JP5717433B2 - Bile acid adsorption composition - Google Patents

Bile acid adsorption composition Download PDF

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JP5717433B2
JP5717433B2 JP2010280680A JP2010280680A JP5717433B2 JP 5717433 B2 JP5717433 B2 JP 5717433B2 JP 2010280680 A JP2010280680 A JP 2010280680A JP 2010280680 A JP2010280680 A JP 2010280680A JP 5717433 B2 JP5717433 B2 JP 5717433B2
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fibrous protein
bile acid
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孝明 宮島
孝明 宮島
啓子 田中
啓子 田中
伸二郎 今井
伸二郎 今井
福留 真一
真一 福留
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Nisshin Seifun Group Inc
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Description

本発明は、胆汁酸を吸着してその排泄を促すことができる組成物に関する。   The present invention relates to a composition that can adsorb bile acids and promote their excretion.

近年、食の欧米化によって脂肪の摂取量が増加すると共に、癌患者数が増加してきている。摂取脂肪と相関が高いとされる癌としては、乳癌と大腸癌が挙げられる。特に大腸癌は、急激に患者数が増加してきており、結腸と直腸を合わせた大腸癌としての死亡者数では、肺癌、胃癌についで第3位となっている。大腸癌の一因としては、脂肪摂取によって胆汁酸の量が増加し、それに伴って、ステロイド代謝産物や2次胆汁酸等の、腸管粘膜傷害性や発癌プロモーターとしての作用を有する胆汁酸の代謝産物が増加するためと考えられている。
一方、胆石症は、胆汁酸または色素のビリルビンが結晶化して起こる疾患であるが、食の欧米化による脂肪摂取量の増加に伴い、胆石症が増加してきている。胆石症の発症にもまた胆汁酸の代謝異常が関与していると考えられている。
In recent years, the intake of fat has increased due to the westernization of food, and the number of cancer patients has increased. Examples of cancers that are highly correlated with ingested fat include breast cancer and colon cancer. In particular, colorectal cancer has rapidly increased in number of patients, and the number of deaths as colorectal cancer combining the colon and rectum is the third highest after lung cancer and stomach cancer. As a cause of colorectal cancer, the amount of bile acids increases due to fat intake. Along with this, the metabolism of bile acids such as steroid metabolites and secondary bile acids has the effect of intestinal mucosal damage and tumor promoters. This is thought to increase the product.
On the other hand, cholelithiasis is a disease caused by crystallization of bile acid or the pigment bilirubin, but cholelithiasis is increasing with the increase in fat intake due to westernization of food. Bile acid metabolism is also considered to be involved in the development of cholelithiasis.

そこで、これらの疾患を予防又は治療すべく、胆汁酸を吸着してその体外への排泄を促進するための胆汁酸吸着素材が従来から既に報告されている。
例えば、特許文献1には、陰イオン樹脂を含む胆汁酸吸着剤や医薬が従来公知であることが記載されている。しかし、これらは合成化合物であるため、安全性の観点からその使用には厳重な注意が必要であり、さらに医薬品の場合は入手に制限があるため、通常の生活の中で使用するには不向きである。
Therefore, in order to prevent or treat these diseases, bile acid adsorbing materials for adsorbing bile acids and promoting their excretion outside the body have already been reported.
For example, Patent Document 1 describes that a bile acid adsorbent and a medicine containing an anion resin are conventionally known. However, since these are synthetic compounds, strict attention is required for their use from the viewpoint of safety, and in the case of pharmaceuticals, the availability is limited, making them unsuitable for use in normal life. It is.

また、食品由来の素材としては、食物繊維や難消化性蛋白が胆汁酸を吸着するという報告があり、ふすまなどの従来廃棄されていた食物繊維を多く含む食品の胆汁酸吸着作用が注目されている。しかしながら、多くの食物繊維は風味が非常に悪く、食用には適さないうえ、多量に摂取しないと効果が得られないという問題があった。   In addition, as a food-derived material, there are reports that dietary fibers and indigestible proteins adsorb bile acids, and the bile acid adsorption action of foods that contain a lot of dietary fibers such as bran that have been discarded in the past has attracted attention. Yes. However, many dietary fibers have a very bad flavor and are not suitable for consumption, and there is a problem that the effect cannot be obtained unless a large amount is consumed.

他の食品由来の素材として、特許文献2には、微生物に由来するエンド・エキソ型のプロテアーゼにて酵素分解された魚節を含む溶液を濾過した濾渣により生成され、胆汁酸吸着能力を有することを特徴とした胆汁酸吸着剤が記載されている。また特許文献3には、キトサン・オロチン酸塩を有効成分とすることを特徴とする胆汁酸吸着剤が記載されている。しかしながら、これらの従来の胆汁酸吸着剤としても、その効果は必ずしも満足のいくものではないのが実状であった。   As another food-derived material, Patent Document 2 discloses that it is produced by a filter residue obtained by filtering a solution containing a fish clause that has been enzymatically decomposed with an endo-exo-type protease derived from microorganisms, and has a bile acid adsorption ability. A bile acid adsorbent characterized by is described. Patent Document 3 describes a bile acid adsorbent characterized by containing chitosan orotate as an active ingredient. However, the effect of these conventional bile acid adsorbents is not always satisfactory.

したがって、胆汁酸吸着能に優れ、且つ安全で継続的に摂取可能な胆汁酸吸着素材が所望されているのが実状である。   Therefore, in reality, there is a demand for a bile acid-adsorbing material that is excellent in bile acid-adsorbing ability and that can be ingested safely and continuously.

特開平7−277993号公報Japanese Patent Laid-Open No. 7-277993 特許第4353746号公報Japanese Patent No. 4353746 特開2004−51615号公報JP 2004-51615 A

本発明は、斯かる従来の問題と実状に鑑み、胆汁酸を吸着する作用を有し、食品として摂取し易く、且つ生体にとって安全性の高い素材を提供することを課題とするものである。   The present invention has been made in view of such conventional problems and circumstances, and has an object to provide a material that has an action of adsorbing bile acids, is easily ingested as food, and is highly safe for a living body.

本発明者は、上記課題を解決すべく、鋭意研究を重ねた結果、繊維状蛋白質の蛋白分解酵素による分解物から得られた水溶性成分が、優れた胆汁酸吸着能を有することを見出し、本発明を完成した。   The present inventor has found that the water-soluble component obtained from the degradation product of the proteolytic enzyme of the fibrous protein has an excellent bile acid adsorption ability as a result of intensive studies to solve the above problems, The present invention has been completed.

