JPWO2018056284A1 - Composition for improving intestinal flora - Google Patents
Composition for improving intestinal flora Download PDFInfo
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- JPWO2018056284A1 JPWO2018056284A1 JP2018541079A JP2018541079A JPWO2018056284A1 JP WO2018056284 A1 JPWO2018056284 A1 JP WO2018056284A1 JP 2018541079 A JP2018541079 A JP 2018541079A JP 2018541079 A JP2018541079 A JP 2018541079A JP WO2018056284 A1 JPWO2018056284 A1 JP WO2018056284A1
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- cocoa
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- luminacoid
- ficalibacterium
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
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Abstract
本発明は、フィーカリバクテリウム属菌の産生を促進するための新規な組成物および用剤並びにフィーカリバクテリウム属菌の産生促進方法の提供をその目的とする。本発明によれば、カカオ由来ルミナコイドを含んでなるフィーカリバクテリウム属菌の産生促進のための組成物およびフィーカリバクテリウム属菌の産生促進剤が提供される。本発明によればまた、有効量のカカオ由来ルミナコイドを摂取させることを含む、フィーカリバクテリウム属菌の産生促進方法が提供される。An object of the present invention is to provide a novel composition and an agent for promoting the production of the genus Ficalibacterium and a method for promoting the production of the genus Ficalibacterium. According to the present invention, there are provided a composition for promoting the production of Ficaribacillus bacteria comprising a cocoa-derived luminacoid and a production promoter of the Ficabacillus bacteria. According to the present invention, there is also provided a method for promoting the production of a genus of Ficalibacterium, which comprises ingesting an effective amount of cocoa-derived luminacoid.
Description
本願は、先行する日本国出願である特願2016−184906(出願日:2016年9月21日)の優先権の利益を享受するものであり、その開示内容全体は引用することにより本明細書の一部とされる。 This application claims the benefit of the priority of prior Japanese Patent Application No. 2016-184906 (filing date: September 21, 2016), the entire disclosure of which is incorporated herein by reference. Be part of
本発明は、腸内菌叢改善促進するための組成物に関し、詳細には、カカオ由来ルミナコイドを含んでなるフィーカリバクテリウム属菌の産生を促進するための組成物に関する。 The present invention relates to a composition for promoting intestinal flora improvement, and in particular to a composition for promoting the production of a ficalibacterium comprising a cocoa-derived luminacoid.
フィーカリバクテリウム属菌(Faecalibacterium)は、クロストリジウム クラスター(Clostridium cluster IV、C. leptum subgroup)に属し、ヒトやヒト以外の哺乳類(ブタ、マウス、子牛など)や家禽でも検出される。フィーカリバクテリウム属菌は、主として大腸上皮粘膜上に分泌された粘液層に付着する短鎖脂肪酸産生菌(主に酪酸を一次代謝産物として産生)である(非特許文献1)。また、フィーカリバクテリウム属菌は、制御性T細胞(Treg)の誘導能を示すことから、抗炎症・抗アレルギー作用が見出されている(非特許文献2)。さらに、フィーカリバクテリウム属菌は、ヒトの腸内菌叢における占有率が数%と高く、フィーカリバクテリウム属菌の減少が、腸内菌共生バランス失調(Dysbiosis)に起因すると考えられる疾病(クローン病など)と関連する可能性が示唆されている(非特許文献3)。 The genus Ficacalibacterium (Faecalibacterium) belongs to the Clostridium cluster (Clostridium cluster IV, C. leptum subgroup) and is also detected in humans and non-human mammals (pig, mouse, calf, etc.) and poultry. Ficalibacterium is a short-chain fatty acid-producing bacterium (mainly producing butyric acid as a primary metabolite) that adheres to the mucus layer mainly secreted on the colonic epithelial mucosa (non-patent document 1). In addition, since the Ficalibacterium bacteria show the ability to induce regulatory T cells (Treg), anti-inflammatory and anti-allergic actions have been found (Non-patent Document 2). Furthermore, a disease in which the occupancy rate in the human intestinal flora is as high as several%, and the decrease in the fish bacteria is considered to be caused by dysfungal symbiotic balance (Dysbiosis). It is suggested that it may be associated with (such as Crohn's disease) (Non-patent Document 3).
カカオ豆は発芽に必要なアミノ酸源やエネルギー源としてたんぱく質や脂質を貯蔵しており、また細胞壁の構造物質として食物繊維を豊富に含んでいる。これらはカカオ豆から調製された菓子原料であるカカオマスにも含まれている。以前より多糖類やリグニン等の食物繊維が整腸やコレステロール排泄等の機能性を示すことはよく知られていたが、最近、プロテアーゼ耐性を示す一部のたんぱく質(難消化性たんぱく質)が、便秘の緩解などの、食物繊維や難消化性デキストリン等と似た生理的機能を示すことが明らかになってきた(非特許文献4)。しかし、カカオ豆由来のルミナコイドに関しての詳細な知見は得られていない。一方で、カカオ豆からアルカリ抽出および酸沈殿にて調製したたんぱく質画分をマウスに摂取させると糞便量が増大したことが報告されている(特許文献1)。 Cocoa beans store proteins and lipids as an amino acid source and energy source necessary for germination, and contain abundant dietary fiber as a structural material of cell walls. These are also contained in cacao mass which is a confectionery material prepared from cacao beans. It has been well known that dietary fibers such as polysaccharides and lignin show functionalities such as intestinal regulation and cholesterol excretion, but some proteins (resistant proteins) resistant to protease have recently been constipated. It has been clarified that it exhibits physiological functions similar to dietary fiber, indigestible dextrin and the like, such as the remission of (non-patent document 4). However, detailed knowledge on luminacoids derived from cocoa beans has not been obtained. On the other hand, it has been reported that the amount of feces increased when a mouse was fed with a protein fraction prepared by alkaline extraction and acid precipitation from cocoa beans (Patent Document 1).
本発明は、新規なフィーカリバクテリウム属菌の産生促進用組成物およびフィーカリバクテリウム属菌の産生促進剤を提供することを目的とする。 An object of the present invention is to provide a novel composition for promoting the production of the genus Ficalibacterium and an agent for promoting the production of the genus Ficalibacterium.
本発明者らは、今般、カカオ豆由来ルミナコイドを高濃度で含有する油脂加工組成物が、ヒト腸内菌叢中のフィーカリバクテリウム属菌の占有率(%)を有意に増加させることを見出した。本発明はこの知見に基づくものである。 The present inventors have now found that a fat and oil processing composition containing a high concentration of cacao bean-derived luminacoid significantly increases the occupancy rate (%) of Ficalibacterium in human intestinal flora. I found it. The present invention is based on this finding.
本発明によれば以下の発明が提供される。
[1]カカオ由来ルミナコイドを含んでなる、フィーカリバクテリウム属菌の産生促進のための組成物(以下、「本発明の組成物」ということがある)およびフィーカリバクテリウム属菌の産生促進剤(以下、「本発明の用剤」ということがある)。
[1−1]カカオ由来ルミナコイドが、カカオ豆由来ルミナコイドである、前記[1]に記載のフィーカリバクテリウム属菌の産生促進用組成物およびフィーカリバクテリウム属菌の産生促進剤
[1−2]カカオ由来ルミナコイドを0.5g以上含んでなるものである、前記[1]または[1−1]に記載のフィーカリバクテリウム属菌の産生促進用組成物およびフィーカリバクテリウム属菌の産生促進剤。
[2]フィーカリバクテリウム属菌の産生促進に有効な1日分の摂取量のカカオ由来ルミナコイドを含んでなる、前記[1]、[1−1]または[1−2]に記載のフィーカリバクテリウム属菌の産生促進用組成物およびフィーカリバクテリウム属菌の産生促進剤。
[3]1日分の有効摂取量ごとに包装されてなる、前記[2]に記載のフィーカリバクテリウム属菌の産生促進用組成物およびフィーカリバクテリウム属菌の産生促進剤。
[4]フィーカリバクテリウム属菌の産生促進に有効な1日分の摂取量が0.5〜11.9g[カカオ由来ルミナコイド量]である、前記[2]または[3]に記載のフィーカリバクテリウム属菌の産生促進用組成物およびフィーカリバクテリウム属菌の産生促進剤。
[5]カカオ由来ルミナコイドを2週間以上摂取させることを特徴とする、前記[1]、[1−1]、[1−2]および[2]〜[4]のいずれかに記載のフィーカリバクテリウム属菌の産生促進用組成物およびフィーカリバクテリウム属菌の産生促進剤。
[5−1]カカオ由来ルミナコイドを、1日当たり0.5〜11.9gで1週間以上摂取させることを特徴とする、前記[1]、[1−1]、[1−2]および[2]〜[5]のいずれかに記載のフィーカリバクテリウム属菌の産生促進用組成物およびフィーカリバクテリウム属菌の産生促進剤。
[6]油脂加工組成物の形態である、前記[1]、[1−1]、[1−2]、[2]〜[5]および[5−1]のいずれかに記載のフィーカリバクテリウム属菌の産生促進用組成物およびフィーカリバクテリウム属菌の産生促進剤。
[7]フィーカリバクテリウム属菌の産生により治療、予防または改善しうる疾患または症状の治療、予防または改善に用いるための、前記[1]、[1−1]、[1−2]、[2]〜[5]、[5−1]および[6]のいずれかに記載の組成物。
[8]有効量のカカオ由来ルミナコイドを摂取させることを含んでなる、フィーカリバクテリウム属菌の産生促進方法。
[9]カカオ由来ルミナコイドをフィーカリバクテリウム属菌の産生促進に有効な1日分の摂取量で1週間以上摂取させることを含んでなる、前記[8]に記載のフィーカリバクテリウム属菌の産生促進方法。
[10]フィーカリバクテリウム属菌の産生促進に有効な1日分の摂取量が0.5〜11.9g(カカオ由来ルミナコイド)である、前記[9]に記載のフィーカリバクテリウム属菌の産生促進方法。
[11]カカオ由来ルミナコイドを油脂加工組成物の形態で摂取させることを特徴とする、前記[8]〜[10]のいずれかに記載のフィーカリバクテリウム属菌の産生促進方法。
[12]有効量のカカオ由来ルミナコイドを摂取させるか、或いは投与することを含んでなる、フィーカリバクテリウム属菌の産生により治療、予防または改善しうる疾患または症状の治療、予防または改善方法。
[13]フィーカリバクテリウム属菌の産生促進剤の製造のための、フィーカリバクテリウム属菌の産生により治療、予防または改善しうる疾患または症状の治療剤、予防剤または改善剤の製造のための、フィーカリバクテリウム属菌の産生促進剤としての、あるいは、フィーカリバクテリウム属菌の産生により治療、予防または改善しうる疾患または症状の治療剤、予防剤または改善剤としての、カカオ由来ルミナコイドの使用。
[14]フィーカリバクテリウム属菌の産生促進用の、あるいは、フィーカリバクテリウム属菌の産生により治療、予防または改善しうる疾患または症状の治療、予防または改善用の、カカオ由来ルミナコイド。According to the present invention, the following inventions are provided.
[1] A composition for promoting the production of Ficaribacterium comprising the cocoa-derived luminacoid (hereinafter sometimes referred to as “the composition of the present invention”) and the production acceleration of the Ficaribacterium Agent (hereinafter sometimes referred to as “agent of the present invention”).
[1-1] The composition for promoting the production of Ficaribacillus bacteria according to the above [1], wherein the cocoa-derived luminacoid is a cocoa bean-derived luminacoid, and the production accelerator of the Ficaribacterium genus [1- [2] The composition for promoting the production of a ficalibacterium according to the above [1] or [1-1], which comprises 0.5 g or more of a cocoa-derived luminacoid Production promoter.
[2] The food according to the above [1], [1-1] or [1-2], which comprises a daily amount of cocoa-derived luminacoid effective for promoting the production of the genus Ficaribacterium. A composition for promoting the production of a bacterium of the genus Calibacterium and a promoter for the production of a bacterium of the genus Ficalibacterium.
[3] The composition for promoting the production of Ficaribacterium according to the above-mentioned [2] and the production promoter of the genus Ficaribacterium, which are packaged per effective intake for one day.
[4] The fee according to the above [2] or [3], wherein the daily intake effective for promoting the production of the ficalibacterium bacteria is 0.5 to 11.9 g [the amount of cacao-derived luminacoid]. A composition for promoting the production of a bacterium of the genus Calibacterium and a promoter for the production of a bacterium of the genus Ficalibacterium.
