JP2022081686A - Medicine for intestinal disorders, antiallergic agent, immunoadjuvant, and agent for improving enteroadherent properties of lactic acid bacteria - Google Patents

Medicine for intestinal disorders, antiallergic agent, immunoadjuvant, and agent for improving enteroadherent properties of lactic acid bacteria Download PDF

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JP2022081686A
JP2022081686A JP2022048591A JP2022048591A JP2022081686A JP 2022081686 A JP2022081686 A JP 2022081686A JP 2022048591 A JP2022048591 A JP 2022048591A JP 2022048591 A JP2022048591 A JP 2022048591A JP 2022081686 A JP2022081686 A JP 2022081686A
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lactic acid
acid bacteria
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敬 佐藤
Takashi Sato
整一 北村
Seiichi Kitamura
仁人 鍔田
Masahito Tsubata
欣也 高垣
Kinya Takagaki
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Toyo Shinyaku Co Ltd
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Abstract

PROBLEM TO BE SOLVED: To provide a medicine for intestinal disorders, an antiallergic agent, an immunoadjuvant and an agent for improving enteroadherent properties of lactic acid bacteria, which can be taken safely, are available inexpensively, and have high effect of improving enteroadherent properties of lactic acid bacteria.
SOLUTION: An agent according to the present invention contains flower extract. The flower is a Lythraceae, Asteraceae, Fabaceae, Rosaceae or Iridaceae flower, preferably, at least one selected from Carthamus tinctorius, Punica granatum, Pueraria plants, Subgen. Cerasus plants, Chrysanthemum plants, Crocus sativus, Prunus persica Batsch and Rosa plants.
SELECTED DRAWING: Figure 1
COPYRIGHT: (C)2022,JPO&INPIT

Description

本発明は、整腸剤、抗アレルギー剤、免疫増強剤及び乳酸菌の腸管接着性向上剤に関する。 The present invention relates to an intestinal regulator, an antiallergic agent, an immunopotentiator, and an intestinal adhesiveness improving agent for lactic acid bacteria.

動物の腸管において乳酸菌の増殖を促進すると、病原菌の侵入や有害菌の増殖を抑制できること、このような整腸作用は、下痢や便秘の改善や予防につながることはよく知られている。乳酸菌が腸管へ定着して増殖する為には、腸管における乳酸菌の付着(接着)が非常に重要であると考えられている。 It is well known that promoting the growth of lactic acid bacteria in the intestinal tract of animals can suppress the invasion of pathogenic bacteria and the growth of harmful bacteria, and that such an intestinal regulating action leads to improvement or prevention of diarrhea and constipation. It is considered that the adhesion (adhesion) of lactic acid bacteria in the intestinal tract is very important for the lactic acid bacteria to settle and proliferate in the intestinal tract.

更に近年、乳酸菌は抗アレルギー作用とも関係することが報告されてきている。
人の免疫システムは複数種のT細胞が司令塔の役割を果たしている。T細胞としては、主としてIgA抗体産生を促し細胞性免疫を活性化させるTh1細胞と、I型アレルギーを引き起こすIgE抗体産生を促進させて液性免疫を活性化させるTh2細胞とが知られている。このTh1細胞とTh2細胞とはお互いに抑制しあい、Th1細胞よりTh2細胞が優位に働くとアレルギー症状がおこりやすい。
腸管には体内の免疫細胞の7割が集中して存在しているとされ、体の免疫システムの主要な役割を果たしている。この腸管免疫に乳酸菌が重要な働きをすることが解明されてきている。例えば乳酸菌の菌体成分は、腸管においてマクロファージや樹状細胞のサイトカイン分泌を促進し、これによりTh1細胞の働きを活発化することや、IgA抗体産生を促すことが知られている。これによりTh2細胞の働きが抑制されてIgE抗体産生が抑制され、アレルギーが改善されると考えられている。乳酸菌(及びその菌体成分)の腸管への接着は、このような腸管免疫刺激作用やそれに伴う抗アレルギー作用を高めるためにも非常に重要と考えられている。
Furthermore, in recent years, it has been reported that lactic acid bacteria are also associated with antiallergic effects.
In the human immune system, multiple types of T cells play the role of a control tower. As T cells, Th1 cells that mainly promote IgA antibody production and activate cell-mediated immunity and Th2 cells that promote IgE antibody production that causes type I allergy and activate humoral immunity are known. The Th1 cells and Th2 cells suppress each other, and when Th2 cells act predominantly over Th1 cells, allergic symptoms are likely to occur.
It is said that 70% of the immune cells in the body are concentrated in the intestinal tract, and play a major role in the body's immune system. It has been elucidated that lactic acid bacteria play an important role in this intestinal immunity. For example, it is known that the bacterial cell component of lactic acid bacteria promotes cytokine secretion of macrophages and dendritic cells in the intestinal tract, thereby activating the function of Th1 cells and promoting IgA antibody production. It is believed that this suppresses the action of Th2 cells, suppresses IgE antibody production, and improves allergies. Adhesion of lactic acid bacteria (and their cell components) to the intestinal tract is considered to be very important for enhancing such intestinal immunostimulatory action and the associated antiallergic action.

従って、乳酸菌の腸管接着性を向上させる経口剤を用い、乳酸菌の腸管接着を促すことができれば整腸並びに抗アレルギーの予防及び改善が期待できる。そのような経口剤には安全性が高いことや安価に入手できることが求められるが、その開発は進んでおらず、患者・消費者の多様なニーズに十分に答えられていない。 Therefore, if an oral agent that improves the intestinal adhesion of lactic acid bacteria can be used to promote the intestinal adhesion of lactic acid bacteria, intestinal regulation and prevention and improvement of antiallergic can be expected. Such oral preparations are required to be highly safe and available at low cost, but their development has not progressed and they have not fully responded to the diverse needs of patients and consumers.

一方、花の抽出物は、健康食品等に利用され、これまで種々の作用が検討されているが(例えば特許文献1)、新たな用途が求められている。 On the other hand, flower extracts are used in health foods and the like, and various actions have been studied so far (for example, Patent Document 1), but new uses are required.

特開 2003-055249号公報Japanese Patent Application Laid-Open No. 2003-055249

従って、本発明の課題は、新たな乳酸菌の腸管接着性向上剤、整腸剤、抗アレルギー剤及び免疫増強剤を提供することにある。 Therefore, an object of the present invention is to provide a new lactic acid bacterium intestinal adhesiveness improving agent, intestinal regulating agent, antiallergic agent and immunopotentiating agent.