すなわち、本発明は、繊維状蛋白質の蛋白分解酵素による分解物か又は蛋白分解酵素と糖分解酵素とによる分解物の、水溶性成分を含有する胆汁酸吸着用組成物を提供することにより、上記課題を解決したものである。
また本発明は、繊維状蛋白質を蛋白分解酵素で分解するか又は蛋白分解酵素と糖分解酵素とで分解し、得られた分解物から水溶性成分を取得することを特徴とする胆汁酸吸着用組成物の製造方法を提供することにより、上記課題を解決したものである。
また本発明は、当該胆汁酸吸着用組成物を含有する医薬、飲食品、及び飼料を提供することにより、上記課題を解決したものである。
That is, the present invention provides a bile acid adsorption composition containing a water-soluble component of a degradation product of a fibrous protein by a proteolytic enzyme or a degradation product of a proteolytic enzyme and a glycolytic enzyme. It solves the problem.
The present invention also provides a method for adsorbing bile acids, characterized by degrading a fibrous protein with a proteolytic enzyme, or decomposing with a proteolytic enzyme and a glycolytic enzyme, and obtaining a water-soluble component from the obtained degradation product. The above-described problems are solved by providing a method for producing a composition.
Moreover, this invention solves the said subject by providing the pharmaceutical, food-drinks, and feed containing the said composition for bile acid adsorption | suction.

本発明の胆汁酸吸着用組成物は、高い胆汁酸吸着能を有し、且つ長期服用しても副作用の心配がなく安全性が高い。従って、本発明の胆汁酸吸着用組成物は、胆汁酸を吸着してその排泄を促進するための医薬、飲食品、及び飼料として、あるいはさらに、大腸癌や胆石等の、その発症に胆汁酸の代謝が関与する疾患を予防及び/又は治療するための医薬、飲食品、及び飼料として利用することができる。   The composition for adsorbing bile acids according to the present invention has high bile acid adsorbing ability and has high safety without causing side effects even when taken for a long time. Therefore, the composition for adsorbing bile acids according to the present invention can be used as a medicine, food and drink, and feed for adsorbing bile acids and promoting their excretion, or for the development of colorectal cancer and gallstones. It can be used as a medicine, food and drink, and feed for preventing and / or treating a disease associated with the metabolism of.

各試験物質の胆汁酸吸着能を示すグラフ。The graph which shows the bile acid adsorption ability of each test substance.

本発明の胆汁酸吸着用組成物は、繊維状蛋白質の蛋白分解酵素による分解物の水溶性成分、好ましくは繊維状蛋白質の蛋白分解酵素と糖分解酵素とによる分解物の水溶性成分を、有効成分として含有する。本発明の胆汁酸吸着用組成物は、繊維状蛋白質の蛋白分解酵素による分解物の水溶性成分、好ましくは繊維状蛋白質の蛋白分解酵素と糖分解酵素とによる分解物の水溶性成分から実質的に構成されるものを含む。
本発明において、繊維状蛋白質とは、三次構造または四次構造として繊維状または網目状の構造を有する蛋白質を指す。繊維状蛋白質としては、筋肉に含まれるアクチンやミオシン、皮膚に含まれるコラーゲン等の動物由来の蛋白質;小麦に含まれるグルテン及びグリアジン、タカキビに含まれるカフィリン、トウモロコシに含まれるゼイン等の植物由来の蛋白質;ならびに納豆菌が産生するポリグルタミン等の微生物由来の蛋白質が挙げられる。これらの中では、入手の容易性、安全性、所望の活性、風味等の点から、グルテン又はカフィリンが好ましい。
The composition for adsorbing bile acids of the present invention is effective in using a water-soluble component of a degradation product of a fibrous protein by a proteolytic enzyme, preferably a water-soluble component of a degradation product of a fibrous protein by a proteolytic enzyme and a glycolytic enzyme. Contains as a component. The composition for adsorbing bile acids of the present invention is substantially composed of a water-soluble component of a degradation product of a fibrous protein by a proteolytic enzyme, preferably a water-soluble component of a degradation product of a fibrous protein by a proteolytic enzyme and a glycolytic enzyme. Including those configured.
In the present invention, the fibrous protein refers to a protein having a fibrous or network structure as a tertiary structure or a quaternary structure. Fibrous proteins include animal-derived proteins such as actin and myosin contained in muscle, collagen contained in skin, gluten and gliadin contained in wheat, caffeine contained in oyster millet, zein contained in corn, etc. And proteins derived from microorganisms such as polyglutamine produced by Bacillus natto. Among these, gluten or kafilin is preferable from the viewpoint of availability, safety, desired activity, flavor, and the like.

グルテンとは、小麦種子に多く含有されることが知られている蛋白質である。本発明において、グルテンとしては、精製したグルテンを用いてもよいが、小麦種子由来の蛋白質(小麦蛋白質)そのものを用いてもよい。例えば、小麦蛋白質中にグルテンは通常80〜90%程度含まれているため、小麦蛋白質を原料として本発明の組成物を得ることができる。本発明のために使用できるグルテンとしては、小麦から適宜調製したグルテン又は蛋白質であってもよく、あるいは市販されているグルテン又は小麦蛋白質等であってもよい。   Gluten is a protein known to be abundant in wheat seeds. In the present invention, purified gluten may be used as gluten, but wheat seed-derived protein (wheat protein) itself may be used. For example, since gluten is usually contained in wheat protein in an amount of about 80 to 90%, the composition of the present invention can be obtained using wheat protein as a raw material. The gluten that can be used for the present invention may be gluten or protein appropriately prepared from wheat, or commercially available gluten or wheat protein.

カフィリンとは、タカキビ(コウリャン)の種子に多く含有されることが知られている蛋白質である。本発明において、カフィリンとしては、市販のあるいは適宜調製した精製カフィリンを用いることができる。あるいは、タカキビ種子を、必要に応じて粉砕若しくは粉体化した後、それを蛋白分解酵素で分解することによっても、本発明の組成物を得ることができる。   Kafilin is a protein that is known to be contained in large amounts in the seeds of oyster millet. In the present invention, commercially available or appropriately prepared purified kaffirin can be used as the kafilin. Alternatively, the composition of the present invention can also be obtained by crushing or pulverizing the seeds of the millet as necessary, and then decomposing it with a proteolytic enzyme.