[5] The food according to any one of the above [1], [1-1], [1-2] and [2] to [4], characterized in that the cocoa-derived luminacoid is ingested for 2 weeks or more. A composition for promoting the production of a bacterium belonging to the genus Bacillus and a promoter for promoting the production of a bacterium belonging to the genus Ficakaribacterium.
[5-1] The cocoa-derived luminacoid is ingested for 1 week or more at 0.5 to 11.9 g per day, characterized in that the above [1], [1-1], [1-2] and [2] The composition for promoting the production of the genus Ficaribacterium according to any one of [1] to [5] and the agent for promoting the production of the genus Ficaribacterium.
[6] The crispy according to any one of the above [1], [1-1], [1-2], [2] to [5] and [5-1], which is in the form of a fat and oil processing composition A composition for promoting the production of a bacterium belonging to the genus Bacillus and a promoter for promoting the production of a bacterium belonging to the genus Ficakaribacterium.
[7] The above-mentioned [1], [1-1], [1-2], for use in the treatment, prevention or amelioration of a disease or condition which can be treated, prevented or ameliorated by the production of a ficalibacterium genus bacteria. The composition in any one of [2]-[5], [5-1], and [6].
[8] A method for promoting the production of the genus Ficalibacterium, which comprises ingesting an effective amount of cacao-derived luminacoid.
[9] A Ficaribacterium genus bacteria according to the above-mentioned [8], which comprises ingesting a cocoa-derived luminacoid at a daily dose effective for promoting the production of the Ficaribacillus bacteria for one week or more How to promote the production of
[10] The Ficalibacterium according to the above [9], wherein the daily intake effective for promoting the production of the Ficalibacterium is 0.5 to 11.9 g (cocoa-derived luminacoid) How to promote the production of
[11] The method for promoting the production of Ficalibacterium according to any of [8] to [10], wherein the cocoa-derived luminacoid is ingested in the form of a fat / oil processing composition.
[12] A method for treating, preventing or ameliorating a disease or condition that can be treated, prevented or ameliorated by the production of a species of Ficalibacterium, comprising ingesting or administering an effective amount of cocoa-derived luminacoid.
[13] For the production of an agent for promoting the production of Ficalibacterium, for producing a therapeutic, preventive or ameliorating agent for a disease or condition that can be treated, prevented or ameliorated by the production of Ficalibacterium. Cacao, as a production promoter of Ficalibacterium spp., Or as a therapeutic, preventive or remedy for diseases or conditions that can be treated, prevented or ameliorated by the production of Ficalibacterium spp. Use of Luminakoid derived.
[14] A cocoa-derived luminacoid for promoting the production of a ficalibacterium, or treating or preventing or ameliorating a disease or condition that can be treated, prevented or ameliorated by the production of a ficalibacterium.
本発明の組成物および用剤は、長年食品の原料として用いられてきたカカオに含まれる成分を利用するものであることから、本発明の組成物および用剤は、長期間にわたって服用しても副作用が少なく、安全性が高い点において有利である。 Since the composition and the preparation of the present invention utilize ingredients contained in cocoa which has been used as a raw material of food for many years, the composition and the preparation of the present invention can be taken over a long period of time It is advantageous in that the side effects are small and the safety is high.
本発明において「カカオ由来ルミナコイド」は、カカオに含まれるルミナコイドを意味し、典型的には、カカオ豆由来ルミナコイドである。従って、本発明においては、カカオの植物体またはその加工品から抽出(粗抽出を含む)あるいは精製(粗精製を含む)したカカオのルミナコイドを本発明の有効成分として使用することができる。 In the present invention, "cocoa-derived luminacoid" means a luminacoid contained in cacao, and typically, it is a cocoa bean-derived luminacoid. Therefore, in the present invention, cocoa luminacoids extracted (including crude extraction) or purified (including crude purification) from cocoa plants or their processed products can be used as the active ingredient of the present invention.
ここで、「ルミナコイド」とは、小腸で消化吸収されず大腸に到達する全ての食品成分の総称で、非デンプン性のルミナコイドとデンプン性のルミナコイドに分類される。非デンプン性のルミナコイドは、難消化性タンパク質(レジスタントプロテイン、RP)、食物繊維、オリゴ糖、糖アルコール、その他に分類される。食物繊維はさらに、リグニンと多糖類に分類される。多糖類には、植物性多糖類、動物性多糖類、微生物性多糖類、化学修飾性多糖類がある。デンプン性ルミナコイドは、難消化性デンプン、難消化性デキストリンがある。カカオ由来ルミナコイドとしては、難消化性たんぱく質および食物繊維が挙げられる。 Here, "luminacoid" is a generic name for all food components that reach the large intestine without being digested and absorbed in the small intestine, and is classified into non-starch luminacoid and starch-based luminacoid. Non-starch luminacoids are classified as resistant proteins (Resistant Protein, RP), dietary fiber, oligosaccharides, sugar alcohols and others. Dietary fiber is further classified into lignin and polysaccharides. The polysaccharides include vegetable polysaccharides, animal polysaccharides, microbial polysaccharides and chemically modifying polysaccharides. Starch luminacoids include resistant starch and resistant dextrin. Cocoa-derived luminacoids include resistant proteins and dietary fibers.
本発明において、カカオ由来ルミナコイドの原料となりうるカカオの植物体またはその加工品としては、カカオ樹皮、カカオ葉、カカオ豆、カカオシェル、カカオマス、脱脂カカオマス、ココアパウダー等、植物体の各種部位またはカカオ豆加工品を挙げることができる。カカオマスはカカオ豆を磨砕したものであり、脱脂カカオマスはカカオマスから油脂を除去することにより得ることができる。油脂の除去方法は特に制限されず、圧搾などの公知の方法に従って行うことができる。脱脂カカオマスを粉砕すればココアパウダーとなる。また、カカオの植物体またはその加工品を原料として抽出を行う場合は、抽出効率の観点から、磨砕、粉砕等の微粒化処理が施されているカカオマスやココアパウダーを用いるのが好ましい。なお、カカオの植物体には、意図してないしは意図せずにカカオの植物体以外の物も含めることができる。また、カカオの植物体またはその加工品を原料として抽出を行う際にも、意図してないしは意図せずにカカオの植物体以外の物も含めることができる。さらに、カカオマスやココアパウダーにも、意図してないしは意図せずにカカオの植物体以外の物も含めることができる。 In the present invention, cacao plants which can be a raw material of cacao-derived luminacoids or their processed products include cacao bark, cacao leaves, cacao beans, cacao shells, cacao mass, defatted cacao mass, cocoa powder etc., various parts of plants or cacao A processed bean product can be mentioned. Cocoa mass is obtained by grinding cocoa beans, and defatted cocoa mass can be obtained by removing fats and oils from cocoa mass. The removal method in particular of fats and oils is not restricted, and it can carry out according to publicly known methods, such as expression. If defatted cocoa mass is crushed, it becomes cocoa powder. When extraction is carried out using a cacao plant or a processed product thereof as a raw material, it is preferable to use cacao mass or cocoa powder which has been subjected to an atomization treatment such as grinding or pulverization from the viewpoint of extraction efficiency. In addition, the plant body of cacao can also contain things other than the plant body of cacao without intention or intention. In addition, when extraction is carried out using a cacao plant or its processed product as a raw material, it is possible to unintentionally or unintentionally include substances other than cacao plants. In addition, cacao mass and cocoa powder may also contain unintentional and unintended objects other than cacao plants.
カカオの植物体またはその加工品を原料とする抽出方法は公知であり、例えば、特開2009−183229号公報や特開2011−93807号公報の記載に従ってカカオ由来ルミナコイド含有組成物を調製することができる。抽出溶媒は、特に限定されるものではないが、水またはアルカリ性の水溶液を用いることが好ましい。また、カカオの植物体またはその加工品を原料とする精製方法は、合成吸着剤、イオン交換樹脂、限外ろ過、活性白土処理等の公知の方法を使用することができ、特に限定されるものではない。 The extraction method which uses the plant body of cocoa or its processed product as a raw material is known, For example, according to the description of Unexamined-Japanese-Patent No. 2009-183229 or 2011-93807, preparing a cacao-derived luminacoid-containing composition it can. The extraction solvent is not particularly limited, but it is preferable to use water or an alkaline aqueous solution. In addition, purification methods using cocoa plants or their processed products as raw materials may be known methods such as synthetic adsorbent, ion exchange resin, ultrafiltration, activated clay treatment, etc., and are particularly limited. is not.
本発明においてカカオ由来ルミナコイド含量は、難消化性たんぱく質含量と食物繊維含量により求められる。難消化性たんぱく質含量は、実施例に記載の難消化性たんぱく質の抽出方法により抽出した後、ケルダール法(たんぱく質定量の公定法)により定量できる。また、実施例に記載の人工消化試験を行うことにより、タンパク質が難消化性たんぱく質であることが確認できる。また、食物繊維含量は、酵素−重量法(エーオーエーシ―インターナショナルAOAC Internationalによる公定法、AOAC Method 985.29、別名:プロスキー法)により定量できる。 In the present invention, the cocoa-derived luminacoid content is determined by the indigestible protein content and the dietary fiber content. The indigestible protein content can be quantified by the Kjeldahl method (the official method of protein determination) after extraction by the method for extracting indigestible proteins described in the examples. In addition, by performing the artificial digestion test described in the Examples, it can be confirmed that the protein is a nondigestible protein. In addition, the dietary fiber content can be quantified by the enzyme-weight method (the official method by AOAC International AOAC International, AOAC Method 985.29, aka: Proski method).
カカオ由来ルミナコイドはカカオの植物体を原料にして調製することができるため、本発明の組成物および用剤は、カカオ由来ルミナコイド以外のカカオ豆由来の成分を含んでいてもよい。そのような成分としては、ポリフェノール、テオブロミン、カフェイン、アミノ酸類、ペプチド、脂肪酸等が挙げられる。また、本発明の組成物および用剤は、カカオに由来しない成分を含んでいてもよい。 Since the cocoa-derived luminacoids can be prepared from cocoa plants, the composition and preparation of the present invention may contain components derived from cocoa beans other than cocoa-derived luminacoids. Such components include polyphenols, theobromine, caffeine, amino acids, peptides, fatty acids and the like. In addition, the composition and preparation of the present invention may contain ingredients not derived from cocoa.
本発明の組成物および用剤は、カカオ由来ルミナコイド単独で提供することができ、あるいは、カカオ由来ルミナコイドと他の成分とを混合して提供することもできる。本発明の組成物および用剤におけるカカオ由来ルミナコイドの配合量は、その目的、用途、形態、剤型、症状、体重等に応じて任意に定めることができ、本発明はこれに限定されない。例えば、本発明の組成物および用剤におけるカカオ由来ルミナコイドの含量は、固形分中の乾燥質量割合で2%以上とすることができ、好ましくは、2〜90質量%、より好ましくは2〜50質量%、より一層好ましくは5〜35質量%、さらに好ましくは10〜21質量%とすることができる。本発明においては、本発明の用剤をカカオ由来ルミナコイドからなるものとし、本発明の組成物をカカオ由来ルミナコイドと他の成分とを含んでなるものとすることができる。 The composition and preparation of the present invention can be provided solely by cocoa-derived luminacoids, or can be provided by mixing cocoa-derived luminacoids with other components. The blending amount of the cocoa-derived luminacoid in the composition and the preparation of the present invention can be arbitrarily determined according to the purpose, use, form, dosage form, symptoms, body weight and the like, and the present invention is not limited thereto. For example, the content of cocoa-derived luminacoid in the composition and preparation of the present invention can be 2% or more in dry mass ratio in solid content, preferably 2 to 90% by mass, more preferably 2 to 50. It can be made into mass%, more preferably 5 to 35 mass%, further preferably 10 to 21 mass%. In the present invention, the preparation of the present invention may be composed of cocoa-derived luminacoid, and the composition of the present invention may be composed of cocoa-derived luminacoid and other components.