本発明者らは、乳酸菌の腸管接着性を高めることができる物質について鋭意検討した。その結果、安価且つ安全に入手可能な素材として、特定の花の抽出物を用いることで乳酸菌の腸管接着性を高めることができることを見出した。 The present inventors have diligently studied substances capable of enhancing the intestinal adhesiveness of lactic acid bacteria. As a result, it was found that the intestinal adhesiveness of lactic acid bacteria can be enhanced by using a specific flower extract as an inexpensive and safely available material.

本発明は前記知見に基づくものであり、ミソハギ科(Lythraceae)、キク科(Asteraceae)、マメ科(Fabaceae)、バラ科(Rosaceae)又はアヤメ科(Iridaceae)の花の抽出物を含有する整腸剤を提供するものである。 The present invention is based on the above findings, and is an intestinal regulator containing an extract of flowers of Lythraceae, Asteraceae, Fabaceae, Rosaceae or Iridaceae. It is to provide.

また本発明は、ミソハギ科(Lythraceae)、キク科(Asteraceae)、マメ科(Fabaceae)、バラ科(Rosaceae)又はアヤメ科(Iridaceae)の花の抽出物を含有する抗アレルギー剤、免疫増強剤及び乳酸菌の腸管接着性向上剤を提供するものである。 The present invention also comprises an antiallergic agent, an immunopotentiator and an extract of flowers of Lythraceae, Asteraceae, Fabaceae, Rosaceae or Iridaceae. It provides an agent for improving intestinal adhesion of lactic acid bacteria.

本発明によれば、安全に摂取でき、安価に入手でき、且つ乳酸菌の腸管接着性向上作用に優れた整腸剤、抗アレルギー剤、免疫増強剤及び乳酸菌の腸管接着性向上剤が提供される。 According to the present invention, there are provided an intestinal regulating agent, an antiallergic agent, an immunopotentiating agent, and an intestinal adhesiveness improving agent for lactic acid bacteria, which can be safely ingested, can be obtained at low cost, and have an excellent effect of improving intestinal adhesiveness of lactic acid bacteria.

また、本発明によれば、特定の花エキスは乳酸菌の腸管接着性が高いことから、これを経口摂取することにより腸管における乳酸菌の作用を高めることができ、ダイエット、美容、健康増進に優れた効果が期待できる。 Further, according to the present invention, since a specific flower extract has high intestinal adhesion to lactic acid bacteria, the action of lactic acid bacteria in the intestinal tract can be enhanced by ingesting it orally, which is excellent in diet, beauty and health promotion. The effect can be expected.

図1は、実施例1~5及び比較例1の剤による腸管接着作用を評価した結果を示すグラフである。FIG. 1 is a graph showing the results of evaluating the intestinal adhesive action of the agents of Examples 1 to 5 and Comparative Example 1. 図2は、実施例6~10及び比較例1の剤による腸管接着作用を評価した結果を示すグラフである。FIG. 2 is a graph showing the results of evaluating the intestinal adhesive action of the agents of Examples 6 to 10 and Comparative Example 1.

以下、本発明をその好ましい実施形態に基づき説明する。本発明の剤は、ミソハギ科(Lythraceae)、キク科(Asteraceae)、マメ科(Fabaceae)、バラ科(Rosaceae)又はアヤメ科(Iridaceae)の花(以下、特定の花ともいう)の抽出物を含有するものである。
以下の説明は特に断らない限り、本発明の整腸剤、抗アレルギー剤、免疫増強剤及び乳酸菌の腸管接着性向上剤のいずれにも当てはまる。
Hereinafter, the present invention will be described based on the preferred embodiment thereof. The agent of the present invention is an extract of a flower (hereinafter, also referred to as a specific flower) of Lythraceae, Asteraceae, Fabaceae, Rosaceae or Iridaceae. It contains.
Unless otherwise specified, the following description applies to any of the intestinal regulators, antiallergic agents, immunopotentiators and lactic acid bacteria intestinal adhesion improvers of the present invention.

(花の抽出物)
本発明は、ミソハギ科(Lythraceae)、キク科(Asteraceae)、マメ科(Fabaceae)、バラ科(Rosaceae)又はアヤメ科(Iridaceae)の花を用いることにより乳酸菌の腸管接着性を効果的に高めることができる。
(Flower extract)
The present invention effectively enhances intestinal adhesion of lactic acid bacteria by using flowers of Lythraceae, Asteraceae, Fabaceae, Rosaceae or Iridaceae. Can be done.

ミソハギ科としては、ザクロ(柘榴、石榴)が好ましく挙げられる。ザクロは、ミソハギ科ザクロ属に属する落葉高木であり、学名をPunica granatumという。 Pomegranate (Pomegranate, Stone) is preferably mentioned as the Lythraceae. Pomegranate is a deciduous tree belonging to the genus Pomegranate of the Lythraceae family, and its scientific name is Punica granatum.

キク科としては、ベニバナ(紅花)及びキク(菊)が好ましく挙げられる。ベニバナは、キク科ベニバナ属の一年草又は越年草をいう。学名をCarthamus tinctorius という。
またキクは、キク科キク属(Chrysanthemum)の植物である。キクとしては、キク科キク属のキク(学名:Chrysanthemum morifolium Ramatulle)又はシマカンギク(学名:Chrysanthemum indicum Linne)が好ましく挙げられる。
Safflower (red flower) and chrysanthemum (chrysanthemum) are preferably mentioned as the Asteraceae. Safflower refers to an annual or perennial herb of the genus Carthamus in the family Asteraceae. The scientific name is Carthamus tinctorius.
Chrysanthemum is a plant of the genus Chrysanthemum in the family Asteraceae. As the chrysanthemum, a chrysanthemum (scientific name: Chrysanthemum morifolium Ramatulle) or a chrysanthemum (scientific name: Chrysanthemum indicum Linne) of the genus Chrysanthemum of the family Chrysanthemum is preferably mentioned.

マメ科としては、クズ(葛)が好ましく挙げられる。クズは、マメ科クズ属(Pueraria)の植物である。クズとしては、プエラリア・トムソニイ(学名:Pueraria thomsonii )、プエラリア・ロバータ(学名:Pueraria lobata)、プエラリア・スンバーギアナ(学名:Pueraria thunbergiana)等を例示できる。 As the legume family, kudzu is preferably mentioned. Kudzu is a plant of the genus Pueraria in the family Leguminosae. Examples of the waste include Pueraria thomsonii (scientific name: Pueraria thomsonii), Pueraria lobata (scientific name: Pueraria lobata), and Pueraria sumbergiana (scientific name: Pueraria thunbergiana).