上記繊維状蛋白質を蛋白分解酵素で、好ましくは蛋白分解酵素と糖分解酵素とで分解し、得られた分解物から水溶性成分を取得することによって、本発明の胆汁酸吸着用組成物を製造することができる。
上記蛋白分解酵素としては、その由来は特に限定されず、動物、植物、微生物等の任意の生物由来のプロテアーゼを用いることができ、これらの1種または2種以上を用いることができる。当該蛋白分解酵素の例としては、例えば、植物由来では、パパイヤやパイナップル等の根茎、果汁から抽出・精製されたプロテアーゼ、微生物由来では、Aspergillus属、Rhizopus属、Streptomyces属、Penicillium属、Bacillus属等から抽出・精製されたプロテアーゼ、動物由来では豚膵臓等から抽出されたペプシンや、ニューラーゼ、キモトリプシン等のプロテアーゼを挙げることができる。これらの中で、蛋白質のアミノ酸鎖の中央から切断するエンドペプチダーゼ活性を有する蛋白分解酵素が好ましく、さらに酸性付近で作用する蛋白分解酵素が好ましい。酸性付近で作用する蛋白分解酵素としては、システインプロテアーゼやアスパラギン酸プロテアーゼが挙げられ、具体的には、パパイン、Aspergillus属由来のプロテアーゼ、ペプシン、カテプシンおよびニューラーゼ等が挙げられる。上記蛋白分解酵素としては、市販の蛋白分解酵素、例えば:プロテアーゼMアマノ(Aspergillus属の微生物由来の酸性プロテアーゼ、天野エンザイム株式会社);ニューラーゼ(ニューラーゼF3G、天野エンザイム株式会社);パパイン(パパインW−40、天野エンザイム株式会社);オリエンターゼ20A(Aspergillus属の微生物由来のプロテアーゼ、エイチビィアイ株式会社);オリエンターゼ90N(Bacillus属の微生物由来のプロテアーゼ、エイチビィアイ株式会社);オリエンターゼONS(Aspergillus属の微生物由来のプロテアーゼ、エイチビィアイ株式会社)、ニューラーゼF3G(Rhizopus属の微生物由来の酸性プロテアーゼ、天野エンザイム株式会社);プロテアーゼAアマノG(Aspergillus属の微生物由来のプロテアーゼ、天野エンザイム株式会社);プロテアーゼNアマノG(Bacillus属の微生物由来のプロテアーゼ、天野エンザイム株式会社);スミチームAP(Aspergillus属の微生物由来の酸性プロテアーゼ、新日本化学工業株式会社);スミチームLP(Aspergillus属の微生物由来のプロテアーゼ、新日本化学工業株式会社)等を用いることもできる。
上記蛋白分解酵素のうち、ペプシン、パパイン、ニューラーゼ、Aspergillus属の微生物由来の酸性プロテアーゼが好ましい。
これらの蛋白分解酵素は単独で使用してもよいが、適宜組み合わせて使用してもよい。
The fibrous protein is decomposed with a proteolytic enzyme, preferably with a proteolytic enzyme and a glycolytic enzyme, and a water-soluble component is obtained from the resulting decomposition product to produce the composition for adsorbing bile acids according to the present invention. can do.
The origin of the proteolytic enzyme is not particularly limited, and proteases derived from any organism such as animals, plants, microorganisms and the like can be used, and one or more of these can be used. Examples of the proteolytic enzymes include, for example, plant-derived rhizomes such as papaya and pineapple, protease extracted and purified from fruit juice, microorganisms-derived Aspergillus genus, Rhizopus genus, Streptomyces genus, Penicillium genus, Bacillus genus, etc. Examples include proteases extracted and purified from psins, and those derived from animals such as pepsin extracted from porcine pancreas and the like, and proteases such as neurase and chymotrypsin. Among these, a proteolytic enzyme having endopeptidase activity that cleaves from the center of the amino acid chain of the protein is preferable, and a proteolytic enzyme that acts in the vicinity of acidity is more preferable. Examples of proteolytic enzymes that act in the vicinity of acidity include cysteine proteases and aspartic proteases, and specific examples include papain, proteases derived from the genus Aspergillus, pepsin, cathepsin, and nuclease. Examples of the proteolytic enzymes include commercially available proteolytic enzymes such as: Protease M Amano (acidic protease derived from microorganisms of the genus Aspergillus, Amano Enzyme Inc.); Newase (Neurase F3G, Amano Enzyme Inc.); Orientase 20A (protease derived from microorganisms belonging to the genus Aspergillus, HTV Inc.); orientase 90N (protease derived from microorganisms belonging to the genus Bacillus, HTVii Inc.); orientase ONS (genus Aspergillus) Protease derived from microorganisms, HIBI Co., Ltd.), Neurase F3G (acidic protease derived from microorganisms belonging to the genus Rhizopus, Amano Enzyme Inc.); Protease A Amano G (proteases derived from microorganisms belonging to the genus Aspergillus, Amano En Im Corp.); Protease N Amano G (Protease derived from microorganisms belonging to the genus Bacillus, Amano Enzyme Inc.); Sumiteam AP (acidic protease derived from microorganisms belonging to the genus Aspergillus, Shinnippon Chemical Co., Ltd.); A microorganism-derived protease, Shin Nippon Chemical Industry Co., Ltd.) and the like can also be used.
Among the proteolytic enzymes, pepsin, papain, neurase, and acidic protease derived from microorganisms belonging to the genus Aspergillus are preferable.
These proteolytic enzymes may be used alone or in appropriate combination.

上記繊維状蛋白質が植物又は細菌由来の場合、蛋白分解酵素による分解と併せてさらに糖分解酵素による分解処理を行うことが好ましい。糖分解酵素によって、繊維状蛋白質の供給源などから不可避的に混入する澱粉質や繊維質等の不純物が分解されるので、活性成分を高収率で得ることができる。
当該糖分解酵素としては、その由来は特に限定されず、動物、植物、微生物等の任意の生物由来のものであってよい。当該糖分解酵素の例としては、α−アミラーゼ、グルコアミラーゼ等のアミラーゼ;α−グルコシダーゼ、トランスグルコシダーゼ等のグルコシダーゼ;プルラナーゼ;イソアミラーゼ;パンクレアチン;セルラーゼ等が挙げられる。あるいは、市販の糖分解酵素、例えば:液化酵素T:(Bacillus属の微生物由来のα−アミラーゼ、エイチビィアイ株式会社);グルクSG(Rhizopus属の微生物由来のグルコアミラーゼ、天野エンザイム株式会社);グルクザイムAF6(Rhizopus属の微生物由来のグルコアミラーゼ、天野エンザイム株式会社);コクラーゼ(Aspergillus属の微生物由来のα−アミラーゼ、三菱化学フーズ 製);スピターゼCP−40FG(Bacillus属の微生物由来のα−アミラーゼ、ナガセケムテックス株式会社);スミチームAS(Aspergillus属の微生物由来のα−アミラーゼ、新日本化学工業株式会社);スミチームAC(Aspergillus属の微生物由来のセルラーゼ、新日本化学工業株式会社);ヘミセルラーゼアマノ90(Aspergillus属の微生物由来のヘミセルラーゼ、新日本化学工業株式会社)等を用いることもできる。
上記糖分解酵素のうち、アミラーゼ、特にBacillus属の微生物由来のα−アミラーゼ、セルラーゼまたはパンクレアチンが好ましい。
これらの糖分解酵素は単独で使用してもよいが、適宜組み合わせて使用してもよい。
糖分解酵素による処理は、蛋白分解酵素による処理の前若しくは後に行ってもよく、又は蛋白分解酵素による処理と並行して行ってもよい。
糖分解酵素と蛋白分解酵素との組み合わせには特に制限はないが、例えば、アミラーゼ若しくは液化酵素Tとペプシン、パパイン、ニューラーゼ若しくはAspergillus属の微生物由来の酸性プロテアーゼとの組み合わせ、又はパンクレアチンとペプシン、パパイン若しくはAspergillus属の微生物由来の酸性プロテアーゼとの組み合わせが好ましい。
When the fibrous protein is derived from a plant or a bacterium, it is preferable to perform a decomposition treatment with a glycolytic enzyme in addition to the decomposition with a proteolytic enzyme. Impurities such as starch and fiber that are inevitably mixed from the source of fibrous protein are decomposed by the glycolytic enzyme, so that the active ingredient can be obtained in high yield.
The origin of the saccharolytic enzyme is not particularly limited, and it may be derived from any organism such as an animal, plant, or microorganism. Examples of the glycolytic enzyme include amylases such as α-amylase and glucoamylase; glucosidases such as α-glucosidase and transglucosidase; pullulanase; isoamylase; pancreatin; Alternatively, commercially available glycolytic enzymes, for example: Liquefaction enzyme T: (α-amylase derived from microorganisms belonging to the genus Bacillus, HTV Corporation); Gluc SG (glucoamylase derived from microorganisms belonging to the genus Rhizopus, Amano Enzyme Corporation); (Glucoamylase derived from microorganisms belonging to the genus Rhizopus, Amano Enzyme Co., Ltd.); Cochase (alpha-amylase derived from microorganisms belonging to the genus Aspergillus, manufactured by Mitsubishi Chemical Foods); Spitase CP-40FG (alpha-amylase derived from microorganisms belonging to the genus Bacillus, Nagase ChemteX Corporation); Sumiteam AS (alpha-amylase derived from microorganisms of the genus Aspergillus, Shinnihon Chemical Industry Co., Ltd.); Sumiteam AC (cellulase derived from microorganisms of the genus Aspergillus, Shinnihon Chemical Industry Co., Ltd.); Hemicellulase Amano 90 (Hemicellulase from Aspergillus sp. This Chemical Industry Co., Ltd.) can also be used.
Among the above glycolytic enzymes, amylase, particularly α-amylase, cellulase or pancreatin derived from microorganisms belonging to the genus Bacillus is preferable.
These glycolytic enzymes may be used alone or in appropriate combination.
The treatment with the glycolytic enzyme may be performed before or after the treatment with the proteolytic enzyme, or may be performed in parallel with the treatment with the proteolytic enzyme.
The combination of the glycolytic enzyme and the proteolytic enzyme is not particularly limited. For example, a combination of amylase or liquefying enzyme T and pepsin, papain, neurase, or an acidic protease derived from a microorganism belonging to the genus Aspergillus, or pancreatin and pepsin. A combination with papain or an acidic protease derived from a microorganism belonging to the genus Aspergillus is preferred.