後記実施例に示されるように、カカオ由来ルミナコイドは腸内菌叢改善促進作用、具体的には、フィーカリバクテリウム属菌の産生促進作用を有する。従って、カカオ由来ルミナコイド(特に、カカオ豆由来ルミナコイド)は腸内菌叢改善促進剤およびフィーカリバクテリウム属菌の産生促進剤として使用することができるとともに、腸内菌叢改善促進方法およびフィーカリバクテリウム属菌の産生促進方法に使用することができる。また、カカオ由来ルミナコイド(特に、カカオ豆由来ルミナコイド)は腸内菌叢改善促進のための組成物およびフィーカリバクテリウム属菌の産生促進のための組成物としても使用することができる。 As shown in the Examples below, the cacao-derived luminacoid has an action to promote intestinal flora improvement, specifically, an action to promote the production of Ficalibacterium bacteria. Therefore, the cacao-derived luminacoid (in particular, cacao bean-derived luminacoid) can be used as an intestinal flora improvement promoter and a Ficaribacterium bacteria production promoter, and a method for promoting intestinal flora improvement and a calico It can be used in a method for promoting the production of a bacterium belonging to the genus Bacillus. In addition, cocoa-derived luminacoids (in particular, cocoa bean-derived luminacoids) can also be used as a composition for promoting the improvement of intestinal flora and a composition for promoting the production of Ficalibacterium bacteria.
ここで、「フィーカリバクテリウム属菌の産生促進」とは、フィーカリバクテリウム属菌の発現や増殖を促進することを意味し、フィーカリバクテリウム属菌の産生促進の程度は、腸内細菌の占有率を指標にして評価することができる(実施例参照)。具体的には、カカオ由来ルミナコイド(特に、カカオ豆由来ルミナコイド)の摂取または投与後の腸内細菌に占めるフィーカリバクテリウム属菌の割合が、摂取または投与前の腸内菌叢中のフィーカリバクテリウム属菌を上回る場合に、好ましくは約1.1倍以上である場合に、より好ましくは約1.2倍以上である場合に、より一層好ましくは約1.3倍以上、さらに好ましくは1.4倍以上、特に好ましくは1.5倍以上、さらに特に好ましくは1.6倍以上、さらに特に好ましくは1.8倍以上、最も好ましくは2倍以上である場合に、フィーカリバクテリウム属菌の産生を促進したと判定することができる。 Here, "promoting the production of Ficalibacterium bacteria" means promoting the expression and growth of Ficalibacillus bacteria, and the degree of promotion of the production of Ficalibacillus bacteria is The occupancy rate of bacteria can be evaluated as an index (see Examples). Specifically, the ratio of Ficalibacterium to enterobacteria after ingestion or administration of cacao-derived luminacoid (in particular, cacao bean-derived luminacoid) is determined by the ratio of Ficusibacteria belonging to the intestinal flora before ingestion or administration. When it is greater than bacteria, it is preferably about 1.1 times or more, more preferably about 1.2 times or more, still more preferably about 1.3 times or more, still more preferably When it is 1.4 times or more, particularly preferably 1.5 times or more, still more preferably 1.6 times or more, still more preferably 1.8 times or more, most preferably 2 times or more. It can be determined that the production of genus bacteria has been promoted.
本発明のフィーカリバクテリウム属菌の産生促進方法は、有効量のカカオ由来ルミナコイドをヒトまたは非ヒト動物に摂取させるか、あるいは投与することにより実施することができる。 The method of the present invention for promoting the production of Ficalibacterium can be carried out by feeding or administering an effective amount of cocoa-derived luminacoid to human or non-human animals.
なお、本発明におけるカカオ由来ルミナコイドの使用はヒトおよび非ヒト動物並びにこれらに由来する試料における使用であってもよく、治療的使用と非治療的使用のいずれもが意図される。ここで、「非治療的」とはヒトを手術、治療または診断する行為(すなわち、ヒトに対する医療行為)を含まないことを意味し、具体的には、医師または医師の指示を受けた者がヒトに対して手術、治療または診断を行う方法を含まないことを意味する。 The use of cocoa-derived luminacoids in the present invention may be in human and non-human animals and samples derived therefrom, and both therapeutic and non-therapeutic uses are contemplated. Here, "non-therapeutic" means that the act of surgery, treatment or diagnosis of a human being (ie, medical act on a human) is not included, and specifically, a doctor or a person who has been instructed by a doctor Means not include methods of performing surgery, treatment or diagnosis on humans.
本発明ではフィーカリバクテリウム属菌の産生促進がその治療、予防または改善に有効である疾患および症状の治療、予防または改善にカカオ由来ルミナコイドを使用することができる。 In the present invention, the cacao-derived luminacoid can be used for the treatment, prevention or amelioration of diseases and conditions in which promotion of the production of Ficalibacterium is effective for the treatment, prevention or amelioration.
フィーカリバクテリウム属菌の産生促進により治療、予防または改善しうる疾患および症状としては、炎症性疾患(例えば、潰瘍性大腸炎やクローン病などの炎症性腸疾患)、アレルギー性疾患(例えば、食品アレルギー、花粉症、喘息、アレルギー性鼻炎、薬物アレルギー、アトピー性皮膚炎、ダニアレルギー)および腸内菌共生バランス失調(Dysbiosis)に起因すると考えられる疾病(例えば、クローン病、大腸がん、炎症性腸疾患、過敏性腸症候群、小腸細菌異常増殖症(SIBO)、偽膜性大腸炎(クロストリジウム・ディフィシル腸炎)、抗菌薬起因性下痢、アルコール性脂肪性肝炎(ASH)や非アルコール性脂肪性肝炎(NASH)などの肝臓疾患、肥満、2型糖尿病、アレルギー疾患、自閉症などの精神疾患、多発性硬化症)が挙げられる。後記実施例に示される通り、カカオ豆由来ルミナコイドはフィーカリバクテリウム属菌の産生を促進することができ、これまでにフィーカリバクテリウム属菌の増加が、抗炎症・抗アレルギー作用に繋がることや、フィーカリバクテリウム属菌の減少が腸内菌共生バランス失調(Dysbiosis)に起因すると考えられる疾病(クローン病など)と関連することが示されている(非特許文献2および3並びにProc. Natl. Acad. Sci. USA. 2013, 105(43): 16731-16736)。従って、カカオ由来ルミナコイドは、炎症性疾患、アレルギー性疾患および腸内菌共生バランス失調(Dysbiosis)に起因すると考えられる疾病(クローン病など)の治療用、予防用または改善用組成物あるいは治療剤、予防剤または改善剤として使用できるとともに、炎症性疾患、アレルギー性疾患および腸内菌共生バランス失調(Dysbiosis)に起因すると考えられる疾病(クローン病など)の治療方法、予防方法および改善方法に使用することができる。
Diseases and conditions that can be treated, prevented or ameliorated by promotion of production of the genus Ficalibacterium include inflammatory diseases (eg, inflammatory bowel diseases such as ulcerative colitis and Crohn's disease), allergic diseases (eg, Food allergy, hay fever, asthma, allergic rhinitis, drug allergy, atopic dermatitis, mite allergy) and diseases thought to be caused by intestinal bacterial symbiosis balance (Dysbiosis) (eg, Crohn's disease, colon cancer, inflammation) Bowel Disease, Irritable Bowel Syndrome, Intestinal Bacterial Hyperplasia (SIBO), Pseudomembranous Colitis (Clostridium difficile enteritis), Antimicrobial agent-induced diarrhea, alcoholic steatohepatitis (ASH) or nonalcoholic steatohepatitis Liver diseases such as (NASH), obesity,
本発明の組成物および用剤、本発明の治療剤、予防剤および改善剤並びに本発明の治療用、予防用および改善用組成物は、医薬品、医薬部外品、飲食品、飼料などの形態で提供することができ、下記の記載に従って実施することができる。また本発明のフィーカリバクテリウム属菌の産生促進方法並びに本発明の治療方法、予防方法および改善方法は下記の記載に従って実施することができる。本発明の治療用、予防用および改善用組成物が医薬品を目的としている場合には、これらは治療用医薬組成物、予防用医薬組成物および改善用医薬組成物とすることができる。 The composition and the agent of the present invention, the therapeutic agent, the preventive agent and the remedy of the present invention, and the therapeutic, preventive and ameliorating composition of the present invention are in the form of pharmaceuticals, quasi drugs, food and drink, feed and the like. Can be provided according to the description below. In addition, the method of the present invention for promoting the production of the genus Ficalibacterium and the method of the present invention for treating, preventing and improving can be carried out according to the following description. When the therapeutic, prophylactic and ameliorating compositions of the present invention are intended for pharmaceutical use, they can be a therapeutic pharmaceutical composition, a prophylactic pharmaceutical composition and a pharmaceutical composition for amelioration.
本発明の有効成分であるカカオ由来ルミナコイドをヒトおよび非ヒト動物に投与ないし摂取させる場合、カカオ豆に由来するルミナコイドの含有率を高めた組成物を使用することができ、このような組成物は、カカオ豆に由来する脂肪分をほとんど含まず、苦味および収斂味をほとんど有しないため、種々の飲食品、医薬品、医薬部外品、飼料、化成品等の素材として有用である。 In the case of administering or ingesting a cocoa-derived luminacoid, which is an active ingredient of the present invention, to humans and non-human animals, a composition having an increased content of luminacoid derived from cocoa beans can be used, and such a composition Since it contains almost no fat derived from cacao beans and has almost no bitter and astringent taste, it is useful as a material for various food and drink products, medicines, quasi-drugs, feeds, chemical products and the like.
本発明の有効成分であるカカオ由来ルミナコイドはヒトおよび非ヒト動物に経口投与することができる。経口剤としては、顆粒剤、散剤、錠剤(糖衣錠を含む)、丸剤、カプセル剤、シロップ剤、乳剤、懸濁剤が挙げられる。これらの製剤は、当分野で通常行われている手法により、薬学上許容される担体を用いて製剤化することができる。薬学上許容される担体としては、賦形剤、結合剤、希釈剤、添加剤、香料、緩衝剤、増粘剤、着色剤、安定剤、乳化剤、分散剤、懸濁化剤、防腐剤等が挙げられる。 The cocoa-derived luminacoid which is an active ingredient of the present invention can be orally administered to human and non-human animals. Oral agents include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, suspensions. These preparations can be formulated using a pharmaceutically acceptable carrier according to a method commonly used in the art. Pharmaceutically acceptable carriers include excipients, binders, diluents, additives, flavors, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, etc. Can be mentioned.
本発明の有効成分であるカカオ由来ルミナコイドはヒトおよび非ヒト動物に経管投与、経鼻管投与、点滴、座薬等の経口投与以外の体内への投与も本発明の組成物および用剤の形状に応じて可能である。例えば、カカオ由来ルミナコイドを含む粘性を有する液状の組成物、または、カカオ由来ルミナコイドを含む半固形状の組成物とすることで、咀嚼や嚥下の機能が低下し、経口摂取ないしは経口投与ができないヒトおよび非ヒト動物に対しても投与することができる。本発明の組成物および用剤を経口摂取以外で摂取させるか、あるいは投与することにより、咀嚼や嚥下の機能が加齢などにより低下したとしても、フィーカリバクテリウム属菌の産生促進が期待でき、これらのヒトおよび非ヒト動物の炎症性疾患、アレルギー性疾患、腸内菌共生バランス失調(Dysbiosis)に起因すると考えられる疾病(クローン病など)の治療、予防および改善が期待できる。 The cocoa-derived luminacoid, which is an active ingredient of the present invention, is also administered to human and non-human animals by intravaginal administration, intranasal administration, instillation, suppository, etc. in the body other than oral administration. It is possible according to. For example, by setting a viscous liquid composition containing cocoa-derived luminacoid or a semi-solid composition containing cocoa-derived luminacoid, the function of chewing and swallowing is reduced, and human beings can not take orally or orally. And can also be administered to non-human animals. Even if the function of chewing and swallowing is deteriorated due to aging or the like by taking or administering the composition and the preparation of the present invention other than oral intake, it can be expected to promote the production of the genus Ficacalibacterium. The treatment, prevention and amelioration of diseases (eg, Crohn's disease) thought to be caused by inflammatory diseases, allergic diseases, and intestinal bacterial symbiotic imbalance (Dysbiosis) in these human and non-human animals can be expected.
本発明の有効成分であるカカオ由来ルミナコイドはヒトおよび非ヒト動物に経口摂取させることができる。カカオ由来ルミナコイドを経口摂取させる場合にカカオ由来ルミナコイドは単離、精製または粗精製された形態のものであっても、カカオ由来ルミナコイドを含む食品あるいは食品の原料の形態であってもよい。また、カカオ由来ルミナコイドはヒトおよび非ヒト動物に経口摂取させるにあたり、常温の状態、温かい状態、冷たい状態等から任意に選択することができる。 Cocoa-derived luminacoid, which is an active ingredient of the present invention, can be orally taken by humans and non-human animals. When the cocoa-derived luminacoid is orally ingested, the cocoa-derived luminacoid may be in an isolated, purified or crudely purified form, or in the form of a food or food material containing the cocoa-derived luminacoid. In addition, the cocoa-derived luminacoid can be arbitrarily selected from normal temperature, warm state, cold state and the like when orally ingested by humans and non-human animals.
