラビアガム１．０ｇ、ステアリン酸マグネシウム０．５ｇ、香料適量の割合で混練して乾燥した後打錠し、ＩｇＡとｐＩｇＲ産生を増強に有用な錠菓の製品１００ｇを得た。なお、味と物性面でガラクトマンナン分解物無添加品と違いは認められなかった。 (Preparation Example 5)
Kneaded at 53.5 g of galactomannan degradation product of Preparation Example 1 in a proportion of powdered sugar 93.5 g, gum arabic 1.0 g, magnesium stearate 0.5 g, perfume appropriate amount, and then tableted to enhance IgA and pIgR production 100 g of a tablet confectionery product useful for the above was obtained. In addition, in the taste and physical properties, no difference was observed from the galactomannan degradation product-free product.

（調製例６）
調製例１のガラクトマンナン分解物粉末５ｇにローファットミルク９５．０ｇを加えＩｇＡとｐＩｇＲ産生を増強の改善に有用な乳飲料の製品１００ｇを得た。なお、味と物性面でガラクトマンナン分解物無添加品と違いは認められなかった。 (Preparation Example 6)
95.0 g of low fat milk was added to 5 g of the galactomannan decomposition product powder of Preparation Example 1 to obtain 100 g of a milk beverage product useful for improving the enhancement of IgA and pIgR production. In addition, in the taste and physical properties, no difference was observed from the galactomannan degradation product-free product.

（調製例７）
調製例２のガラクトマンナン分解物粉末３．０ｇにピーチピューレ４０．０ｇ、果糖ブドウ糖液糖１０．０ｇ、クエン酸０．１ｇ、ビタミンＣ０．０３ｇ、フレーバー適量、水４６．８ｇを加えＩｇＡとｐＩｇＲ産生を増強に有用な清涼飲料水の製品１００ｇを得た。なお、味と物性面でガラクトマンナン分解物無添加品と違いは認められなかった。 (Preparation Example 7)
Add peach puree 40.0g, fructose glucose liquid sugar 10.0g, citric acid 0.1g, vitamin C 0.03g, flavor appropriate amount, water 46.8g to IgA and pIgR 100 g of soft drink product useful for enhancing production was obtained. In addition, in the taste and physical properties, no difference was observed from the galactomannan degradation product-free product.

（調製例８）
調製例２のガラクトマンナン分解物粉末５．０ｇに強力粉５１．０ｇ、砂糖１５．０ｇ、食塩７．０ｇ、イースト８．０ｇ、イースト１．０ｇ、バター１０．０ｇ、水３０．０ｇの配合でパン焼き機を利用してＩｇＡとｐＩｇＲ産生を増強に有用な食パンの製品１１０ｇを得た。なお、味と物性面でガラクトマンナン分解物無添加品と違いは認められなかった。 (Preparation Example 8)
In a blend of 5.0 g of galactomannan degradation product powder of Preparation Example 2 with 51.0 g of strong powder, 15.0 g of sugar, 7.0 g of salt, 8.0 g of yeast, 1.0 g of yeast, 10.0 g of butter and 30.0 g of water. Using a baking machine, 110 g of a bread product useful for enhancing IgA and pIgR production was obtained. In addition, in the taste and physical properties, no difference was observed from the galactomannan degradation product-free product.

（調製例９）
調製例３のガラクトマンナン分解物粉末４．０ｇにグラニュー糖３０．０ｇ、水あめ３５．０ｇ、ペクチン１．０ｇ、１／５アップル果汁２．０ｇ、水２８．０ｇで混合し８５℃まで加熱した後、５０℃まで冷却しＩｇＡとｐＩｇＲ産生を増強に有用なゼリーの製品１００ｇを得た。なお、味と物性面でガラクトマンナン分解物無添加品と違いは認められなかった。 (Preparation Example 9)
4.0 g of galactomannan decomposition product powder of Preparation Example 3 was mixed with 30.0 g of granulated sugar, 35.0 g of syrup, 1.0 g of pectin, 2.0 g of 1/5 apple juice, and 28.0 g of water, and heated to 85 ° C. Thereafter, the mixture was cooled to 50 ° C. to obtain 100 g of a jelly product useful for enhancing IgA and pIgR production. In addition, in the taste and physical properties, no difference was observed from the galactomannan degradation product-free product.