上記繊維状蛋白質に、上記蛋白分解酵素を作用させて、あるいは上記蛋白分解酵素と糖分解酵素とを同時に又は順次作用させて、繊維状蛋白質の酵素分解物を調製する。その際、酵素を担体等に固定化し、繊維状蛋白質を溶解又は分散させた溶液に前記担体を接触させて当該繊維状蛋白質に酵素を作用させてもよいし、適当な媒体に繊維状蛋白質と酵素の両者を溶解または分散させて当該繊維状蛋白質に酵素を作用させてもよい。
繊維状蛋白質を溶解又は分散させる媒体としては、水性液体、例えば、純水、蒸留水、水道水、酸性水、アルカリ水、中性水、電解水、リン酸緩衝液などの緩衝液等が挙げられ、その種類や温度、pHなどの条件は、製造する環境や用いる繊維状蛋白質の溶解性等の性質に合わせて適宜決定する。酵素反応の条件(温度、pH、時間等)は、基質の量、使用する酵素の至適条件、同時に使用する酵素の至適条件等を考慮して適宜決定する。
酵素によって水溶性の分解物が最大限得られるまで反応を進行させることが好ましい。蛋白質の分解が不完全である場合、不溶性の残渣が多く残る結果、本発明の組成物の収率が低下する。
酵素による分解反応を終了するには、酵素を担体に固定化している場合には担体を溶液から除去すればよく、また酵素を溶解又は分散させている場合には、pHを用いる酵素の至適pHから大きく解離する方法や、溶液の温度を上昇させて酵素を失活させる方法など、適宜公知の方法を適用できる。
The proteolytic enzyme is allowed to act on the fibrous protein, or the proteolytic enzyme and the glycolytic enzyme are allowed to act simultaneously or sequentially to prepare an enzymatic degradation product of the fibrous protein. At that time, the enzyme may be immobilized on a carrier, and the enzyme may act on the fibrous protein by contacting the carrier with a solution in which the fibrous protein is dissolved or dispersed. Both enzymes may be dissolved or dispersed to allow the enzyme to act on the fibrous protein.
Examples of the medium for dissolving or dispersing the fibrous protein include aqueous liquids such as pure water, distilled water, tap water, acidic water, alkaline water, neutral water, electrolytic water, and buffer solutions such as phosphate buffers. The conditions such as the type, temperature and pH are appropriately determined according to the environment such as the production environment and the properties of the fibrous protein used. The enzyme reaction conditions (temperature, pH, time, etc.) are appropriately determined in consideration of the amount of the substrate, the optimum conditions for the enzyme used, the optimum conditions for the enzyme used simultaneously, and the like.
The reaction is preferably allowed to proceed until the maximum amount of water-soluble degradation product is obtained by the enzyme. If the protein degradation is incomplete, many insoluble residues remain, resulting in a decrease in the yield of the composition of the present invention.
In order to complete the enzymatic degradation reaction, the carrier may be removed from the solution when the enzyme is immobilized on the carrier, and the pH-optimized enzyme is optimal when the enzyme is dissolved or dispersed. Known methods such as a method of largely dissociating from pH and a method of inactivating the enzyme by raising the temperature of the solution can be appropriately applied.

次いで、上記酵素処理で得られた分解物を、乾燥、遠心、ろ過、分配等の任意の手段にかけることによって、当該分解物から水溶性成分を分離することができる。
本発明において、水溶性成分とは、上記分解物から、温度が5〜80℃、好ましくは8〜65℃、より好ましくは15〜50℃付近、pHが2〜11、好ましくは3〜10、より好ましくは4〜8付近で、水性液体に溶解又はコロイドを形成することのできる成分を指す。当該水性液体としては、純水、蒸留水、水道水、酸性水、アルカリ水、中性水、リン酸緩衝液などの緩衝液等が挙げられる。
通常、繊維状蛋白質の酵素分解が十分に行われていれば、温度やpHが多少変化しても本発明の水溶性成分中の成分が変化することはない。従って、上記分解物から水溶性成分を分離する際には、当該分解物をそのままの状態で分離操作にかけてもよく、あるいは分離操作を行いやすい温度等の条件にしてもよい。
例えば、上述の繊維状蛋白質溶液を蛋白分解酵素で処理して得られた分解物の溶液を、2500〜30000g、好ましくは3500〜23000g、より好ましくは4500〜18000g、さらに好ましくは5000〜15000gで、10〜60分間、好ましくは20分間遠心分離し、その上清を回収することによって、上記分解物から水溶性成分を分離することができる。
Next, the degradation product obtained by the enzyme treatment can be separated from the degradation product by subjecting it to any means such as drying, centrifugation, filtration, and distribution.
In the present invention, the water-soluble component is a temperature of 5 to 80 ° C., preferably 8 to 65 ° C., more preferably around 15 to 50 ° C., and a pH of 2 to 11, preferably 3 to 10, from the decomposition product. More preferably, it refers to a component capable of dissolving or forming a colloid in an aqueous liquid at around 4-8. Examples of the aqueous liquid include pure water, distilled water, tap water, acidic water, alkaline water, neutral water, and buffer solutions such as phosphate buffer solutions.
Usually, if the enzymatic degradation of the fibrous protein is sufficiently performed, the components in the water-soluble component of the present invention will not change even if the temperature or pH changes somewhat. Therefore, when the water-soluble component is separated from the decomposition product, the decomposition product may be subjected to a separation operation as it is, or may be subjected to conditions such as a temperature at which the separation operation is easily performed.
For example, a solution of a degradation product obtained by treating the above fibrous protein solution with a proteolytic enzyme is 2500 to 30000 g, preferably 3500 to 23000 g, more preferably 4500 to 18000 g, and further preferably 5000 to 15000 g. The water-soluble component can be separated from the decomposition product by centrifuging for 10 to 60 minutes, preferably 20 minutes, and collecting the supernatant.