本発明の有効成分であるカカオ由来ルミナコイドを食品として提供する場合には、カカオ由来ルミナコイドをそのまま食品に含有させることができ、該食品はカカオ由来ルミナコイドを有効量含有した食品である。ここで、カカオ由来ルミナコイドを「有効量含有した」とは、個々の食品において通常喫食される量を摂取した場合に後述するような範囲でカカオ由来ルミナコイドが摂取されるような含有量をいう。また「食品」とは、健康食品、機能性食品、保健機能食品(例えば、特定保健用食品、栄養機能食品、機能性表示食品)、特別用途食品(例えば、幼児用食品、妊産婦用食品、病者用食品)を含む意味で用いられる。「食品」の形態は特に限定されるものではなく、例えば、飲料の形態であっても、半液体やゲル状の形態であっても、固形状の形態であってもよい。 When the cocoa-derived luminacoid which is the active ingredient of the present invention is provided as a food, the cacao-derived luminacoid can be contained as it is in a food, and the food is a food containing an effective amount of cacao-derived luminacoid. Here, the phrase "containing an effective amount of cacao-derived luminacoid" refers to a content such that cacao-derived luminacoid is ingested within the range described later when the amount that is usually consumed in individual foods is ingested. Also, "food" refers to health food, functional food, health food (for example, food for specified health use, nutrition food for functional use, food for functional indication), special purpose food (for example, food for infants, food for pregnant women, disease) It is used in the meaning including the food for the elderly. The form of the “food” is not particularly limited, and may be, for example, a form of a beverage, a semi-liquid or gel form, or a solid form.
カカオ由来ルミナコイドはフィーカリバクテリウム属菌の産生促進作用を有するため、日常摂取する食品や、サプリメントとして摂取する食品に含有させて提供することができる。本発明で提供される食品としては、その形態や形状に特に制限はないが、好ましくは、カカオ豆を主原料とする食品が挙げられ、より好ましくは、油脂加工組成物であり、より一層好ましくはチョコレートおよびココアなどの油脂加工食品である。 Since the cacao-derived luminacoid has an action to promote the production of Ficalibacterium bacteria, it can be provided by being contained in foods taken daily as well as foods taken as supplements. The food provided by the present invention is not particularly limited in its form or shape, but preferably includes foods that use cocoa beans as a main raw material, more preferably a fat-processing composition, and even more preferably Are fats and oils processed foods such as chocolate and cocoa.
前記の通り、カカオ豆由来ルミナコイドを効率よく摂取させるためには濃縮されたカカオ豆由来ルミナコイド組成物を本発明に使用することができる。従って、カカオ豆を主原料とする食品およびサプリメントは、例えば、カカオ豆由来ルミナコイドを高濃度で含むものであることが好ましく、より好ましくはカカオ豆由来ルミナコイドを高濃度で含む油脂加工組成物であり、より一層好ましくはカカオ豆由来ルミナコイドを高濃度で含む油脂加工食品(具体的には、チョコレートおよびココア)である。 As described above, the concentrated cocoa bean-derived luminacoid composition can be used in the present invention for efficiently ingesting the cocoa bean-derived luminacoid. Therefore, it is preferable that the food and supplement containing cocoa beans as a main ingredient are, for example, those containing a high concentration of lucocoid derived from lucocoa beans, more preferably a fat and oil processing composition containing lumonacoids derived from cocoa beans from high concentrations, More preferable are fat-processed foods (specifically, chocolate and cocoa) containing a high concentration of cocoa bean-derived luminacoid.
ここで、食品およびサプリメント中のカカオ豆由来ルミナコイドの含有量はカカオ豆由来ルミナコイドの摂取が可能である限り特に限定されるものではないが、カカオ豆由来ルミナコイドの効率的な摂取の観点から、油脂加工組成物中の含有量は組成物の固形分当たり、例えば、2〜90質量%とすることができ、好ましくは2〜50質量%、より好ましくは5〜35質量%、より一層好ましくは10〜21質量%である。また、食品およびサプリメント中のカカオ豆由来ルミナコイドの含有量はカカオ豆由来ルミナコイドの摂取が可能である限り特に限定されるものではないが、カカオ豆由来ルミナコイドの効率的な摂取の観点から、油脂加工組成物中の含有量は組成物の固形分25g当たり、例えば、好ましくは0.5〜11.9g、より好ましくは1.4〜8.8g、さらに好ましくは2.6〜5.2gである。 Here, the content of the cocoa bean-derived luminacoid in the food and the supplement is not particularly limited as long as consumption of the cocoa bean-derived luminacoid is possible, but from the viewpoint of efficient intake of the cocoa bean-derived luminacoid The content in the processing composition can be, for example, 2 to 90% by mass, preferably 2 to 50% by mass, more preferably 5 to 35% by mass, and still more preferably 10 based on the solid content of the composition. It is -21 mass%. In addition, the content of cocoa bean-derived luminacoid in foods and supplements is not particularly limited as long as the intake of cacao bean-derived luminacoid is possible, but from the viewpoint of efficient intake of cacao bean-derived luminacoid, oil and fat processing The content in the composition is, for example, preferably 0.5 to 11.9 g, more preferably 1.4 to 8.8 g, still more preferably 2.6 to 5.2 g, per 25 g of solid content of the composition. .
ここで、食品およびサプリメント中のカカオ豆由来食物繊維の含有量はカカオ豆由来難消化性タンパク質の摂取が可能である限り特に限定されるものではないが、カカオ豆由来食物繊維の効率的な摂取の観点から、油脂加工組成物中の含有量は組成物の固形分当たり、例えば、1〜40質量%とすることができ、好ましくは4〜28質量%、より好ましくは6〜20質量%、より一層好ましくは8〜16質量%である。また、食品およびサプリメント中のカカオ豆由来食物繊維の含有量はカカオ豆由来難消化性タンパク質の摂取が可能である限り特に限定されるものではないが、カカオ豆由来食物繊維の効率的な摂取の観点から、油脂加工組成物中の含有量は組成物の固形分25g当たり、例えば、好ましくは0.3〜9.4g、より好ましくは1.0〜7.0g、さらに好ましくは2.0〜4.0gである。 Here, the content of cocoa bean-derived dietary fiber in foods and supplements is not particularly limited as long as consumption of cocoa bean-derived indigestible protein is possible, but efficient intake of cocoa bean-derived dietary fiber From the point of view, the content in the oil-fat processing composition can be, for example, 1 to 40% by mass, preferably 4 to 28% by mass, more preferably 6 to 20% by mass, based on the solid content of the composition. Still more preferably, it is 8 to 16% by mass. Also, the content of cocoa bean-derived dietary fiber in foods and supplements is not particularly limited as long as consumption of cocoa bean-derived indigestible protein is possible, but the efficient intake of cocoa bean-derived dietary fiber From the viewpoint, the content in the oil-fat processing composition is, for example, preferably 0.3 to 9.4 g, more preferably 1.0 to 7.0 g, and still more preferably 2.0 to 25 g of solid content of the composition. It is 4.0g.
ここで、食品およびサプリメント中のカカオ豆由来難消化性タンパク質の含有量はカカオ豆由来難消化性タンパク質の摂取が可能である限り特に限定されるものではないが、カカオ豆由来難消化性タンパク質の効率的な摂取の観点から、油脂加工組成物中の含有量は組成物の固形分当たり、例えば、0.5〜15質量%とすることができ、好ましくは1〜10質量%、より好ましくは1.5〜8質量%、より一層好ましくは2〜5質量%である。また、食品およびサプリメント中のカカオ豆由来難消化性タンパク質の含有量はカカオ豆由来難消化性タンパク質の摂取が可能である限り特に限定されるものではないが、カカオ豆由来難消化性タンパク質の効率的な摂取の観点から、油脂加工組成物中の含有量は組成物の25g固形分当たり、例えば、好ましくは0.2〜2.5g、より好ましくは0.4〜1.8g、さらに好ましくは0.6〜1.2gである。 Here, the content of the cocoa bean-derived indigestible protein in the food and the supplement is not particularly limited as long as consumption of the cocoa bean-derived indigestible protein is possible, but the cocoa bean-derived indigestible protein is not particularly limited. From the viewpoint of efficient intake, the content in the oil and fat processing composition can be, for example, 0.5 to 15% by mass, preferably 1 to 10% by mass, and more preferably, per solid content of the composition. It is 1.5 to 8% by mass, still more preferably 2 to 5% by mass. In addition, the content of cocoa bean-derived indigestible protein in foods and supplements is not particularly limited as long as consumption of cocoa bean-derived indigestible protein is possible, but the efficiency of cocoa bean-derived indigestible protein From the viewpoint of dietary intake, the content in the oil-fat processing composition is, for example, preferably 0.2 to 2.5 g, more preferably 0.4 to 1.8 g, and still more preferably 25 g solid content of the composition. It is 0.6 to 1.2 g.
本発明で提供される食品としては、チョコレートやココアのようにカカオ豆を主原料とする食品はもちろんのこと、カカオ由来ルミナコイドを含有させることができる食品であれば特に限定されない。例えば、パン類、ビスケット類、麺類、クラッカー、栄養補給バー等の澱粉系食品;キャンディー類、ガム類、グミ、スナック等の各種菓子類;牛乳、加工乳、アイスクリーム類、発酵乳(ヨーグルト等)、乳飲料、チーズ類、バター類、クリーム類等の乳および乳製品;プリン、ゼリー、ババロア、ムース等のデザート類;非アルコール飲料、アルコール飲料等の飲料類;ハム、ソーセージ等の畜肉加工品;カマボコ、竹輪、魚肉ソーセージ等の魚肉加工品;ジャム、ピューレ等の果実加工品;ルウ、ソース等の調味料類等が挙げられる。カカオ豆由来ルミナコイドは各食品の特性、目的に応じ、適当な製造工程の段階で適宜配合することができる。 The food provided by the present invention is not particularly limited as long as it is a food that can contain cocoa-derived luminacoid as well as a food that mainly contains cocoa beans, such as chocolate and cocoa. For example, starch-based foods such as breads, biscuits, noodles, crackers, feeding bars; various confectioneries such as candies, gums, gummi, snacks; milk, processed milk, ice cream, fermented milk (yoghurt etc. ), Milk and dairy products such as milk drinks, cheeses, butters and creams; Desserts such as puddings, jellies, bavarois and mousses; Beverages such as non-alcoholic beverages and alcoholic beverages; Meat and meat processing such as hams and sausages Products: processed fish meat products such as kamaboko, bamboo rings, fish meat sausages; processed fruit products such as jams and purees; seasonings such as roux and sauces. The cocoa bean-derived luminacoid can be appropriately blended at the stage of an appropriate production process depending on the properties of the respective food and purpose.
本発明の医薬品および食品は、食品として古くから重用されていたカカオに含まれる成分を利用することから、それを必要とする哺乳動物(例えば、ヒト、マウス、ラット、ウサギ、イヌ、ネコ、ウシ、ウマ、ブタ、サル等)に対し安全に用いることができる。カカオ由来ルミナコイド(特に、カカオ豆由来ルミナコイド)の投与量または摂取量は、受容者の性別、年齢および体重、症状、投与時間、剤形、投与経路並びに組み合わせる薬剤等に依存して決定できる。例えば、カカオ由来ルミナコイド(特に、カカオ豆由来ルミナコイド)を医薬として経口投与する場合、成人1日当たり、0.5〜11.9g、好ましくは1.4〜8.8g、より好ましくは2.6〜5.2gの範囲となるように、投与することができる。また、カカオ由来ルミナコイド(特に、カカオ豆由来ルミナコイド)を食品として摂取させる場合には、成人1日当たり、0.5〜11.9g、好ましくは1.4〜8.8g、より好ましくは2.6〜5.2gの範囲となるように、投与することができる。 The medicines and foods of the present invention utilize ingredients contained in cocoa which has been heavily used as foods, and therefore mammals (eg, humans, mice, rats, rabbits, dogs, cats, cattle, etc.) which need them. , Horses, pigs, monkeys, etc.). The dose or intake of cocoa-derived luminacoids (in particular, cocoa bean-derived luminacoids) can be determined depending on the sex, age and body weight of the recipient, symptoms, time of administration, dosage form, route of administration, drugs to be combined, etc. For example, when orally administering cacao-derived luminacoid (in particular, cacao bean-derived luminacoid) as a pharmaceutical, 0.5 to 11.9 g, preferably 1.4 to 8.8 g, more preferably 2.6 to 1 day per adult It can be administered in the range of 5.2 g. When a cocoa-derived luminacoid (in particular, cocoa bean-derived luminacoid) is taken as a food, it is preferably 0.5 to 11.9 g, preferably 1.4 to 8.8 g, more preferably 2.6 per adult per day. It can be administered in a range of ̃5.2 g.