バラ科としては、サクラ(桜、櫻)、モモ(桃)、バラ(薔薇)が好ましく挙げられる。
サクラは、バラ科サクラ属の植物のうち、ウメ、モモ、アンズなどを除いた総称であり、一般にはサクラ亜属 (Subgen. Cerasus) に属する植物を言う。
モモはバラ科モモ属に属し、学名はPrunus persica BatschまたはPrunus persica Batsch var. davidiana Maximowiczという。モモの品種としては、例えば、ハクトウ(白桃)、オウトウ(黄桃)、ネクタリンなどが挙げられる。
バラは、バラ科バラ属(Rosa)の植物を言う。
Preferred examples of the Rosaceae include cherry blossoms (cherry blossoms, sakura), peaches (peaches), and roses (roses).
Sakura is a general term for plants belonging to the genus Cerasus of the Rosaceae family, excluding plums, peaches, apricots, etc., and generally refers to plants belonging to the subgenus Cerasus.
Peach belongs to the genus Plum of the Rosaceae family, and its scientific name is Prunus persica Batsch or Prunus persica Batsch var. Davidiana Maximowicz. Examples of peach varieties include hakuto (white peach), outou (yellow peach), nectarine and the like.
Rose refers to a plant belonging to the genus Rosa of the Rosaceae family.

アヤメ科としては、サフラン(学名:Crocus sativus)が好ましく挙げられる。サフランは、地中海沿岸を原産とするアヤメ科の多年草である。 As the Iridaceae, saffron (scientific name: Crocus sativus) is preferably mentioned. Saffron is a perennial of the Iridaceae family native to the Mediterranean coast.

花は、蕾から全開した花までのいずれの段階で採集した花であってもよい。また、開花後の花は、花の全体であってもよく、花弁、萼、雄しべ、雌しべ、柱頭、花床(未成熟期のもの)のいずれか1以上であってもよい。例えばサフランとしてはめしべを用いることが好ましく、クズは蕾を用いることが好ましい。 The flower may be a flower collected at any stage from the bud to the fully opened flower. Further, the flower after flowering may be the whole flower, or may be one or more of petals, calyxes, stamens, pistils, stigmas, and flower beds (in the immature stage). For example, it is preferable to use a pistil as the saffron, and it is preferable to use a bud as the waste.

これらの花の抽出物を得るための抽出処理としては、水や有機溶媒等の抽出溶媒を用いた処理が挙げられる。抽出溶媒としては極性溶媒が挙げられる。極性溶媒としては、例えば、水、メタノール、エタノール、イソプロパノール、アセトン、1,3-ブチレングリコール、エチレングリコール、プロピレングリコール、グリセリン、酢酸、酢酸エチル、エーテル、ヘキサン等が挙げられる。これらのうち、水、メタノール、エタノール、含水エタノールが好ましい。尚、これらは1種のみ用いても良いし、2種以上併用しても良い。また抽出溶媒を用いずに生の花を搾汁することも抽出処理に含まれる。 Examples of the extraction treatment for obtaining these flower extracts include treatment using an extraction solvent such as water or an organic solvent. Examples of the extraction solvent include polar solvents. Examples of the polar solvent include water, methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, acetic acid, ethyl acetate, ether, hexane and the like. Of these, water, methanol, ethanol, and hydrous ethanol are preferable. It should be noted that these may be used alone or in combination of two or more. In addition, squeezing raw flowers without using an extraction solvent is also included in the extraction process.

抽出は生の花に対して行っても良いし、乾燥、加熱、切断や粉砕等を施した花に行っても良い。また抽出時に抽出溶媒は加温してもしなくてもよいが、加温する場合の溶媒温度は特に限定されるものではなく、花の抽出物を得るために一般に用いられる温度、例えば40℃以上沸点以下が挙げられる。例えば、水であれば熱水であってもなくてもよい。熱水とは温度が70℃以上の水のことを指す。 Extraction may be carried out on fresh flowers, or on flowers that have been dried, heated, cut or crushed. The extraction solvent may or may not be heated at the time of extraction, but the solvent temperature at the time of heating is not particularly limited, and is a temperature generally used for obtaining a flower extract, for example, 40 ° C. or higher. Below the boiling point. For example, if it is water, it may or may not be hot water. Hot water refers to water having a temperature of 70 ° C. or higher.

得られた抽出液に希釈、濃縮、乾燥、精製等の処理を施し、最終加工品である抽出物を得る。精製方法としては、例えば、活性炭処理、樹脂吸着処理、シリカゲル処理、イオン交換樹脂、液-液向流分配、膜分離等の方法が挙げられる。本発明の花の抽出物は、発酵過程(例えば抽出前原料の発酵過程又は抽出液の発酵過程)を経て得られたものであってもよく、これらの発酵過程を経ずに得られたものであってもよい。 The obtained extract is subjected to treatments such as dilution, concentration, drying and purification to obtain an extract as a final processed product. Examples of the purification method include methods such as activated carbon treatment, resin adsorption treatment, silica gel treatment, ion exchange resin, liquid-liquid countercurrent distribution, and membrane separation. The flower extract of the present invention may be obtained through a fermentation process (for example, a fermentation process of a pre-extraction raw material or a fermentation process of an extract), or a product obtained without these fermentation processes. May be.

本発明の剤において、特定の花の抽出物は液状、ペースト状、ジェル状、固体状のいずれであってもよく、固体状であることが品質の安定性等の点から好ましい。固体状としては、粉末状、粒状、顆粒状、細粒状、錠状、棒状、板状、ブロック状、固形状等が挙げられる。 In the agent of the present invention, the specific flower extract may be in the form of liquid, paste, gel or solid, and the solid form is preferable from the viewpoint of quality stability and the like. Examples of the solid state include powder, granule, granule, fine grain, tablet, rod, plate, block, solid and the like.

本発明の剤は、乳酸菌の腸管接着作用が特に高い点から、特定の花の抽出物としてザクロ、ベニバナ、クズ、サクラ、サフラン、モモ及びバラから選ばれる少なくとも1種を含むことがとりわけ好ましい。 It is particularly preferable that the agent of the present invention contains at least one selected from pomegranate, safflower, kudzu, cherry, saffron, peach and rose as a specific flower extract because the intestinal adhesive action of lactic acid bacteria is particularly high.