上記のような手段により分離された水溶性成分を回収することによって、繊維状蛋白質の蛋白分解酵素による分解物の水溶性成分、好ましくは蛋白分解酵素と糖分解酵素とによる分解物の水溶性成分を取得することができる。
あるいは、当該水溶性成分の例としては、国際公開番号WO03/074071に製造例1として記載されたグルタミンペプチドの製造方法によって得られる、小麦グルテンのプロテアーゼ及びアミラーゼ分解処理物の水溶性成分が挙げられる。
上記水溶性成分は、必要に応じて、さらに希釈、濃縮、乾固、凍結乾燥、固形化、液状化、顆粒若しくは粉末化等の処理を施されていてもよい。
By recovering the water-soluble component separated by the above means, the water-soluble component of the degradation product of the fibrous protein by the proteolytic enzyme, preferably the water-soluble component of the degradation product by the proteolytic enzyme and the glycolytic enzyme Can be obtained.
Alternatively, examples of the water-soluble components include water-soluble components of wheat gluten protease and amylase degradation product obtained by the method for producing a glutamine peptide described as Production Example 1 in International Publication No. WO03 / 074071. .
The water-soluble component may be further subjected to treatments such as dilution, concentration, drying, freeze-drying, solidification, liquefaction, granulation, or powdering as necessary.

上記繊維状蛋白質の蛋白分解酵素による分解物の水溶性成分、又は蛋白分解酵素と糖分解酵素とによる分解物の水溶性成分(まとめて、繊維状蛋白質の酵素分解物の水溶性成分と称する)を含有する本発明の胆汁酸吸着用組成物は、後記実施例に示されるように、従来胆汁酸吸着効果が知られている食物繊維と比較して、顕著に優れた胆汁酸吸着能を有する。従って、本発明の組成物は、胆汁酸の吸着及び排泄に優れた効果を発揮することができ、あるいは大腸癌や胆石等の、その発症に胆汁酸の代謝が関与する疾患の予防及び/又は治療に優れた効果を発揮することができる。   Water-soluble component of the degradation product of the above-mentioned fibrous protein by proteolytic enzyme, or water-soluble component of the degradation product of proteolytic enzyme and glycolytic enzyme (collectively referred to as water-soluble component of the enzymatic degradation product of fibrous protein) The composition for adsorbing bile acids according to the present invention, which contains, as shown in the Examples below, has a significantly superior bile acid adsorption ability compared to dietary fibers that are conventionally known to have a bile acid adsorption effect. . Therefore, the composition of the present invention can exert an excellent effect on the adsorption and excretion of bile acids, or can prevent and / or prevent diseases such as colorectal cancer and gallstones that involve bile acid metabolism. It can exert an excellent effect on treatment.

本発明の胆汁酸吸着用組成物の原料となる上記に挙げた繊維状蛋白質、例えばグルテンやカフェリンは、従来食品材料として使用されている物質であり、長期服用しても副作用の心配がないので、健常者や成人だけでなく、小児、高齢者及び病弱者に対しても、安全に使用することができる。したがって、本発明の胆汁酸吸着用組成物は、ヒト又は動物用の医薬、飲食品、飼料等として、あるいはそれらを製造するために使用することができる。
従って、本発明はまた、上記本発明の胆汁酸吸着用組成物を含有する医薬、飲食品、及び飼料を提供する。
The above-described fibrous proteins, such as gluten and caffeine, which are used as raw materials for the composition for adsorbing bile acids according to the present invention, are substances that have been used as food materials in the past, and there are no side effects even if they are taken for a long time. Therefore, it can be safely used not only for healthy persons and adults but also for children, the elderly and the sick. Therefore, the composition for adsorbing bile acids of the present invention can be used as a medicine for humans or animals, food or drink, feed, or the like, or for producing them.
Therefore, this invention also provides the pharmaceutical, food-drinks, and feed containing the said composition for bile acid adsorption | suction of this invention.

本発明の医薬は、上記本発明の胆汁酸吸着用組成物を有効成分として含有する胆汁酸吸着剤であり得る。
当該医薬は、経口及び非経口投与を含む任意の剤型で投与され得る。経口投与のための剤型としては、錠剤、被覆錠剤、顆粒剤、散剤、カプセル剤のような固形製剤、あるいはエリキシロール、シロップおよび懸濁液のような液体製剤が挙げられる。非経口投与のための剤型としては、注射、輸液、経皮、経粘膜、経鼻、経腸、吸入、坐剤、ボーラス等が挙げられる。
The medicament of the present invention can be a bile acid adsorbent containing the bile acid adsorption composition of the present invention as an active ingredient.
The medicament can be administered in any dosage form including oral and parenteral administration. Dosage forms for oral administration include solid preparations such as tablets, coated tablets, granules, powders, capsules, or liquid preparations such as elixirol, syrups and suspensions. Examples of the dosage form for parenteral administration include injection, infusion, transdermal, transmucosal, nasal, enteral, inhalation, suppository, bolus and the like.