本発明の組成物および用剤は、他の経口摂取できる組成物と併用することに制限はない。例えば、抗炎症・抗アレルギー作用、腸内菌共生バランス失調(Dysbiosis)に起因すると考えられる疾病(クローン病など)の予防、治療または改善効果が期待できる素材や組成物と併用することで、フィーカリバクテリウム属菌の産生促進効果をさらに高めることができる。 The compositions and preparations of the present invention are not limited in combination with other orally ingestible compositions. For example, it can be used in combination with a material or composition that can be expected to have an effect of preventing, treating or ameliorating a disease (such as Crohn's disease) that is considered to be caused by anti-inflammatory and anti-allergic actions and intestinal bacterial symbiotic balance imbalance (Dysbiosis) It is possible to further enhance the production promoting effect of Kalibacterium bacteria.
本発明の組成物および用剤は、フィーカリバクテリウム属菌の産生促進に有効な1日分の摂取量のカカオ由来ルミナコイドを含んでなる組成物で提供することができる。この場合、本発明の組成物および用剤は、1日分の有効摂取量を摂取できるように包装されていてもよく、1日分の有効摂取量が摂取できる限り、包装形態は一包装であっても、複数包装であってもよい。包装形態で提供する場合、1日分の有効摂取量が摂取できるように摂取量に関する記載が包装になされているか、または該記載がなされた文書を一緒に提供することが望ましい。また、1日分の有効摂取量を複数包装で提供する場合には、摂取の便宜上、1日分の有効摂取量の複数包装をセットで提供することもできる。 The composition and use according to the present invention can be provided as a composition comprising a daily intake of cocoa-derived luminacoid effective to promote the production of the genus Ficaribacterium. In this case, the composition and the preparation of the present invention may be packaged so as to be able to take an effective intake for one day, and the package form is one package as long as an effective intake for one day can be taken Even if there are, it may be a plurality of packages. When provided in the form of a package, it is desirable that the description of the intake be provided on the package so that an effective intake for one day can be taken, or a document with the description is provided together. Moreover, when providing the effective intake amount for 1 day with multiple packages, the package of the effective intake amount for 1 day can also be provided by a set for convenience of intake.
本発明の組成物および用剤を提供するための包装形態は一定量を規定する形態であれば特に限定されず、例えば、包装紙、袋、ソフトバック、紙容器、缶、ボトル、カプセルなどの収容可能な容器などが挙げられる。 The package form for providing the composition and the preparation of the present invention is not particularly limited as long as it is a form that defines a fixed amount, and, for example, wrapping paper, bag, soft bag, paper container, can, bottle, capsule, etc. The container etc. which can be accommodated are mentioned.
本発明の組成物および用剤は、その効果をよりよく発揮させるために、1週間以上継続的に投与または摂取させることが好ましく、投与および摂取期間はより好ましくは1〜2週間、特に好ましくは1〜4週間である。ここで、「継続的に」とは毎日投与または摂取を続けることを意味する。本発明の組成物および用剤を包装形態で提供する場合には、継続的摂取のために一定期間(例えば、1週間)の有効摂取量をセットで提供してもよい。 The composition and preparation of the present invention are preferably administered or ingested continuously for 1 week or more, and the administration and intake period is more preferably 1 to 2 weeks, particularly preferably, in order to exert their effects better. 1 to 4 weeks. Here, "continuously" means continuing administration or intake daily. When the composition and the preparation of the present invention are provided in the form of a package, an effective intake for a fixed period (for example, one week) may be provided as a set for continuous intake.
本発明の別の面によれば、有効量のカカオ由来ルミナコイドをヒトまたは非ヒト動物に摂取させるか、或いは投与することを含んでなる、腸内菌叢改善促進方法およびフィーカリバクテリウム属菌の産生促進方法が提供される。本発明の促進方法は、本発明の組成物および用剤に関する記載に従って実施することができる。 According to another aspect of the present invention, there is provided a method of promoting intestinal flora improvement and a method of promoting Ficusalobacterium, which comprises ingesting or administering an effective amount of cocoa-derived luminacoid to human or non-human animals. Methods of promoting the production of The promotion method of the present invention can be carried out according to the description of the composition and preparation of the present invention.
本発明のさらに別の面によれば、有効量のカカオ由来ルミナコイドをヒトまたは非ヒト動物に摂取させるか、或いは投与することを含んでなる、フィーカリバクテリウム属菌の産生促進により治療、予防または改善しうる疾患または症状の治療、予防または改善方法が提供される。本発明の治療、予防または改善方法は、本発明の組成物および用剤に関する記載に従って実施することができる。 According to still another aspect of the present invention, treatment or prevention is achieved by promoting the production of a species of Ficalibacterium bacteria, which comprises ingesting or administering an effective amount of cocoa-derived luminacoid to human or non-human animals. There is provided a method for treating, preventing or ameliorating a disease or condition that can be ameliorated or improved. The treatment, prevention or amelioration method of the present invention can be practiced according to the description of the composition and agent of the present invention.
本発明のさらにまた別の面によれば、腸内菌叢改善促進剤またはフィーカリバクテリウム属菌の産生促進剤の製造のための、カカオ由来ルミナコイドの使用と、腸内菌叢改善促進剤またはフィーカリバクテリウム属菌の産生促進剤としての、カカオ由来ルミナコイドの使用が提供される。本発明によればまた、フィーカリバクテリウム属菌の産生促進により治療、予防または改善しうる疾患または症状の治療剤、予防剤または改善剤の製造のための、カカオ由来ルミナコイドの使用と、フィーカリバクテリウム属菌の産生促進により治療、予防または改善しうる疾患または症状の治療剤、予防剤または改善剤としての、カカオ由来ルミナコイドの使用が提供される。本発明の使用は、本発明の組成物および用剤に関する記載に従って実施することができる。 According to still another aspect of the present invention, there is provided a use of a cocoa-derived luminacoid for the preparation of an intestinal flora improvement promoter or a Ficaribacterium production enhancer, and an intestinal flora improvement promoter. Alternatively, there is provided the use of a cocoa-derived luminacoid as a production promoter of Ficalibacterium. According to the present invention, there is also provided the use of a cocoa-derived luminacoid for the manufacture of an agent for treating, preventing or ameliorating a disease or condition which can be treated, prevented or ameliorated by promoting the production of the genus Ficalibacterium. The use of a cocoa-derived luminacoid as a therapeutic, prophylactic or ameliorating agent for a disease or condition that can be treated, prevented or ameliorated by promoting the production of a Kalibacterium bacteria is provided. The use of the present invention can be carried out according to the description of the composition and preparation of the present invention.
本発明のさらにまた別の面によれば、腸内菌叢改善促進に用いるための、あるいは、フィーカリバクテリウム属菌の産生促進に用いるための、カカオ由来ルミナコイドが提供される。本発明によればまた、フィーカリバクテリウム属菌の産生促進により治療、予防または改善しうる疾患または症状の治療、予防または改善に用いるための、カカオ由来ルミナコイドが提供される。上記のカカオ由来ルミナコイドは、本発明の組成物および用剤に関する記載に従って実施することができる。 According to still another aspect of the present invention, there is provided a cacao-derived luminacoid for use in promoting intestinal flora improvement or for use in promoting the production of Ficaribacterium. According to the present invention, there is also provided a cocoa-derived luminacoid for use in the treatment, prevention or amelioration of a disease or condition which can be treated, prevented or ameliorated by promoting the production of a species of Ficalibacterium. The above-mentioned cocoa-derived luminacoids can be practiced according to the description of the composition and preparation of the present invention.
以下の例に基づいて本発明をより具体的に説明するが、本発明はこれらの例に限定されるものではない。 The present invention will be more specifically described based on the following examples, but the present invention is not limited to these examples.
試験例1:カカオ豆由来ルミナコイドによるフィーカリバクテリウム属菌の産生促進効果の検討(1)
カカオ豆由来ルミナコイドがフィーカリバクテリウム属菌の産生に与える影響を検証するために以下の試験を行った。 Test Example 1: Examination of the production promoting effect of Ficaribacterium bacteria by cacao bean-derived luminacoid (1)
The following tests were conducted to verify the influence of the cocoa bean-derived luminacoid on the production of the genus Ficaribacterium.
20歳以上50歳未満の健康な日本人女性で、スクリーニングにより選抜した40名を被験者とし、評価者盲検並行群間比較試験を行った。途中で試験を中断した9名を除いて、試験食品群16名、対照食品群15名の結果が得られた。試験期間中は、食事制限およびその他の制限(食事制限およびその他の制限の詳細は、下記に示す。)を行った。 The subjects were 40 healthy Japanese women aged 20 to 50 years old who were screened and screened, and an evaluator blinded parallel group comparison test was conducted. The results were obtained for 16 in the test food group and 15 in the control food group, except for 9 people who discontinued the test on the way. During the study, food restrictions and other restrictions (details of food restrictions and other restrictions are given below) were performed.
スクリーニングは、摂取開始7日前(−7日目、−1W)に、生活習慣アンケート(年齢、既往歴、合併症、食物アレルギーの有無、医薬品や健康食品の摂取状況、飲酒等の確認)、自覚アンケート(整腸に関する自覚症状の調査)、理学的検査(身長、体重、血圧、脈拍数、BMI)を実施し、排便の状態(排便回数、便性、便量)、年齢、食習慣(カカオ製品、納豆、乳製品等の日常的な摂取状況)による除外基準を満たした(除外基準の詳細は、下記に示す。)、排便回数が週平均4回以下の40名を選抜した。 Screening 7 days before intake start (day -7, -1W), lifestyle questionnaire (age, medical history, complications, presence or absence of food allergy, intake status of medicines and health food, confirmation of drinking etc.), awareness Questionnaire (investigation of symptoms related to intestinal adjustment), physical examination (height, weight, blood pressure, pulse rate, BMI), defecation status (number of stools, feces, stool volume), age, eating habits (cacao) Products, natto, dairy products, etc.) We have met the exclusion criteria for daily use (the details of the exclusion criteria are shown below) and selected 40 people with an average stool frequency of 4 times or less weekly.
スクリーニングにおける除外基準
以下の者をスクリーニング対象から除外した。
・現在、何らかの慢性疾患を有し、薬物治療を受けている者
・チョコレート、牛乳、大豆にアレルギーを有する者
・乳糖不耐症を有する者
・スクリーニング前3か月間に、カカオ製品を週4回以上摂取している者
・スクリーニング前3か月間に、納豆を週4回以上摂取している者
・スクリーニング前3か月間に、ヨーグルト、乳酸菌飲料、整腸剤等の乳酸菌含有食品を週4回以上摂取している者
・本試験結果に影響する可能性がある医薬品、医薬部外品、サプリメント、健康食品、特定保健用食品(トクホ)を日常において服用・摂取している者、または試験中に服用・摂取する予定のある者
・スクリーニング前1か月間に、他の臨床試験およびモニター試験に参加した者、あるいは本臨床試験同意後に他の臨床試験に参加する予定のある者
・妊娠している者、試験期間中に妊娠の予定、希望がある者
・授乳中の者
・アルコール多飲用者(純アルコール換算で、1日平均60g以上を超える飲酒者)
・その他、被験者として不適当と判断した者 Those who were below the exclusion criteria for screening were excluded from screening.