本発明の剤における特定の花の抽出物は、本発明の剤中、乾燥質量で0.0001質量%以上であることが好ましく、0.0005質量%以上50質量%以下であることがより好ましく、0.001質量%以上30質量%以下であることが特に好ましい。 The specific flower extract in the agent of the present invention preferably has a dry mass of 0.0001% by mass or more, more preferably 0.0005% by mass or more and 50% by mass or less, in the agent of the present invention. , 0.001% by mass or more and 30% by mass or less is particularly preferable.

本発明の剤は、植物由来成分として、実質的に特定の花の抽出物のみからなるものであってもよく、その他の植物由来成分を有していてもよい。例えば、本発明の剤における特定の花の抽出物以外の植物由来成分は、例えば本発明の剤中、80質量%以下であることが好ましく、50質量%以下であることがより好ましい。 The agent of the present invention may consist substantially only of a specific flower extract as a plant-derived component, or may have other plant-derived components. For example, the plant-derived component other than the specific flower extract in the agent of the present invention is preferably 80% by mass or less, more preferably 50% by mass or less in the agent of the present invention.

本発明の剤は、乳酸菌を非含有であってもよいが、乳酸菌を含有していることが、乳酸菌の腸管接着効果をより高める点から好ましい。乳酸菌は生菌である場合は腸内環境改善の点から好ましいが、死菌であってもよい。これは生菌のみならず死菌の菌体成分も腸管免疫を刺激するものとされていることや、死菌の菌体成分が生菌乳酸菌と餌となることなどに基づく。なお死菌である乳酸菌は腸管において有害物質を吸着することも知られている。本発明で使用される乳酸菌としては、代謝産物として乳酸を産生するものであれば特に限定されず、ヒトなどの動物において従来経口摂取されているものが挙げられ、例えば、Bifidobacterium属、Lactbacillus属、Enterococcus属、Leuconostoc属、Pediococcus属、Staphylococcus属、Tetragenococcus属、Bacillus属のものが挙げられる。
Bifidobacterium属としては、Bifidobacterium bifidum、Bifidobacterium breve、Bifidobacterium infantis、Bifidobacterium lactis、Bifidobacterium longum、Bifidobacterium adolescentis、Bifidobacterium mongolienseが挙げられる。
Lactbacillus属としては、Lactbacillus brevis、Lactbacillus gasseri、Lactobacillus acidophilus、Lactobacillus buchneri、Lactobacillus bulgaricus、Lactobacillus delburvecki、Lactobacillus casei、Lactobacillus crispatus、Lactobacillus curvatus、Lactobacillus halivaticus、Lactobacillus pentosus、Lactobacillus plantarum、Lactobacilus paracasei、Lactobacillus rhamnosus、Lactobacillus salivarius、Lactobacillus sporogenes、Lactobacillus sakei、Lactobacillus fructivorans、Lactobacillus hilgardii、Lactobacillus reuteri、Lactobacillus fermentumが挙げられる。
Enterococcusとしては、Enterococcus faecalis(Streptococcus faecalis と称されることもある)、Enterococcus faesium(Streptococcus faesiumと称されることもある)、Streptococcus thermophilus、Lactococcus lactis(Streptococcus lactisと称されることもある) が挙げられる。
Leuconostoc属としては、Leuconostoc mesenteroides、Leuconostoc oenos が挙げられる。
Pediococcus属としては、Pediococcus acidilactici、Pediococcus pentosaceusが挙げられる。
Staphylococcus属としては、Staphylococcus carnosus、Staphylococcus xylosusが挙げられる。
Tetragenococcus属としては、Tetragenococcus halophilusが挙げられる。Bacillus属としては、Bacillus coagulans、及びBacillus mesentericusなどが挙げられる。
とりわけ、Bacillus coagulans、Enterococcus faecalis、Bifidobacterium bifidum、Enterococcus faesium、Lactobacillus acidophilusが好ましい。これらは、1種を単独で使用してもよいし、2種以上を併用してもよい。
The agent of the present invention may not contain lactic acid bacteria, but it is preferable that the agent contains lactic acid bacteria from the viewpoint of further enhancing the intestinal adhesive effect of lactic acid bacteria. When the lactic acid bacterium is a live bacterium, it is preferable from the viewpoint of improving the intestinal environment, but it may be a dead bacterium. This is based on the fact that not only live bacteria but also the bacterial cell components of dead bacteria stimulate intestinal immunity, and that the bacterial cell components of dead bacteria feed on live lactic acid bacteria. It is also known that lactic acid bacteria, which are dead bacteria, adsorb harmful substances in the intestinal tract. The lactic acid bacterium used in the present invention is not particularly limited as long as it produces lactic acid as a metabolite, and examples thereof include those conventionally orally ingested in animals such as humans, and examples thereof include Bifidobacterium, Lactbacillus, and the like. Examples include those of the genera Enterococcus, Leuconostoc, Pediococcus, Staphylococcus, Tetragenococcus, and Bacillus.
Examples of the genus Bifidobacterium include Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium adolescentis, and Bifidobacterium mongoliense.
Lactbacillus属としては、Lactbacillus brevis、Lactbacillus gasseri、Lactobacillus acidophilus、Lactobacillus buchneri、Lactobacillus bulgaricus、Lactobacillus delburvecki、Lactobacillus casei、Lactobacillus crispatus、Lactobacillus curvatus、Lactobacillus halivaticus、Lactobacillus pentosus、Lactobacillus plantarum、Lactobacilus paracasei、Lactobacillus rhamnosus、Lactobacillus salivarius、 Lactobacillus sporogenes, Lactobacillus sakei, Lactobacillus fructivorans, Lactobacillus hilgardii, Lactobacillus reuteri, Lactobacillus fermentum.
Enterococcus includes Enterococcus faecalis (sometimes referred to as Streptococcus faecalis), Enterococcus faesium (sometimes referred to as Streptococcus faesium), Streptococcus thermophilus, and Lactococcus lactis (sometimes referred to as Streptococcus lactis). Will be.
Examples of the genus Leuconostoc include Leuconostoc mesenteroides and Leuconostoc oenos.
Examples of the genus Pediococcus include Pediococcus acidilactici and Pediococcus pentosaceus.
Examples of the genus Staphylococcus include Staphylococcus carnosus and Staphylococcus xylosus.
Examples of the genus Tetragenococcus include Tetragenococcus halophilus. Examples of the genus Bacillus include Bacillus coagulans and Bacillus mesentericus.
In particular, Bacillus coagulans, Enterococcus faecalis, Bifidobacterium bifidum, Enterococcus faesium, and Lactobacillus acidophilus are preferable. These may be used alone or in combination of two or more.