本発明の飲食品又は飼料は、上記本発明の胆汁酸吸着用組成物を有効成分として含有し、且つ胆汁酸吸着効果を企図して、その旨を表示した機能性飲食品、病者用飲食品、特定保健用飲食品、家畜用飼料、ペットフード等であり得る。
当該飲食品又は飼料の形態は、特に限定されないが、例えば、飲料の形態としては、茶飲料、コーヒー飲料、乳飲料、果汁飲料、炭酸飲料、アルコール飲料、清涼飲料等が挙げられ、食品又は飼料の形態としては、固形、半固形または液状であり得、錠剤形態、丸剤形態、カプセル形態、液剤形態、シロップ形態、粉末形態、顆粒形態等が挙げられる。具体的な食品の形態としては、パン類、麺類、ゼリー状食品や各種スナック類、焼き菓子、ケーキ類、チョコレート、ガム、飴、タブレット、カプセル、スープ類、乳製品、冷凍食品、インスタント食品、サプリメント、その他加工食品、調味料およびそれらの材料等が挙げられる。
The food / beverage product or feed of the present invention contains the composition for adsorbing bile acids of the present invention as an active ingredient, and is intended for the effect of adsorbing bile acids, and is a functional food / beverage product or food / beverage for the sick. Product, food and drink for specified health use, livestock feed, pet food and the like.
Although the form of the said food / beverage products or feed is not specifically limited, For example, as a drink form, tea drink, coffee drink, milk drink, fruit juice drink, carbonated drink, alcoholic drink, soft drink etc. are mentioned, food or feed The form may be solid, semi-solid or liquid and includes tablet form, pill form, capsule form, liquid form, syrup form, powder form, granule form and the like. Specific food forms include breads, noodles, jelly-like foods and various snacks, baked goods, cakes, chocolate, gum, candy, tablets, capsules, soups, dairy products, frozen foods, instant foods, Examples include supplements, other processed foods, seasonings, and materials thereof.

本発明の胆汁酸吸着用組成物、医薬、飲食品又は飼料は、必要に応じて、上記繊維状蛋白質の酵素分解物の水溶性成分以外の他の成分、例えば、他の有効成分及び/又は通常利用される添加物若しくは担体を含有していてもよい。
医薬の場合、当該他の成分としては、例えば、他の薬効成分、美容成分、栄養成分、ならびに賦形剤、崩壊剤、結合剤、滑沢剤、界面活性剤、水溶性高分子、希釈剤、浸透圧調整剤、pH調整剤、乳化剤、防腐剤、緩衝剤、安定化剤、酸化防止剤、増粘剤、紫外線吸収剤、活性増強剤、着色剤、甘味料、矯味剤、矯臭剤、酸味料等が挙げられ、これらは適宜組み合わせて使用される。
飲食品又は飼料の場合、当該他の成分としては、例えば、他の飲食品材料、栄養成分、美容成分、ならびに溶剤、油、軟化剤、乳化剤、防腐剤、安定剤、酸化防止剤、着色剤、紫外線吸収剤、保湿剤、増粘剤、光沢剤、甘味料、香料等の添加物が挙げられ、これらは適宜組み合わせて使用される。
The bile acid-adsorbing composition, medicine, food / drink or feed of the present invention, if necessary, other components other than the water-soluble component of the enzymatic degradation product of the fibrous protein, such as other active ingredients and / or It may contain commonly used additives or carriers.
In the case of medicine, the other ingredients include, for example, other medicinal ingredients, cosmetic ingredients, nutrition ingredients, and excipients, disintegrants, binders, lubricants, surfactants, water-soluble polymers, diluents. , Osmotic pressure adjusting agent, pH adjusting agent, emulsifier, preservative, buffer, stabilizer, antioxidant, thickener, ultraviolet absorber, activity enhancer, colorant, sweetener, flavoring agent, flavoring agent, A sour agent etc. are mentioned, These are used in combination suitably.
In the case of food and drink or feed, examples of the other ingredients include other food and drink materials, nutritional ingredients, cosmetic ingredients, and solvents, oils, softeners, emulsifiers, preservatives, stabilizers, antioxidants, and coloring agents. , Ultraviolet absorbers, moisturizers, thickeners, brighteners, sweeteners, fragrances and the like, and these are used in appropriate combinations.

上記本発明の組成物、医薬、飲食品又は飼料における、上記繊維状蛋白質の酵素分解物の水溶性成分の含有量は、それらの剤型や形態により異なるが、乾燥固形分換算で、通常、全質量に対して、医薬の場合、1〜90質量%、好ましくは5〜70質量%であり、飲食品又は飼料の場合、5〜100質量%、好ましくは10〜90質量%である。
本発明の胆汁酸吸着用組成物の投与又は摂取量は、通常、上記繊維状蛋白質の酵素分解物の水溶性成分の乾燥固形分換算で、成人一日あたり2g〜30g、好ましくは6〜30gである。上記投与又は摂取量は、用法及び適用対象に応じて適宜調整され得る。
In the composition of the present invention, medicine, food or drink or feed, the content of the water-soluble component of the enzymatic degradation product of the fibrous protein varies depending on the dosage form and form, but in terms of dry solids, In the case of a pharmaceutical, it is 1-90 mass% with respect to the total mass, Preferably it is 5-70 mass%, and in the case of food-drinks or feed, it is 5-100 mass%, Preferably it is 10-90 mass%.
The administration or intake of the composition for adsorbing bile acids according to the present invention is usually 2 g to 30 g, preferably 6 to 30 g per day for an adult in terms of dry solid content of the water-soluble component of the enzymatic degradation product of the fibrous protein. It is. The administration or intake amount can be appropriately adjusted according to the usage and application target.

次に実施例を示して本発明を更に詳細に説明するが、本発明は以下の実施例に限定されるものではない。   EXAMPLES Next, although an Example is shown and this invention is demonstrated further in detail, this invention is not limited to a following example.