-Currently having some chronic disease and receiving drug treatment-Person who is allergic to chocolate, milk and soy-Person who has lactose intolerance-
・ Others who are judged inappropriate as subjects
試験期間中の食事制限およびその他の制限
被験者には、試験期間中は通常通りの生活を送らせるとともに、次の制限事項を遵守するよう指導した。
食事、飲み物および嗜好品に関する事項
・食事は、これまでの食生活(食事量、食事内容)を大きく変えず、日常範囲を大きく逸脱する過度な節食や過食は控える。但し、スクリーニングから摂取2週後の採便が終了するまで、納豆の摂取を禁止する。
・飲料の摂取は、緑茶やコーヒー等、摂取量や回数は制限しないが、これまでの摂取の程度(量、種類等)を大きく変えることは控える。
・間食は、原則として自由とするが、通常摂取している量を超えないようにする。但し、スクリーニングから摂取2週後の採便が終了するまで、試験食品以外のカカオを含む飲食品の摂取を禁止する。
・アルコールの摂取は、原則として制限しないが、これまでのアルコール摂取の程度(量、種類等)を大きく変えることは控える。
・本試験に影響を及ぼす可能性がある医薬品(一般用医薬品を含む)、医薬部外品、サプリメント、特定保健用食品または健康食品は、スクリーニング時から、摂取2週後の採便が終了するまで使用や摂取を禁止する。抗生物質、下剤、便秘薬、整腸剤、便秘や、下痢、消化不良を改善する作用を有する芍薬、黄柏、大黄、大棗、桂皮、人蔘等を含む漢方処方(桂枝加芍薬大黄湯、人蔘湯、五苓散料、半夏瀉心湯、加味逍遥散、大柴胡湯、乙字湯、桃核承気湯、防風通聖散)および生薬(芍薬、黄柏、大黄、大棗、桂皮、人蔘等)を含有する医薬品(一般用医薬品を含む)、医薬部外品、サプリメント、特定保健用食品(トクホ)または健康食品が該当する。
・試験期間中、生活日誌は毎日記録する。
・スクリーニング時から、摂取2週後の採便が終了するまで、大きな生活の変化は、可能な限り控える。 Dietary restriction and other restricted subjects during the study were instructed to have a normal life during the study and to comply with the following restrictions.
Matters related to meals, drinks and specialties, and meals do not significantly change the diets (meal amount and content of meals) so far, and excessive dieting and overeating that largely deviate from the daily range are avoided. However, the intake of natto is prohibited from screening until the completion of stool collection two weeks after intake.
・ The intake of drinks does not limit the amount and frequency of intake, such as green tea and coffee, but we do not largely change the degree (amount, type, etc.) of previous intake.
・ Snacks should be free in principle, but should not exceed the amount usually consumed. However, the intake of food and drink containing cacao other than the test food is prohibited from screening to collection of stool two weeks after intake is completed.
・ Alcohol intake is not limited in principle, but we do not largely change the level (amount, type, etc.) of alcohol intake so far.
・ Pharmaceuticals (including over-the-counter drugs), quasi-drugs, supplements, food for specified health use or health food that may affect this study will stop collecting stool two weeks after intake from the time of screening. Prohibit use or intake. Chinese medicine prescription including antibiotics, laxatives, constipation medicines, intestinal conditioners, constipation and aphrodisiacs that have the effect of improving diarrhea and indigestion, jaundice, large yellow rice, largepox, cinnamon, ginseng etc. Yu-Tang, Go-San, HanSan-Shin-Tang, Kamiso-San-Hang-Shu, Daejeo-Shu-Tang, Jing-San-Tang, Tao-Feng-Sen-Tang, Bofu-Tshou-San) and herbal medicines Drugs (including over-the-counter drugs), quasi-drugs, supplements, food for specified health use (Tokuho), or health food, which contains chewing etc., falls under this category.
・ Record daily life diary during the examination period.
• From the time of screening until the end of the
試験食品は、市販のカカオ豆由来ルミナコイド高含有油脂加工組成物(「チョコレート効果カカオ72%」株式会社明治)を毎日25g(1枚5gの油脂加工組成物を5枚)ずつ2週間継続して摂取させた。上記油脂加工組成物は1枚当たりカカオポリフェノールを127mg(総ポリフェノール量)含んでいることから、被験者が1日に摂取するカカオポリフェノールは635mgとなる。また、上記油脂加工組成物は1枚当たり食物繊維0.6g、難消化性たんぱく質0.18gを含んでいることから、被験者が1日に摂取する食物繊維量は3.0gとなり、難消化性たんぱく質量は0.88gとなる。すなわち、被験者が1日に摂取するカカオ豆由来ルミナコイド量は3.88gとなる。対照食品は、市販のチョコレート(「ホワイトチョコレート」株式会社明治)を毎日25g(1枚4.2gの油脂加工組成物を6枚)ずつ2週間継続して摂取させた。対照食品は、ポリフェノール、食物繊維、難消化性たんぱく質を含まない。 The test food is a continuous cocoa bean-derived luminacoid high content oil processing composition ("chocolate effect cocoa 72%" Meiji Co., Ltd.) 25 g (5 sheets of oil processing composition per sheet) each day for two weeks I had it ingested. Since the above-mentioned fat processing composition contains 127 mg (total polyphenol amount) of cocoa polyphenols per sheet, the cocoa polyphenol consumed by the subject per day is 635 mg. In addition, since the above-mentioned oil processing composition contains 0.6 g of dietary fiber and 0.18 g of indigestible protein per sheet, the amount of dietary fiber consumed by a subject per day is 3.0 g, which is indigestible The amount of protein is 0.88 g. That is, the amount of lucocoid derived from cocoa beans consumed by the subject per day is 3.88 g. As a control food, commercially available chocolate ("White Chocolate", Meiji, Ltd.) was continuously taken every 25 g (6 sheets of 4.2 g of oil-processed composition) daily for two weeks. The control food is free of polyphenols, dietary fiber and resistant proteins.
また、試験食品における、1日に摂取する1〜4量体のポリフェノールの含量は76mgであった。主な成分の内訳として、カテキン(単量体)が10.4mg、エピカテキン(単量体)が27.8mg、プロシアニジンB2(2量体)が15.8mg、プロシアニジンB5(2量体)が4.4mg、プロシアニジンC1(3量体)が9.6mg、シンナムタンニンA2(4量体)が7.1mgであった。なお、各成分については、HPLCを用いて測定した。カラムは、Deverosil−ODS−HG5(4.6mm×250mm、φ5μ、野村化学株式会社製)を使用した。溶離液は、A液とB液で構成され、A液は0.1%トリフルオロ酢酸水溶液、B液は0.1%トリフルオロ酢酸/アセトニトリル溶液を使用した。カラムへ通す溶離液の流速は0.8ml/分、グラジェントの条件は、溶離液全体に占めるB液の割合を、開始時点で10%、開始5分後で10%、開始35分後で25%、開始40分後で100%、開始45分後で100%とした。サンプルインジェクション量は10μLであり、エピカテキンを標準品として、各成分をエピカテキン当量で定量した。また、ポリフェノール含量は、プルシアンブルー法により測定した。具体的には、Martin L. Price and Larry G. Butler, J. Agric Food Chem. 1977, 25(6): 1268-1273に記載の方法に従い、市販のエピカテキンを標準物質としてポリフェノール含量を算出した。 Moreover, in the test food, the content of 1 to 4 mer polyphenols to be ingested per day was 76 mg. Breakdown of main components: 10.4 mg of catechin (monomer), 27.8 mg of epicatechin (monomer), 15.8 mg of procyanidin B2 (dimer), procyanidin B5 (dimer) It was 4.4 mg, procyanidin C1 (trimer) 9.6 mg, and cinnamtanin A2 (tetramer) 7.1 mg. In addition, about each component, it measured using HPLC. As a column, Deverosil-ODS-HG5 (4.6 mm × 250 mm, φ5 μ, manufactured by Nomura Chemical Co., Ltd.) was used. The eluent consisted of solution A and solution B. Solution A used a 0.1% aqueous solution of trifluoroacetic acid, and solution B used a solution of 0.1% trifluoroacetic acid / acetonitrile. The flow rate of the eluent through the column is 0.8 ml / min, and the condition of the gradient is that the proportion of solution B in the whole eluent is 10% at the start point, 10% at 5 minutes and 10% at 35 minutes after the start 25%, 100% after 40 minutes starting, and 100% after 45 minutes starting. The amount of sample injection was 10 μL, and each component was quantified by epicatechin equivalent using epicatechin as a standard. Moreover, polyphenol content was measured by Prussian blue method. Specifically, polyphenol content was calculated using commercially available epicatechin as a standard substance according to the method described in Martin L. Price and Larry G. Butler, J. Agric Food Chem. 1977, 25 (6): 1268-1273. .
また、試験食品における、1日に摂取する食物繊維の含量は3.0gであった。具体的には(エーオーエーシ―インターナショナルAOAC Internationalによる公定法)である酵素−重量法により算出した。 Moreover, in the test food, the content of dietary fiber consumed per day was 3.0 g. Specifically, it was calculated by the enzyme-weight method which is (the official method of AOACS International AOAC International).
また、試験食品における、1日に摂取する難消化性タンパク質の含量は0.88gであった。具体的には、下記、難消化性タンパク質の抽出方法に従い抽出したたんぱく質量を、ケルダール法(たんぱく質定量の公定法)により算出した。また、下記、人工消化試験により、抽出したたんぱく質が難消化性タンパク質であることを確認した。 In addition, the content of indigestible protein to be ingested in one day in the test food was 0.88 g. Specifically, the amount of protein extracted according to the following extraction method of indigestible protein was calculated by the Kjeldahl method (the official method of protein determination). In addition, it was confirmed by the following artificial digestion test that the extracted protein was a nondigestible protein.
難消化性たんぱく質の抽出方法
チョコレートを湯煎にて溶解し、チョコレートの5倍量のヘキサンを添加して3時間撹拌した。10,000rpm、4℃で10分遠心し、沈殿を回収した。回収した沈殿を、初発チョコレート量の3倍量のヘキサンに懸濁し1時間撹拌した。10,000rpm、4℃で10分遠心し、沈殿を一晩風乾した(チョコパウダーという)。前述のチョコパウダーを20倍量の脱イオン水に懸濁し、10分ほど撹拌した。pHを確認し、NaOHでpH12に調整した。再び10分撹拌した後、pHを確認し、NaOHでpH12に調整した。50℃に加温し、到達したらpHを確認し、NaOHでpH12に調整した。70℃に加温し、到達したら30分抽出した。10,000rpm、10分、室温で遠心し、上清を回収した。得られた上清にリン酸を添加してpHを2.0に調整し、一晩4℃で静置した。10,000rpm、で10分、室温で遠心し、沈殿を回収した。沈殿に原料(チョコパウダー重量)の5倍量の脱イオン水を加えて懸濁し、10,000rpm、で10分、25℃で遠心し上清を除去した。洗浄は2回実施した。沈殿を回収し80℃で72時間減圧乾燥した。 Extraction Method of Indigestible Protein The chocolate was dissolved in hot water, and 5 times the amount of hexane of chocolate was added and stirred for 3 hours. The precipitate was collected by centrifugation at 10,000 rpm for 10 minutes at 4 ° C. The collected precipitate was suspended in hexane three times the amount of the initial chocolate and stirred for 1 hour. The mixture was centrifuged at 10,000 rpm for 10 minutes at 4 ° C., and the precipitate was air-dried overnight (referred to as chocolate powder). The aforementioned chocolate powder was suspended in 20 volumes of deionized water and stirred for about 10 minutes. The pH was checked and adjusted to
人工消化試験
(1)ペプシン消化
被験サンプルに水を加えて10%とした後、塩酸でpHを2.0に調整した。そこにペプシン(163−00642、和光純薬工業社)を採取量の1/100を添加して37℃で4時間反応させた。 Artificial digestion test (1) pepsin digestion After adding water to the test sample to make it 10%, the pH was adjusted to 2.0 with hydrochloric acid. Pepsin (163-00642, Wako Pure Chemical Industries, Ltd.) was added thereto 1/100 of the amount collected and reacted at 37 ° C. for 4 hours.
(2)パンクレアチン消化
上記(1)の反応物を水酸化ナトリウムでpHを8〜10に調整し、パンクレアチン(163−00142、和光純薬工業社)を採取量の1/50を添加して37℃で16時間反応させた。酵素反応終了後、100℃、5分間加熱して酵素反応を止めた。また、(1)、(2)ともに、酵素に代えて酵素添加量と等量(重量)の水を加え、他を酵素処理と同様に操作したブランク区を検体と同時に処理した。(2) Pancreatin digestion The reaction product of (1) above was adjusted to pH 8-10 with sodium hydroxide, and pancreatin (163-00142, Wako Pure Chemical Industries, Ltd.) was added at 1/50 of the collected amount. The reaction was allowed to proceed at 37.degree. C. for 16 hours. After completion of the enzyme reaction, the enzyme reaction was stopped by heating at 100 ° C. for 5 minutes. Further, in both (1) and (2), water was added in an amount (weight) equivalent to the amount of enzyme added instead of the enzyme, and a blank area operated in the same manner as the enzyme treatment was treated simultaneously with the sample.