本発明の剤が乳酸菌を含有する場合、乳酸菌の含有量は特に限定されないが、例えば菌体数として、本発明の剤中、1×103個以上、好ましくは1×105個以上1×1020個以下、更に好ましくは1×107個以上1×1015個以下とすることが、製剤の容易性及び乳酸菌の腸管付着効果を高める点から好ましい。 When the agent of the present invention contains lactic acid bacteria, the content of the lactic acid bacteria is not particularly limited, but for example, the number of cells in the agent of the present invention is 1 × 103 or more, preferably 1 × 105 or more and 1 × 1020. Hereinafter, it is more preferable that the number is 1 × 107 or more and 1 × 1015 or less from the viewpoint of ease of preparation and enhancement of the intestinal adhesion effect of lactic acid bacteria.

本発明の剤は乳酸菌を含有する場合、乳酸菌と特定の花の抽出物とが同一剤に含まれていてもよく別々の剤に含まれていてもよい。別々の剤に含まれている場合は、本発明の剤は2剤以上の多剤型となる。同一剤に含まれている場合、本発明の剤は、1剤型であっても多剤型であってもよいが1剤型であることが摂取の簡便性等の点で好ましい。本発明の
剤の剤形は、1剤型及び多剤型のいずれに関わらず、固体状、液状、ペースト状、ゲル状
などが挙げられる。例えば、固体状としては、粉末状、粒状、顆粒状、錠状、棒状、板状、ブロック状、固形状、ハードカプセルやソフトカプセルのようなカプセル状、カプレット状、タブレット状、チュアブル状、スティック状等の各形態が挙げられる。液状としては例えば流動状、シロップ状等が挙げられる。これらは薬学的に許容される基材や担体を添加して、公知の製剤方法によって、各種の剤形に製剤可能である。
When the agent of the present invention contains lactic acid bacteria, the lactic acid bacteria and the extract of a specific flower may be contained in the same agent or may be contained in different agents. When contained in separate agents, the agent of the present invention is a multi-dose form of two or more agents. When contained in the same agent, the agent of the present invention may be a one-drug type or a multi-drug type, but the one-drug type is preferable in terms of ease of ingestion and the like. The dosage form of the agent of the present invention may be solid, liquid, paste, gel or the like regardless of whether it is a one-agent type or a multi-agent type. For example, as solids, powders, granules, granules, tablets, rods, plates, blocks, solids, capsules such as hard capsules and soft capsules, capsules, tablets, chewables, sticks, etc. Each form of is mentioned. Examples of the liquid include a fluid and a syrup. These can be formulated into various dosage forms by a known formulation method by adding a pharmaceutically acceptable base material or carrier.

例えば、乳酸菌を含有する本発明の剤の好ましい剤型としては、乳酸菌と前記特定の花の抽出物とを含み、粉末状、細粒状、顆粒状、錠状、ソフトカプセルやハードカプセル等のカプセル状、液状のいずれかである1剤型の形態や、前記特定の花の抽出物を含み、粉末状、細粒状、顆粒状、錠状、ソフトカプセルやハードカプセル等のカプセル状、液状である第1剤と、乳酸菌を含み、粉末状、細粒状、顆粒状、錠状、ソフトカプセルやハードカプセル等のカプセル状、液状のいずれかである第2剤とを有する2剤型の形態などが挙げられる。なお、本発明においては前記特定の花の抽出物を含む第1剤を単独で使用することにより、腸内に存在する乳酸菌やビフィズス菌の腸管接着性を向上させることもできる。本発明の剤が2剤に分かれている場合、上述した本発明の剤における特定の花の抽出物の好ましい割合は、2剤の合計量に対する割合とすることができる。 For example, the preferred dosage form of the agent of the present invention containing lactic acid bacteria includes lactic acid bacteria and the extract of the specific flower, and is in the form of powder, fine granules, granules, tablets, capsules such as soft capsules and hard capsules. The first dosage form, which is either liquid or contains the above-mentioned specific flower extract, is powdery, fine-grained, granular, tablet-like, capsule-like such as soft capsules and hard capsules, and liquid first preparation. , A two-dosage form containing lactic acid bacteria, powdery, finely granular, granular, tablety, capsule-like such as soft capsules and hard capsules, and a second agent which is either liquid or the like. In the present invention, the intestinal adhesiveness of lactic acid bacteria and bifidobacteria present in the intestine can be improved by using the first agent containing the specific flower extract alone. When the agent of the present invention is divided into two agents, the preferable ratio of the extract of a specific flower in the agent of the present invention described above can be a ratio to the total amount of the two agents.

本発明の剤の経口摂取方法は限定されず、そのまま摂取するのであってもよく、また剤を水やお湯、牛乳、ヨーグルトなどに分散又は溶解させたものを摂取するのであってもよい。また本発明の剤が多剤型である場合は、複数剤を同時に摂取してもよく、別のタイミングで摂取してもよい。別のタイミングで摂取する場合は、例えば乳酸菌含有剤を花の抽出物含有剤より先に摂取してもよく、逆に花の抽出物含有剤を乳酸菌含有剤よりも先に摂取してもよいが、両者の摂取の時間差としては24時間以内が好ましく、18時間以内がより好ましく、15時間以内が特に好ましい。また2剤の摂取方法は、同じであっても異なっていてもよく、異なる場合は例えば、乳酸菌含有剤はそのまま摂取し、花の抽出物含有剤は水やお湯、牛乳、ヨーグルトなどに分散して摂取する、という例があげられ、これは逆であってもよい。 The oral ingestion method of the agent of the present invention is not limited, and the agent may be ingested as it is, or may be ingested by dispersing or dissolving the agent in water, hot water, milk, yogurt or the like. When the agent of the present invention is in a multi-dose form, a plurality of agents may be ingested at the same time, or may be ingested at different timings. When ingesting at a different timing, for example, the lactic acid bacterium-containing agent may be ingested before the flower extract-containing agent, and conversely, the flower extract-containing agent may be ingested before the lactic acid bacterium-containing agent. However, the time difference between the two intakes is preferably within 24 hours, more preferably within 18 hours, and particularly preferably within 15 hours. The method of ingesting the two agents may be the same or different. If they are different, for example, the lactic acid bacterium-containing agent is ingested as it is, and the flower extract-containing agent is dispersed in water, hot water, milk, yogurt, etc. There is an example of ingesting, and this may be the opposite.