（調製例１０）
調製例３のガラクトマンナン分解物粉末４．０ｇにグラニュー糖３０．０ｇ、水あめ３５．０ｇ、ペクチン１．０ｇ、１／５アップル果汁２．０ｇ、水２８．０ｇで混合し８５℃まで加熱した後、５０℃まで冷却しＩｇＡとｐＩｇＲ産生を増強に有用なゼリーの製品１００ｇを得た。なお、味と物性面でガラクトマンナン分解物無添加品と違いは認められなかった。 (Preparation Example 10)
4.0 g of galactomannan degradation product powder of Preparation Example 3 was mixed with 30.0 g of granulated sugar, 35.0 g of starch syrup, 1.0 g of pectin, 2.0 g of 1/5 apple juice, and 28.0 g of water, and heated to 85 ° C. Thereafter, the mixture was cooled to 50 ° C. to obtain 100 g of a jelly product useful for enhancing IgA and pIgR production. In addition, in the taste and physical properties, no difference was observed from the galactomannan degradation product-free product.

（調製例１１）
調製例４のガラクトマンナン分解物末２．０ｇとアラビノガラクタン２．０ｇにグラニュー糖３０．０ｇ、水あめ３５．０ｇ、ペクチン１．０ｇ、１／５アップル果汁２．０ｇ、水２８．０ｇで混合し８５℃まで加熱した後、５０℃まで冷却しＩｇＡとｐＩｇＲ産生を増強に有用なゼリーの製品１００ｇを得た。なお、味と物性面でガラクトマンナン分解物無添加品と違いは認められなかった。 (Preparation Example 11)
With 2.0 g of the galactomannan degradation product powder of Preparation Example 4 and 2.0 g of arabinogalactan, 30.0 g of granulated sugar, 35.0 g of starch syrup, 1.0 g of pectin, 2.0 g of 1/5 apple juice and 28.0 g of water After mixing and heating to 85 ° C., cooling to 50 ° C. yielded 100 g of a jelly product useful for enhancing IgA and pIgR production. In addition, in the taste and physical properties, no difference was observed from the galactomannan degradation product-free product.

本発明の粘膜免疫賦活組成物は、ガラクトマンナンの効果により、効果的にＩｇＡとｐＩｇＲ産生を増強することができる。   The mucosal immunostimulatory composition of the present invention can effectively enhance IgA and pIgR production by the effect of galactomannan.

実施例１での大腸内のｐＩｇＲ産生量Production amount of pIgR in the large intestine in Example 1 実施例２での大腸内のｐＩｇＲ産生量Production amount of pIgR in the large intestine in Example 2

Claims (4)

ガラクトマンナンを含有することを特徴とする粘膜免疫賦活組成物。 A mucosal immunostimulatory composition comprising galactomannan. 腸管粘膜におけるＩｇＡ産生増強作用を有する請求項１記載の粘膜免疫賦活組成物。 The mucosal immunostimulatory composition according to claim 1, which has an effect of enhancing IgA production in the intestinal mucosa. 腸管上皮細胞におけるポリメリックＩｇ受容体（ｐＩｇＲ）の産生増強作用を有する請求項１記載の粘膜免疫賦活組成物。 The mucosal immunity stimulating composition according to claim 1, which has an effect of enhancing production of polymeric Ig receptor (pIgR) in intestinal epithelial cells. 請求項１〜３のいずれか記載の粘膜免疫賦活組成物を含有する飲食品 Food-drinks containing the mucosal immunostimulatory composition according to any one of claims 1 to 3

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