実施例1 グルテンの酵素分解物の水溶性成分の調製
(1)反応釜に、イオン交換水9,700L、無水クエン酸38kg及び小麦グルテン(活性グルテン:George Weston Foods Limited)1,500kgを仕込み、45℃に加温した後、蛋白分解酵素(プロテアーゼMアマノ;天野エンザイム株式会社)2.2kg及び糖分解酵素(液化酵素T;エイチビィアイ株式会社)1.1kgを加えて、45℃で5時間加水分解反応を行い、次いで25%水酸化ナトリウム水溶液を用いて反応液のpHを4.4〜4.5に調整して5時間保って酵素処理を行った。
(2)次いで、反応液を80℃に20分間保ってプロテアーゼを失活させた後、65℃に冷却し、そこに糖分解酵素(液化酵素T;エイチビィアイ株式会社)0.5kgを加えて小麦グルテン中に含まれていた糖質を加水分解させた後、液を90℃に20分間保ってアミラーゼを失活させた。
(3)次いで、反応液を10℃以下に冷却した後、再度55℃に加熱し、そこに活性炭(武田薬品工業株式会社製「タケコール」)100kgを加えて55℃で30分間攪拌した。
(4)液温を45℃にし、濃過助剤(昭和化学工業株式会社製「ラヂオライト」)を加えて、加圧濾過装置を使用して濾過を行い、濾液7,000Lを回収した。
(5)上記(4)で回収した濾液をBrix値が20〜40になるまで減圧下で濃縮した後、プレートヒーターを使用して110℃で20秒間加熱して殺菌し、次いで55℃まで冷却した。
(6)上記(5)で得られた液を、噴霧乾燥装置を使用して送風温度160℃、排風温度80℃の条件下に噴霧乾燥して、小麦蛋白質の加水分解物を、粉末の形態で約1,000kg得た。
(7)上記(6)で得られた小麦蛋白質の加水分解物粉未を、60メッシュ篩(目開き0.246mm)を用いて分級し、60メッシュ篩を通過した微粉を回収し、本発明組成物とした。
Example 1 Preparation of Water-Soluble Component of Enzymatic Degradation Product of Gluten (1) 9,700 L of ion exchange water, 38 kg of anhydrous citric acid and 1,500 kg of wheat gluten (active gluten: George Weston Foods Limited) were charged in a reaction kettle, After heating to 45 ° C., 2.2 kg of protease (Protease M Amano; Amano Enzyme Co., Ltd.) and 1.1 kg of saccharolytic enzyme (Liquefied enzyme T; HBI Co., Ltd.) are added, and water is added at 45 ° C. for 5 hours. The decomposition reaction was carried out, and then the enzyme treatment was carried out by adjusting the pH of the reaction solution to 4.4 to 4.5 using a 25% aqueous sodium hydroxide solution and keeping it for 5 hours.
(2) Next, the reaction solution was kept at 80 ° C. for 20 minutes to inactivate the protease, then cooled to 65 ° C., and 0.5 kg of a saccharide-degrading enzyme (liquefied enzyme T; HTV Corporation) was added to the wheat. After the carbohydrate contained in gluten was hydrolyzed, the liquid was kept at 90 ° C. for 20 minutes to inactivate amylase.
(3) Next, the reaction solution was cooled to 10 ° C. or lower and then heated again to 55 ° C., and 100 kg of activated carbon (“Takecol” manufactured by Takeda Pharmaceutical Co., Ltd.) was added thereto and stirred at 55 ° C. for 30 minutes.
(4) The liquid temperature was set to 45 ° C., a concentrated auxiliary agent (“Radiolite” manufactured by Showa Chemical Industry Co., Ltd.) was added, and filtration was performed using a pressure filtration device, and 7,000 L of the filtrate was recovered.
(5) The filtrate collected in (4) above is concentrated under reduced pressure until the Brix value is 20-40, then sterilized by heating at 110 ° C. for 20 seconds using a plate heater, and then cooled to 55 ° C. did.
(6) The liquid obtained in (5) above is spray-dried using a spray drying device under conditions of an air blowing temperature of 160 ° C. and an exhaust air temperature of 80 ° C. About 1,000 kg was obtained in the form.
(7) The wheat protein hydrolyzate powder obtained in (6) above is classified using a 60 mesh sieve (aperture 0.246 mm), and the fine powder that has passed through the 60 mesh sieve is recovered, and the present invention It was set as the composition.

実施例2 タカキビの酵素分解物の水溶性成分の調製
(1)タカキビ種子(株式会社GNS)を粉砕し、粉砕物の10倍量(w/v)の純水を加え、濃塩酸でpHを2.0に調整した。ここにタカキビ種子粉砕物の質量比1%のペプシン(ブタ胃粘膜由来:和光純薬工業)を添加し、37℃で4時間反応させた。反応液にTris−HClを終濃度25mMとなるよう添加し、次いで、濃水酸化ナトリウムでpHを8.0に調整し、タカキビ種子粉砕物の質量比2%のパンクレアチン(ブタ膵臓由来:和光純薬工業)を添加し、37℃で24時間反応させた。
(2)上記(1)の反応液を15,000Gで20分間遠心し、上清を対飽和度80%で硫酸アンモニウムを添加溶解し、振盪攪拌し、4℃で12時間静置した。
(3)次いで、これを1,700Gで15分間遠心分離し、沈殿物を10mMリン酸緩衝液に溶解した。溶解液を分子量3,500カットの透析膜に入れ、100倍量の10mMリン酸緩衝液中で透析を行った。透析液を凍結乾燥し、本発明組成物として回収した。
Example 2 Preparation of Water-Soluble Component of Enzyme Degradation Product of Pepper Millet (1) Peanut seed (GNS Co., Ltd.) is crushed, 10 times (w / v) pure water of crushed product is added, and pH is adjusted with concentrated hydrochloric acid Adjusted to 2.0. To this, pepsin (derived from porcine stomach mucosa: Wako Pure Chemical Industries, Ltd.) having a mass ratio of ground millet seeds of 1% was added and reacted at 37 ° C. for 4 hours. Tris-HCl was added to the reaction solution to a final concentration of 25 mM, and then the pH was adjusted to 8.0 with concentrated sodium hydroxide. Pancreatine (pig pancreas origin: sum) (Optical Pure Chemical Industries, Ltd.) was added and the reaction was allowed to proceed at 37 ° C. for 24 hours.
(2) The reaction solution of (1) was centrifuged at 15,000 G for 20 minutes, and the supernatant was dissolved by adding ammonium sulfate at a saturation degree of 80%, shaken and stirred, and allowed to stand at 4 ° C. for 12 hours.
(3) Next, this was centrifuged at 1,700 G for 15 minutes, and the precipitate was dissolved in 10 mM phosphate buffer. The lysate was placed in a dialysis membrane having a molecular weight of 3,500 cuts, and dialyzed in a 100-fold amount of 10 mM phosphate buffer. The dialysate was lyophilized and recovered as a composition of the present invention.

試験例1 胆汁酸吸着試験
(1)胆汁酸混合液の調製
タウロコール酸(和光純薬工業)242mg、グルココール酸(CALBIOCHEM)658.3mgを混合し、10mMリン酸緩衝液(pH=6.8)20mLに溶解した。10mMリン酸緩衝液(pH=6.8)を用いて50mLにメスアップし、36mM胆汁酸混合液(ストック液)を調製した。
(2)胆汁酸吸着
試験物質200mgを遠心管に秤量し、これに(1)で調製したストック液の50倍希釈液を4mL添加した。これにパンクレアチン溶液(パンクレアチン(ブタ膵臓由来:和光純薬工業)10mg/mL 100mMリン酸緩衝液)をさらに添加し、37℃で1時間反応させた。反応液を10万G、18分間遠心分離し、上清を分取した。沈殿に100mMリン酸緩衝液を5mL添加して懸濁後、10万G、18分間遠心分離し、上清を分取して先の上清と合一した。
(3)胆汁酸吸着率の測定
上記上清中の胆汁酸濃度を、胆汁酸測定キット(和光純薬工業「総胆汁酸テストワコー」)により常法にて測定し、次式により胆汁酸吸着率を決定した。

試験物質の胆汁酸吸着率(%)=
((陰性対照の胆汁酸濃度−試験物質の胆汁酸濃度)/陰性対照の胆汁酸濃度)×100
Test Example 1 Bile acid adsorption test (1) Preparation of bile acid mixed solution 242 mg of taurocholic acid (Wako Pure Chemical Industries) and 658.3 mg of glucocholic acid (CALBIOCHEM) were mixed, and 10 mM phosphate buffer solution (pH = 6.8). ) Dissolved in 20 mL. The volume was made up to 50 mL with 10 mM phosphate buffer (pH = 6.8) to prepare a 36 mM bile acid mixture (stock solution).
(2) Bile acid adsorption 200 mg of the test substance was weighed into a centrifuge tube, and 4 mL of a 50-fold diluted solution of the stock solution prepared in (1) was added thereto. A pancreatin solution (pancreatin (pig pancreas origin: Wako Pure Chemical Industries) 10 mg / mL 100 mM phosphate buffer) was further added thereto, and the mixture was reacted at 37 ° C. for 1 hour. The reaction solution was centrifuged at 100,000 G for 18 minutes, and the supernatant was collected. The precipitate was suspended by adding 5 mL of 100 mM phosphate buffer, centrifuged at 100,000 G for 18 minutes, and the supernatant was collected and combined with the previous supernatant.
(3) Measurement of bile acid adsorption rate The bile acid concentration in the above supernatant was measured by a conventional method using a bile acid measurement kit (Wako Pure Chemical Industries, Ltd., “Total Bile Acid Test Wako”). The rate was determined.