(3)未消化物(残渣)の回収
上記(2)の反応物を塩酸でpHを2.0に調整し、10,000rpm、10分、4℃で遠心し、沈殿を回収した。回収した沈殿物に、試料採取量の5倍量の水を加えて沈殿物を溶解・洗浄して再度遠心分離(10,000rpm、10分、4℃)を行った。この操作を合計2回行った。(3) Recovery of undigested substance (residue) The reaction product of (2) above was adjusted to pH 2.0 with hydrochloric acid, centrifuged at 10,000 rpm for 10 minutes at 4 ° C., and the precipitate was recovered. To the collected precipitate, 5 times the amount of sampled water was added to dissolve and wash the precipitate, and centrifugation (10,000 rpm, 10 minutes, 4 ° C.) was performed again. This operation was performed twice in total.
(4)乾燥
回収した沈殿は凍結乾燥した。その際、凍結乾燥前後における重量(以下、残渣回収量とする)を測定した。なお成分量はケルダール法にて求めた。
以下の計算式にて消化率を算出した。(4) Drying The collected precipitate was lyophilized. At that time, the weight before and after lyophilization (hereinafter referred to as the amount of recovered residue) was measured. The amounts of components were determined by the Kjeldahl method.
The digestibility was calculated by the following formula.
結果、難消化性たんぱく質含有物中のタンパク質の消化率は20%、同時に試験を実施したカゼインは99.3%であった。 As a result, the digestibility of protein in the indigestible protein-containing product was 20%, and that of casein tested at the same time was 99.3%.
以上のことからチョコレートより抽出したたんぱく質が難消化性であることが確認できた。 From the above, it can be confirmed that the protein extracted from chocolate is indigestible.
評価および結果
摂取開始日を1日目とし、摂取開始7日前(−7日目、−1W)から摂取最終日(14日目、2W)までの間、生活日誌(試験食品摂取の確認、自覚症状の記録、摂取開始日7日前よりの排便状況(排便回数、便性、便量)、性周期等、医薬品の服用状況等の記録)による記録を行った。摂取開始7日前(−7日目、−1W)および摂取最終日(14日目、2W)に、生活習慣アンケート、自覚アンケート、理学的検査(身長、体重、血圧、脈拍数、BMI)採便を実施した。また、便中菌叢解析(Nagashima法による便中菌叢のT-RFLP解析)、便中ビフィズス菌数および総菌数の定量・ビフィズス菌占有率の測定(リアルタイムPCR法)、便の網羅的菌叢解析(DGGE法、次世代アンプリコンシーケンス法:メタゲノム解析による被験者腸内菌叢(属レベル)の評価を行った。得られたデータは平均値±標準誤差で示した。統計解析は以下の通り行った。便色・便量などの群間比較:「独立サンプルのt検定」(解析ソフトウェア:「IBM SPSS Statistics 23」)。排便回数の群間比較:「Mann-WhitneyのU検定」(解析ソフトウェア:「IBM SPSS Statistics 23」)。網羅的菌叢解析の群間比較:エクセル統計(SSRI)を用い、対照食品群と試験食品群の比較をt−testで評価した(有意水準は5%未満とした)。 Evaluation and results The intake start day is the first day, and from 7 days before the intake start (day -7, -1W) to the last day of intake (
排便回数は、試験食品群において顕著な経時的増加を示すとともに、−7日目〜−1日目(−1W〜0W)に対して、0日目〜7日目(0W〜1W)、8日目〜14日目(1W〜2W)ともに有意差(危険率(p値)5%未満)があった。対照食品群に比べ試験食品群において明らかな排便回数の増加が認められた(図1)。
The frequency of defecation shows a marked increase with time in the test food group, and the
便性は、便色と排便量により評価した。便色は5段階の便色スコアにより評価した。具体的には、便色スコア値は、1:黄色〜黄褐色、2:褐色、3:茶褐色、4:暗褐色、5:黒褐色〜黒色とし(腸内細菌学雑誌.2004, 18(2); 107-115参照)、被験者には、目視にて比色するため、上記5段階の便色スコア値および名称が表記され、対応する便色がカラー印刷された便色スケールを渡し、便の色を被験者自身に観測させた。その結果、試験食品群の摂取14日後の便色スコア値が、対照食品群の便色スコア値よりも有意に低い値を示していた(図2)。すなわち、便色において試験食品摂取群に摂取14日後には改善傾向がみられたが、対照食品摂取群では、ほとんど変化がみられなかった(図2)。便量については、−7日目〜−1日目(−1W〜0W)の摂取前1週間の全排便量(前)に対する0日目〜7日目(0W〜1W)、または8日目〜14日目(1W〜2W)までのそれぞれ1週間の全排便量の比を求めた。その結果、試験食品群の便量が経時的に増加する傾向がみられた(データ示さず)。
Fecal properties were evaluated by stool color and defecation volume. The stool color was evaluated by a 5-step stool color score. Specifically, the stool color score value is 1: yellow to yellowish brown 2: brown to 4: dark brown to 5: dark brown to black (Intestinal Bacteriology Journal. 2004, 18 (2) 107-115), the test subjects are marked with the above-mentioned 5 levels of stool color score value and name, and the corresponding stool color passes the color printed stool color scale for visual comparison. The subject was allowed to observe the color himself. As a result, the stool
図1および図2の結果から、カカオ豆由来ルミナコイド摂取により排便回数、排便量が増加すること、便色が改善することが確認された。 From the results of FIG. 1 and FIG. 2, it is confirmed that the number of stools and the amount of stools increase and the stool color is improved by the consumption of the cocoa bean-derived luminacoid.
また、次世代アンプリコンシーケンス法(Proc Natl Acad Sci U S A. 2011, 108(Suppl 1): 4516-4522参照)を用いたメタゲノム解析をMiSeqシステム(イルミナ社製)により実施した。菌叢を構成する各菌の分類は、16SrDNA配列情報に従って行った(Nucl Acids Res. 2007, 35:18. e120参照)。その結果、被験者腸内菌叢(属レベル)では、腸内菌叢全菌数を100%とした場合のフィーカリバクテリウム属菌の占有率が、試験食品摂取群において、摂取前(0日目)と比較して摂取後(14日目)で有意に増加した(図3)。すなわち、排便回数の増加、排便量の増加、便色の改善は、フィーカリバクテリウム属菌の増加によるものであることが確認された。 In addition, metagenomic analysis using the next-generation amplicon sequencing method (see Proc Natl Acad Sci USA 2011 (108) (Suppl 1): 4516-4522) was performed using the MiSeq system (manufactured by Illumina). Classification of each bacterium constituting the flora was performed according to 16S rDNA sequence information (see Nucl Acids Res. 2007, 35:18. E120). As a result, in the test subject intestinal flora (genus level), the occupancy rate of the Ficalibacterium bacteria when the total number of bacteria in the intestinal flora is 100% is before intake (0 day in the test food intake group) It significantly increased after ingestion (day 14) compared to the eye (Figure 3). That is, it was confirmed that the increase in the number of stools, the increase in the amount of stools, and the improvement in stool color were due to the increase in the genus Ficalibacterium.
以上の結果から、カカオ豆由来ルミナコイドはフィーカリバクテリウム属菌の産生を促進することが確認された。従って、カカオ豆由来ルミナコイドは、炎症性疾患、アレルギー疾患、腸内菌共生バランス失調(Dysbiosis)に起因すると考えられる疾病(クローン病など)などのフィーカリバクテリウム属菌の産生促進により改善される疾患や病状の改善効果を有することが示された。 From the above results, it was confirmed that cacao bean-derived luminacoid promotes the production of a ficalibacterium. Therefore, cacao bean-derived luminacoids are improved by promoting the production of Ficalibacterium such as inflammatory diseases, allergic diseases, and diseases (eg, Crohn's disease) that are considered to be caused by intestinal bacterial symbiotic imbalance (Dysbiosis). It has been shown to have an improvement effect on diseases and medical conditions.
試験例2:カカオ豆由来ルミナコイドによるフィーカリバクテリウム属菌の産生促進効果の検討(2)
カカオ豆由来ルミナコイドがフィーカリバクテリウム属菌の産生に与える影響を検証するために、チョコレートから抽出したルミナコイドを用いて以下の試験を行った。 Test Example 2: Examination of the production promoting effect of Ficaribacterium by Luminousoid derived from cocoa beans (2)
In order to verify the influence that the cocoa bean-derived luminacoid exerts on the production of the ficalibacterium bacteria, the following test was performed using the luminacoid extracted from chocolate.
(1)ルミナコイドの調製
市販のカカオ豆由来ルミナコイド高含有油脂加工組成物(「チョコレート効果カカオ72%」株式会社明治)1603gを湯煎で溶かし、チョコレートの5倍量のヘキサン(8L)を添加後、3時間撹拌することで脱脂した。遠心分離後(10000rpm、10分、4℃)、上清を除去し沈殿物を回収した。沈殿物にチョコレートの3倍量のヘキサン(4.8L)を添加後、1時間撹拌した。遠心分離後、上清を除去し沈殿物を回収後、ドラフト内で一晩乾燥させた。乾燥させた沈殿物をミルサーで粉砕することでチョコレートパウダー981gを得た。(1) Preparation of Luminacoid Dissolve 1603 g of a commercial cocoa bean-derived high luminacoid-containing fat and oil processing composition ("Chocolate effect cacao 72%" Meiji Co., Ltd. Meiji) with hot water and add 5 times the amount of hexane (8 L) of chocolate, It degreased by stirring for 3 hours. After centrifugation (10000 rpm, 10 minutes, 4 ° C.), the supernatant was removed and the precipitate was recovered. After adding 3 times the amount of hexane (4.8 L) to the precipitate, it was stirred for 1 hour. After centrifugation, the supernatant was removed and the precipitate was collected and dried overnight in a fume hood. The dried precipitate was pulverized with a mill to obtain 981 g of chocolate powder.
上記のようにして得たチョコレートパウダー(981g)を20倍量の水(19.6L)に懸濁し、8N NaOHを用いてpH12.0に調整後、70℃に加温し30分間抽出を行った。遠心分離後(10000rpm、10分、25℃)、上清を回収した。 The chocolate powder (981 g) obtained as described above is suspended in 20 volumes of water (19.6 L), adjusted to pH 12.0 with 8 N NaOH, heated to 70 ° C., and extracted for 30 minutes. The After centrifugation (10000 rpm, 10 minutes, 25 ° C.), the supernatant was recovered.
回収した上清をリン酸でpH2.0に調整し、4℃で一晩静置した。遠心分離後(10000rpm、10分、25℃)、上清を除去し沈殿物を回収した。 The collected supernatant was adjusted to pH 2.0 with phosphoric acid and allowed to stand overnight at 4 ° C. After centrifugation (10000 rpm, 10 minutes, 25 ° C.), the supernatant was removed and the precipitate was recovered.
沈殿物に、チョコレートパウダーの5倍量の水(4.9L)を加え水洗を行い、遠心分離後(10000rpm、10分、25℃)、上清を捨てた。水洗を2回繰り返して得られた沈殿物を80℃で6時間、減圧乾燥機にて乾燥させ、カカオプロテイン含有物129gを得た(たんぱく質:46.6%、食物繊維:43.3%)。得られたカカオプロテイン含有物に含まれるたんぱく質と食物繊維は難消化性であることから、カカオプロテイン含有物はカカオ豆由来ルミナコイドに相当する。 To the precipitate, 5 volumes of water (4.9 L) of chocolate powder was added to perform washing with water, and after centrifugation (10000 rpm, 10 minutes, 25 ° C.), the supernatant was discarded. The precipitate obtained by repeating the water washing twice was dried at 80 ° C. for 6 hours in a vacuum drier to obtain 129 g of a cocoa protein-containing substance (protein: 46.6%, dietary fiber: 43.3%) . Since the protein and dietary fiber contained in the obtained cocoa protein-containing substance are resistant to digestion, the cocoa protein-containing substance corresponds to the cocoa bean-derived luminacoid.