本発明の剤は前記特定の花の抽出物及び乳酸菌以外に、通常使用される他の成分を、本発明の効果を損なわない範囲で含有してもよい。このような成分としては、種々の賦形剤、結合剤、光沢剤、滑沢剤、安定剤、希釈剤、増量剤、増粘剤、乳化剤、酸化防止剤、pH調整剤、着色料、香料、添加剤などを挙げることができる。その他の成分の含有量は、本発明の剤の形態等に応じて適宜選択することができる。また本発明の剤が多剤型である場合、いずれの剤にいずれの他の成分を含有するかについても、その剤の形態に応じて適宜選択される。 In addition to the specific flower extract and lactic acid bacteria, the agent of the present invention may contain other commonly used components as long as the effects of the present invention are not impaired. Such ingredients include various excipients, binders, brighteners, lubricants, stabilizers, diluents, bulking agents, thickeners, emulsifiers, antioxidants, pH regulators, colorants, fragrances. , Additives and the like. The content of other components can be appropriately selected depending on the form of the agent of the present invention and the like. Further, when the agent of the present invention is in a multi-dose form, which agent contains which other component is appropriately selected according to the form of the agent.

本発明の剤の1日の経口投与量は前記特定の花の抽出物の乾燥質量として0.1mg以上であることが好ましい。本発明の剤は、連続的に、例えば毎日でも投与でき、長期的、例えば1ヶ月以上の間投与を継続して差し支えない。 The daily oral dose of the agent of the present invention is preferably 0.1 mg or more as the dry mass of the extract of the specific flower. The agent of the present invention can be administered continuously, for example daily, and may be continuously administered for a long period of time, for example, for one month or longer.

本発明の剤が乳酸菌を含有する場合もしない場合も、前記特定の花の抽出物の経口投与量を前提として、乳酸菌の1日の経口投与量は1×103個以上、特に1×105個以上1×1020
個以下であることが好ましい。
Whether or not the agent of the present invention contains lactic acid bacteria, the daily oral dose of lactic acid bacteria is 1 × 103 or more, particularly 1 × 105, assuming the oral dose of the specific flower extract. More than 1 × 1020
It is preferably less than or equal to.

本発明の剤は、後述する実施例の記載から明らかな通り、前記特定の花の抽出物の作用により乳酸菌の腸管接着性を高めることができる。ここでいう腸管接着性とは、好ましくは腸管上皮(腸管上皮細胞)への接着性をいう。腸管接着性としては、個々の乳酸菌の接着性であってもよく、また集合体としての乳酸菌の接着性(集合体中の腸管接着(付着)した菌の割合)であってもよい。
このため、本発明の剤はこれを経口摂取することで、腸管における乳酸菌の作用を高めることができ、例えば整腸剤として用いることができる。整腸作用としては、有益腸内細菌(乳酸菌を含む)の増殖を促進する作用や有害腸内細菌の増殖を抑制する作用を挙げることができる。例えば、特許文献1に記載された、モモの花による瀉下作用及びこれを用いた抗便秘作用は、本発明でいう整腸作用に含まれない。また例えば、PPAR活性化によりもたらされる抗炎症作用は本発明でいう整腸作用に含まれない。
As is clear from the description of Examples described later, the agent of the present invention can enhance the intestinal adhesiveness of lactic acid bacteria by the action of the specific flower extract. The term "intestinal adhesiveness" as used herein preferably means adhesion to intestinal epithelium (intestinal epithelial cells). The intestinal adhesiveness may be the adhesiveness of individual lactic acid bacteria, or the adhesiveness of lactic acid bacteria as an aggregate (the ratio of intestinal adhesive (adhered) bacteria in the aggregate).
Therefore, the agent of the present invention can enhance the action of lactic acid bacteria in the intestinal tract by ingesting it orally, and can be used, for example, as an intestinal regulating agent. Examples of the intestinal regulating action include an action of promoting the growth of beneficial intestinal bacteria (including lactic acid bacteria) and an action of suppressing the growth of harmful intestinal bacteria. For example, the laxative action of peach flowers and the anti-constipation action using the same described in Patent Document 1 are not included in the intestinal regulating action referred to in the present invention. Further, for example, the anti-inflammatory action brought about by PPAR activation is not included in the intestinal regulating action referred to in the present invention.

本発明の剤は乳酸菌の腸管接着性を高めることができるため、腸管免疫等の免疫増強剤として用いることができるほか、アトピー性皮膚炎、アレルギー性鼻炎、花粉症、湿疹、蕁麻疹等の発疹、下痢や嘔吐等のアレルギー症状の予防や改善を図ることができる。前記の免疫増強剤の作用は、腸管においてTh1細胞の働きを活発化したり、IgA抗体産生を促すことを含む。 Since the agent of the present invention can enhance the intestinal adhesion of lactic acid bacteria, it can be used as an immunopotentiator for intestinal immunity, and rashes such as atopic dermatitis, allergic rhinitis, hay fever, eczema, and urticaria. , It is possible to prevent or improve allergic symptoms such as diarrhea and vomiting. The action of the immunopotentiator includes activating the function of Th1 cells in the intestinal tract and promoting IgA antibody production.

本発明の剤は、ヒトに対して好適に適用されるものであるが、それぞれの作用効果が奏される限り、ヒト以外の動物(例えば、マウス、ラット、ハムスター、イヌ、ネコ、ウシ、ブタ、サル等)に対して適用することもできる。 The agent of the present invention is suitably applied to humans, but animals other than humans (for example, mice, rats, hamsters, dogs, cats, cows, pigs) as long as the respective actions and effects are exhibited. , Monkeys, etc.).

本発明の剤により腸管接着(付着)性を高める対象となる乳酸菌としては、本発明の剤に含有されていてもよい乳酸菌として前記で上げたものと同様のものを挙げることができる。本発明は更に、本発明の剤を含有する食品又は医薬品、医薬部外品などを提供する。
本発明は乳酸菌とともに本発明の剤を摂取して腸管における乳酸菌接着を促す方法(但し医療行為を除く)を提供する。
Examples of the lactic acid bacterium to be targeted for enhancing the intestinal adhesiveness (adhesion) by the agent of the present invention include the same lactic acid bacteria as those mentioned above as the lactic acid bacterium that may be contained in the agent of the present invention. The present invention further provides foods or pharmaceuticals containing the agents of the present invention, quasi-drugs, and the like.
The present invention provides a method (excluding medical practice) of ingesting the agent of the present invention together with lactic acid bacteria to promote adhesion of lactic acid bacteria in the intestinal tract.