Test substance bile acid adsorption rate (%) =
((Negative control bile acid concentration-bile acid concentration of test substance) / negative control bile acid concentration) × 100

なお、試験物質としては、以下を用いた。
実施例1 本発明組成物(グルテンの酵素分解物の水溶性成分)
実施例2 本発明組成物(タカキビの酵素分解物の水溶性成分)
比較例1 小麦グルテン(活性グルテン:George Weston Foods Limited)
比較例2 タカキビ種子(株式会社GNS)粉砕物
比較例3 タカキビの蛋白分解酵素分解物の不溶性成分
陽性対照 コレスチラミン(SIGMA)
陰性対照 セルロース(SIGMA)
In addition, the following was used as a test substance.
Example 1 Composition of the present invention (water-soluble component of gluten enzyme degradation product)
Example 2 Composition of the Present Invention (Water-Soluble Component of Enzyme Degradation Product of Prickly Millet)
Comparative Example 1 Wheat gluten (active gluten: George Weston Foods Limited)
Comparative example 2 Ground millet seed (GNS Co., Ltd.) Comparative example 3 Insoluble component of proteolytic enzyme degradation product of red millet Positive control Cholestyramine (SIGMA)
Negative control Cellulose (SIGMA)

参考として、比較例3のタカキビのペプシン分解物の不溶性成分の製法を以下に記載する。
比較例2 タカキビのペプシン分解物の不溶性成分
タカキビ種子を粉砕し、粉砕物の10倍量(w/v)の純水を加え、濃塩酸でpHを2.0に調整した。ここにタカキビ種子粉砕物の質量比1%のペプシン(ブタ胃粘膜由来:和光純薬工業)を添加し、37℃で4時間反応させた。反応液にTris−HClを終濃度25mMとなるよう添加し、次いで、濃水酸化ナトリウムでpHを8.0に調整し、タカキビ種子粉砕物の質量比2%のパンクレアチン(ブタ膵臓由来:和光純薬工業)を添加し、37℃で24時間反応させた。次いで、反応液を15,000Gで20分間遠心し、沈殿物を分取した。
For reference, a method for producing an insoluble component of the pepsin degradation product of oyster mill of Comparative Example 3 is described below.
Comparative Example 2 Insoluble component of pepsin degradation product of oyster millet Seed millet seed was pulverized, 10 times the amount (w / v) of pure water was added, and the pH was adjusted to 2.0 with concentrated hydrochloric acid. To this, pepsin (derived from porcine stomach mucosa: Wako Pure Chemical Industries, Ltd.) having a mass ratio of ground millet seeds of 1% was added and reacted at 37 ° C. for 4 hours. Tris-HCl was added to the reaction solution to a final concentration of 25 mM, and then the pH was adjusted to 8.0 with concentrated sodium hydroxide. Pancreatine (pig pancreas origin: sum) (Optical Pure Chemical Industries, Ltd.) was added and the reaction was allowed to proceed at 37 ° C. for 24 hours. Next, the reaction solution was centrifuged at 15,000 G for 20 minutes to collect a precipitate.

(4)結果
結果を下記表1及び図1に示す。本発明の組成物は、食物繊維であるセルロース、ならびに酵素処理をしていないグルテンやタカキビ、及びタカキビ分解物不溶性成分と比較して、高い胆汁酸結合能を有していることが示された。
(4) Results The results are shown in Table 1 below and FIG. It was shown that the composition of the present invention has a high bile acid binding ability as compared with cellulose which is dietary fiber, and gluten and oyster mill which have not been subjected to enzyme treatment, and an insoluble component of oyster mill degradation product. .

Claims (8)

繊維状蛋白質の蛋白分解酵素と糖分解酵素とによる分解物の、水溶性成分を含有する胆汁酸吸着用組成物であって、
該蛋白分解酵素がペプシン、パパイン、ニューラーゼ、Aspergillus属の微生物由来の酸性プロテアーゼから選択される1種以上であり、
該糖分解酵素がアミラーゼ及び/又はパンクレアチンである、
胆汁酸吸着用組成物
The decomposition product by the white enzymes and glycolytic enzymes fibrous protein, a bile acid composition containing a water-soluble component,
The proteolytic enzyme is at least one selected from pepsin, papain, neurase, acidic protease derived from microorganisms of the genus Aspergillus,
The glycolytic enzyme is amylase and / or pancreatin,
A composition for adsorbing bile acids .
前記繊維状蛋白質が穀物由来である請求項1記載の組成物。   The composition according to claim 1, wherein the fibrous protein is derived from cereal grains. 前記繊維状蛋白質がグルテン又はカフィリンである請求項1記載の組成物。   The composition according to claim 1, wherein the fibrous protein is gluten or kafilin. 前記繊維状蛋白質が、小麦から調製した蛋白質、又はタカキビ種子である、請求項1記載の組成物。The composition according to claim 1, wherein the fibrous protein is a protein prepared from wheat or a millet seed. 繊維状蛋白質を蛋白分解酵素と糖分解酵素とで分解し、得られた分解物から水溶性成分を取得することを特徴とする胆汁酸吸着用組成物の製造方法であって、
該蛋白分解酵素がペプシン、パパイン、ニューラーゼ、Aspergillus属の微生物由来の酸性プロテアーゼから選択される1種以上であり、
該糖分解酵素がアミラーゼ及び/又はパンクレアチンである、
方法
The fibrous protein was degraded in the white enzymes and glycolytic enzymes, a process for the preparation of the resulting decomposed product bile acid composition characterized in that to obtain the water-soluble components from,
The proteolytic enzyme is at least one selected from pepsin, papain, neurase, acidic protease derived from microorganisms of the genus Aspergillus,
The glycolytic enzyme is amylase and / or pancreatin,
Way .
前記繊維状蛋白質が穀物由来である請求項記載の方法。 The method according to claim 5 , wherein the fibrous protein is derived from cereal grains. 前記繊維状蛋白質がグルテン又はカフィリンである請求項記載の方法。 6. The method according to claim 5 , wherein the fibrous protein is gluten or kafilin. 前記繊維状蛋白質が、小麦から調製した蛋白質、又はタカキビ種子である、請求項5記載の組成物。The composition according to claim 5, wherein the fibrous protein is a protein prepared from wheat or oyster millet seeds.
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