(2)試験方法
試験は、上記(1)で調製したカカオ豆由来ルミナコイド(カカオプロテイン含有物)を配合した飼料(試験飼料)を摂取させる試験飼料群と、カカオ豆由来ルミナコイドを配合しない飼料(対照飼料)を摂取させる対照飼料群の2群に対して行った。試験飼料としては、AIN93Gの5%セルロース分を5%カカオプロテイン含有物に置換した飼料を用いた。対照飼料としては、AIN93Gのうち不溶性食物繊維である5%セルロース分を5%コーンスターチに置換した飼料を用いた。AIN93Gからセルロース分を除いた飼料は、オリエンタル酵母工業社製のものを用いた。(2) Test method In the test, a test feed group ingesting a feed (test feed) containing the cocoa bean-derived luminacoid (cocoa protein-containing material) prepared in (1) above, and a feed not containing the cocoa bean-derived luminacoid ( The control feed was performed on two groups of the control feed group receiving the control feed. As a test feed, a feed in which the 5% cellulose content of AIN93G was replaced with a 5% cocoa protein-containing content was used. As a control feed, a feed in which 5% cellulose, which is insoluble dietary fiber in AIN 93 G, was replaced with 5% corn starch was used. The feed produced by removing cellulose from AIN 93G was produced by Oriental Yeast Co., Ltd.
BALB/cAマウス(メス、6週齢、日本クレア社)12匹を対照飼料にて1週間予備飼育した後、平均体重が同等となるように群分けを行った。群分けは各群6匹となるようにした。 After 12 rats of BALB / cA mice (female, 6 weeks old, CLEA Japan, Inc.) were preliminarily bred with a control diet for 1 week, they were divided into groups so that the average body weights would be equal. Grouping was made to be 6 animals in each group.
試験開始時から各飼料および水は自由摂取とした。週に2回の体重測定および摂餌量測定を行った。また、試験開始後11〜13日目の2日分の糞便を回収し、凍結乾燥後、乾燥重量を測定した。 Each feed and water was free intake from the start of the study. Body weight and food intake measurements were taken twice a week. In addition, feces for 2 days on the 11th to 13th days after the start of the test were collected, and after freeze-drying, the dry weight was measured.
試験開始後14日目にイソフルラン麻酔下にて腹部下行大静脈より全採血を行った。盲腸内容物を採取後、重量を測定し−80℃にて保存した。また、盲腸内短鎖脂肪酸濃度の測定は、以下の測定機器および条件で行った。
測定機器:島津有機酸分析システム
カラム:Shim-Pack SCR-102(H),300mm×8mm ID、2本直列で使用
ガードカラム:Shim-Pack SCR-102(H),50mm×6mm ID
溶離液:5mmol/L p−トルエンスルホン酸
反応液:5mmol/L p−トルエンスルホン酸、100μmol/L EDTA、20mmol/L Bis−Tris
流速:0.8mL/分
オーブン温度:45℃
検出器:電気伝導度検出器CDD−10A
参照文献:Advances in Microbiology. 2015, 5(7):531-540およびBenef Microbes. 2016 Jun, 7(3):337-344On the 14th day after the start of the test, whole blood was collected from the abdominal descending vena cava under isoflurane anesthesia. The cecal contents were collected, weighed and stored at -80 ° C. Moreover, the measurement of the cecal short chain fatty acid concentration was performed on the following measuring devices and conditions.
Measuring instrument: Shimadzu organic acid analysis system Column: Shim-Pack SCR-102 (H), 300 mm x 8 mm ID, 2 columns used in series Guard column: Shim-Pack SCR- 102 (H), 50 mm x 6 mm ID
Eluent: 5 mmol / L p-toluenesulfonic acid reaction solution: 5 mmol / L p-toluenesulfonic acid, 100 μmol / L EDTA, 20 mmol / L Bis-Tris
Flow rate: 0.8 mL / min Oven temperature: 45 ° C.
Detector: Conductivity detector CDD-10A
References: Advances in Microbiology. 2015, 5 (7): 531-540 and Benef Microbes. 2016 Jun, 7 (3): 337-344
得られたデータは平均値±標準誤差で示した。統計解析はエクセル統計 (SSRI)を用い、対照飼料群と試験飼料群の比較をt−testで評価した。有意水準は5%未満とした。なお、試験開始時および終了時の体重と総摂餌量については、いずれも各群間に有意な差はなかった(データ示さず)。 The data obtained are shown as mean ± standard error. Statistical analysis used Excel statistics (SSRI), and the comparison of the control feed group and the test feed group was evaluated by t-test. The significance level was less than 5%. There were no significant differences between the groups in the body weight and the total food consumption at the start and end of the test (data not shown).
(3)結果
試験開始後11〜13日目の乾燥糞便重量は図4に、解剖時の盲腸内容物重量は図5にそれぞれ示す。また、盲腸内の短鎖脂肪酸量(酪酸、プロピオン酸、酢酸)は図6A、図6Bおよび図6Cに示す。(3) Results The weight of dried feces 11 to 13 days after the start of the test is shown in FIG. 4, and the weight of cecal contents at dissection is shown in FIG. Also, the amount of short-chain fatty acids (butyric acid, propionic acid, acetic acid) in the cecum is shown in FIG. 6A, FIG. 6B and FIG. 6C.
図4に示されるように、対照飼料群と比較して、試験飼料群において糞便重量の有意な増加が認められた。この結果は、試験例1における「チョコレート効果カカオ72%」の摂取による便通改善効果の有効成分がカカオプロテイン含有物(ルミナコイド)であることを示している。 As shown in FIG. 4, a significant increase in fecal weight was observed in the test feed group as compared to the control feed group. This result shows that the active ingredient of the stool improvement effect by ingestion of "chocolate effect cocoa 72%" in Test Example 1 is a cocoa protein-containing substance (luminacoid).
また、図5に示されるように、対照飼料群と比較して、試験飼料群において盲腸内容物重量の有意な増加が認められた。さらに、図6A、図6Bおよび図6Cに示されるように、対照飼料群と比較して、試験飼料群において盲腸内の短鎖脂肪酸量の有意な増加が認められた。これらのことから、カカオプロテイン含有物(ルミナコイド)は、便の嵩増し効果による糞便量増加に加えて、盲腸内の短鎖脂肪酸の産生による糞便量増加効果を有することが示された。盲腸内の短鎖脂肪酸は、フィーカリバクテリウム属菌により産生され、フィーカリバクテリウム属菌の占有率の変化量とヒト糞便中の短鎖脂肪酸濃度の変化量との間には強い正の相関が見られることから(例えば、Brit J Nutr. 2010, 104(5): 693-700参照)、試験例1の結果と併せると、カカオプロテイン含有物(ルミナコイド)は、フィーカリバクテリウム属菌の産生を促進し、腸内菌叢の改善を促進する効果を有することが示された。 Also, as shown in FIG. 5, a significant increase in cecal content weight was observed in the test feed group as compared to the control feed group. Furthermore, as shown in FIGS. 6A, 6B and 6C, a significant increase in the amount of short-chain fatty acids in the cecum was observed in the test feed group as compared to the control feed group. From these results, it was shown that the cocoa protein-containing substance (luminacoid) has an effect of increasing the amount of feces due to the production of short-chain fatty acids in the cecum, in addition to the increase of feces due to the bulking effect of feces. The short-chain fatty acids in the cecum are produced by Ficalibacterium spp. And are strongly positive between the change in occupancy rate of Ficalibacterium spp. And the change in short-chain fatty acid concentration in human feces. From the fact that a correlation is observed (for example, see Brit J Nutr. 2010, 104 (5): 693-700), in combination with the results of Test Example 1, the cocoa protein-containing substance (luminacoid) is Have been shown to have the effect of promoting the improvement of intestinal flora.
試験例3:カカオ豆由来ルミナコイドによるフィーカリバクテリウム属菌の産生促進効果の検討(3)
カカオ豆由来ルミナコイドが糞便中の短鎖脂肪酸の産生に与える影響を検証するために以下の試験を行った。 Test Example 3: Examination of the production promoting effect of Ficaribacterium bacteria by cacao bean-derived luminacoid (3)
The following tests were conducted to examine the influence of cocoa bean-derived luminacoid on the production of short chain fatty acids in feces.
20歳以上50歳未満の健康な日本人女性から被験者をスクリーニングにより選抜し、評価者盲検並行群間比較試験を行った(試験食品群、対照食品群、各30名)。試験期間中は、食事制限およびその他の制限を行った。試験期間中の食事制限およびその他の制限、並びに食事、飲み物および嗜好品に関する事項については、試験例1に記載された基準と同じ基準を採用した。 The subjects were selected by screening from healthy Japanese women aged 20 to 50 years old, and evaluator blinded parallel group comparison tests were conducted (test food group, control food group, 30 people each). Food and other restrictions were performed during the study. The same criteria as those described in Test Example 1 were adopted for food restriction and other restrictions during the test period, as well as matters relating to food, drinks and luxury items.
スクリーニングは、摂取開始7日前(−7日目、−1W)に、生活習慣アンケート(年齢、既往歴、合併症、食物アレルギーの有無、医薬品や健康食品の摂取状況、飲酒等の確認)、自覚アンケート(整腸に関する自覚症状の調査)、理学的検査(身長、体重、血圧、脈拍数、BMI)を実施し、排便の状態(排便回数、便性、便量)、年齢、食習慣(カカオ製品、納豆、乳酸菌含有食品等の日常的な摂取状況)による所定の除外基準を満たした、排便回数が週平均4回の60名を選抜した。スクリーニングにおける除外基準は、試験例1に記載される基準と同じ基準を採用した。 Screening 7 days before intake start (day -7, -1W), lifestyle questionnaire (age, medical history, complications, presence or absence of food allergy, intake status of medicines and health food, confirmation of drinking etc.), awareness Questionnaire (investigation of symptoms related to intestinal adjustment), physical examination (height, weight, blood pressure, pulse rate, BMI), defecation status (number of stools, feces, stool volume), age, eating habits (cacao) The average number of stools per week was 60, which met an average of 4 times per week, and met the prescribed exclusion criteria for products, natto, foods containing lactic acid bacteria, etc.). The exclusion criteria for screening adopted the same criteria as those described in Test Example 1.
試験食品と対照食品は、試験例1に記載された手順と同様の手順で調製し、評価したものを用いた。 As the test food and the control food, those prepared and evaluated in the same procedure as described in Test Example 1 were used.
評価は以下の通り行った。摂取開始日を1日目とし、摂取開始7日前(−7日目、−1W)から摂取最終日(14日目、2W)までの間、生活日誌(試験食品摂取の確認、自覚症状の記録、摂取開始日7日前よりの排便状況(排便回数、便性、便量)、性周期等、医薬品の服用状況等の記録)による記録を行った。摂取開始7日前(−7日目、−1W)および摂取最終日(14日目、2W)に、生活習慣アンケート、自覚アンケート、理学的検査(身長、体重、血圧、脈拍数、BMI)、採便を実施した。
The evaluation was as follows.
また、便中の短鎖脂肪酸濃度を測定した。便中短鎖脂肪酸濃度は、試験例2に記載された測定機器を用いて、試験例2に記載された条件に従って測定した。その結果、試験食品を摂取させることにより便中短鎖脂肪酸濃度が増大することが確認された(データ示さず)。大腸内の短鎖脂肪酸は、フィーカリバクテリウム属菌により産生され、フィーカリバクテリウム属菌の占有率の変化量とヒト糞便中の短鎖脂肪酸濃度の変化量との間には強い正の相関が見られることから(例えば、Brit J Nutr. 2010, 104(5): 693-700参照)、試験例1の結果と併せると、カカオプロテイン含有物(ルミナコイド)は、フィーカリバクテリウム属菌の産生を促進し、腸内菌叢の改善を促進する効果を有することが本試験例でも示された。 In addition, short chain fatty acid concentration in stool was measured. The stool short-chain fatty acid concentration was measured according to the conditions described in Test Example 2 using the measurement device described in Test Example 2. As a result, it was confirmed that the short chain fatty acid concentration in feces increased by ingesting the test food (data not shown). Short-chain fatty acids in the large intestine are produced by Ficalibacterium spp., And are strongly positive between the change in occupancy rate of Ficalibacterium spp. And the change in short-chain fatty acid concentration in human feces. From the fact that a correlation is observed (for example, see Brit J Nutr. 2010, 104 (5): 693-700), in combination with the results of Test Example 1, the cocoa protein-containing substance (luminacoid) is It was shown also in this test example that it has an effect of promoting the production of and improving the intestinal flora.
Claims (14)
A cocoa-derived luminacoid for use in promoting the production of Ficalibacterium, or in treating, preventing or ameliorating a disease or condition that can be treated, prevented or ameliorated by the production of Ficalibacterium.
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