以下、実施例を挙げて本発明を更に詳細に説明する。しかし本発明の範囲はかかる実施例に限定されない。以下、特に断らない場合「%」は質量%、「部」は質量部を表す。 Hereinafter, the present invention will be described in more detail with reference to examples. However, the scope of the present invention is not limited to such examples. Hereinafter, unless otherwise specified, "%" represents mass% and "parts" represents mass parts.

〔実施例1~10、比較例1〕
(被験物質)
特定の花の抽出物として、以下の粉末を用いた。
・ベニバナ:ベニバナの花を水で抽出して得られた、市販の抽出物の粉末
・クズ:クズの花を熱水で抽出して得られた、市販の抽出物粉末
・バラ:バラの花びらを熱水で抽出して得られた、市販の抽出物粉末
・ザクロ:ザクロの花を含水エタノールで抽出して得られた、市販の抽出物粉末
・サクラ:サクラの花を含水エタノールで抽出して得られた、市販の抽出物粉末
・キク:キクの花を水で抽出して得られた、市販の抽出物粉末
・サフラン:サフランのめしべを含水エタノールで抽出して得られた、市販の抽出物の粉末
・モモ:白桃の花を熱水で抽出して得られた、市販の抽出物粉末
[Examples 1 to 10, Comparative Example 1]
(Test substance)
The following powders were used as specific flower extracts.
・ Benibana: Commercially available extract powder obtained by extracting Benibana flowers with water ・ Kuzu: Commercially available extract powder obtained by extracting Kuzu flowers with hot water ・ Rose: Rose petals Commercially available extract powder obtained by extracting with hot water ・ Pomegranate: Pomegranate flower extracted with hydrous ethanol, commercially available extract powder ・ Sakura: Sakura flower extracted with hydrous ethanol Commercially available extract powder, Kiku: obtained by extracting Kiku flowers with water, commercially available extract powder, Saffron: obtained by extracting saffron mess with hydrous ethanol, commercially available Extract powder ・ Momo: Commercially available extract powder obtained by extracting white peach blossoms with hot water.

(接着能試験)
(1)ヒト結腸癌由来細胞Caco-2の培養および播種
(1-1)Passage 20の腸管上皮細胞株Caco-2細胞を用いた。
(1-2)トリプシン処理により浮遊させたCaco-2細胞を、75cm2フラスコから96 well plateに4.0×104/wellの細胞密度で播種した。
(1-3)培養培地を用い、37℃、5体積%CO2インキュベーター内で4日間培養した。この通常培地は、DMEMを10% FBS (Fatal Bovin Serum)、1%ペニシリン-ストレプトマイシン、1% NEAA(Non-Essential Amino Acids、SIGMA社)になるように調製した。この培養によりwell内でcaco-2の単層膜(腸管モデル)を作成した。
(1-4)(5)の試験の数時間前に試験培地に置換した。試験培地は、DMEMを2% FBS、1% NEAAになるように調製した。
(Adhesive ability test)
(1) Culture and dissemination of human colon cancer-derived cells Caco-2 (1-1) Passage 20 intestinal epithelial cell line Caco-2 cells were used.
(1-2) Caco-2 cells suspended by trypsin treatment were seeded from a 75 cm2 flask into a 96 well plate at a cell density of 4.0 × 104 / well.
(1-3) Using a culture medium, the cells were cultured at 37 ° C. in a 5 volume% CO2 incubator for 4 days. This normal medium was prepared so that DMEM was 10% FBS (Fatal Bovin Serum), 1% penicillin-streptomycin, and 1% NEAA (Non-Essential Amino Acids, SIGMA). By this culture, a monolayer membrane (intestinal tract model) of caco-2 was prepared in the well.
(1-4) The test medium was replaced with a test medium several hours before the test of (5). The test medium was prepared so that DMEM was 2% FBS and 1% NEAA.

(2)Bacillus coagulansのグリセロールストック及び前培養
(2-1)粉体状の乳酸菌Bacillus coagulansをMRS液体培地にて72時間、37℃で培養した。
(2-2)培養液を採取し、グリセロールが30%になるように培養液を混ぜ、試験を行うまで-80℃で保存した(グリセロールストック)。
(2-3)B.coagulansのグリセロールストックを室温に戻し、37℃で温めたMRS液体培地へ播種し、同温で24時間培養後に下記(3)の蛍光標識及び(4)の検量線用サンプルの作製に用いた。
(2) Bacillus coagulans glycerol stock and preculture (2-1) Powdered lactic acid bacterium Bacillus coagulans was cultured in MRS liquid medium for 72 hours at 37 ° C.
(2-2) The culture broth was collected, mixed with the culture broth so that the glycerol content was 30%, and stored at -80 ° C until the test was performed (glycerol stock).
(2-3) The glycerol stock of B. coagulans is returned to room temperature, seeded in an MRS liquid medium warmed at 37 ° C., cultured at the same temperature for 24 hours, and then for the fluorescent label of (3) below and the calibration curve of (4). It was used to prepare a sample.

(3)B. coagulansの蛍光標識
(3-1)B. coagulans菌を(2)で前培養した後の菌液100μL採取し、900mLのリン酸緩衝生理食塩液(PBS)へ懸濁、1000g×3分間遠心分離した。得られたペレットを1000μL PBSへ懸濁し、15μL carboxyfluorescein diacetate(CFDA、同仁化学研究所社製)を加え、30分間遮光、室温でインキュベートした。
(3-2)1000g×3分間遠心分離し、ペレットを1mL PBSで懸濁し、再度1000gx3分間遠心分離した。この操作を2回行った。
(3-3)ペレットを試験培地で懸濁し、得られた懸濁物を下記(5)の試験に用いた。
(3) Fluorescent labeling of B. coagulans (3-1) After pre-culturing B. coagulans in (2), 100 μL of the bacterial solution was collected and suspended in 900 mL of phosphate buffered saline (PBS), 1000 g. × Centrifuged for 3 minutes. The obtained pellet was suspended in 1000 μL PBS, 15 μL carboxyfluorescein diacetate (CFDA, manufactured by Dojin Chemical Research Institute) was added, and the mixture was incubated for 30 minutes at room temperature.
(3-2) Centrifugation was performed at 1000 g x 3 minutes, the pellet was suspended in 1 mL PBS, and the pellet was centrifuged again at 1000 g x 3 minutes. This operation was performed twice.
(3-3) The pellet was suspended in a test medium, and the obtained suspension was used in the test of (5) below.

(4)検量線用サンプルの作製
(4-1)上記(3-1)で蛍光標識した乳酸菌の一部をホルマリン固定した。
(4-2)同じ前培養したサンプルをBCP培地にて37℃、3日間培養し、BCP培地上のコロニー数を測定した(plate count)。
(4-3)plate countから細菌数を計算し、(4-1)でホルマリン固定したサンプルを既知数サンプルとして検量線用サンプルとした。
(4) Preparation of sample for calibration curve (4-1) A part of the lactic acid bacteria fluorescently labeled in (3-1) above was fixed with formalin.
(4-2) The same pre-cultured sample was cultured in BCP medium at 37 ° C. for 3 days, and the number of colonies on the BCP medium was measured (plate count).
(4-3) The number of bacteria was calculated from the plate count, and the sample fixed with formalin in (4-1) was used as a known number sample and used as a calibration curve sample.

(5)定着能比較試験
(5-1)下記表1の被験物質である 花抽出物粉末10mg量り取り、50mLファルコンチューブに入れ、1mg/mLになるように試験培地を加えた。ボルテックス後、各被験物質の最終濃度が下記表1の濃度となるように試験培地で希釈した。
(5-2)(5-1)において被験物質含有又は非含有の試験培地へ菌数を1x108/mLに調整した菌懸濁液を加え、B. coagulans濃度1x106/mLとした。(1-4)の細胞に1well当たり100μLとなる量で添加し(B. coagulans最終濃度1x105/well)、2時間37℃で培養した。なお比較例1では、被験物質非含有の試験培地を同量添加した。
(5-3) 培養終了後、各wellに150μL ホルマリン液を加え、4℃で30分以上固定した。
(5-4) PBSでwellを2回洗浄し、varioskanにて蛍光強度(励起光495nm、蛍光515nm)を測定した。
(5-5) (4-3)の検量線用サンプルをvarioskanにて蛍光強度を測定することで検量線を作成した。得られた検量線に基づき、(5-4)で測定した蛍光強度からCaco-2単層膜へ接着したB. coagulansの菌数を計算した。
(5-6)
得られた菌数の比較例1に対する相対値(%)を図1及び図2に示す。
(5) Fixation ability comparison test (5-1) 10 mg of flower extract powder, which is the test substance in Table 1 below, was weighed, placed in a 50 mL falcon tube, and a test medium was added to a concentration of 1 mg / mL. After vortexing, the test medium was diluted with the test medium so that the final concentration of each test substance was the concentration shown in Table 1 below.
(5-2) In (5-1), a bacterial suspension adjusted to a bacterial count of 1x108 / mL was added to the test medium containing or not containing the test substance to obtain a B. coagulans concentration of 1x106 / mL. The cells of (1-4) were added in an amount of 100 μL per well (B. coagulans final concentration 1x105 / well) and cultured at 37 ° C. for 2 hours. In Comparative Example 1, the same amount of test medium containing no test substance was added.
(5-3) After completion of the culture, 150 μL formalin solution was added to each well, and the cells were fixed at 4 ° C. for 30 minutes or longer.
(5-4) The well was washed twice with PBS, and the fluorescence intensity (excitation light 495 nm, fluorescence 515 nm) was measured with varioskan.
(5-5) A calibration curve was prepared by measuring the fluorescence intensity of the calibration curve sample of (4-3) with varioskan. Based on the obtained calibration curve, the number of B. coagulans adhered to the Caco-2 monolayer membrane was calculated from the fluorescence intensity measured in (5-4).
(5-6)
The relative values (%) of the obtained bacterial numbers with respect to Comparative Example 1 are shown in FIGS. 1 and 2.

Figure 2022081686000002
Figure 2022081686000002

図1及び図2の結果から、特定の花の抽出物は、乳酸菌の腸管接着率を高めることが判る。また、本発明の剤は、乳酸菌の腸管接着性が高いことから、これを経口摂取することにより腸管における乳酸菌の作用を高めることができ、整腸作用や抗アレルギー作用、免疫増強作用、ダイエット、美容、健康増進に優れた効果が期待できる。 From the results of FIGS. 1 and 2, it can be seen that the specific flower extract enhances the intestinal adhesion rate of lactic acid bacteria. In addition, since the agent of the present invention has high intestinal adhesion to lactic acid bacteria, the action of lactic acid bacteria in the intestinal tract can be enhanced by ingesting it, and the intestinal regulating action, antiallergic action, immunopotentiating action, diet, etc. It can be expected to have excellent effects on beauty and health promotion.

Claims (4)

ミソハギ科(Lythraceae)、キク科(Asteraceae)、マメ科(Fabaceae)、バラ科(Rosaceae)又はアヤメ科(Iridaceae)から選ばれる少なくとも1種の花の抽出物を含有する整腸剤。 An intestinal regulator containing at least one flower extract selected from Lythraceae, Asteraceae, Fabaceae, Rosaceae or Iridaceae. ミソハギ科(Lythraceae)、キク科(Asteraceae)、マメ科(Fabaceae)、バラ科(Rosaceae)又はアヤメ科(Iridaceae)から選ばれる少なくとも1種の花の抽出物を含有する抗アレルギー剤。 An antiallergic agent containing an extract of at least one flower selected from Lythraceae, Asteraceae, Fabaceae, Rosaceae or Iridaceae. ミソハギ科(Lythraceae)、キク科(Asteraceae)、マメ科(Fabaceae)、バラ科(Rosaceae)又はアヤメ科(Iridaceae)から選ばれる少なくとも1種の花の抽出物を含有する免疫増強剤。 An immunopotentiator containing at least one flower extract selected from Lythraceae, Asteraceae, Fabaceae, Rosaceae or Iridaceae. ミソハギ科(Lythraceae)、キク科(Asteraceae)、マメ科(Fabaceae)、バラ科(Rosaceae)又はアヤメ科(Iridaceae)から選ばれる少なくとも1種の花の抽出物を含有する乳酸菌の腸管接着性向上剤。 An intestinal adhesion improver for lactic acid bacteria containing at least one flower extract selected from Lythraceae, Asteraceae, Fabaceae, Rosaceae or Iridaceae. ..
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